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Continuum solvent models have become a standard technique in the context of electronic structure calculations, yet no implementations have been reported capable to perform molecular dynamics at solid-liquid interfaces. We propose here such a continuum approach in a density functional theory framework using plane-wave basis sets and periodic boundary conditions. Our work stems from a recent model designed for Car–Parrinello simulations of quantum solutes in a dielectric medium [D. A. Scherlis et al., J. Chem. Phys. 124, 074103 (2006)], for which the permittivity of the solvent is defined as a function of the electronic density of the solute. This strategy turns out to be inadequate for systems extended in two dimensions: the dependence of the dielectric function on the electronic density introduces a new term in the Kohn–Sham potential, which becomes unphysically large at the interfacial region, seriously affecting the convergence of the self-consistent calculations. If the dielectric medium is properly redefined as a function of the atomic coordinates, a good convergence is obtained and the constant of motion is conserved during the molecular dynamics simulations. The Poisson problem is solved using a multigrid method, and in this way Car–Parrinello molecular dynamics simulations of solid-liquid interfaces can be performed at a very moderate computational cost. This scheme is employed to investigate the acid-base equilibrium at the TiO2-water interface. The aqueous behavior of titania surfaces has stimulated a large amount of experimental research, but many open questions remain concerning the molecular mechanisms determining the chemistry of the interface. Here we make an attempt to answer some of them, putting to the test our continuum model. [ABSTRACT FROM AUTHOR]

Los datos provenientes de los radares meteorológicos son de suma importancia para el diagnóstico y monitoreo de los sistemas que producen precipitación y sus posibles fenómenos severos asociados. Los ecos causados por objetivos no meteorológicos introducen errores en la información por lo que es necesario detectar la presencia de los mismos previo a la utilización de los datos. Este trabajo presenta cuatro técnicas de clasificación supervisada basadas en diferentes modelos estadísticos que buscan dar una respuesta a este problema. Asimismo como parte importante de este trabajo, se aplicaron técnicas de remuestreo estadísticas sobre los datos de entrenamiento, las que permitieron hacer un análisis más completo sobre los resultados. En la actualidad, las técnicas de remuestreo son herramientas fundamentales en la estadística moderna. Las mismas, a partir de simulaciones sobre los datos, permiten obtener información adicional sobre los modelos planteados. Para este trabajo se realizó un estudio de caso con datos provenientes del radar meteorológico Doppler banda C de doble polarización ubicado en la Estación Experimental Agropecuaria INTA Anguil (La Pampa). Partiendo de la clasificación manual de un experto, se aplicaron cuatro métodos de clasificación supervisada de diferentes grados de flexibilidad en su estructura: Modelo lineal, Modelo Cuadrático, Modelo Logístico y Modelo de Bayes Naive. Luego se compararon los resultados y se evaluó el desempeño de cada uno de ellos. Si bien se encontraron dificultades a la hora de clasificar las zonas de frontera entre clases, los resultados obtenidos fueron adecuados, mostrando el mejor desempeño el modelo menos flexible, el modelo lineal. Se considera necesario seguir avanzando en esta línea de investigación a fin de incorporar una mayor cantidad de casos y tener una mayor significancia de los resultados. [ABSTRACT FROM AUTHOR]

In this paper, we propose a new procedure to estimate the distribution of a variable y when there are missing data. To compensate the presence of missing responses, it is assumed that a covariate vector x is observed and that y and x are related by means of a semi-parametric regression model. Observed residuals are combined with predicted values to estimate the missing response distribution. Once the responses distribution is consistently estimated, we can estimate any parameter defined through a continuous functional T using a plug in procedure. We prove that the proposed estimators have high breakdown point. [ABSTRACT FROM AUTHOR]

In a missing-data setting, we want to estimate the mean of a scalar outcome, based on a sample in which an explanatory variable is observed for every subject while responses are missing by happenstance for some of them. We consider two kinds of estimates of the mean response when the explanatory variable is functional. One is based on the average of the predicted values and the second one is a functional adaptation of the Horvitz–Thompson estimator. We show that the infinite dimensionality of the problem does not affect the rates of convergence by stating that the estimates are root-nconsistent, under missing at random (MAR) assumption. These asymptotic features are completed by simulated experiments illustrating the easiness of implementation and the good behaviour on finite sample sizes of the method. This is the first paper emphasizing that the insensitiveness of averaged estimates, well known in multivariate non-parametric statistics, remains true for an infinite-dimensional covariable. In this sense, this work opens the way for various other results of this kind in functional data analysis. [ABSTRACT FROM AUTHOR]

In a missing data setting, we have a sample in which a vector of explanatory variables ${\bf x}_i$ is observed for every subject i, while scalar responses $y_i$ are missing by happenstance on some individuals. In this work we propose robust estimators of the distribution of the responses assuming missing at random (MAR) data, under a semiparametric regression model. Our approach allows the consistent estimation of any weakly continuous functional of the response's distribution. In particular, strongly consistent estimators of any continuous location functional, such as the median, L-functionals and M-functionals, are proposed. A robust fit for the regression model combined with the robust properties of the location functional gives rise to a robust recipe for estimating the location parameter. Robustness is quantified through the breakdown point of the proposed procedure. The asymptotic distribution of the location estimators is also derived. The proofs of the theorems are presented in Supplementary Material available online. The Canadian Journal of Statistics 41: 111-132; 2013 © 2012 Statistical Society of Canada [ABSTRACT FROM AUTHOR]

Abstract Due to increased recording capability, functional data analysis has become an important research topic. For functional data, the study of outlier detection and/or the development of robust statistical procedures started only recently. One robust alternative to the sample covariance operator is the sample spatial sign covariance operator. In this paper, we study the asymptotic behavior of the sample spatial sign covariance operator centered at an estimated location. Among possible applications of our results, we derive the asymptotic distribution of the principal directions obtained from the sample spatial sign covariance operator and we develop a testing procedure to detect differences between the scatter operators of two populations. The test performance is illustrated through a Monte Carlo study for small sample sizes. [ABSTRACT FROM AUTHOR]

In many situations, when dealing with several populations, equality of the covariance operators is assumed. An important issue is to study whether this assumption holds before making other inferences. In this paper, we develop a test for comparing covariance operators of several functional data samples. The proposed test is based on the Hilbert-Schmidt norm of the difference between estimated covariance operators. In particular, when dealing with two populations, the test statistic is just the squared norm of the difference between the two covariance operators estimators. The asymptotic behaviour of the test statistic under both the null hypothesis and local alternatives is obtained. The computation of the quantiles of the null asymptotic distribution is not feasible in practice. To overcome this problem, a bootstrap procedure is considered. The performance of the test statistic for small sample sizes is illustrated through a Monte Carlo study and on a real data set. [ABSTRACT FROM AUTHOR]

Motivation: Hemeproteins have many diverse functions that largely depend on the rate at which they uptake or release small ligands, like oxygen. These proteins have been extensively studied using either simulations or experiments, albeit only qualitatively and one or two proteins at a time. Results: We present a physical-chemical model, which uses data obtained exclusively from computer simulations, to describe the uptake and release of oxygen in a family of hemeproteins, called truncated hemoglobins (trHbs). Through a rigorous statistical analysis we demonstrate that our model successfully recaptures all the reported experimental oxygen association and dissociation kinetic rate constants, thus allowing us to establish the key factors that determine the rates at which these hemeproteins uptake and release oxygen. We found that internal tunnels as well as the distal site water molecules control ligand uptake, whereas oxygen stabilization by distal site residues controls ligand release. Because these rates largely determine the functions of these hemeproteins, these approaches will also be important tools in characterizing the trHbs members with unknown functions. [ABSTRACT FROM AUTHOR]

The mechanisms involved in bidirectional transport along microtubules remain largely unknown. We explored the collective action of kinesin-2 and dynein motors during transport of melanosomes in Xenopus laevis melanophores. These motors are attached to organelles through accessory proteins establishing a complex molecular linker. We determined both the stiffness of this linker and the organelles speed and observed that these parameters depended on the organelle size and cargo direction. Our results suggest that melanosome transport is driven by two dissimilar teams: whereas dynein motors compete with kinesin-2 affecting the properties of plus-end directed organelles, kinesin-2 does not seem to play a similar role during minus-end transport. [ABSTRACT FROM AUTHOR]

In this work, we propose a different 'surgical modified model' for the construction of counterfactual variables under non-parametric structural equation models. This approach allows the simultaneous representation of counterfactual responses and observed treatment assignment, at least when the intervention is done in one node. Using the new proposal, the d-separation criterion is used to verify conditions related with ignorability or conditional ignorability, and a new proof of the back door theorem is provided under this framework [ABSTRACT FROM AUTHOR]

In this article, we develop a nonparametric estimator for the Hölder constant of a density function. We consider a simulation study to evaluate the performance of the proposal and construct smooth bootstrap confidence intervals. Also, we give a brief review over the impossibility to decide whether a density function is Hölder. [ABSTRACT FROM PUBLISHER]

Recently proposed double-robust estimators for a population mean from incomplete data and for a finite number of counterfactual means can have much higher efficiency than the usual double-robust estimators under misspecification of the outcome model. In this paper, we derive a new class of double-robust estimators for the parameters of regression models with incomplete cross-sectional or longitudinal data, and of marginal structural mean models for cross-sectional data with similar efficiency properties. Unlike the recent proposals, our estimators solve outcome regression estimating equations. In a simulation study, the new estimator shows improvements in variance relative to the standard double-robust estimator that are in agreement with those suggested by asymptotic theory. [ABSTRACT FROM PUBLISHER]

Abstract: In many situations, when dealing with several populations with different covariance operators, equality of the operators is assumed. Usually, if this assumption does not hold, one estimates the covariance operator of each group separately, which leads to a large number of parameters. As in the multivariate setting, this is not satisfactory since the covariance operators may exhibit some common structure. In this paper, we discuss the extension to the functional setting of the common principal component model that has been widely studied when dealing with multivariate observations. Moreover, we also consider a proportional model in which the covariance operators are assumed to be equal up to a multiplicative constant. For both models, we present estimators of the unknown parameters and we obtain their asymptotic distribution. A test for equality against proportionality is also considered. [Copyright &y& Elsevier]

In this‐30 work we propose a model selection criterion to estimate the points of independence of a random vector, producing a decomposition of the vector distribution function into independent blocks. The method, based on a general estimator of the distribution function, can be applied for discrete or continuous random vectors, and for i.i.d. data or dependent time series. We prove the consistency of the approach under general conditions on the estimator of the distribution function and we show that the consistency holds for i.i.d. data and discrete time series with mixing conditions. We also propose an efficient algorithm to approximate the estimator and show the performance of the method on simulated data. We apply the method in a real dataset to estimate the distribution of the flow over several locations on a river, observed at different time points. [ABSTRACT FROM AUTHOR]

Objectives: Early life represents a sensitive and critical period for an individual. Nutrition plays a crucial role in the maturation and functional development of the central nervous system. Inadequate nutrition before birth and during the postnatal life can seriously interfere with brain development and lead to behavioral and neurological disorders such as learning disabilities and psychiatric diseases. In addition, the quality of mother–infant interactions represents an important adaptive pathway that prepares offspring for the conditions of life. In this work, we asked if protein malnutrition alters maternal care and offspring development and if these phenotypes can be transmitted to next generation. Methods: Female mice were fed with a normal or hypoproteic diet during pregnancy and lactation. Nurturing behaviors, i.e. arched, blanket and passive nursing, and liking and grooming of the pups, were evaluated from postnatal day 1 (PD1) to postnatal day 7 (PD7). The same protocol was employed to evaluate maternal behavior for filial generation 1 (F1) and filial generation 2 (F2) dams. Offspring development was evaluated for F1, F2, and F3 generations. Developmental landmarks and neurological reflexes were assessed from PD8 until complete development of the landmark or acquisition of the reflex. Results: Our results show that malnourished dams provide a lesser and more fragmented maternal care than their normally fed counterparts. This altered maternal behavior as well as the delay in the physical and neurological development observed in the offspring from malnourished mothers was transmitted up to two generations at least. Conclusion: These results highlight the harmful effects of protein malnutrition even for generations that are not directly exposed to this environmental adversity. [ABSTRACT FROM AUTHOR]

The calculation of free energy profiles is central in understanding differential enzymatic activity, for instance, involving chemical reactions that require QM‐MM tools, ligand migration, and conformational rearrangements that can be modeled using classical potentials. The use of steered molecular dynamics (sMD) together with the Jarzynski equality is a popular approach in calculating free energy profiles. Here, we first briefly review the application of the Jarzynski equality to sMD simulations, then revisit the so‐called stiff‐spring approximation and the consequent expectation of Gaussian work distributions and, finally, reiterate the practical utility of the second‐order cumulant expansion, as it coincides with the parametric maximum‐likelihood estimator in this scenario. We illustrate this procedure using simulations of CO, both in aqueous solution and in a carbon nanotube as a model system for biologically relevant nanoheterogeneous environments. We conclude the use of the second‐order cumulant expansion permits the use of faster pulling velocities in sMD simulations, without introducing bias due to large dispersion in the non‐equilibrium work distribution. [ABSTRACT FROM AUTHOR]

Abstract We consider model-based sufficient dimension reduction for generalized linear models and prove the consistency and asymptotic normality of the prediction estimator studied empirically for the normal case by Adragni and Cook (2009) when a sample version of the sufficient dimension reduction is used. Moreover, we provide a formula for the prediction that does need require explicitly computing the reduction. [ABSTRACT FROM AUTHOR]

The Jarzynski equality is one of the most widely celebrated and scrutinized nonequilibrium work theorems, relating free energy to the external work performed in nonequilibrium transitions. In practice, the required ensemble average of the Boltzmann weights of infinite nonequilibrium transitions is estimated as a finite sample average, resulting in the so‐called Jarzynski estimator, ΔF^J. Alternatively, the second‐order approximation of the Jarzynski equality, though seldom invoked, is exact for Gaussian distributions and gives rise to the Fluctuation‐Dissipation estimator ΔF^FD. Here we derive the parametric maximum‐likelihood estimator (MLE) of the free energy ΔF^ML considering unidirectional work distributions belonging to Gaussian or Gamma families, and compare this estimator to ΔF^J. We further consider bidirectional work distributions belonging to the same families, and compare the corresponding bidirectional ΔF^ML∗ to the Bennett acceptance ratio (ΔF^BAR) estimator. We show that, for Gaussian unidirectional work distributions, ΔF^FD is in fact the parametric MLE of the free energy, and as such, the most efficient estimator for this statistical family. We observe that ΔF^ML and ΔF^ML∗ perform better than ΔF^J and ΔF^BAR, for unidirectional and bidirectional distributions, respectively. These results illustrate that the characterization of the underlying work distribution permits an optimal use of the Jarzynski equality. © 2018 Wiley Periodicals, Inc. The Jarzynski equality is routinely used to compute equilibrium free‐energy differences from a set of non‐equilibrium work values. From a computational approach, these non‐equilibrium work values are often generated using steered Molecular Dynamics, and, under certain conditions a Gaussian distribution of nonequilibrium work values is to be anticipated. We highlight the advantage of parametric maximum‐likelihood estimators over the conventional use of the Jarzynski equality, when information about the distribution of nonequilibirum work values is available. [ABSTRACT FROM AUTHOR]

Background Intracellular transport requires molecular motors that step along cytoskeletal filaments actively dragging cargoes through the crowded cytoplasm. Here, we explore the interplay of the opposed polarity motors kinesin-1 and cytoplasmic dynein during peroxisome transport along microtubules in Drosophila S2 cells. Methods We used single particle tracking with nanometer accuracy and millisecond time resolution to extract quantitative information on the bidirectional motion of organelles. The transport performance was studied in cells expressing a slow chimeric plus-end directed motor or the kinesin heavy chain. We also analyzed the influence of peroxisomes membrane fluidity in methyl-β-ciclodextrin treated cells. The experimental data was also confronted with numerical simulations of two well-established tug of war scenarios. Results and conclusions The velocity distributions of retrograde and anterograde peroxisomes showed a multimodal pattern suggesting that multiple motor teams drive transport in either direction. The chimeric motors interfered with the performance of anterograde transport and also reduced the speed of the slowest retrograde team. In addition, increasing the fluidity of peroxisomes membrane decreased the speed of the slowest anterograde and retrograde teams. General significance Our results support the existence of a crosstalk between opposed-polarity motor teams. Moreover, the slowest teams seem to mechanically communicate with each other through the membrane to trigger transport. [ABSTRACT FROM AUTHOR]

Background: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. Methodology/Findings: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05–0.5 parasites/mL whereas specific kDNA tests detected 5.10−3 par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/µl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/µl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3–94.4%, specificity of 85–95%, accuracy of 86.8–89.5% and kappa index of 0.7–0.8 compared to consensus PCR reports of the 16 good performing tests and 63–69%, 100%, 71.4–76.2% and 0.4–0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. Conclusion/Significance: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples. Author Summary: A century after its discovery, Chagas disease, caused by the parasite Trypanosoma cruzi, still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The polymerase chain reaction (PCR) has been proposed as a sensitive laboratory tool for detection of T. cruzi infection and monitoring of parasitological treatment outcome. However, high variation in accuracy and lack of international quality controls has precluded reliable applications in the clinical practice and comparisons of data among cohorts and geographical regions. In an effort towards harmonization of PCR strategies, 26 expert laboratories from 16 countries evaluated their current PCR procedures against sets of control samples, composed by serial dilutions of T.cruzi DNA from culture stocks belonging to different lineages, human blood spiked with parasite cells and blood samples from Chagas disease patients. A high variability in sensitivities and specificities was found among the 48 reported PCR tests. Out of them, four tests with best performance were selected and further evaluated. This study represents a crucial first step towards device of a standardized operative procedure for T. cruzi PCR. [ABSTRACT FROM AUTHOR]

Background: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods indetection of Trypanosoma cruzi DNA by an external quality evaluation. Methodology/Findings: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.1023 par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/ml of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/ml for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. Conclusion/Significance: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples. [ABSTRACT FROM AUTHOR]

Stochastic ordinary differential equations may have solutions that explode in finite or infinite time. In this article we design an adaptive numerical scheme that reproduces the explosive behavior. The time step is adapted according to the size of the computed solution in such a way that, under adequate hypotheses, the explosion of the solutions is reproduced. [ABSTRACT FROM AUTHOR]