6,446 research outputs found

    Semi-Parametric Maximum Likelihood Estimates for ROC Curves of Continuous-Scale Tests

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    In this paper, we propose a semi-parametric maximum likelihood estimate of an ROC curve that satisfies the property of invariance of the ROC curve. In our simulation studies, we demonstrate that the proposed estimator has the best performance among all the existing semi-parametric estimators considered here. Finally, we illustrate the application of the proposed estimator using a real data set

    Semi-Parametric Maximum Likelihood Estimates for ROC Curves of Continuous-Scale Tests

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    In this paper, we propose a new semi-parametric maximum likelihood (ML) estimate of an ROC curve that satisfies the property of invariance of the ROC curve and is easy to compute. We show that our new estimator is [Formula: see text]-consistent and has an asymptotically normal distribution. Our extensive simulation studies show the proposed method is efficient, robust, and simple to compute. Finally, we illustrate the application of the proposed estimator in a real data set

    A Semi-Parametric Two-Part Mixed-Effects Heteroscedastic Transformation Model for Correlated Right-Skewed Semi-Continuous Data

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    In longitudinal or hierarchical structure studies, we often encounter a semi-continuous variable that has a certain proportion of a single value and a continuous and skewed distribution among the rest of values. In the paper, we propose a new semi-parametric two-part mixed-effects transformation model to fit correlated skewed semi-continuous data. In our model, we allow the transformation to be non-parametric. Fitting the proposed model faces computational challenges due to intractable numerical integrations. We derive the estimates for the parameter and the transformation function based on an approximate likelihood, which has high order accuracy but less computational burden. We also propose an estimator for the expected value of the semi-continuous outcome on the original-scale. Finally, we apply the proposed methods to a clinical study on effectiveness of a collaborative care treatment on late life depression on health care costs

    Microbial Interactions in Biofilms: Impacts on Homeostasis and Pathogenesis

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    Microbes in nature or in the human body are predominantly associated with surfaces and living in biofilms. Species diversity, high cell density and close proximity of cells are typical of life in biofilms, where organisms interact with each other and develop complex interactions that can be either competitive or cooperative. Competition between species is a well-recognized ecological force to drive microbial metabolism, diversity and evolution. However, it was not until recently that microbial cooperative activities are also recognized to play important roles in microbial physiology and ecology. Importantly, these microbial interactions in biofilms profoundly affect their overall function, biomass, diversity and pathogenesis. It is now known that every human body contains a personalized microbiome that is essential to maintain host health. Remarkably, the indigenous species in most microbial communities often maintain a relatively stable and harmless relationship with the hosts despite regular exposure to minor environmental perturbations and host defence factors. Such stability or homeostasis results from a dynamic balance of microbial–microbial and microbial–host interactions. Under some circumstances, however, the homeostasis may breakdown, predisposing a site to diseases. The evidence has accumulated that such biofilm or community-based diseases can be prevented or treated not only by targeting putative pathogens, but also by interfering with the processes that drive breakdown of the homeostasis in biofilms

    Structural and functional insights into a quorum-sensing signal peptide receptor, the ComD histidine protein kinase of streptococcus mutans

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    Quorum sensing activation by signal peptide pheromones (SP) in Gram-positive bacteria depends on a membrane-associated histidine kinase receptor, which senses the signal and triggers the signaling cascade for various cell density-dependent activities. However, relatively little is known of peptide pheromone-receptor interactions in these bacteria, largely because of technical challenges in working with membrane-associated proteins in these bacteria. Recently, we have described a genetic approach and several analysis methods to studying membrane topology and structure-function interaction of a quorum sensing pheromone receptor ComD in a Gram-positive bacterium Streptococcus mutans. Using these methods, we confirm that the membrane-spanning domain of the ComD protein forms six transmembrane segments and three extracellular loops, loopA, loopB and loopC. By mutational analyses of these three extracellular loops, we demonstrate that both loopC and loopB are required for signal recognition and quorum sensing activation, while loopA plays little role in signal detection. In particular, a deletion or substitution mutation of four residues NVIP within loopC abolishes signal recognition for quorum sensing activation. Consistent with these findings, the loopC and loopB mutants are completely or partially defective in bacteriocin production. We conclude that both loopC and loopB are required to form the signal peptide receptor and the residues NVIP of loopC are essential for signal recognition and quorum sensing activation in S. mutans

    Synthesis and characterization of 2-(2-benzhydrylnaphthyliminomethyl)pyridylnickel halides: formation of branched polyethylene

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    A series of 2-(2-benzhydrylnaphthyliminomethyl)pyridine derivatives (L1–L3) was prepared and used to synthesize the corresponding bis-ligated nickel(II) halide complexes (Ni1–Ni6) in good yield. The molecular structures of representative complexes, namely the bromide Ni3 and the chloride complex Ni6, were confirmed by single crystal X-ray diffraction, and revealed a distorted octahedral geometry at nickel. Upon activation with either methylaluminoxane (MAO) or modified methylaluminoxane (MMAO), all nickel complex pre-catalysts exhibited high activities (up to 2.02 × 10⁷ g(PE) mol⁻¹(Ni) h⁻¹) towards ethylene polymerization, producing branched polyethylene of low molecular weight and narrow polydispersity. The influence of the reaction parameters and the nature of the ligands on the catalytic behavior of the title nickel complexes were investigated
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