Variational Bayes Estimation of Discrete-Margined Copula Models with Application to Time Series

We propose a new variational Bayes estimator for high-dimensional copulas with discrete, or a combination of discrete and continuous, margins. The method is based on a variational approximation to a tractable augmented posterior, and is faster than previous likelihood-based approaches. We use it to estimate drawable vine copulas for univariate and multivariate Markov ordinal and mixed time series. These have dimension $rT$, where $T$ is the number of observations and $r$ is the number of series, and are difficult to estimate using previous methods. The vine pair-copulas are carefully selected to allow for heteroskedasticity, which is a feature of most ordinal time series data. When combined with flexible margins, the resulting time series models also allow for other common features of ordinal data, such as zero inflation, multiple modes and under- or over-dispersion. Using six example series, we illustrate both the flexibility of the time series copula models, and the efficacy of the variational Bayes estimator for copulas of up to 792 dimensions and 60 parameters. This far exceeds the size and complexity of copula models for discrete data that can be estimated using previous methods

Caenorhabditis elegans as a model system for studying drug induced mitochondrial toxicity

Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegansto study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase

Using Counterexample Generation and Theory Exploration to Suggest Missing Hypotheses

Newcomers to ACL2 are sometimes surprised that ACL2 rejects formulas that they believe should be theorems, such as (REVERSE (REVERSE X)) = X. Experienced ACL2 users will recognize that the theorem only holds for intended values of X, and given ACL2's total logic, there are many counterexamples for which this formula is simply not true. Counterexample generation (cgen) is a technique that helps by giving the user a number of counterexamples (and also witnesses) to the formula, e.g., letting the user know that the intended theorem is false when X is equal to 10. In this paper we describe a tool called DrLA that goes further by suggesting additional hypotheses that will make the theorem true. In this case, for example, DrLA may suggest that X needs to be either a TRUE-LIST or a STRING. The suggestions are discovered using the ideas of theory exploration and subsumption from automated theorem proving.Comment: In Proceedings ACL2-2023, arXiv:2311.0837

Applying Multiple Imputation with Geostatistical Models to Account for Item Nonresponse in Environmental Data

Methods proposed to solve the missing data problem in estimation procedures should consider the type of missing data, the missing data mechanism, the sampling design and the availability of auxiliary variables correlated with the process of interest. This article explores the use of geostatistical models with multiple imputation to deal with missing data in environmental surveys. The method is applied to the analysis of data generated from a probability survey to estimate Coho salmon abundance in streams located in western Oregon watersheds

Gestión de almacenes para mejorar el nivel de servicio al cliente en una empresa agrícola Chepén 2021

La presente investigación tuvo como objetivo Determinar de qué manera la gestión de almacenes mejorará el nivel de servicio al cliente en la empresa agrícola Chepén 2021. Se utilizó una metodología deductiva, enfoque cuantitativo, tipo descriptivo, no experimental y corte transversal, la cual incluyó a una población de 67 con una muestra de 57 colaboradores. Se aplicó como instrumento el cuestionario, cuyos resultados se procesaron con el Programa IBM SPSS Statistics v.25. Los resultados obtenidos reflejan, que en la variable independiente y dependiente expresan que el 34% y el 44% en un nivel Medio, dando un grado de confiabilidad de 0.895 y 0.842 correspondientemente, ante ello se acepta la hipótesis de investigación con un Sig. bilateral 0,000<0,05 alterna, en donde la gestión de almacenes mejora el nivel de servicio al cliente de la Empresa Agrícola Chepén 2021.TesisGestión empresarial y emprendimient

Mannose binding lectin is required for alphavirus-induced arthritis/myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.This work was supported by NIH/NIAMS R01 AR 047190 awarded to MTH

Silencing CHALCONE SYNTHASE in maize impedes the incorporation of tricin into lignin and increases lignin content

Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant produces highly reduced levels of apigenin-and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in beta-beta and beta-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production