Multivariate Distributions of Correlated Binary Variables Generated by Pair-Copulas

Correlated binary data are prevalent in a wide range of scientific disciplines, including healthcare and medicine. The generalized estimating equations (GEEs) and the multivariate probit (MP) model are two of the popular methods for analyzing such data. However, both methods have some significant drawbacks. The GEEs may not have an underlying likelihood and the MP model may fail to generate a multivariate binary distribution with specified marginals and bivariate correlations. In this paper, we study multivariate binary distributions that are based on D-vine pair-copula models as a superior alternative to these methods. We elucidate the construction of these binary distributions in two and three dimensions with numerical examples. For higher dimensions, we provide a method of constructing a multidimensional binary distribution with specified marginals and equicorrelated correlation matrix. We present a real-life data analysis to illustrate the application of our results

D-Vine Copula Model For Dependent Binary Data

High-dimensional dependent binary data are prevalent in a wide range of scientific disciplines. A popular method for analyzing such data is the Multivariate Probit (MP) model. But the MP model sometimes fails even within a feasible range of binary correlations, because the underlying correlation matrix of the latent variables may not be positive definite. In this research, we proposed pair copula models, assuming the dependence between the binary variables is first order autoregressive (AR(1))or equicorrelated structure. Also, when Archimediean copula is used, most paper converted Kendall Tau to corresponding copula parameter, there is no explicit function of Pearson’s correlation coefficient with copula parameter. Therefore, we obtain the relationship between binary variable coefficient with copula parameter in the study as well. The outline of this poster presentation is as follows: we start with the definition of the copula and pictorially illustrate the relation between the copula parameter and the binary correlation. We illustrate pair copula constructions of multivariate binary distributions using D-vines and C-vines. We show the application of our method on a real life data. Finally, we briefly discuss our ongoing research.https://digitalcommons.odu.edu/gradposters2020_sciences/1003/thumbnail.jp

B\"{a}cklund transformations for high-order constrained flows of the AKNS hierarchy: canonicity and spectrality property

New infinite number of one- and two-point B\"{a}cklund transformations (BTs) with explicit expressions are constructed for the high-order constrained flows of the AKNS hierarchy. It is shown that these BTs are canonical transformations including B\"{a}cklund parameter $\eta$ and a spectrality property holds with respect to $\eta$ and the 'conjugated' variable $\mu$ for which the point $(\eta, \mu)$ belongs to the spectral curve. Also the formulas of m-times repeated Darboux transformations for the high-order constrained flows of the AKNS hierarchy are presented.Comment: 21 pages, Latex, to be published in J. Phys.

A role for heritable transcriptomic variation in maize adaptation to temperate environments

Background: Transcription bridges genetic information and phenotypes. Here, we evaluated how changes in transcriptional regulation enable maize (Zea mays), a crop originally domesticated in the tropics, to adapt to temperate environments. Result: We generated 572 unique RNA-seq datasets from the roots of 340 maize genotypes. Genes involved in core processes such as cell division, chromosome organization and cytoskeleton organization showed lower heritability of gene expression, while genes involved in anti-oxidation activity exhibited higher expression heritability. An expression genome-wide association study (eGWAS) identified 19,602 expression quantitative trait loci (eQTLs) associated with the expression of 11,444 genes. A GWAS for alternative splicing identified 49,897 splicing QTLs (sQTLs) for 7614 genes. Genes harboring both cis-eQTLs and cis-sQTLs in linkage disequilibrium were disproportionately likely to encode transcription factors or were annotated as responding to one or more stresses. Independent component analysis of gene expression data identified loci regulating co-expression modules involved in oxidation reduction, response to water deprivation, plastid biogenesis, protein biogenesis, and plant-pathogen interaction. Several genes involved in cell proliferation, flower development, DNA replication, and gene silencing showed lower gene expression variation explained by genetic factors between temperate and tropical maize lines. A GWAS of 27 previously published phenotypes identified several candidate genes overlapping with genomic intervals showing signatures of selection during adaptation to temperate environments. Conclusion: Our results illustrate how maize transcriptional regulatory networks enable changes in transcriptional regulation to adapt to temperate regions

A role for heritable transcriptomic variation in maize adaptation to temperate environments

Background: Transcription bridges genetic information and phenotypes. Here, we evaluated how changes in transcriptional regulation enable maize (Zea mays), a crop originally domesticated in the tropics, to adapt to temperate environments. Result: We generated 572 unique RNA-seq datasets from the roots of 340 maize genotypes. Genes involved in core processes such as cell division, chromosome organization and cytoskeleton organization showed lower heritability of gene expression, while genes involved in anti-oxidation activity exhibited higher expression heritability. An expression genome-wide association study (eGWAS) identified 19,602 expression quantitative trait loci (eQTLs) associated with the expression of 11,444 genes. A GWAS for alternative splicing identified 49,897 splicing QTLs (sQTLs) for 7614 genes. Genes harboring both cis-eQTLs and cis-sQTLs in linkage disequilibrium were disproportionately likely to encode transcription factors or were annotated as responding to one or more stresses. Independent component analysis of gene expression data identified loci regulating co-expression modules involved in oxidation reduction, response to water deprivation, plastid biogenesis, protein biogenesis, and plant-pathogen interaction. Several genes involved in cell proliferation, flower development, DNA replication, and gene silencing showed lower gene expression variation explained by genetic factors between temperate and tropical maize lines. A GWAS of 27 previously published phenotypes identified several candidate genes overlapping with genomic intervals showing signatures of selection during adaptation to temperate environments. Conclusion: Our results illustrate how maize transcriptional regulatory networks enable changes in transcriptional regulation to adapt to temperate regions

Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins.

The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P < 0.006) or hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-microns section averaged 47% +/- 4% (P < 0.001) and 37% +/- 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66%, respectively. No retinal toxicity was observed by light microscopy. These data demonstrate VEGF's causal role in retinal angiogenesis and prove the potential of VEGF inhibition as a specific therapy for ischemic retinal disease

An Immunoassay for Dibutyl Phthalate Based on Direct Hapten Linkage to the Polystyrene Surface of Microtiter Plates

BACKGROUND: Dibutyl phthalate (DBP) is predominantly used as a plasticizer inplastics to make them flexible. Extensive use of phthalates in both industrial processes and other consumer products has resulted in the ubiquitous presence of phthalates in the environment. In order to better determine the level of pollution in the environment and evaluate the potential adverse effects of exposure to DBP, immunoassay for DBP was developed. METHODOLOGY/PRINCIPAL FINDINGS: A monoclonal antibody specific to DBP was produced from a stable hybridoma cell line generated by lymphocyte hybridoma technique. An indirect competitive enzyme-linked immunosorbent assay (icELISA) employing direct coating of hapten on polystyrene microtiter plates was established for the detection of DBP. Polystyrene surface was first oxidized by permanganate in dilute sulfuric acid to generate carboxyl groups. Then dibutyl 4-aminophthalate, which is an analogue of DBP, was covalently linked to the carboxyl groups of polystyrene surface with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Compared with conjugate coated format (IC(50)=106 ng/mL), the direct hapten coated format (IC(50)=14.6 ng/mL) improved assay sensitivity after careful optimization of assay conditions. The average recovery of DBP from spiked water sample was 104.4% and the average coefficient of variation was 9.95%. Good agreement of the results obtained by the hapten coated icELISA and gas chromatography-mass spectrometry further confirmed the reliability and accuracy of the icELISA for the detection of DBP in certain plastic and cosmetic samples. CONCLUSIONS/SIGNIFICANCE: The stable and efficient hybridoma cell line obtained is an unlimited source of sensitive and specific antibody to DBP. The hapten coated format is proposed as generally applicable because the carboxyl groups on modified microtiter plate surface enables stable immobilization of aminated or hydroxylated hapten with EDC. The developed hapten coated icELISA can be used as a convenient quantitative tool for the sensitive and accurate monitoring DBP in water, plastic and cosmetic samples

Observation of ηc→ωω\eta_c\to\omega\omega in J/ψ→γωωJ/\psi\to\gamma\omega\omega

Using a sample of $(1310.6\pm7.0)\times10^6$ $J/\psi$ events recorded with the BESIII detector at the symmetric electron positron collider BEPCII, we report the observation of the decay of the $(1^1 S_0)$ charmonium state $\eta_c$ into a pair of $\omega$ mesons in the process $J/\psi\to\gamma\omega\omega$. The branching fraction is measured for the first time to be $\mathcal{B}(\eta_c\to\omega\omega)= (2.88\pm0.10\pm0.46\pm0.68)\times10^{-3}$, where the first uncertainty is statistical, the second systematic and the third is from the uncertainty of $\mathcal{B}(J/\psi\to\gamma\eta_c)$. The mass and width of the $\eta_c$ are determined as $M=(2985.9\pm0.7\pm2.1)\,$MeV/$c^2$ and $\Gamma=(33.8\pm1.6\pm4.1)\,$MeV.Comment: 13 pages, 6 figure

Observation and study of the decay J/ψ→ϕηη′J/\psi\rightarrow\phi\eta\eta'

We report the observation and study of the decay $J/\psi\rightarrow\phi\eta\eta'$ using $1.3\times{10^9}$ $J/\psi$ events collected with the BESIII detector. Its branching fraction, including all possible intermediate states, is measured to be $(2.32\pm0.06\pm0.16)\times{10^{-4}}$. We also report evidence for a structure, denoted as $X$, in the $\phi\eta'$ mass spectrum in the $2.0-2.1$ GeV/$c^2$ region. Using two decay modes of the $\eta'$ meson ($\gamma\pi^+\pi^-$ and $\eta\pi^+\pi^-$), a simultaneous fit to the $\phi\eta'$ mass spectra is performed. Assuming the quantum numbers of the $X$ to be $J^P = 1^-$, its significance is found to be 4.4$\sigma$, with a mass and width of $(2002.1 \pm 27.5 \pm 21.4)$ MeV/$c^2$ and $(129 \pm 17 \pm 9)$ MeV, respectively, and a product branching fraction $\mathcal{B}(J/\psi\rightarrow\eta{}X)\times{}\mathcal{B}(X\rightarrow\phi\eta')=(9.8 \pm 1.2 \pm 1.7)\times10^{-5}$. Alternatively, assuming $J^P = 1^+$, the significance is 3.8$\sigma$, with a mass and width of $(2062.8 \pm 13.1 \pm 7.2)$ MeV/$c^2$ and $(177 \pm 36 \pm 35)$ MeV, respectively, and a product branching fraction $\mathcal{B}(J/\psi\rightarrow\eta{}X)\times{}\mathcal{B}(X\rightarrow\phi\eta')=(9.6 \pm 1.4 \pm 2.0)\times10^{-5}$. The angular distribution of $J/\psi\rightarrow\eta{}X$ is studied and the two $J^P$ assumptions of the $X$ cannot be clearly distinguished due to the limited statistics. In all measurements the first uncertainties are statistical and the second systematic.Comment: 10 pages, 6 figures and 4 table