Ordinal Probit Functional Regression Models with Application to Computer-Use Behavior in Rhesus Monkeys

Research in functional regression has made great strides in expanding to non-Gaussian functional outcomes, however the exploration of ordinal functional outcomes remains limited. Motivated by a study of computer-use behavior in rhesus macaques (\emph{Macaca mulatta}), we introduce the Ordinal Probit Functional Regression Model or OPFRM to perform ordinal function-on-scalar regression. The OPFRM is flexibly formulated to allow for the choice of different basis functions including penalized B-splines, wavelets, and O'Sullivan splines. We demonstrate the operating characteristics of the model in simulation using a variety of underlying covariance patterns showing the model performs reasonably well in estimation under multiple basis functions. We also present and compare two approaches for conducting posterior inference showing that joint credible intervals tend to out perform point-wise credible. Finally, in application, we determine demographic factors associated with the monkeys' computer use over the course of a year and provide a brief analysis of the findings

Model Selection in Variational Mixed Effects Models

Variational inference is an alternative estimation technique for Bayesian models. Recent work shows that variational methods provide consistent estimation via efficient, deterministic algorithms. Other tools, such as model selection using variational AICs (VAIC) have been developed and studied for the linear regression case. While mixed effects models have enjoyed some study in the variational context, tools for model selection are lacking. One important feature of model selection in mixed effects models, particularly longitudinal models, is the selection of the random effects which in turn determine the covariance structure for the repeatedly sampled outcome. To address this, we derive a VAIC specifically for variational mixed effects (VME) models. We also implement a parameter-efficient VME as part of our study which reduces any general random effects structure down to a single subject-specific score. This model accommodates a wide range of random effect structures including random intercept and slope models as well as random functional effects. Our VAIC can model and perform selection on a variety of VME models including more classic longitudinal models as well as longitudinal scalar-on-function regression. As we demonstrate empirically, our VAIC performs well in discriminating between correctly and incorrectly specified random effects structures. Finally, we illustrate the use of VAICs for VMEs on two datasets: a study of lead levels in children and a study of diffusion tensor imaging

Bayesian Analysis of Multivariate Matched Proportions with Sparse Response

Multivariate matched proportions (MMP) data appears in a variety of contexts including post-market surveillance of adverse events in pharmaceuticals, disease classification, and agreement between care providers. It consists of multiple sets of paired binary measurements taken on the same subject. While recent work proposes non-Bayesian methods to address the complexities of MMP data, the issue of sparse response, where no or very few "yes" responses are recorded for one or more sets, is unaddressed. The presence of sparse response sets results in underestimates of variance, loss of coverage, and lowered power in existing methods. Bayesian methods have not previously been considered for MMP data but provide a useful framework when sparse responses are present. In particular, the Bayesian probit model provides an elegant solution to the problem of variance underestimation. We examine three approaches built on that model: a naive analysis with flat priors, a penalized analysis using half-Cauchy priors on the mean model variances, and a multivariate analysis with a Bayesian functional principal component analysis (FPCA) to model the latent covariance. We show that the multivariate analysis performs well on MMP data with sparse responses and outperforms existing non-Bayesian methods. In a re-analysis of data from a study of the system of care (SOC) framework for children with mental and behavioral disorders, we are able to provide a more complete picture of the relationships in the data. Our analysis provides additional insights into the functioning on the SOC that a previous univariate analysis missed

Heads or tails: L1 insertion-associated 5' homopolymeric sequences

<p>Abstract</p> <p>Background</p> <p>L1s are one of the most successful autonomous mobile elements in primate genomes. These elements comprise as much as 17% of primate genomes with the majority of insertions occurring via target primed reverse transcription (TPRT). Twin priming, a variant of TPRT, can result in unusual DNA sequence architecture. These insertions appear to be inverted, truncated L1s flanked by target site duplications.</p> <p>Results</p> <p>We report on loci with sequence architecture consistent with variants of the twin priming mechanism and introduce dual priming, a mechanism that could generate similar sequence characteristics. These insertions take the form of truncated L1s with hallmarks of classical TPRT insertions but having a poly(T) simple repeat at the 5' end of the insertion. We identified loci using computational analyses of the human, chimpanzee, orangutan, rhesus macaque and marmoset genomes. Insertion site characteristics for all putative loci were experimentally verified.</p> <p>Conclusions</p> <p>The 39 loci that passed our computational and experimental screens probably represent inversion-deletion events which resulted in a 5' inverted poly(A) tail. Based on our observations of these loci and their local sequence properties, we conclude that they most probably represent twin priming events with unusually short non-inverted portions. We postulate that dual priming could, theoretically, produce the same patterns. The resulting homopolymeric stretches associated with these insertion events may promote genomic instability and create potential target sites for future retrotransposition events.</p

Variability and Proper Motion of X-ray Knots in the Jet of Centaurus A

Accepted to ApJ, 14 pages, 8 figures, 2 tablesWe report results from Chandra observations analyzed for evidence of variability and proper motion in the X-ray jet of Centaurus A. Using data spanning 15 yr, collective proper motion of 11.3 ± 3.3 mas yr -1 , or 0.68 ± 0.20c, is detected for the fainter X-ray knots and other substructure present within the jet. The three brightest knots (AX1A, AX1C, and BX2) are found to be stationary to an upper limit of . Brightness variations up to 27% are detected for several X-ray knots in the jet. For the fading knots, BX2 and AX1C, the changes in spectral slope expected to accompany synchrotron cooling are not found, ruling it out and placing upper limits of ≃80 μG for each of their magnetic field strengths. Adiabatic expansion can account for the observed decreases in brightness. Constraints on models for the origin of the knots are established. Jet plasma overrunning an obstacle is favored as the generator of stationary knots, while moving knots are likely produced either by internal differences in jet speed or the late stages of jet interaction with nebular or cloud material.Peer reviewe

Stability transitions for axisymmetric relative equilibria of Euclidean symmetric Hamiltonian systems

In the presence of noncompact symmetry, the stability of relative equilibria under momentum-preserving perturbations does not generally imply robust stability under momentum-changing perturbations. For axisymmetric relative equilibria of Hamiltonian systems with Euclidean symmetry, we investigate different mechanisms of stability: stability by energy-momentum confinement, KAM, and Nekhoroshev stability, and we explain the transitions between these. We apply our results to the Kirchhoff model for the motion of an axisymmetric underwater vehicle, and we numerically study dissipation induced instability of KAM stable relative equilibria for this system.Comment: Minor revisions. Typographical errors correcte

A comprehensive fate map by intracellular injection of identified blastomeres in the marine polychaete Capitella teleta

<p>Abstract</p> <p>Background</p> <p>The polychaete annelid <it>Capitella teleta </it>(formerly <it>Capitella </it>sp. I) develops by spiral cleavage and has been the focus of several recent developmental studies aided by a fully sequenced genome. Fate mapping in polychaetes has lagged behind other spiralian taxa, because of technical limitations.</p> <p>Results</p> <p>To generate a modern fate map for <it>C. teleta</it>, we injected 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) into individual identified blastomeres through fourth-quartet micromere formation. Confocal laser scanning microscopy at single-cell resolution was used to characterize blastomere fates during larval stages. Our results corroborate previous observations from classic studies, and show a number of similarities with other spiralian fate maps, including unique and stereotypic fates for individual blastomeres, presence of four discrete body domains arising from the A, B, C and D cell quadrants, generation of anterior ectoderm from first quartet micromeres, and contributions to trunk ectoderm and ventral nerve cord by the 2d somatoblast. Of particular interest are several instances in which the <it>C. teleta </it>fate map deviates from other spiralian fate maps. For example, we identified four to seven distinct origins of mesoderm, all ectomesodermal. In addition, the left and right mesodermal bands arise from 3d and 3c, respectively, whereas 4d generates a small number of trunk muscle cells, the primordial germ cells and the anus. We identified a complex set of blastomere contributions to the posterior gut in <it>C. teleta</it>, which establishes the most complete map of posterior gut territories to date.</p> <p>Conclusions</p> <p>Our detailed cellular descriptions reveal previously underappreciated complexity in the ontogenetic contributions to several spiralian larval tissues, including the mesoderm, nervous system and gut. The formation of the mesodermal bands by 3c and 3d is in stark contrast to other spiralians, in which 4d generates the mesodermal bands. The results of this study provide a framework for future phylogenetic comparisons and functional analyses of cell-fate specification.</p

Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-derived Mesenchymal Stem Cells

Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARγ are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSCs). As assessed by ChIP-sequencing and RNA-sequencing analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPβ, retinoid X receptor, and vitamin D receptor binding sites, whereas adipocyte differentiation favored PPARγ, retinoid X receptor, C/EBPα, and C/EBPβ binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg, and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment, as assessed by staining, gene expression, and ChIP-quantitative PCR analysis. The osteogenic default pathway may be subverted during pathological conditions, leading to skeletal fragility and increased marrow adiposity during aging, estrogen deficiency, and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies