Sex, lies and self-reported counts: Bayesian mixture models for heaping in longitudinal count data via birth-death processes

Surveys often ask respondents to report nonnegative counts, but respondents may misremember or round to a nearby multiple of 5 or 10. This phenomenon is called heaping, and the error inherent in heaped self-reported numbers can bias estimation. Heaped data may be collected cross-sectionally or longitudinally and there may be covariates that complicate the inferential task. Heaping is a well-known issue in many survey settings, and inference for heaped data is an important statistical problem. We propose a novel reporting distribution whose underlying parameters are readily interpretable as rates of misremembering and rounding. The process accommodates a variety of heaping grids and allows for quasi-heaping to values nearly but not equal to heaping multiples. We present a Bayesian hierarchical model for longitudinal samples with covariates to infer both the unobserved true distribution of counts and the parameters that control the heaping process. Finally, we apply our methods to longitudinal self-reported counts of sex partners in a study of high-risk behavior in HIV-positive youth.Comment: Published at http://dx.doi.org/10.1214/15-AOAS809 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Implementation of a standard format for GPS common view data

A new format for standardizing common view time transfer data, recommended by the Consultative Committee for the Definition of the Second, is being implemented in receivers commonly used for contributing data for the generation of International Atomic Time. We discuss three aspects of this new format that potentially improve GPS common-view time transfer: (1) the standard specifies the method for treating short term data, (2) it presents data in consistent formats including needed terms not previously available, and (3) the standard includes a header of parameters important for the GPS common-view process. In coordination with the release of firmware conforming to this new format the Bureau International des Poids et Mesures will release future international track schedules consistent with the new standard

A comparison of GPS broadcast and DMA precise ephemerides

We compare the broadcast ephemerides from Global Positioning Satellites (GPS) to the postprocessed ephemerides from the Defense Mapping Agency (DMA). We find significant energy in the spectrum of the residuals at 1 cycle/day and higher multiples. We estimate the time variance of the residuals and show that the short term residuals, from 15 min, exhibit power law processes with greater low frequency perturbations than white phase modulation. We discuss the significance of these results for the performance of the GPS Kalman filter which estimates the broadcast orbits

3He-Driven Mixing in Low-Mass Red Giants: Convective Instability in Radiative and Adiabatic Limits

We examine the stability and observational consequences of mixing induced by 3He burning in the envelopes of first ascent red giants. We demonstrate that there are two unstable modes: a rapid, nearly adiabatic mode that we cannot identify with an underlying physical mechanism, and a slow, nearly radiative mode that can be identified with thermohaline convection. We present observational constraints that make the operation of the rapid mode unlikely to occur in real stars. Thermohaline convection turns out to be fast enough only if fluid elements have finger-like structures with a length to diameter ratio l/d > 10. We identify some potentially serious obstacles for thermohaline convection as the predominant mixing mechanism for giants. We show that rotation-induced horizontal turbulent diffusion may suppress the 3He-driven thermohaline convection. Another potentially serious problem for it is to explain observational evidence of enhanced extra mixing. The 3He exhaustion in stars approaching the red giant branch (RGB) tip should make the 3He mixing inefficient on the asymptotic giant branch (AGB). In spite of this, there are observational data indicating the presence of extra mixing in low-mass AGB stars similar to that operating on the RGB. Overmixing may also occur in carbon-enhanced metal-poor stars.Comment: 25 pages, 6 figures, modified version, accepted by Ap

Multi-island single-electron devices from self-assembled colloidal nanocrystal chains

We report the fabrication of multi-island single-electron devices made by lithographic contacting of self-assembled alkanethiol-coated gold nanocrystals. The advantages of this method, which bridges the dimensional gap between lithographic and NC sizes, are (1) that all tunnel junctions are defined by self-assembly rather than lithography and (2) that the ratio of gate capacitance to total capacitance is high. The rich electronic behavior of a double-island device, measured at 4.2 K, is predicted in detail by combining finite element and Monte Carlo simulations with the standard theory of Coulomb blockade with very few adjustable parameters.Comment: 4 page

Gene expression in Leishmania is regulated predominantly by gene dosage

ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy

Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity

Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation) are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for ‘synthetic cellular heterogeneity’ that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism), demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a ‘phenotypic sensitivity analysis’ method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in isolation, and its impact on overall system performance once integrated.National Institutes of Health (U.S.) (NIH NIGMS grant R01GM086881)National Science Foundation (U.S.) (NSF Award #1001092)National Science Foundation (U.S.) (NSF Graduate Research Fellowship Program)Swiss National Science Foundation (SystemsX.ch grant

Markers of Inflammation and Fibrosis in Alcoholic Hepatitis and Viral Hepatitis C

High levels of profibrinogenic cytokine transforming factor beta (TGF-β), metalloprotease (MMP2), and tissue inhibitor of matrix metalloprotease 1 (TIMP1) contribute to fibrogenesis in hepatitis C virus (HCV) infection and in alcohol-induced liver disease (ALD). The aim of our study was to correlate noninvasive serum markers in ALD and HCV patients with various degrees of inflammation and fibrosis in their biopsies. Methods. Serum cytokines levels in HCV-infected individuals in the presence or absence of ALD were measured. Student's-t-test with Bonferroni correction determined the significance between the groups. Results. Both tumor-necrosis-factor- (TNF)-α and TGF-β levels increased significantly with the severity of inflammation and fibrosis. TGF-β levels increased significantly in ALD patients versus the HCV patients. Proinflammatory cytokines' responses to viral and/or toxic injury differed with the severity of liver inflammation. A combination of these markers was useful in predicting and diagnosing the stages of inflammation and fibrosis in HCV and ALD. Conclusion. Therapeutic monitoring of TGF-β and metalloproteases provides important insights into fibrosis