Computational Aspects of Optional P\'{o}lya Tree

Optional P\'{o}lya Tree (OPT) is a flexible non-parametric Bayesian model for density estimation. Despite its merits, the computation for OPT inference is challenging. In this paper we present time complexity analysis for OPT inference and propose two algorithmic improvements. The first improvement, named Limited-Lookahead Optional P\'{o}lya Tree (LL-OPT), aims at greatly accelerate the computation for OPT inference. The second improvement modifies the output of OPT or LL-OPT and produces a continuous piecewise linear density estimate. We demonstrate the performance of these two improvements using simulations

In vivo quantification of embryonic and placental growth during gestation in mice using micro-ultrasound

<p>Abstract</p> <p>Background</p> <p>Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains.</p> <p>Methods</p> <p>We used 30–40 MHz ultrasound to quantify embryonic and placental morphometry in isoflurane-anesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5.</p> <p>Results</p> <p>Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%.</p> <p>Conclusion</p> <p>Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero.</p

Satellite assessment of land surface evapotranspiration for the pan-Arctic domain

Regional evapotranspiration (ET), including water loss from plant transpiration and soil evaporation, is essential to understanding interactions between land-atmosphere surface energy and water balances. Vapor pressure deficit (VPD) and surface air temperature are key variables for stomatal conductance and ET estimation. We developed an algorithm to estimate ET using the Penman-Monteith approach driven by Moderate Resolution Imaging Spectroradiometer (MODIS)-derived vegetation data and daily surface meteorological inputs including incoming solar radiation, air temperature, and VPD. The model was applied using alternate daily meteorological inputs, including (1) site level weather station observations, (2) VPD and air temperature derived from the Advanced Microwave Scanning Radiometer (AMSR-E) on the EOS Aqua satellite, and (3) Global Modeling and Assimilation Office (GMAO) reanalysis meteorology-based surface air temperature, humidity, and solar radiation data. Model performance was assessed across a North American latitudinal transect of six eddy covariance flux towers representing northern temperate grassland, boreal forest, and tundra biomes. Model results derived from the three meteorology data sets agree well with observed tower fluxes (r \u3e 0.7; P \u3c 0.003; root mean square error of latent heat flux \u3c30 W m−2) and capture spatial patterns and seasonal variability in ET. The MODIS-AMSR-E–derived ET results also show similar accuracy to ET results derived from GMAO, while ET estimation error was generally more a function of algorithm parameterization than differences in meteorology drivers. Our results indicate significant potential for regional mapping and monitoring daily land surface ET using synergistic information from satellite optical IR and microwave remote sensing

Reducing Interanalyst Variability in Photovoltaic Degradation Rate Assessments

The economic return on investment of a commercial photovoltaic system depends greatly on its performance over the long term and, hence, its degradation rate. Many methods have been proposed for assessing system degradation rates from outdoor performance data. However, comparing reported values from one analyst and research group to another requires a common baseline of performance; consistency between methods and analysts can be a challenge. An interlaboratory study was conducted involving different volunteer analysts reporting on the same photovoltaic performance data using different methodologies. Initial variability of the reported degradation rates was so high that analysts could not come to a consensus whether a system degraded or not. More consistent values are received when written guidance is provided to each analyst. Further improvements in analyst variance was accomplished by using the free open-source software RdTools, allowing a reduction in variance between analysts by more than two orders of magnitude over the first round, where multiple analysis methods are allowed. This article highlights many pitfalls in conducting 'routine' degradation analysis, and it addresses some of the factors that must be considered when comparing degradation results reported by different analysts or methods

High resolution ultrasound-guided microinjection for interventional studies of early embryonic and placental development in vivo in mice

BACKGROUND: In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5–E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure. RESULTS: In 40 MHz ultrasound images at E6.5, the ectoplacental cone region and proamniotic cavity could be visualized. The ectoplacental cone region was successfully targeted with 13.8 nL of a fluorescent bead suspension with few or no beads off-target in 51% of concepti microinjected at E6.5 (28/55 injected). Seventy eight percent of the embryos survived 2 to 12 days post injection (93/119), 73% (41/56) survived to term of which 68% (38/56) survived and appeared normal one week after birth. At E7.5, the amniotic and exocoelomic cavities, and ectoplacental cone region were discernable. Our success at targeting with few or no beads off-target was 90% (36/40) for the ectoplacental cone region and 81% (35/43) for the exocoelomic cavity but tended to be less, 68% (34/50), for the smaller amniotic cavity. At E11.5, beads microinjected at E7.5 into the ectoplacental cone region were found in the placental spongiotrophoblast layer, those injected into the exocoelomic cavity were found on the surface or within the placental labyrinth, and those injected into the amniotic cavity were found on the surface or within the embryo. Following microinjection at E7.5, survival one week after birth was 60% (26/43) when the amniotic cavity was the target and 66% (19/29) when the target was the ectoplacental cone region. The survival rate was similar in sham experiments, 54% (33/61), for which procedures were identical but no microinjection was performed, suggesting that surgery and manipulation of the uterus were the main causes of embryonic death. CONCLUSION: Ultrasound-guided microinjection into the ectoplacental cone region at E6.5 or E7.5 and the amniotic cavity at E7.5 was achieved with a 7 day postnatal survival of ≥60%. Target accuracy of these sites and of the exocoelomic cavity at E7.5 was ≥51%. We suggest that this approach may be useful for exploring gene function during early placental and embryonic development

Separating the influence of temperature, drought, and fire on interannual variability in atmospheric CO 2

The response of the carbon cycle in prognostic Earth system models (ESMs) contributes significant uncertainty to projections of global climate change. Quantifying contributions of known drivers of interannual variability in the growth rate of atmospheric carbon dioxide (CO 2 ) is important for improving the representation of terrestrial ecosystem processes in these ESMs. Several recent studies have identified the temperature dependence of tropical net ecosystem exchange (NEE) as a primary driver of this variability by analyzing a single, globally averaged time series of CO 2 anomalies. Here we examined how the temporal evolution of CO 2 in different latitude bands may be used to separate contributions from temperature stress, drought stress, and fire emissions to CO 2 variability. We developed atmospheric CO 2 patterns from each of these mechanisms during 1997–2011 using an atmospheric transport model. NEE responses to temperature, NEE responses to drought, and fire emissions all contributed significantly to CO 2 variability in each latitude band, suggesting that no single mechanism was the dominant driver. We found that the sum of drought and fire contributions to CO 2 variability exceeded direct NEE responses to temperature in both the Northern and Southern Hemispheres. Additional sensitivity tests revealed that these contributions are masked by temporal and spatial smoothing of CO 2 observations. Accounting for fires, the sensitivity of tropical NEE to temperature stress decreased by 25% to 2.9 ± 0.4 Pg C yr −1  K −1 . These results underscore the need for accurate attribution of the drivers of CO 2 variability prior to using contemporary observations to constrain long‐term ESM responses. Key Points Accurate attribution of CO 2 variability is required to constrain coupled models Combined influence of drought and fire exceed ecosystem responses to temperature Temporal and spatial smoothing of CO 2 observations masks variability from firePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109962/1/gbc20215.pd

An ensemble approach to accurately detect somatic mutations using SomaticSeq

SomaticSeq is an accurate somatic mutation detection pipeline implementing a stochastic boosting algorithm to produce highly accurate somatic mutation calls for both single nucleotide variants and small insertions and deletions. The workflow currently incorporates five state-of-the-art somatic mutation callers, and extracts over 70 individual genomic and sequencing features for each candidate site. A training set is provided to an adaptively boosted decision tree learner to create a classifier for predicting mutation statuses. We validate our results with both synthetic and real data. We report that SomaticSeq is able to achieve better overall accuracy than any individual tool incorporated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0758-2) contains supplementary material, which is available to authorized users

Multiple Transporters Associated with Malaria Parasite Responses to Chloroquine and Quinine

Mutations and/or overexpression of various transporters are known to confer drug resistance in a variety of organisms. In the malaria parasite Plasmodium falciparum, a homologue of P-glycoprotein, PfMDR1, has been implicated in responses to chloroquine (CO), quinine (ON) and other drugs, and a putative transporter, PfCRT, was recently demonstrated to be the key molecule in CO resistance. However, other unknown molecules are probably involved, as different parasite clones carrying the same pfcrt and pfmdr1 alleles show a wide range of quantitative responses to CO and ON. Such molecules may contribute to increasing incidences of ON treatment failure, the molecular basis of which is not understood. To identify additional genes involved in parasite CO and ON responses, we assayed the in vitro susceptibilities of 97 culture-adapted cloned isolates to CO and ON and searched for single nucleotide polymorphisms (SNPs) in DNA encoding 49 putative transporters (total 113 kb) and in 39 housekeeping genes that acted as negative controls. SNPs in 11 of the putative transporter genes, including pfcrt and pfmdr1, showed significant associations with decreased sensitivity to CQ and/or ON in P. faliparum. Significant linkage disequilibria within and between these genes were also detected, suggesting interactions among the transporter genes. This study provides specific leads for better understanding of complex drug resistances in malaria parasite