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At least 19 records

flowVS: channel-specific variance stabilization in flow cytometry

Abstract Background Comparing phenotypes of heterogeneous cell populations from multiple biological conditions is at the heart of scientific discovery based on flow cytometry (FC). When the biological signal is measured by the average expression of a biomarker, standard statistical methods require that variance be approximately stabilized in populations to be compared. Since the mean and variance of a cell population are often correlated in fluorescence-based FC measurements, a preprocessing step is needed to stabilize the within-population variances. Results We present a variance-stabilization algorithm, called flowVS, that removes the mean-variance correlations from cell populations identified in each fluorescence channel. flowVS transforms each channel from all samples of a data set by the inverse hyperbolic sine (asinh) transformation. For each channel, the parameters of the transformation are optimally selected by Bartlett’s likelihood-ratio test so that the populations attain homogeneous variances. The optimum parameters are then used to transform the corresponding channels in every sample. flowVS is therefore an explicit variance-stabilization method that stabilizes within-population variances in each channel by evaluating the homoskedasticity of clusters with a likelihood-ratio test. With two publicly available datasets, we show that flowVS removes the mean-variance dependence from raw FC data and makes the within-population variance relatively homogeneous. We demonstrate that alternative transformation techniques such as flowTrans, flowScape, logicle, and FCSTrans might not stabilize variance. Besides flow cytometry, flowVS can also be applied to stabilize variance in microarray data. With a publicly available data set we demonstrate that flowVS performs as well as the VSN software, a state-of-the-art approach developed for microarrays. Conclusions The homogeneity of variance in cell populations across FC samples is desirable when extracting features uniformly and comparing cell populations with different levels of marker expressions. The newly developed flowVS algorithm solves the variance-stabilization problem in FC and microarrays by optimally transforming data with the help of Bartlett’s likelihood-ratio test. On two publicly available FC datasets, flowVS stabilizes within-population variances more evenly than the available transformation and normalization techniques. flowVS-based variance stabilization can help in performing comparison and alignment of phenotypically identical cell populations across different samples. flowVS and the datasets used in this paper are publicly available in Bioconductor.

60 APPLIED LIFE SCIENCES↗

Spectral analysis of mammographic images using a multitaper method

Purpose: Power spectral analysis in radiographic images is conventionally performed using a windowed overlapping averaging periodogram. This study describes an alternative approach using a multitaper technique and compares its performance with that of the standard method. This tool will be valuable in power spectrum estimation of images, whose content deviates significantly from uniform white noise. The performance of the multitaper approach will be evaluated in terms of spectral stability, variance reduction, bias, and frequency precision. The ultimate goal is the development of a useful tool for image quality assurance. Methods: A multitaper approach uses successive data windows of increasing order. This mitigates spectral leakage allowing one to calculate a reduced-variance power spectrum. The multitaper approach will be compared with the conventional power spectrum method in several typical situations, including the noise power spectra (NPS) measurements of simulated projection images of a uniform phantom, NPS measurement of real detector images of a uniform phantom for two clinical digital mammography systems, and the estimation of the anatomic noise in mammographic images (simulated images and clinical mammograms). Results: Examination of spectrum variance versus frequency resolution and bias indicates that the multitaper approach is superior to the conventional single taper methods in the prevention of spectrum leakage and variance reduction. More than four times finer frequency precision can be achieved with equivalent or less variance and bias. Conclusions: Without any shortening of the image data length, the bias is smaller and the frequency resolution is higher with the multitaper method, and the need to compromise in the choice of regions of interest size to balance between the reduction of variance and the loss of frequency resolution is largely eliminated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A mixed model approach for evaluating yield improvements in interspecific hybrids of shrub willow, a dedicated bioenergy crop

Lignocellulosic bioenergy crops such as shrub willow (Salix spp.) are expected to have a significant role in climate mitigation strategies. Yield is perhaps the most important trait for genetic selection and development of biomass feedstocks, but the selection process is complicated by the strong influence that environmental factors has on cultivar performance. Understanding the genotype-by-environment interactions using regional yield trials of shrub willow will inform future breeding efforts and improve the ability to make regionally-specific cultivar recommendations. Here we analyzed two yield trial datasets containing genotypes from successive rounds of breeding using a series of mixed models. Stability variance parameters were used together with overall yields to identify genotypes with stable yields or specific adaptation. Analysis of the first dataset revealed a group of triploid interspecific hybrid cultivars with exceptional performance and specific adaptation to either poor or good quality environments. The best performing cultivar showed a 14% yield improvement over the mean of the check cultivars. In the second dataset, new selections were assessed along with the top performing cultivars from dataset 1. New triploid hybrids had yields 19 to 27% greater than the check cultivar and exhibited similar patterns of specific adaptation as some of the selections from the first dataset. Partial least squares regression analysis indicated that top-yielding genotypes were favored in environments with higher temperatures and greater growing degree days. This analysis demonstrates incremental improvements in yield with successive rounds of breeding through the development of interspecific triploid hybrids.

09 BIOMASS FUELS↗

Denoising of polychromatic CT images based on their own noise properties

Purpose: Because of high diagnostic accuracy and fast scan time, computed tomography (CT) has been widely used in various clinical applications. Since the CT scan introduces radiation exposure to patients, however, dose reduction has recently been recognized as an important issue in CT imaging. However, low-dose CT causes an increase of noise in the image and thereby deteriorates the accuracy of diagnosis. In this paper, the authors develop an efficient denoising algorithm for low-dose CT images obtained using a polychromatic x-ray source. The algorithm is based on two steps: (i) estimation of space variant noise statistics, which are uniquely determined according to the system geometry and scanned object, and (ii) subsequent novel conversion of the estimated noise to Gaussian noise so that an existing high performance Gaussian noise filtering algorithm can be directly applied to CT images with non-Gaussian noise. Methods: For efficient polychromatic CT image denoising, the authors first reconstruct an image with the iterative maximum-likelihood polychromatic algorithm for CT to alleviate the beam-hardening problem. We then estimate the space-variant noise variance distribution on the image domain. Since there are many high performance denoising algorithms available for the Gaussian noise, image denoising can become much more efficient if they can be used. Hence, the authors propose a novel conversion scheme to transform the estimated space-variant noise to near Gaussian noise. In the suggested scheme, the authors first convert the image so that its mean and variance can have a linear relationship, and then produce a Gaussian image via variance stabilizing transform. The authors then apply a block matching 4D algorithm that is optimized for noise reduction of the Gaussian image, and reconvert the result to obtain a final denoised image. To examine the performance of the proposed method, an XCAT phantom simulation and a physical phantom experiment were conducted. Results: Both simulation and experimental results show that, unlike the existing denoising algorithms, the proposed algorithm can effectively reduce the noise over the whole region of CT images while preventing degradation of image resolution. Conclusions: To effectively denoise polychromatic low-dose CT images, a novel denoising algorithm is proposed. Because this algorithm is based on the noise statistics of a reconstructed polychromatic CT image, the spatially varying noise on the image is effectively reduced so that the denoised image will have homogeneous quality over the image domain. Through a simulation and a real experiment, it is verified that the proposed algorithm can deliver considerably better performance compared to the existing denoising algorithms.

60 APPLIED LIFE SCIENCES↗

SIMPLIFIED PREDICTIVE MODELS FOR CO₂ SEQUESTRATION PERFORMANCE ASSESSMENT RESEARCH TOPICAL REPORT ON TASK #3 STATISTICAL LEARNING BASED MODELS

We compare two approaches for building a statistical proxy model (metamodel) for CO₂ geologic sequestration from the results of full-physics compositional simulations. The first approach involves a classical Box-Behnken or Augmented Pairs experimental design with a quadratic polynomial response surface. The second approach used a space-filling maxmin Latin Hypercube sampling or maximum entropy design with the choice of five different meta-modeling techniques: quadratic polynomial, kriging with constant and quadratic trend terms, multivariate adaptive regression spline (MARS) and additivity and variance stabilization (AVAS). Simulations results for CO₂ injection into a reservoir-caprock system with 9 design variables (and 97 samples) were used to generate the data for developing the proxy models. The fitted models were validated with using an independent data set and a cross-validation approach for three different performance metrics: total storage efficiency, CO₂ plume radius and average reservoir pressure. The Box-Behnken–quadratic polynomial metamodel performed the best, followed closely by the maximin LHS–kriging metamodel.

Mishra, Srikanta↗

Laser Speckle Pattern Stability in Hypersonic Regimes for Experimental Mechanics and Metrological Studies

Here, an empirical study assessing the suitability of laser speckle patterns for use in experimental mechanics research conducted at hypersonic conditions is presented. Speckle patterns generated via coherent optical scattering from a gold-coated graphite surface inserted into a Mach 10 air stream were collected and analyzed using Computer-Aided Speckle Interferometry using two methodologies: a typical spanwise approach involving increasing temporal span between image pairs, and a sequential approach that utilizes a combination of temporal re-referencing and spatial resampling. Results were characterized for spatial-temporal stability and variance. Our observations demonstrate that optical methods relying on stable and properly formed speckle patterns can be used in a hypersonic regime at various Reynolds numbers and common camera frame rates, but the technique is sensitive to the conditions of the airflow and the processing methodology chosen.

42 ENGINEERING↗

SU-F-R-52: A Comparison of the Performance of Radiomic Features From Free Breathing and 4DCT Scans in Predicting Disease Recurrence in Lung Cancer SBRT Patients

Purpose: There is a clinical need to identify patients who are at highest risk of recurrence after being treated with stereotactic body radiation therapy (SBRT). Radiomics offers a non-invasive approach by extracting quantitative features from medical images based on tumor phenotype that is predictive of an outcome. Lung cancer patients treated with SBRT routinely undergo free breathing (FB image) and 4DCT (average intensity projection (AIP) image) scans for treatment planning to account for organ motion. The aim of the current study is to evaluate and compare the prognostic performance of radiomic features extracted from FB and AIP images in lung cancer patients treated with SBRT to identify which image type would generate an optimal predictive model for recurrence. Methods: FB and AIP images of 113 Stage I-II NSCLC patients treated with SBRT were analysed. The prognostic performance of radiomic features for distant metastasis (DM) was evaluated by their concordance index (CI). Radiomic features were compared with conventional imaging metrics (e.g. diameter). All p-values were corrected for multiple testing using the false discovery rate. Results: All patients received SBRT and 20.4% of patients developed DM. From each image type (FB or AIP), nineteen radiomic features were selected based on stability and variance. Both image types had five common and fourteen different radiomic features. One FB (CI=0.70) and five AIP (CI range=0.65–0.68) radiomic features were significantly prognostic for DM (p<0.05). None of the conventional features derived from FB images (range CI=0.60–0.61) were significant but all AIP conventional features were (range CI=0.64–0.66). Conclusion: Features extracted from different types of CT scans have varying prognostic performances. AIP images contain more prognostic radiomic features for DM than FB images. These methods can provide personalized medicine approaches at low cost, as FB and AIP data are readily available within a large number of radiation oncology departments. R.M. had consulting interest with Amgen (ended in 2015).

60 APPLIED LIFE SCIENCES↗

Evaluation of idealized large-eddy simulations performed with the Weather Research and Forecasting model using turbulence measurements from a 250 m meteorological mast

Abstract. We investigate the ability of the Weather Research and Forecasting model to perform large-eddy simulation of canonical flows. This is achieved through comparison of the simulation outputs with measurements from sonic anemometers on a 250 m meteorological mast located at Østerild, in northern Denmark. Østerild is on a flat and rough area, and for the predominant wind directions, the atmospheric flow can be considered to be close to homogeneous. The idealized simulated flows aim at representing atmospheric boundary layer turbulence under unstable, neutral, and stable stability conditions at the surface, which are statistically significant conditions observed at Østerild. We found that the resolved fields from the simulations appear to have the characteristics of the three stability regimes. Vertical profiles of observed mean wind speeds and direction are well reproduced by the simulations, with the largest differences under near-neutral conditions, where the effect of the subgrid-scale model is evident on the vertical wind shear close to the surface. Vertical profiles of observed eddy fluxes are also well reproduced by the simulations, with the largest differences for the three velocity component variances under stable stability conditions, although nearly always within the observed variability. With regards to turbulent kinetic energy, we find good agreement between observations and simulations at all vertical levels. Simulated and observed velocity spectra match very well and show very similar behavior with height and with atmospheric stability within the low-frequency interval; at the effective resolution, the simulated spectra show the typical drop-off of finite differences. Our findings demonstrate that these idealized simulations reproduce the characteristics of atmospheric stability regimes often observed at a high turbulent and flat site within a direction sector, where the air flows over nearly homogeneous land.

17 WIND ENERGY↗

Optimization Stability in Excited-State-Specific Variational Monte Carlo

Here, we investigate the issue of optimization stability in variance-based state-specific variational Monte Carlo, discussing the roles of the objective function, the complexity of wave function ansatz, the amount of sampling effort, and the choice of minimization algorithm. Using a small cyanine dye molecule as a test case, we systematically perform minimizations using variants of the linear method as both a standalone algorithm and in a hybrid combination with accelerated descent. We demonstrate that adaptive step control is crucial for maintaining the linear method's stability when optimizing complicated wave functions and that the hybrid method enjoys both greater stability and minimization performance.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Enhanced Performance Controller Design for Stochastic Systems by Adding Extra State Estimation onto the Existing Closed Loop Control

To enhance the performance of the tracking property , this paper presents a novel control algorithm for a class of linear dynamic stochastic systems with unmeasurable states, where the performance enhancement loop is established based on Kalman filter. Without changing the existing closed loop with the PI controller, the compensative controller is designed to minimize the variances of the tracking errors using the estimated states and the propagation of state variances. Moreover, the stability of the closed-loop systems has been analyzed in the mean-square sense. A simulated example is included to show the effectiveness of the presented control algorithm, where encouraging results have been obtained.

Stochastic coupling attenuation↗

Collaborative Project: Ocean-Atmosphere Interaction From Meso- to Planetary-Scale: Mechanisms, Parameterization, and Variability

The project focused on the dynamics and scale dependence of the boundary layer response, the coupled responses in the Pacific, and low frequency oceanic processes. Using theory and model simulations, we found coupling of sea surface temperatures associated with the ocean eddy field and the atmospheric boundary layer be dependent on scale, and captured in wave-number space by transfer functions. Investigations of coupled processes focused on the sea surface temperatures scales of eastern boundary upwelling system, and showed stability and eddy variance in the Kuroshio Extension to be predictable with lead times of several years through ocean Rossby waves and coupling with the atmosphere. In addition to these dynamical processes, we found that a significant part of the ocean evolution is associated with density compensating temperature and salinity anomalies, that, unlike Rossby waves, behave like passive tracers and follow the mean circulation.

54 ENVIRONMENTAL SCIENCES↗

Tailoring Magnetic Skyrmions by Geometric Confinement of Magnetic Structures

Nanoscale magnetic skyrmions have interesting static and transport properties that make them candidates for future spintronic devices. Control and manipulation of the size and behavior of skyrmions is thus of crucial importance. Here, using a Ginzburg-Landau approach, we show theoretically that skyrmions and skyrmion lattices can be stabilized by a spatial modulation of the uniaxial magnetic anisotropy in a thin film of a centro-symmetric ferromagnet. Remarkably, the skyrmion size is determined by the ratio of the exchange length and the period of the spatial modulation of the anisotropy, at variance with conventional skyrmions stabilized by dipolar and Dzyaloshinskii–Moriya interactions.

36 MATERIALS SCIENCE↗

In-Home Mobility Frequency and Stability in Older Adults Living Alone With or Without MCI: Introduction of New Metrics

Background: Older adults spend a considerable amount of time inside their residences; however, most research investigates out-of-home mobility and its health correlates. We measured indoor mobility using room-to-room transitions, tested their psychometric properties, and correlated indoor mobility with cognitive and functional status. Materials and Methods: Community-dwelling older adults living alone ( n = 139; age = 78.1 ± 8.6 years) from the Oregon Center for Aging & Technology (ORCATECH) and Minority Aging Research Study (MARS) were included in the study. Two indoor mobility features were developed using non-parametric parameters (frequency; stability): Indoor mobility frequency (room-to-room transitions/day) was detected using passive infrared (PIR) motion sensors fixed on the walls in four geographic locations (bathroom; bedroom; kitchen; living room) and using door contact sensors attached to the egress door in the entrance. Indoor mobility stability was estimated by variances of number of room-to-room transitions over a week. Test-retest reliability (Intra-class coefficient, ICC) and the minimal clinically important difference (MCID) defined as the standard error of measurement (SEM) were generated. Generalized estimating equations models related mobility features with mild cognitive impairment (MCI) and functional status (gait speed). Results: An average of 206 days (±127) of sensor data were analyzed per individual. Indoor mobility frequency and stability showed good to excellent test-retest reliability (ICCs = 0.91[0.88–0.94]; 0.59[0.48–0.70]). The MCIDs of mobility frequency and mobility stability were 18 and 0.09, respectively. On average, a higher indoor mobility frequency was associated with faster gait speed (β = 0.53, p = 0.04), suggesting an increase of 5.3 room-to-room transitions per day was associated with an increase of 10 cm/s gait speed. A decrease in mobility stability was associated with MCI (β = −0.04, p = 0.03). Discussion: Mobility frequency and stability in the home are clinically meaningful and reliable features. Pervasive-sensing systems deployed in homes can objectively reveal cognitive and functional status in older adults who live alone.

Wu, Chao-Yi↗

A hybrid approach to excited-state-specific variational Monte Carlo and doubly excited states

We extend our hybrid linear-method/accelerated-descent variational Monte Carlo optimization approach to excited states and investigate its efficacy in double excitations. In addition to showing a superior statistical efficiency when compared to the linear method, our tests on small molecules show good energetic agreement with benchmark methods. We also demonstrate the ability to treat double excitations in systems that are too large for a full treatment by using selected configuration interaction methods via an application to 4-aminobenzonitrile. Finally, we investigate the stability of state-specific variance optimization against collapse to other states’ variance minima and find that symmetry, Ansatz quality, and sample size all have roles to play in achieving stability.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Sources of Technical Variability in Quantitative LC-MS Proteomics: Human Brain Tissue Sample Analysis.

To design a robust quantitative proteomics study, an understanding of both the inherent heterogeneity of the biological samples being studied as well as the technical variability of the proteomics methods and platform is needed. Additionally, accurately identifying the technical steps associated with the largest variability would provide valuable information for the improvement and design of future processing pipelines. We present an experimental strategy that allows for a detailed examination of the variability of the quantitative LC-MS proteomics measurements. By replicating analyses at different stages of processing, various technical components can be estimated and their individual contribution to technical variability can be dissected. This design can be easily adapted to other quantitative proteomics pipelines. Herein, we applied this methodology to our label-free workflow for the processing of human brain tissue. For this application, the pipeline was divided into four critical components: Tissue dissection and homogenization (extraction), protein denaturation followed by trypsin digestion and SPE clean-up (digestion), short-term run-to-run instrumental response fluctuation (instrumental variance), and long-term drift of the quantitative response of the LC-MS/MS platform over the 2 week period of continuous analysis (instrumental stability). From this analysis, we found the following contributions to variability: extraction (72%) >> instrumental variance (16%) > instrumental stability (8.4%) > digestion (3.1%). Furthermore, the stability of the platform and its’ suitability for discovery proteomics studies is demonstrated.

Environmental Molecular Sciences Laboratory↗

Laser frequency stabilization using bichromatic crossover spectroscopy

We propose a Doppler-free spectroscopic method named bichromatic crossover spectroscopy (BCS), which we then use for the frequency stabilization of an off-resonant frequency that does not correspond to an atomic transition. The observed BCS in the 5S{sub 1/2} → 5P{sub 1/2} transition of {sup 87}Rb is related to the hyperfine structure of the conventional saturated absorption spectrum of this transition. Furthermore, the Doppler-free BCS is numerically calculated by considering all of the degenerate magnetic sublevels of the 5S{sub 1/2} → 5P{sub 1/2} transition in an atomic vapor cell, and is found to be in good agreement with the experimental results. Finally, we successfully achieve modulation-free off-resonant locking at the center frequency between the two 5S{sub 1/2}(F = 1 and 2) → 5P{sub 1/2}(F′ = 1) transitions using a polarization rotation of the BCS. The laser frequency stability was estimated to be the Allan variance of 2.1 × 10{sup −10} at 1 s.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Radium/Barium Waste Project

The treatment, shipping, and disposal of a highly radioactive radium/barium waste stream have presented a complex set of challenges requiring several years of effort. The project illustrates the difficulty and high cost of managing even small quantities of highly radioactive Resource Conservation and Recovery Act (RCRA)-regulated waste. Pacific Northwest National Laboratory (PNNL) research activities produced a Type B quantity of radium chloride low-level mixed waste (LLMW) in a number of small vials in a facility hot cell. The resulting waste management project involved a mock-up RCRA stabilization treatment, a failed in-cell treatment, a second, alternative RCRA treatment approach, coordinated regulatory variances and authorizations, alternative transportation authorizations, additional disposal facility approvals, and a final radiological stabilization process.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Radium/Barium waste project - 15043

The treatment, shipping, and disposal of a highly radioactive radium/barium waste stream have presented a complex set of challenges requiring several years of effort. The project illustrates the difficulty and high cost of managing even small quantities of highly radioactive Resource Conservation and Recovery Act (RCRA)-regulated waste. Pacific Northwest National Laboratory (PNNL) research activities produced a Type B quantity of radium chloride low-level mixed waste (LLMW) in a number of small vials in a facility hot cell. The resulting waste management project involved a mock-up RCRA stabilization treatment, a failed in-cell treatment, a second, alternative RCRA treatment approach, coordinated regulatory variances and authorizations, alternative transportation authorizations, additional disposal facility approvals, and a final radiological stabilization process. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗