Sample records for local sensitivity analysis

  1. Sensitivity analysis of a wing aeroelastic response

    NASA Technical Reports Server (NTRS)

    Kapania, Rakesh K.; Eldred, Lloyd B.; Barthelemy, Jean-Francois M.

    1991-01-01

    A variation of Sobieski's Global Sensitivity Equations (GSE) approach is implemented to obtain the sensitivity of the static aeroelastic response of a three-dimensional wing model. The formulation is quite general and accepts any aerodynamics and structural analysis capability. An interface code is written to convert one analysis's output to the other's input, and visa versa. Local sensitivity derivatives are calculated by either analytic methods or finite difference techniques. A program to combine the local sensitivities, such as the sensitivity of the stiffness matrix or the aerodynamic kernel matrix, into global sensitivity derivatives is developed. The aerodynamic analysis package FAST, using a lifting surface theory, and a structural package, ELAPS, implementing Giles' equivalent plate model are used.

  2. SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool

    PubMed Central

    Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

    2008-01-01

    Background It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. Results This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. Conclusion SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes. PMID:18706080

  3. SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

    PubMed

    Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

    2008-08-15

    It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.

  4. Space shuttle SRM plume expansion sensitivity analysis. [flow characteristics of exhaust gases from solid propellant rocket engines

    NASA Technical Reports Server (NTRS)

    Smith, S. D.; Tevepaugh, J. A.; Penny, M. M.

    1975-01-01

    The exhaust plumes of the space shuttle solid rocket motors can have a significant effect on the base pressure and base drag of the shuttle vehicle. A parametric analysis was conducted to assess the sensitivity of the initial plume expansion angle of analytical solid rocket motor flow fields to various analytical input parameters and operating conditions. The results of the analysis are presented and conclusions reached regarding the sensitivity of the initial plume expansion angle to each parameter investigated. Operating conditions parametrically varied were chamber pressure, nozzle inlet angle, nozzle throat radius of curvature ratio and propellant particle loading. Empirical particle parameters investigated were mean size, local drag coefficient and local heat transfer coefficient. Sensitivity of the initial plume expansion angle to gas thermochemistry model and local drag coefficient model assumptions were determined.

  5. Characterization of emission microscopy and liquid crystal thermography in IC fault localization

    NASA Astrophysics Data System (ADS)

    Lau, C. K.; Sim, K. S.

    2013-05-01

    This paper characterizes two fault localization techniques - Emission Microscopy (EMMI) and Liquid Crystal Thermography (LCT) by using integrated circuit (IC) leakage failures. The majority of today's semiconductor failures do not reveal a clear visual defect on the die surface and therefore require fault localization tools to identify the fault location. Among the various fault localization tools, liquid crystal thermography and frontside emission microscopy are commonly used in most semiconductor failure analysis laboratories. Many people misunderstand that both techniques are the same and both are detecting hot spot in chip failing with short or leakage. As a result, analysts tend to use only LCT since this technique involves very simple test setup compared to EMMI. The omission of EMMI as the alternative technique in fault localization always leads to incomplete analysis when LCT fails to localize any hot spot on a failing chip. Therefore, this research was established to characterize and compare both the techniques in terms of their sensitivity in detecting the fault location in common semiconductor failures. A new method was also proposed as an alternative technique i.e. the backside LCT technique. The research observed that both techniques have successfully detected the defect locations resulted from the leakage failures. LCT wass observed more sensitive than EMMI in the frontside analysis approach. On the other hand, EMMI performed better in the backside analysis approach. LCT was more sensitive in localizing ESD defect location and EMMI was more sensitive in detecting non ESD defect location. Backside LCT was proven to work as effectively as the frontside LCT and was ready to serve as an alternative technique to the backside EMMI. The research confirmed that LCT detects heat generation and EMMI detects photon emission (recombination radiation). The analysis results also suggested that both techniques complementing each other in the IC fault localization. It is necessary for a failure analyst to use both techniques when one of the techniques produces no result.

  6. Adjoint sensitivity analysis of a tumor growth model and its application to spatiotemporal radiotherapy optimization.

    PubMed

    Fujarewicz, Krzysztof; Lakomiec, Krzysztof

    2016-12-01

    We investigate a spatial model of growth of a tumor and its sensitivity to radiotherapy. It is assumed that the radiation dose may vary in time and space, like in intensity modulated radiotherapy (IMRT). The change of the final state of the tumor depends on local differences in the radiation dose and varies with the time and the place of these local changes. This leads to the concept of a tumor's spatiotemporal sensitivity to radiation, which is a function of time and space. We show how adjoint sensitivity analysis may be applied to calculate the spatiotemporal sensitivity of the finite difference scheme resulting from the partial differential equation describing the tumor growth. We demonstrate results of this approach to the tumor proliferation, invasion and response to radiotherapy (PIRT) model and we compare the accuracy and the computational effort of the method to the simple forward finite difference sensitivity analysis. Furthermore, we use the spatiotemporal sensitivity during the gradient-based optimization of the spatiotemporal radiation protocol and present results for different parameters of the model.

  7. Perturbation Selection and Local Influence Analysis for Nonlinear Structural Equation Model

    ERIC Educational Resources Information Center

    Chen, Fei; Zhu, Hong-Tu; Lee, Sik-Yum

    2009-01-01

    Local influence analysis is an important statistical method for studying the sensitivity of a proposed model to model inputs. One of its important issues is related to the appropriate choice of a perturbation vector. In this paper, we develop a general method to select an appropriate perturbation vector and a second-order local influence measure…

  8. Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection

    PubMed Central

    Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

    2015-01-01

    Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close “neighborhood” of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa. PMID:26327290

  9. Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection.

    PubMed

    Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

    2015-01-01

    Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close "neighborhood" of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa.

  10. Perturbation analysis for patch occupancy dynamics

    USGS Publications Warehouse

    Martin, Julien; Nichols, James D.; McIntyre, Carol L.; Ferraz, Goncalo; Hines, James E.

    2009-01-01

    Perturbation analysis is a powerful tool to study population and community dynamics. This article describes expressions for sensitivity metrics reflecting changes in equilibrium occupancy resulting from small changes in the vital rates of patch occupancy dynamics (i.e., probabilities of local patch colonization and extinction). We illustrate our approach with a case study of occupancy dynamics of Golden Eagle (Aquila chrysaetos) nesting territories. Examination of the hypothesis of system equilibrium suggests that the system satisfies equilibrium conditions. Estimates of vital rates obtained using patch occupancy models are used to estimate equilibrium patch occupancy of eagles. We then compute estimates of sensitivity metrics and discuss their implications for eagle population ecology and management. Finally, we discuss the intuition underlying our sensitivity metrics and then provide examples of ecological questions that can be addressed using perturbation analyses. For instance, the sensitivity metrics lead to predictions about the relative importance of local colonization and local extinction probabilities in influencing equilibrium occupancy for rare and common species.

  11. Preoperative localization strategies for primary hyperparathyroidism: an economic analysis.

    PubMed

    Lubitz, Carrie C; Stephen, Antonia E; Hodin, Richard A; Pandharipande, Pari

    2012-12-01

    Strategies for localizing parathyroid pathology preoperatively vary in cost and accuracy. Our purpose was to compute and compare comprehensive costs associated with common localization strategies. A decision-analytic model was developed to evaluate comprehensive, short-term costs of parathyroid localization strategies for patients with primary hyperparathyroidism. Eight strategies were compared. Probabilities of accurate localization were extracted from the literature, and costs associated with each strategy were based on 2011 Medicare reimbursement schedules. Differential cost considerations included outpatient versus inpatient surgeries, operative time, and costs of imaging. Sensitivity analyses were performed to determine effects of variability in key model parameters upon model results. Ultrasound (US) followed by 4D-CT was the least expensive strategy ($5,901), followed by US alone ($6,028), and 4D-CT alone ($6,110). Strategies including sestamibi (SM) were more expensive, with associated expenditures of up to $6,329 for contemporaneous US and SM. Four-gland, bilateral neck exploration (BNE) was the most expensive strategy ($6,824). Differences in cost were dependent upon differences in the sensitivity of each strategy for detecting single-gland disease, which determined the proportion of patients able to undergo outpatient minimally invasive parathyroidectomy. In sensitivity analysis, US alone was preferred over US followed by 4D-CT only when both the sensitivity of US alone for detecting an adenoma was ≥ 94 %, and the sensitivity of 4D-CT following negative US was ≤ 39 %. 4D-CT alone was the least costly strategy when US sensitivity was ≤ 31 %. Among commonly used strategies for preoperative localization of parathyroid pathology, US followed by selective 4D-CT is the least expensive.

  12. Importance analysis for Hudson River PCB transport and fate model parameters using robust sensitivity studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, S.; Toll, J.; Cothern, K.

    1995-12-31

    The authors have performed robust sensitivity studies of the physico-chemical Hudson River PCB model PCHEPM to identify the parameters and process uncertainties contributing the most to uncertainty in predictions of water column and sediment PCB concentrations, over the time period 1977--1991 in one segment of the lower Hudson River. The term ``robust sensitivity studies`` refers to the use of several sensitivity analysis techniques to obtain a more accurate depiction of the relative importance of different sources of uncertainty. Local sensitivity analysis provided data on the sensitivity of PCB concentration estimates to small perturbations in nominal parameter values. Range sensitivity analysismore » provided information about the magnitude of prediction uncertainty associated with each input uncertainty. Rank correlation analysis indicated which parameters had the most dominant influence on model predictions. Factorial analysis identified important interactions among model parameters. Finally, term analysis looked at the aggregate influence of combinations of parameters representing physico-chemical processes. The authors scored the results of the local and range sensitivity and rank correlation analyses. The authors considered parameters that scored high on two of the three analyses to be important contributors to PCB concentration prediction uncertainty, and treated them probabilistically in simulations. They also treated probabilistically parameters identified in the factorial analysis as interacting with important parameters. The authors used the term analysis to better understand how uncertain parameters were influencing the PCB concentration predictions. The importance analysis allowed us to reduce the number of parameters to be modeled probabilistically from 16 to 5. This reduced the computational complexity of Monte Carlo simulations, and more importantly, provided a more lucid depiction of prediction uncertainty and its causes.« less

  13. Prostate lesion detection and localization based on locality alignment discriminant analysis

    NASA Astrophysics Data System (ADS)

    Lin, Mingquan; Chen, Weifu; Zhao, Mingbo; Gibson, Eli; Bastian-Jordan, Matthew; Cool, Derek W.; Kassam, Zahra; Chow, Tommy W. S.; Ward, Aaron; Chiu, Bernard

    2017-03-01

    Prostatic adenocarcinoma is one of the most commonly occurring cancers among men in the world, and it also the most curable cancer when it is detected early. Multiparametric MRI (mpMRI) combines anatomic and functional prostate imaging techniques, which have been shown to produce high sensitivity and specificity in cancer localization, which is important in planning biopsies and focal therapies. However, in previous investigations, lesion localization was achieved mainly by manual segmentation, which is time-consuming and prone to observer variability. Here, we developed an algorithm based on locality alignment discriminant analysis (LADA) technique, which can be considered as a version of linear discriminant analysis (LDA) localized to patches in the feature space. Sensitivity, specificity and accuracy generated by the proposed algorithm in five prostates by LADA were 52.2%, 89.1% and 85.1% respectively, compared to 31.3%, 85.3% and 80.9% generated by LDA. The delineation accuracy attainable by this tool has a potential in increasing the cancer detection rate in biopsies and in minimizing collateral damage of surrounding tissues in focal therapies.

  14. Global Sensitivity and Data-Worth Analyses in iTOUGH2: User's Guide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wainwright, Haruko Murakami; Finsterle, Stefan

    2016-07-15

    This manual explains the use of local sensitivity analysis, the global Morris OAT and Sobol’ methods, and a related data-worth analysis as implemented in iTOUGH2. In addition to input specification and output formats, it includes some examples to show how to interpret results.

  15. Sensitivity Analysis of the Static Aeroelastic Response of a Wing

    NASA Technical Reports Server (NTRS)

    Eldred, Lloyd B.

    1993-01-01

    A technique to obtain the sensitivity of the static aeroelastic response of a three dimensional wing model is designed and implemented. The formulation is quite general and accepts any aerodynamic and structural analysis capability. A program to combine the discipline level, or local, sensitivities into global sensitivity derivatives is developed. A variety of representations of the wing pressure field are developed and tested to determine the most accurate and efficient scheme for representing the field outside of the aerodynamic code. Chebyshev polynomials are used to globally fit the pressure field. This approach had some difficulties in representing local variations in the field, so a variety of local interpolation polynomial pressure representations are also implemented. These panel based representations use a constant pressure value, a bilinearly interpolated value. or a biquadraticallv interpolated value. The interpolation polynomial approaches do an excellent job of reducing the numerical problems of the global approach for comparable computational effort. Regardless of the pressure representation used. sensitivity and response results with excellent accuracy have been produced for large integrated quantities such as wing tip deflection and trim angle of attack. The sensitivities of such things as individual generalized displacements have been found with fair accuracy. In general, accuracy is found to be proportional to the relative size of the derivatives to the quantity itself.

  16. SensA: web-based sensitivity analysis of SBML models.

    PubMed

    Floettmann, Max; Uhlendorf, Jannis; Scharp, Till; Klipp, Edda; Spiesser, Thomas W

    2014-10-01

    SensA is a web-based application for sensitivity analysis of mathematical models. The sensitivity analysis is based on metabolic control analysis, computing the local, global and time-dependent properties of model components. Interactive visualization facilitates interpretation of usually complex results. SensA can contribute to the analysis, adjustment and understanding of mathematical models for dynamic systems. SensA is available at http://gofid.biologie.hu-berlin.de/ and can be used with any modern browser. The source code can be found at https://bitbucket.org/floettma/sensa/ (MIT license) © The Author 2014. Published by Oxford University Press.

  17. A new similarity index for nonlinear signal analysis based on local extrema patterns

    NASA Astrophysics Data System (ADS)

    Niknazar, Hamid; Motie Nasrabadi, Ali; Shamsollahi, Mohammad Bagher

    2018-02-01

    Common similarity measures of time domain signals such as cross-correlation and Symbolic Aggregate approximation (SAX) are not appropriate for nonlinear signal analysis. This is because of the high sensitivity of nonlinear systems to initial points. Therefore, a similarity measure for nonlinear signal analysis must be invariant to initial points and quantify the similarity by considering the main dynamics of signals. The statistical behavior of local extrema (SBLE) method was previously proposed to address this problem. The SBLE similarity index uses quantized amplitudes of local extrema to quantify the dynamical similarity of signals by considering patterns of sequential local extrema. By adding time information of local extrema as well as fuzzifying quantized values, this work proposes a new similarity index for nonlinear and long-term signal analysis, which extends the SBLE method. These new features provide more information about signals and reduce noise sensitivity by fuzzifying them. A number of practical tests were performed to demonstrate the ability of the method in nonlinear signal clustering and classification on synthetic data. In addition, epileptic seizure detection based on electroencephalography (EEG) signal processing was done by the proposed similarity to feature the potentials of the method as a real-world application tool.

  18. Modelling responses of the inert-gas washout and MRI to bronchoconstriction.

    PubMed

    Foy, Brody H; Kay, David; Bordas, Rafel

    2017-01-01

    Many lung diseases lead to an increase in ventilation heterogeneity (VH). Two clinical practices for the measurement of patient VH are in vivo imaging, and the inert gas multiple breath washout (MBW). In this study computational modelling was used to compare the responses of MBW indices LCI and s cond and MRI measured global and local ventilation indices, σ r and σ local , to constriction of airways in the conducting zone of the lungs. The simulations show that s cond , LCI and σ r behave quite similarly to each other, all being sensitive to increases in the severity of constriction, while exhibiting little sensitivity to the depth at which constriction occurs. In contrast, the local MRI index σ local shows strong sensitivity to depth of constriction, but lowered sensitivity to constriction severity. We finish with an analysis of the sensitivity of MRI indices to grid sizes, showing that results should be interpreted with reference to the image resolution. Overall we conclude that the application of both local and global VH measures may help to classify different types of bronchoconstriction. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. CO2 Push-Pull Dual (Conjugate) Faults Injection Simulations

    DOE Data Explorer

    Oldenburg, Curtis (ORCID:0000000201326016); Lee, Kyung Jae; Doughty, Christine; Jung, Yoojin; Borgia, Andrea; Pan, Lehua; Zhang, Rui; Daley, Thomas M.; Altundas, Bilgin; Chugunov, Nikita

    2017-07-20

    This submission contains datasets and a final manuscript associated with a project simulating carbon dioxide push-pull into a conjugate fault system modeled after Dixie Valley- sensitivity analysis of significant parameters and uncertainty prediction by data-worth analysis. Datasets include: (1) Forward simulation runs of standard cases (push & pull phases), (2) Local sensitivity analyses (push & pull phases), and (3) Data-worth analysis (push & pull phases).

  20. Application of global sensitivity analysis methods to Takagi-Sugeno-Kang rainfall-runoff fuzzy models

    NASA Astrophysics Data System (ADS)

    Jacquin, A. P.; Shamseldin, A. Y.

    2009-04-01

    This study analyses the sensitivity of the parameters of Takagi-Sugeno-Kang rainfall-runoff fuzzy models previously developed by the authors. These models can be classified in two types, where the first type is intended to account for the effect of changes in catchment wetness and the second type incorporates seasonality as a source of non-linearity in the rainfall-runoff relationship. The sensitivity analysis is performed using two global sensitivity analysis methods, namely Regional Sensitivity Analysis (RSA) and Sobol's Variance Decomposition (SVD). In general, the RSA method has the disadvantage of not being able to detect sensitivities arising from parameter interactions. By contrast, the SVD method is suitable for analysing models where the model response surface is expected to be affected by interactions at a local scale and/or local optima, such as the case of the rainfall-runoff fuzzy models analysed in this study. The data of six catchments from different geographical locations and sizes are used in the sensitivity analysis. The sensitivity of the model parameters is analysed in terms of two measures of goodness of fit, assessing the model performance from different points of view. These measures are the Nash-Sutcliffe criterion and the index of volumetric fit. The results of the study show that the sensitivity of the model parameters depends on both the type of non-linear effects (i.e. changes in catchment wetness or seasonality) that dominates the catchment's rainfall-runoff relationship and the measure used to assess the model performance. Acknowledgements: This research was supported by FONDECYT, Research Grant 11070130. We would also like to express our gratitude to Prof. Kieran M. O'Connor from the National University of Ireland, Galway, for providing the data used in this study.

  1. Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects.

    PubMed

    Dresch, Jacqueline M; Liu, Xiaozhou; Arnosti, David N; Ay, Ahmet

    2010-10-24

    Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context. We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity. Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary context to determine how modeling results should be interpreted in biological systems.

  2. Local influence for generalized linear models with missing covariates.

    PubMed

    Shi, Xiaoyan; Zhu, Hongtu; Ibrahim, Joseph G

    2009-12-01

    In the analysis of missing data, sensitivity analyses are commonly used to check the sensitivity of the parameters of interest with respect to the missing data mechanism and other distributional and modeling assumptions. In this article, we formally develop a general local influence method to carry out sensitivity analyses of minor perturbations to generalized linear models in the presence of missing covariate data. We examine two types of perturbation schemes (the single-case and global perturbation schemes) for perturbing various assumptions in this setting. We show that the metric tensor of a perturbation manifold provides useful information for selecting an appropriate perturbation. We also develop several local influence measures to identify influential points and test model misspecification. Simulation studies are conducted to evaluate our methods, and real datasets are analyzed to illustrate the use of our local influence measures.

  3. Anderson localization of shear waves observed by magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Papazoglou, S.; Klatt, D.; Braun, J.; Sack, I.

    2010-07-01

    In this letter we present for the first time an experimental investigation of shear wave localization using motion-sensitive magnetic resonance imaging (MRI). Shear wave localization was studied in gel phantoms containing arrays of randomly positioned parallel glass rods. The phantoms were exposed to continuous harmonic vibrations in a frequency range from 25 to 175 Hz, yielding wavelengths on the order of the elastic mean free path, i.e. the Ioffe-Regel criterion of Anderson localization was satisfied. The experimental setup was further chosen such that purely shear horizontal waves were induced to avoid effects due to mode conversion and pressure waves. Analysis of the distribution of shear wave intensity in experiments and simulations revealed a significant deviation from Rayleigh statistics indicating that shear wave energy is localized. This observation is further supported by experiments on weakly scattering samples exhibiting Rayleigh statistics and an analysis of the multifractality of wave functions. Our results suggest that motion-sensitive MRI is a promising tool for studying Anderson localization of time-harmonic shear waves, which are increasingly used in dynamic elastography.

  4. Distributed Evaluation of Local Sensitivity Analysis (DELSA), with application to hydrologic models

    USGS Publications Warehouse

    Rakovec, O.; Hill, Mary C.; Clark, M.P.; Weerts, A. H.; Teuling, A. J.; Uijlenhoet, R.

    2014-01-01

    This paper presents a hybrid local-global sensitivity analysis method termed the Distributed Evaluation of Local Sensitivity Analysis (DELSA), which is used here to identify important and unimportant parameters and evaluate how model parameter importance changes as parameter values change. DELSA uses derivative-based “local” methods to obtain the distribution of parameter sensitivity across the parameter space, which promotes consideration of sensitivity analysis results in the context of simulated dynamics. This work presents DELSA, discusses how it relates to existing methods, and uses two hydrologic test cases to compare its performance with the popular global, variance-based Sobol' method. The first test case is a simple nonlinear reservoir model with two parameters. The second test case involves five alternative “bucket-style” hydrologic models with up to 14 parameters applied to a medium-sized catchment (200 km2) in the Belgian Ardennes. Results show that in both examples, Sobol' and DELSA identify similar important and unimportant parameters, with DELSA enabling more detailed insight at much lower computational cost. For example, in the real-world problem the time delay in runoff is the most important parameter in all models, but DELSA shows that for about 20% of parameter sets it is not important at all and alternative mechanisms and parameters dominate. Moreover, the time delay was identified as important in regions producing poor model fits, whereas other parameters were identified as more important in regions of the parameter space producing better model fits. The ability to understand how parameter importance varies through parameter space is critical to inform decisions about, for example, additional data collection and model development. The ability to perform such analyses with modest computational requirements provides exciting opportunities to evaluate complicated models as well as many alternative models.

  5. A high figure of merit localized surface plasmon sensor based on a gold nanograting on the top of a gold planar film

    NASA Astrophysics Data System (ADS)

    Zhang, Zu-Yin; Wang, Li-Na; Hu, Hai-Feng; Li, Kang-Wen; Ma, Xun-Peng; Song, Guo-Feng

    2013-10-01

    We investigate the sensitivity and figure of merit (FOM) of a localized surface plasmon (LSP) sensor with gold nanograting on the top of planar metallic film. The sensitivity of the localized surface plasmon sensor is 317 nm/RIU, and the FOM is predicted to be above 8, which is very high for a localized surface plasmon sensor. By employing the rigorous coupled-wave analysis (RCWA) method, we analyze the distribution of the magnetic field and find that the sensing property of our proposed system is attributed to the interactions between the localized surface plasmon around the gold nanostrips and the surface plasmon polarition on the surface of the gold planar metallic film. These findings are important for developing high FOM localized surface plasmon sensors.

  6. Superconducting-Gravimeter Tests of Local Lorentz Invariance

    NASA Astrophysics Data System (ADS)

    Flowers, Natasha A.; Goodge, Casey; Tasson, Jay D.

    2017-11-01

    Superconducting-gravimeter measurements are used to test the local Lorentz invariance of the gravitational interaction and of matter-gravity couplings. The best laboratory sensitivities to date are achieved via a maximum-reach analysis for 13 Lorentz-violating operators, with some improvements exceeding an order of magnitude.

  7. Superconducting-Gravimeter Tests of Local Lorentz Invariance.

    PubMed

    Flowers, Natasha A; Goodge, Casey; Tasson, Jay D

    2017-11-17

    Superconducting-gravimeter measurements are used to test the local Lorentz invariance of the gravitational interaction and of matter-gravity couplings. The best laboratory sensitivities to date are achieved via a maximum-reach analysis for 13 Lorentz-violating operators, with some improvements exceeding an order of magnitude.

  8. Automated Detection, Localization, and Classification of Traumatic Vertebral Body Fractures in the Thoracic and Lumbar Spine at CT

    PubMed Central

    Burns, Joseph E.; Yao, Jianhua; Muñoz, Hector

    2016-01-01

    Purpose To design and validate a fully automated computer system for the detection and anatomic localization of traumatic thoracic and lumbar vertebral body fractures at computed tomography (CT). Materials and Methods This retrospective study was HIPAA compliant. Institutional review board approval was obtained, and informed consent was waived. CT examinations in 104 patients (mean age, 34.4 years; range, 14–88 years; 32 women, 72 men), consisting of 94 examinations with positive findings for fractures (59 with vertebral body fractures) and 10 control examinations (without vertebral fractures), were performed. There were 141 thoracic and lumbar vertebral body fractures in the case set. The locations of fractures were marked and classified by a radiologist according to Denis column involvement. The CT data set was divided into training and testing subsets (37 and 67 subsets, respectively) for analysis by means of prototype software for fully automated spinal segmentation and fracture detection. Free-response receiver operating characteristic analysis was performed. Results Training set sensitivity for detection and localization of fractures within each vertebra was 0.82 (28 of 34 findings; 95% confidence interval [CI]: 0.68, 0.90), with a false-positive rate of 2.5 findings per patient. The sensitivity for fracture localization to the correct vertebra was 0.88 (23 of 26 findings; 95% CI: 0.72, 0.96), with a false-positive rate of 1.3. Testing set sensitivity for the detection and localization of fractures within each vertebra was 0.81 (87 of 107 findings; 95% CI: 0.75, 0.87), with a false-positive rate of 2.7. The sensitivity for fracture localization to the correct vertebra was 0.92 (55 of 60 findings; 95% CI: 0.79, 0.94), with a false-positive rate of 1.6. The most common cause of false-positive findings was nutrient foramina (106 of 272 findings [39%]). Conclusion The fully automated computer system detects and anatomically localizes vertebral body fractures in the thoracic and lumbar spine on CT images with a high sensitivity and a low false-positive rate. © RSNA, 2015 Online supplemental material is available for this article. PMID:26172532

  9. Parametric Sensitivity Analysis of Oscillatory Delay Systems with an Application to Gene Regulation.

    PubMed

    Ingalls, Brian; Mincheva, Maya; Roussel, Marc R

    2017-07-01

    A parametric sensitivity analysis for periodic solutions of delay-differential equations is developed. Because phase shifts cause the sensitivity coefficients of a periodic orbit to diverge, we focus on sensitivities of the extrema, from which amplitude sensitivities are computed, and of the period. Delay-differential equations are often used to model gene expression networks. In these models, the parametric sensitivities of a particular genotype define the local geometry of the evolutionary landscape. Thus, sensitivities can be used to investigate directions of gradual evolutionary change. An oscillatory protein synthesis model whose properties are modulated by RNA interference is used as an example. This model consists of a set of coupled delay-differential equations involving three delays. Sensitivity analyses are carried out at several operating points. Comments on the evolutionary implications of the results are offered.

  10. Local sensitivity of per-recruit fishing mortality reference points.

    PubMed

    Cadigan, N G; Wang, S

    2016-12-01

    We study the sensitivity of fishery management per-recruit harvest rates which may be part of a quantitative harvest strategy designed to achieve some objective for catch or population size. We use a local influence sensitivity analysis to derive equations that describe how these reference harvest rates are affected by perturbations to productivity processes. These equations give a basic theoretical understanding of sensitivity that can be used to predict what the likely impacts of future changes in productivity will be. Our results indicate that per-recruit reference harvest rates are more sensitive to perturbations when the equilibrium catch or population size per recruit, as functions of the harvest rate, have less curvature near the reference point. Overall our results suggest that per recruit reference points will, with some exceptions, usually increase if (1) growth rates increase, (2) natural mortality rates increase, or (3) fishery selectivity increases to an older age.

  11. Selective parathyroid venous sampling in primary hyperparathyroidism: A systematic review and meta-analysis.

    PubMed

    Ibraheem, Kareem; Toraih, Eman A; Haddad, Antoine B; Farag, Mahmoud; Randolph, Gregory W; Kandil, Emad

    2018-05-14

    Minimally invasive parathyroidectomy requires accurate preoperative localization techniques. There is considerable controversy about the effectiveness of selective parathyroid venous sampling (sPVS) in primary hyperparathyroidism (PHPT) patients. The aim of this meta-analysis is to examine the diagnostic accuracy of sPVS as a preoperative localization modality in PHPT. Studies evaluating the diagnostic accuracy of sPVS for PHPT were electronically searched in the PubMed, EMBASE, Web of Science, and Cochrane Controlled Trials Register databases. Two independent authors reviewed the studies, and revised quality assessment of diagnostic accuracy study tool was used for the quality assessment. Study heterogeneity and pooled estimates were calculated. Two hundred and two unique studies were identified. Of those, 12 studies were included in the meta-analysis. Pooled sensitivity, specificity, and positive likelihood ratio (PLR) of sPVS were 74%, 41%, and 1.55, respectively. The area-under-the-receiver operating characteristic curve was 0.684, indicating an average discriminatory ability of sPVS. On comparison between sPVS and noninvasive imaging modalities, sensitivity, PLR, and positive posttest probability were significantly higher in sPVS compared to noninvasive imaging modalities. Interestingly, super-selective venous sampling had the highest sensitivity, accuracy, and positive posttest probability compared to other parathyroid venous sampling techniques. This is the first meta-analysis to examine the accuracy of sPVS in PHPT. sPVS had higher pooled sensitivity when compared to noninvasive modalities in revision parathyroid surgery. However, the invasiveness of this technique does not favor its routine use for preoperative localization. Super-selective venous sampling was the most accurate among all other parathyroid venous sampling techniques. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Analysis of airfoil leading edge separation bubbles

    NASA Technical Reports Server (NTRS)

    Carter, J. E.; Vatsa, V. N.

    1982-01-01

    A local inviscid-viscous interaction technique was developed for the analysis of low speed airfoil leading edge transitional separation bubbles. In this analysis an inverse boundary layer finite difference analysis is solved iteratively with a Cauchy integral representation of the inviscid flow which is assumed to be a linear perturbation to a known global viscous airfoil analysis. Favorable comparisons with data indicate the overall validity of the present localized interaction approach. In addition numerical tests were performed to test the sensitivity of the computed results to the mesh size, limits on the Cauchy integral, and the location of the transition region.

  13. A perceptual space of local image statistics.

    PubMed

    Victor, Jonathan D; Thengone, Daniel J; Rizvi, Syed M; Conte, Mary M

    2015-12-01

    Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice - a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4min. In sum, local image statistics form a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A perceptual space of local image statistics

    PubMed Central

    Victor, Jonathan D.; Thengone, Daniel J.; Rizvi, Syed M.; Conte, Mary M.

    2015-01-01

    Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice – a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14 min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4 min. In sum, local image statistics forms a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. PMID:26130606

  15. An Innovative Technique to Assess Spontaneous Baroreflex Sensitivity with Short Data Segments: Multiple Trigonometric Regressive Spectral Analysis.

    PubMed

    Li, Kai; Rüdiger, Heinz; Haase, Rocco; Ziemssen, Tjalf

    2018-01-01

    Objective: As the multiple trigonometric regressive spectral (MTRS) analysis is extraordinary in its ability to analyze short local data segments down to 12 s, we wanted to evaluate the impact of the data segment settings by applying the technique of MTRS analysis for baroreflex sensitivity (BRS) estimation using a standardized data pool. Methods: Spectral and baroreflex analyses were performed on the EuroBaVar dataset (42 recordings, including lying and standing positions). For this analysis, the technique of MTRS was used. We used different global and local data segment lengths, and chose the global data segments from different positions. Three global data segments of 1 and 2 min and three local data segments of 12, 20, and 30 s were used in MTRS analysis for BRS. Results: All the BRS-values calculated on the three global data segments were highly correlated, both in the supine and standing positions; the different global data segments provided similar BRS estimations. When using different local data segments, all the BRS-values were also highly correlated. However, in the supine position, using short local data segments of 12 s overestimated BRS compared with those using 20 and 30 s. In the standing position, the BRS estimations using different local data segments were comparable. There was no proportional bias for the comparisons between different BRS estimations. Conclusion: We demonstrate that BRS estimation by the MTRS technique is stable when using different global data segments, and MTRS is extraordinary in its ability to evaluate BRS in even short local data segments (20 and 30 s). Because of the non-stationary character of most biosignals, the MTRS technique would be preferable for BRS analysis especially in conditions when only short stationary data segments are available or when dynamic changes of BRS should be monitored.

  16. Sensitivity analysis, calibration, and testing of a distributed hydrological model using error‐based weighting and one objective function

    USGS Publications Warehouse

    Foglia, L.; Hill, Mary C.; Mehl, Steffen W.; Burlando, P.

    2009-01-01

    We evaluate the utility of three interrelated means of using data to calibrate the fully distributed rainfall‐runoff model TOPKAPI as applied to the Maggia Valley drainage area in Switzerland. The use of error‐based weighting of observation and prior information data, local sensitivity analysis, and single‐objective function nonlinear regression provides quantitative evaluation of sensitivity of the 35 model parameters to the data, identification of data types most important to the calibration, and identification of correlations among parameters that contribute to nonuniqueness. Sensitivity analysis required only 71 model runs, and regression required about 50 model runs. The approach presented appears to be ideal for evaluation of models with long run times or as a preliminary step to more computationally demanding methods. The statistics used include composite scaled sensitivities, parameter correlation coefficients, leverage, Cook's D, and DFBETAS. Tests suggest predictive ability of the calibrated model typical of hydrologic models.

  17. A sensitivity analysis for a thermomechanical model of the Antarctic ice sheet and ice shelves

    NASA Astrophysics Data System (ADS)

    Baratelli, F.; Castellani, G.; Vassena, C.; Giudici, M.

    2012-04-01

    The outcomes of an ice sheet model depend on a number of parameters and physical quantities which are often estimated with large uncertainty, because of lack of sufficient experimental measurements in such remote environments. Therefore, the efforts to improve the accuracy of the predictions of ice sheet models by including more physical processes and interactions with atmosphere, hydrosphere and lithosphere can be affected by the inaccuracy of the fundamental input data. A sensitivity analysis can help to understand which are the input data that most affect the different predictions of the model. In this context, a finite difference thermomechanical ice sheet model based on the Shallow-Ice Approximation (SIA) and on the Shallow-Shelf Approximation (SSA) has been developed and applied for the simulation of the evolution of the Antarctic ice sheet and ice shelves for the last 200 000 years. The sensitivity analysis of the model outcomes (e.g., the volume of the ice sheet and of the ice shelves, the basal melt rate of the ice sheet, the mean velocity of the Ross and Ronne-Filchner ice shelves, the wet area at the base of the ice sheet) with respect to the model parameters (e.g., the basal sliding coefficient, the geothermal heat flux, the present-day surface accumulation and temperature, the mean ice shelves viscosity, the melt rate at the base of the ice shelves) has been performed by computing three synthetic numerical indices: two local sensitivity indices and a global sensitivity index. Local sensitivity indices imply a linearization of the model and neglect both non-linear and joint effects of the parameters. The global variance-based sensitivity index, instead, takes into account the complete variability of the input parameters but is usually conducted with a Monte Carlo approach which is computationally very demanding for non-linear complex models. Therefore, the global sensitivity index has been computed using a development of the model outputs in a neighborhood of the reference parameter values with a second-order approximation. The comparison of the three sensitivity indices proved that the approximation of the non-linear model with a second-order expansion is sufficient to show some differences between the local and the global indices. As a general result, the sensitivity analysis showed that most of the model outcomes are mainly sensitive to the present-day surface temperature and accumulation, which, in principle, can be measured more easily (e.g., with remote sensing techniques) than the other input parameters considered. On the other hand, the parameters to which the model resulted less sensitive are the basal sliding coefficient and the mean ice shelves viscosity.

  18. Global sensitivity analysis in stochastic simulators of uncertain reaction networks.

    PubMed

    Navarro Jimenez, M; Le Maître, O P; Knio, O M

    2016-12-28

    Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol's decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

  19. Global sensitivity analysis in stochastic simulators of uncertain reaction networks

    DOE PAGES

    Navarro Jimenez, M.; Le Maître, O. P.; Knio, O. M.

    2016-12-23

    Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol’s decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes thatmore » the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. Here, a sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.« less

  20. Global sensitivity analysis in stochastic simulators of uncertain reaction networks

    NASA Astrophysics Data System (ADS)

    Navarro Jimenez, M.; Le Maître, O. P.; Knio, O. M.

    2016-12-01

    Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol's decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

  1. What do we mean by sensitivity analysis? The need for comprehensive characterization of "global" sensitivity in Earth and Environmental systems models

    NASA Astrophysics Data System (ADS)

    Razavi, Saman; Gupta, Hoshin V.

    2015-05-01

    Sensitivity analysis is an essential paradigm in Earth and Environmental Systems modeling. However, the term "sensitivity" has a clear definition, based in partial derivatives, only when specified locally around a particular point (e.g., optimal solution) in the problem space. Accordingly, no unique definition exists for "global sensitivity" across the problem space, when considering one or more model responses to different factors such as model parameters or forcings. A variety of approaches have been proposed for global sensitivity analysis, based on different philosophies and theories, and each of these formally characterizes a different "intuitive" understanding of sensitivity. These approaches focus on different properties of the model response at a fundamental level and may therefore lead to different (even conflicting) conclusions about the underlying sensitivities. Here we revisit the theoretical basis for sensitivity analysis, summarize and critically evaluate existing approaches in the literature, and demonstrate their flaws and shortcomings through conceptual examples. We also demonstrate the difficulty involved in interpreting "global" interaction effects, which may undermine the value of existing interpretive approaches. With this background, we identify several important properties of response surfaces that are associated with the understanding and interpretation of sensitivities in the context of Earth and Environmental System models. Finally, we highlight the need for a new, comprehensive framework for sensitivity analysis that effectively characterizes all of the important sensitivity-related properties of model response surfaces.

  2. Field-sensitivity To Rheological Parameters

    NASA Astrophysics Data System (ADS)

    Freund, Jonathan; Ewoldt, Randy

    2017-11-01

    We ask this question: where in a flow is a quantity of interest Q quantitatively sensitive to the model parameters θ-> describing the rheology of the fluid? This field sensitivity is computed via the numerical solution of the adjoint flow equations, as developed to expose the target sensitivity δQ / δθ-> (x) via the constraint of satisfying the flow equations. Our primary example is a sphere settling in Carbopol, for which we have experimental data. For this Carreau-model configuration, we simultaneously calculate how much a local change in the fluid intrinsic time-scale λ, limit-viscosities ηo and η∞, and exponent n would affect the drag D. Such field sensitivities can show where different fluid physics in the model (time scales, elastic versus viscous components, etc.) are important for the target observable and generally guide model refinement based on predictive goals. In this case, the computational cost of solving the local sensitivity problem is negligible relative to the flow. The Carreau-fluid/sphere example is illustrative; the utility of field sensitivity is in the design and analysis of less intuitive flows, for which we provide some additional examples.

  3. Sensitivity Analysis for Steady State Groundwater Flow Using Adjoint Operators

    NASA Astrophysics Data System (ADS)

    Sykes, J. F.; Wilson, J. L.; Andrews, R. W.

    1985-03-01

    Adjoint sensitivity theory is currently being considered as a potential method for calculating the sensitivity of nuclear waste repository performance measures to the parameters of the system. For groundwater flow systems, performance measures of interest include piezometric heads in the vicinity of a waste site, velocities or travel time in aquifers, and mass discharge to biosphere points. The parameters include recharge-discharge rates, prescribed boundary heads or fluxes, formation thicknesses, and hydraulic conductivities. The derivative of a performance measure with respect to the system parameters is usually taken as a measure of sensitivity. To calculate sensitivities, adjoint sensitivity equations are formulated from the equations describing the primary problem. The solution of the primary problem and the adjoint sensitivity problem enables the determination of all of the required derivatives and hence related sensitivity coefficients. In this study, adjoint sensitivity theory is developed for equations of two-dimensional steady state flow in a confined aquifer. Both the primary flow equation and the adjoint sensitivity equation are solved using the Galerkin finite element method. The developed computer code is used to investigate the regional flow parameters of the Leadville Formation of the Paradox Basin in Utah. The results illustrate the sensitivity of calculated local heads to the boundary conditions. Alternatively, local velocity related performance measures are more sensitive to hydraulic conductivities.

  4. Summary of Research Report

    NASA Technical Reports Server (NTRS)

    Elishakoff, Isaac

    1998-01-01

    Ten papers, published in various publications, on buckling, and the effects of imperfections on various structures are presented. These papers are: (1) Buckling mode localization in elastic plates due to misplacement in the stiffner location; (2) On vibrational imperfection sensitivity on Augusti's model structure in the vicinity of a non-linear static state; (3) Imperfection sensitivity due to elastic moduli in the Roorda Koiter frame; (4) Buckling mode localization in a multi-span periodic structure with a disorder in a single span; (5) Prediction of natural frequency and buckling load variability due to uncertainty in material properties by convex modeling; (6) Derivation of multi-dimensional ellipsoidal convex model for experimental data; (7) Passive control of buckling deformation via Anderson localization phenomenon; (8)Effect of the thickness and initial im perfection on buckling on composite cylindrical shells: asymptotic analysis and numerical results by BOSOR4 and PANDA2; (9) Worst case estimation of homology design by convex analysis; (10) Buckling of structures with uncertain imperfections - Personal perspective.

  5. Spatial Analysis for Monitoring Forest Health

    Treesearch

    Francis A. Roesch

    1994-01-01

    A plan for the spatial analysis for the sample design for the detection monitoring phase in the joint USDA Forest Service/EPA Forest Health Monitoring Program (FHM) in the United States is discussed. The spatial analysis procedure is intended to more quickly identify changes in forest health by providing increased sensitivity to localized changes. The procedure is...

  6. Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using /sup 125/I-alpha scorpion toxin. I. Preferential labeling of glial cells on the presynaptic side

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boudier, J.L.; Jover, E.; Cau, P.

    1988-05-01

    Alpha-scorpion toxins bind specifically to the voltage-sensitive sodium channel in excitable membranes, and binding is potential-dependent. The radioiodinated toxin II from the scorpion Androctonus australis Hector (alpha ScTx) was used to localize voltage-sensitive sodium channels on the presynaptic side of mouse neuromuscular junctions (NMJ) by autoradiography using both light and electron microscopy. Silver grain localization was analyzed by the cross-fire method. At the light-microscopic level, grain density over NMJ appeared 6-8x higher than over nonjunctional muscle membrane. The specificity of labeling was verified by competition/displacement with an excess of native alpha ScTx. Labeling was also inhibited by incubation in depolarizingmore » conditions, showing its potential-dependence. At the electron-microscopic level, analysis showed that voltage-sensitive sodium channels labeled with alpha ScTx were almost exclusively localized on membranes, as expected. Due to washout after incubation, appreciable numbers of binding sites were not found on the postsynaptic membranes. However, on the presynaptic side, alpha ScTx-labeled voltage-sensitive sodium channels were localized on the membrane of non-myelin-forming Schwann cells covering NMJ. The axonal presynaptic membrane was not labeled. These results show that voltage-sensitive sodium channels are present on glial cells in vivo, as already demonstrated in vitro. It is proposed that these glial channels could be indirectly involved in the ionic homeostasis of the axonal environment.« less

  7. Edge crack sensitivity of lightweight materials under different load conditions

    NASA Astrophysics Data System (ADS)

    Tsoupis, I.; Merklein, M.

    2016-11-01

    This study addresses the analysis of edge crack sensitivity of DP800 steel and AA5182 aluminum alloy in dependency of punching and machining operation as well as load case of subsequent forming. The inserting of a round hole by punching with defined punch-to- die-clearance, milling and drilling is compared. Subsequent forming is performed by standardized hole expansion test and by Nakajima-tests with three different specimen geometries. Local strain distribution at the surface for Nakajima-tests is measured by optical strain measurement technique and investigated in order to evaluate local deformation before failure. Additionally, resulting hole expansion ratio λ is determined. Significant higher X as well as local strain values ε max are achieved by machined holes. This is directly coupled to higher local formability and stretchability for both materials. Furthermore, the load condition has a strong impact on the edge crack sensitivity of the material. Prior failure is observed with changing stress conditions using different specimen geometries also influencing the reachable maximum failure strain. Higher edge crack sensitivity is observed for DP800, which is in good accordance to the material properties in terms of ductility and strength. These data in dependency of the process parameter can be used for the design of automotive components.

  8. Multi-Response Parameter Interval Sensitivity and Optimization for the Composite Tape Winding Process.

    PubMed

    Deng, Bo; Shi, Yaoyao; Yu, Tao; Kang, Chao; Zhao, Pan

    2018-01-31

    The composite tape winding process, which utilizes a tape winding machine and prepreg tapes, provides a promising way to improve the quality of composite products. Nevertheless, the process parameters of composite tape winding have crucial effects on the tensile strength and void content, which are closely related to the performances of the winding products. In this article, two different object values of winding products, including mechanical performance (tensile strength) and a physical property (void content), were respectively calculated. Thereafter, the paper presents an integrated methodology by combining multi-parameter relative sensitivity analysis and single-parameter sensitivity analysis to obtain the optimal intervals of the composite tape winding process. First, the global multi-parameter sensitivity analysis method was applied to investigate the sensitivity of each parameter in the tape winding processing. Then, the local single-parameter sensitivity analysis method was employed to calculate the sensitivity of a single parameter within the corresponding range. Finally, the stability and instability ranges of each parameter were distinguished. Meanwhile, the authors optimized the process parameter ranges and provided comprehensive optimized intervals of the winding parameters. The verification test validated that the optimized intervals of the process parameters were reliable and stable for winding products manufacturing.

  9. Multi-Response Parameter Interval Sensitivity and Optimization for the Composite Tape Winding Process

    PubMed Central

    Yu, Tao; Kang, Chao; Zhao, Pan

    2018-01-01

    The composite tape winding process, which utilizes a tape winding machine and prepreg tapes, provides a promising way to improve the quality of composite products. Nevertheless, the process parameters of composite tape winding have crucial effects on the tensile strength and void content, which are closely related to the performances of the winding products. In this article, two different object values of winding products, including mechanical performance (tensile strength) and a physical property (void content), were respectively calculated. Thereafter, the paper presents an integrated methodology by combining multi-parameter relative sensitivity analysis and single-parameter sensitivity analysis to obtain the optimal intervals of the composite tape winding process. First, the global multi-parameter sensitivity analysis method was applied to investigate the sensitivity of each parameter in the tape winding processing. Then, the local single-parameter sensitivity analysis method was employed to calculate the sensitivity of a single parameter within the corresponding range. Finally, the stability and instability ranges of each parameter were distinguished. Meanwhile, the authors optimized the process parameter ranges and provided comprehensive optimized intervals of the winding parameters. The verification test validated that the optimized intervals of the process parameters were reliable and stable for winding products manufacturing. PMID:29385048

  10. Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

    PubMed

    Zeng, Xiaohui; Li, Jianhe; Peng, Liubao; Wang, Yunhua; Tan, Chongqing; Chen, Gannong; Wan, Xiaomin; Lu, Qiong; Yi, Lidan

    2014-01-01

    Maintenance gefitinib significantly prolonged progression-free survival (PFS) compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC) after four chemotherapeutic cycles (21 days per cycle) of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY) gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP) threshold of $16,349 (3 × per-capita gross domestic product of China). The sensitivity analyses all suggested that the model was robust. Maintenance gefitinib following first-line platinum-based chemotherapy for patients with locally advanced/metastatic NSCLC with unknown EGFR mutations is not cost-effective. Decreasing the price of gefitinib may be a preferential choice for meeting widely treatment demands in China.

  11. Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

    PubMed

    Silva, M M; Lemos, J M; Coito, A; Costa, B A; Wigren, T; Mendonça, T

    2014-01-01

    This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Highly specific preoperative selection of solitary parathyroid adenoma cases in primary hyperparathyroidism by quantitative image analysis of the early-phase Technetium-99m sestamibi scan.

    PubMed

    Kim, DaeHee; Rhodes, Jeffrey A; Hashim, Jeffrey A; Rickabaugh, Lawrence; Brams, David M; Pinkus, Edward; Dou, Yamin

    2018-06-07

    Highly specific preoperative localizing test is required to select patients for minimally invasive parathyroidectomy (MIP) in lieu of traditional four-gland exploration. We hypothesized that Tc-99m sestamibi scan interpretation incorporating numerical measurements on the degree of asymmetrical activity from bilateral thyroid beds can be useful in localizing single adenoma for MIP. We devised a quantitative interpretation method for Tc-99m sestamibi scan based on the numerically graded asymmetrical activity on early phase. The numerical ratio value of each scan was obtained by dividing the number of counts from symmetrically drawn regions of interest (ROI) over bilateral thyroid beds. The final pathology and clinical outcome of 109 patients were used to perform receiver operating curve (ROC) analysis. Receiver operating curve analysis revealed the area under the curve (AUC) was calculated to be 0.71 (P = 0.0032), validating this method as a diagnostic tool. The optimal cut-off point for the ratio value with maximal combined sensitivity and specificity was found with corresponding sensitivity of 67.9% (56.5-77.2%, 95% CI) and specificity of 75.0% (52.8-91.8%, 95% CI). An additional higher cut-off with higher specificity with minimal possible sacrifice on sensitivity was also selected, yielding sensitivity of 28.6% (18.8-38.6%, 95% CI) and specificity of 90.0% (69.6-98.8%, 95% CI). Our results demonstrated that the more asymmetrical activity on the initial phase, the more successful it is to localize a single parathyroid adenoma on sestamibi scans. Using early-phase Tc-99m sestamibi scan only, we were able to select patients for minimally invasive parathyroidectomy with 90% specificity. © 2018 The Royal Australian and New Zealand College of Radiologists.

  13. Local connected fractal dimension analysis in gill of fish experimentally exposed to toxicants.

    PubMed

    Manera, Maurizio; Giari, Luisa; De Pasquale, Joseph A; Sayyaf Dezfuli, Bahram

    2016-06-01

    An operator-neutral method was implemented to objectively assess European seabass, Dicentrarchus labrax (Linnaeus, 1758) gill pathology after experimental exposure to cadmium (Cd) and terbuthylazine (TBA) for 24 and 48h. An algorithm-derived local connected fractal dimension (LCFD) frequency measure was used in this comparative analysis. Canonical variates (CVA) and linear discriminant analysis (LDA) were used to evaluate the discrimination power of the method among exposure classes (unexposed, Cd exposed, TBA exposed). Misclassification, sensitivity and specificity, both with original and cross-validated cases, were determined. LCFDs frequencies enhanced the differences among classes which were visually selected after their means, respective variances and the differences between Cd and TBA exposed means, with respect to unexposed mean, were analyzed by scatter plots. Selected frequencies were then scanned by means of LDA, stepwise analysis, and Mahalanobis distance to detect the most discriminative frequencies out of ten originally selected. Discrimination resulted in 91.7% of cross-validated cases correctly classified (22 out of 24 total cases), with sensitivity and specificity, respectively, of 95.5% (1 false negative with respect to 21 really positive cases) and 75% (1 false positive with respect to 3 really negative cases). CVA with convex hull polygons ensured prompt, visually intuitive discrimination among exposure classes and graphically supported the false positive case. The combined use of semithin sections, which enhanced the visual evaluation of the overall lamellar structure; of LCFD analysis, which objectively detected local variation in complexity, without the possible bias connected to human personnel; and of CVA/LDA, could be an objective, sensitive and specific approach to study fish gill lamellar pathology. Furthermore this approach enabled discrimination with sufficient confidence between exposure classes or pathological states and avoided misdiagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Theoretical analyses of localized surface plasmon resonance spectrum with nanoparticles imprinted polymers

    NASA Astrophysics Data System (ADS)

    Li, Hong; Peng, Wei; Wang, Yanjie; Hu, Lingling; Liang, Yuzhang; Zhang, Xinpu; Yao, Wenjuan; Yu, Qi; Zhou, Xinlei

    2011-12-01

    Optical sensors based on nanoparticles induced Localized Surface Plasmon Resonance are more sensitive to real-time chemical and biological sensing, which have attracted intensive attentions in many fields. In this paper, we establish a simulation model based on nanoparticles imprinted polymer to increase sensitivity of the LSPR sensor by detecting the changes of Surface Plasmon Resonance signals. Theoretical analysis and numerical simulation of parameters effects to absorption peak and light field distribution are highlighted. Two-dimensional simulated color maps show that LSPR lead to centralization of the light energy around the gold nanoparticles, Transverse Magnetic wave and total reflection become the important factors to enhance the light field in our simulated structure. Fast Fourier Transfer analysis shows that the absorption peak of the surface plasmon resonance signal resulted from gold nanoparticles is sharper while its wavelength is bigger by comparing with silver nanoparticles; a double chain structure make the amplitude of the signals smaller, and make absorption wavelength longer; the absorption peak of enhancement resulted from nanopore arrays has smaller wavelength and weaker amplitude in contrast with nanoparticles. These simulation results of the Localized Surface Plasmon Resonance can be used as an enhanced transduction mechanism for enhancement of sensitivity in recognition and sensing of target analytes in accordance with different requirements.

  15. Quantitative method to determine the regional drinking water odorant regulation goals based on odor sensitivity distribution: illustrated using 2-MIB.

    PubMed

    Yu, Jianwei; An, Wei; Cao, Nan; Yang, Min; Gu, Junong; Zhang, Dong; Lu, Ning

    2014-07-01

    Taste and odor (T/O) in drinking water often cause consumer complaints and are thus regulated in many countries. However, people in different regions may exhibit different sensitivities toward T/O. This study proposed a method to determine the regional drinking water odorant regulation goals (ORGs) based on the odor sensitivity distribution of the local population. The distribution of odor sensitivity to 2-methylisoborneol (2-MIB) by the local population in Beijing, China was revealed by using a normal distribution function/model to describe the odor complaint response to a 2-MIB episode in 2005, and a 2-MIB concentration of 12.9 ng/L and FPA (flavor profile analysis) intensity of 2.5 was found to be the critical point to cause odor complaints. Thus the Beijing ORG for 2-MIB was determined to be 12.9 ng/L. Based on the assumption that the local FPA panel can represent the local population in terms of sensitivity to odor, and that the critical FPA intensity causing odor complaints was 2.5, this study tried to determine the ORGs for seven other cities of China by performing FPA tests using an FPA panel from the corresponding city. ORG values between 12.9 and 31.6 ng/L were determined, showing that a unified ORG may not be suitable for drinking water odor regulations. This study presents a novel approach for setting drinking water odor regulations. Copyright © 2014. Published by Elsevier B.V.

  16. Testing local Lorentz invariance with short-range gravity

    DOE PAGES

    Kostelecký, V. Alan; Mewes, Matthew

    2017-01-10

    The Newton limit of gravity is studied in the presence of Lorentz-violating gravitational operators of arbitrary mass dimension. The linearized modified Einstein equations are obtained and the perturbative solutions are constructed and characterized. We develop a formalism for data analysis in laboratory experiments testing gravity at short range and demonstrate that these tests provide unique sensitivity to deviations from local Lorentz invariance.

  17. Influence of local demography on asymptotic and transient dynamics of a yellow-bellied marmot metapopulation.

    PubMed

    Ozgul, Arpat; Oli, Madan K; Armitage, Kenneth B; Blumstein, Daniel T; Van Vuren, Dirk H

    2009-04-01

    Despite recent advances in biodemography and metapopulation ecology, we still have limited understanding of how local demographic parameters influence short- and long-term metapopulation dynamics. We used long-term data from 17 local populations, along with the recently developed methods of matrix metapopulation modeling and transient sensitivity analysis, to investigate the influence of local demography on long-term (asymptotic) versus short-term (transient) dynamics of a yellow-bellied marmot metapopulation in Colorado. Both long- and short-term dynamics depended primarily on a few colony sites and were highly sensitive to changes in demography at these sites, particularly in survival of reproductive adult females. Interestingly, the relative importance of sites differed between long- and short-term dynamics; the spatial structure and local population sizes, while insignificant for asymptotic dynamics, were influential on transient dynamics. However, considering the spatial structure was uninformative about the relative influence of local demography on metapopulation dynamics. The vital rates that were the most influential on local dynamics were also the most influential on both long- and short-term metapopulation dynamics. Our results show that an explicit consideration of local demography is essential for a complete understanding of the dynamics and persistence of spatially structured populations.

  18. Dynamical Model of Drug Accumulation in Bacteria: Sensitivity Analysis and Experimentally Testable Predictions

    DOE PAGES

    Vesselinova, Neda; Alexandrov, Boian; Wall, Michael E.

    2016-11-08

    We present a dynamical model of drug accumulation in bacteria. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation. In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal drug during acclimation. Global sensitivity analysis, local sensitivity analysis, and Bayesian sensitivity analysis of the model provide information about the robustness of these estimates, and about the relative importance of different parameters in determining the features of the accumulation time coursesmore » in three different bacterial species: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results lead to experimentally testable predictions of the effects of membrane permeability, drug efflux and trapping (e.g., by DNA binding) on drug accumulation. A key prediction is that a sudden increase in ofloxacin accumulation in both E. coli and S. aureus is accompanied by a decrease in membrane permeability.« less

  19. Dynamical Model of Drug Accumulation in Bacteria: Sensitivity Analysis and Experimentally Testable Predictions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vesselinova, Neda; Alexandrov, Boian; Wall, Michael E.

    We present a dynamical model of drug accumulation in bacteria. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation. In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal drug during acclimation. Global sensitivity analysis, local sensitivity analysis, and Bayesian sensitivity analysis of the model provide information about the robustness of these estimates, and about the relative importance of different parameters in determining the features of the accumulation time coursesmore » in three different bacterial species: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results lead to experimentally testable predictions of the effects of membrane permeability, drug efflux and trapping (e.g., by DNA binding) on drug accumulation. A key prediction is that a sudden increase in ofloxacin accumulation in both E. coli and S. aureus is accompanied by a decrease in membrane permeability.« less

  20. The management of patients with T1 adenocarcinoma of the low rectum: a decision analysis.

    PubMed

    Johnston, Calvin F; Tomlinson, George; Temple, Larissa K; Baxter, Nancy N

    2013-04-01

    Decision making for patients with T1 adenocarcinoma of the low rectum, when treatment options are limited to a transanal local excision or abdominoperineal resection, is challenging. The aim of this study was to develop a contemporary decision analysis to assist patients and clinicians in balancing the goals of maximizing life expectancy and quality of life in this situation. We constructed a Markov-type microsimulation in open-source software. Recurrence rates and quality-of-life parameters were elicited by systematic literature reviews. Sensitivity analyses were performed on key model parameters. Our base case for analysis was a 65-year-old man with low-lying T1N0 rectal cancer. We determined the sensitivity of our model for sex, age up to 80, and T stage. The main outcome measured was quality-adjusted life-years. In the base case, selecting transanal local excision over abdominoperineal resection resulted in a loss of 0.53 years of life expectancy but a gain of 0.97 quality-adjusted life-years. One-way sensitivity analysis demonstrated a health state utility value threshold for permanent colostomy of 0.93. This value ranged from 0.88 to 1.0 based on tumor recurrence risk. There were no other model sensitivities. Some model parameter estimates were based on weak data. In our model, transanal local excision was found to be the preferable approach for most patients. An abdominoperineal resection has a 3.5% longer life expectancy, but this advantage is lost when the quality-of-life reduction reported by stoma patients is weighed in. The minority group in whom abdominoperineal resection is preferred are those who are unwilling to sacrifice 7% of their life expectancy to avoid a permanent stoma. This is estimated to be approximately 25% of all patients. The threshold increases to 12% of life expectancy in high-risk tumors. No other factors are found to be relevant to the decision.

  1. Benchmark Data Set for Wheat Growth Models: Field Experiments and AgMIP Multi-Model Simulations.

    NASA Technical Reports Server (NTRS)

    Asseng, S.; Ewert, F.; Martre, P.; Rosenzweig, C.; Jones, J. W.; Hatfield, J. L.; Ruane, A. C.; Boote, K. J.; Thorburn, P.J.; Rotter, R. P.

    2015-01-01

    The data set includes a current representative management treatment from detailed, quality-tested sentinel field experiments with wheat from four contrasting environments including Australia, The Netherlands, India and Argentina. Measurements include local daily climate data (solar radiation, maximum and minimum temperature, precipitation, surface wind, dew point temperature, relative humidity, and vapor pressure), soil characteristics, frequent growth, nitrogen in crop and soil, crop and soil water and yield components. Simulations include results from 27 wheat models and a sensitivity analysis with 26 models and 30 years (1981-2010) for each location, for elevated atmospheric CO2 and temperature changes, a heat stress sensitivity analysis at anthesis, and a sensitivity analysis with soil and crop management variations and a Global Climate Model end-century scenario.

  2. Singularity-sensitive gauge-based radar rainfall adjustment methods for urban hydrological applications

    NASA Astrophysics Data System (ADS)

    Wang, L.-P.; Ochoa-Rodríguez, S.; Onof, C.; Willems, P.

    2015-09-01

    Gauge-based radar rainfall adjustment techniques have been widely used to improve the applicability of radar rainfall estimates to large-scale hydrological modelling. However, their use for urban hydrological applications is limited as they were mostly developed based upon Gaussian approximations and therefore tend to smooth off so-called "singularities" (features of a non-Gaussian field) that can be observed in the fine-scale rainfall structure. Overlooking the singularities could be critical, given that their distribution is highly consistent with that of local extreme magnitudes. This deficiency may cause large errors in the subsequent urban hydrological modelling. To address this limitation and improve the applicability of adjustment techniques at urban scales, a method is proposed herein which incorporates a local singularity analysis into existing adjustment techniques and allows the preservation of the singularity structures throughout the adjustment process. In this paper the proposed singularity analysis is incorporated into the Bayesian merging technique and the performance of the resulting singularity-sensitive method is compared with that of the original Bayesian (non singularity-sensitive) technique and the commonly used mean field bias adjustment. This test is conducted using as case study four storm events observed in the Portobello catchment (53 km2) (Edinburgh, UK) during 2011 and for which radar estimates, dense rain gauge and sewer flow records, as well as a recently calibrated urban drainage model were available. The results suggest that, in general, the proposed singularity-sensitive method can effectively preserve the non-normality in local rainfall structure, while retaining the ability of the original adjustment techniques to generate nearly unbiased estimates. Moreover, the ability of the singularity-sensitive technique to preserve the non-normality in rainfall estimates often leads to better reproduction of the urban drainage system's dynamics, particularly of peak runoff flows.

  3. Non-parametric correlative uncertainty quantification and sensitivity analysis: Application to a Langmuir bimolecular adsorption model

    NASA Astrophysics Data System (ADS)

    Feng, Jinchao; Lansford, Joshua; Mironenko, Alexander; Pourkargar, Davood Babaei; Vlachos, Dionisios G.; Katsoulakis, Markos A.

    2018-03-01

    We propose non-parametric methods for both local and global sensitivity analysis of chemical reaction models with correlated parameter dependencies. The developed mathematical and statistical tools are applied to a benchmark Langmuir competitive adsorption model on a close packed platinum surface, whose parameters, estimated from quantum-scale computations, are correlated and are limited in size (small data). The proposed mathematical methodology employs gradient-based methods to compute sensitivity indices. We observe that ranking influential parameters depends critically on whether or not correlations between parameters are taken into account. The impact of uncertainty in the correlation and the necessity of the proposed non-parametric perspective are demonstrated.

  4. On the sensitivity of complex, internally coupled systems

    NASA Technical Reports Server (NTRS)

    Sobieszczanskisobieski, Jaroslaw

    1988-01-01

    A method is presented for computing sensitivity derivatives with respect to independent (input) variables for complex, internally coupled systems, while avoiding the cost and inaccuracy of finite differencing performed on the entire system analysis. The method entails two alternative algorithms: the first is based on the classical implicit function theorem formulated on residuals of governing equations, and the second develops the system sensitivity equations in a new form using the partial (local) sensitivity derivatives of the output with respect to the input of each part of the system. A few application examples are presented to illustrate the discussion.

  5. Eigenvalue sensitivity analysis of planar frames with variable joint and support locations

    NASA Technical Reports Server (NTRS)

    Chuang, Ching H.; Hou, Gene J. W.

    1991-01-01

    Two sensitivity equations are derived in this study based upon the continuum approach for eigenvalue sensitivity analysis of planar frame structures with variable joint and support locations. A variational form of an eigenvalue equation is first derived in which all of the quantities are expressed in the local coordinate system attached to each member. Material derivative of this variational equation is then sought to account for changes in member's length and orientation resulting form the perturbation of joint and support locations. Finally, eigenvalue sensitivity equations are formulated in either domain quantities (by the domain method) or boundary quantities (by the boundary method). It is concluded that the sensitivity equation derived by the boundary method is more efficient in computation but less accurate than that of the domain method. Nevertheless, both of them in terms of computational efficiency are superior to the conventional direct differentiation method and the finite difference method.

  6. Stochastic sensitivity measure for mistuned high-performance turbines

    NASA Technical Reports Server (NTRS)

    Murthy, Durbha V.; Pierre, Christophe

    1992-01-01

    A stochastic measure of sensitivity is developed in order to predict the effects of small random blade mistuning on the dynamic aeroelastic response of turbomachinery blade assemblies. This sensitivity measure is based solely on the nominal system design (i.e., on tuned system information), which makes it extremely easy and inexpensive to calculate. The measure has the potential to become a valuable design tool that will enable designers to evaluate mistuning effects at a preliminary design stage and thus assess the need for a full mistuned rotor analysis. The predictive capability of the sensitivity measure is illustrated by examining the effects of mistuning on the aeroelastic modes of the first stage of the oxidizer turbopump in the Space Shuttle Main Engine. Results from a full analysis mistuned systems confirm that the simple stochastic sensitivity measure predicts consistently the drastic changes due to misturning and the localization of aeroelastic vibration to a few blades.

  7. Perceptual interaction of local motion signals

    PubMed Central

    Nitzany, Eyal I.; Loe, Maren E.; Palmer, Stephanie E.; Victor, Jonathan D.

    2016-01-01

    Motion signals are a rich source of information used in many everyday tasks, such as segregation of objects from background and navigation. Motion analysis by biological systems is generally considered to consist of two stages: extraction of local motion signals followed by spatial integration. Studies using synthetic stimuli show that there are many kinds and subtypes of local motion signals. When presented in isolation, these stimuli elicit behavioral and neurophysiological responses in a wide range of species, from insects to mammals. However, these mathematically-distinct varieties of local motion signals typically co-exist in natural scenes. This study focuses on interactions between two kinds of local motion signals: Fourier and glider. Fourier signals are typically associated with translation, while glider signals occur when an object approaches or recedes. Here, using a novel class of synthetic stimuli, we ask how distinct kinds of local motion signals interact and whether context influences sensitivity to Fourier motion. We report that local motion signals of different types interact at the perceptual level, and that this interaction can include subthreshold summation and, in some subjects, subtle context-dependent changes in sensitivity. We discuss the implications of these observations, and the factors that may underlie them. PMID:27902829

  8. Perceptual interaction of local motion signals.

    PubMed

    Nitzany, Eyal I; Loe, Maren E; Palmer, Stephanie E; Victor, Jonathan D

    2016-11-01

    Motion signals are a rich source of information used in many everyday tasks, such as segregation of objects from background and navigation. Motion analysis by biological systems is generally considered to consist of two stages: extraction of local motion signals followed by spatial integration. Studies using synthetic stimuli show that there are many kinds and subtypes of local motion signals. When presented in isolation, these stimuli elicit behavioral and neurophysiological responses in a wide range of species, from insects to mammals. However, these mathematically-distinct varieties of local motion signals typically co-exist in natural scenes. This study focuses on interactions between two kinds of local motion signals: Fourier and glider. Fourier signals are typically associated with translation, while glider signals occur when an object approaches or recedes. Here, using a novel class of synthetic stimuli, we ask how distinct kinds of local motion signals interact and whether context influences sensitivity to Fourier motion. We report that local motion signals of different types interact at the perceptual level, and that this interaction can include subthreshold summation and, in some subjects, subtle context-dependent changes in sensitivity. We discuss the implications of these observations, and the factors that may underlie them.

  9. Deterministic Local Sensitivity Analysis of Augmented Systems - II: Applications to the QUENCH-04 Experiment Using the RELAP5/MOD3.2 Code System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ionescu-Bujor, Mihaela; Jin Xuezhou; Cacuci, Dan G.

    2005-09-15

    The adjoint sensitivity analysis procedure for augmented systems for application to the RELAP5/MOD3.2 code system is illustrated. Specifically, the adjoint sensitivity model corresponding to the heat structure models in RELAP5/MOD3.2 is derived and subsequently augmented to the two-fluid adjoint sensitivity model (ASM-REL/TF). The end product, called ASM-REL/TFH, comprises the complete adjoint sensitivity model for the coupled fluid dynamics/heat structure packages of the large-scale simulation code RELAP5/MOD3.2. The ASM-REL/TFH model is validated by computing sensitivities to the initial conditions for various time-dependent temperatures in the test bundle of the Quench-04 reactor safety experiment. This experiment simulates the reflooding with water ofmore » uncovered, degraded fuel rods, clad with material (Zircaloy-4) that has the same composition and size as that used in typical pressurized water reactors. The most important response for the Quench-04 experiment is the time evolution of the cladding temperature of heated fuel rods. The ASM-REL/TFH model is subsequently used to perform an illustrative sensitivity analysis of this and other time-dependent temperatures within the bundle. The results computed by using the augmented adjoint sensitivity system, ASM-REL/TFH, highlight the reliability, efficiency, and usefulness of the adjoint sensitivity analysis procedure for computing time-dependent sensitivities.« less

  10. Sensitivity of charge transport measurements to local inhomogeneities

    NASA Astrophysics Data System (ADS)

    Koon, Daniel; Wang, Fei; Hjorth Petersen, Dirch; Hansen, Ole

    2012-02-01

    We derive analytic expressions for the sensitivity of resistive and Hall measurements to local variations in a specimen's material properties in the combined linear limit of both small magnetic fields and small perturbations, presenting exact, algebraic expressions both for four-point probe measurements on an infinite plane and for symmetric, circular van der Pauw discs. We then generalize the results to obtain corrections to the sensitivities both for finite magnetic fields and for finite perturbations. Calculated functions match published results and computer simulations, and provide an intuitive, visual explanation for experimental misassignment of carrier type in n-type ZnO and agree with published experimental results for holes in a uniform material. These results simplify calculation and plotting of the sensitivities on an NxN grid from a problem of order N^5 to one of order N^3 in the arbitrary case and of order N^2 in the handful of cases that can be solved exactly, putting a powerful tool for inhomogeneity analysis in the hands of the researcher: calculation of the sensitivities requires little more than the solution of Laplace's equation on the specimen geometry.

  11. Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B–induced local skin hypersensitization in healthy subjects: a machine-learned analysis

    PubMed Central

    Lötsch, Jörn; Geisslinger, Gerd; Heinemann, Sarah; Lerch, Florian; Oertel, Bruno G.; Ultsch, Alfred

    2018-01-01

    Abstract The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models. PMID:28700537

  12. The Scaffold Attachment Factor SAFB1: A New Player in G2/M Checkpoint Control

    DTIC Science & Technology

    2007-04-01

    RNA was obtained from locally advanced breast tumors in 24 patients before they underwent four cycles of neoadjuvant docetaxel treatment . Gene...expression analysis was performed and correlated to the treatment response to determine genes that are differentially expressed in docetaxel-sensitive...decreased sensitivity to drugs, depending on the chemotherapeutic agent used 2) Association of SAFB1 loss with resistance to docetaxel treatment , both

  13. Quantitative relationship between the local lymph node assay and human skin sensitization assays.

    PubMed

    Schneider, K; Akkan, Z

    2004-06-01

    The local lymph node assay (LLNA) is a new test method which allows for the quantitative assessment of sensitizing potency in the mouse. Here, we investigate the quantitative correlation between results from the LLNA and two human sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs). Data for 57 substances were evaluated, of which 46 showed skin sensitizing properties in human tests, whereas 11 yielded negative results in humans. For better comparability data from mouse and human tests were transformed to applied doses per skin area, which ranged over four orders of magnitude for the substances considered. Regression analysis for the 46 human sensitizing substances revealed a significant positive correlation between the LLNA and human tests. The correlation was better between LLNA and HRIPT data (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed scattering of data points is related to various uncertainties, in part associated with insufficiencies of data from older HMT studies. Predominantly negative results in the LLNA for another 11 substances which showed no skin sensitizing activity in human maximization tests further corroborate the correspondence between LLNA and human tests. Based on this analysis, the LLNA can be considered a reliable basis for relative potency assessments for skin sensitizers. Proposals are made for the regulatory exploitation of the LLNA: four potency groups can be established, and assignment of substances to these groups according to the outcome of the LLNA can be used to characterize skin sensitizing potency in substance-specific assessments. Moreover, based on these potency groups, a more adequate consideration of sensitizing substances in preparations becomes possible. It is proposed to replace the current single concentration limit for skin sensitizers in preparations, which leads to an all or nothing classification of a preparation as sensitizing to skin ("R43") in the European Union, by differentiated concentration limits derived from the limits for the four potency groups.

  14. Managing the environmental impacts of land transport: integrating environmental analysis with urban planning.

    PubMed

    Irving, Paul; Moncrieff, Ian

    2004-12-01

    Ecological systems have limits or thresholds that vary by pollutant type, emissions sources and the sensitivity of a given location. Human health can also indicate sensitivity. Good environmental management requires any problem to be defined to obtain efficient and effective solutions. Cities are where transport activities, effects and resource management decisions are often most focussed. The New Zealand Ministry of Transport has developed two environmental management tools. The Vehicle Fleet Model (VFM) is a predictive database of the environmental performance of the New Zealand traffic fleet (and rail fleet). It calculates indices of local air quality, stormwater, and greenhouse gases emissions. The second is an analytical process based on Environmental Capacity Analysis (ECA). Information on local traffic is combined with environmental performance data from the Vehicle Fleet Model. This can be integrated within a live, geo-spatially defined analysis of the overall environmental effects within a defined local area. Variations in urban form and activity (traffic and other) that contribute to environmental effects can be tracked. This enables analysis of a range of mitigation strategies that may contribute, now or in the future, to maintaining environmental thresholds or meeting targets. A case study of the application of this approach was conducted within Waitakere City. The focus was on improving the understanding of the relative significance of stormwater contaminants derived from land transport.

  15. Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

    PubMed Central

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

    2017-01-01

    Purpose To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. Results 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. Conclusions CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR. PMID:28042958

  16. Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile.

    PubMed

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

    2017-01-31

    To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR.

  17. Comparative Diagnostic Performance of Ultrasonography and 99mTc-Sestamibi Scintigraphy for Parathyroid Adenoma in Primary Hyperparathyroidism; Systematic Review and Meta- Analysis

    PubMed

    Nafisi Moghadam, Reza; Amlelshahbaz, Amir Pasha; Namiranian, Nasim; Sobhan-Ardekani, Mohammad; Emami-Meybodi, Mahmood; Dehghan, Ali; Rahmanian, Masoud; Razavi-Ratki, Seid Kazem

    2017-12-28

    Objective: Ultrasonography (US) and parathyroid scintigraphy (PS) with 99mTc-MIBI are common methods for preoperative localization of parathyroid adenomas but there discrepancies exist with regard to diagnostic accuracy. The aim of the study was to compare PS and US for localization of parathyroid adenoma with a systematic review and meta-analysis of the literature. Methods: Pub Med, Scopus (EMbase), Web of Science and the reference lists of all included studies were searched up to 1st January 2016. The search strategy was according PICO characteristics. Heterogeneity between the studies was accounted by P < 0.1. Point estimates were pooled estimate of sensitivity, specificity and positive predictive value of SPECT and ultrasonography with 99% confidence intervals (CIs) by pooling available data. Data analysis was performed using Meta-DiSc software (version 1.4). Results: Among 188 studies and after deletion of duplicated studies (75), a total of 113 titles and abstracts were studied. From these, 12 studies were selected. The meta-analysis determined a pooled sensitivity for scintigraphy of 83% [99% confidence interval (CI) 96.358 -97.412] and for ultra-sonography of 80% [99% confidence interval (CI) 76-83]. Similar results for specificity were also obtained for both approache. Conclusion: According this meta- analysis, there were no significant differences between the two methods in terms of sensitivity and specificity. There were overlaps in 99% confidence intervals. Also features of the two methods are similar. Creative Commons Attribution License

  18. Acoustic-articulatory mapping in vowels by locally weighted regression

    PubMed Central

    McGowan, Richard S.; Berger, Michael A.

    2009-01-01

    A method for mapping between simultaneously measured articulatory and acoustic data is proposed. The method uses principal components analysis on the articulatory and acoustic variables, and mapping between the domains by locally weighted linear regression, or loess [Cleveland, W. S. (1979). J. Am. Stat. Assoc. 74, 829–836]. The latter method permits local variation in the slopes of the linear regression, assuming that the function being approximated is smooth. The methodology is applied to vowels of four speakers in the Wisconsin X-ray Microbeam Speech Production Database, with formant analysis. Results are examined in terms of (1) examples of forward (articulation-to-acoustics) mappings and inverse mappings, (2) distributions of local slopes and constants, (3) examples of correlations among slopes and constants, (4) root-mean-square error, and (5) sensitivity of formant frequencies to articulatory change. It is shown that the results are qualitatively correct and that loess performs better than global regression. The forward mappings show different root-mean-square error properties than the inverse mappings indicating that this method is better suited for the forward mappings than the inverse mappings, at least for the data chosen for the current study. Some preliminary results on sensitivity of the first two formant frequencies to the two most important articulatory principal components are presented. PMID:19813812

  19. Design and analysis for detection monitoring of forest health

    Treesearch

    F. A. Roesch

    1995-01-01

    An analysis procedure is proposed for the sample design of the Forest Health Monitoring Program (FHM) in the United States. The procedure is intended to provide increased sensitivity to localized but potentially important changes in forest health by explicitly accounting for the spatial relationships between plots in the FHM design. After a series of median sweeps...

  20. Heat-Energy Analysis for Solar Receivers

    NASA Technical Reports Server (NTRS)

    Lansing, F. L.

    1982-01-01

    Heat-energy analysis program (HEAP) solves general heat-transfer problems, with some specific features that are "custom made" for analyzing solar receivers. Can be utilized not only to predict receiver performance under varying solar flux, ambient temperature and local heat-transfer rates but also to detect locations of hotspots and metallurgical difficulties and to predict performance sensitivity of neighboring component parameters.

  1. Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay.

    PubMed

    Dearman, Rebecca J; Betts, Catherine J; Farr, Craig; McLaughlin, James; Berdasco, Nancy; Wiench, Karin; Kimber, Ian

    2007-10-01

    There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose-response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (<10%) and weak (>10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential.

  2. Effects of strain differences and vehicles on results of local lymph node assays.

    PubMed

    Anzai, Takayuki; Ullmann, Ludwig G; Hayashi, Daisuke; Satoh, Tetsuo; Kumazawa, Takeshi; Sato, Keizo

    2010-01-01

    The Local Lymph Node Assay (LLNA) is now regarded as the worldwide standard. The analysis of accumulated LLNA data reveals that the animal strains and vehicles employed are likely to affect LLNA results. Here we show that an obvious strain difference in the local lymph node response was observed between DMSO-treated CBA/CaOlaHsd and CBA/CaHsdRcc mice. We also show that a vehicle difference in the response was observed when CBA/CaHsdRcc mice were exposed to 6 vehicles; 4:1 v/v acetone/olive oil (AOO), ethanol/water (70% EtOH), N,N-dimethylformamide (DMF), 2-butanone (BN), propylene glycol (PG), and dimethylsulfoxide (DMSO). The dpm/LN level was lowest in the 70% EtOH group and highest in the DMSO group. When alpha-hexylcinnamaldehyde (HCA) was used as a sensitizer for the LLNA, HCA was a weak sensitizer when AOO or DMSO was used as a vehicle, but a moderate sensitizer when the other 4 vehicles were used. This study showed that there are vehicle differences in the local lymph node response (dpm/LN level) in the LLNA and that the sensitization potency of HCA may be classified in different categories when using different vehicles. This suggests that careful consideration should be exercised in selecting a vehicle for the LLNA. A further comprehensive study will be needed to investigate why vehicle differences are observed in the LLNA.

  3. Modification of YAPE keypoint detection algorithm for wide local contrast range images

    NASA Astrophysics Data System (ADS)

    Lukoyanov, A.; Nikolaev, D.; Konovalenko, I.

    2018-04-01

    Keypoint detection is an important tool of image analysis, and among many contemporary keypoint detection algorithms YAPE is known for its computational performance, allowing its use in mobile and embedded systems. One of its shortcomings is high sensitivity to local contrast which leads to high detection density in high-contrast areas while missing detections in low-contrast ones. In this work we study the contrast sensitivity of YAPE and propose a modification which compensates for this property on images with wide local contrast range (Yet Another Contrast-Invariant Point Extractor, YACIPE). As a model example, we considered the traffic sign recognition problem, where some signs are well-lighted, whereas others are in shadows and thus have low contrast. We show that the number of traffic signs on the image of which has not been detected any keypoints is 40% less for the proposed modification compared to the original algorithm.

  4. Normalized Polarization Ratios for the Analysis of Cell Polarity

    PubMed Central

    Shimoni, Raz; Pham, Kim; Yassin, Mohammed; Ludford-Menting, Mandy J.; Gu, Min; Russell, Sarah M.

    2014-01-01

    The quantification and analysis of molecular localization in living cells is increasingly important for elucidating biological pathways, and new methods are rapidly emerging. The quantification of cell polarity has generated much interest recently, and ratiometric analysis of fluorescence microscopy images provides one means to quantify cell polarity. However, detection of fluorescence, and the ratiometric measurement, is likely to be sensitive to acquisition settings and image processing parameters. Using imaging of EGFP-expressing cells and computer simulations of variations in fluorescence ratios, we characterized the dependence of ratiometric measurements on processing parameters. This analysis showed that image settings alter polarization measurements; and that clustered localization is more susceptible to artifacts than homogeneous localization. To correct for such inconsistencies, we developed and validated a method for choosing the most appropriate analysis settings, and for incorporating internal controls to ensure fidelity of polarity measurements. This approach is applicable to testing polarity in all cells where the axis of polarity is known. PMID:24963926

  5. Pneumothorax detection in chest radiographs using local and global texture signatures

    NASA Astrophysics Data System (ADS)

    Geva, Ofer; Zimmerman-Moreno, Gali; Lieberman, Sivan; Konen, Eli; Greenspan, Hayit

    2015-03-01

    A novel framework for automatic detection of pneumothorax abnormality in chest radiographs is presented. The suggested method is based on a texture analysis approach combined with supervised learning techniques. The proposed framework consists of two main steps: at first, a texture analysis process is performed for detection of local abnormalities. Labeled image patches are extracted in the texture analysis procedure following which local analysis values are incorporated into a novel global image representation. The global representation is used for training and detection of the abnormality at the image level. The presented global representation is designed based on the distinctive shape of the lung, taking into account the characteristics of typical pneumothorax abnormalities. A supervised learning process was performed on both the local and global data, leading to trained detection system. The system was tested on a dataset of 108 upright chest radiographs. Several state of the art texture feature sets were experimented with (Local Binary Patterns, Maximum Response filters). The optimal configuration yielded sensitivity of 81% with specificity of 87%. The results of the evaluation are promising, establishing the current framework as a basis for additional improvements and extensions.

  6. SENSITIVITY OF BLIND PULSAR SEARCHES WITH THE FERMI LARGE AREA TELESCOPE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dormody, M.; Johnson, R. P.; Atwood, W. B.

    2011-12-01

    We quantitatively establish the sensitivity to the detection of young to middle-aged, isolated, gamma-ray pulsars through blind searches of Fermi Large Area Telescope (LAT) data using a Monte Carlo simulation. We detail a sensitivity study of the time-differencing blind search code used to discover gamma-ray pulsars in the first year of observations. We simulate 10,000 pulsars across a broad parameter space and distribute them across the sky. We replicate the analysis in the Fermi LAT First Source Catalog to localize the sources, and the blind search analysis to find the pulsars. We analyze the results and discuss the effect ofmore » positional error and spin frequency on gamma-ray pulsar detections. Finally, we construct a formula to determine the sensitivity of the blind search and present a sensitivity map assuming a standard set of pulsar parameters. The results of this study can be applied to population studies and are useful in characterizing unidentified LAT sources.« less

  7. {sup 18}F-Choline Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging for the Detection of Early Local Recurrence of Prostate Cancer Initially Treated by Radiation Therapy: Comparison With Systematic 3-Dimensional Transperineal Mapping Biopsy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kanoun, Salim, E-mail: Salim.kanoun@gmail.com; LE2I UMR6306, Centre national de la recherche scientifique, Arts et Métiers, Université Bourgogne Franche-Comté, Dijon; MRI Unit, Centre Hospitalier Régional Universitaire, Hôpital François Mitterrand, Dijon

    Purpose: To compare the diagnostic performance of {sup 18}F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT), multiparametric prostate magnetic resonance imaging (mpMRI), and a combination of both techniques for the detection of local recurrence of prostate cancer initially treated by radiation therapy. Methods and Materials: This was a retrospective, single-institution study of 32 patients with suspected prostate cancer recurrence who underwent both FCH-PET/CT and 3T mpMRI within 3 months of one another for the detection of recurrence. All included patients had to be cleared for metastatic recurrence. The reference procedure was systematic 3-dimensional (3D)-transperineal prostate biopsy for the final assessment of local recurrence.more » Both imaging modalities were analyzed by 2 experienced readers blinded to clinical data. The analysis was made per-patient and per-segment using a 4-segment model. Results: The median prostate-specific antigen value at the time of imaging was 2.92 ng/mL. The mean prostate-specific antigen doubling time was 14 months. Of the 32 patients, 31 had a positive 3D-transperineal mapping biopsy for a local relapse. On a patient-based analysis, the detection rate was 71% (22 of 31) for mpMRI and 74% (23 of 31) for FCH-PET/CT. On a segment-based analysis, the sensitivity and specificity were, respectively, 32% and 87% for mpMRI, 34% and 87% for FCH-PET/CT, and 43% and 83% for the combined analysis of both techniques. Accuracy was 64%, 65%, and 66%, respectively. The interobserver agreement was κ = 0.92 for FCH-PET/CT and κ = 0.74 for mpMRI. Conclusions: Both mpMRI and FCH-PET/CT show limited sensitivity but good specificity for the detection of local cancer recurrence after radiation therapy, when compared with 3D-transperineal mapping biopsy. Prostate biopsy still seems to be mandatory to diagnose local relapse and select patients who could benefit from local salvage therapy.« less

  8. Comparative sensitivities of functional MRI sequences in detection of local recurrence of prostate carcinoma after radical prostatectomy or external-beam radiotherapy.

    PubMed

    Roy, Catherine; Foudi, Fatah; Charton, Jeanne; Jung, Michel; Lang, Hervé; Saussine, Christian; Jacqmin, Didier

    2013-04-01

    The aim of this retrospective study was to determine the respective accuracies of three types of functional MRI sequences-diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and 3D (1)H-MR spectroscopy (MRS)-in the depiction of local prostate cancer recurrence after two different initial therapy options. From a cohort of 83 patients with suspicion of local recurrence based on prostate-specific antigen (PSA) kinetics who were imaged on a 3-T MRI unit using an identical protocol including the three functional sequences with an endorectal coil, we selected 60 patients (group A, 28 patients who underwent radical prostatectomy; group B, 32 patients who underwent external-beam radiation) who had local recurrence ascertained on the basis of a transrectal ultrasound-guided biopsy results and a reduction in PSA level after salvage therapy. All patients presented with a local relapse. Sensitivity with T2-weighted MRI and 3D (1)H-MRS sequences was 57% and 53%, respectively, for group A and 71% and 78%, respectively, for group B. DCE-MRI alone showed a sensitivity of 100% and 96%, respectively, for groups A and B. DWI alone had a higher sensitivity for group B (96%) than for group A (71%). The combination of T2-weighted imaging plus DWI plus DCE-MRI provided a sensitivity as high as 100% in group B. The performance of functional imaging sequences for detecting recurrence is different after radical prostatectomy and external-beam radiotherapy. DCE-MRI is a valid and efficient tool to detect prostate cancer recurrence in radical prostatectomy as well as in external-beam radiotherapy. The combination of DCE-MRI and DWI is highly efficient after radiation therapy. Three-dimensional (1)H-MRS needs to be improved. Even though it is not accurate enough, T2-weighted imaging remains essential for the morphologic analysis of the area.

  9. Pavement thickness design for local roads in Iowa : tech brief.

    DOT National Transportation Integrated Search

    2010-01-01

    The main objectives of this research are to: 1) identify the most critical design input parameters, 2) determine the minimum pavement thickness, and 3) develop new pavement design and sensitivity analysis (PD&SA) software which can provide the most a...

  10. Reduction and Uncertainty Analysis of Chemical Mechanisms Based on Local and Global Sensitivities

    NASA Astrophysics Data System (ADS)

    Esposito, Gaetano

    Numerical simulations of critical reacting flow phenomena in hypersonic propulsion devices require accurate representation of finite-rate chemical kinetics. The chemical kinetic models available for hydrocarbon fuel combustion are rather large, involving hundreds of species and thousands of reactions. As a consequence, they cannot be used in multi-dimensional computational fluid dynamic calculations in the foreseeable future due to the prohibitive computational cost. In addition to the computational difficulties, it is also known that some fundamental chemical kinetic parameters of detailed models have significant level of uncertainty due to limited experimental data available and to poor understanding of interactions among kinetic parameters. In the present investigation, local and global sensitivity analysis techniques are employed to develop a systematic approach of reducing and analyzing detailed chemical kinetic models. Unlike previous studies in which skeletal model reduction was based on the separate analysis of simple cases, in this work a novel strategy based on Principal Component Analysis of local sensitivity values is presented. This new approach is capable of simultaneously taking into account all the relevant canonical combustion configurations over different composition, temperature and pressure conditions. Moreover, the procedure developed in this work represents the first documented inclusion of non-premixed extinction phenomena, which is of great relevance in hypersonic combustors, in an automated reduction algorithm. The application of the skeletal reduction to a detailed kinetic model consisting of 111 species in 784 reactions is demonstrated. The resulting reduced skeletal model of 37--38 species showed that the global ignition/propagation/extinction phenomena of ethylene-air mixtures can be predicted within an accuracy of 2% of the full detailed model. The problems of both understanding non-linear interactions between kinetic parameters and identifying sources of uncertainty affecting relevant reaction pathways are usually addressed by resorting to Global Sensitivity Analysis (GSA) techniques. In particular, the most sensitive reactions controlling combustion phenomena are first identified using the Morris Method and then analyzed under the Random Sampling -- High Dimensional Model Representation (RS-HDMR) framework. The HDMR decomposition shows that 10% of the variance seen in the extinction strain rate of non-premixed flames is due to second-order effects between parameters, whereas the maximum concentration of acetylene, a key soot precursor, is affected by mostly only first-order contributions. Moreover, the analysis of the global sensitivity indices demonstrates that improving the accuracy of the reaction rates including the vinyl radical, C2H3, can drastically reduce the uncertainty of predicting targeted flame properties. Finally, the back-propagation of the experimental uncertainty of the extinction strain rate to the parameter space is also performed. This exercise, achieved by recycling the numerical solutions of the RS-HDMR, shows that some regions of the parameter space have a high probability of reproducing the experimental value of the extinction strain rate between its own uncertainty bounds. Therefore this study demonstrates that the uncertainty analysis of bulk flame properties can effectively provide information on relevant chemical reactions.

  11. Structural optimization: Status and promise

    NASA Astrophysics Data System (ADS)

    Kamat, Manohar P.

    Chapters contained in this book include fundamental concepts of optimum design, mathematical programming methods for constrained optimization, function approximations, approximate reanalysis methods, dual mathematical programming methods for constrained optimization, a generalized optimality criteria method, and a tutorial and survey of multicriteria optimization in engineering. Also included are chapters on the compromise decision support problem and the adaptive linear programming algorithm, sensitivity analyses of discrete and distributed systems, the design sensitivity analysis of nonlinear structures, optimization by decomposition, mixed elements in shape sensitivity analysis of structures based on local criteria, and optimization of stiffened cylindrical shells subjected to destabilizing loads. Other chapters are on applications to fixed-wing aircraft and spacecraft, integrated optimum structural and control design, modeling concurrency in the design of composite structures, and tools for structural optimization. (No individual items are abstracted in this volume)

  12. A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

    PubMed Central

    Mueller, Jenna L.; Fu, Henry L.; Mito, Jeffrey K.; Whitley, Melodi J.; Chitalia, Rhea; Erkanli, Alaattin; Dodd, Leslie; Cardona, Diana M.; Geradts, Joseph; Willett, Rebecca M.; Kirsch, David G.; Ramanujam, Nimmi

    2015-01-01

    The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence. PMID:25994353

  13. Online and offline tools for head movement compensation in MEG.

    PubMed

    Stolk, Arjen; Todorovic, Ana; Schoffelen, Jan-Mathijs; Oostenveld, Robert

    2013-03-01

    Magnetoencephalography (MEG) is measured above the head, which makes it sensitive to variations of the head position with respect to the sensors. Head movements blur the topography of the neuronal sources of the MEG signal, increase localization errors, and reduce statistical sensitivity. Here we describe two novel and readily applicable methods that compensate for the detrimental effects of head motion on the statistical sensitivity of MEG experiments. First, we introduce an online procedure that continuously monitors head position. Second, we describe an offline analysis method that takes into account the head position time-series. We quantify the performance of these methods in the context of three different experimental settings, involving somatosensory, visual and auditory stimuli, assessing both individual and group-level statistics. The online head localization procedure allowed for optimal repositioning of the subjects over multiple sessions, resulting in a 28% reduction of the variance in dipole position and an improvement of up to 15% in statistical sensitivity. Offline incorporation of the head position time-series into the general linear model resulted in improvements of group-level statistical sensitivity between 15% and 29%. These tools can substantially reduce the influence of head movement within and between sessions, increasing the sensitivity of many cognitive neuroscience experiments. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Evaluating the quality of NMR structures by local density of protons.

    PubMed

    Ban, Yih-En Andrew; Rudolph, Johannes; Zhou, Pei; Edelsbrunner, Herbert

    2006-03-01

    Evaluating the quality of experimentally determined protein structural models is an essential step toward identifying potential errors and guiding further structural refinement. Herein, we report the use of proton local density as a sensitive measure to assess the quality of nuclear magnetic resonance (NMR) structures. Using 256 high-resolution crystal structures with protons added and optimized, we show that the local density of different proton types display distinct distributions. These distributions can be characterized by statistical moments and are used to establish local density Z-scores for evaluating both global and local packing for individual protons. Analysis of 546 crystal structures at various resolutions shows that the local density Z-scores increase as the structural resolution decreases and correlate well with the ClashScore (Word et al. J Mol Biol 1999;285(4):1711-1733) generated by all atom contact analysis. Local density Z-scores for NMR structures exhibit a significantly wider range of values than for X-ray structures and demonstrate a combination of potentially problematic inflation and compression. Water-refined NMR structures show improved packing quality. Our analysis of a high-quality structural ensemble of ubiquitin refined against order parameters shows proton density distributions that correlate nearly perfectly with our standards derived from crystal structures, further validating our approach. We present an automated analysis and visualization tool for proton packing to evaluate the quality of NMR structures. 2005 Wiley-Liss, Inc.

  15. Addressing global uncertainty and sensitivity in first-principles based microkinetic models by an adaptive sparse grid approach

    NASA Astrophysics Data System (ADS)

    Döpking, Sandra; Plaisance, Craig P.; Strobusch, Daniel; Reuter, Karsten; Scheurer, Christoph; Matera, Sebastian

    2018-01-01

    In the last decade, first-principles-based microkinetic modeling has been developed into an important tool for a mechanistic understanding of heterogeneous catalysis. A commonly known, but hitherto barely analyzed issue in this kind of modeling is the presence of sizable errors from the use of approximate Density Functional Theory (DFT). We here address the propagation of these errors to the catalytic turnover frequency (TOF) by global sensitivity and uncertainty analysis. Both analyses require the numerical quadrature of high-dimensional integrals. To achieve this efficiently, we utilize and extend an adaptive sparse grid approach and exploit the confinement of the strongly non-linear behavior of the TOF to local regions of the parameter space. We demonstrate the methodology on a model of the oxygen evolution reaction at the Co3O4 (110)-A surface, using a maximum entropy error model that imposes nothing but reasonable bounds on the errors. For this setting, the DFT errors lead to an absolute uncertainty of several orders of magnitude in the TOF. We nevertheless find that it is still possible to draw conclusions from such uncertain models about the atomistic aspects controlling the reactivity. A comparison with derivative-based local sensitivity analysis instead reveals that this more established approach provides incomplete information. Since the adaptive sparse grids allow for the evaluation of the integrals with only a modest number of function evaluations, this approach opens the way for a global sensitivity analysis of more complex models, for instance, models based on kinetic Monte Carlo simulations.

  16. Coupling 3D groundwater modeling with CFC-based age dating to classify local groundwater circulation in an unconfined crystalline aquifer

    NASA Astrophysics Data System (ADS)

    Kolbe, Tamara; Marçais, Jean; Thomas, Zahra; Abbott, Benjamin W.; de Dreuzy, Jean-Raynald; Rousseau-Gueutin, Pauline; Aquilina, Luc; Labasque, Thierry; Pinay, Gilles

    2016-12-01

    Nitrogen pollution of freshwater and estuarine environments is one of the most urgent environmental crises. Shallow aquifers with predominantly local flow circulation are particularly vulnerable to agricultural contaminants. Water transit time and flow path are key controls on catchment nitrogen retention and removal capacity, but the relative importance of hydrogeological and topographical factors in determining these parameters is still uncertain. We used groundwater dating and numerical modeling techniques to assess transit time and flow path in an unconfined aquifer in Brittany, France. The 35.5 km2 study catchment has a crystalline basement underneath a ∼60 m thick weathered and fractured layer, and is separated into a distinct upland and lowland area by an 80 m-high butte. We used groundwater discharge and groundwater ages derived from chlorofluorocarbon (CFC) concentration to calibrate a free-surface flow model simulating groundwater flow circulation. We found that groundwater flow was highly local (mean travel distance = 350 m), substantially smaller than the typical distance between neighboring streams (∼1 km), while CFC-based ages were quite old (mean = 40 years). Sensitivity analysis revealed that groundwater travel distances were not sensitive to geological parameters (i.e. arrangement of geological layers and permeability profile) within the constraints of the CFC age data. However, circulation was sensitive to topography in the lowland area where the water table was near the land surface, and to recharge rate in the upland area where water input modulated the free surface of the aquifer. We quantified these differences with a local groundwater ratio (rGW-LOCAL), defined as the mean groundwater travel distance divided by the mean of the reference surface distances (the distance water would have to travel across the surface of the digital elevation model). Lowland, rGW-LOCAL was near 1, indicating primarily topographical controls. Upland, rGW-LOCAL was 1.6, meaning the groundwater recharge area is almost twice as large as the topographically-defined catchment for any given point. The ratio rGW-LOCAL is sensitive to recharge conditions as well as topography and it could be used to compare controls on groundwater circulation within or between catchments.

  17. Identifying key sources of uncertainty in the modelling of greenhouse gas emissions from wastewater treatment.

    PubMed

    Sweetapple, Christine; Fu, Guangtao; Butler, David

    2013-09-01

    This study investigates sources of uncertainty in the modelling of greenhouse gas emissions from wastewater treatment, through the use of local and global sensitivity analysis tools, and contributes to an in-depth understanding of wastewater treatment modelling by revealing critical parameters and parameter interactions. One-factor-at-a-time sensitivity analysis is used to screen model parameters and identify those with significant individual effects on three performance indicators: total greenhouse gas emissions, effluent quality and operational cost. Sobol's method enables identification of parameters with significant higher order effects and of particular parameter pairs to which model outputs are sensitive. Use of a variance-based global sensitivity analysis tool to investigate parameter interactions enables identification of important parameters not revealed in one-factor-at-a-time sensitivity analysis. These interaction effects have not been considered in previous studies and thus provide a better understanding wastewater treatment plant model characterisation. It was found that uncertainty in modelled nitrous oxide emissions is the primary contributor to uncertainty in total greenhouse gas emissions, due largely to the interaction effects of three nitrogen conversion modelling parameters. The higher order effects of these parameters are also shown to be a key source of uncertainty in effluent quality. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Feasibility and effectiveness of a low cost campaign on antibiotic prescribing in Italy: community level, controlled, non-randomised trial.

    PubMed

    Formoso, Giulio; Paltrinieri, Barbara; Marata, Anna Maria; Gagliotti, Carlo; Pan, Angelo; Moro, Maria Luisa; Capelli, Oreste; Magrini, Nicola

    2013-09-12

    To test the hypothesis that a multifaceted, local public campaign could be feasible and influence antibiotic prescribing for outpatients. Community level, controlled, non-randomised trial. Provinces of Modena and Parma in Emilia-Romagna, northern Italy, November 2011 to February 2012. 1,150,000 residents of Modena and Parma (intervention group) and 3,250,000 residents in provinces in the same region but where no campaign had been implemented (control group). Campaign materials (mainly posters, brochures, and advertisements on local media, plus a newsletter on local antibiotic resistance targeted at doctors and pharmacists). General practitioners and paediatricians in the intervention area participated in designing the campaign messages. Primary outcome was the average change in prescribing rates of antibiotics for outpatient in five months, measured as defined daily doses per 1000 inhabitants/day, using health districts as the unit of analysis. Antibiotic prescribing was reduced in the intervention area compared with control area (-4.3%, 95% confidence interval -7.1% to -1.5%). This result was robust to "sensitivity analysis" modifying the baseline period from two months (main analysis) to one month. A higher decrease was observed for penicillins resistant to β lactamase and a lower decrease for penicillins susceptible to β lactamase, consistent with the content of the newsletter on antibiotic resistance directed at health professionals. The decrease in expenditure on antibiotics was not statistically significant in a district level analysis with a two month baseline period (main analysis), but was statistically significant in sensitivity analyses using either a one month baseline period or a more powered doctor level analysis. Knowledge and attitudes of the target population about the correct use of antibiotics did not differ between the intervention and control areas. A local low cost information campaign targeted at citizens, combined with a newsletter on local antibiotic resistance targeted at doctors and pharmacists, was associated with significantly decreased total rates of antibiotic prescribing but did not affect the population's knowledge and attitudes about antibiotic resistance. ClinicalTrials.gov NCT01604096.

  19. Synthesis, crystal structure analysis, molecular docking studies and density functional theory predictions of the local reactive properties and degradation properties of a novel halochalcone

    NASA Astrophysics Data System (ADS)

    Arshad, Suhana; Pillai, Renjith Raveendran; Zainuri, Dian Alwani; Khalib, Nuridayanti Che; Razak, Ibrahim Abdul; Armaković, Stevan; Armaković, Sanja J.

    2017-09-01

    In the present study, single crystals of E)-3-(3,5-dichlorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one, were prepared and structurally characterized by single crystal X-ray diffraction analysis. The molecular structure crystallized in monoclinic crystal system with P21/c space group. Sensitivity of the title molecule towards electrophilic attacks has been examined by calculations of average localized ionization energies (ALIE) and their mapping to electron density surface. Further determination of atoms that could be important reactive centres has been performed by calculations of Fukui functions. Sensitivity of title molecule towards autoxidation and hydrolysis mechanisms has been assessed by calculations of bond dissociation energies and radial distribution functions (RDF), respectively. Also, in order to explore possible binding mode of the title compound towards Dihydrofolate reductase enzyme, we have utilized in silico molecular docking to explore possible binding modes of the title compound with the DHFR enzyme.

  20. What Do We Mean By Sensitivity Analysis? The Need For A Comprehensive Characterization Of Sensitivity In Earth System Models

    NASA Astrophysics Data System (ADS)

    Razavi, S.; Gupta, H. V.

    2014-12-01

    Sensitivity analysis (SA) is an important paradigm in the context of Earth System model development and application, and provides a powerful tool that serves several essential functions in modelling practice, including 1) Uncertainty Apportionment - attribution of total uncertainty to different uncertainty sources, 2) Assessment of Similarity - diagnostic testing and evaluation of similarities between the functioning of the model and the real system, 3) Factor and Model Reduction - identification of non-influential factors and/or insensitive components of model structure, and 4) Factor Interdependence - investigation of the nature and strength of interactions between the factors, and the degree to which factors intensify, cancel, or compensate for the effects of each other. A variety of sensitivity analysis approaches have been proposed, each of which formally characterizes a different "intuitive" understanding of what is meant by the "sensitivity" of one or more model responses to its dependent factors (such as model parameters or forcings). These approaches are based on different philosophies and theoretical definitions of sensitivity, and range from simple local derivatives and one-factor-at-a-time procedures to rigorous variance-based (Sobol-type) approaches. In general, each approach focuses on, and identifies, different features and properties of the model response and may therefore lead to different (even conflicting) conclusions about the underlying sensitivity. This presentation revisits the theoretical basis for sensitivity analysis, and critically evaluates existing approaches so as to demonstrate their flaws and shortcomings. With this background, we discuss several important properties of response surfaces that are associated with the understanding and interpretation of sensitivity. Finally, a new approach towards global sensitivity assessment is developed that is consistent with important properties of Earth System model response surfaces.

  1. FDG-PET, CT, MRI for diagnosis of local residual or recurrent nasopharyngeal carcinoma, which one is the best? A systematic review.

    PubMed

    Liu, Tao; Xu, Wen; Yan, Wei-Li; Ye, Ming; Bai, Yong-Rui; Huang, Gang

    2007-12-01

    To perform a systematic review to compare FDG-PET, CT, and MRI imaging for diagnosis of local residual or recurrent nasopharyngeal carcinoma. MEDLINE, EMBASE, the CBMdisc databases and some other databases were searched for relevant original articles published from January 1990 to June 2007. Inclusion criteria were as follows: Articles were reported in English or Chinese; FDG-PET, CT, or MRI was used to detect local residual or recurrent nasopharyngeal carcinoma; histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months were the reference standard. Two reviewers independently extracted data. A software called "Meta-DiSc" was used to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves, and the Q* index. Twenty-one articles fulfilled all inclusion criteria. The pooled sensitivity estimates for PET (95%) were significantly higher than CT (76%) (P<0.001) and MRI (78%) (P<0.001). The pooled specificity estimates for PET (90%) were significantly higher than CT (59%) (P<0.001) and MRI (76%) (P<0.001). The pooled DOR estimates for PET (96.51) were significantly higher than CT (7.01) (P<0.001) and MRI (8.68) (P<0.001). SROC curve for FDG-PET showed better diagnostic accuracy than CT and MRI. The Q* index for PET (0.92) was significantly higher than CT (0.72) (P<0.001) and MRI (0.76) (P<0.01). For PET, the sensitivity and diagnostic OR for using qualitative analysis were significantly higher than using both qualitative and quantitative analyses (P<0.01). For CT, the sensitivity, specificity, diagnostic OR, and the Q* index for dual-section helical and multi-section helical were all significantly higher than nonhelical and single-section helical (P<0.01). And the sensitivity for 'section thickness <5 mm' was significantly lower than ' =5 mm' (P<0.01), while the specificity was significantly higher (P<0.01). For MRI, there were no significant differences found between magnetic field strength <1.5 and > or =1.5 T (P>0.05). FDG-PET was the best modality for diagnosis of local residual or recurrent nasopharyngeal carcinoma. The type of analysis for PET imaging and the section thickness for CT would affect the diagnostic results. Dual-section helical and multi-section helical CT were better than nonhelical and single-section helical CT.

  2. Cost-effectiveness of Stereotactic Body Radiation Therapy versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Markov Modeling Study.

    PubMed

    Pollom, Erqi L; Lee, Kyueun; Durkee, Ben Y; Grade, Madeline; Mokhtari, Daniel A; Wahl, Daniel R; Feng, Mary; Kothary, Nishita; Koong, Albert C; Owens, Douglas K; Goldhaber-Fiebert, Jeremy; Chang, Daniel T

    2017-05-01

    Purpose To assess the cost-effectiveness of stereotactic body radiation therapy (SBRT) versus radiofrequency ablation (RFA) for patients with inoperable localized hepatocellular carcinoma (HCC) who are eligible for both SBRT and RFA. Materials and Methods A decision-analytic Markov model was developed for patients with inoperable, localized HCC who were eligible for both RFA and SBRT to evaluate the cost-effectiveness of the following treatment strategies: (a) SBRT as initial treatment followed by SBRT for local progression (SBRT-SBRT), (b) RFA followed by RFA for local progression (RFA-RFA), (c) SBRT followed by RFA for local progression (SBRT-RFA), and (d) RFA followed by SBRT for local progression (RFA-SBRT). Probabilities of disease progression, treatment characteristics, and mortality were derived from published studies. Outcomes included health benefits expressed as discounted quality-adjusted life years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results In the base case, SBRT-SBRT yielded the most QALYs (1.565) and cost $197 557. RFA-SBRT yielded 1.558 QALYs and cost $193 288. SBRT-SBRT was not cost-effective, at $558 679 per QALY gained relative to RFA-SBRT. RFA-SBRT was the preferred strategy, because RFA-RFA and SBRT-RFA were less effective and more costly. In all evaluated scenarios, SBRT was preferred as salvage therapy for local progression after RFA. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100 000 per QALY gained, RFA-SBRT was preferred in 65.8% of simulations. Conclusion SBRT for initial treatment of localized, inoperable HCC is not cost-effective. However, SBRT is the preferred salvage therapy for local progression after RFA. © RSNA, 2017 Online supplemental material is available for this article.

  3. Source localization of rhythmic ictal EEG activity: a study of diagnostic accuracy following STARD criteria.

    PubMed

    Beniczky, Sándor; Lantz, Göran; Rosenzweig, Ivana; Åkeson, Per; Pedersen, Birthe; Pinborg, Lars H; Ziebell, Morten; Jespersen, Bo; Fuglsang-Frederiksen, Anders

    2013-10-01

    Although precise identification of the seizure-onset zone is an essential element of presurgical evaluation, source localization of ictal electroencephalography (EEG) signals has received little attention. The aim of our study was to estimate the accuracy of source localization of rhythmic ictal EEG activity using a distributed source model. Source localization of rhythmic ictal scalp EEG activity was performed in 42 consecutive cases fulfilling inclusion criteria. The study was designed according to recommendations for studies on diagnostic accuracy (STARD). The initial ictal EEG signals were selected using a standardized method, based on frequency analysis and voltage distribution of the ictal activity. A distributed source model-local autoregressive average (LAURA)-was used for the source localization. Sensitivity, specificity, and measurement of agreement (kappa) were determined based on the reference standard-the consensus conclusion of the multidisciplinary epilepsy surgery team. Predictive values were calculated from the surgical outcome of the operated patients. To estimate the clinical value of the ictal source analysis, we compared the likelihood ratios of concordant and discordant results. Source localization was performed blinded to the clinical data, and before the surgical decision. Reference standard was available for 33 patients. The ictal source localization had a sensitivity of 70% and a specificity of 76%. The mean measurement of agreement (kappa) was 0.61, corresponding to substantial agreement (95% confidence interval (CI) 0.38-0.84). Twenty patients underwent resective surgery. The positive predictive value (PPV) for seizure freedom was 92% and the negative predictive value (NPV) was 43%. The likelihood ratio was nine times higher for the concordant results, as compared with the discordant ones. Source localization of rhythmic ictal activity using a distributed source model (LAURA) for the ictal EEG signals selected with a standardized method is feasible in clinical practice and has a good diagnostic accuracy. Our findings encourage clinical neurophysiologists assessing ictal EEGs to include this method in their armamentarium. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  4. Cost-effectiveness of Stereotactic Body Radiation Therapy versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Markov Modeling Study

    PubMed Central

    Lee, Kyueun; Durkee, Ben Y.; Grade, Madeline; Mokhtari, Daniel A.; Wahl, Daniel R.; Feng, Mary; Kothary, Nishita; Koong, Albert C.; Owens, Douglas K.; Goldhaber-Fiebert, Jeremy; Chang, Daniel T.

    2017-01-01

    Purpose To assess the cost-effectiveness of stereotactic body radiation therapy (SBRT) versus radiofrequency ablation (RFA) for patients with inoperable localized hepatocellular carcinoma (HCC) who are eligible for both SBRT and RFA. Materials and Methods A decision-analytic Markov model was developed for patients with inoperable, localized HCC who were eligible for both RFA and SBRT to evaluate the cost-effectiveness of the following treatment strategies: (a) SBRT as initial treatment followed by SBRT for local progression (SBRT-SBRT), (b) RFA followed by RFA for local progression (RFA-RFA), (c) SBRT followed by RFA for local progression (SBRT-RFA), and (d) RFA followed by SBRT for local progression (RFA-SBRT). Probabilities of disease progression, treatment characteristics, and mortality were derived from published studies. Outcomes included health benefits expressed as discounted quality-adjusted life years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results In the base case, SBRT-SBRT yielded the most QALYs (1.565) and cost $197 557. RFA-SBRT yielded 1.558 QALYs and cost $193 288. SBRT-SBRT was not cost-effective, at $558 679 per QALY gained relative to RFA-SBRT. RFA-SBRT was the preferred strategy, because RFA-RFA and SBRT-RFA were less effective and more costly. In all evaluated scenarios, SBRT was preferred as salvage therapy for local progression after RFA. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100 000 per QALY gained, RFA-SBRT was preferred in 65.8% of simulations. Conclusion SBRT for initial treatment of localized, inoperable HCC is not cost-effective. However, SBRT is the preferred salvage therapy for local progression after RFA. © RSNA, 2017 Online supplemental material is available for this article. PMID:28045603

  5. Detection of PCT and urinary β2 -MG enhances the accuracy for localization diagnosing pediatric urinary tract infection.

    PubMed

    Fang, Jian; Luan, Jiangwei; Zhu, Gaohong; Qi, Chang; Wang, Dandan

    2017-09-01

    The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary β 2 -MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI). Levels of PCT and urinary β 2 -MG in both UUTI and LUTI patients were measured and compared. The level of PCT and β 2 -MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary β 2 -MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. Both PCT and β 2 -MG could be used to localize the UTI. Introducing urinary β 2 -MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice. © 2016 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

  6. Mixed kernel function support vector regression for global sensitivity analysis

    NASA Astrophysics Data System (ADS)

    Cheng, Kai; Lu, Zhenzhou; Wei, Yuhao; Shi, Yan; Zhou, Yicheng

    2017-11-01

    Global sensitivity analysis (GSA) plays an important role in exploring the respective effects of input variables on an assigned output response. Amongst the wide sensitivity analyses in literature, the Sobol indices have attracted much attention since they can provide accurate information for most models. In this paper, a mixed kernel function (MKF) based support vector regression (SVR) model is employed to evaluate the Sobol indices at low computational cost. By the proposed derivation, the estimation of the Sobol indices can be obtained by post-processing the coefficients of the SVR meta-model. The MKF is constituted by the orthogonal polynomials kernel function and Gaussian radial basis kernel function, thus the MKF possesses both the global characteristic advantage of the polynomials kernel function and the local characteristic advantage of the Gaussian radial basis kernel function. The proposed approach is suitable for high-dimensional and non-linear problems. Performance of the proposed approach is validated by various analytical functions and compared with the popular polynomial chaos expansion (PCE). Results demonstrate that the proposed approach is an efficient method for global sensitivity analysis.

  7. Factors dominating 3-dimensional ozone distribution during high tropospheric ozone period.

    PubMed

    Chen, Xiaoyang; Liu, Yiming; Lai, Anqi; Han, Shuangshuang; Fan, Qi; Wang, Xuemei; Ling, Zhenhao; Huang, Fuxiang; Fan, Shaojia

    2018-01-01

    Data from an in situ monitoring network and five ozone sondes are analysed during August of 2012, and a high tropospheric ozone episode is observed around the 8th of AUG. The Community Multi-scale Air Quality (CMAQ) model and its process analysis tool were used to study factors and mechanisms for high ozone mixing ratio at different levels of ozone vertical profiles. A sensitive scenario without chemical initial and boundary conditions (ICBCs) from MOZART4-GEOS5 was applied to study the impact of stratosphere-troposphere exchange (STE) on vertical ozone. The simulation results indicated that the first high ozone peak near the tropopause was dominated by STE. Results from process analysis showed that: in the urban area, the second peak at approximately 2 km above ground height was mainly caused by local photochemical production. The third peak (near surface) was mainly caused by the upwind transportation from the suburban/rural areas; in the suburban/rural areas, local photochemical production of ozone dominated the high ozone mixing ratio from the surface to approximately 3 km height. Furthermore, the capability of indicators to distinguish O 3 -precursor sensitivity along the vertical O 3 profiles was investigated. Two sensitive scenarios, which had cut 30% anthropogenic NO X or VOC emissions, showed that O 3 -precursor indicators, specifically the ratios of O 3 /NOy, H 2 O 2 /HNO 3 or H 2 O 2 /NO Z , could partly distinguish the O 3 -precursor sensitivity between VOCs-sensitive and NOx-sensitive along the vertical profiles. In urban area, the O 3 -precursor relationship transferred from VOCs-sensitive within the boundary layer to NOx-sensitive at approximately 1-3 km above ground height, further confirming the dominant roles of transportation and photochemical production in high O 3 peaks at the near-ground layer and 2 km above ground height, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

    PubMed

    Rhee, H; Thomas, P; Shepherd, B; Gustafson, S; Vela, I; Russell, P J; Nelson, C; Chung, E; Wood, G; Malone, G; Wood, S; Heathcote, P

    2016-10-01

    Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

    PubMed

    Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

    2018-06-01

    To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

  10. Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B-induced local skin hypersensitization in healthy subjects: a machine-learned analysis.

    PubMed

    Lötsch, Jörn; Geisslinger, Gerd; Heinemann, Sarah; Lerch, Florian; Oertel, Bruno G; Ultsch, Alfred

    2017-08-16

    The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  11. Origins of chemoreceptor curvature sorting in Escherichia coli

    PubMed Central

    Draper, Will; Liphardt, Jan

    2017-01-01

    Bacterial chemoreceptors organize into large clusters at the cell poles. Despite a wealth of structural and biochemical information on the system's components, it is not clear how chemoreceptor clusters are reliably targeted to the cell pole. Here, we quantify the curvature-dependent localization of chemoreceptors in live cells by artificially deforming growing cells of Escherichia coli in curved agar microchambers, and find that chemoreceptor cluster localization is highly sensitive to membrane curvature. Through analysis of multiple mutants, we conclude that curvature sensitivity is intrinsic to chemoreceptor trimers-of-dimers, and results from conformational entropy within the trimer-of-dimers geometry. We use the principles of the conformational entropy model to engineer curvature sensitivity into a series of multi-component synthetic protein complexes. When expressed in E. coli, the synthetic complexes form large polar clusters, and a complex with inverted geometry avoids the cell poles. This demonstrates the successful rational design of both polar and anti-polar clustering, and provides a synthetic platform on which to build new systems. PMID:28322223

  12. Diagnostic staging laparoscopy in gastric cancer treatment: A cost-effectiveness analysis.

    PubMed

    Li, Kevin; Cannon, John G D; Jiang, Sam Y; Sambare, Tanmaya D; Owens, Douglas K; Bendavid, Eran; Poultsides, George A

    2018-05-01

    Accurate preoperative staging helps avert morbidity, mortality, and cost associated with non-therapeutic laparotomy in gastric cancer (GC) patients. Diagnostic staging laparoscopy (DSL) can detect metastases with high sensitivity, but its cost-effectiveness has not been previously studied. We developed a decision analysis model to assess the cost-effectiveness of preoperative DSL in GC workup. Analysis was based on a hypothetical cohort of GC patients in the U.S. for whom initial imaging shows no metastases. The cost-effectiveness of DSL was measured as cost per quality-adjusted life-year (QALY) gained. Drivers of cost-effectiveness were assessed in sensitivity analysis. Preoperative DSL required an investment of $107 012 per QALY. In sensitivity analysis, DSL became cost-effective at a threshold of $100 000/QALY when the probability of occult metastases exceeded 31.5% or when test sensitivity for metastases exceeded 86.3%. The likelihood of cost-effectiveness increased from 46% to 93% when both parameters were set at maximum reported values. The cost-effectiveness of DSL for GC patients is highly dependent on patient and test characteristics, and is more likely when DSL is used selectively where procedure yield is high, such as for locally advanced disease or in detecting peritoneal and superficial versus deep liver lesions. © 2017 Wiley Periodicals, Inc.

  13. Use of local noise power spectrum and wavelet analysis in quantitative image quality assurance for EPIDs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Soyoung

    Purpose: To investigate the use of local noise power spectrum (NPS) to characterize image noise and wavelet analysis to isolate defective pixels and inter-subpanel flat-fielding artifacts for quantitative quality assurance (QA) of electronic portal imaging devices (EPIDs). Methods: A total of 93 image sets including custom-made bar-pattern images and open exposure images were collected from four iViewGT a-Si EPID systems over three years. Global quantitative metrics such as modulation transform function (MTF), NPS, and detective quantum efficiency (DQE) were computed for each image set. Local NPS was also calculated for individual subpanels by sampling region of interests within each subpanelmore » of the EPID. The 1D NPS, obtained by radially averaging the 2D NPS, was fitted to a power-law function. The r-square value of the linear regression analysis was used as a singular metric to characterize the noise properties of individual subpanels of the EPID. The sensitivity of the local NPS was first compared with the global quantitative metrics using historical image sets. It was then compared with two commonly used commercial QA systems with images collected after applying two different EPID calibration methods (single-level gain and multilevel gain). To detect isolated defective pixels and inter-subpanel flat-fielding artifacts, Haar wavelet transform was applied on the images. Results: Global quantitative metrics including MTF, NPS, and DQE showed little change over the period of data collection. On the contrary, a strong correlation between the local NPS (r-square values) and the variation of the EPID noise condition was observed. The local NPS analysis indicated image quality improvement with the r-square values increased from 0.80 ± 0.03 (before calibration) to 0.85 ± 0.03 (after single-level gain calibration) and to 0.96 ± 0.03 (after multilevel gain calibration), while the commercial QA systems failed to distinguish the image quality improvement between the two calibration methods. With wavelet analysis, defective pixels and inter-subpanel flat-fielding artifacts were clearly identified as spikes after thresholding the inversely transformed images. Conclusions: The proposed local NPS (r-square values) showed superior sensitivity to the noise level variations of individual subpanels compared with global quantitative metrics such as MTF, NPS, and DQE. Wavelet analysis was effective in detecting isolated defective pixels and inter-subpanel flat-fielding artifacts. The proposed methods are promising for the early detection of imaging artifacts of EPIDs.« less

  14. Simulation of a Real-Time Local Data Integration System over East-Central Florida

    NASA Technical Reports Server (NTRS)

    Case, Jonathan

    1999-01-01

    The Applied Meteorology Unit (AMU) simulated a real-time configuration of a Local Data Integration System (LDIS) using data from 15-28 February 1999. The objectives were to assess the utility of a simulated real-time LDIS, evaluate and extrapolate system performance to identify the hardware necessary to run a real-time LDIS, and determine the sensitivities of LDIS. The ultimate goal for running LDIS is to generate analysis products that enhance short-range (less than 6 h) weather forecasts issued in support of the 45th Weather Squadron, Spaceflight Meteorology Group, and Melbourne National Weather Service operational requirements. The simulation used the Advanced Regional Prediction System (ARPS) Data Analysis System (ADAS) software on an IBM RS/6000 workstation with a 67-MHz processor. This configuration ran in real-time, but not sufficiently fast for operational requirements. Thus, the AMU recommends a workstation with a 200-MHz processor and 512 megabytes of memory to run the AMU's configuration of LDIS in real-time. This report presents results from two case studies and several data sensitivity experiments. ADAS demonstrates utility through its ability to depict high-resolution cloud and wind features in a variety of weather situations. The sensitivity experiments illustrate the influence of disparate data on the resulting ADAS analyses.

  15. Parameterization and Sensitivity Analysis of a Complex Simulation Model for Mosquito Population Dynamics, Dengue Transmission, and Their Control

    PubMed Central

    Ellis, Alicia M.; Garcia, Andres J.; Focks, Dana A.; Morrison, Amy C.; Scott, Thomas W.

    2011-01-01

    Models can be useful tools for understanding the dynamics and control of mosquito-borne disease. More detailed models may be more realistic and better suited for understanding local disease dynamics; however, evaluating model suitability, accuracy, and performance becomes increasingly difficult with greater model complexity. Sensitivity analysis is a technique that permits exploration of complex models by evaluating the sensitivity of the model to changes in parameters. Here, we present results of sensitivity analyses of two interrelated complex simulation models of mosquito population dynamics and dengue transmission. We found that dengue transmission may be influenced most by survival in each life stage of the mosquito, mosquito biting behavior, and duration of the infectious period in humans. The importance of these biological processes for vector-borne disease models and the overwhelming lack of knowledge about them make acquisition of relevant field data on these biological processes a top research priority. PMID:21813844

  16. Single molecule fluorescence microscopy for ultra-sensitive RNA expression profiling

    NASA Astrophysics Data System (ADS)

    Hesse, Jan; Jacak, Jaroslaw; Regl, Gerhard; Eichberger, Thomas; Aberger, Fritz; Schlapak, Robert; Howorka, Stefan; Muresan, Leila; Frischauf, Anna-Maria; Schütz, Gerhard J.

    2007-02-01

    We developed a microarray analysis platform for ultra-sensitive RNA expression profiling of minute samples. It utilizes a novel scanning system for single molecule fluorescence detection on cm2 size samples in combination with specialized biochips, optimized for low autofluorescence and weak unspecific adsorption. 20 μg total RNA was extracted from 10 6 cells of a human keratinocyte cell line (HaCaT) and reversely transcribed in the presence of Alexa647-aha-dUTP. 1% of the resulting labeled cDNA was used for complex hybridization to a custom-made oligonucleotide microarray representing a set of 125 different genes. For low abundant genes, individual cDNA molecules hybridized to the microarray spots could be resolved. Single cDNA molecules hybridized to the chip surface appeared as diffraction limited features in the fluorescence images. The à trous wavelet method was utilized for localization and counting of the separated cDNA signals. Subsequently, the degree of labeling of the localized cDNA molecules was determined by brightness analysis for the different genes. Variations by factors up to 6 were found, which in conventional microarray analysis would result in a misrepresentation of the relative abundance of mRNAs.

  17. Combining EEG and MEG for the Reconstruction of Epileptic Activity Using a Calibrated Realistic Volume Conductor Model

    PubMed Central

    Aydin, Ümit; Vorwerk, Johannes; Küpper, Philipp; Heers, Marcel; Kugel, Harald; Galka, Andreas; Hamid, Laith; Wellmer, Jörg; Kellinghaus, Christoph; Rampp, Stefan; Wolters, Carsten Hermann

    2014-01-01

    To increase the reliability for the non-invasive determination of the irritative zone in presurgical epilepsy diagnosis, we introduce here a new experimental and methodological source analysis pipeline that combines the complementary information in EEG and MEG, and apply it to data from a patient, suffering from refractory focal epilepsy. Skull conductivity parameters in a six compartment finite element head model with brain anisotropy, constructed from individual MRI data, are estimated in a calibration procedure using somatosensory evoked potential (SEP) and field (SEF) data. These data are measured in a single run before acquisition of further runs of spontaneous epileptic activity. Our results show that even for single interictal spikes, volume conduction effects dominate over noise and need to be taken into account for accurate source analysis. While cerebrospinal fluid and brain anisotropy influence both modalities, only EEG is sensitive to skull conductivity and conductivity calibration significantly reduces the difference in especially depth localization of both modalities, emphasizing its importance for combining EEG and MEG source analysis. On the other hand, localization differences which are due to the distinct sensitivity profiles of EEG and MEG persist. In case of a moderate error in skull conductivity, combined source analysis results can still profit from the different sensitivity profiles of EEG and MEG to accurately determine location, orientation and strength of the underlying sources. On the other side, significant errors in skull modeling are reflected in EEG reconstruction errors and could reduce the goodness of fit to combined datasets. For combined EEG and MEG source analysis, we therefore recommend calibrating skull conductivity using additionally acquired SEP/SEF data. PMID:24671208

  18. Fractal dimension based damage identification incorporating multi-task sparse Bayesian learning

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Li, Hui; Wu, Stephen; Yang, Yongchao

    2018-07-01

    Sensitivity to damage and robustness to noise are critical requirements for the effectiveness of structural damage detection. In this study, a two-stage damage identification method based on the fractal dimension analysis and multi-task Bayesian learning is presented. The Higuchi’s fractal dimension (HFD) based damage index is first proposed, directly examining the time-frequency characteristic of local free vibration data of structures based on the irregularity sensitivity and noise robustness analysis of HFD. Katz’s fractal dimension is then presented to analyze the abrupt irregularity change of the spatial curve of the displacement mode shape along the structure. At the second stage, the multi-task sparse Bayesian learning technique is employed to infer the final damage localization vector, which borrow the dependent strength of the two fractal dimension based damage indication information and also incorporate the prior knowledge that structural damage occurs at a limited number of locations in a structure in the absence of its collapse. To validate the capability of the proposed method, a steel beam and a bridge, named Yonghe Bridge, are analyzed as illustrative examples. The damage identification results demonstrate that the proposed method is capable of localizing single and multiple damages regardless of its severity, and show superior robustness under heavy noise as well.

  19. Assessment of statistic analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example.

    PubMed

    Takeyoshi, Masahiro; Sawaki, Masakuni; Yamasaki, Kanji; Kimber, Ian

    2003-09-30

    The murine local lymph node assay (LLNA) is used for the identification of chemicals that have the potential to cause skin sensitization. However, it requires specific facility and handling procedures to accommodate a radioisotopic (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA based on BrdU incorporation to avoid a use of RI. Although this alternative method appears viable in principle, it is somewhat less sensitive than the standard assay. In this study, we report investigations to determine the use of statistical analysis to improve the sensitivity of a non-RI LLNA procedure with alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the alternative non-RI method required HCA concentrations of greater than 25% to elicit a positive response based on the criterion for classification as a skin sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the alternative method were consistent in both experiments and we examined whether the use of an endpoint based upon the statistical significance of induced changes in LNC turnover, rather than an SI of 3 or greater, might provide for additional sensitivity. The results reported here demonstrate that with HCA at least significant responses were, in each of two experiments, recorded following exposure of mice to 25% of HCA. These data suggest that this approach may be more satisfactory-at least when BrdU incorporation is measured. However, this modification of the LLNA is rather less sensitive than the standard method if employing statistical endpoint. Taken together the data reported here suggest that a modified LLNA in which BrdU is used in place of radioisotope incorporation shows some promise, but that in its present form, even with the use of a statistical endpoint, lacks some of the sensitivity of the standard method. The challenge is to develop strategies for further refinement of this approach.

  20. On simulation of local fluxes in molecular junctions

    NASA Astrophysics Data System (ADS)

    Cabra, Gabriel; Jensen, Anders; Galperin, Michael

    2018-05-01

    We present a pedagogical review of the current density simulation in molecular junction models indicating its advantages and deficiencies in analysis of local junction transport characteristics. In particular, we argue that current density is a universal tool which provides more information than traditionally simulated bond currents, especially when discussing inelastic processes. However, current density simulations are sensitive to the choice of basis and electronic structure method. We note that while discussing the local current conservation in junctions, one has to account for the source term caused by the open character of the system and intra-molecular interactions. Our considerations are illustrated with numerical simulations of a benzenedithiol molecular junction.

  1. Use of social network analysis and global sensitivity and uncertainty analyses to better understand an influenza outbreak.

    PubMed

    Liu, Jianhua; Jiang, Hongbo; Zhang, Hao; Guo, Chun; Wang, Lei; Yang, Jing; Nie, Shaofa

    2017-06-27

    In the summer of 2014, an influenza A(H3N2) outbreak occurred in Yichang city, Hubei province, China. A retrospective study was conducted to collect and interpret hospital and epidemiological data on it using social network analysis and global sensitivity and uncertainty analyses. Results for degree (χ2=17.6619, P<0.0001) and betweenness(χ2=21.4186, P<0.0001) centrality suggested that the selection of sampling objects were different between traditional epidemiological methods and newer statistical approaches. Clique and network diagrams demonstrated that the outbreak actually consisted of two independent transmission networks. Sensitivity analysis showed that the contact coefficient (k) was the most important factor in the dynamic model. Using uncertainty analysis, we were able to better understand the properties and variations over space and time on the outbreak. We concluded that use of newer approaches were significantly more efficient for managing and controlling infectious diseases outbreaks, as well as saving time and public health resources, and could be widely applied on similar local outbreaks.

  2. Highly sensitive nano-porous lattice biosensor based on localized surface plasmon resonance and interference.

    PubMed

    Yeom, Se-Hyuk; Kim, Ok-Geun; Kang, Byoung-Ho; Kim, Kyu-Jin; Yuan, Heng; Kwon, Dae-Hyuk; Kim, Hak-Rin; Kang, Shin-Won

    2011-11-07

    We propose a design for a highly sensitive biosensor based on nanostructured anodized aluminum oxide (AAO) substrates. A gold-deposited AAO substrate exhibits both optical interference and localized surface plasmon resonance (LSPR). In our sensor, application of these disparate optical properties overcomes problems of limited sensitivity, selectivity, and dynamic range seen in similar biosensors. We fabricated uniform periodic nanopore lattice AAO templates by two-step anodizing and assessed their suitability for application in biosensors by characterizing the change in optical response on addition of biomolecules to the AAO template. To determine the suitability of such structures for biosensing applications, we immobilized a layer of C-reactive protein (CRP) antibody on a gold coating atop an AAO template. We then applied a CRP antigen (Ag) atop the immobilized antibody (Ab) layer. The shift in reflectance is interpreted as being caused by the change in refractive index with membrane thickness. Our results confirm that our proposed AAO-based biosensor is highly selective toward detection of CRP antigen, and can measure a change in CRP antigen concentration of 1 fg/ml. This method can provide a simple, fast, and sensitive analysis for protein detection in real-time.

  3. Preventive behaviors by the level of perceived infection sensitivity during the Korea outbreak of Middle East Respiratory Syndrome in 2015.

    PubMed

    Lee, Soon Young; Yang, Hee Jeong; Kim, Gawon; Cheong, Hae-Kwan; Choi, Bo Youl

    2016-01-01

    This study was performed to investigate the relationship between community residents' infection sensitivity and their levels of preventive behaviors during the 2015 Middle East Respiratory Syndrome (MERS) outbreak in Korea. Seven thousands two hundreds eighty one participants from nine areas in Gyeonggi-do including Pyeongtaek, the origin of the outbreak in 2015 agreed to participate in the survey and the data from 6,739 participants were included in the final analysis. The data on the perceived infection sensitivity were subjected to cluster analysis. The levels of stress, reliability/practice of preventive behaviors, hand washing practice and policy credibility during the outbreak period were analyzed for each cluster. Cluster analysis of infection sensitivity due to the MERS outbreak resulted in classification of participants into four groups: the non-sensitive group (14.5%), social concern group (17.4%), neutral group (29.1%), and overall sensitive group (39.0%). A logistic regression analysis found that the overall sensitive group with high sensitivity had higher stress levels (17.80; 95% confidence interval [CI], 13.77 to 23.00), higher reliability on preventive behaviors (5.81; 95% CI, 4.84 to 6.98), higher practice of preventive behaviors (4.53; 95% CI, 3.83 to 5.37) and higher practice of hand washing (2.71; 95% CI, 2.13 to 3.43) during the outbreak period, compared to the non-sensitive group. Infection sensitivity of community residents during the MERS outbreak correlated with gender, age, occupation, and health behaviors. When there is an outbreak in the community, there is need to maintain a certain level of sensitivity while reducing excessive stress, as well as promote the practice of preventive behaviors among local residents. In particular, target groups need to be notified and policies need to be established with a consideration of the socio-demographic characteristics of the community.

  4. High-sensitivity visualization of localized electric fields using low-energy electron beam deflection

    NASA Astrophysics Data System (ADS)

    Jeong, Samuel; Ito, Yoshikazu; Edwards, Gary; Fujita, Jun-ichi

    2018-06-01

    The visualization of localized electronic charges on nanocatalysts is expected to yield fundamental information about catalytic reaction mechanisms. We have developed a high-sensitivity detection technique for the visualization of localized charges on a catalyst and their corresponding electric field distribution, using a low-energy beam of 1 to 5 keV electrons and a high-sensitivity scanning transmission electron microscope (STEM) detector. The highest sensitivity for visualizing a localized electric field was ∼0.08 V/µm at a distance of ∼17 µm from a localized charge at 1 keV of the primary electron energy, and a weak local electric field produced by 200 electrons accumulated on the carbon nanotube (CNT) apex can be visualized. We also observed that Au nanoparticles distributed on a CNT forest tended to accumulate a certain amount of charges, about 150 electrons, at a ‑2 V bias.

  5. Sensitivity analysis of periodic errors in heterodyne interferometry

    NASA Astrophysics Data System (ADS)

    Ganguly, Vasishta; Kim, Nam Ho; Kim, Hyo Soo; Schmitz, Tony

    2011-03-01

    Periodic errors in heterodyne displacement measuring interferometry occur due to frequency mixing in the interferometer. These nonlinearities are typically characterized as first- and second-order periodic errors which cause a cyclical (non-cumulative) variation in the reported displacement about the true value. This study implements an existing analytical periodic error model in order to identify sensitivities of the first- and second-order periodic errors to the input parameters, including rotational misalignments of the polarizing beam splitter and mixing polarizer, non-orthogonality of the two laser frequencies, ellipticity in the polarizations of the two laser beams, and different transmission coefficients in the polarizing beam splitter. A local sensitivity analysis is first conducted to examine the sensitivities of the periodic errors with respect to each input parameter about the nominal input values. Next, a variance-based approach is used to study the global sensitivities of the periodic errors by calculating the Sobol' sensitivity indices using Monte Carlo simulation. The effect of variation in the input uncertainty on the computed sensitivity indices is examined. It is seen that the first-order periodic error is highly sensitive to non-orthogonality of the two linearly polarized laser frequencies, while the second-order error is most sensitive to the rotational misalignment between the laser beams and the polarizing beam splitter. A particle swarm optimization technique is finally used to predict the possible setup imperfections based on experimentally generated values for periodic errors.

  6. Local sensitivity analysis for inverse problems solved by singular value decomposition

    USGS Publications Warehouse

    Hill, M.C.; Nolan, B.T.

    2010-01-01

    Local sensitivity analysis provides computationally frugal ways to evaluate models commonly used for resource management, risk assessment, and so on. This includes diagnosing inverse model convergence problems caused by parameter insensitivity and(or) parameter interdependence (correlation), understanding what aspects of the model and data contribute to measures of uncertainty, and identifying new data likely to reduce model uncertainty. Here, we consider sensitivity statistics relevant to models in which the process model parameters are transformed using singular value decomposition (SVD) to create SVD parameters for model calibration. The statistics considered include the PEST identifiability statistic, and combined use of the process-model parameter statistics composite scaled sensitivities and parameter correlation coefficients (CSS and PCC). The statistics are complimentary in that the identifiability statistic integrates the effects of parameter sensitivity and interdependence, while CSS and PCC provide individual measures of sensitivity and interdependence. PCC quantifies correlations between pairs or larger sets of parameters; when a set of parameters is intercorrelated, the absolute value of PCC is close to 1.00 for all pairs in the set. The number of singular vectors to include in the calculation of the identifiability statistic is somewhat subjective and influences the statistic. To demonstrate the statistics, we use the USDA’s Root Zone Water Quality Model to simulate nitrogen fate and transport in the unsaturated zone of the Merced River Basin, CA. There are 16 log-transformed process-model parameters, including water content at field capacity (WFC) and bulk density (BD) for each of five soil layers. Calibration data consisted of 1,670 observations comprising soil moisture, soil water tension, aqueous nitrate and bromide concentrations, soil nitrate concentration, and organic matter content. All 16 of the SVD parameters could be estimated by regression based on the range of singular values. Identifiability statistic results varied based on the number of SVD parameters included. Identifiability statistics calculated for four SVD parameters indicate the same three most important process-model parameters as CSS/PCC (WFC1, WFC2, and BD2), but the order differed. Additionally, the identifiability statistic showed that BD1 was almost as dominant as WFC1. The CSS/PCC analysis showed that this results from its high correlation with WCF1 (-0.94), and not its individual sensitivity. Such distinctions, combined with analysis of how high correlations and(or) sensitivities result from the constructed model, can produce important insights into, for example, the use of sensitivity analysis to design monitoring networks. In conclusion, the statistics considered identified similar important parameters. They differ because (1) with CSS/PCC can be more awkward because sensitivity and interdependence are considered separately and (2) identifiability requires consideration of how many SVD parameters to include. A continuing challenge is to understand how these computationally efficient methods compare with computationally demanding global methods like Markov-Chain Monte Carlo given common nonlinear processes and the often even more nonlinear models.

  7. Sensitivity analysis of the parameters of an HIV/AIDS model with condom campaign and antiretroviral therapy

    NASA Astrophysics Data System (ADS)

    Marsudi, Hidayat, Noor; Wibowo, Ratno Bagus Edy

    2017-12-01

    In this article, we present a deterministic model for the transmission dynamics of HIV/AIDS in which condom campaign and antiretroviral therapy are both important for the disease management. We calculate the effective reproduction number using the next generation matrix method and investigate the local and global stability of the disease-free equilibrium of the model. Sensitivity analysis of the effective reproduction number with respect to the model parameters were carried out. Our result shows that efficacy rate of condom campaign, transmission rate for contact with the asymptomatic infective, progression rate from the asymptomatic infective to the pre-AIDS infective, transmission rate for contact with the pre-AIDS infective, ARV therapy rate, proportion of the susceptible receiving condom campaign and proportion of the pre-AIDS receiving ARV therapy are highly sensitive parameters that effect the transmission dynamics of HIV/AIDS infection.

  8. An Analysis of Spacecraft Localization from Descent Image Data for Pinpoint Landing on Mars and other Cratered Bodies Data Acquisition

    NASA Technical Reports Server (NTRS)

    Ansar, Adnan; Cheng, Yang

    2005-01-01

    A pinpoint landing capability will be a critical component for many planned NASA missions to Mars and beyond. Implicit in the requirement is the ability to accurately localize the spacecraft with respect to the terrain during descent. In this paper, we present evidence that a vision-based solution using craters as landmarks is both practical and will meet the requirements of next generation missions. Our emphasis in this paper is on the feasibility of such a system in terms of (a) localization accuracy and (b) applicability to Martian terrain. We show that accuracy of well under 100 meters can be expected under suitable conditions. We also present a sensitivity analysis that makes an explicit connection between input data and robustness of our pose estimate. In addition, we present an analysis of the susceptibility of our technique to inherently ambiguous configurations of craters. We show that probability of failure due to such ambiguity is becoming increasingly small.

  9. Test battery with the human cell line activation test, direct peptide reactivity assay and DEREK based on a 139 chemical data set for predicting skin sensitizing potential and potency of chemicals.

    PubMed

    Takenouchi, Osamu; Fukui, Shiho; Okamoto, Kenji; Kurotani, Satoru; Imai, Noriyasu; Fujishiro, Miyuki; Kyotani, Daiki; Kato, Yoshinao; Kasahara, Toshihiko; Fujita, Masaharu; Toyoda, Akemi; Sekiya, Daisuke; Watanabe, Shinichi; Seto, Hirokazu; Hirota, Morihiko; Ashikaga, Takao; Miyazawa, Masaaki

    2015-11-01

    To develop a testing strategy incorporating the human cell line activation test (h-CLAT), direct peptide reactivity assay (DPRA) and DEREK, we created an expanded data set of 139 chemicals (102 sensitizers and 37 non-sensitizers) by combining the existing data set of 101 chemicals through the collaborative projects of Japan Cosmetic Industry Association. Of the additional 38 chemicals, 15 chemicals with relatively low water solubility (log Kow > 3.5) were selected to clarify the limitation of testing strategies regarding the lipophilic chemicals. Predictivities of the h-CLAT, DPRA and DEREK, and the combinations thereof were evaluated by comparison to results of the local lymph node assay. When evaluating 139 chemicals using combinations of three methods based on integrated testing strategy (ITS) concept (ITS-based test battery) and a sequential testing strategy (STS) weighing the predictive performance of the h-CLAT and DPRA, overall similar predictivities were found as before on the 101 chemical data set. An analysis of false negative chemicals suggested a major limitation of our strategies was the testing of low water-soluble chemicals. When excluded the negative results for chemicals with log Kow > 3.5, the sensitivity and accuracy of ITS improved to 97% (91 of 94 chemicals) and 89% (114 of 128). Likewise, the sensitivity and accuracy of STS to 98% (92 of 94) and 85% (111 of 129). Moreover, the ITS and STS also showed good correlation with local lymph node assay on three potency classifications, yielding accuracies of 74% (ITS) and 73% (STS). Thus, the inclusion of log Kow in analysis could give both strategies a higher predictive performance. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Retinal Ganglion Cell Layer Thickness and Local Visual Field Sensitivity in Glaucoma

    PubMed Central

    Raza, Ali S.; Cho, Jungsuk; de Moraes, Carlos G. V.; Wang, Min; Zhang, Xian; Kardon, Randy H.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

    2015-01-01

    Objective To compare loss in sensitivity measured using standard automated perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured using frequency-domain optical coherence tomography in the macula of patients with glaucoma. Methods To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC + IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC + IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea. Results The RGC + IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman ρ = 0.71–0.74). Agreement was worse (0.53–0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC + IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°. Conclusion In the central 7.2°, local RGC + IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement. PMID:22159673

  11. The influence of local spring temperature variance on temperature sensitivity of spring phenology.

    PubMed

    Wang, Tao; Ottlé, Catherine; Peng, Shushi; Janssens, Ivan A; Lin, Xin; Poulter, Benjamin; Yue, Chao; Ciais, Philippe

    2014-05-01

    The impact of climate warming on the advancement of plant spring phenology has been heavily investigated over the last decade and there exists great variability among plants in their phenological sensitivity to temperature. However, few studies have explicitly linked phenological sensitivity to local climate variance. Here, we set out to test the hypothesis that the strength of phenological sensitivity declines with increased local spring temperature variance, by synthesizing results across ground observations. We assemble ground-based long-term (20-50 years) spring phenology database (PEP725 database) and the corresponding climate dataset. We find a prevalent decline in the strength of phenological sensitivity with increasing local spring temperature variance at the species level from ground observations. It suggests that plants might be less likely to track climatic warming at locations with larger local spring temperature variance. This might be related to the possibility that the frost risk could be higher in a larger local spring temperature variance and plants adapt to avoid this risk by relying more on other cues (e.g., high chill requirements, photoperiod) for spring phenology, thus suppressing phenological responses to spring warming. This study illuminates that local spring temperature variance is an understudied source in the study of phenological sensitivity and highlight the necessity of incorporating this factor to improve the predictability of plant responses to anthropogenic climate change in future studies. © 2013 John Wiley & Sons Ltd.

  12. Parameter optimization, sensitivity, and uncertainty analysis of an ecosystem model at a forest flux tower site in the United States

    USGS Publications Warehouse

    Wu, Yiping; Liu, Shuguang; Huang, Zhihong; Yan, Wende

    2014-01-01

    Ecosystem models are useful tools for understanding ecological processes and for sustainable management of resources. In biogeochemical field, numerical models have been widely used for investigating carbon dynamics under global changes from site to regional and global scales. However, it is still challenging to optimize parameters and estimate parameterization uncertainty for complex process-based models such as the Erosion Deposition Carbon Model (EDCM), a modified version of CENTURY, that consider carbon, water, and nutrient cycles of ecosystems. This study was designed to conduct the parameter identifiability, optimization, sensitivity, and uncertainty analysis of EDCM using our developed EDCM-Auto, which incorporated a comprehensive R package—Flexible Modeling Framework (FME) and the Shuffled Complex Evolution (SCE) algorithm. Using a forest flux tower site as a case study, we implemented a comprehensive modeling analysis involving nine parameters and four target variables (carbon and water fluxes) with their corresponding measurements based on the eddy covariance technique. The local sensitivity analysis shows that the plant production-related parameters (e.g., PPDF1 and PRDX) are most sensitive to the model cost function. Both SCE and FME are comparable and performed well in deriving the optimal parameter set with satisfactory simulations of target variables. Global sensitivity and uncertainty analysis indicate that the parameter uncertainty and the resulting output uncertainty can be quantified, and that the magnitude of parameter-uncertainty effects depends on variables and seasons. This study also demonstrates that using the cutting-edge R functions such as FME can be feasible and attractive for conducting comprehensive parameter analysis for ecosystem modeling.

  13. The problem and promise of scale dependency in community phylogenetics.

    PubMed

    Swenson, Nathan G; Enquist, Brian J; Pither, Jason; Thompson, Jill; Zimmerman, Jess K

    2006-10-01

    The problem of scale dependency is widespread in investigations of ecological communities. Null model investigations of community assembly exemplify the challenges involved because they typically include subjectively defined "regional species pools." The burgeoning field of community phylogenetics appears poised to face similar challenges. Our objective is to quantify the scope of the problem of scale dependency by comparing the phylogenetic structure of assemblages across contrasting geographic and taxonomic scales. We conduct phylogenetic analyses on communities within three tropical forests, and perform a sensitivity analysis with respect to two scaleable inputs: taxonomy and species pool size. We show that (1) estimates of phylogenetic overdispersion within local assemblages depend strongly on the taxonomic makeup of the local assemblage and (2) comparing the phylogenetic structure of a local assemblage to a species pool drawn from increasingly larger geographic scales results in an increased signal of phylogenetic clustering. We argue that, rather than posing a problem, "scale sensitivities" are likely to reveal general patterns of diversity that could help identify critical scales at which local or regional influences gain primacy for the structuring of communities. In this way, community phylogenetics promises to fill an important gap in community ecology and biogeography research.

  14. Quantification of Lewis's Woodpecker habitat using Forest Inventory and Analysis data

    Treesearch

    Chris Witt

    2009-01-01

    The Utah Department of Natural Resources' Division of Wildlife Resources (UDWR) placed Lewis's Woodpecker (Melanerpes lewis) on their Sensitive Species Tier II list due to declining populations and suspected local extirpations throughout the state. It is thought that the decline in burned coniferous forest has reduced the amount of suitable...

  15. Automatic localization of cerebral cortical malformations using fractal analysis.

    PubMed

    De Luca, A; Arrigoni, F; Romaniello, R; Triulzi, F M; Peruzzo, D; Bertoldo, A

    2016-08-21

    Malformations of cortical development (MCDs) encompass a variety of brain disorders affecting the normal development and organization of the brain cortex. The relatively low incidence and the extreme heterogeneity of these disorders hamper the application of classical group level approaches for the detection of lesions. Here, we present a geometrical descriptor for a voxel level analysis based on fractal geometry, then define two similarity measures to detect the lesions at single subject level. The pipeline was applied to 15 normal children and nine pediatric patients affected by MCDs following two criteria, maximum accuracy (WACC) and minimization of false positives (FPR), and proved that our lesion detection algorithm is able to detect and locate abnormalities of the brain cortex with high specificity (WACC  =  85%, FPR  =  96%), sensitivity (WACC  =  83%, FPR  =  63%) and accuracy (WACC  =  85%, FPR  =  90%). The combination of global and local features proves to be effective, making the algorithm suitable for the detection of both focal and diffused malformations. Compared to other existing algorithms, this method shows higher accuracy and sensitivity.

  16. Automatic localization of cerebral cortical malformations using fractal analysis

    NASA Astrophysics Data System (ADS)

    De Luca, A.; Arrigoni, F.; Romaniello, R.; Triulzi, F. M.; Peruzzo, D.; Bertoldo, A.

    2016-08-01

    Malformations of cortical development (MCDs) encompass a variety of brain disorders affecting the normal development and organization of the brain cortex. The relatively low incidence and the extreme heterogeneity of these disorders hamper the application of classical group level approaches for the detection of lesions. Here, we present a geometrical descriptor for a voxel level analysis based on fractal geometry, then define two similarity measures to detect the lesions at single subject level. The pipeline was applied to 15 normal children and nine pediatric patients affected by MCDs following two criteria, maximum accuracy (WACC) and minimization of false positives (FPR), and proved that our lesion detection algorithm is able to detect and locate abnormalities of the brain cortex with high specificity (WACC  =  85%, FPR  =  96%), sensitivity (WACC  =  83%, FPR  =  63%) and accuracy (WACC  =  85%, FPR  =  90%). The combination of global and local features proves to be effective, making the algorithm suitable for the detection of both focal and diffused malformations. Compared to other existing algorithms, this method shows higher accuracy and sensitivity.

  17. Automatic network coupling analysis for dynamical systems based on detailed kinetic models.

    PubMed

    Lebiedz, Dirk; Kammerer, Julia; Brandt-Pollmann, Ulrich

    2005-10-01

    We introduce a numerical complexity reduction method for the automatic identification and analysis of dynamic network decompositions in (bio)chemical kinetics based on error-controlled computation of a minimal model dimension represented by the number of (locally) active dynamical modes. Our algorithm exploits a generalized sensitivity analysis along state trajectories and subsequent singular value decomposition of sensitivity matrices for the identification of these dominant dynamical modes. It allows for a dynamic coupling analysis of (bio)chemical species in kinetic models that can be exploited for the piecewise computation of a minimal model on small time intervals and offers valuable functional insight into highly nonlinear reaction mechanisms and network dynamics. We present results for the identification of network decompositions in a simple oscillatory chemical reaction, time scale separation based model reduction in a Michaelis-Menten enzyme system and network decomposition of a detailed model for the oscillatory peroxidase-oxidase enzyme system.

  18. Modeling Nitrogen Dynamics in a Waste Stabilization Pond System Using Flexible Modeling Environment with MCMC.

    PubMed

    Mukhtar, Hussnain; Lin, Yu-Pin; Shipin, Oleg V; Petway, Joy R

    2017-07-12

    This study presents an approach for obtaining realization sets of parameters for nitrogen removal in a pilot-scale waste stabilization pond (WSP) system. The proposed approach was designed for optimal parameterization, local sensitivity analysis, and global uncertainty analysis of a dynamic simulation model for the WSP by using the R software package Flexible Modeling Environment (R-FME) with the Markov chain Monte Carlo (MCMC) method. Additionally, generalized likelihood uncertainty estimation (GLUE) was integrated into the FME to evaluate the major parameters that affect the simulation outputs in the study WSP. Comprehensive modeling analysis was used to simulate and assess nine parameters and concentrations of ON-N, NH₃-N and NO₃-N. Results indicate that the integrated FME-GLUE-based model, with good Nash-Sutcliffe coefficients (0.53-0.69) and correlation coefficients (0.76-0.83), successfully simulates the concentrations of ON-N, NH₃-N and NO₃-N. Moreover, the Arrhenius constant was the only parameter sensitive to model performances of ON-N and NH₃-N simulations. However, Nitrosomonas growth rate, the denitrification constant, and the maximum growth rate at 20 °C were sensitive to ON-N and NO₃-N simulation, which was measured using global sensitivity.

  19. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Richard, Patrick, E-mail: patrjr@uw.edu; Phillips, Mark; Smith, Wade

    Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with themore » largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.« less

  20. "Developing culturally sensitive affect scales for global mental health research and practice: Emotional balance, not named syndromes, in Indian Adivasi subjective well-being".

    PubMed

    Snodgrass, Jeffrey G; Lacy, Michael G; Upadhyay, Chakrapani

    2017-08-01

    We present a perspective to analyze mental health without either a) imposing Western illness categories or b) adopting local or "native" categories of mental distress. Our approach takes as axiomatic only that locals within any culture share a cognitive and verbal lexicon of salient positive and negative emotional experiences, which an appropriate and repeatable set of ethnographic procedures can elicit. Our approach is provisionally agnostic with respect to either Western or native nosological categories, and instead focuses on persons' relative frequency of experiencing emotions. Putting this perspective into practice in India, our ethnographic fieldwork (2006-2014) and survey analysis (N = 219) resulted in a 40-item Positive and Negative Affect Scale (PANAS), which we used to assess the mental well-being of Indigenous persons (the tribal Sahariya) in the Indian states of Rajasthan and Madhya Pradesh. Generated via standard cognitive anthropological procedures that can be replicated elsewhere, measures such as this possess features of psychiatric scales favored by leaders in global mental health initiatives. Though not capturing locally named distress syndromes, our scale is nonetheless sensitive to local emotional experiences, frames of meaning, and "idioms of distress." By sharing traits of both global and also locally-derived diagnoses, approaches like ours can help identify synergies between them. For example, employing data reduction techniques such as factor analysis-where diagnostic and screening categories emerge inductively ex post facto from emotional symptom clusters, rather than being deduced or assigned a priori by either global mental health experts or locals themselves-reveals hidden overlaps between local wellness idioms and global ones. Practically speaking, our perspective, which assesses both emotional frailty and also potential sources of emotional resilience and balance, while eschewing all named illness categories, can be deployed in mental health initiatives in ways that minimize stigma and increase both the acceptability and validity of assessment instruments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. On the sensitivity of 4 different CPV module technologies to relevant ambient and operation conditions

    NASA Astrophysics Data System (ADS)

    Domínguez, César; Besson, Pierre

    2014-09-01

    The sensitivity of four different CPV module technologies to most operating conditions relevant to CPV systems has been studied, namely DNI, spectrum, cell and lens temperature and clearness of the sky. In order to isolate the influence of a single operation parameter, the analysis of long-term outdoor monitoring data is required. The effect of lens temperature on cell current has been found to vary greatly between modules due to the different optical architectures studied. Maximum sensitivity is found for silicone-on-glass primary lenses. The VOC thermal coefficient was found to vary between module technologies, probably due to differences in maximum local effective concentration.

  2. Automated Optimization of Potential Parameters

    PubMed Central

    Michele, Di Pierro; Ron, Elber

    2013-01-01

    An algorithm and software to refine parameters of empirical energy functions according to condensed phase experimental measurements are discussed. The algorithm is based on sensitivity analysis and local minimization of the differences between experiment and simulation as a function of potential parameters. It is illustrated for a toy problem of alanine dipeptide and is applied to folding of the peptide WAAAH. The helix fraction is highly sensitive to the potential parameters while the slope of the melting curve is not. The sensitivity variations make it difficult to satisfy both observations simultaneously. We conjecture that there is no set of parameters that reproduces experimental melting curves of short peptides that are modeled with the usual functional form of a force field. PMID:24015115

  3. Sensitivity analysis of Jacobian determinant used in treatment planning for lung cancer

    NASA Astrophysics Data System (ADS)

    Shao, Wei; Gerard, Sarah E.; Pan, Yue; Patton, Taylor J.; Reinhardt, Joseph M.; Durumeric, Oguz C.; Bayouth, John E.; Christensen, Gary E.

    2018-03-01

    Four-dimensional computed tomography (4DCT) is regularly used to visualize tumor motion in radiation therapy for lung cancer. These 4DCT images can be analyzed to estimate local ventilation by finding a dense correspondence map between the end inhalation and the end exhalation CT image volumes using deformable image registration. Lung regions with ventilation values above a threshold are labeled as regions of high pulmonary function and are avoided when possible in the radiation plan. This paper investigates a sensitivity analysis of the relative Jacobian error to small registration errors. We present a linear approximation of the relative Jacobian error. Next, we give a formula for the sensitivity of the relative Jacobian error with respect to the Jacobian of perturbation displacement field. Preliminary sensitivity analysis results are presented using 4DCT scans from 10 individuals. For each subject, we generated 6400 random smooth biologically plausible perturbation vector fields using a cubic B-spline model. We showed that the correlation between the Jacobian determinant and the Frobenius norm of the sensitivity matrix is close to -1, which implies that the relative Jacobian error in high-functional regions is less sensitive to noise. We also showed that small displacement errors on the average of 0.53 mm may lead to a 10% relative change in Jacobian determinant. We finally showed that the average relative Jacobian error and the sensitivity of the system for all subjects are positively correlated (close to +1), i.e. regions with high sensitivity has more error in Jacobian determinant on average.

  4. Prostate cancer localization with multispectral MRI using cost-sensitive support vector machines and conditional random fields.

    PubMed

    Artan, Yusuf; Haider, Masoom A; Langer, Deanna L; van der Kwast, Theodorus H; Evans, Andrew J; Yang, Yongyi; Wernick, Miles N; Trachtenberg, John; Yetik, Imam Samil

    2010-09-01

    Prostate cancer is a leading cause of cancer death for men in the United States. Fortunately, the survival rate for early diagnosed patients is relatively high. Therefore, in vivo imaging plays an important role for the detection and treatment of the disease. Accurate prostate cancer localization with noninvasive imaging can be used to guide biopsy, radiotherapy, and surgery as well as to monitor disease progression. Magnetic resonance imaging (MRI) performed with an endorectal coil provides higher prostate cancer localization accuracy, when compared to transrectal ultrasound (TRUS). However, in general, a single type of MRI is not sufficient for reliable tumor localization. As an alternative, multispectral MRI, i.e., the use of multiple MRI-derived datasets, has emerged as a promising noninvasive imaging technique for the localization of prostate cancer; however almost all studies are with human readers. There is a significant inter and intraobserver variability for human readers, and it is substantially difficult for humans to analyze the large dataset of multispectral MRI. To solve these problems, this study presents an automated localization method using cost-sensitive support vector machines (SVMs) and shows that this method results in improved localization accuracy than classical SVM. Additionally, we develop a new segmentation method by combining conditional random fields (CRF) with a cost-sensitive framework and show that our method further improves cost-sensitive SVM results by incorporating spatial information. We test SVM, cost-sensitive SVM, and the proposed cost-sensitive CRF on multispectral MRI datasets acquired from 21 biopsy-confirmed cancer patients. Our results show that multispectral MRI helps to increase the accuracy of prostate cancer localization when compared to single MR images; and that using advanced methods such as cost-sensitive SVM as well as the proposed cost-sensitive CRF can boost the performance significantly when compared to SVM.

  5. Accumulation mechanisms and the weathering of Antarctic equilibrated ordinary chondrites

    NASA Astrophysics Data System (ADS)

    Benoit, P. H.; Sears, D. W. G.

    1999-06-01

    Induced thermoluminescence (TL) is used to quantitatively evaluate the degree of weathering of meteorites found in Antarctica. We find a weak correlation between TL sensitivity and descriptions of weathering in hand specimens, the highly weathered meteorites having lower TL sensitivity than unweathered meteorites. Analysis of samples taken throughout large meteorites shows that the heterogeneity in TL sensitivity within meteorite finds is not large relative to the range exhibited by different weathered meteorites. The TL sensitivity values can be restored by minimal acid washing, suggesting the lower TL sensitivities of weathered meteorites reflects thin weathering rims on mineral grains or coating of these grains by iron oxides produced by hydration and oxidation of metal and sulfides. Small meteorites may tend to be more highly weathered than large meteorites at the Allan Hills ice fields. We find that meteorite fragments >150 g may take up to 300,000 years to reach the highest degrees of weathering, while meteorites <150 g require <40,000 years. However, at other fields, local environmental conditions and variability in terrestrial history are more important in determining weathering than size alone. Weathering correlates poorly with surface exposure duration, presumably because weathering occurs primarily during interglacial periods. The Allan Hills locality has served as a fairly stable surface over the last 100,000 years or so and has efficiently preserved both small and large meteorites. Meteorites from Lewis Cliff, however, have experienced extensive weathering, probably because of increased surface melt water from nearby outcrops. Meteorites from the Elephant Moraine locality tend to exhibit only minor degrees of weathering, but small meteorites are less weathered than large meteorites, which we suggest is due to the loss of small meteorites by aeolian transport.

  6. Assessment of cardiac fibrosis: a morphometric method comparison for collagen quantification.

    PubMed

    Schipke, Julia; Brandenberger, Christina; Rajces, Alexandra; Manninger, Martin; Alogna, Alessio; Post, Heiner; Mühlfeld, Christian

    2017-04-01

    Fibrotic remodeling of the heart is a frequent condition linked to various diseases and cardiac dysfunction. Collagen quantification is an important objective in cardiac fibrosis research; however, a variety of different histological methods are currently used that may differ in accuracy. Here, frequently applied collagen quantification techniques were compared. A porcine model of early stage heart failure with preserved ejection fraction was used as an example. Semiautomated threshold analyses were imprecise, mainly due to inclusion of noncollagen structures or failure to detect certain collagen deposits. In contrast, collagen assessment by automated image analysis and light microscopy (LM)-stereology was more sensitive. Depending on the quantification method, the amount of estimated collagen varied and influenced intergroup comparisons. PicroSirius Red, Masson's trichrome, and Azan staining protocols yielded similar results, whereas the measured collagen area increased with increasing section thickness. Whereas none of the LM-based methods showed significant differences between the groups, electron microscopy (EM)-stereology revealed a significant collagen increase between cardiomyocytes in the experimental group, but not at other localizations. In conclusion, in contrast to the staining protocol, section thickness and the quantification method being used directly influence the estimated collagen content and thus, possibly, intergroup comparisons. EM in combination with stereology is a precise and sensitive method for collagen quantification if certain prerequisites are considered. For subtle fibrotic alterations, consideration of collagen localization may be necessary. Among LM methods, LM-stereology and automated image analysis are appropriate to quantify fibrotic changes, the latter depending on careful control of algorithm and comparable section staining. NEW & NOTEWORTHY Direct comparison of frequently applied histological fibrosis assessment techniques revealed a distinct relation of measured collagen and utilized quantification method as well as section thickness. Besides electron microscopy-stereology, which was precise and sensitive, light microscopy-stereology and automated image analysis proved to be appropriate for collagen quantification. Moreover, consideration of collagen localization might be important in revealing minor fibrotic changes. Copyright © 2017 the American Physiological Society.

  7. Development of a microbial contamination susceptibility model for private domestic groundwater sources

    NASA Astrophysics Data System (ADS)

    Hynds, Paul D.; Misstear, Bruce D.; Gill, Laurence W.

    2012-12-01

    Groundwater quality analyses were carried out on samples from 262 private sources in the Republic of Ireland during the period from April 2008 to November 2010, with microbial quality assessed by thermotolerant coliform (TTC) presence. Assessment of potential microbial contamination risk factors was undertaken at all sources, and local meteorological data were also acquired. Overall, 28.9% of wells tested positive for TTC, with risk analysis indicating that source type (i.e., borehole or hand-dug well), local bedrock type, local subsoil type, groundwater vulnerability, septic tank setback distance, and 48 h antecedent precipitation were all significantly associated with TTC presence (p < 0.05). A number of source-specific design parameters were also significantly associated with bacterial presence. Hierarchical logistic regression with stepwise parameter entry was used to develop a private well susceptibility model, with the final model exhibiting a mean predictive accuracy of >80% (TTC present or absent) when compared to an independent validation data set. Model hierarchies of primary significance are source design (20%), septic tank location (11%), hydrogeological setting (10%), and antecedent 120 h precipitation (2%). Sensitivity analysis shows that the probability of contamination is highly sensitive to septic tank setback distance, with probability increasing linearly with decreases in setback distance. Likewise, contamination probability was shown to increase with increasing antecedent precipitation. Results show that while groundwater vulnerability category is a useful indicator of aquifer susceptibility to contamination, its suitability with regard to source contamination is less clear. The final model illustrates that both localized (well-specific) and generalized (aquifer-specific) contamination mechanisms are involved in contamination events, with localized bypass mechanisms dominant. The susceptibility model developed here could be employed in the appropriate location, design, construction, and operation of private groundwater wells, thereby decreasing the contamination risk, and hence health risk, associated with these sources.

  8. Sensitivity analysis of a new dual-porosity hydroloigcal model coupled with the SOSlope model for the numerical simulations of rainfall triggered shallow landslides.

    NASA Astrophysics Data System (ADS)

    Schwarz, Massimiliano; Cohen, Denis

    2017-04-01

    Morphology and extent of hydrological pathways, in combination with the spatio-temporal variability of rainfall events and the heterogeneities of hydro-mechanical properties of soils, has a major impact on the hydrological conditions that locally determine the triggering of shallow landslides. The coupling of these processes at different spatial scales is an enormous challenge for slope stability modeling at the catchment scale. In this work we present a sensitivity analysis of a new dual-porosity hydrological model implemented in the hydro-mechanical model SOSlope for the modeling of shallow landslides on vegetated hillslopes. The proposed model links the calculation of the saturation dynamic of preferential flow-paths based on hydrological and topographical characteristics of the landscape to the hydro-mechanical behavior of the soil along a potential failure surface due to the changes of soil matrix saturation. Furthermore, the hydro-mechanical changes of soil conditions are linked to the local stress-strain properties of the (rooted-)soil that ultimately determine the force redistribution and related deformations at the hillslope scale. The model considers forces to be redistributed through three types of solicitations: tension, compression, and shearing. The present analysis shows how the conditions of deformation due to the passive earth pressure mobilized at the toe of the landslide are particularly important in defining the timing and extension of shallow landslides. The model also shows that, in densely rooted hillslopes, lateral force redistribution under tension through the root-network may substantially contribute to stabilizing slopes, avoiding crack formation and large deformations. The results of the sensitivity analysis are discussed in the context of protection forest management and bioengineering techniques.

  9. BSA-coated nanoparticles for improved SERS-based intracellular pH sensing.

    PubMed

    Zheng, Xiao-Shan; Hu, Pei; Cui, Yan; Zong, Cheng; Feng, Jia-Min; Wang, Xin; Ren, Bin

    2014-12-16

    Local microenvironment pH sensing is one of the key parameters for the understanding of many biological processes. As a noninvasive and high sensitive technique, surface-enhanced Raman spectroscopy (SERS) has attracted considerable interest in the detection of the local pH of live cells. We herein develop a facile way to prepare Au-(4-MPy)-BSA (AMB) pH nanosensor. The 4-MPy (4-mercaptopyridine) was used as the pH sensing molecule. The modification of the nanoparticles with BSA not only provides a high sensitive response to pH changes ranging from pH 4.0 to 9.0 but also exhibits a high sensitivity and good biocompatibility, stability, and reliability in various solutions (including the solutions of high ionic strength or with complex composition such as the cell culture medium), both in the aggregation state or after long-term storage. The AMB pH nanosensor shows great advantages for reliable intracellular pH analysis and has been successfully used to monitor the pH distribution of live cells and can address the grand challenges in SERS-based pH sensing for practical biological applications.

  10. Sensitivity of drainage efficiency of cranberry fields to edaphic conditions

    NASA Astrophysics Data System (ADS)

    Periard, Yann; José Gumiere, Silvio; Rousseau, Alain N.; Caron, Jean; Hallema, Dennis W.

    2014-05-01

    Water management on a cranberry farm requires intelligent irrigation and drainage strategies to sustain strong productivity and minimize environmental impact. For example, to avoid propagation of disease and meet evapotranspiration demand, it is imperative to maintain optimal moisture conditions in the root zone, which depends on an efficient drainage system. However, several drainage problems have been identified in cranberry fields. Most of these drainage problems are due to the presence of a restrictive layer in the soil profile (Gumiere et al., 2014). The objective of this work is to evaluate the effects of a restrictive layer on the drainage efficiency by the bias of a multi-local sensitivity analysis. We have tested the sensitivity of the drainage efficiency to different input parameters set of soil hydraulic properties, geometrical parameters and climatic conditions. Soil water flux dynamic for every input parameters set was simulated with finite element model Hydrus 1D (Simanek et al., 2008). Multi-local sensitivity was calculated with the Gâteaux directional derivatives with the procedure described by Cheviron et al. (2010). Results indicate that drainage efficiency is more sensitive to soil hydraulic properties than geometrical parameters and climatic conditions. Then, the geometrical parameters of the depth are more sensitive than the thickness. The drainage efficiency was very insensitive to the climatic conditions. Understanding the sensitivity of drainage efficiency according to soil hydraulic properties, geometrical and climatic conditions are essential for diagnosis drainage problems. However, it becomes important to identify the mechanisms involved in the genesis of anthropogenic soils cranberry to identify conditions that may lead to the formation of a restrictive layer. References: Cheviron, B., S.J. Gumiere, Y. Le Bissonnais, R. Moussa and D. Raclot. 2010. Sensitivity analysis of distributed erosion models: Framework. Water Resources Research 46: W08508. doi:10.1029/2009WR007950. Gumiere, S.J., J. Lafond, D. W. Hallema, Y. Périard, J. Caron et J. Gallichand. 2014. Mapping soil hydraulic conductivity and matric potential for water management of cranberry: Characterization and spatial interpolation methods. Biosystems Engineering.

  11. Sensitivity computation of the ell1 minimization problem and its application to dictionary design of ill-posed problems

    NASA Astrophysics Data System (ADS)

    Horesh, L.; Haber, E.

    2009-09-01

    The ell1 minimization problem has been studied extensively in the past few years. Recently, there has been a growing interest in its application for inverse problems. Most studies have concentrated in devising ways for sparse representation of a solution using a given prototype dictionary. Very few studies have addressed the more challenging problem of optimal dictionary construction, and even these were primarily devoted to the simplistic sparse coding application. In this paper, sensitivity analysis of the inverse solution with respect to the dictionary is presented. This analysis reveals some of the salient features and intrinsic difficulties which are associated with the dictionary design problem. Equipped with these insights, we propose an optimization strategy that alleviates these hurdles while utilizing the derived sensitivity relations for the design of a locally optimal dictionary. Our optimality criterion is based on local minimization of the Bayesian risk, given a set of training models. We present a mathematical formulation and an algorithmic framework to achieve this goal. The proposed framework offers the design of dictionaries for inverse problems that incorporate non-trivial, non-injective observation operators, where the data and the recovered parameters may reside in different spaces. We test our algorithm and show that it yields improved dictionaries for a diverse set of inverse problems in geophysics and medical imaging.

  12. Sensitive and accurate identification of protein–DNA binding events in ChIP-chip assays using higher order derivative analysis

    PubMed Central

    Barrett, Christian L.; Cho, Byung-Kwan

    2011-01-01

    Immuno-precipitation of protein–DNA complexes followed by microarray hybridization is a powerful and cost-effective technology for discovering protein–DNA binding events at the genome scale. It is still an unresolved challenge to comprehensively, accurately and sensitively extract binding event information from the produced data. We have developed a novel strategy composed of an information-preserving signal-smoothing procedure, higher order derivative analysis and application of the principle of maximum entropy to address this challenge. Importantly, our method does not require any input parameters to be specified by the user. Using genome-scale binding data of two Escherichia coli global transcription regulators for which a relatively large number of experimentally supported sites are known, we show that ∼90% of known sites were resolved to within four probes, or ∼88 bp. Over half of the sites were resolved to within two probes, or ∼38 bp. Furthermore, we demonstrate that our strategy delivers significant quantitative and qualitative performance gains over available methods. Such accurate and sensitive binding site resolution has important consequences for accurately reconstructing transcriptional regulatory networks, for motif discovery, for furthering our understanding of local and non-local factors in protein–DNA interactions and for extending the usefulness horizon of the ChIP-chip platform. PMID:21051353

  13. The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay.

    PubMed

    Jowsey, Ian R; Clapp, Catherine J; Safford, Bob; Gibbons, Ben T; Basketter, David A

    2008-01-01

    The identification and characterization of chemicals that possess skin-sensitizing potential are typically performed using predictive tests. However, human exposure to skin-sensitizing chemicals often occurs via a matrix (vehicle) that differs from that used in these tests. It is thus important to account for the potential impact of vehicle differences when undertaking quantitative risk assessment for skin sensitization. This is achieved through the application of a specific sensitization assessment factor (SAF), scaled between 1 and 10, when identifying an acceptable exposure level. The objective of the analysis described herein is to determine the impact of vehicle differences on local lymph node assay (LLNA) EC3 values (concentrations of test chemical required to provoke a 3-fold increase in lymph node cell proliferation). Initially, the inherent variability of the LLNA was investigated by examining the reproducibility of EC3 values for 14 chemicals that have been tested more than once in the same vehicle (4:1 acetone:olive oil, AOO). This analysis reveals that the variability in EC3 value for these chemicals following multiple assessments is <5-fold. Next, data from the literature and previously unpublished studies were compiled for 18 chemicals that had been assessed in the LLNA using at least 2 of 15 different vehicles. These data demonstrate that often the variability in EC3 values observed for a given chemical in different vehicles is no greater than the 5-fold inherent variability observed when assessing a chemical in the same vehicle on multiple occasions. However, there are examples where EC3 values for a chemical differ by a factor of more than 10 between different vehicles. These observations were often associated with an apparent underestimation of potency (higher EC3 values) with predominantly aqueous vehicles or propylene glycol. These data underscore the need to consider vehicle effects in the context of skin-sensitization risk assessments.

  14. A systems approach for the development of a sustainable community--the application of the sensitivity model (SM).

    PubMed

    Chan, Shih-Liang; Huang, Shu-Li

    2004-09-01

    Corresponding to the concept of 'Think globally, act locally and plan regionally' of sustainable development, this paper discusses the approach of planning a sustainable community in terms of systems thinking. We apply a systems tool, the sensitivity model (SM), to build a model of the development of the community of Ping-Ding, located adjacent to the Yang-Ming-Shan National Park, Taiwan. The major issue in the development of Ping-Ding is the conflict between environmental conservation and the development of a local tourism industry. With the involvement of local residents, planners, and interest groups, a system model of 26 variables was defined to identify characteristics of Ping-Ding through pattern recognition. Two scenarios concerning the sustainable development of Ping-Ding are simulated with interlinked feedbacks from variables. The results of the analysis indicate that the development of Ping-Ding would be better served by the planning of agriculture and the tourism industry. The advantages and shortfalls of applying SM in the current planning environment of Taiwan are also discussed to conclude this paper.

  15. Local sensor based on nanowire field effect transistor from inhomogeneously doped silicon on insulator

    NASA Astrophysics Data System (ADS)

    Presnov, Denis E.; Bozhev, Ivan V.; Miakonkikh, Andrew V.; Simakin, Sergey G.; Trifonov, Artem S.; Krupenin, Vladimir A.

    2018-02-01

    We present the original method for fabricating a sensitive field/charge sensor based on field effect transistor (FET) with a nanowire channel that uses CMOS-compatible processes only. A FET with a kink-like silicon nanowire channel was fabricated from the inhomogeneously doped silicon on insulator wafer very close (˜100 nm) to the extremely sharp corner of a silicon chip forming local probe. The single e-beam lithographic process with a shadow deposition technique, followed by separate two reactive ion etching processes, was used to define the narrow semiconductor nanowire channel. The sensors charge sensitivity was evaluated to be in the range of 0.1-0.2 e /√{Hz } from the analysis of their transport and noise characteristics. The proposed method provides a good opportunity for the relatively simple manufacture of a local field sensor for measuring the electrical field distribution, potential profiles, and charge dynamics for a wide range of mesoscopic objects. Diagnostic systems and devices based on such sensors can be used in various fields of physics, chemistry, material science, biology, electronics, medicine, etc.

  16. Innovative Tools and Technology for Analysis of Single Cells and Cell-Cell Interaction.

    PubMed

    Konry, Tania; Sarkar, Saheli; Sabhachandani, Pooja; Cohen, Noa

    2016-07-11

    Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities. Additionally, microscale techniques permit rapid, high-throughput, multiparametric screening that has become essential for -omics research. This review highlights innovative applications of microscale platforms in genetic, proteomic, and metabolic detection in single cells; cell sorting strategies; and heterotypic cell-cell interaction. We discuss key design aspects of single-cell localization and isolation in microfluidic systems, dynamic and endpoint analyses, and approaches that integrate highly multiplexed detection of various intracellular species.

  17. An Analysis of the Utility of Handheld PET Probes for the Intraoperative Localization of Malignant Tissue

    PubMed Central

    González, Segundo Jaime; González, Lorena; Wong, Joyce; Brader, Peter; Zakowski, Maureen; Gönen, Mithat; Daghighian, Farhad; Fong, Yuman

    2012-01-01

    Introduction The intraoperative localization of suspicious lesions detected by positron emission tomography (PET) scan remains a challenge. To solve this, two novel probes have been created to accurately detect the 18F-FDG radiotracer intraoperatively. Methods Nude rats were inoculated with mesothelioma. When PET scans detected 10-mm tumors, animals were dissected and the PET probes analyzed the intraoperative radiotracer uptake of these lesions as tumor to background ratio (TBR). Results The 17 suspicious lesions seen on PET scan were localized intraoperatively (by their high TBR) using the PET probes and found malignant on pathology. Interestingly, smaller tumors not visualized on PET scan were detected intraoperatively by their high TBR and found malignant on pathology. Furthermore, using a TBR threshold as low as 2.0, both gamma (sensitivity, 100%; specificity, 80%; positive predictive value (PPV), 96%; and negative predictive value (NPV), 100%) and beta (sensitivity, 100%; specificity, 60%; PPV, 93%; and NPV, 100%) probes reliably detected suspicious lesions on PET scan imaging. They also showed an excellent area under the curve of 0.9 and 0.97 (95% CI of 0.81–0.99 and 0.93–1.0) for gamma and beta probes, respectively, in the receiver operating characteristic analysis for detecting malignancy. Conclusion This novel tool could be used synergistically with a PET scan imaging to maximize tissue selection intraoperatively. PMID:21108016

  18. Imaging electric field dynamics with graphene optoelectronics.

    PubMed

    Horng, Jason; Balch, Halleh B; McGuire, Allister F; Tsai, Hsin-Zon; Forrester, Patrick R; Crommie, Michael F; Cui, Bianxiao; Wang, Feng

    2016-12-16

    The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts, a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.

  19. Sensitivity analysis of an optimization-based trajectory planner for autonomous vehicles in urban environments

    NASA Astrophysics Data System (ADS)

    Hardy, Jason; Campbell, Mark; Miller, Isaac; Schimpf, Brian

    2008-10-01

    The local path planner implemented on Cornell's 2007 DARPA Urban Challenge entry vehicle Skynet utilizes a novel mixture of discrete and continuous path planning steps to facilitate a safe, smooth, and human-like driving behavior. The planner first solves for a feasible path through the local obstacle map using a grid based search algorithm. The resulting path is then refined using a cost-based nonlinear optimization routine with both hard and soft constraints. The behavior of this optimization is influenced by tunable weighting parameters which govern the relative cost contributions assigned to different path characteristics. This paper studies the sensitivity of the vehicle's performance to these path planner weighting parameters using a data driven simulation based on logged data from the National Qualifying Event. The performance of the path planner in both the National Qualifying Event and in the Urban Challenge is also presented and analyzed.

  20. Analysis of Composite Panels Subjected to Thermo-Mechanical Loads

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Peters, Jeanne M.

    1999-01-01

    The results of a detailed study of the effect of cutout on the nonlinear response of curved unstiffened panels are presented. The panels are subjected to combined temperature gradient through-the-thickness combined with pressure loading and edge shortening or edge shear. The analysis is based on a first-order, shear deformation, Sanders-Budiansky-type shell theory with the effects of large displacements, moderate rotations, transverse shear deformation, and laminated anisotropic material behavior included. A mixed formulation is used with the fundamental unknowns consisting of the generalized displacements and the stress resultants of the panel. The nonlinear displacements, strain energy, principal strains, transverse shear stresses, transverse shear strain energy density, and their hierarchical sensitivity coefficients are evaluated. The hierarchical sensitivity coefficients measure the sensitivity of the nonlinear response to variations in the panel parameters, as well as in the material properties of the individual layers. Numerical results are presented for cylindrical panels and show the effects of variations in the loading and the size of the cutout on the global and local response quantities as well as their sensitivity to changes in the various panel, layer, and micromechanical parameters.

  1. Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

    PubMed

    Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

    2017-10-05

    The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results suggest that multi-endpoint analysis in the LLNA leads to a better determination of the sensitizing potential of test substances. We also show that the gene expression of CXCL1 and/or CXCL2, which is involved in elicitation of contact hypersensitivity (CHS), can be a possible additional endpoint for discrimination of sensitizing compounds in LLNA. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Detection of Local Tumor Recurrence After Definitive Treatment of Head and Neck Squamous Cell Carcinoma: Histogram Analysis of Dynamic Contrast-Enhanced T1-Weighted Perfusion MRI.

    PubMed

    Choi, Sang Hyun; Lee, Jeong Hyun; Choi, Young Jun; Park, Ji Eun; Sung, Yu Sub; Kim, Namkug; Baek, Jung Hwan

    2017-01-01

    This study aimed to explore the added value of histogram analysis of the ratio of initial to final 90-second time-signal intensity AUC (AUCR) for differentiating local tumor recurrence from contrast-enhancing scar on follow-up dynamic contrast-enhanced T1-weighted perfusion MRI of patients treated for head and neck squamous cell carcinoma (HNSCC). AUCR histogram parameters were assessed among tumor recurrence (n = 19) and contrast-enhancing scar (n = 27) at primary sites and compared using the t test. ROC analysis was used to determine the best differentiating parameters. The added value of AUCR histogram parameters was assessed when they were added to inconclusive conventional MRI results. Histogram analysis showed statistically significant differences in the 50th, 75th, and 90th percentiles of the AUCR values between the two groups (p < 0.05). The 90th percentile of the AUCR values (AUCR 90 ) was the best predictor of local tumor recurrence (AUC, 0.77; 95% CI, 0.64-0.91) with an estimated cutoff of 1.02. AUCR 90 increased sensitivity by 11.7% over that of conventional MRI alone when added to inconclusive results. Histogram analysis of AUCR can improve the diagnostic yield for local tumor recurrence during surveillance after treatment for HNSCC.

  3. Sensitivity analysis of Repast computational ecology models with R/Repast.

    PubMed

    Prestes García, Antonio; Rodríguez-Patón, Alfonso

    2016-12-01

    Computational ecology is an emerging interdisciplinary discipline founded mainly on modeling and simulation methods for studying ecological systems. Among the existing modeling formalisms, the individual-based modeling is particularly well suited for capturing the complex temporal and spatial dynamics as well as the nonlinearities arising in ecosystems, communities, or populations due to individual variability. In addition, being a bottom-up approach, it is useful for providing new insights on the local mechanisms which are generating some observed global dynamics. Of course, no conclusions about model results could be taken seriously if they are based on a single model execution and they are not analyzed carefully. Therefore, a sound methodology should always be used for underpinning the interpretation of model results. The sensitivity analysis is a methodology for quantitatively assessing the effect of input uncertainty in the simulation output which should be incorporated compulsorily to every work based on in-silico experimental setup. In this article, we present R/Repast a GNU R package for running and analyzing Repast Simphony models accompanied by two worked examples on how to perform global sensitivity analysis and how to interpret the results.

  4. Qualitative and quantitative evaluation of a local lymph node assay based on ex vivo interleukin-2 production.

    PubMed

    Azam, Philippe; Peiffer, Jean-Luc; Ourlin, Jean-Claude; Bonnet, Pierre-Antoine; Tissier, Marie-Hélène; Vian, Laurence; Fabre, Isabelle

    2005-01-15

    The local lymph node assay (LLNA) is a regular method for the detection of sensitizing chemicals in mice which measures the incorporation of tritiated thymidine in lymph node cells. We have evaluated an alternative to this method based on the interleukin-2 (IL-2) production of lymph node cells. At the mRNA level, no change in the IL-2 gene expression level was detected by real-time PCR analysis. At the protein level, various experimental conditions were checked in order to improve the irritant versus sensitizer discrimination with a restricted set of prototypic compounds. In particular, the use of phytohemagglutinin A (PHA) in an ex vivo cell culture step showed an improvement of both signal and discrimination. In these optimised conditions, a panel of irritants and potency-graded sensitizers was used to assess the performance of the modified method. IFN-gamma production was used as a positive control. For each compound, a dose-response was performed and stimulation indexes (SI) were determined. Effective concentrations (EC) for each sensitizers were then extracted and compared to the literature data of the regular LLNA. The IL-2-based LLNA showed similar performances at both qualitative and quantitative levels compared to regular LLNA.

  5. Local staging and assessment of colon cancer with 1.5-T magnetic resonance imaging

    PubMed Central

    Blake, Helena; Jeyadevan, Nelesh; Abulafi, Muti; Swift, Ian; Toomey, Paul; Brown, Gina

    2016-01-01

    Objective: The aim of this study was to assess the accuracy of 1.5-T MRI in the pre-operative local T and N staging of colon cancer and identification of extramural vascular invasion (EMVI). Methods: Between 2010 and 2012, 60 patients with adenocarcinoma of the colon were prospectively recruited at 2 centres. 55 patients were included for final analysis. Patients received pre-operative 1.5-T MRI with high-resolution T2 weighted, gadolinium-enhanced T1 weighted and diffusion-weighted images. These were blindly assessed by two expert radiologists. Accuracy of the T-stage, N-stage and EMVI assessment was evaluated using post-operative histology as the gold standard. Results: Results are reported for two readers. Identification of T3 disease demonstrated an accuracy of 71% and 51%, sensitivity of 74% and 42% and specificity of 74% and 83%. Identification of N1 disease demonstrated an accuracy of 57% for both readers, sensitivity of 26% and 35% and specificity of 81% and 74%. Identification of EMVI demonstrated an accuracy of 74% and 69%, sensitivity 63% and 26% and specificity 80% and 91%. Conclusion: 1.5-T MRI achieved a moderate accuracy in the local evaluation of colon cancer, but cannot be recommended to replace CT on the basis of this study. Advances in knowledge: This study confirms that MRI is a viable alternative to CT for the local assessment of colon cancer, but this study does not reproduce the very high accuracy reported in the only other study to assess the accuracy of MRI in colon cancer staging. PMID:27226219

  6. Design of experiments for identification of complex biochemical systems with applications to mitochondrial bioenergetics.

    PubMed

    Vinnakota, Kalyan C; Beard, Daniel A; Dash, Ranjan K

    2009-01-01

    Identification of a complex biochemical system model requires appropriate experimental data. Models constructed on the basis of data from the literature often contain parameters that are not identifiable with high sensitivity and therefore require additional experimental data to identify those parameters. Here we report the application of a local sensitivity analysis to design experiments that will improve the identifiability of previously unidentifiable model parameters in a model of mitochondrial oxidative phosphorylation and tricaboxylic acid cycle. Experiments were designed based on measurable biochemical reactants in a dilute suspension of purified cardiac mitochondria with experimentally feasible perturbations to this system. Experimental perturbations and variables yielding the most number of parameters above a 5% sensitivity level are presented and discussed.

  7. Polarization sensitive localization based super-resolution microscopy with a birefringent wedge

    NASA Astrophysics Data System (ADS)

    Sinkó, József; Gajdos, Tamás; Czvik, Elvira; Szabó, Gábor; Erdélyi, Miklós

    2017-03-01

    A practical method has been presented for polarization sensitive localization based super-resolution microscopy using a birefringent dual wedge. The measurement of the polarization degree at the single molecule level can reveal the chemical and physical properties of the local environment of the fluorescent dye molecule and can hence provide information about the sub-diffraction sized structure of biological samples. Polarization sensitive STORM imaging of the F-Actins proved correlation between the orientation of fluorescent dipoles and the axis of the fibril.

  8. Experimental evaluation of the sensitivity to fuel utilization and air management on a 100 kW SOFC system

    NASA Astrophysics Data System (ADS)

    Santarelli, M.; Leone, P.; Calì, M.; Orsello, G.

    The tubular SOFC generator CHP-100, built by Siemens Power Generation (SPG) Stationary Fuel Cells (SFC), is running at the Gas Turbine Technologies (GTT) in Torino (Italy), in the framework of the EOS Project. The nominal load of the generator ensures a produced electric power of around 105 kW e ac and around 60 kW t of thermal power at 250 °C to be used for the custom tailored HVAC system. Several experimental sessions have been scheduled on the generator; the aim is to characterize the operation through the analysis of some global performance index and the detailed control of the operation of the different bundles of the whole stack. All the scheduled tests have been performed by applying the methodology of design of experiment; the main obtained results show the effect of the change of the analysed operating factors in terms of distribution of voltage and temperature over the stack. Fuel consumption tests give information about the sensitivity of the voltage and temperature distribution along the single bundles. On the other hand, since the generator is an air cooled system, the results of the tests on the air stoichs have been used to analyze the generator thermal management (temperature distribution and profiles) and its effect on the polarization. The sensitivity analysis of the local voltage to the overall fuel consumption modifications can be used as a powerful procedure to deduce the local distribution of fuel utilization (FU) along the single bundles: in fact, through a model obtained by deriving the polarization curve respect to FU, it is possible to link the distribution of voltage sensitivities to FC to the distribution of the local FU. The FU distribution will be shown as non-uniform, and this affects the local voltage and temperatures, causing a high warming effect in some rows of the generator. Therefore, a discussion around the effectiveness of the thermal regulation made by the air stoichs, in order to reduce the non-uniform distribution of temperature and the overheating (increasing therefore the voltage behavior along the generator) has been performed. It is demonstrated that the utilization of one air plenum is not effective in the thermal regulation of the whole generator, in particular in the reduction of the temperature gradients linked to the non-uniform fuel distribution.

  9. Technological advances in cosmogenic neutron detectors for measuring soil water content

    NASA Astrophysics Data System (ADS)

    Zreda, M. G.; Schrön, M.; Köhli, M.

    2017-12-01

    The cosmic-ray neutron probe is used for measuring area-average soil water content at the hectometer scale. Early work showed a simple exponential decrease with distance of the instrument's sensitivity and a footprint 300 m in radius. Recent research suggested a much higher sensitivity to local neutrons and reduced footprint. We show results confirming the high sensitivity to local neutrons, describe two ways to reduce local and increase far-field effects, and propose ways of measuring neutrons at different spatial scales. Measurements with moderated detectors across a 10-m-wide creek and a 2-m-wide water tank show a decrease by 30% and 20%, respectively, of neutron intensity over water compared to that over land nearby. These results mean that the detector is sensitive to meter-scale heterogeneities of water content. This sensitivity can be reduced by rising the detector or by shielding it from local neutrons. The effect of local water distributions on the measured neutron intensity decreases with height. In the water tank experiment it disappeared almost completely at the height of 2 m, leading to the conjecture that the height roughly equal to the horizontal scale of heterogeneity would eliminate the sensitivity. This may or may not be practical. Shielding the detector below by a hydrogenous material removes a substantial fraction of the local neutrons. The shielded detector has a reduced count rate, reduced sensitivity to local neutrons and increased sensitivity to neutrons farther afield, and a larger footprint. Such a detector could be preferable to the current cosmogenic-neutron probe under heterogeneous soil water conditions. The shielding experiments also inspired the development of a local-area neutron detector. It has hydrogenous neutron shields on all sides except the bottom, substantially blocking the neutrons coming from afar, while allowing the neutrons coming directly from below. Its footprint is equal to its physical dimension when the detector is placed on the surface. Once this detector is calibrated, it can be useful in calibrating the wide-area detector, for example over stony soils that are difficult to sample physically for water content determination, and in high-resolution mapping of neutron intensity and soil moisture.

  10. Documentation for a Structural Optimization Procedure Developed Using the Engineering Analysis Language (EAL)

    NASA Technical Reports Server (NTRS)

    Martin, Carl J., Jr.

    1996-01-01

    This report describes a structural optimization procedure developed for use with the Engineering Analysis Language (EAL) finite element analysis system. The procedure is written primarily in the EAL command language. Three external processors which are written in FORTRAN generate equivalent stiffnesses and evaluate stress and local buckling constraints for the sections. Several built-up structural sections were coded into the design procedures. These structural sections were selected for use in aircraft design, but are suitable for other applications. Sensitivity calculations use the semi-analytic method, and an extensive effort has been made to increase the execution speed and reduce the storage requirements. There is also an approximate sensitivity update method included which can significantly reduce computational time. The optimization is performed by an implementation of the MINOS V5.4 linear programming routine in a sequential liner programming procedure.

  11. Procedures for adjusting regional regression models of urban-runoff quality using local data

    USGS Publications Warehouse

    Hoos, A.B.; Sisolak, J.K.

    1993-01-01

    Statistical operations termed model-adjustment procedures (MAP?s) can be used to incorporate local data into existing regression models to improve the prediction of urban-runoff quality. Each MAP is a form of regression analysis in which the local data base is used as a calibration data set. Regression coefficients are determined from the local data base, and the resulting `adjusted? regression models can then be used to predict storm-runoff quality at unmonitored sites. The response variable in the regression analyses is the observed load or mean concentration of a constituent in storm runoff for a single storm. The set of explanatory variables used in the regression analyses is different for each MAP, but always includes the predicted value of load or mean concentration from a regional regression model. The four MAP?s examined in this study were: single-factor regression against the regional model prediction, P, (termed MAP-lF-P), regression against P,, (termed MAP-R-P), regression against P, and additional local variables (termed MAP-R-P+nV), and a weighted combination of P, and a local-regression prediction (termed MAP-W). The procedures were tested by means of split-sample analysis, using data from three cities included in the Nationwide Urban Runoff Program: Denver, Colorado; Bellevue, Washington; and Knoxville, Tennessee. The MAP that provided the greatest predictive accuracy for the verification data set differed among the three test data bases and among model types (MAP-W for Denver and Knoxville, MAP-lF-P and MAP-R-P for Bellevue load models, and MAP-R-P+nV for Bellevue concentration models) and, in many cases, was not clearly indicated by the values of standard error of estimate for the calibration data set. A scheme to guide MAP selection, based on exploratory data analysis of the calibration data set, is presented and tested. The MAP?s were tested for sensitivity to the size of a calibration data set. As expected, predictive accuracy of all MAP?s for the verification data set decreased as the calibration data-set size decreased, but predictive accuracy was not as sensitive for the MAP?s as it was for the local regression models.

  12. Evidence for validity of five secondary data sources for enumerating retail food outlets in seven American Indian communities in North Carolina.

    PubMed

    Fleischhacker, Sheila E; Rodriguez, Daniel A; Evenson, Kelly R; Henley, Amanda; Gizlice, Ziya; Soto, Dolly; Ramachandran, Gowri

    2012-11-22

    Most studies on the local food environment have used secondary sources to describe the food environment, such as government food registries or commercial listings (e.g., Reference USA). Most of the studies exploring evidence for validity of secondary retail food data have used on-site verification and have not conducted analysis by data source (e.g., sensitivity of Reference USA) or by food outlet type (e.g., sensitivity of Reference USA for convenience stores). Few studies have explored the food environment in American Indian communities. To advance the science on measuring the food environment, we conducted direct, on-site observations of a wide range of food outlets in multiple American Indian communities, without a list guiding the field observations, and then compared our findings to several types of secondary data. Food outlets located within seven State Designated Tribal Statistical Areas in North Carolina (NC) were gathered from online Yellow Pages, Reference USA, Dun & Bradstreet, local health departments, and the NC Department of Agriculture and Consumer Services. All TIGER/Line 2009 roads (>1,500 miles) were driven in six of the more rural tribal areas and, for the largest tribe, all roads in two of its cities were driven. Sensitivity, positive predictive value, concordance, and kappa statistics were calculated to compare secondary data sources to primary data. 699 food outlets were identified during primary data collection. Match rate for primary data and secondary data differed by type of food outlet observed, with the highest match rates found for grocery stores (97%), general merchandise stores (96%), and restaurants (91%). Reference USA exhibited almost perfect sensitivity (0.89). Local health department data had substantial sensitivity (0.66) and was almost perfect when focusing only on restaurants (0.91). Positive predictive value was substantial for Reference USA (0.67) and moderate for local health department data (0.49). Evidence for validity was comparatively lower for Dun & Bradstreet, online Yellow Pages, and the NC Department of Agriculture. Secondary data sources both over- and under-represented the food environment; they were particularly problematic for identifying convenience stores and specialty markets. More attention is needed to improve the validity of existing data sources, especially for rural local food environments.

  13. Evidence for validity of five secondary data sources for enumerating retail food outlets in seven American Indian Communities in North Carolina

    PubMed Central

    2012-01-01

    Background Most studies on the local food environment have used secondary sources to describe the food environment, such as government food registries or commercial listings (e.g., Reference USA). Most of the studies exploring evidence for validity of secondary retail food data have used on-site verification and have not conducted analysis by data source (e.g., sensitivity of Reference USA) or by food outlet type (e.g., sensitivity of Reference USA for convenience stores). Few studies have explored the food environment in American Indian communities. To advance the science on measuring the food environment, we conducted direct, on-site observations of a wide range of food outlets in multiple American Indian communities, without a list guiding the field observations, and then compared our findings to several types of secondary data. Methods Food outlets located within seven State Designated Tribal Statistical Areas in North Carolina (NC) were gathered from online Yellow Pages, Reference USA, Dun & Bradstreet, local health departments, and the NC Department of Agriculture and Consumer Services. All TIGER/Line 2009 roads (>1,500 miles) were driven in six of the more rural tribal areas and, for the largest tribe, all roads in two of its cities were driven. Sensitivity, positive predictive value, concordance, and kappa statistics were calculated to compare secondary data sources to primary data. Results 699 food outlets were identified during primary data collection. Match rate for primary data and secondary data differed by type of food outlet observed, with the highest match rates found for grocery stores (97%), general merchandise stores (96%), and restaurants (91%). Reference USA exhibited almost perfect sensitivity (0.89). Local health department data had substantial sensitivity (0.66) and was almost perfect when focusing only on restaurants (0.91). Positive predictive value was substantial for Reference USA (0.67) and moderate for local health department data (0.49). Evidence for validity was comparatively lower for Dun & Bradstreet, online Yellow Pages, and the NC Department of Agriculture. Conclusions Secondary data sources both over- and under-represented the food environment; they were particularly problematic for identifying convenience stores and specialty markets. More attention is needed to improve the validity of existing data sources, especially for rural local food environments. PMID:23173781

  14. Modeling Nitrogen Dynamics in a Waste Stabilization Pond System Using Flexible Modeling Environment with MCMC

    PubMed Central

    Mukhtar, Hussnain; Lin, Yu-Pin; Shipin, Oleg V.; Petway, Joy R.

    2017-01-01

    This study presents an approach for obtaining realization sets of parameters for nitrogen removal in a pilot-scale waste stabilization pond (WSP) system. The proposed approach was designed for optimal parameterization, local sensitivity analysis, and global uncertainty analysis of a dynamic simulation model for the WSP by using the R software package Flexible Modeling Environment (R-FME) with the Markov chain Monte Carlo (MCMC) method. Additionally, generalized likelihood uncertainty estimation (GLUE) was integrated into the FME to evaluate the major parameters that affect the simulation outputs in the study WSP. Comprehensive modeling analysis was used to simulate and assess nine parameters and concentrations of ON-N, NH3-N and NO3-N. Results indicate that the integrated FME-GLUE-based model, with good Nash–Sutcliffe coefficients (0.53–0.69) and correlation coefficients (0.76–0.83), successfully simulates the concentrations of ON-N, NH3-N and NO3-N. Moreover, the Arrhenius constant was the only parameter sensitive to model performances of ON-N and NH3-N simulations. However, Nitrosomonas growth rate, the denitrification constant, and the maximum growth rate at 20 °C were sensitive to ON-N and NO3-N simulation, which was measured using global sensitivity. PMID:28704958

  15. Communication: Localized molecular orbital analysis of the effect of electron correlation on the anomalous isotope effect in the NMR spin-spin coupling constant in methane

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zarycz, M. Natalia C., E-mail: mnzarycz@gmail.com; Provasi, Patricio F., E-mail: patricio@unne.edu.ar; Sauer, Stephan P. A., E-mail: sauer@kiku.dk

    2014-10-21

    We discuss the effect of electron correlation on the unexpected differential sensitivity (UDS) in the {sup 1}J(C–H) coupling constant of CH{sub 4} using a decomposition into contributions from localized molecular orbitals and compare with the {sup 1}J(N–H) coupling constant in NH{sub 3}. In particular, we discuss the well known fact that uncorrelated coupled Hartree-Fock (CHF) calculations are not able to reproduce the UDS in methane. For this purpose we have implemented for the first time a localized molecular orbital analysis for the second order polarization propagator approximation with coupled cluster singles and doubles amplitudes—SOPPA(CCSD) in the DALTON program. Comparing themore » changes in the localized orbital contributions at the correlated SOPPA and SOPPA(CCSD) levels and at the uncorrelated CHF level, we find that the latter overestimates the effect of stretching the bond between the coupled atoms on the contribution to the coupling from the localized bonding orbital between these atoms. This disturbs the subtle balance between the molecular orbital contributions, which lead to the UDS in methane.« less

  16. Coulomb blockade in a single tunnel junction directly connected to a multiwalled carbon nanotube

    NASA Astrophysics Data System (ADS)

    Haruyama, Junji; Takesue, Izumi; Sato, Yuki

    2000-10-01

    We report on Coulomb blockade in a single tunnel junction directly connected to a multiwalled carbon nanotube (MWNT) by utilizing a nanoporous alumina film. The MWNT exhibits a weak localization effect with strong spin flip scattering. Experimental results and analysis suggest that a high-impedance external environment caused by the weak localization in the MWNT can yield Coulomb blockade, in accordance with phase correlation theory in a single junction system. It is also revealed that the Coulomb blockade is very sensitive to phase modulation in the MWNT, which also acts as a high-impedance transmission line.

  17. Silicon solar cell process development, fabrication and analysis

    NASA Technical Reports Server (NTRS)

    Leung, D. C.; Iles, P. A.

    1983-01-01

    Measurements of minority carrier diffusion lengths were made on the small mesa diodes from HEM Si and SILSO Si. The results were consistent with previous Voc and Isc measurements. Only the medium grain SILSO had a distinct advantage for the non grain boundary diodes. Substantial variations were observed for the HEM ingot 4141C. Also a quantitatively scaled light spot scan was being developed for localized diffusion length measurements in polycrystalline silicon solar cells. A change to a more monochromatic input for the light spot scan results in greater sensitivity and in principle, quantitative measurement of local material qualities is now possible.

  18. MEG source localization of spatially extended generators of epileptic activity: comparing entropic and hierarchical bayesian approaches.

    PubMed

    Chowdhury, Rasheda Arman; Lina, Jean Marc; Kobayashi, Eliane; Grova, Christophe

    2013-01-01

    Localizing the generators of epileptic activity in the brain using Electro-EncephaloGraphy (EEG) or Magneto-EncephaloGraphy (MEG) signals is of particular interest during the pre-surgical investigation of epilepsy. Epileptic discharges can be detectable from background brain activity, provided they are associated with spatially extended generators. Using realistic simulations of epileptic activity, this study evaluates the ability of distributed source localization methods to accurately estimate the location of the generators and their sensitivity to the spatial extent of such generators when using MEG data. Source localization methods based on two types of realistic models have been investigated: (i) brain activity may be modeled using cortical parcels and (ii) brain activity is assumed to be locally smooth within each parcel. A Data Driven Parcellization (DDP) method was used to segment the cortical surface into non-overlapping parcels and diffusion-based spatial priors were used to model local spatial smoothness within parcels. These models were implemented within the Maximum Entropy on the Mean (MEM) and the Hierarchical Bayesian (HB) source localization frameworks. We proposed new methods in this context and compared them with other standard ones using Monte Carlo simulations of realistic MEG data involving sources of several spatial extents and depths. Detection accuracy of each method was quantified using Receiver Operating Characteristic (ROC) analysis and localization error metrics. Our results showed that methods implemented within the MEM framework were sensitive to all spatial extents of the sources ranging from 3 cm(2) to 30 cm(2), whatever were the number and size of the parcels defining the model. To reach a similar level of accuracy within the HB framework, a model using parcels larger than the size of the sources should be considered.

  19. MEG Source Localization of Spatially Extended Generators of Epileptic Activity: Comparing Entropic and Hierarchical Bayesian Approaches

    PubMed Central

    Chowdhury, Rasheda Arman; Lina, Jean Marc; Kobayashi, Eliane; Grova, Christophe

    2013-01-01

    Localizing the generators of epileptic activity in the brain using Electro-EncephaloGraphy (EEG) or Magneto-EncephaloGraphy (MEG) signals is of particular interest during the pre-surgical investigation of epilepsy. Epileptic discharges can be detectable from background brain activity, provided they are associated with spatially extended generators. Using realistic simulations of epileptic activity, this study evaluates the ability of distributed source localization methods to accurately estimate the location of the generators and their sensitivity to the spatial extent of such generators when using MEG data. Source localization methods based on two types of realistic models have been investigated: (i) brain activity may be modeled using cortical parcels and (ii) brain activity is assumed to be locally smooth within each parcel. A Data Driven Parcellization (DDP) method was used to segment the cortical surface into non-overlapping parcels and diffusion-based spatial priors were used to model local spatial smoothness within parcels. These models were implemented within the Maximum Entropy on the Mean (MEM) and the Hierarchical Bayesian (HB) source localization frameworks. We proposed new methods in this context and compared them with other standard ones using Monte Carlo simulations of realistic MEG data involving sources of several spatial extents and depths. Detection accuracy of each method was quantified using Receiver Operating Characteristic (ROC) analysis and localization error metrics. Our results showed that methods implemented within the MEM framework were sensitive to all spatial extents of the sources ranging from 3 cm2 to 30 cm2, whatever were the number and size of the parcels defining the model. To reach a similar level of accuracy within the HB framework, a model using parcels larger than the size of the sources should be considered. PMID:23418485

  20. Fragment-based prediction of skin sensitization using recursive partitioning

    NASA Astrophysics Data System (ADS)

    Lu, Jing; Zheng, Mingyue; Wang, Yong; Shen, Qiancheng; Luo, Xiaomin; Jiang, Hualiang; Chen, Kaixian

    2011-09-01

    Skin sensitization is an important toxic endpoint in the risk assessment of chemicals. In this paper, structure-activity relationships analysis was performed on the skin sensitization potential of 357 compounds with local lymph node assay data. Structural fragments were extracted by GASTON (GrAph/Sequence/Tree extractiON) from the training set. Eight fragments with accuracy significantly higher than 0.73 ( p < 0.1) were retained to make up an indicator descriptor fragment. The fragment descriptor and eight other physicochemical descriptors closely related to the endpoint were calculated to construct the recursive partitioning tree (RP tree) for classification. The balanced accuracy of the training set, test set I, and test set II in the leave-one-out model were 0.846, 0.800, and 0.809, respectively. The results highlight that fragment-based RP tree is a preferable method for identifying skin sensitizers. Moreover, the selected fragments provide useful structural information for exploring sensitization mechanisms, and RP tree creates a graphic tree to identify the most important properties associated with skin sensitization. They can provide some guidance for designing of drugs with lower sensitization level.

  1. Perception of biomechanical motions by infants: implementation of various processing constraints.

    PubMed

    Bertenthal, B I; Proffitt, D R; Kramer, S J

    1987-11-01

    Geometry informs us that there exist a large number of possible connectivity patterns consistent with a point-light display of a person walking. Yet there is only one pattern consistent with a "stick figure" representation of the human form, and that pattern is uniquely specified by those pairwise connections that remain locally rigid. In this study, sensitivity to local rigidity in biomechanical displays was investigated in 3- and 5-month-old infants. The results of Experiment 1 revealed that by 5 months of age, infants discriminate a locally rigid point-light walker display from one in which local rigidity is perturbed. In Experiment 2 we tested infants' sensitivity to the same stimuli when those stimuli were inverted. Contrary to the preceding experiment, the results revealed no evidence of discrimination. Taken together, these findings suggest that infants are sensitive to local rigidity in biomechanical displays but that this sensitivity is orientation specific. Possible mechanisms for this specificity are discussed in the context of additional constraints on the processing of biomechanical displays.

  2. Functional, structural and phylogenetic analysis of domains underlying the Al-sensitivity of the aluminium-activated malate/anion transporter, TaALMT1

    USDA-ARS?s Scientific Manuscript database

    TaALMT1 (Triticum aestivum Aluminum Activated Malate Transporter) is the founding member of a novel gene family of anion transporters (ALMTs) that mediate the efflux of organic acids. A small subgroup of root-localized ALMTs, including TaALMT1, is physiologically associated with in planta aluminum (...

  3. Erbium Laser Technology vs Traditional Drilling for Caries Removal: A Systematic Review with Meta-Analysis.

    PubMed

    Tao, Siying; Li, Lan; Yuan, He; Tao, Sibei; Cheng, Yiming; He, Libang; Li, Jiyao

    2017-12-01

    The study aimed to assess the efficacy of erbium laser technology compared with traditional drilling for caries removal. A systematic search was conducted through Medline via PubMed, Embase, Cochrane databases, CNKI till December 2016. Randomised controlled trials, quasi-randomized controlled trials, or controlled clinical trials with data comparing the efficacy of erbium laser technology versus traditional drilling for caries removal were included. Fourteen studies were selected in our meta-analysis. Erbium laser technology showed an increased time when removing caries compared with drilling (mean difference: 3.48, 95% confidence interval: 1.90-5.06, P < .0001). However, erbium laser technology reduced the requirement for local anesthesia (risk ratio: 0.28, 95% confidence interval: 0.13-0.62, P = .002). Erbium laser technology was also not significantly different to traditional drilling with regard to restoration loss, pulpal vitality, and postoperative sensitivity. Erbium laser technology showed an increased time for cavity preparation compared with traditional drilling. However, erbium laser technology reduced the requirement for local anesthesia. There was no significant difference between erbium laser technology and traditional drilling regarding restoration loss, pulpal vitality, and postoperative sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. X-ray Absorption and Emission Spectroscopy of CrIII (Hydr)Oxides: Analysis of the K-Pre-Edge Region

    NASA Astrophysics Data System (ADS)

    Frommer, Jakob; Nachtegaal, Maarten; Czekaj, Izabela; Weng, Tsu-Chien; Kretzschmar, Ruben

    2009-10-01

    Pre-edge spectral features below the main X-ray absorption K-edge of transition metals show a pronounced chemical sensitivity and are promising sources of structural information. Nevertheless, the use of pre-edge analysis in applied research is limited because of the lack of definite theoretical peak-assignments. The aim of this study was to determine the factors affecting the chromium K-pre-edge features in trivalent chromium-bearing oxides and oxyhydroxides. The selected phases varied in the degree of octahedral polymerization and the degree of iron-for-chromium substitution in the crystal structure. We investigated the pre-edge fine structure by means of high-energy-resolution fluorescence detected X-ray absorption spectroscopy and by 1s2p resonant X-ray emission spectroscopy. Multiplet theory and full multiple-scattering calculations were used to analyze the experimental data. We show that the chromium K-pre-edge contains localized and nonlocalized transitions. Contributions arising from nonlocalized metal-metal transitions are sensitive to the nearest metal type and to the linkage mode between neighboring metal octahedra. Analyzing these transitions opens up new opportunities for investigating the local coordination environment of chromium in poorly ordered solids of environmental relevance.

  5. Capturing strain localization behind a geosynthetic-reinforced soil wall

    NASA Astrophysics Data System (ADS)

    Lai, Timothy Y.; Borja, Ronaldo I.; Duvernay, Blaise G.; Meehan, Richard L.

    2003-04-01

    This paper presents the results of finite element (FE) analyses of shear strain localization that occurred in cohesionless soils supported by a geosynthetic-reinforced retaining wall. The innovative aspects of the analyses include capturing of the localized deformation and the accompanying collapse mechanism using a recently developed embedded strong discontinuity model. The case study analysed, reported in previous publications, consists of a 3.5-m tall, full-scale reinforced wall model deforming in plane strain and loaded by surcharge at the surface to failure. Results of the analysis suggest strain localization developing from the toe of the wall and propagating upward to the ground surface, forming a curved failure surface. This is in agreement with a well-documented failure mechanism experienced by the physical wall model showing internal failure surfaces developing behind the wall as a result of the surface loading. Important features of the analyses include mesh sensitivity studies and a comparison of the localization properties predicted by different pre-localization constitutive models, including a family of three-invariant elastoplastic constitutive models appropriate for frictional/dilatant materials. Results of the analysis demonstrate the potential of the enhanced FE method for capturing a collapse mechanism characterized by the presence of a failure, or slip, surface through earthen materials.

  6. Bayley-III Cognitive and Language Scales in Preterm Children.

    PubMed

    Spencer-Smith, Megan M; Spittle, Alicia J; Lee, Katherine J; Doyle, Lex W; Anderson, Peter J

    2015-05-01

    This study aimed to assess the sensitivity and specificity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), Cognitive and Language scales at 24 months for predicting cognitive impairments in preterm children at 4 years. Children born <30 weeks' gestation completed the Bayley-III at 24 months and the Differential Ability Scale, Second Edition (DAS-II), at 4 years to assess cognitive functioning. Test norms and local term-born reference data were used to classify delay on the Bayley-III Cognitive and Language scales. Impairment on the DAS-II Global Conceptual Ability, Verbal, and Nonverbal Reasoning indices was classified relative to test norms. Scores < -1 SD relative to the mean were classified as mild/moderate delay or impairment, and scores < -2 SDs were classified as moderate delay or impairment. A total of 105 children completed the Bayley-III and DAS-II. The sensitivity of mild/moderate cognitive delay on the Bayley-III for predicting impairment on DAS-II indices ranged from 29.4% to 38.5% and specificity ranged from 92.3% to 95.5%. The sensitivity of mild/moderate language delay on the Bayley-III for predicting impairment on DAS-II indices ranged from 40% to 46.7% and specificity ranged from 81.1% to 85.7%. The use of local reference data at 24 months to classify delay increased sensitivity but reduced specificity. Receiver operating curve analysis identified optimum cut-point scores for the Bayley-III that were more consistent with using local reference data than Bayley-III normative data. In our cohort of very preterm children, delay on the Bayley-III Cognitive and Language scales was not strongly predictive of future impairments. More children destined for later cognitive impairment were identified by using cut-points based on local reference data than Bayley-III norms. Copyright © 2015 by the American Academy of Pediatrics.

  7. Power Doppler Ultrasonography and Shear Wave Elastography as Complementary Imaging Methods for Suspected Local Breast Cancer Recurrence.

    PubMed

    Jales, Rodrigo Menezes; Dória, Maira Teixeira; Serra, Kátia Piton; Miranda, Mila Meneguelli; Menossi, Carlos Alberto; Schumacher, Klaus; Sarian, Luis Otávio

    2018-06-01

    To prospectively investigate the diagnostic accuracy and clinical consequences of power Doppler morphologic criteria and shear wave elastography (SWE) as complementary imaging methods for evaluation of suspected local breast cancer recurrence in the ipsilateral breast or chest wall. Thirty-two breast masses with a suspicion of local breast cancer recurrence on B-mode ultrasonography underwent complementary power Doppler and SWE evaluations. Power Doppler morphologic criteria were classified as avascular, hypovascular, or hypervascular. Shear wave elastography was classified according to a 5-point scale (SWE score) and SWE maximum elasticity. Diagnostic accuracy was assessed by the sensitivity, specificity, and area under the curve. A decision curve analysis assessed clinical consequences of each method. The reference standard for diagnosis was defined as core needle or excisional biopsy. Histopathologic examinations revealed 9 (28.2%) benign and 23 (71.8%) malignant cases. Power Doppler ultrasonography (US) had sensitivity of 34.8% (95% confidence interval [CI], 6.6%-62.9%) and specificity of 45.4% (95% CI, 19.3%-71.5%). The SWE score (≥3) had sensitivity of 87.0% (95% CI, 66.4%-97.2%) and specificity of 44.4% (95% CI, 13.7%-78.8%). The SWE maximum elasticity (velocity > 6.5cm/s) had sensitivity of 87% (95% CI, 66.4%-97.2%) and specificity of 77.8% (95% CI, 40.0% to 97.2%). The areas under the curves for the SWE score and SWE maximum elasticity were 0.71 (95% CI, 0.53-0.87) and 0.82 (95% CI, 0.64-0.93), respectively (P = .32). Power Doppler US is unsuitable for discrimination between local breast cancer recurrence and fibrosis. Although the SWE score and SWE maximum elasticity can make this discrimination, the use of these methods to determine biopsy may lead to poorer clinical outcomes than the current practice of performing biopsies of all suspicious masses. © 2017 by the American Institute of Ultrasound in Medicine.

  8. Laser Doppler assessment of dermal circulatory changes in people with coronary artery disease.

    PubMed

    Agarwal, Sharad C; Allen, John; Murray, Alan; Purcell, Ian F

    2012-07-01

    Dermal microcirculation provides an easily accessible vasculature bed which can be used to assess endothelial mediated vasodilatation. We studied and compared microcirculatory changes in response to acetylcholine iontophoresis (ACh), local heating of the skin and reactive hyperaemia in patients with coronary artery disease (CAD). Forty eight patients with CAD were studied and compared with 25 age and sex matched control subjects. Vasodilatory changes in the dermal microcirculation were assessed in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia using a laser Doppler flowmeter (LDF). Body mass index (BMI) and systolic BP were higher in people with CAD, (p=0.001, 0.043). The perfusion change (measured as absolute in agreement with our previous publish results) in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia, in healthy controls was 234 (190-286), 90 (69-118), 139(106-172) arbitrary perfusion units (APU) compared to 161 (121-214), 50 (39-63), 116(77-143) APU in patients with CAD; p<0.03. The time to peak perfusion in response to reactive hyperaemia was significantly higher in patients with CAD, 14.1±4.0 vs 10.9±1.7s; p=0.001. There was a small but significant positive correlation between the perfusion change in response to ACh iontophoresis and local heating (r=0.31, p=0.035). On ROC curve analysis, perfusion changes with heating had higher sensitivity and specificity in discriminating patients with CAD from the healthy controls with an area under the curve (AUC) of 0.86, with a specificity of 92% and sensitivity of 77% compared to a perfusion changes by reactive hyperaemia, AUC of 0.68 (41% sensitivity and 91% specificity) and ACh iontophoresis, AUC of 0.76 (88% sensitivity and 60% specificity). Vasodilatation in the dermal microcirculation measured by the three techniques is attenuated in patients with coronary artery disease. Local heating of the skin is a better discriminator of patients with CAD than ACh iontophoresis and reactive hyperaemia. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Locally refined block-centred finite-difference groundwater models: Evaluation of parameter sensitivity and the consequences for inverse modelling

    USGS Publications Warehouse

    Mehl, S.; Hill, M.C.

    2002-01-01

    Models with local grid refinement, as often required in groundwater models, pose special problems for model calibration. This work investigates the calculation of sensitivities and the performance of regression methods using two existing and one new method of grid refinement. The existing local grid refinement methods considered are: (a) a variably spaced grid in which the grid spacing becomes smaller near the area of interest and larger where such detail is not needed, and (b) telescopic mesh refinement (TMR), which uses the hydraulic heads or fluxes of a regional model to provide the boundary conditions for a locally refined model. The new method has a feedback between the regional and local grids using shared nodes, and thereby, unlike the TMR methods, balances heads and fluxes at the interfacing boundary. Results for sensitivities are compared for the three methods and the effect of the accuracy of sensitivity calculations are evaluated by comparing inverse modelling results. For the cases tested, results indicate that the inaccuracies of the sensitivities calculated using the TMR approach can cause the inverse model to converge to an incorrect solution.

  10. Locally refined block-centered finite-difference groundwater models: Evaluation of parameter sensitivity and the consequences for inverse modelling and predictions

    USGS Publications Warehouse

    Mehl, S.; Hill, M.C.

    2002-01-01

    Models with local grid refinement, as often required in groundwater models, pose special problems for model calibration. This work investigates the calculation of sensitivities and performance of regression methods using two existing and one new method of grid refinement. The existing local grid refinement methods considered are (1) a variably spaced grid in which the grid spacing becomes smaller near the area of interest and larger where such detail is not needed and (2) telescopic mesh refinement (TMR), which uses the hydraulic heads or fluxes of a regional model to provide the boundary conditions for a locally refined model. The new method has a feedback between the regional and local grids using shared nodes, and thereby, unlike the TMR methods, balances heads and fluxes at the interfacing boundary. Results for sensitivities are compared for the three methods and the effect of the accuracy of sensitivity calculations are evaluated by comparing inverse modelling results. For the cases tested, results indicate that the inaccuracies of the sensitivities calculated using the TMR approach can cause the inverse model to converge to an incorrect solution.

  11. DHA-fluorescent probe is sensitive to membrane order and reveals molecular adaptation of DHA in ordered lipid microdomains☆

    PubMed Central

    Teague, Heather; Ross, Ron; Harris, Mitchel; Mitchell, Drake C.; Shaikh, Saame Raza

    2012-01-01

    Docosahexaenoic acid (DHA) disrupts the size and order of plasma membrane lipid microdomains in vitro and in vivo. However, it is unknown how the highly disordered structure of DHA mechanistically adapts to increase the order of tightly packed lipid microdomains. Therefore, we studied a novel DHA-Bodipy fluorescent probe to address this issue. We first determined if the DHA-Bodipy probe localized to the plasma membrane of primary B and immortal EL4 cells. Image analysis revealed that DHA-Bodipy localized into the plasma membrane of primary B cells more efficiently than EL4 cells. We then determined if the probe detected changes in plasma membrane order. Quantitative analysis of time-lapse movies established that DHA-Bodipy was sensitive to membrane molecular order. This allowed us to investigate how DHA-Bodipy physically adapted to ordered lipid microdomains. To accomplish this, we employed steady-state and time-resolved fluorescence anisotropy measurements in lipid vesicles of varying composition. Similar to cell culture studies, the probe was highly sensitive to membrane order in lipid vesicles. Moreover, these experiments revealed, relative to controls, that upon incorporation into highly ordered microdomains, DHA-Bodipy underwent an increase in its fluorescence lifetime and molecular order. In addition, the probe displayed a significant reduction in its rotational diffusion compared to controls. Altogether, DHA-Bodipy was highly sensitive to membrane order and revealed for the first time that DHA, despite its flexibility, could become ordered with less rotational motion inside ordered lipid microdomains. Mechanistically, this explains how DHA acyl chains can increase order upon formation of lipid microdomains in vivo. PMID:22841541

  12. [Insulinoma of the pancreas: analysis of a clinical series of 30 cases].

    PubMed

    Andronesi, D; Andronesi, A; Tonea, A; Andrei, S; Herlea, V; Lupescu, I; Ionescu-Târgovişte, C; Coculescu, M; Fica, S; Ionescu, M; Gheorghe, C; Popescu, I

    2009-01-01

    Insulinoma is the most frequent neuroendocrine pancreatic tumor and is the main cause for hypoglicemia due to endogenous hyperinsulinism. We performed an analysis of a clinical series in order to study the clinical and biological spectrum of presentation, the preoperatory imagistic diagnosis and results of the surgical approach. Between 1986-2009, 30 patients with symptoms suggesting an insulinoma were hospitalized in our department. Preoperatory localization of insulinomas was possible in 16 patients. The most sensitive imagistic methods were ecoendoscopy and magnetic resonance. Intraoperatory ultrasound was performed in 16 patients and its sensitivity in detection of insulinomas was 93%; the combination between intraoperative ultrasound and manual exploration of pancreas by the surgeon reached a 100% sensitivity. Before the intraoperatory ultrasound was used the tumor excision was predominantly done by extensive pancreatic resection, while after this was available in our centre more conservative (enucleo-resection) procedures were chosen. In 1 patient the resection was done by laparoscopy, and in 1 patient by robotic surgery. The dimensions of the tumor were less than 2 cm in most of the patients; 2 had nesidioblastosis and 2 had multiple insulinomas; all 28 patients proved to have benign insulinomas at histological specimens. Following surgery, the symptoms disappear in all patients. The most common complication following extensive pancreatic resections was acute pancreatitis, while after enucleation pancreatic fistula occurred more frequently. Due to small dimensions, the preoperative diagnosis of insulinomas is usually difficult, ecoendoscopy being the most sensitive method. Intraoperative ultrasound is essential for insulinoma localization and for chosing the optimal type of excision. Enucleation is the resection method to be chosen whenever this it is technical possible. In benign insulinomas the prognosis is excellent, surgical resection being curative in all cases.

  13. Sensitivity enhancement of traveling wave MRI using free local resonators: an experimental demonstration.

    PubMed

    Zhang, Xiaoliang

    2017-04-01

    Traveling wave MR uses the far fields in signal excitation and reception, therefore its acquisition efficiency is low in contrast to the conventional near field magnetic resonance (MR). Here we show a simple and efficient method based on the local resonator to improving sensitivity of traveling wave MR technique. The proposed method utilizes a standalone or free local resonator to amplify the radio frequency magnetic fields in the interested target. The resonators have no wire connections to the MR system and thus can be conveniently placed to any place around imaging simples. A rectangular loop L/C resonator to be used as the free local resonator was tuned to the proton Larmor frequency at 7T. Traveling wave MR experiments with and without the wireless free local resonator were performed on a living rat using a 7T whole body MR scanner. The signal-to-noise ratio (SNR) or sensitivity of the images acquired was compared and evaluated. In vivo 7T imaging results show that traveling wave MR with a wireless free local resonator placed near the head of a living rat achieves at least 10-fold SNR gain over the images acquired on the same rat using conventional traveling wave MR method, i.e. imaging with no free local resonators. The proposed free local resonator technique is able to enhance the MR sensitivity and acquisition efficiency of traveling wave MR at ultrahigh fields in vivo . This method can be a simple solution to alleviating low sensitivity problem of traveling wave MRI.

  14. Development and Utilization of an Ex Vivo Bromodeoxyuridine Local Lymph Node Assay (LLNA) Protocol for Assessing Potential Chemical Sensitizers

    EPA Science Inventory

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

  15. Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

    PubMed

    Park, H S; Nahm, D

    1996-08-01

    Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms.

  16. Simulation of localized heavy precipitation in South Korea on 20 June 2014: sensitivity test of integration time-step size and an effect of topographic resolution using WRF model

    NASA Astrophysics Data System (ADS)

    Roh, Joon-Woo; Jee, Joon-Bum; Lim, A.-Young; Choi, Young-Jean

    2015-04-01

    Korean warm-season rainfall, accounting for about three-fourths of the annual precipitation, is primarily caused by Changma front, which is a kind of the East Asian summer monsoon, and localized heavy rainfall with convective instability. Various physical mechanisms potentially exert influences on heavy precipitation over South Korea. Representatively, the middle latitude and subtropical weather fronts, associated with a quasi-stationary moisture convergence zone among varying air masses, make up one of the main rain-bearing synoptic scale systems. Localized heavy rainfall events in South Korea generally arise from mesoscale convective systems embedded in these synoptic scale disturbances along the Changma front or convective instabilities resulted from unstable air mass including the direct or indirect effect of typhoons. In recent years, torrential rainfalls, which are more than 30mm/hour of precipitation amount, in warm-season has increased threefold in Seoul, which is a metropolitan city in South Korea. In order to investigate multiple potential causes of warm-season localized heavy precipitation in South Korea, a localized heavy precipitation case took place on 20 June 2014 at Seoul. This case was mainly seen to be caused by short-wave trough, which is associated with baroclinic instability in the northwest of Korea, and a thermal low, which has high moist and warm air through analysis. This structure showed convective scale torrential rain was embedded in the dynamic and in the thermodynamic structures. In addition to, a sensitivity of rainfall amount and maximum rainfall location to the integration time-step sizes was investigated in the simulations of a localized heavy precipitation case using Weather Research and Forecasting model. The simulation of time-step sizes of 9-27s corresponding to a horizontal resolution of 4.5km and 1.5km varied slightly difference of the maximum rainfall amount. However, the sensitivity of spatial patterns and temporal variations in rainfall were relatively small for the time-step sizes. The effect of topography was also important in the localized heavy precipitation simulation.

  17. SIG-VISA: Signal-based Vertically Integrated Seismic Monitoring

    NASA Astrophysics Data System (ADS)

    Moore, D.; Mayeda, K. M.; Myers, S. C.; Russell, S.

    2013-12-01

    Traditional seismic monitoring systems rely on discrete detections produced by station processing software; however, while such detections may constitute a useful summary of station activity, they discard large amounts of information present in the original recorded signal. We present SIG-VISA (Signal-based Vertically Integrated Seismic Analysis), a system for seismic monitoring through Bayesian inference on seismic signals. By directly modeling the recorded signal, our approach incorporates additional information unavailable to detection-based methods, enabling higher sensitivity and more accurate localization using techniques such as waveform matching. SIG-VISA's Bayesian forward model of seismic signal envelopes includes physically-derived models of travel times and source characteristics as well as Gaussian process (kriging) statistical models of signal properties that combine interpolation of historical data with extrapolation of learned physical trends. Applying Bayesian inference, we evaluate the model on earthquakes as well as the 2009 DPRK test event, demonstrating a waveform matching effect as part of the probabilistic inference, along with results on event localization and sensitivity. In particular, we demonstrate increased sensitivity from signal-based modeling, in which the SIGVISA signal model finds statistical evidence for arrivals even at stations for which the IMS station processing failed to register any detection.

  18. Assessment of local variability by high-throughput e-beam metrology for prediction of patterning defect probabilities

    NASA Astrophysics Data System (ADS)

    Wang, Fuming; Hunsche, Stefan; Anunciado, Roy; Corradi, Antonio; Tien, Hung Yu; Tang, Peng; Wei, Junwei; Wang, Yongjun; Fang, Wei; Wong, Patrick; van Oosten, Anton; van Ingen Schenau, Koen; Slachter, Bram

    2018-03-01

    We present an experimental study of pattern variability and defectivity, based on a large data set with more than 112 million SEM measurements from an HMI high-throughput e-beam tool. The test case is a 10nm node SRAM via array patterned with a DUV immersion LELE process, where we see a variation in mean size and litho sensitivities between different unique via patterns that leads to a seemingly qualitative differences in defectivity. The large available data volume enables further analysis to reliably distinguish global and local CDU variations, including a breakdown into local systematics and stochastics. A closer inspection of the tail end of the distributions and estimation of defect probabilities concludes that there is a common defect mechanism and defect threshold despite the observed differences of specific pattern characteristics. We expect that the analysis methodology can be applied for defect probability modeling as well as general process qualification in the future.

  19. Impacts of tropical deforestation. Part I: Process analysis of local climatic change

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, H.; Henderson-Sellers, A.; McGuffie, K.

    1996-07-01

    The potential impacts of deforestation in the humid Tropics are examined using a version of the National Center for Atmospheric Research`s CCM1 coupled with the Biosphere-Atmosphere Transfer Scheme package. Tropical deforestation in South America, Africa, and Southeast Asia is studied using the results from an 11-yr deforestation experiment and a 25-yr control integration. It is found that the local-scale impact (here defined as within the area deforested) varies greatly between the three deforested regions due to the differing controls on the local atmospheric circulation: the Southeast Asian monsoon is much less sensitive to deforestation than the low-level flow over Southmore » America. The analysis of the changes in cloud radiative forcing suggests that reduction in cloud amount can significantly mitigate the imposed increases in surface albedo. The importance of water recycling by the forest canopy is stressed in the simulation of local precipitation changes. Correlation analysis of the changes resulting from the deforestation has been used to determine the nature of the processes that follow from the removal of the forest canopy and to suggest the important processes. The role of large-scale dynamics is explored in a companion paper. 44 refs., 9 figs., 5 tabs.« less

  20. On understanding the relationship between structure in the potential surface and observables in classical dynamics: A functional sensitivity analysis approach

    NASA Astrophysics Data System (ADS)

    Judson, Richard S.; Rabitz, Herschel

    1987-04-01

    The relationship between structure in the potential surface and classical mechanical observables is examined by means of functional sensitivity analysis. Functional sensitivities provide maps of the potential surface, highlighting those regions that play the greatest role in determining the behavior of observables. A set of differential equations for the sensitivities of the trajectory components are derived. These are then solved using a Green's function method. It is found that the sensitivities become singular at the trajectory turning points with the singularities going as η-3/2, with η being the distance from the nearest turning point. The sensitivities are zero outside of the energetically and dynamically allowed region of phase space. A second set of equations is derived from which the sensitivities of observables can be directly calculated. An adjoint Green's function technique is employed, providing an efficient method for numerically calculating these quantities. Sensitivity maps are presented for a simple collinear atom-diatom inelastic scattering problem and for two Henon-Heiles type Hamiltonians modeling intramolecular processes. It is found that the positions of the trajectory caustics in the bound state problem determine regions of the highest potential surface sensitivities. In the scattering problem (which is impulsive, so that ``sticky'' collisions did not occur), the positions of the turning points of the individual trajectory components determine the regions of high sensitivity. In both cases, these lines of singularities are superimposed on a rich background structure. Most interesting is the appearance of classical interference effects. The interference features in the sensitivity maps occur most noticeably where two or more lines of turning points cross. The important practical motivation for calculating the sensitivities derives from the fact that the potential is a function, implying that any direct attempt to understand how local potential regions affect the behavior of the observables by repeatedly and systematically altering the potential will be prohibitively expensive. The functional sensitivity method enables one to perform this analysis at a fraction of the computational labor required for the direct method.

  1. Nondestructive Analysis of Tumor-Associated Membrane Protein Integrating Imaging and Amplified Detection in situ Based on Dual-Labeled DNAzyme.

    PubMed

    Chen, Xiaoxia; Zhao, Jing; Chen, Tianshu; Gao, Tao; Zhu, Xiaoli; Li, Genxi

    2018-01-01

    Comprehensive analysis of the expression level and location of tumor-associated membrane proteins (TMPs) is of vital importance for the profiling of tumor cells. Currently, two kinds of independent techniques, i.e. ex situ detection and in situ imaging, are usually required for the quantification and localization of TMPs respectively, resulting in some inevitable problems. Methods: Herein, based on a well-designed and fluorophore-labeled DNAzyme, we develop an integrated and facile method, in which imaging and quantification of TMPs in situ are achieved simultaneously in a single system. The labeled DNAzyme not only produces localized fluorescence for the visualization of TMPs but also catalyzes the cleavage of a substrate to produce quantitative fluorescent signals that can be collected from solution for the sensitive detection of TMPs. Results: Results from the DNAzyme-based in situ imaging and quantification of TMPs match well with traditional immunofluorescence and western blotting. In addition to the advantage of two-in-one, the DNAzyme-based method is highly sensitivity, allowing the detection of TMPs in only 100 cells. Moreover, the method is nondestructive. Cells after analysis could retain their physiological activity and could be cultured for other applications. Conclusion: The integrated system provides solid results for both imaging and quantification of TMPs, making it a competitive method over some traditional techniques for the analysis of TMPs, which offers potential application as a toolbox in the future.

  2. Poly(dimethylsiloxane) photonic microbioreactors based on segmented waveguides for local absorbance measurement.

    PubMed

    Demming, Stefanie; Vila-Planas, Jordi; Aliasghar Zadeh, Sobehir; Edlich, Astrid; Franco-Lara, Ezequiel; Radespiel, Rolf; Büttgenbach, Stephanus; Llobera, Andreu

    2011-02-01

    We present the development of microbioreactors (MBRs) based on poly(dimethylsiloxane) (PDMS) segmented waveguides (SWG) for local absorbance measurements. Two different MBRs were studied, either using symmetric or asymmetric SWG (being defined as MBR-S and MBR-A, respectively). Their optical and fluidic performances were numerically analyzed, showing robustness from an optical point of view and distinct fluid flow profile. The optical characterization was done in two steps. Initially, the experimental limit of detection (LOD) and the sensitivity were determined for two different analytes (fluorescein and methylorange). With both systems, a similar limit of detection for both analytes was obtained, being in the micromolar level. Their sensitivities were 20.2±0.3 (×10⁻³) A.U./μM and 5.5±0.2 (×10⁻³) A.U./μM for fluorescein and methylorange, respectively. Once validated its applicability for local absorbance measurements, a continuous cultivation of Saccharomyces cerevisiae was done to test the viability of the proposed systems for photonic MBRs. Concretely, the cell growth was locally monitored inside the MBR during 33 h. Spectral analysis showed that the determination of the culture parameters were wavelength dependant, with a growth rate of 0.39±0.02 h⁻¹ and a doubling time of 1.65±0.09 h at an optimal wavelength of 469.9±0.3 nm. Besides the easy and monolithic integration of the SWG into poly(dimethylsiloxane) microfluidic systems, the results presented here are very promising for the application in any disposable photonic lab-on-a-chip systems used for online analysis or photonic MBRs. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Detection and Site Localization of Phosphorylcholine-Modified Peptides by NanoLC-ESI-MS/MS Using Precursor Ion Scanning and Multiple Reaction Monitoring Experiments

    NASA Astrophysics Data System (ADS)

    Timm, Thomas; Lenz, Christof; Merkel, Dietrich; Sadiffo, Christian; Grabitzki, Julia; Klein, Jochen; Lochnit, Guenter

    2015-03-01

    Phosphorylcholine (PC)-modified biomolecules like lipopolysaccharides, glycosphingolipids, and (glyco)proteins are widespread, highly relevant antigens of parasites, since this small hapten shows potent immunomodulatory capacity, which allows the establishment of long-lasting infections of the host. Especially for PC-modified proteins, structural data is rare because of the zwitterionic nature of the PC substituent, resulting in low sensitivities and unusual but characteristic fragmentation patterns. We have developed a targeted mass spectrometric approach using hybrid triple quadrupole/linear ion trap (QTRAP) mass spectrometry coupled to nanoflow chromatography for the sensitive detection of PC-modified peptides from complex proteolytic digests, and the localization of the PC-modification within the peptide backbone. In a first step, proteolytic digests are screened using precursor ion scanning for the marker ions of choline ( m/z 104.1) and phosphorylcholine ( m/z 184.1) to establish the presence of PC-modified peptides. Potential PC-modified precursors are then subjected to a second analysis using multiple reaction monitoring (MRM)-triggered product ion spectra for the identification and site localization of the modified peptides. The approach was first established using synthetic PC-modified synthetic peptides and PC-modified model digests. Following the optimization of key parameters, we then successfully applied the method to the detection of PC-peptides in the background of a proteolytic digest of a whole proteome. This methodological invention will greatly facilitate the detection of PC-substituted biomolecules and their structural analysis.

  4. Global sensitivity analysis of a local water balance model predicting evaporation, water yield and drought

    NASA Astrophysics Data System (ADS)

    Speich, Matthias; Zappa, Massimiliano; Lischke, Heike

    2017-04-01

    Evaporation and transpiration affect both catchment water yield and the growing conditions for vegetation. They are driven by climate, but also depend on vegetation, soil and land surface properties. In hydrological and land surface models, these properties may be included as constant parameters, or as state variables. Often, little is known about the effect of these variables on model outputs. In the present study, the effect of surface properties on evaporation was assessed in a global sensitivity analysis. To this effect, we developed a simple local water balance model combining state-of-the-art process formulations for evaporation, transpiration and soil water balance. The model is vertically one-dimensional, and the relative simplicity of its process formulations makes it suitable for integration in a spatially distributed model at regional scale. The main model outputs are annual total evaporation (TE, i.e. the sum of transpiration, soil evaporation and interception), and a drought index (DI), which is based on the ratio of actual and potential transpiration. This index represents the growing conditions for forest trees. The sensitivity analysis was conducted in two steps. First, a screening analysis was applied to identify unimportant parameters out of an initial set of 19 parameters. In a second step, a statistical meta-model was applied to a sample of 800 model runs, in which the values of the important parameters were varied. Parameter effect and interactions were analyzed with effects plots. The model was driven with forcing data from ten meteorological stations in Switzerland, representing a wide range of precipitation regimes across a strong temperature gradient. Of the 19 original parameters, eight were identified as important in the screening analysis. Both steps highlighted the importance of Plant Available Water Capacity (AWC) and Leaf Area Index (LAI). However, their effect varies greatly across stations. For example, while a transition from a sparse to a closed forest canopy has almost no effect on annual TE at warm and dry sites, it increases TE by up to 100 mm/year at cold-humid and warm-humid sites. Further parameters of importance describe infiltration, as well as canopy resistance and its response to environmental variables. This study offers insights for future development of hydrological and ecohydrological models. First, it shows that although local water balance is primarily controlled by climate, the vegetation and soil parameters may have a large impact on the outputs. Second, it indicates that modeling studies should prioritize a realistic parameterization of LAI and AWC, while other parameters may be set to fixed values. Third, it illustrates to which extent parameter effect and interactions depend on local climate.

  5. Development of Sound Localization Strategies in Children with Bilateral Cochlear Implants

    PubMed Central

    Zheng, Yi; Godar, Shelly P.; Litovsky, Ruth Y.

    2015-01-01

    Localizing sounds in our environment is one of the fundamental perceptual abilities that enable humans to communicate, and to remain safe. Because the acoustic cues necessary for computing source locations consist of differences between the two ears in signal intensity and arrival time, sound localization is fairly poor when a single ear is available. In adults who become deaf and are fitted with cochlear implants (CIs) sound localization is known to improve when bilateral CIs (BiCIs) are used compared to when a single CI is used. The aim of the present study was to investigate the emergence of spatial hearing sensitivity in children who use BiCIs, with a particular focus on the development of behavioral localization patterns when stimuli are presented in free-field horizontal acoustic space. A new analysis was implemented to quantify patterns observed in children for mapping acoustic space to a spatially relevant perceptual representation. Children with normal hearing were found to distribute their responses in a manner that demonstrated high spatial sensitivity. In contrast, children with BiCIs tended to classify sound source locations to the left and right; with increased bilateral hearing experience, they developed a perceptual map of space that was better aligned with the acoustic space. The results indicate experience-dependent refinement of spatial hearing skills in children with CIs. Localization strategies appear to undergo transitions from sound source categorization strategies to more fine-grained location identification strategies. This may provide evidence for neural plasticity, with implications for training of spatial hearing ability in CI users. PMID:26288142

  6. Development of Sound Localization Strategies in Children with Bilateral Cochlear Implants.

    PubMed

    Zheng, Yi; Godar, Shelly P; Litovsky, Ruth Y

    2015-01-01

    Localizing sounds in our environment is one of the fundamental perceptual abilities that enable humans to communicate, and to remain safe. Because the acoustic cues necessary for computing source locations consist of differences between the two ears in signal intensity and arrival time, sound localization is fairly poor when a single ear is available. In adults who become deaf and are fitted with cochlear implants (CIs) sound localization is known to improve when bilateral CIs (BiCIs) are used compared to when a single CI is used. The aim of the present study was to investigate the emergence of spatial hearing sensitivity in children who use BiCIs, with a particular focus on the development of behavioral localization patterns when stimuli are presented in free-field horizontal acoustic space. A new analysis was implemented to quantify patterns observed in children for mapping acoustic space to a spatially relevant perceptual representation. Children with normal hearing were found to distribute their responses in a manner that demonstrated high spatial sensitivity. In contrast, children with BiCIs tended to classify sound source locations to the left and right; with increased bilateral hearing experience, they developed a perceptual map of space that was better aligned with the acoustic space. The results indicate experience-dependent refinement of spatial hearing skills in children with CIs. Localization strategies appear to undergo transitions from sound source categorization strategies to more fine-grained location identification strategies. This may provide evidence for neural plasticity, with implications for training of spatial hearing ability in CI users.

  7. Reliability Sensitivity Analysis and Design Optimization of Composite Structures Based on Response Surface Methodology

    NASA Technical Reports Server (NTRS)

    Rais-Rohani, Masoud

    2003-01-01

    This report discusses the development and application of two alternative strategies in the form of global and sequential local response surface (RS) techniques for the solution of reliability-based optimization (RBO) problems. The problem of a thin-walled composite circular cylinder under axial buckling instability is used as a demonstrative example. In this case, the global technique uses a single second-order RS model to estimate the axial buckling load over the entire feasible design space (FDS) whereas the local technique uses multiple first-order RS models with each applied to a small subregion of FDS. Alternative methods for the calculation of unknown coefficients in each RS model are explored prior to the solution of the optimization problem. The example RBO problem is formulated as a function of 23 uncorrelated random variables that include material properties, thickness and orientation angle of each ply, cylinder diameter and length, as well as the applied load. The mean values of the 8 ply thicknesses are treated as independent design variables. While the coefficients of variation of all random variables are held fixed, the standard deviations of ply thicknesses can vary during the optimization process as a result of changes in the design variables. The structural reliability analysis is based on the first-order reliability method with reliability index treated as the design constraint. In addition to the probabilistic sensitivity analysis of reliability index, the results of the RBO problem are presented for different combinations of cylinder length and diameter and laminate ply patterns. The two strategies are found to produce similar results in terms of accuracy with the sequential local RS technique having a considerably better computational efficiency.

  8. 3D MR flow analysis in realistic rapid-prototyping model systems of the thoracic aorta: comparison with in vivo data and computational fluid dynamics in identical vessel geometries.

    PubMed

    Canstein, C; Cachot, P; Faust, A; Stalder, A F; Bock, J; Frydrychowicz, A; Küffer, J; Hennig, J; Markl, M

    2008-03-01

    The knowledge of local vascular anatomy and function in the human body is of high interest for the diagnosis and treatment of cardiovascular disease. A comprehensive analysis of the hemodynamics in the thoracic aorta is presented based on the integration of flow-sensitive 4D MRI with state-of-the-art rapid prototyping technology and computational fluid dynamics (CFD). Rapid prototyping was used to transform aortic geometries as measured by contrast-enhanced MR angiography into realistic vascular models with large anatomical coverage. Integration into a flow circuit with patient-specific pulsatile in-flow conditions and application of flow-sensitive 4D MRI permitted detailed analysis of local and global 3D flow dynamics in a realistic vascular geometry. Visualization of characteristic 3D flow patterns and quantitative comparisons of the in vitro experiments with in vivo data and CFD simulations in identical vascular geometries were performed to evaluate the accuracy of vascular model systems. The results indicate the potential of such patient-specific model systems for detailed experimental simulation of realistic vascular hemodynamics. Further studies are warranted to examine the influence of refined boundary conditions of the human circulatory system such as fluid-wall interaction and their effect on normal and pathological blood flow characteristics associated with vascular geometry. (c) 2008 Wiley-Liss, Inc.

  9. Innovative Ge Quantum Dot Functional Sensing/Metrology Devices

    DTIC Science & Technology

    2015-05-20

    sensitive to charge number and local temperature with unprecedented precision. Accordingly we have made progresses in the innovative functionalities...sensors feature excellent sensitivity on charge number, local temperature, and photoresponsivity in the visible to near IR wavelength.  “Designer” Ge...Detailed knowledge and understanding of how the QDs are created, and especially their interactions with their local environments are therefore crucial to

  10. Electron-beam-induced topographical, chemical, and structural patterning of amorphous titanium oxide films.

    PubMed

    Kern, P; Müller, Y; Patscheider, J; Michler, J

    2006-11-30

    Electrolytically deposited amorphous TiO2 films on steel are remarkably sensitive to electron beam (e-beam) irradiation at moderate energies at 20 keV, resulting in controlled local oxide reduction and crystallization, opening the possibility for local topographical, chemical, and structural modifications within a biocompatible, amorphous, and semiconducting matrix. The sensitivity is shown to vary significantly with the annealing temperature of as-deposited films. Well-defined irradiation conditions in terms of probe current IP (5 microA) and beam size were achieved with an electron probe microanalyzer. As shown by atomic force and optical microscopy, micro-Raman spectroscopy, wavelength-dispersive X-ray (WDX), and Auger analyses, e-beam exposure below 1 Acm-2 immediately leads to electron-stimulated oxygen desorption, resulting in a well-defined volume loss primarily limited to the irradiated zone under the electron probe and in a blue color shift in this zone because of the presence of Ti2O3. Irradiation at 5 Acm(-2) (IP = 5 microA) results in local crystallization into anatase phase within 1 s of exposure and in reduction to TiO after an extended exposure of 60 s. Further reduction to the metallic state could be observed after 60 s of exposure at approximately 160 Acm(-2). The local reduction could be qualitatively sensed with WDX analysis and Auger line scans. An estimation of the film temperature in the beam center indicates that crystallization occurs at less than 150 degrees C, well below the atmospheric crystallization temperature of the present films. The high e-beam sensitivity in combination with the well-defined volume loss from oxygen desorption allows for precise electron lithographic topographical patterning of the present oxides. Irradiation effects leading to the observed reduction and crystallization phenomena under moderate electron energies are discussed.

  11. Cost-Sensitive Local Binary Feature Learning for Facial Age Estimation.

    PubMed

    Lu, Jiwen; Liong, Venice Erin; Zhou, Jie

    2015-12-01

    In this paper, we propose a cost-sensitive local binary feature learning (CS-LBFL) method for facial age estimation. Unlike the conventional facial age estimation methods that employ hand-crafted descriptors or holistically learned descriptors for feature representation, our CS-LBFL method learns discriminative local features directly from raw pixels for face representation. Motivated by the fact that facial age estimation is a cost-sensitive computer vision problem and local binary features are more robust to illumination and expression variations than holistic features, we learn a series of hashing functions to project raw pixel values extracted from face patches into low-dimensional binary codes, where binary codes with similar chronological ages are projected as close as possible, and those with dissimilar chronological ages are projected as far as possible. Then, we pool and encode these local binary codes within each face image as a real-valued histogram feature for face representation. Moreover, we propose a cost-sensitive local binary multi-feature learning method to jointly learn multiple sets of hashing functions using face patches extracted from different scales to exploit complementary information. Our methods achieve competitive performance on four widely used face aging data sets.

  12. A Multimodal Imaging Protocol, (123)I/(99)Tc-Sestamibi, SPECT, and SPECT/CT, in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization.

    PubMed

    Lee, Grace S; McKenzie, Travis J; Mullan, Brian P; Farley, David R; Thompson, Geoffrey B; Richards, Melanie L

    2016-03-01

    Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown. Patients with 1°HPT, who underwent parathyroidectomy in 2012-2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of (123)I/(99)Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed. Of 360 patients who were identified, a curative operation was performed in 96%, using pre-operative imaging and IOPTH. Imaging analysis showed that (123)I/(99)Tc-sestamibi had a sensitivity of 86% (95% CI 82-90%), positive predictive value (PPV) 93%, and accuracy 81%, based on correct lateralization. SPECT had a sensitivity of 77% (95% CI 72-82%), PPV 92% and accuracy 72%. SPECT/CT had a sensitivity of 75% (95% CI 70-80%), PPV of 94%, and accuracy 71%. There were 3 of 45 (7%) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87%) with positive uptake on sestamibi (93% true positive, 7% false positive), concordant findings were present in 86% SPECT and 84% SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, (123)I/(99)Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold. (123)I/(99)Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with (123)I/(99)Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.

  13. A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

    PubMed

    Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

    2016-12-01

    An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Lumbar Facet Joint Compressive Injury Induces Lasting Changes in Local Structure, Nociceptive Scores, and Inflammatory Mediators in a Novel Rat Model

    PubMed Central

    Henry, James L.; Yashpal, Kiran; Vernon, Howard; Kim, Jaesung; Im, Hee-Jeong

    2012-01-01

    Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6) facet joint was exposed and compressed to ~1 mm with modified clamps applied for three minutes; sham-operated and naïve animals were used as control groups. After five days, animals were tested for hind-paw sensitivity using von Frey filaments and axial deep tissue sensitivity by algometer on assigned days up to 28 days. Animals were sacrificed at selected times for histological and biochemical analysis. Results. Histological sections revealed site-specific loss of cartilage in model animals only. Tactile hypersensitivity was observed for the ipsi- and contralateral paws lasting 28 days. The threshold at which deep tissue pressure just elicited vocalization was obtained at three lumbar levels; sensitivity at L1 > L3/4 > L6. Biochemical analyses revealed increases in proinflammatory cytokines, especially TNF-α, IL-1α, and IL-1β. Conclusions. These data suggest that compression of a facet joint induces a novel model of local cartilage loss accompanied by increased sensitivity to mechanical stimuli and by increases in inflammatory mediators. This new model may be useful for studies on mechanisms and treatment of lumbar facet joint pain and osteoarthritis. PMID:22966427

  15. The Hsp90 Inhibitor, 17-AAG, Prevents the Ligand-Independent Nuclear Localization of Androgen Receptor in Refractory Prostate Cancer Cells

    PubMed Central

    Saporita, Anthony J.; Ai, Junkui; Wang, Zhou

    2010-01-01

    BACKGROUND Androgen receptor (AR) is the key molecule in androgen-refractory prostate cancer. Despite androgen ablative conditions, AR remains active and is necessary for the growth of androgen-refractory prostate cancer cells. Nuclear localization of AR is a prerequisite for its transcriptional activation. We examined AR localization in androgen-dependent and androgen-refractory prostate cancer cells. METHODS AND RESULTS We demonstrate increased nuclear localization of a GFP-tagged AR in the absence of hormone in androgen-refractory C4-2 cells compared to parental androgen-sensitive human prostate cancer LNCaP cells. Analysis of AR mutants impaired in ligand-binding indicates that the nuclear localization of AR in C4-2 cells is truly androgen-independent. The hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), inhibits basal PSA expression and disrupts the ligand-independent nuclear localization of AR at doses much lower than required to inhibit androgen-induced nuclear import. CONCLUSIONS Hsp90 is a key regulator of ligand-independent nuclear localization and activation of AR in androgen-refractory prostate cancer cells. PMID:17221841

  16. Correlation between experimental human and murine skin sensitization induction thresholds.

    PubMed

    Api, Anne Marie; Basketter, David; Lalko, Jon

    2015-01-01

    Quantitative risk assessment for skin sensitization is directed towards the determination of levels of exposure to known sensitizing substances that will avoid the induction of contact allergy in humans. A key component of this work is the predictive identification of relative skin sensitizing potency, achieved normally by the measurement of the threshold (the "EC3" value) in the local lymph node assay (LLNA). In an extended series of studies, the accuracy of this murine induction threshold as the predictor of the absence of a sensitizing effect has been verified by conduct of a human repeated insult patch test (HRIPT). Murine and human thresholds for a diverse set of 57 fragrance chemicals spanning approximately four orders of magnitude variation in potency have been compared. The results confirm that there is a useful correlation, with the LLNA EC3 value helping particularly to identify stronger sensitizers. Good correlation (with half an order of magnitude) was seen with three-quarters of the dataset. The analysis also helps to identify potential outlier types of (fragrance) chemistry, exemplified by hexyl and benzyl salicylates (an over-prediction) and trans-2-hexenal (an under-prediction).

  17. Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

    PubMed Central

    Park, H. S.; Nahm, D.

    1996-01-01

    Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms. PMID:8878807

  18. Sensitivity Analysis for Probabilistic Neural Network Structure Reduction.

    PubMed

    Kowalski, Piotr A; Kusy, Maciej

    2018-05-01

    In this paper, we propose the use of local sensitivity analysis (LSA) for the structure simplification of the probabilistic neural network (PNN). Three algorithms are introduced. The first algorithm applies LSA to the PNN input layer reduction by selecting significant features of input patterns. The second algorithm utilizes LSA to remove redundant pattern neurons of the network. The third algorithm combines the proposed two and constitutes the solution of how they can work together. PNN with a product kernel estimator is used, where each multiplicand computes a one-dimensional Cauchy function. Therefore, the smoothing parameter is separately calculated for each dimension by means of the plug-in method. The classification qualities of the reduced and full structure PNN are compared. Furthermore, we evaluate the performance of PNN, for which global sensitivity analysis (GSA) and the common reduction methods are applied, both in the input layer and the pattern layer. The models are tested on the classification problems of eight repository data sets. A 10-fold cross validation procedure is used to determine the prediction ability of the networks. Based on the obtained results, it is shown that the LSA can be used as an alternative PNN reduction approach.

  19. Identification and topographic localization of metallic foreign bodies by metal detector.

    PubMed

    Muensterer, Oliver J; Joppich, Ingolf

    2004-08-01

    Exact localization of ingested metal objects is necessary to guide therapy. This study prospectively evaluates the accuracy of foreign body (FB) identification and localization by metal detector (MTD) in a systematic topographic fashion. Patients who presented after an alleged or witnessed metal FB ingestion were scanned with an MTD. In case of a positive signal, the location was recorded in a topographic diagram, and radiographs were obtained. The diagnostic accuracy of the MTD scan for FB identification and topographic localization was determined by chi(2) analysis, and concordance was calculated by the McNemar test and expressed as kappa. A total of 70 MTD examinations were performed on 65 patients (age 6 months to 16 years); 5 patients were scanned twice on different days. The majority had swallowed coins and button batteries (n = 41). Of these, 29 items were correctly identified, and 11 of 12 were correctly ruled out (coins and button batteries: sensitivity, 100% [95% Confidence Interval 95% to 100%]; specificity, 91.7% [95% CI 76% to 100%], kappa = 0.94). When all metallic objects were included, 41 of 46 were correctly identified, and 22 of 24 were correctly ruled out (sensitivity, 89.1% [95% CI 80% to 98%]; specificity, 91.7% [95% CI 81% to 100%], kappa = 0.78). Five miscellaneous objects were not identified (sensitivity for items other than coins and button batteries 71% [95% CI 49% to 92%], kappa = 0.56). Localization by MTD was correct in 30 of 41 identified objects (73%). The error rates of junior and senior pediatric surgery residents did not differ significantly (P =.82). Ingested coins and button batteries can be safely and accurately found by metal detector. For these indications, the MTD is a radiation-free diagnostic alternative to conventional radiographs. Other items, however, cannot be ruled out reliably by MTD. In these cases, radiographic imaging is still indicated.

  20. Localization of multilayer networks by optimized single-layer rewiring.

    PubMed

    Jalan, Sarika; Pradhan, Priodyuti

    2018-04-01

    We study localization properties of principal eigenvectors (PEVs) of multilayer networks (MNs). Starting with a multilayer network corresponding to a delocalized PEV, we rewire the network edges using an optimization technique such that the PEV of the rewired multilayer network becomes more localized. The framework allows us to scrutinize structural and spectral properties of the networks at various localization points during the rewiring process. We show that rewiring only one layer is enough to attain a MN having a highly localized PEV. Our investigation reveals that a single edge rewiring of the optimized MN can lead to the complete delocalization of a highly localized PEV. This sensitivity in the localization behavior of PEVs is accompanied with the second largest eigenvalue lying very close to the largest one. This observation opens an avenue to gain a deeper insight into the origin of PEV localization of networks. Furthermore, analysis of multilayer networks constructed using real-world social and biological data shows that the localization properties of these real-world multilayer networks are in good agreement with the simulation results for the model multilayer network. This paper is relevant to applications that require understanding propagation of perturbation in multilayer networks.

  1. Localization of multilayer networks by optimized single-layer rewiring

    NASA Astrophysics Data System (ADS)

    Jalan, Sarika; Pradhan, Priodyuti

    2018-04-01

    We study localization properties of principal eigenvectors (PEVs) of multilayer networks (MNs). Starting with a multilayer network corresponding to a delocalized PEV, we rewire the network edges using an optimization technique such that the PEV of the rewired multilayer network becomes more localized. The framework allows us to scrutinize structural and spectral properties of the networks at various localization points during the rewiring process. We show that rewiring only one layer is enough to attain a MN having a highly localized PEV. Our investigation reveals that a single edge rewiring of the optimized MN can lead to the complete delocalization of a highly localized PEV. This sensitivity in the localization behavior of PEVs is accompanied with the second largest eigenvalue lying very close to the largest one. This observation opens an avenue to gain a deeper insight into the origin of PEV localization of networks. Furthermore, analysis of multilayer networks constructed using real-world social and biological data shows that the localization properties of these real-world multilayer networks are in good agreement with the simulation results for the model multilayer network. This paper is relevant to applications that require understanding propagation of perturbation in multilayer networks.

  2. Imaging electric field dynamics with graphene optoelectronics

    DOE PAGES

    Horng, Jason; Balch, Halleh B.; McGuire, Allister F.; ...

    2016-12-16

    The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts,more » a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.« less

  3. Fluorescence detection of white-beam X-ray absorption anisotropy: towards element-sensitive projections of local atomic structure

    PubMed Central

    Korecki, P.; Tolkiehn, M.; Dąbrowski, K. M.; Novikov, D. V.

    2011-01-01

    Projections of the atomic structure around Nb atoms in a LiNbO3 single crystal were obtained from a white-beam X-ray absorption anisotropy (XAA) pattern detected using Nb K fluorescence. This kind of anisotropy results from the interference of X-rays inside a sample and, owing to the short coherence length of a white beam, is visible only at small angles around interatomic directions. Consequently, the main features of the recorded XAA corresponded to distorted real-space projections of dense-packed atomic planes and atomic rows. A quantitative analysis of XAA was carried out using a wavelet transform and allowed well resolved projections of Nb atoms to be obtained up to distances of 10 Å. The signal of nearest O atoms was detected indirectly by a comparison with model calculations. The measurement of white-beam XAA using characteristic radiation indicates the possibility of obtaining element-sensitive projections of the local atomic structure in more complex samples. PMID:21997909

  4. Imaging electric field dynamics with graphene optoelectronics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Horng, Jason; Balch, Halleh B.; McGuire, Allister F.

    The use of electric fields for signalling and control in liquids is widespread, spanning bioelectric activity in cells to electrical manipulation of microstructures in lab-on-a-chip devices. However, an appropriate tool to resolve the spatio-temporal distribution of electric fields over a large dynamic range has yet to be developed. Here we present a label-free method to image local electric fields in real time and under ambient conditions. Our technique combines the unique gate-variable optical transitions of graphene with a critically coupled planar waveguide platform that enables highly sensitive detection of local electric fields with a voltage sensitivity of a few microvolts,more » a spatial resolution of tens of micrometres and a frequency response over tens of kilohertz. Our imaging platform enables parallel detection of electric fields over a large field of view and can be tailored to broad applications spanning lab-on-a-chip device engineering to analysis of bioelectric phenomena.« less

  5. Subcellular localization patterns and their relationship to photodynamic activity of pyropheophorbide-a derivatives.

    PubMed

    MacDonald, I J; Morgan, J; Bellnier, D A; Paszkiewicz, G M; Whitaker, J E; Litchfield, D J; Dougherty, T J

    1999-11-01

    To determine if subcellular localization is important to photodynamic therapy (PDT) efficacy, an in vitro fluorescence microscopy study was conducted with a congeneric series of pyropheophorbide-a derivatives in human pharyngeal squamous cell carcinoma (FaDu) cells and murine radiation-induced fibrosarcoma (RIF) mutant cells. In the FaDu cells the octyl, decyl and dodecyl ether derivatives localized to the lysosomes at extracellular concentrations less than needed to produce a 50% cell kill (LD50). At extracellular concentrations equal or greater than the LD50 the compounds localized mainly to mitochondria. The propyl, pentyl, hexyl and heptyl ether derivatives localized mainly to the mitochondria at all concentrations studied. This suggested that mitochondria are a sensitive PDT target for these derivatives. Similar experiments were performed with two Photofrin-PDT resistant RIF cell lines, one of which was found to be resistant to hexyl ether derivative (C6) mediated-PDT and the other sensitive to C6-PDT relative to the parent line. At extracellular concentrations of C6 below the LD50 of each cell line, the mutants exhibited lysosomal localization. At concentrations above these values the patterns shifted to a mainly mitochondrial pattern. In these cell lines mitochondrial localization also correlated with PDT sensitivity. Localization to mitochondria or lysosomes appeared to be affected by the aggregation state of the congeners, all of which are highly aggregated in aqueous medium. Monomers apparently were the active fraction of these compounds because equalizing the extracellular monomer concentrations produced equivalent intracellular concentrations, photoxicity and localization patterns. Compounds that were mainly aggregates localized to the lysosomes where they were rendered less active. Mitochondria appear to be a sensitive target for pyropheophorbide-a-mediated photodamage, and the degree of aggregation seems to be a determinant of the localization site.

  6. The National Map: Benefits at what cost?

    USGS Publications Warehouse

    Halsing, D.L.; Theissen, K.M.; Bernknopf, R.L.

    2004-01-01

    The U.S. Geological Survey has conducted a cost-benefit analysis of The National Map, and determined that, during its 30-year projected lifespan, the project will likely bring a net present value of benefits to society of $2.05 billion. Such a survey enhances the United States' ability to access, integrate, and apply geospatial data at global, national, and local scales. This paper gives an overview on the underlying economic model for evaluating program benefits and presents the primary findings as well as a sensitivity analysis assessing the robustness of the results.

  7. Differentiating the origin of outflow tract ventricular arrhythmia using a simple, novel approach.

    PubMed

    Efimova, Elena; Dinov, Borislav; Acou, Willem-Jan; Schirripa, Valentina; Kornej, Jelena; Kosiuk, Jedrzej; Rolf, Sascha; Sommer, Philipp; Richter, Sergio; Bollmann, Andreas; Hindricks, Gerhard; Arya, Arash

    2015-07-01

    Numerous electrocardiographic (ECG) criteria have been proposed to identify localization of outflow tract ventricular arrhythmias (OT-VAs); however, in some cases, it is difficult to accurately localize the origin of OT-VA using the surface ECG. The purpose of this study was to assess a simple criterion for localization of OT-VAs during electrophysiology study. We measured the interval from the onset of the earliest QRS complex of premature ventricular contractions (PVCs) to the distal right ventricular apical signal (the QRS-RVA interval) in 66 patients (31 men aged 53.3 ± 14.0 years; right ventricular outflow tract [RVOT] origin in 37) referred for ablation of symptomatic outflow tract PVCs. We prospectively validated this criterion in 39 patients (22 men aged 52 ± 15 years; RVOT origin in 19). Compared with patients with RVOT PVCs, the QRS-RVA interval was significantly longer in patients with left ventricular outflow tract (LVOT) PVCs (70 ± 14 vs 33.4±10 ms, P < .001). Receiver operating characteristic analysis showed that a QRS-RVA interval ≥49 ms had sensitivity, specificity, and positive and negative predictive values of 100%, 94.6%, 93.5%, and 100%, respectively, for prediction of an LVOT origin. The same analysis in the validation cohort showed sensitivity, specificity, and positive and negative predictive values of 94.7%, 95%, 95%, and 94.7%, respectively. When these data were combined, a QRS-RVA interval ≥49 ms had sensitivity, specificity, and positive and negative predictive values of 98%, 94.6%, 94.1%, and 98.1%, respectively, for prediction of an LVOT origin. A QRS-RVA interval ≥49 ms suggests an LVOT origin. The QRS-RVA interval is a simple and accurate criterion for differentiating the origin of outflow tract arrhythmia during electrophysiology study; however, the accuracy of this criterion in identifying OT-VA from the right coronary cusp is limited. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  8. Local indicators of climate change: The potential contribution of local knowledge to climate research

    PubMed Central

    Reyes-García, Victoria; Fernández-Llamazares, Álvaro; Guèze, Maximilien; Garcés, Ariadna; Mallo, Miguel; Vila-Gómez, Margarita; Vilaseca, Marina

    2016-01-01

    Local knowledge has been proposed as a place-based tool to ground-truth climate models and to narrow their geographic sensitivity. To assess the potential role of local knowledge in our quest to understand better climate change and its impacts, we first need to critically review the strengths and weaknesses of local knowledge of climate change and the potential complementarity with scientific knowledge. With this aim, we conducted a systematic, quantitative meta-analysis of published peer-reviewed documents reporting local indicators of climate change (including both local observations of climate change and observed impacts on the biophysical and the social systems). Overall, primary data on the topic are not abundant, the methodological development is incipient, and the geographical extent is unbalanced. On the 98 case studies documented, we recorded the mention of 746 local indicators of climate change, mostly corresponding to local observations of climate change (40%), but also to observed impacts on the physical (23%), the biological (19%), and the socioeconomic (18%) systems. Our results suggest that, even if local observations of climate change are the most frequently reported type of change, the rich and fine-grained knowledge in relation to impacts on biophysical systems could provide more original contributions to our understanding of climate change at local scale. PMID:27642368

  9. Local-global classifier fusion for screening chest radiographs

    NASA Astrophysics Data System (ADS)

    Ding, Meng; Antani, Sameer; Jaeger, Stefan; Xue, Zhiyun; Candemir, Sema; Kohli, Marc; Thoma, George

    2017-03-01

    Tuberculosis (TB) is a severe comorbidity of HIV and chest x-ray (CXR) analysis is a necessary step in screening for the infective disease. Automatic analysis of digital CXR images for detecting pulmonary abnormalities is critical for population screening, especially in medical resource constrained developing regions. In this article, we describe steps that improve previously reported performance of NLM's CXR screening algorithms and help advance the state of the art in the field. We propose a local-global classifier fusion method where two complementary classification systems are combined. The local classifier focuses on subtle and partial presentation of the disease leveraging information in radiology reports that roughly indicates locations of the abnormalities. In addition, the global classifier models the dominant spatial structure in the gestalt image using GIST descriptor for the semantic differentiation. Finally, the two complementary classifiers are combined using linear fusion, where the weight of each decision is calculated by the confidence probabilities from the two classifiers. We evaluated our method on three datasets in terms of the area under the Receiver Operating Characteristic (ROC) curve, sensitivity, specificity and accuracy. The evaluation demonstrates the superiority of our proposed local-global fusion method over any single classifier.

  10. Adherence to infection control guidelines in surgery on MRSA positive patients : A cost analysis.

    PubMed

    Saegeman, V; Schuermans, A

    2016-09-01

    In surgical units, similar to other healthcare departments, guidelines are used to curb transmission of methicillin resistant Staphylococcus aureus (MRSA). The aim of this study was to calculate the extra costs for material and extra working hours for compliance to MRSA infection control guidelines in the operating rooms of a University Hospital. The study was based on observations of surgeries on MRSA positive patients. The average cost per surgery was calculated utilizing local information on unit costs. Robustness of the calculations was evaluated with a sensitivity analysis. The total extra costs of adherence to MRSA infection control guidelines averaged € 340.46 per surgical procedure (range € 207.76- € 473.15). A sensitivity analysis based on a standardized operating room hourly rate reached a cost of € 366.22. The extra costs of adherence to infection control guidelines are considerable. To reduce costs, the logistical planning of surgeries could be improved by for instance a dedicated room.

  11. Study of effects of fuel properties in turbine-powered business aircraft

    NASA Technical Reports Server (NTRS)

    Powell, F. D.; Biegen, R. J.; Weitz, P. G., Jr.; Duke, A. M.

    1984-01-01

    Increased interest in research and technology concerning aviation turbine fuels and their properties was prompted by recent changes in the supply and demand situation of these fuels. The most obvious change is the rapid increase in fuel price. For commercial airplanes, fuel costs now approach 50 percent of the direct operating costs. In addition, there were occasional local supply disruptions and gradual shifts in delivered values of certain fuel properties. Dwindling petroleum reserves and the politically sensitive nature of the major world suppliers make the continuation of these trends likely. A summary of the principal findings, and conclusions are presented. Much of the material, especially the tables and graphs, is considered in greater detail later. The economic analysis and examination of operational considerations are described. Because some of the assumptions on which the economic analysis is founded are not easily verified, the sensitivity of the analysis to alternates for these assumptions is examined. The data base on which the analyses are founded is defined in a set of appendices.

  12. Case Study: Sensitivity Analysis of the Barataria Basin Barrier Shoreline Wetland Value Assessment Model

    DTIC Science & Technology

    2014-07-01

    wetlands in providing resting, foraging , breeding, and nursery habitat to a diverse assemblage of fish and wildlife species in coastal Louisiana (EWG...services, including fish and wildlife production, storm damage reduction, and recreation. Federal, state, and local partners have jointly pursued large...habitat units” (HU) provided by a given alternative. Whereas traditional HEP models focused on specific taxa, WVA assesses the fish and wildlife community

  13. Population genetic structure and tolerance to dioxin-like compounds of a migratory marine fish (Menidia menidia) at polychlorinated biphenyl-contaminated and reference sites.

    PubMed

    Roark, Shaun A; Kelble, Mary A; Nacci, Diane; Champlin, Denise; Coiro, Laura; Guttman, Sheldon I

    2005-03-01

    The present study was conducted to evaluate evidence of genetic adaptation to local contaminants in populations of the migratory marine fish Menidia menidia residing seasonally in reference sites or an industrial harbor contaminated with dioxin-like compounds (DLCs). For this purpose, we compared DLC sensitivity and genetic patterns of populations sampled from sites both inside and outside New Bedford Harbor (NBH; MA, USA), a U.S. Environmental Protection Agency Superfund site with extreme polychlorinated biphenyl (PCB) contamination. Offspring of M. menidia collected from NBH were significantly less sensitive regarding embryonic exposure to the dioxin-like PCB congener 3,3',4,4',5-pentachlorobiphenyl (PCB 126) than offspring of M. menidia from a reference site. Analysis of 10 polymorphic enzymatic loci indicated little genetic differentiation among populations in the study area. However, genotype frequencies of juveniles from both NBH and an adjacent site in Massachusetts exhibited significant deviations from Hardy-Weinberg equilibrium expectations at one locus, phosphoglucomutase (PGM*). Genetic analysis of survivors of embryonic laboratory exposure to PCB 126 indicated that genotypes at PGM* were related to survivorship. Although a relationship was identified between DLC tolerance and PGM* genotype, regional mixing of M. menidia populations during migration and absence of multigeneration exposure at contaminated sites may limit localized adaptation.

  14. Experimental study on the crack detection with optimized spatial wavelet analysis and windowing

    NASA Astrophysics Data System (ADS)

    Ghanbari Mardasi, Amir; Wu, Nan; Wu, Christine

    2018-05-01

    In this paper, a high sensitive crack detection is experimentally realized and presented on a beam under certain deflection by optimizing spatial wavelet analysis. Due to the crack existence in the beam structure, a perturbation/slop singularity is induced in the deflection profile. Spatial wavelet transformation works as a magnifier to amplify the small perturbation signal at the crack location to detect and localize the damage. The profile of a deflected aluminum cantilever beam is obtained for both intact and cracked beams by a high resolution laser profile sensor. Gabor wavelet transformation is applied on the subtraction of intact and cracked data sets. To improve detection sensitivity, scale factor in spatial wavelet transformation and the transformation repeat times are optimized. Furthermore, to detect the possible crack close to the measurement boundaries, wavelet transformation edge effect, which induces large values of wavelet coefficient around the measurement boundaries, is efficiently reduced by introducing different windowing functions. The result shows that a small crack with depth of less than 10% of the beam height can be localized with a clear perturbation. Moreover, the perturbation caused by a crack at 0.85 mm away from one end of the measurement range, which is covered by wavelet transform edge effect, emerges by applying proper window functions.

  15. Signatures of mountain building: Detrital zircon U/Pb ages from northeast Tibet

    USGS Publications Warehouse

    Lease, Richard O.; Burbank, Douglas W.; Gehrels, George E.; Wang, Zhicai; Yuan, Daoyang

    2007-01-01

    Although detrital zircon has proven to be a powerful tool for determining provenance, past work has focused primarily on delimiting regional source terranes. Here we explore the limits of spatial resolution and stratigraphic sensitivity of detrital zircon in ascertaining provenance, and we demonstrate its ability to detect source changes for terranes separated by only a few tens of kilometers. For such an analysis to succeed for a given mountain, discrete intrarange source terranes must have unique U/Pb zircon age signatures and sediments eroded from the range must have well-defined depositional ages. Here we use ∼1400 single-grain U/Pb zircon ages from northeastern Tibet to identify and analyze an area that satisfies these conditions. This analysis shows that the edges of intermontane basins are stratigraphically sensitive to discrete, punctuated changes in local source terranes. By tracking eroding rock units chronologically through the stratigraphic record, this sensitivity permits the detection of the differential rock uplift and progressive erosion that began ca. 8 Ma in the Laji Shan, a 10-25-km-wide range in northeastern Tibet with a unique U/Pb age signature.

  16. Emulation and Sobol' sensitivity analysis of an atmospheric dispersion model applied to the Fukushima nuclear accident

    NASA Astrophysics Data System (ADS)

    Girard, Sylvain; Mallet, Vivien; Korsakissok, Irène; Mathieu, Anne

    2016-04-01

    Simulations of the atmospheric dispersion of radionuclides involve large uncertainties originating from the limited knowledge of meteorological input data, composition, amount and timing of emissions, and some model parameters. The estimation of these uncertainties is an essential complement to modeling for decision making in case of an accidental release. We have studied the relative influence of a set of uncertain inputs on several outputs from the Eulerian model Polyphemus/Polair3D on the Fukushima case. We chose to use the variance-based sensitivity analysis method of Sobol'. This method requires a large number of model evaluations which was not achievable directly due to the high computational cost of Polyphemus/Polair3D. To circumvent this issue, we built a mathematical approximation of the model using Gaussian process emulation. We observed that aggregated outputs are mainly driven by the amount of emitted radionuclides, while local outputs are mostly sensitive to wind perturbations. The release height is notably influential, but only in the vicinity of the source. Finally, averaging either spatially or temporally tends to cancel out interactions between uncertain inputs.

  17. Local connectome phenotypes predict social, health, and cognitive factors

    PubMed Central

    Powell, Michael A.; Garcia, Javier O.; Yeh, Fang-Cheng; Vettel, Jean M.

    2018-01-01

    The unique architecture of the human connectome is defined initially by genetics and subsequently sculpted over time with experience. Thus, similarities in predisposition and experience that lead to similarities in social, biological, and cognitive attributes should also be reflected in the local architecture of white matter fascicles. Here we employ a method known as local connectome fingerprinting that uses diffusion MRI to measure the fiber-wise characteristics of macroscopic white matter pathways throughout the brain. This fingerprinting approach was applied to a large sample (N = 841) of subjects from the Human Connectome Project, revealing a reliable degree of between-subject correlation in the local connectome fingerprints, with a relatively complex, low-dimensional substructure. Using a cross-validated, high-dimensional regression analysis approach, we derived local connectome phenotype (LCP) maps that could reliably predict a subset of subject attributes measured, including demographic, health, and cognitive measures. These LCP maps were highly specific to the attribute being predicted but also sensitive to correlations between attributes. Collectively, these results indicate that the local architecture of white matter fascicles reflects a meaningful portion of the variability shared between subjects along several dimensions. PMID:29911679

  18. Local connectome phenotypes predict social, health, and cognitive factors.

    PubMed

    Powell, Michael A; Garcia, Javier O; Yeh, Fang-Cheng; Vettel, Jean M; Verstynen, Timothy

    2018-01-01

    The unique architecture of the human connectome is defined initially by genetics and subsequently sculpted over time with experience. Thus, similarities in predisposition and experience that lead to similarities in social, biological, and cognitive attributes should also be reflected in the local architecture of white matter fascicles. Here we employ a method known as local connectome fingerprinting that uses diffusion MRI to measure the fiber-wise characteristics of macroscopic white matter pathways throughout the brain. This fingerprinting approach was applied to a large sample ( N = 841) of subjects from the Human Connectome Project, revealing a reliable degree of between-subject correlation in the local connectome fingerprints, with a relatively complex, low-dimensional substructure. Using a cross-validated, high-dimensional regression analysis approach, we derived local connectome phenotype (LCP) maps that could reliably predict a subset of subject attributes measured, including demographic, health, and cognitive measures. These LCP maps were highly specific to the attribute being predicted but also sensitive to correlations between attributes. Collectively, these results indicate that the local architecture of white matter fascicles reflects a meaningful portion of the variability shared between subjects along several dimensions.

  19. A methodology for optimal MSW management, with an application in the waste transportation of Attica Region, Greece

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Economopoulou, M.A.; Economopoulou, A.A.; Economopoulos, A.P., E-mail: eco@otenet.gr

    2013-11-15

    Highlights: • A two-step (strategic and detailed optimal planning) methodology is used for solving complex MSW management problems. • A software package is outlined, which can be used for generating detailed optimal plans. • Sensitivity analysis compares alternative scenarios that address objections and/or wishes of local communities. • A case study shows the application of the above procedure in practice and demonstrates the results and benefits obtained. - Abstract: The paper describes a software system capable of formulating alternative optimal Municipal Solid Wastes (MSWs) management plans, each of which meets a set of constraints that may reflect selected objections and/ormore » wishes of local communities. The objective function to be minimized in each plan is the sum of the annualized capital investment and annual operating cost of all transportation, treatment and final disposal operations involved, taking into consideration the possible income from the sale of products and any other financial incentives or disincentives that may exist. For each plan formulated, the system generates several reports that define the plan, analyze its cost elements and yield an indicative profile of selected types of installations, as well as data files that facilitate the geographic representation of the optimal solution in maps through the use of GIS. A number of these reports compare the technical and economic data from all scenarios considered at the study area, municipality and installation level constituting in effect sensitivity analysis. The generation of alternative plans offers local authorities the opportunity of choice and the results of the sensitivity analysis allow them to choose wisely and with consensus. The paper presents also an application of this software system in the capital Region of Attica in Greece, for the purpose of developing an optimal waste transportation system in line with its approved waste management plan. The formulated plan was able to: (a) serve 113 Municipalities and Communities that generate nearly 2 million t/y of comingled MSW with distinctly different waste collection patterns, (b) take into consideration several existing waste transfer stations (WTS) and optimize their use within the overall plan, (c) select the most appropriate sites among the potentially suitable (new and in use) ones, (d) generate the optimal profile of each WTS proposed, and (e) perform sensitivity analysis so as to define the impact of selected sets of constraints (limitations in the availability of sites and in the capacity of their installations) on the design and cost of the ensuing optimal waste transfer system. The results show that optimal planning offers significant economic savings to municipalities, while reducing at the same time the present levels of traffic, fuel consumptions and air emissions in the congested Athens basin.« less

  20. Sensitivity and accuracy of hybrid fluorescence-mediated tomography in deep tissue regions.

    PubMed

    Rosenhain, Stefanie; Al Rawashdeh, Wa'el; Kiessling, Fabian; Gremse, Felix

    2017-09-01

    Fluorescence-mediated tomography (FMT) enables noninvasive assessment of the three-dimensional distribution of near-infrared fluorescence in mice. The combination with micro-computed tomography (µCT) provides anatomical data, enabling improved fluorescence reconstruction and image analysis. The aim of our study was to assess sensitivity and accuracy of µCT-FMT under realistic in vivo conditions in deeply-seated regions. Accordingly, we acquired fluorescence reflectance images (FRI) and µCT-FMT scans of mice which were prepared with rectal insertions with different amounts of fluorescent dye. Default and high-sensitivity scans were acquired and background signal was analyzed for three FMT channels (670 nm, 745 nm, and 790 nm). Analysis was performed for the original and an improved FMT reconstruction using the µCT data. While FRI and the original FMT reconstruction could detect 100 pmol, the improved FMT reconstruction could detect 10 pmol and significantly improved signal localization. By using a finer sampling grid and increasing the exposure time, the sensitivity could be further improved to detect 0.5 pmol. Background signal was highest in the 670 nm channel and most prominent in the gastro-intestinal tract and in organs with high relative amounts of blood. In conclusion, we show that µCT-FMT allows sensitive and accurate assessment of fluorescence in deep tissue regions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Towards an atrio-ventricular delay optimization assessed by a computer model for cardiac resynchronization therapy

    NASA Astrophysics Data System (ADS)

    Ojeda, David; Le Rolle, Virginie; Tse Ve Koon, Kevin; Thebault, Christophe; Donal, Erwan; Hernández, Alfredo I.

    2013-11-01

    In this paper, lumped-parameter models of the cardiovascular system, the cardiac electrical conduction system and a pacemaker are coupled to generate mitral ow pro les for di erent atrio-ventricular delay (AVD) con gurations, in the context of cardiac resynchronization therapy (CRT). First, we perform a local sensitivity analysis of left ventricular and left atrial parameters on mitral ow characteristics, namely E and A wave amplitude, mitral ow duration, and mitral ow time integral. Additionally, a global sensitivity analysis over all model parameters is presented to screen for the most relevant parameters that a ect the same mitral ow characteristics. Results provide insight on the in uence of left ventricle and atrium in uence on mitral ow pro les. This information will be useful for future parameter estimation of the model that could reproduce the mitral ow pro les and cardiovascular hemodynamics of patients undergoing AVD optimization during CRT.

  2. Reproducibility of EEG-fMRI results in a patient with fixation-off sensitivity.

    PubMed

    Formaggio, Emanuela; Storti, Silvia Francesca; Galazzo, Ilaria Boscolo; Bongiovanni, Luigi Giuseppe; Cerini, Roberto; Fiaschi, Antonio; Manganotti, Paolo

    2014-07-01

    Blood oxygenation level-dependent (BOLD) activation associated with interictal epileptiform discharges in a patient with fixation-off sensitivity (FOS) was studied using a combined electroencephalography-functional magnetic resonance imaging (EEG-fMRI) technique. An automatic approach for combined EEG-fMRI analysis and a subject-specific hemodynamic response function was used to improve general linear model analysis of the fMRI data. The EEG showed the typical features of FOS, with continuous epileptiform discharges during elimination of central vision by eye opening and closing and fixation; modification of this pattern was clearly visible and recognizable. During all 3 recording sessions EEG-fMRI activations indicated a BOLD signal decrease related to epileptiform activity in the parietal areas. This study can further our understanding of this EEG phenomenon and can provide some insight into the reliability of the EEG-fMRI technique in localizing the irritative zone.

  3. A hybrid cloud read aligner based on MinHash and kmer voting that preserves privacy

    NASA Astrophysics Data System (ADS)

    Popic, Victoria; Batzoglou, Serafim

    2017-05-01

    Low-cost clouds can alleviate the compute and storage burden of the genome sequencing data explosion. However, moving personal genome data analysis to the cloud can raise serious privacy concerns. Here, we devise a method named Balaur, a privacy preserving read mapper for hybrid clouds based on locality sensitive hashing and kmer voting. Balaur can securely outsource a substantial fraction of the computation to the public cloud, while being highly competitive in accuracy and speed with non-private state-of-the-art read aligners on short read data. We also show that the method is significantly faster than the state of the art in long read mapping. Therefore, Balaur can enable institutions handling massive genomic data sets to shift part of their analysis to the cloud without sacrificing accuracy or exposing sensitive information to an untrusted third party.

  4. A hybrid cloud read aligner based on MinHash and kmer voting that preserves privacy

    PubMed Central

    Popic, Victoria; Batzoglou, Serafim

    2017-01-01

    Low-cost clouds can alleviate the compute and storage burden of the genome sequencing data explosion. However, moving personal genome data analysis to the cloud can raise serious privacy concerns. Here, we devise a method named Balaur, a privacy preserving read mapper for hybrid clouds based on locality sensitive hashing and kmer voting. Balaur can securely outsource a substantial fraction of the computation to the public cloud, while being highly competitive in accuracy and speed with non-private state-of-the-art read aligners on short read data. We also show that the method is significantly faster than the state of the art in long read mapping. Therefore, Balaur can enable institutions handling massive genomic data sets to shift part of their analysis to the cloud without sacrificing accuracy or exposing sensitive information to an untrusted third party. PMID:28508884

  5. Analysis and prediction of calcium-binding pockets from apo-protein structures exhibiting calcium-induced localized conformational changes

    PubMed Central

    Wang, Xue; Zhao, Kun; Kirberger, Michael; Wong, Hing; Chen, Guantao; Yang, Jenny J

    2010-01-01

    Calcium binding in proteins exhibits a wide range of polygonal geometries that relate directly to an equally diverse set of biological functions. The binding process stabilizes protein structures and typically results in local conformational change and/or global restructuring of the backbone. Previously, we established the MUG program, which utilized multiple geometries in the Ca2+-binding pockets of holoproteins to identify such pockets, ignoring possible Ca2+-induced conformational change. In this article, we first report our progress in the analysis of Ca2+-induced conformational changes followed by improved prediction of Ca2+-binding sites in the large group of Ca2+-binding proteins that exhibit only localized conformational changes. The MUGSR algorithm was devised to incorporate side chain torsional rotation as a predictor. The output from MUGSR presents groups of residues where each group, typically containing two to five residues, is a potential binding pocket. MUGSR was applied to both X-ray apo structures and NMR holo structures, which did not use calcium distance constraints in structure calculations. Predicted pockets were validated by comparison with homologous holo structures. Defining a “correct hit” as a group of residues containing at least two true ligand residues, the sensitivity was at least 90%; whereas for a “correct hit” defined as a group of residues containing at least three true ligand residues, the sensitivity was at least 78%. These data suggest that Ca2+-binding pockets are at least partially prepositioned to chelate the ion in the apo form of the protein. PMID:20512971

  6. Distribution Analysis of Anthocyanins, Sugars, and Organic Acids in Strawberry Fruits Using Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry.

    PubMed

    Enomoto, Hirofumi; Sato, Kei; Miyamoto, Koji; Ohtsuka, Akira; Yamane, Hisakazu

    2018-05-16

    Anthocyanins, sugars, and organic acids contribute to the appearance, health benefits, and taste of strawberries. However, their spatial distribution in the ripe fruit has been fully unrevealed. Therefore, we performed matrix-assisted laser desorption/ionization, MALDI-IMS, analysis to investigate their spatial distribution in ripe strawberries. The detection sensitivity was improved by using the TM-Sprayer for matrix application. In the receptacle, pelargonidins were distributed in the skin, cortical, and pith tissues, whereas cyanidins and delphinidins were slightly localized in the skin. In the achene, mainly cyanidins were localized in the outside of the skin. Citric acid was mainly distributed in the upper and bottom side of cortical tissue. Although hexose was distributed almost equally throughout the fruits, sucrose was mainly distributed in the upper side of cortical and pith tissues. These results suggest that using the TM-Sprayer in MALDI-IMS was useful for microscopic distribution analysis of anthocyanins, sugars, and organic acids in strawberries.

  7. Weather Research and Forecasting Model Wind Sensitivity Study at Edwards Air Force Base, CA

    NASA Technical Reports Server (NTRS)

    Watson, Leela R.; Bauman, William H., III; Hoeth, Brian

    2009-01-01

    This abstract describes work that will be done by the Applied Meteorology Unit (AMU) in assessing the success of different model configurations in predicting "wind cycling" cases at Edwards Air Force Base, CA (EAFB), in which the wind speeds and directions oscillate among towers near the EAFB runway. The Weather Research and Forecasting (WRF) model allows users to choose among two dynamical cores - the Advanced Research WRF (ARW) and the Non-hydrostatic Mesoscale Model (NMM). There are also data assimilation analysis packages available for the initialization of the WRF model - the Local Analysis and Prediction System (LAPS) and the Advanced Regional Prediction System (ARPS) Data Analysis System (ADAS). Having a series of initialization options and WRF cores, as well as many options within each core, creates challenges for local forecasters, such as determining which configuration options are best to address specific forecast concerns. The goal of this project is to assess the different configurations available and determine which configuration will best predict surface wind speed and direction at EAFB.

  8. Population analysis of the cingulum bundle using the tubular surface model for schizophrenia detection

    NASA Astrophysics Data System (ADS)

    Mohan, Vandana; Sundaramoorthi, Ganesh; Kubicki, Marek; Terry, Douglas; Tannenbaum, Allen

    2010-03-01

    We propose a novel framework for population analysis of DW-MRI data using the Tubular Surface Model. We focus on the Cingulum Bundle (CB) - a major tract for the Limbic System and the main connection of the Cingulate Gyrus, which has been associated with several aspects of Schizophrenia symptomatology. The Tubular Surface Model represents a tubular surface as a center-line with an associated radius function. It provides a natural way to sample statistics along the length of the fiber bundle and reduces the registration of fiber bundle surfaces to that of 4D curves. We apply our framework to a population of 20 subjects (10 normal, 10 schizophrenic) and obtain excellent results with neural network based classification (90% sensitivity, 95% specificity) as well as unsupervised clustering (k-means). Further, we apply statistical analysis to the feature data and characterize the discrimination ability of local regions of the CB, as a step towards localizing CB regions most relevant to Schizophrenia.

  9. Orthogonal sparse linear discriminant analysis

    NASA Astrophysics Data System (ADS)

    Liu, Zhonghua; Liu, Gang; Pu, Jiexin; Wang, Xiaohong; Wang, Haijun

    2018-03-01

    Linear discriminant analysis (LDA) is a linear feature extraction approach, and it has received much attention. On the basis of LDA, researchers have done a lot of research work on it, and many variant versions of LDA were proposed. However, the inherent problem of LDA cannot be solved very well by the variant methods. The major disadvantages of the classical LDA are as follows. First, it is sensitive to outliers and noises. Second, only the global discriminant structure is preserved, while the local discriminant information is ignored. In this paper, we present a new orthogonal sparse linear discriminant analysis (OSLDA) algorithm. The k nearest neighbour graph is first constructed to preserve the locality discriminant information of sample points. Then, L2,1-norm constraint on the projection matrix is used to act as loss function, which can make the proposed method robust to outliers in data points. Extensive experiments have been performed on several standard public image databases, and the experiment results demonstrate the performance of the proposed OSLDA algorithm.

  10. A new statistical tool for NOAA local climate studies

    NASA Astrophysics Data System (ADS)

    Timofeyeva, M. M.; Meyers, J. C.; Hollingshead, A.

    2011-12-01

    The National Weather Services (NWS) Local Climate Analysis Tool (LCAT) is evolving out of a need to support and enhance the National Oceanic and Atmospheric Administration (NOAA) National Weather Service (NWS) field offices' ability to efficiently access, manipulate, and interpret local climate data and characterize climate variability and change impacts. LCAT will enable NOAA's staff to conduct regional and local climate studies using state-of-the-art station and reanalysis gridded data and various statistical techniques for climate analysis. The analysis results will be used for climate services to guide local decision makers in weather and climate sensitive actions and to deliver information to the general public. LCAT will augment current climate reference materials with information pertinent to the local and regional levels as they apply to diverse variables appropriate to each locality. The LCAT main emphasis is to enable studies of extreme meteorological and hydrological events such as tornadoes, flood, drought, severe storms, etc. LCAT will close a very critical gap in NWS local climate services because it will allow addressing climate variables beyond average temperature and total precipitation. NWS external partners and government agencies will benefit from the LCAT outputs that could be easily incorporated into their own analysis and/or delivery systems. Presently we identified five existing requirements for local climate: (1) Local impacts of climate change; (2) Local impacts of climate variability; (3) Drought studies; (4) Attribution of severe meteorological and hydrological events; and (5) Climate studies for water resources. The methodologies for the first three requirements will be included in the LCAT first phase implementation. Local rate of climate change is defined as a slope of the mean trend estimated from the ensemble of three trend techniques: (1) hinge, (2) Optimal Climate Normals (running mean for optimal time periods), (3) exponentially-weighted moving average. Root mean squared error is used to determine the best fit of trend to the observations with the least error. The studies of climate variability impacts on local extremes use composite techniques applied to various definitions of local variables: from specified percentiles to critical thresholds. Drought studies combine visual capabilities of Google maps with statistical estimates of drought severity indices. The process of development will be linked to local office interactions with users to ensure the tool will meet their needs as well as provide adequate training. A rigorous internal and tiered peer-review process will be implemented to ensure the studies are scientifically-sound that will be published and submitted to the local studies catalog (database) and eventually to external sources, such as the Climate Portal.

  11. A Tree Locality-Sensitive Hash for Secure Software Testing

    DTIC Science & Technology

    2017-09-14

    errors, or to look for vulnerabilities that could allow a nefarious actor to use our software against us. Ultimately, all testing is designed to find...and an equivalent number of feasible paths discovered by Klee. 1.5 Summary This document the Tree Locality-Sensitive Hash (TLSH), a locality-senstive...performing two groups of tests that verify the accuracy and usefulness of TLSH. Chapter 5 summarizes the contents of the dissertation and lists avenues

  12. Automated Age-related Macular Degeneration screening system using fundus images.

    PubMed

    Kunumpol, P; Umpaipant, W; Kanchanaranya, N; Charoenpong, T; Vongkittirux, S; Kupakanjana, T; Tantibundhit, C

    2017-07-01

    This work proposed an automated screening system for Age-related Macular Degeneration (AMD), and distinguishing between wet or dry types of AMD using fundus images to assist ophthalmologists in eye disease screening and management. The algorithm employs contrast-limited adaptive histogram equalization (CLAHE) in image enhancement. Subsequently, discrete wavelet transform (DWT) and locality sensitivity discrimination analysis (LSDA) were used to extract features for a neural network model to classify the results. The results showed that the proposed algorithm was able to distinguish between normal eyes, dry AMD, or wet AMD with 98.63% sensitivity, 99.15% specificity, and 98.94% accuracy, suggesting promising potential as a medical support system for faster eye disease screening at lower costs.

  13. Parameter Estimation and Sensitivity Analysis of an Urban Surface Energy Balance Parameterization at a Tropical Suburban Site

    NASA Astrophysics Data System (ADS)

    Harshan, S.; Roth, M.; Velasco, E.

    2014-12-01

    Forecasting of the urban weather and climate is of great importance as our cities become more populated and considering the combined effects of global warming and local land use changes which make urban inhabitants more vulnerable to e.g. heat waves and flash floods. In meso/global scale models, urban parameterization schemes are used to represent the urban effects. However, these schemes require a large set of input parameters related to urban morphological and thermal properties. Obtaining all these parameters through direct measurements are usually not feasible. A number of studies have reported on parameter estimation and sensitivity analysis to adjust and determine the most influential parameters for land surface schemes in non-urban areas. Similar work for urban areas is scarce, in particular studies on urban parameterization schemes in tropical cities have so far not been reported. In order to address above issues, the town energy balance (TEB) urban parameterization scheme (part of the SURFEX land surface modeling system) was subjected to a sensitivity and optimization/parameter estimation experiment at a suburban site in, tropical Singapore. The sensitivity analysis was carried out as a screening test to identify the most sensitive or influential parameters. Thereafter, an optimization/parameter estimation experiment was performed to calibrate the input parameter. The sensitivity experiment was based on the "improved Sobol's global variance decomposition method" . The analysis showed that parameters related to road, roof and soil moisture have significant influence on the performance of the model. The optimization/parameter estimation experiment was performed using the AMALGM (a multi-algorithm genetically adaptive multi-objective method) evolutionary algorithm. The experiment showed a remarkable improvement compared to the simulations using the default parameter set. The calibrated parameters from this optimization experiment can be used for further model validation studies to identify inherent deficiencies in model physics.

  14. Local and global responses in complex gene regulation networks

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Masa; Selvarajoo, Kumar; Piras, Vincent; Tomita, Masaru; Giuliani, Alessandro

    2009-04-01

    An exacerbated sensitivity to apparently minor stimuli and a general resilience of the entire system stay together side-by-side in biological systems. This apparent paradox can be explained by the consideration of biological systems as very strongly interconnected network systems. Some nodes of these networks, thanks to their peculiar location in the network architecture, are responsible for the sensitivity aspects, while the large degree of interconnection is at the basis of the resilience properties of the system. One relevant feature of the high degree of connectivity of gene regulation networks is the emergence of collective ordered phenomena influencing the entire genome and not only a specific portion of transcripts. The great majority of existing gene regulation models give the impression of purely local ‘hard-wired’ mechanisms disregarding the emergence of global ordered behavior encompassing thousands of genes while the general, genome wide, aspects are less known. Here we address, on a data analysis perspective, the discrimination between local and global scale regulations, this goal was achieved by means of the examination of two biological systems: innate immune response in macrophages and oscillating growth dynamics in yeast. Our aim was to reconcile the ‘hard-wired’ local view of gene regulation with a global continuous and scalable one borrowed from statistical physics. This reconciliation is based on the network paradigm in which the local ‘hard-wired’ activities correspond to the activation of specific crucial nodes in the regulation network, while the scalable continuous responses can be equated to the collective oscillations of the network after a perturbation.

  15. Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation.

    PubMed

    Zaman, Junaid A B; Sauer, William H; Alhusseini, Mahmood I; Baykaner, Tina; Borne, Ryan T; Kowalewski, Christopher A B; Busch, Sonia; Zei, Paul C; Park, Shirley; Viswanathan, Mohan N; Wang, Paul J; Brachmann, Johannes; Krummen, David E; Miller, John M; Rappel, Wouter Jan; Narayan, Sanjiv M; Peters, Nicholas S

    2018-01-01

    The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation. We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms. Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation. © 2018 American Heart Association, Inc.

  16. Locally advanced rectal cancer: post-chemoradiotherapy ADC histogram analysis for predicting a complete response.

    PubMed

    Cho, Seung Hyun; Kim, Gab Chul; Jang, Yun-Jin; Ryeom, Hunkyu; Kim, Hye Jung; Shin, Kyung-Min; Park, Jun Seok; Choi, Gyu-Seog; Kim, See Hyung

    2015-09-01

    The value of diffusion-weighted imaging (DWI) for reliable differentiation between pathologic complete response (pCR) and residual tumor is still unclear. Recently, a few studies reported that histogram analysis can be helpful to monitor the therapeutic response in various cancer research. To investigate whether post-chemoradiotherapy (CRT) apparent diffusion coefficient (ADC) histogram analysis can be helpful to predict a pCR in locally advanced rectal cancer (LARC). Fifty patients who underwent preoperative CRT followed by surgery were enrolled in this retrospective study, non-pCR (n = 41) and pCR (n = 9), respectively. ADC histogram analysis encompassing the whole tumor was performed on two post-CRT ADC600 and ADC1000 (b factors 0, 600 vs. 0, 1000 s/mm(2)) maps. Mean, minimum, maximum, SD, mode, 10th, 25th, 50th, 75th, 90th percentile ADCs, skewness, and kurtosis were derived. Diagnostic performance for predicting pCR was evaluated and compared. On both maps, 10th and 25th ADCs showed better diagnostic performance than that using mean ADC. Tenth percentile ADCs revealed the best diagnostic performance on both ADC600 (AZ 0.841, sensitivity 100%, specificity 70.7%) and ADC1000 (AZ 0.821, sensitivity 77.8%, specificity 87.8%) maps. In comparison between 10th percentile and mean ADC, the specificity was significantly improved on both ADC600 (70.7% vs. 53.7%; P = 0.031) and ADC1000 (87.8% vs. 73.2%; P = 0.039) maps. Post-CRT ADC histogram analysis is helpful for predicting pCR in LARC, especially, in improving the specificity, compared with mean ADC. © The Foundation Acta Radiologica 2014.

  17. Sensitivity of future U.S. water shortages to socioeconomic and climate drivers: A case study in Georgia using an integrated human-earth system modeling framework

    DOE PAGES

    Scott, Michael J.; Daly, Don S.; Hejazi, Mohamad I.; ...

    2016-02-06

    Here, one of the most important interactions between humans and climate is in the demand and supply of water. Humans withdraw, use, and consume water and return waste water to the environment for a variety of socioeconomic purposes, including domestic, commercial, and industrial use, production of energy resources and cooling thermal-electric power plants, and growing food, fiber, and chemical feed stocks for human consumption. Uncertainties in the future human demand for water interact with future impacts of climatic change on water supplies to impinge on water management decisions at the international, national, regional, and local level, but until recently toolsmore » were not available to assess the uncertainties surrounding these decisions. This paper demonstrates the use of a multi-model framework in a structured sensitivity analysis to project and quantify the sensitivity of future deficits in surface water in the context of climate and socioeconomic change for all U.S. states and sub-basins. The framework treats all sources of water demand and supply consistently from the world to local level. The paper illustrates the capabilities of the framework with sample results for a river sub-basin in the U.S. state of Georgia.« less

  18. English-Medium Instruction and Intercultural Sensitivity: A Korean Case Study

    ERIC Educational Resources Information Center

    Kim, Jeongyeon; Choi, Jinsook; Tatar, Bradley

    2017-01-01

    This case study examined the reactions of local students to the diversity in student population. Specifically, it investigated how the local students' intercultural sensitivity to the international students is interrelated with their perception of the English-medium instruction (EMI) policy. The quantitative and qualitative analyses of the…

  19. DIETARY VITAMIN A ENHANCES SENSITIVITY OF THE LOCAL LYMPH NODE ASSAY

    EPA Science Inventory

    Murine assays such as the mouse ear swelling test (MEST) and the local lymph node assay (LLNA) are popular alternatives to guinea pig models for the identification of contact sensitizers, yet there has been concern over the effectiveness of these assays to detect weak and moderat...

  20. Analysis of TPA Pulsed-Laser-Induced Single-Event Latchup Sensitive-Area

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Peng; Sternberg, Andrew L.; Kozub, John A.

    Two-photon absorption (TPA) testing is employed to analyze the laser-induced latchup sensitive-volume (SV) of a specially designed test structure. This method takes into account the existence of an onset region in which the probability of triggering latchup transitions from zero to one as the laser pulse energy increases. This variability is attributed to pulse-to-pulse variability, uncertainty in measurement of the pulse energy, and variation in local carrier density and temperature. For each spatial position, the latchup probability associated with a given energy is calculated from multiple pulses. The latchup probability data are well-described by a Weibull distribution. The results showmore » that the area between p-n-p-n cell structures is more sensitive than the p+ and n+ source areas, and locations far from the well contacts are more sensitive than those near the contact region. The transition from low probability of latchup to high probability is more abrupt near the source contacts than it is for the surrounding areas.« less

  1. Analysis of TPA Pulsed-Laser-Induced Single-Event Latchup Sensitive-Area

    DOE PAGES

    Wang, Peng; Sternberg, Andrew L.; Kozub, John A.; ...

    2017-12-07

    Two-photon absorption (TPA) testing is employed to analyze the laser-induced latchup sensitive-volume (SV) of a specially designed test structure. This method takes into account the existence of an onset region in which the probability of triggering latchup transitions from zero to one as the laser pulse energy increases. This variability is attributed to pulse-to-pulse variability, uncertainty in measurement of the pulse energy, and variation in local carrier density and temperature. For each spatial position, the latchup probability associated with a given energy is calculated from multiple pulses. The latchup probability data are well-described by a Weibull distribution. The results showmore » that the area between p-n-p-n cell structures is more sensitive than the p+ and n+ source areas, and locations far from the well contacts are more sensitive than those near the contact region. The transition from low probability of latchup to high probability is more abrupt near the source contacts than it is for the surrounding areas.« less

  2. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Anal Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hodges, Joseph C., E-mail: joseph.hodges@utsouthwestern.edu; Beg, Muhammad S.; Das, Prajnan

    2014-07-15

    Purpose: To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. Methods and Materials: A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivitymore » analysis. Results: In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. Conclusions: In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.« less

  3. The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

    PubMed

    Hanna, T P; Shafiq, J; Delaney, G P; Vinod, S K; Thompson, S R; Barton, M B

    2018-02-01

    To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  4. Local adaptations and climate change: converging sensitivity of bud break in black spruce provenances.

    PubMed

    Rossi, Sergio

    2015-07-01

    Species with transcontinental distribution or spread over wide geographical regions develop populations with growth traits genetically adapted to the local climate. The aim of this study was to investigate the ecotypic sensitivity of bud break, a strong adaptive trait, to a changing environment. Six phenological phases of bud break were monitored daily on black spruce [Picea mariana (Mill.) BSP] seedlings submitted to different temperatures (12, 16 and 20 °C) and photoperiods (14, 18 and 22 h). Six provenances were tested in growth chambers, produced from seeds collected along the whole latitudinal range of the closed boreal forest in Quebec, Canada. Bud break lasted 13.3 days on average and occurred earlier in seedlings from colder sites. The annual temperature of the sites suitably tracked the clinal variation among ecotypes, providing a clear biological explanation for the environmental signal driving the adaptive divergence of populations to the local climate. Increasing temperature induced an earlier bud break according to a non-linear pattern with greater advancements observed between 12 and 16 °C. Photoperiod was significant, but sensitivity analysis indicated that its effect on bud break was marginal with respect to temperature. No interaction of provenance × treatment was observed, demonstrating an ecotypic convergence of the responses to both factors. Changes in the growing conditions could substantially modify the synchronization between bud phenology and climate, thus exposing the developing meristems of black spruce to frost damage. However, similar advancements of bud break could be expected in the different ecotypes subjected to warmer temperatures or longer day lengths.

  5. Comparison of the Sensitivity of Surface Downward Longwave Radiation to Changes in Water Vapor at Two High Elevation Sites

    NASA Technical Reports Server (NTRS)

    Chen, Yonghua; Naud, Catherine M.; Rangwala, Imtiaz; Landry, Christopher C.; Miller, James R.

    2014-01-01

    Among the potential reasons for enhanced warming rates in many high elevation regions is the nonlinear relationship between surface downward longwave radiation (DLR) and specific humidity (q). In this study we use ground-based observations at two neighboring high elevation sites in Southwestern Colorado that have different local topography and are 1.3 kilometers apart horizontally and 348 meters vertically. We examine the spatial consistency of the sensitivities (partial derivatives) of DLR with respect to changes in q, and the sensitivities are obtained from the Jacobian matrix of a neural network analysis. Although the relationship between DLR and q is the same at both sites, the sensitivities are higher when q is smaller, which occurs more frequently at the higher elevation site. There is a distinct hourly distribution in the sensitivities at both sites especially for high sensitivity cases, although the range is greater at the lower elevation site. The hourly distribution of the sensitivities relates to that of q. Under clear skies during daytime, q is similar between the two sites, however under cloudy skies or at night, it is not. This means that the DLR-q sensitivities are similar at the two sites during daytime but not at night, and care must be exercised when using data from one site to infer the impact of water vapor feedbacks at another site, particularly at night. Our analysis suggests that care should be exercised when using the lapse rate adjustment to infill high frequency data in a complex topographical region, particularly when one of the stations is subject to cold air pooling as found here.

  6. Emulation of simulations of atmospheric dispersion at Fukushima for Sobol' sensitivity analysis

    NASA Astrophysics Data System (ADS)

    Girard, Sylvain; Korsakissok, Irène; Mallet, Vivien

    2015-04-01

    Polyphemus/Polair3D, from which derives IRSN's operational model ldX, was used to simulate the atmospheric dispersion at the Japan scale of radionuclides after the Fukushima disaster. A previous study with the screening method of Morris had shown that - The sensitivities depend a lot on the considered output; - Only a few of the inputs are non-influential on all considered outputs; - Most influential inputs have either non-linear effects or are interacting. These preliminary results called for a more detailed sensitivity analysis, especially regarding the characterization of interactions. The method of Sobol' allows for a precise evaluation of interactions but requires large simulation samples. Gaussian process emulators for each considered outputs were built in order to relieve this computational burden. Globally aggregated outputs proved to be easy to emulate with high accuracy, and associated Sobol' indices are in broad agreement with previous results obtained with the Morris method. More localized outputs, such as temporal averages of gamma dose rates at measurement stations, resulted in lesser emulator performances: tests simulations could not satisfactorily be reproduced by some emulators. These outputs are of special interest because they can be compared to available observations, for instance for calibration purpose. A thorough inspection of prediction residuals hinted that the model response to wind perturbations often behaved in very distinct regimes relatively to some thresholds. Complementing the initial sample with wind perturbations set to the extreme values allowed for sensible improvement of some of the emulators while other remained too unreliable to be used in a sensitivity analysis. Adaptive sampling or regime-wise emulation could be tried to circumvent this issue. Sobol' indices for local outputs revealed interesting patterns, mostly dominated by the winds, with very high interactions. The emulators will be useful for subsequent studies. Indeed, our goal is to characterize the model output uncertainty but too little information is available about input uncertainties. Hence, calibration of the input distributions with observation and a Bayesian approach seem necessary. This would probably involve methods such as MCMC which would be intractable without emulators.

  7. Systematic parameter estimation and sensitivity analysis using a multidimensional PEMFC model coupled with DAKOTA.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Chao Yang; Luo, Gang; Jiang, Fangming

    2010-05-01

    Current computational models for proton exchange membrane fuel cells (PEMFCs) include a large number of parameters such as boundary conditions, material properties, and numerous parameters used in sub-models for membrane transport, two-phase flow and electrochemistry. In order to successfully use a computational PEMFC model in design and optimization, it is important to identify critical parameters under a wide variety of operating conditions, such as relative humidity, current load, temperature, etc. Moreover, when experimental data is available in the form of polarization curves or local distribution of current and reactant/product species (e.g., O2, H2O concentrations), critical parameters can be estimated inmore » order to enable the model to better fit the data. Sensitivity analysis and parameter estimation are typically performed using manual adjustment of parameters, which is also common in parameter studies. We present work to demonstrate a systematic approach based on using a widely available toolkit developed at Sandia called DAKOTA that supports many kinds of design studies, such as sensitivity analysis as well as optimization and uncertainty quantification. In the present work, we couple a multidimensional PEMFC model (which is being developed, tested and later validated in a joint effort by a team from Penn State Univ. and Sandia National Laboratories) with DAKOTA through the mapping of model parameters to system responses. Using this interface, we demonstrate the efficiency of performing simple parameter studies as well as identifying critical parameters using sensitivity analysis. Finally, we show examples of optimization and parameter estimation using the automated capability in DAKOTA.« less

  8. Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qu, Xuanlu M.; Louie, Alexander V.; Ashman, Jonathan

    Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon ofmore » 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.« less

  9. Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq)-A Method for High-Throughput Analysis of Differentially Methylated CCGG Sites in Plants with Large Genomes.

    PubMed

    Chwialkowska, Karolina; Korotko, Urszula; Kosinska, Joanna; Szarejko, Iwona; Kwasniewski, Miroslaw

    2017-01-01

    Epigenetic mechanisms, including histone modifications and DNA methylation, mutually regulate chromatin structure, maintain genome integrity, and affect gene expression and transposon mobility. Variations in DNA methylation within plant populations, as well as methylation in response to internal and external factors, are of increasing interest, especially in the crop research field. Methylation Sensitive Amplification Polymorphism (MSAP) is one of the most commonly used methods for assessing DNA methylation changes in plants. This method involves gel-based visualization of PCR fragments from selectively amplified DNA that are cleaved using methylation-sensitive restriction enzymes. In this study, we developed and validated a new method based on the conventional MSAP approach called Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq). We improved the MSAP-based approach by replacing the conventional separation of amplicons on polyacrylamide gels with direct, high-throughput sequencing using Next Generation Sequencing (NGS) and automated data analysis. MSAP-Seq allows for global sequence-based identification of changes in DNA methylation. This technique was validated in Hordeum vulgare . However, MSAP-Seq can be straightforwardly implemented in different plant species, including crops with large, complex and highly repetitive genomes. The incorporation of high-throughput sequencing into MSAP-Seq enables parallel and direct analysis of DNA methylation in hundreds of thousands of sites across the genome. MSAP-Seq provides direct genomic localization of changes and enables quantitative evaluation. We have shown that the MSAP-Seq method specifically targets gene-containing regions and that a single analysis can cover three-quarters of all genes in large genomes. Moreover, MSAP-Seq's simplicity, cost effectiveness, and high-multiplexing capability make this method highly affordable. Therefore, MSAP-Seq can be used for DNA methylation analysis in crop plants with large and complex genomes.

  10. Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq)—A Method for High-Throughput Analysis of Differentially Methylated CCGG Sites in Plants with Large Genomes

    PubMed Central

    Chwialkowska, Karolina; Korotko, Urszula; Kosinska, Joanna; Szarejko, Iwona; Kwasniewski, Miroslaw

    2017-01-01

    Epigenetic mechanisms, including histone modifications and DNA methylation, mutually regulate chromatin structure, maintain genome integrity, and affect gene expression and transposon mobility. Variations in DNA methylation within plant populations, as well as methylation in response to internal and external factors, are of increasing interest, especially in the crop research field. Methylation Sensitive Amplification Polymorphism (MSAP) is one of the most commonly used methods for assessing DNA methylation changes in plants. This method involves gel-based visualization of PCR fragments from selectively amplified DNA that are cleaved using methylation-sensitive restriction enzymes. In this study, we developed and validated a new method based on the conventional MSAP approach called Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq). We improved the MSAP-based approach by replacing the conventional separation of amplicons on polyacrylamide gels with direct, high-throughput sequencing using Next Generation Sequencing (NGS) and automated data analysis. MSAP-Seq allows for global sequence-based identification of changes in DNA methylation. This technique was validated in Hordeum vulgare. However, MSAP-Seq can be straightforwardly implemented in different plant species, including crops with large, complex and highly repetitive genomes. The incorporation of high-throughput sequencing into MSAP-Seq enables parallel and direct analysis of DNA methylation in hundreds of thousands of sites across the genome. MSAP-Seq provides direct genomic localization of changes and enables quantitative evaluation. We have shown that the MSAP-Seq method specifically targets gene-containing regions and that a single analysis can cover three-quarters of all genes in large genomes. Moreover, MSAP-Seq's simplicity, cost effectiveness, and high-multiplexing capability make this method highly affordable. Therefore, MSAP-Seq can be used for DNA methylation analysis in crop plants with large and complex genomes. PMID:29250096

  11. Raman and photothermal spectroscopies for explosive detection

    NASA Astrophysics Data System (ADS)

    Finot, Eric; Brulé, Thibault; Rai, Padmnabh; Griffart, Aurélien; Bouhélier, Alexandre; Thundat, Thomas

    2013-06-01

    Detection of explosive residues using portable devices for locating landmine and terrorist weapons must sat- isfy the application criteria of high reproducibility, specificity, sensitivity and fast response time. Vibrational spectroscopies such as Raman and infrared spectroscopies have demonstrated their potential to distinguish the members of the chemical family of more than 30 explosive materials. The characteristic chemical fingerprints in the spectra of these explosives stem from the unique bond structure of each compound. However, these spectroscopies, developed in the early sixties, suffer from a poor sensitivity. On the contrary, MEMS-based chemical sensors have shown to have very high sensitivity lowering the detection limit down to less than 1 picogram, (namely 10 part per trillion) using sensor platforms based on microcantilevers, plasmonics, or surface acoustic waves. The minimum amount of molecules that can be detected depends actually on the transducer size. The selectivity in MEMS sensors is usually realized using chemical modification of the active surface. However, the lack of sufficiently selective receptors that can be immobilized on MEMS sensors remains one of the most critical issues. Microcantilever based sensors offer an excellent opportunity to combine both the infrared photothermal spectroscopy in their static mode and the unique mass sensitivity in their dynamic mode. Optical sensors based on localized plasmon resonance can also take up the challenge of addressing the selectivity by monitoring the Surface Enhanced Raman spectrum down to few molecules. The operating conditions of these promising localized spectroscopies will be discussed in terms of reliability, compactness, data analysis and potential for mass deployment.

  12. Local Atopy in Childhood Adenotonsillar Hypertrophy.

    PubMed

    Cho, Kyu-Sup; Kim, Seong Heon; Hong, Sung-Lyong; Lee, Jaeyoung; Mun, Sue Jean; Roh, Young Eun; Kim, Young Mi; Kim, Hye-Young

    2018-05-01

    Background Although the cause of adenotonsillar hypertrophy remains unknown, some studies have shown that allergy may be a risk factor. Purpose This study determined the levels of allergen-specific immunoglobulin E (sIgE) in the adenotonsillar tissues of children with adenotonsillar hypertrophy and evaluated the clinical significance of local atopy in adenotonsillar tissues. Methods We measured 21 types of specific immunoglobulin E in the serum and adenotonsillar tissues of 102 children with adenotonsillar hypertrophy and compared the sensitization patterns of the serum and local tissues. The patients were divided into three groups-atopy, local atopy, and nonatopy-according to the sensitization of serum and adenotonsillar tissues, and the clinical symptoms among the groups were analyzed. Results Seventy-two (70.6%) children with adenotonsillar hypertrophy were sensitized to more than one allergen in the serum and/or adenotonsillar tissue. Thirty (29.4%) children had no IgE positivity to any allergen in both serum and adenotonsillar tissues. Fifty-five (53.9%) were sensitized to at least one allergen in the serum. Seventy (68.6%) were sensitized to at least one allergen in the adenotonsillar tissue. Seventeen (36.2%) of 47 children with specific immunoglobulin E-negative serum had specific immunoglobulin E-positive adenotonsillar tissues. The rate of specific immunoglobulin E was significantly higher in local tissues than in serum. The rate of inhalant allergen specific immunoglobulin E was significantly higher in the adenoids than in the tonsils. However, the rate of food allergen specific immunoglobulin E was significantly higher in the tonsils than adenoids. The lifetime prevalence of asthma and allergic rhinitis, recent symptoms or treatment of allergic rhinitis, and severity of nasal symptoms (rhinorrhea, sneezing, and nasal itching) were significantly higher in children with local atopy than with nonatopy. Conclusions These results confirm that allergic response may be a risk factor for adenotonsillar hypertrophy. Local allergic inflammation may play an important role in childhood adenotonsillar hypertrophy, and local atopy in adenotonsillar tissues can cause respiratory allergic symptoms in children.

  13. Parametric imaging of experimentally simulated Wolff-Parkinson-White syndrome conduction abnormalities in dogs: a concise communication

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Weismueller, P.H.; Henze, E.; Adam, W.E.

    1986-01-01

    In order to test the diagnostic potential of phase analysis of radionuclide ventriculography (RNV) for localizing accessory bundles in Wolff-Parkinson-White (WPW) syndrome, 24 experimental runs were performed in three open chest instrumented dogs. After a baseline study, WPW syndrome was simulated by stimulation at seven different sites around the base of the ventricles, and RNV's were obtained. Subsequent data processing including Fourier transformation allowed the localization of the site of the first inward motion of the ventricles by an isophasic wave display. In sinus rhythm, the septum contracted first. During ectopic premature ventricular stimulation by triggering the atrial signal, themore » phase scan was altered only when the stimulus was applied earlier than 20 ms before the expected QRS complex during sinus rhythm. During stimulation with fixed frequency, only the left lateral positions of the premature stimulation were detected by phase analysis with a sensitivity of 86%. Neither the antero- or posteroseptal nor the right ventricular premature contraction pattern could be exactly localized.« less

  14. Hydrologic sensitivity of headwater catchments to climate and landscape variability

    NASA Astrophysics Data System (ADS)

    Kelleher, Christa; Wagener, Thorsten; McGlynn, Brian; Nippgen, Fabian; Jencso, Kelsey

    2013-04-01

    Headwater streams cumulatively represent an extensive portion of the United States stream network, yet remain largely unmonitored and unmapped. As such, we have limited understanding of how these systems will respond to change, knowledge that is important for preserving these unique ecosystems, the services they provide, and the biodiversity they support. We compare responses across five adjacent headwater catchments located in Tenderfoot Creek Experimental Forest in Montana, USA, to understand how local differences may affect the sensitivity of headwaters to change. We utilize global, variance-based sensitivity analysis to understand which aspects of the physical system (e.g., vegetation, topography, geology) control the variability in hydrologic behavior across these basins, and how this varies as a function of time (and therefore climate). Basin fluxes and storages, including evapotranspiration, snow water equivalent and melt, soil moisture and streamflow, are simulated using the Distributed Hydrology-Vegetation-Soil Model (DHSVM). Sensitivity analysis is applied to quantify the importance of different physical parameters to the spatial and temporal variability of different water balance components, allowing us to map similarities and differences in these controls through space and time. Our results show how catchment influences on fluxes vary across seasons (thus providing insight into transferability of knowledge in time), and how they vary across catchments with different physical characteristics (providing insight into transferability in space).

  15. Defining the consequences of genetic variation on a proteome–wide scale

    PubMed Central

    Chick, Joel M.; Munger, Steven C.; Simecek, Petr; Huttlin, Edward L.; Choi, Kwangbom; Gatti, Daniel M.; Raghupathy, Narayanan; Svenson, Karen L.; Churchill, Gary A.; Gygi, Steven P.

    2016-01-01

    Genetic variation modulates protein expression through both transcriptional and post-transcriptional mechanisms. To characterize the consequences of natural genetic diversity on the proteome, here we combine a multiplexed, mass spectrometry-based method for protein quantification with an emerging outbred mouse model containing extensive genetic variation from eight inbred founder strains. By measuring genome-wide transcript and protein expression in livers from 192 Diversity outbred mice, we identify 2,866 protein quantitative trait loci (pQTL) with twice as many local as distant genetic variants. These data support distinct transcriptional and post-transcriptional models underlying the observed pQTL effects. Using a sensitive approach to mediation analysis, we often identified a second protein or transcript as the causal mediator of distant pQTL. Our analysis reveals an extensive network of direct protein–protein interactions. Finally, we show that local genotype can provide accurate predictions of protein abundance in an independent cohort of collaborative cross mice. PMID:27309819

  16. Automated feature extraction in color retinal images by a model based approach.

    PubMed

    Li, Huiqi; Chutatape, Opas

    2004-02-01

    Color retinal photography is an important tool to detect the evidence of various eye diseases. Novel methods to extract the main features in color retinal images have been developed in this paper. Principal component analysis is employed to locate optic disk; A modified active shape model is proposed in the shape detection of optic disk; A fundus coordinate system is established to provide a better description of the features in the retinal images; An approach to detect exudates by the combined region growing and edge detection is proposed. The success rates of disk localization, disk boundary detection, and fovea localization are 99%, 94%, and 100%, respectively. The sensitivity and specificity of exudate detection are 100% and 71%, correspondingly. The success of the proposed algorithms can be attributed to the utilization of the model-based methods. The detection and analysis could be applied to automatic mass screening and diagnosis of the retinal diseases.

  17. Application of uncertainty and sensitivity analysis to the air quality SHERPA modelling tool

    NASA Astrophysics Data System (ADS)

    Pisoni, E.; Albrecht, D.; Mara, T. A.; Rosati, R.; Tarantola, S.; Thunis, P.

    2018-06-01

    Air quality has significantly improved in Europe over the past few decades. Nonetheless we still find high concentrations in measurements mainly in specific regions or cities. This dimensional shift, from EU-wide to hot-spot exceedances, calls for a novel approach to regional air quality management (to complement EU-wide existing policies). The SHERPA (Screening for High Emission Reduction Potentials on Air quality) modelling tool was developed in this context. It provides an additional tool to be used in support to regional/local decision makers responsible for the design of air quality plans. It is therefore important to evaluate the quality of the SHERPA model, and its behavior in the face of various kinds of uncertainty. Uncertainty and sensitivity analysis techniques can be used for this purpose. They both reveal the links between assumptions and forecasts, help in-model simplification and may highlight unexpected relationships between inputs and outputs. Thus, a policy steered SHERPA module - predicting air quality improvement linked to emission reduction scenarios - was evaluated by means of (1) uncertainty analysis (UA) to quantify uncertainty in the model output, and (2) by sensitivity analysis (SA) to identify the most influential input sources of this uncertainty. The results of this study provide relevant information about the key variables driving the SHERPA output uncertainty, and advise policy-makers and modellers where to place their efforts for an improved decision-making process.

  18. Observation of Anderson localization in disordered nanophotonic structures

    NASA Astrophysics Data System (ADS)

    Sheinfux, Hanan Herzig; Lumer, Yaakov; Ankonina, Guy; Genack, Azriel Z.; Bartal, Guy; Segev, Mordechai

    2017-06-01

    Anderson localization is an interference effect crucial to the understanding of waves in disordered media. However, localization is expected to become negligible when the features of the disordered structure are much smaller than the wavelength. Here we experimentally demonstrate the localization of light in a disordered dielectric multilayer with an average layer thickness of 15 nanometers, deep into the subwavelength regime. We observe strong disorder-induced reflections that show that the interplay of localization and evanescence can lead to a substantial decrease in transmission, or the opposite feature of enhanced transmission. This deep-subwavelength Anderson localization exhibits extreme sensitivity: Varying the thickness of a single layer by 2 nanometers changes the reflection appreciably. This sensitivity, approaching the atomic scale, holds the promise of extreme subwavelength sensing.

  19. Image Description with Local Patterns: An Application to Face Recognition

    NASA Astrophysics Data System (ADS)

    Zhou, Wei; Ahrary, Alireza; Kamata, Sei-Ichiro

    In this paper, we propose a novel approach for presenting the local features of digital image using 1D Local Patterns by Multi-Scans (1DLPMS). We also consider the extentions and simplifications of the proposed approach into facial images analysis. The proposed approach consists of three steps. At the first step, the gray values of pixels in image are represented as a vector giving the local neighborhood intensity distrubutions of the pixels. Then, multi-scans are applied to capture different spatial information on the image with advantage of less computation than other traditional ways, such as Local Binary Patterns (LBP). The second step is encoding the local features based on different encoding rules using 1D local patterns. This transformation is expected to be less sensitive to illumination variations besides preserving the appearance of images embedded in the original gray scale. At the final step, Grouped 1D Local Patterns by Multi-Scans (G1DLPMS) is applied to make the proposed approach computationally simpler and easy to extend. Next, we further formulate boosted algorithm to extract the most discriminant local features. The evaluated results demonstrate that the proposed approach outperforms the conventional approaches in terms of accuracy in applications of face recognition, gender estimation and facial expression.

  20. Taking the Next Step: Using Water Quality Data in a Decision Support System for County, State, and Federal Land Managers

    NASA Astrophysics Data System (ADS)

    Raby, K. S.; Williams, M. W.

    2004-12-01

    Each passing year amplifies the demands placed on communities across the US in terms of population growth, increased tourism, and stresses resulting from escalated use. The conflicting concerns of recreational users, local citizens, environmentalists, and traditional economic interests cause land managers to contend with controversial decisions regarding development and protection of watersheds. Local history and culture, politics, economic goals, and science are all influential factors in land use decision making. Here we report on a scientific study to determine the sensitivity of alpine areas, and the adaptation of this study into a decision support framework. We use water quality data as an indicator of ecosystem health across a variety of alpine and subalpine landscapes, and input this information into a spatially-based decision support tool that planners can use to make informed land use decisions. We develop this tool in a case study in San Juan County, Colorado, a site chosen because its largest town, Silverton, is a small mountain community experiencing a recent surge in tourism and development, and its fragile high elevation locale makes it more sensitive to environmental changes. Extensive field surveys were conducted in priority drainages throughout the county to map the spatial distribution and aerial extent of landscape types during the summers of 2003 and 2004. Surface water samples were collected and analyzed for inorganic and organic solutes, and water quality values were associated with different land covers to enable sensitivity analysis at the landscape scale. Water quality results for each watershed were entered into a module linked to a geographic information system (GIS), which displays maps of sensitive areas based on criteria selected by the user. The decision support system initially incorporates two major water quality parameters: acid neutralizing capacity (ANC) and nitrate (NO3-) concentration, and several categories of sensitivity were created based on ANC and NO3- levels (e.g., pristine, slightly sensitive, moderately sensitive, highly sensitive, sensitive but unimpacted, disturbance impacted). We based threshold concentrations for these water quality parameters on first principles developed at the Niwot Ridge LTER site. Additional parameters such as specific conductance, base cation concentration, sulfate concentration, and dissolved organic carbon concentration may be added for a particular landscape type. Superimposed on this categorization, federal, state, and county planners are able to make decisions about the degree of potential impairment or enhancement produced by a particular project, or the maximum level of acceptable impairment to a particular area. Because water quality parameters are correlated with landscape types, the model returns a map of the watershed, partitioned by landscape type, presenting the sensitivity level of each area. This format provides land use managers with spatial criteria for project implementation.

  1. Using Real-time Event Tracking Sensitivity Analysis to Overcome Sensor Measurement Uncertainties of Geo-Information Management in Drilling Disasters

    NASA Astrophysics Data System (ADS)

    Tavakoli, S.; Poslad, S.; Fruhwirth, R.; Winter, M.

    2012-04-01

    This paper introduces an application of a novel EventTracker platform for instantaneous Sensitivity Analysis (SA) of large scale real-time geo-information. Earth disaster management systems demand high quality information to aid a quick and timely response to their evolving environments. The idea behind the proposed EventTracker platform is the assumption that modern information management systems are able to capture data in real-time and have the technological flexibility to adjust their services to work with specific sources of data/information. However, to assure this adaptation in real time, the online data should be collected, interpreted, and translated into corrective actions in a concise and timely manner. This can hardly be handled by existing sensitivity analysis methods because they rely on historical data and lazy processing algorithms. In event-driven systems, the effect of system inputs on its state is of value, as events could cause this state to change. This 'event triggering' situation underpins the logic of the proposed approach. Event tracking sensitivity analysis method describes the system variables and states as a collection of events. The higher the occurrence of an input variable during the trigger of event, the greater its potential impact will be on the final analysis of the system state. Experiments were designed to compare the proposed event tracking sensitivity analysis with existing Entropy-based sensitivity analysis methods. The results have shown a 10% improvement in a computational efficiency with no compromise for accuracy. It has also shown that the computational time to perform the sensitivity analysis is 0.5% of the time required compared to using the Entropy-based method. The proposed method has been applied to real world data in the context of preventing emerging crises at drilling rigs. One of the major purposes of such rigs is to drill boreholes to explore oil or gas reservoirs with the final scope of recovering the content of such reservoirs; both in onshore regions as well as in offshore regions. Drilling a well is always guided by technical, economic and security constraints to prevent crew, equipment and environment from injury, damage and pollution. Although risk assessment and local practice provides a high degree of security, uncertainty is given by the behaviour of the formation which may cause crucial situations at the rig. To overcome such uncertainties real-time sensor measurements form a base to predict and thus prevent such crises, the proposed method supports the identification of the data necessary for that.

  2. The status of BAT detector

    NASA Astrophysics Data System (ADS)

    Lien, Amy; Markwardt, Craig B.; Krimm, Hans Albert; Barthelmy, Scott D.; Cenko, Bradley

    2018-01-01

    We will present the current status of the Swift/BAT detector. In particular, we will report the updated detector gain calibration, the number of enable detectors, and the global bad time intervals with potential calibration issues. We will also summarize the results of the yearly BAT calibration using the Crab nebula. Finally, we will discuss the effects on the BAT survey, such as the sensitivity, localization, and spectral analysis, due to the changes in detector status.

  3. Simultaneous Aerodynamic and Structural Design Optimization (SASDO) for a 3-D Wing

    NASA Technical Reports Server (NTRS)

    Gumbert, Clyde R.; Hou, Gene J.-W.; Newman, Perry A.

    2001-01-01

    The formulation and implementation of an optimization method called Simultaneous Aerodynamic and Structural Design Optimization (SASDO) is shown as an extension of the Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) method. It is extended by the inclusion of structure element sizing parameters as design variables and Finite Element Method (FEM) analysis responses as constraints. The method aims to reduce the computational expense. incurred in performing shape and sizing optimization using state-of-the-art Computational Fluid Dynamics (CFD) flow analysis, FEM structural analysis and sensitivity analysis tools. SASDO is applied to a simple. isolated, 3-D wing in inviscid flow. Results show that the method finds the saine local optimum as a conventional optimization method with some reduction in the computational cost and without significant modifications; to the analysis tools.

  4. Temporal model of an optically pumped co-doped solid state laser

    NASA Technical Reports Server (NTRS)

    Wangler, T. G.; Swetits, J. J.; Buoncristiani, A. M.

    1993-01-01

    Currently, research is being conducted on the optical properties of materials associated with the development of solid state lasers in the two micron region. In support of this effort, a mathematical model describing the energy transfer in a holmium laser sensitized with thulium is developed. In this paper, we establish some qualitative properties of the solution of the model, such as non-negativity, boundedness, and integrability. A local stability analysis is then performed from which conditions for asymptotic stability are attained. Finally, we report on our numerical analysis of the system and how it compares with experimental results.

  5. Closed-Loop Estimation of Retinal Network Sensitivity by Local Empirical Linearization

    PubMed Central

    2018-01-01

    Abstract Understanding how sensory systems process information depends crucially on identifying which features of the stimulus drive the response of sensory neurons, and which ones leave their response invariant. This task is made difficult by the many nonlinearities that shape sensory processing. Here, we present a novel perturbative approach to understand information processing by sensory neurons, where we linearize their collective response locally in stimulus space. We added small perturbations to reference stimuli and tested if they triggered visible changes in the responses, adapting their amplitude according to the previous responses with closed-loop experiments. We developed a local linear model that accurately predicts the sensitivity of the neural responses to these perturbations. Applying this approach to the rat retina, we estimated the optimal performance of a neural decoder and showed that the nonlinear sensitivity of the retina is consistent with an efficient encoding of stimulus information. Our approach can be used to characterize experimentally the sensitivity of neural systems to external stimuli locally, quantify experimentally the capacity of neural networks to encode sensory information, and relate their activity to behavior. PMID:29379871

  6. A Chain of Modeling Tools For Gas and Aqueous Phase Chemstry

    NASA Astrophysics Data System (ADS)

    Audiffren, N.; Djouad, R.; Sportisse, B.

    Atmospheric chemistry is characterized by the use of large set of chemical species and reactions. Handling with the set of data required for the definition of the model is a quite difficult task. We prsent in this short article a preprocessor for diphasic models (gas phase and aqueous phase in cloud droplets) named SPACK. The main interest of SPACK is the automatic generation of lumped species related to fast equilibria. We also developped a linear tangent model using the automatic differentiation tool named ODYSSEE in order to perform a sensitivity analysis of an atmospheric multi- phase mechanism based on RADM2 kinetic scheme.Local sensitivity coefficients are computed for two different scenarii. We focus in this study on the sensitivity of the ozone,NOx,HOx, system with respect to some aqueous phase reactions and we inves- tigate the influence of the reduction in the photolysis rates in the area below the cloud region.

  7. Bifocal Fresnel Lens Based on the Polarization-Sensitive Metasurface

    NASA Astrophysics Data System (ADS)

    Markovich, Hen; Filonov, Dmitrii; Shishkin, Ivan; Ginzburg, Pavel

    2018-05-01

    Thin structured surfaces allow flexible control over propagation of electromagnetic waves. Focusing and polarization state analysis are among functions, required for effective manipulation of radiation. Here a polarization sensitive Fresnel zone plate lens is proposed and experimentally demonstrated for GHz spectral range. Two spatially separated focal spots for orthogonal polarizations are obtained by designing metasurface pattern, made of overlapping tightly packed cross and rod shaped antennas with a strong polarization selectivity. Optimized subwavelength pattern allows multiplexing two different lenses with low polarization crosstalk on the same substrate and provides a control over focal spots of the lens only by changing of the polarization state of the incident wave. More than a wavelength separation between the focal spots was demonstrated for a broad spectral range, covering half a decade in frequency. The proposed concept could be straightforwardly extended for THz and visible spectra, where polarization-sensitive elements utilize localized plasmon resonance phenomenon.

  8. Specific conditions of distress in the dental situation.

    PubMed

    Hentschel, U; Allander, L; Winholt, A S

    1977-01-01

    The general feeling of distress in the dental situation has been studied in 60 female dental patients and correlated to the following variables: Experimentally evaluated sensitivity to pain, self-rating and the dentist's rating of sensitivity to pain, the pain-threshold value in the teeth, the need of local anesthesia, extraversion-introversion, neuroticism, and some percept-genetic psychological measures of adaptive behavior. The subjects have also answered a questionnaire for grading their distress in regard to different aspects of the treatment-situation, which were combined into eight groups using factor analysis and then correlated to the general distress. The variables having a significant relation to distress in the dental situation were: the dentist's rating of the patient's sensitivity, the need of anesthesia, four groups of treatment-components and two of the percept-genetic measures. There was also a certain relation to the pain threshold in the teeth.

  9. Evaluation of a toxicogenomic approach to the local lymph node assay (LLNA).

    PubMed

    Boverhof, Darrell R; Gollapudi, B Bhaskar; Hotchkiss, Jon A; Osterloh-Quiroz, Mandy; Woolhiser, Michael R

    2009-02-01

    Genomic technologies have the potential to enhance and complement existing toxicology endpoints; however, assessment of these approaches requires a systematic evaluation including a robust experimental design with genomic endpoints anchored to traditional toxicology endpoints. The present study was conducted to assess the sensitivity of genomic responses when compared with the traditional local lymph node assay (LLNA) endpoint of lymph node cell proliferation and to evaluate the responses for their ability to provide insights into mode of action. Female BALB/c mice were treated with the sensitizer trimellitic anhydride (TMA), following the standard LLNA dosing regimen, at doses of 0.1, 1, or 10% and traditional tritiated thymidine ((3)HTdR) incorporation and gene expression responses were monitored in the auricular lymph nodes. Additional mice dosed with either vehicle or 10% TMA and sacrificed on day 4 or 10, were also included to examine temporal effects on gene expression. Analysis of (3)HTdR incorporation revealed TMA-induced stimulation indices of 2.8, 22.9, and 61.0 relative to vehicle with an EC(3) of 0.11%. Examination of the dose-response gene expression responses identified 9, 833, and 2122 differentially expressed genes relative to vehicle for the 0.1, 1, and 10% TMA dose groups, respectively. Calculation of EC(3) values for differentially expressed genes did not identify a response that was more sensitive than the (3)HTdR value, although a number of genes displayed comparable sensitivity. Examination of temporal responses revealed 1760, 1870, and 953 differentially expressed genes at the 4-, 6-, and 10-day time points respectively. Functional analysis revealed many responses displayed dose- and time-specific induction patterns within the functional categories of cellular proliferation and immune response, including numerous immunoglobin genes which were highly induced at the day 10 time point. Overall, these experiments have systematically illustrated the potential utility of genomic endpoints to enhance the LLNA and support further exploration of this approach through examination of a more diverse array of chemicals.

  10. Moving beyond 'rates, roads and rubbish': How do local governments make choices about healthy public policy to prevent obesity?

    PubMed Central

    Allender, Steven; Gleeson, Erin; Crammond, Brad; Sacks, Gary; Lawrence, Mark; Peeters, Anna; Loff, Bebe; Swinburn, Boyd

    2009-01-01

    While the causes of obesity are well known traditional education and treatment strategies do not appear to be making an impact. One solution as part of a broader complimentary set of strategies may be regulatory intervention at local government level to create environments for healthy nutrition and increased physical activity. Semi structured interviews were conducted with representatives of local government in Australia. Factors most likely to facilitate policy change were those supported by external funding, developed from an evidence base and sensitive to community and market forces. Barriers to change included a perceived or real lack of power to make change and the complexity of the legislative framework. The development of a systematic evidence base to provide clear feedback on the size and scope of the obesity epidemic at a local level, coupled with cost benefit analysis for any potential regulatory intervention, are crucial to developing a regulatory environment which creates the physical and social environment required to prevent obesity. PMID:19698170

  11. Accurate Sound Localization in Reverberant Environments is Mediated by Robust Encoding of Spatial Cues in the Auditory Midbrain

    PubMed Central

    Devore, Sasha; Ihlefeld, Antje; Hancock, Kenneth; Shinn-Cunningham, Barbara; Delgutte, Bertrand

    2009-01-01

    In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener’s ears, distorting the spatial cues for sound localization. Yet, human listeners have little difficulty localizing sounds in most settings. Because reverberant energy builds up over time, the source location is represented relatively faithfully during the early portion of a sound, but this representation becomes increasingly degraded later in the stimulus. We show that the directional sensitivity of single neurons in the auditory midbrain of anesthetized cats follows a similar time course, although onset dominance in temporal response patterns results in more robust directional sensitivity than expected, suggesting a simple mechanism for improving directional sensitivity in reverberation. In parallel behavioral experiments, we demonstrate that human lateralization judgments are consistent with predictions from a population rate model decoding the observed midbrain responses, suggesting a subcortical origin for robust sound localization in reverberant environments. PMID:19376072

  12. Allergic contact dermatitis from ethyl chloride and benzocaine.

    PubMed

    Carazo, Juan Luis Anguita; Morera, Blanca Sáenz de San Pedro; Colom, Luis Palacios; Gálvez Lozano, José Manuel

    2009-01-01

    Ethyl chloride (EC) or chloroethane (C2H5Cl) is a volatile halogenated hydrocarbon. Reports of contact sensitivity to this gas are infrequent considering its widespread use as a local anesthetic, and it may have a relatively low sensitization potential. Benzocaine is another local anesthetic derivative of the ethyl ester of para-aminobenzoic acid, previously reported as a causative agent of delayed hypersensitivity reactions. We present a patient who developed a generalized itching dermatitis after the application of a medical aerosol containing EC, as well as facial angioedema and tongue swelling after the local application of benzocaine. Patch-test results were positive for EC "as is" (++), benzocaine 5% in petrolatum (++), and caine mix (+++) at 96 hours (day 4). The possibility of cross-sensitization between both drugs would not have been chemically plausible. We report the first published clinical case of contact allergic dermatitis from two chemically unrelated local anesthetics (EC and benzocaine) in the same patient.

  13. A transfer matrix approach to vibration localization in mistuned blade assemblies

    NASA Technical Reports Server (NTRS)

    Ottarson, Gisli; Pierre, Chritophe

    1993-01-01

    A study of mode localization in mistuned bladed disks is performed using transfer matrices. The transfer matrix approach yields the free response of a general, mono-coupled, perfectly cyclic assembly in closed form. A mistuned structure is represented by random transfer matrices, and the expansion of these matrices in terms of the small mistuning parameter leads to the definition of a measure of sensitivity to mistuning. An approximation of the localization factor, the spatially averaged rate of exponential attenuation per blade-disk sector, is obtained through perturbation techniques in the limits of high and low sensitivity. The methodology is applied to a common model of a bladed disk and the results verified by Monte Carlo simulations. The easily calculated sensitivity measure may prove to be a valuable design tool due to its system-independent quantification of mistuning effects such as mode localization.

  14. Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

    PubMed

    Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

    2018-04-01

    It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

  15. ctDNA Determination of EGFR Mutation Status in European and Japanese Patients with Advanced NSCLC: The ASSESS Study.

    PubMed

    Reck, Martin; Hagiwara, Koichi; Han, Baohui; Tjulandin, Sergei; Grohé, Christian; Yokoi, Takashi; Morabito, Alessandro; Novello, Silvia; Arriola, Edurne; Molinier, Olivier; McCormack, Rose; Ratcliffe, Marianne; Normanno, Nicola

    2016-10-01

    To offer patients with EGFR mutation-positive advanced NSCLC appropriate EGFR tyrosine kinase inhibitor treatment, mutation testing of tumor samples is required. However, tissue/cytologic samples are not always available or evaluable. The large, noninterventional diagnostic ASSESS study (NCT01785888) evaluated the utility of circulating free tumor-derived DNA (ctDNA) from plasma for EGFR mutation testing. ASSESS was conducted in 56 centers (in Europe and Japan). Eligible patients (with newly diagnosed locally advanced/metastatic treatment-naive advanced NSCLC) provided diagnostic tissue/cytologic and plasma samples. DNA extracted from tissue/cytologic samples was subjected to EGFR mutation testing using local practices; designated laboratories performed DNA extraction/mutation testing of blood samples. The primary end point was level of concordance of EGFR mutation status between matched tissue/cytologic and plasma samples. Of 1311 patients enrolled, 1288 were eligible. Concordance of mutation status in 1162 matched samples was 89% (sensitivity 46%, specificity 97%, positive predictive value 78%, and negative predictive value 90%). A group of 25 patients with apparent false-positive plasma results was overrepresented for cytologic samples, use of less sensitive tissue testing methodologies, and smoking habits associated with high EGFR mutation frequency, indicative of false-negative tumor results. In cases in which plasma and tumor samples were tested with identical highly sensitive methods, positive predictive value/sensitivity were generally improved. These real-world data suggest that ctDNA is a feasible sample for EGFR mutation analysis. It is important to conduct mutation testing of both tumor and plasma samples in specialized laboratories, using robust/sensitive methods to ensure that patients receive appropriate treatments that target the molecular features of their disease. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  16. Lipopolysaccharide Specific Immunochromatography Based Lateral Flow Assay for Serogroup Specific Diagnosis of Leptospirosis in India

    PubMed Central

    Vanithamani, Shanmugam; Shanmughapriya, Santhanam; Narayanan, Ramasamy; Raja, Veerapandian; Kanagavel, Murugesan; Sivasankari, Karikalacholan; Natarajaseenivasan, Kalimuthusamy

    2015-01-01

    Background Leptospirosis is a re-emerging infectious disease that is under-recognized due to low-sensitivity and cumbersome serological tests. MAT is the gold standard test and it is the only serogroup specific test used till date. Rapid reliable alternative serogroup specific tests are needed for surveillance studies to identify locally circulating serogroups in the study area. Methods/Principal Findings In the present investigation the serological specificity of leptospiral lipopolysaccharides (LPS) was evaluated by enzyme linked immunosorbent assay (ELISA), dot blot assay and rapid immunochromatography based lateral flow assay (ICG-LFA). Sera samples from 120 MAT positive cases, 174 cases with febrile illness other than leptospirosis, and 121 seronegative healthy controls were evaluated for the diagnostic sensitivity and specificity of the developed assays. LPS was extracted from five locally predominant circulating serogroups including: Australis (27.5%), Autumnalis (11.7%), Ballum (25.8%), Grippotyphosa (12.5%), Pomona (10%) and were used as antigens in the diagnostics to detect IgM antibodies in patients’ sera. The sensitivity observed by IgM ELISA and dot blot assay using various leptospiral LPS was >90% for homologous sera. Except for Ballum LPS, no other LPS showed cross-reactivity to heterologous sera. An attempt was made to develop LPS based ICG-LFA for rapid and sensitive serogroup specific diagnostics of leptospirosis. The developed ICG-LFA showed sensitivity in the range between 93 and 100% for homologous sera. The Wilcoxon analysis showed LPS based ICG-LFA did not differ significantly from the gold standard MAT (P>0.05). Conclusion The application of single array of LPS for serogroup specific diagnosis is first of its kind. The developed assay could potentially be evaluated and employed for as MAT alternative. PMID:26340095

  17. Sources of sensitization, cross-reactions, and occupational sensitization to topical anaesthetics among general dermatology patients.

    PubMed

    Jussi, Liippo; Lammintausta, Kaija

    2009-03-01

    Contact sensitization to local anaesthetics is often from topical medicaments. Occupational sensitization to topical anaesthetics may occur in certain occupations. The aim of the study was to analyse the occurrence of contact sensitization to topical anaesthetics in general dermatology patients. Patch testing with topical anaesthetics was carried out in 620 patients. Possible sources of sensitization and the clinical histories of the patients are analysed. Positive patch test reactions to one or more topical anaesthetics were seen in 25/620 patients. Dibucaine reactions were most common (20/25), and lidocaine sensitization was seen in two patients. Six patients had reactions to ester-type and/or amide-type anaesthetics concurrently. Local preparations for perianal conditions were the most common sensitizers. One patient had developed occupational sensitization to procaine with multiple cross-reactions and with concurrent penicillin sensitization from procaine penicillin. Dibucaine-containing perianal medicaments are the major source of contact sensitization to topical anaesthetics. Although sensitization to multiple anaesthetics can be seen, cross-reactions are possible. Contact sensitization to lidocaine is not common, and possible cross-reactions should be determined when reactions to lidocaine are seen. Occupational procaine sensitization from veterinary medicaments is a risk among animal workers.

  18. Geometrical optimization of a local ballistic magnetic sensor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kanda, Yuhsuke; Hara, Masahiro; Nomura, Tatsuya

    2014-04-07

    We have developed a highly sensitive local magnetic sensor by using a ballistic transport property in a two-dimensional conductor. A semiclassical simulation reveals that the sensitivity increases when the geometry of the sensor and the spatial distribution of the local field are optimized. We have also experimentally demonstrated a clear observation of a magnetization process in a permalloy dot whose size is much smaller than the size of an optimized ballistic magnetic sensor fabricated from a GaAs/AlGaAs two-dimensional electron gas.

  19. Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers.

    PubMed

    Zane, Lee T; Hughes, Matilda H; Shakib, Sepehr

    2016-10-01

    Inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis often present in sensitive and thin-skinned areas that are at higher risk for topical treatment-related skin irritation (e.g., burning, stinging). Our objective was to address the need for topical treatments that can be safely applied to these areas. We assessed the local tolerability of crisaborole topical ointment when applied to sensitive and thin-skinned areas of healthy volunteers. In this phase I, randomized, double-blind, vehicle-controlled, single-center study, 32 subjects were randomized 3:1 to twice-daily application of crisaborole topical ointment, 2 %, (n = 24) or vehicle ointment (n = 8) for 21 days to 13 anatomic skin areas, including the face/hairline, genitals, extensor, and intertriginous areas. The primary endpoint was assessment of the frequency and severity of local tolerability symptoms (burning/stinging, erythema, and pruritus) using the Local Tolerability Scale. Overall, 98.8 % of all tolerability assessments had a grade of 0 (no signs/symptoms of irritation) and 0.1 % had a grade >1 (mild); no differences were observed in the frequency of local tolerability scores between treatment groups. The total frequency of local tolerability assessments graded >0 (none) was lower across all application sites with crisaborole ointment (0.0-2.2 %) than with vehicle ointment (2.4-7.1 %). Local tolerability did not change over time, and was comparable between sensitive and nonsensitive skin areas. Crisaborole ointment application to sensitive skin areas was well tolerated in healthy volunteers, supporting its potential role as a topical treatment alternative for patients with AD or psoriasis.

  20. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

    PubMed

    Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; DeCarli, Charles

    2012-06-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Local calcium signalling is mediated by mechanosensitive ion channels in mesenchymal stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chubinskiy-Nadezhdin, Vladislav I., E-mail: vchubinskiy@gmail.com; Vasileva, Valeria Y.; Pugovkina, Natalia A.

    Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs). Functional expression of native mechanosensitive stretch-activated channels (SACs) and calcium-sensitive potassium channels of different conductances inmore » hMESCs was shown. Single current analysis of stretch-induced channel activity revealed functional coupling of SACs and BK channels in plasma membrane. The combination of cell-attached and inside-out experiments have indicated that highly localized Ca{sup 2+} entry via SACs triggers BK channel activity. At the same time, SK channels are not coupled with SACs despite of high calcium sensitivity as compared to BK. Our data demonstrate novel mechanism controlling BK channel activity in native cells. We conclude that SACs and BK channels are clusterized in functional mechanosensitive domains in the plasma membrane of hMESCs. Co-clustering of ion channels may significantly contribute to mechano-dependent calcium signalling in stem cells. - Highlights: • Stretch-induced channel activity in human mesenchymal stem cells was analyzed. • Functional expression of SACs and Ca{sup 2+}-sensitive BK and SK channels was shown. • Local Ca{sup 2+} influx via stretch-activated channels triggers BK channel activity. • SK channels are not coupled with SACs despite higher sensitivity to [Ca{sup 2+}]{sub i}. • Functional clustering of SACs and BK channels in stem cell membrane is proposed.« less

  2. Molecular Determinants of the Human α2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic

    PubMed Central

    Pullikuth, Ashok K.; Guidry, Jessie J.

    2015-01-01

    The human α2C-adrenergic receptor (α2C-AR) is localized intracellularly at physiologic temperature. Decreasing the environmental temperature strongly stimulates the receptor transport to the cell surface. In contrast, rat and mouse α2C-AR plasma membrane levels are less sensitive to decrease in temperature, whereas the opossum α2C-AR cell surface levels are not changed in these conditions. Structural analysis demonstrated that human α2C-AR has a high number of arginine residues in the third intracellular loop and in the C-terminus, organized as putative RXR motifs. Although these motifs do not affect the receptor subcellular localization at 37°C, deletion of the arginine clusters significantly enhanced receptor plasma membrane levels at reduced temperature. We found that this exaggerated transport of the human receptor is mediated by two functional arginine clusters, one in the third intracellular loop and one in the C-terminus. This effect is mediated by interactions with COPI vesicles, but not by 14-3-3 proteins. In rat α2C-AR, the arginine cluster from the third intracellular loop is shifted to the left due to three missing residues. Reinsertion of these residues in the rat α2C-AR restored the same temperature sensitivity as in the human receptor. Proteomic and coimmunoprecipitation experiments identified pontin as a molecule having stronger interactions with human α2C-AR compared with rat α2C-AR. Inhibition of pontin activity enhanced human receptor plasma membrane levels and signaling at 37°C. Our results demonstrate that human α2C-AR has a unique temperature-sensitive traffic pattern within the G protein–coupled receptor class due to interactions with different molecular chaperones, mediated in part by strict spatial localization of specific arginine residues. PMID:25680754

  3. Anomalous vibrational properties in the continuum limit of glasses

    NASA Astrophysics Data System (ADS)

    Shimada, Masanari; Mizuno, Hideyuki; Ikeda, Atsushi

    2018-02-01

    The low-temperature thermal properties of glasses are anomalous with respect to those of crystals. These thermal anomalies indicate that the low-frequency vibrational properties of glasses differ from those of crystals. Recent studies revealed that, in the simplest model of glasses, i.e., the harmonic potential system, phonon modes coexist with soft localized modes in the low-frequency (continuum) limit. However, the nature of low-frequency vibrational modes of more realistic models is still controversial. In the present work, we study the Lennard-Jones (LJ) system using large-scale molecular-dynamics (MD) simulation and establish that the vibrational property of the LJ glass converges to coexistence of the phonon modes and the soft localized modes in the continuum limit as in the case of the harmonic potential system. Importantly, we find that the low-frequency vibrations are rather sensitive to the numerical scheme of potential truncation, which is usually implemented in the MD simulation, and this is the reason why contradictory arguments have been reported by previous works. We also discuss the physical origin of this sensitiveness by means of a linear stability analysis.

  4. STFT or CWT for the detection of Doppler ultrasound embolic signals.

    PubMed

    Gonçalves, Ivo B; Leiria, Ana; Moura, M M M

    2013-09-01

    Aiming reliable detection and localization of cerebral blood flow and emboli, embolic signals were added to simulated middle cerebral artery Doppler signals and analysed. Short-time Fourier transform (STFT) and continuous wavelet transform (CWT) were used in the evaluation. The following parameters were used in this study: the powers of the embolic signals added were 5, 6, 6.5, 7, 7.5, 8 and 9 dB; the mother wavelets for CWT analysis were Morlet, Mexican hat, Meyer, Gaussian (order 4) and Daubechies (orders 4 and 8); and the thresholds for detection (equated in terms of false positive, false negative and sensitivity) were 2 and 3.5 dB for the CWT and STFT, respectively. The results indicate that although the STFT allows accurately detecting emboli, better time localization can be achieved with the CWT. Among the CWT, the current best overall results were obtained with Mexican Hat mother wavelet, with optimal results for sensitivity (100% detection rate) for nearly all emboli power values studied. Copyright © 2013 John Wiley & Sons, Ltd.

  5. A Comparison of Tissue Spray and Lipid Extract Direct Injection Electrospray Ionization Mass Spectrometry for the Differentiation of Eutopic and Ectopic Endometrial Tissues

    NASA Astrophysics Data System (ADS)

    Chagovets, Vitaliy; Wang, Zhihao; Kononikhin, Alexey; Starodubtseva, Natalia; Borisova, Anna; Salimova, Dinara; Popov, Igor; Kozachenko, Andrey; Chingin, Konstantin; Chen, Huanwen; Frankevich, Vladimir; Adamyan, Leila; Sukhikh, Gennady

    2018-02-01

    Recent research revealed that tissue spray mass spectrometry enables rapid molecular profiling of biological tissues, which is of great importance for the search of disease biomarkers as well as for online surgery control. However, the payback for the high speed of analysis in tissue spray analysis is the generally lower chemical sensitivity compared with the traditional approach based on the offline chemical extraction and electrospray ionization mass spectrometry detection. In this study, high resolution mass spectrometry analysis of endometrium tissues of different localizations obtained using direct tissue spray mass spectrometry in positive ion mode is compared with the results of electrospray ionization analysis of lipid extracts. Identified features in both cases belong to three lipid classes: phosphatidylcholines, phosphoethanolamines, and sphingomyelins. Lipids coverage is validated by hydrophilic interaction liquid chromatography with mass spectrometry of lipid extracts. Multivariate analysis of data from both methods reveals satisfactory differentiation of eutopic and ectopic endometrium tissues. Overall, our results indicate that the chemical information provided by tissue spray ionization is sufficient to allow differentiation of endometrial tissues by localization with similar reliability but higher speed than in the traditional approach relying on offline extraction.

  6. Prostate-cancer diagnosis by non-invasive prostatic Zinc mapping using X-Ray Fluorescence (XRF)

    NASA Astrophysics Data System (ADS)

    Cortesi, Marco

    At present, the major screening tools (PSA, DRE, TRUS) for prostate cancer lack sensitivity and specificity, and none can distinguish between low-grade indolent cancer and high-grade lethal one. The situation calls for the promotion of alternative approaches, with better detection sensitivity and specificity, to provide more efficient selection of patients to biopsy and with possible guidance of the biopsy needles. The prime objective of the present work was the development of a novel non-invasive method and tool for promoting detection, localization, diagnosis and follow-up of PCa. The method is based on in-vivo imaging of Zn distribution in the peripheral zone of the prostate, by a trans-rectal X-ray fluorescence (XRF) probe. Local Zn levels, measured in 1--4 mm3 fresh tissue biopsy segments from an extensive clinical study involving several hundred patients, showed an unambiguous correlation with the histological classification of the tissue (Non-Cancer or PCa), and a systematic positive correlation of its depletion level with the cancer-aggressiveness grade (Gleason classification). A detailed analysis of computer-simulated Zn-concentration images (with input parameters from clinical data) disclosed the potential of the method to provide sensitive and specific detection and localization of the lesion, its grade and extension. Furthermore, it also yielded invaluable data on some requirements, such as the image resolution and counting-statistics, requested from a trans-rectal XRF probe for in-vivo recording of prostatic-Zn maps in patients. By means of systematic table-top experiments on prostate-phantoms comprising tumor-like inclusions, followed by dedicated Monte Carlo simulations, the XRF-probe and its components have been designed and optimized. Multi-parameter analysis of the experimental data confirmed the simulation estimations of the XRF detection system in terms of: delivered dose, counting statistics, scanning resolution, target-volume size and the accuracy of locating at various depths of small-volume tumor-like inclusions in tissue-phantoms. The clinical study, the Monte Carlo simulations and the analysis of Zn-map images provided essential information and promising vision on the potential performance of the Zn-based PCa detection concept. Simulations focusing on medical-probe design and its performance at permissible radiation doses yielded positive results - confirmed by a series of systematic laboratory experiments with a table-top XRF system.

  7. Solar energy system economic evaluation: IBM System 4, Clinton, Mississippi

    NASA Technical Reports Server (NTRS)

    1980-01-01

    An economic analysis of the solar energy system was developed for five sites, typical of a wide range of environmental and economic conditions in the continental United States. The analysis was based on the technical and economic models in the F-chart design procedure, with inputs based on the characteristic of the installed system and local conditions. The results are of the economic parameters of present worth of system cost over a 20 year time span: life cycle savings, year of positive savings and year of payback for the optimized solar energy system at each of the analysis sites. The sensitivity of the economic evaluation to uncertainties in constituent system and economic variables is also investigated.

  8. Development of a micro-X-ray fluorescence system based on polycapillary X-ray optics for non-destructive analysis of archaeological objects

    NASA Astrophysics Data System (ADS)

    Cheng, Lin; Ding, Xunliang; Liu, Zhiguo; Pan, Qiuli; Chu, Xuelian

    2007-08-01

    A new micro-X-ray fluorescence (micro-XRF) system based on rotating anode X-ray generator and polycapillary X-ray optics has been set up in XOL Lab, BNU, China, in order to be used for analysis of archaeological objects. The polycapillary X-ray optics used here can focus the primary X-ray beam down to tens of micrometers in diameter that allows for non-destructive and local analysis of sub-mm samples with minor/trace level sensitivity. The analytical characteristics and potential of this micro-XRF system in archaeological research are discussed. Some described uses of this instrument include studying Chinese ancient porcelain.

  9. Cost effectiveness of universal umbilical cord blood gas and lactate analysis in a tertiary level maternity unit.

    PubMed

    White, Christopher R H; Doherty, Dorota A; Cannon, Jeffrey W; Kohan, Rolland; Newnham, John P; Pennell, Craig E

    2016-07-01

    There is an increasing body of literature supporting universal umbilical cord blood gas analysis (UCBGA) into all maternity units. A significant impediment to UCBGA's introduction is the perceived expense of the introduction and associated ongoing costs. Consequently, this study set out to conduct the first cost-effectiveness analysis of introducing universal UCBGA. Analysis was based on 42,100 consecutive deliveries ≥23 weeks of gestation at a single tertiary obstetric unit. Within 4 years of UCBGA's introduction there was a 45% reduction in term special care nursery (SCN) admissions >2499 g. Incurred costs included initial and ongoing costs associated with universal UCBGA. Averted costs were based on local diagnosis-related grouping costs for reduction in term SCN admissions. Incremental cost-effectiveness ratio (ICER) and sensitivity analysis results were reported. Under the base-case scenario, the adoption of universal UCBGA was less costly and more effective than selective UCBGA over 4 years and resulted in saving of AU$641,532 while adverting 376 SCN admissions. Sensitivity analysis showed that UCBGA was cost-effective in 51.8%, 83.3%, 99.6% and 100% of simulations in years 1, 2, 3 and 4. These conclusions were not sensitive to wide, clinically possible variations in parameter values for neonatal intensive care unit and SCN admissions, magnitude of averted SCN admissions, cumulative delivery numbers, and SCN admission costs. Universal UCBGA is associated with significant initial and ongoing costs; however, potential averted costs (due to reduced SCN admissions) exceed incurred costs in most scenarios.

  10. Tracking sensitive source areas of different weather pollution types using GRAPES-CUACE adjoint model

    NASA Astrophysics Data System (ADS)

    Wang, Chao; An, Xingqin; Zhai, Shixian; Hou, Qing; Sun, Zhaobin

    2018-02-01

    In this study, the sustained pollution processes were selected during which daily PM2.5 concentration exceeded 75 μg/m3 for three days continuously based on the hourly data of Beijing observation sites from July 2012 to December 2015. Using the China Meteorological Administration (CMA) MICAPS meteorological processing system, synoptic situation during PM2.5 pollution processes was classified into five weather types: low pressure and weak high pressure alternating control, weak high pressure, low pressure control, high rear, and uniform pressure field. Then, we chose the representative pollution cases corresponding to each type, adopted the GRAPES-CUACE adjoint model tracking the sensitive source areas of the five types, and analyzed the critical discharge periods of Beijing and neighboring provinces as well as their contribution to the PM2.5 peak concentration in Beijing. The results showed that the local source plays the main theme in the 30 h before the objective time, and prior to 72 h before the objective time contribution of local sources for the five pollution types are 37.5%, 25.0%, 39.4%, 31.2%, and 42.4%, respectively; the Hebei source contributes constantly in the 57 h ahead of the objective time with the contribution proportion ranging from 37% to 64%; the contribution period and rate of Tianjin and Shanxi sources are shorter and smaller. Based on the adjoint sensitivity analysis, we further discussed the effect of emission reduction control measures in different types, finding that the effect of local source reduction in the first 20 h of the objective time is better, and if the local source is reduced 50% within 72 h before the objective time, the decline rates of PM2.5 in the five types are 11.6%, 9.4%, 13.8%, 9.9% and 15.2% respectively. And the reduction effect of the neighboring sources is better within the 3-57 h before the objective time.

  11. Collaborative Completion of Transcription Factor Binding Profiles via Local Sensitive Unified Embedding.

    PubMed

    Zhu, Lin; Guo, Wei-Li; Lu, Canyi; Huang, De-Shuang

    2016-12-01

    Although the newly available ChIP-seq data provides immense opportunities for comparative study of regulatory activities across different biological conditions, due to cost, time or sample material availability, it is not always possible for researchers to obtain binding profiles for every protein in every sample of interest, which considerably limits the power of integrative studies. Recently, by leveraging related information from measured data, Ernst et al. proposed ChromImpute for predicting additional ChIP-seq and other types of datasets, it is demonstrated that the imputed signal tracks accurately approximate the experimentally measured signals, and thereby could potentially enhance the power of integrative analysis. Despite the success of ChromImpute, in this paper, we reexamine its learning process, and show that its performance may degrade substantially and sometimes may even fail to output a prediction when the available data is scarce. This limitation could hurt its applicability to important predictive tasks, such as the imputation of TF binding data. To alleviate this problem, we propose a novel method called Local Sensitive Unified Embedding (LSUE) for imputing new ChIP-seq datasets. In LSUE, the ChIP-seq data compendium are fused together by mapping proteins, samples, and genomic positions simultaneously into the Euclidean space, thereby making their underling associations directly evaluable using simple calculations. In contrast to ChromImpute which mainly makes use of the local correlations between available datasets, LSUE can better estimate the overall data structure by formulating the representation learning of all involved entities as a single unified optimization problem. Meanwhile, a novel form of local sensitive low rank regularization is also proposed to further improve the performance of LSUE. Experimental evaluations on the ENCODE TF ChIP-seq data illustrate the performance of the proposed model. The code of LSUE is available at https://github.com/ekffar/LSUE.

  12. Localization of the ANG II type 2 receptor in the microcirculation of skeletal muscle

    NASA Technical Reports Server (NTRS)

    Nora, E. H.; Munzenmaier, D. H.; Hansen-Smith, F. M.; Lombard, J. H.; Greene, A. S.; Cowley, A. W. (Principal Investigator)

    1998-01-01

    Only functional studies have suggested the presence of the ANG II type 2 (AT2) receptor in the microcirculation. To determine the distribution of this receptor in the rat skeletal muscle microcirculation, a polyclonal rabbit anti-rat antiserum was developed and used for immunohistochemistry and Western blot analysis. The antiserum was prepared against a highly specific and antigenic AT2-receptor synthetic peptide and was validated by competition and sensitivity assays. Western blot analysis demonstrated a prominent, single band at approximately 40 kDa in cremaster and soleus muscle. Immunohistochemical analysis revealed a wide distribution of AT2 receptors throughout the skeletal muscle microcirculation in large and small microvessels. Microanatomic studies displayed an endothelial localization of the AT2 receptor, whereas dual labeling with smooth muscle alpha-actin also showed colocalization of the AT2 receptor with vascular smooth muscle cells. Other cells associated with the microvessels also stained positive for AT2 receptors. Briefly, this study confirms previous functional data and localizes the AT2 receptor to the microcirculation. These studies demonstrate that the AT2 receptor is present on a variety of vascular cell types and that it is situated in a fashion that would allow it to directly oppose ANG II type 1 receptor actions.

  13. Local cellular neighborhood controls proliferation in cell competition

    PubMed Central

    Bove, Anna; Gradeci, Daniel; Fujita, Yasuyuki; Banerjee, Shiladitya; Charras, Guillaume; Lowe, Alan R.

    2017-01-01

    Cell competition is a quality-control mechanism through which tissues eliminate unfit cells. Cell competition can result from short-range biochemical inductions or long-range mechanical cues. However, little is known about how cell-scale interactions give rise to population shifts in tissues, due to the lack of experimental and computational tools to efficiently characterize interactions at the single-cell level. Here, we address these challenges by combining long-term automated microscopy with deep-learning image analysis to decipher how single-cell behavior determines tissue makeup during competition. Using our high-throughput analysis pipeline, we show that competitive interactions between MDCK wild-type cells and cells depleted of the polarity protein scribble are governed by differential sensitivity to local density and the cell type of each cell’s neighbors. We find that local density has a dramatic effect on the rate of division and apoptosis under competitive conditions. Strikingly, our analysis reveals that proliferation of the winner cells is up-regulated in neighborhoods mostly populated by loser cells. These data suggest that tissue-scale population shifts are strongly affected by cellular-scale tissue organization. We present a quantitative mathematical model that demonstrates the effect of neighbor cell–type dependence of apoptosis and division in determining the fitness of competing cell lines. PMID:28931601

  14. Unsupervised Gaussian Mixture-Model With Expectation Maximization for Detecting Glaucomatous Progression in Standard Automated Perimetry Visual Fields.

    PubMed

    Yousefi, Siamak; Balasubramanian, Madhusudhanan; Goldbaum, Michael H; Medeiros, Felipe A; Zangwill, Linda M; Weinreb, Robert N; Liebmann, Jeffrey M; Girkin, Christopher A; Bowd, Christopher

    2016-05-01

    To validate Gaussian mixture-model with expectation maximization (GEM) and variational Bayesian independent component analysis mixture-models (VIM) for detecting glaucomatous progression along visual field (VF) defect patterns (GEM-progression of patterns (POP) and VIM-POP). To compare GEM-POP and VIM-POP with other methods. GEM and VIM models separated cross-sectional abnormal VFs from 859 eyes and normal VFs from 1117 eyes into abnormal and normal clusters. Clusters were decomposed into independent axes. The confidence limit (CL) of stability was established for each axis with a set of 84 stable eyes. Sensitivity for detecting progression was assessed in a sample of 83 eyes with known progressive glaucomatous optic neuropathy (PGON). Eyes were classified as progressed if any defect pattern progressed beyond the CL of stability. Performance of GEM-POP and VIM-POP was compared to point-wise linear regression (PLR), permutation analysis of PLR (PoPLR), and linear regression (LR) of mean deviation (MD), and visual field index (VFI). Sensitivity and specificity for detecting glaucomatous VFs were 89.9% and 93.8%, respectively, for GEM and 93.0% and 97.0%, respectively, for VIM. Receiver operating characteristic (ROC) curve areas for classifying progressed eyes were 0.82 for VIM-POP, 0.86 for GEM-POP, 0.81 for PoPLR, 0.69 for LR of MD, and 0.76 for LR of VFI. GEM-POP was significantly more sensitive to PGON than PoPLR and linear regression of MD and VFI in our sample, while providing localized progression information. Detection of glaucomatous progression can be improved by assessing longitudinal changes in localized patterns of glaucomatous defect identified by unsupervised machine learning.

  15. An experimental study to evaluate the technological limitations in the understanding of the haemodynamic change in pre-eclampsia.

    PubMed

    Sengupta

    1998-08-01

    BACKGROUND: Conventional indices could not define the pathogenesis of pre-eclampsia and its predictability. It has also not been possible to record these indices from the local uteroplacental system where the pathology lies. OBJECTIVE: To investigate the limitations of the currently available blood pressure-flow measuring indices and techniques commonly used in pregnancy.METHOD: Blood pressure and velocity profiles were obtained under various pathophysiological conditions for pregnant and non-pregnant animals and human subjects. The data were analysed using both conventional and computer-based spectral methods. RESULTS: Continuous monitoring of blood pressure and velocity together with their spectral analysis appeared to be a useful sensitive indicator in pregnancy beyond the commonly available conventional analytical method. In high-resistance flow such as in hypertension and in pre-eclampsia, the power amplitude was relatively low at low frequency. Power amplitude remained high at low frequency in normal low-resistance state of pregnancy. CONCLUSION: The results suggest the need to develop a highly sensitive instrumentation whereby any minute variation in mean arterial pressure that is of clinical significance can be measured. Alternatively, analytical advancement, such as use of power spectrum analysers, might prove to be useful and sensitive. Variability of heart rate is an important determinant of the underlying pathophysiology in pregnancy. It is concluded that the heart rate of pre-eclamptics and hypertensives has to increase in order to maintain a constant organic blood flow whereas in normal pregnancy bloow flow can rise even without an incrase in heart rate. Future research should be directed towards blood flow mapping, power spectral analysis and image processing of the blood pressure-flow profile obtained from local and systemic compartments under different pathophysiological conditions of pregnancy.

  16. Optimizing EFL Learners' Sensitizing Reading Skill: Development of Local Content-Based Textbook

    ERIC Educational Resources Information Center

    Arifani, Yudhi

    2016-01-01

    The development of local wisdom based sensitizing reading material is aimed at penetrating one of the imperishable gaps between authentic and non-authentic reading materials dispute in an EFL teaching context. Promoting EFL learners' needs for the first semester students of English department at university level, who rarely or even never have a…

  17. Recharge and Topographical Controls on Groundwater Circulation in Shallow Crystalline Rock Aquifers revealed by CFC-based Age Data

    NASA Astrophysics Data System (ADS)

    Kolbe, T.; Abbott, B. W.; Marçais, J.; Thomas, Z.; Aquilina, L.; Labasque, T.; Pinay, G.; De Dreuzy, J. R.

    2016-12-01

    Groundwater transit time and flow path are key factors controlling nitrogen retention and removal capacity at the catchment scale (Abbott et al., 2016), but the relative importance of hydrogeological and topographical factors in determining these parameters remains uncertain (Kolbe et al., 2016). To address this unknown, we used numerical modelling techniques calibrated with CFC groundwater age data to quantify transit time and flow path in an unconfined aquifer in Brittany, France. We assessed the relative importance of parameters (aquifer depth, porosity, arrangement of geological layers, and permeability profile), hydrology (recharge rate), and topography in determining characteristic flow distances (Leray et al., 2016). We found that groundwater flow was highly local (mean travel distance of 350 m) but also relatively old (mean CFC age of 40 years). Sensitivity analysis revealed that groundwater travel distances were not sensitive to geological parameters within the constraints of the CFC age data. However, circulation was sensitive to topography in lowland areas where the groundwater table was close to the land surface, and to recharge rate in upland areas where water input modulated the free surface of the aquifer. We quantified these differences with a local groundwater ratio (rGW-LOCAL) defined as the mean groundwater travel distance divided by the equivalent surface distance water would have traveled along the land surface. Lowland rGW-LOCAL was near 1, indicating primarily topographic controls. Upland rGW-LOCALwas 1.6, meaning the groundwater recharge area was substantially larger than the topographically-defined catchment. This ratio was applied to other catchments in Brittany to test its relevance in comparing controls on groundwater circulation within and among catchments. REFERENCES Abbott et al., 2016, Using multi-tracer inference to move beyond single-catchment ecohydrology. Earth-Science Reviews. Kolbe et al., 2016, Coupling 3D groundwater modeling with CFC-based age dating to classify local groundwater circulation in an unconfined crystalline aquifer. J. Hydrol. Leray et al., 2016, Residence time distributions for hydrologic systems: Mechanistic foundations and steady-state analytical solutions. J. Hydrol.

  18. Coherent Doppler Lidar for Boundary Layer Studies and Wind Energy

    NASA Astrophysics Data System (ADS)

    Choukulkar, Aditya

    This thesis outlines the development of a vector retrieval technique, based on data assimilation, for a coherent Doppler LIDAR (Light Detection and Ranging). A detailed analysis of the Optimal Interpolation (OI) technique for vector retrieval is presented. Through several modifications to the OI technique, it is shown that the modified technique results in significant improvement in velocity retrieval accuracy. These modifications include changes to innovation covariance portioning, covariance binning, and analysis increment calculation. It is observed that the modified technique is able to make retrievals with better accuracy, preserves local information better, and compares well with tower measurements. In order to study the error of representativeness and vector retrieval error, a lidar simulator was constructed. Using the lidar simulator a thorough sensitivity analysis of the lidar measurement process and vector retrieval is carried out. The error of representativeness as a function of scales of motion and sensitivity of vector retrieval to look angle is quantified. Using the modified OI technique, study of nocturnal flow in Owens' Valley, CA was carried out to identify and understand uncharacteristic events on the night of March 27th 2006. Observations from 1030 UTC to 1230 UTC (0230 hr local time to 0430 hr local time) on March 27 2006 are presented. Lidar observations show complex and uncharacteristic flows such as sudden bursts of westerly cross-valley wind mixing with the dominant up-valley wind. Model results from Coupled Ocean/Atmosphere Mesoscale Prediction System (COAMPS RTM) and other in-situ instrumentations are used to corroborate and complement these observations. The modified OI technique is used to identify uncharacteristic and extreme flow events at a wind development site. Estimates of turbulence and shear from this technique are compared to tower measurements. A formulation for equivalent wind speed in the presence of variations in wind speed and direction, combined with shear is developed and used to determine wind energy content in presence of turbulence.

  19. Newtonian noise and ambient ground motion for gravitational wave detectors

    NASA Astrophysics Data System (ADS)

    Beker, M. G.; van den Brand, J. F. J.; Hennes, E.; Rabeling, D. S.

    2012-06-01

    Fluctuations of the local gravitational field as a result of seismic and atmospheric displacements will limit the sensitivity of ground based gravitational wave detectors at frequencies below 10 Hz. We discuss the implications of Newtonian noise for future third generation gravitational wave detectors. The relevant seismic wave fields are predominately of human origin and are dependent on local infrastructure and population density. Seismic studies presented here show that considerable seismic noise reduction is possible compared to current detector locations. A realistic seismic amplitude spectral density of a suitably quiet site should not exceed 0.5 nm/(Hz/f)2 above 1 Hz. Newtonian noise models have been developed both analytically and by finite element analysis. These show that the contribution to Newtonian noise from surface waves due to distance sources significantly reduces with depth. Seismic displacements from local sources and body waves then become the dominant contributors to the Newtonian fluctuations.

  20. Interpretive Analysis of the Joint Maritime Command Information System (JMCIS) Sensitive Compartmented Information (SCI) Local Area Network (LAN) security Requirements

    DTIC Science & Technology

    1994-09-01

    as Copernicus brought about a revolutionary paradigm shift in astronomy , the Copernicus Architecture was so named because it represents a...34 ........................................ 7 3. The Navy’s Copernicus Architecture .......................................... 8 B . SY ST E M S...evolution of JMCIS are DoD’s Corporate Information Management (CIM), The Joint Staffs "C41 for the Warrior", and the Navy’s Copernicus architecture programs

  1. Small Crack Growth and Its Influence in Near Alpha-Titanium Alloys

    DTIC Science & Technology

    1989-06-01

    geometries via finite element and boundary-collocation analysis 8 , 9 . Elastic plastic fracture mechanics ( EPFM ) 1 0 , 1 1 and local crack tip field...correlation was found between experimental and predicted data, general application of the model is not possible as both 0 and rp are sensitive to changes in...cracks at low AK the load reduction schemes should be altered to remove the residual deformations, perhaps via machining or the application of large

  2. Magnetic resonance T1 gradient-echo imaging in hepatolithiasis.

    PubMed

    Safar, F; Kamura, T; Okamuto, K; Sasai, K; Gejyo, F

    2005-01-01

    We examined the role of magnetic resonance T1-weighted gradient-echo (MRT1-GE) imaging in hepatolithiasis. MRT1-GE, precontrast computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) of 10 patients with hepatolithiasis were compared for their diagnostic accuracies in the detection and localization of intrahepatic calculi. The diagnosis of hepatolithiasis was confirmed by surgery. For localization of the stone, we divided the bile ducts into six areas: right and left hepatic ducts and bile ducts of the lateral, medial, right anterior, and right posterior segments of the liver. Chemical analysis of the stones was performed in eight patients. The total number of segments proved by surgery to contain stones was 18. Although not significantly different, the sensitivity of MRT1-GE was 77.8% (14 of 18 segments), higher than that of MRCP (66.7%, 12 of 18 segments) and that of CT (50%, nine of 18 segments). The sensitivity of magnetic resonance imaging (MRCP + MRT1) was significantly higher than that of CT (p < 0.01). Multiple logistic regression analysis showed that the result of surgery was significantly affected only by the result of magnetic resonance imaging. On MRT1-GE, all the depicted stones appeared as high-intensity signal areas within the low-intensity bile duct irrespective of their chemical composition. MRT1-GE imaging provides complementary information concerning hepatolithiasis.

  3. Multi-disciplinary optimization of aeroservoelastic systems

    NASA Technical Reports Server (NTRS)

    Karpel, Mardechay

    1992-01-01

    The purpose of the research project was to continue the development of new methods for efficient aeroservoelastic analysis and optimization. The main targets were as follows: to complete the development of analytical tools for the investigation of flutter with large stiffness changes; to continue the work on efficient continuous gust response and sensitivity derivatives; and to advance the techniques of calculating dynamic loads with control and unsteady aerodynamic effects. An efficient and highly accurate mathematical model for time-domain analysis of flutter during which large structural changes occur was developed in cooperation with Carol D. Wieseman of NASA LaRC. The model was based on the second-year work 'Modal Coordinates for Aeroelastic Analysis with Large Local Structural Variations'. The work on continuous gust response was completed. An abstract of the paper 'Continuous Gust Response and Sensitivity Derivatives Using State-Space Models' was submitted for presentation in the 33rd Israel Annual Conference on Aviation and Astronautics, Feb. 1993. The abstract is given in Appendix A. The work extends the optimization model to deal with continuous gust objectives in a way that facilitates their inclusion in the efficient multi-disciplinary optimization scheme. Currently under development is a work designed to extend the analysis and optimization capabilities to loads and stress considerations. The work is on aircraft dynamic loads in response to impulsive and non-impulsive excitation. The work extends the formulations of the mode-displacement and summation-of-forces methods to include modes with significant local distortions, and load modes. An abstract of the paper,'Structural Dynamic Loads in Response to Impulsive Excitation' is given in appendix B. Another work performed this year under the Grant was 'Size-Reduction Techniques for the Determination of Efficient Aeroservoelastic Models' given in Appendix C.

  4. Feasibility of A-mode ultrasound attenuation as a monitoring method of local hyperthermia treatment.

    PubMed

    Manaf, Noraida Abd; Aziz, Maizatul Nadwa Che; Ridzuan, Dzulfadhli Saffuan; Mohamad Salim, Maheza Irna; Wahab, Asnida Abd; Lai, Khin Wee; Hum, Yan Chai

    2016-06-01

    Recently, there is an increasing interest in the use of local hyperthermia treatment for a variety of clinical applications. The desired therapeutic outcome in local hyperthermia treatment is achieved by raising the local temperature to surpass the tissue coagulation threshold, resulting in tissue necrosis. In oncology, local hyperthermia is used as an effective way to destroy cancerous tissues and is said to have the potential to replace conventional treatment regime like surgery, chemotherapy or radiotherapy. However, the inability to closely monitor temperature elevations from hyperthermia treatment in real time with high accuracy continues to limit its clinical applicability. Local hyperthermia treatment requires real-time monitoring system to observe the progression of the destroyed tissue during and after the treatment. Ultrasound is one of the modalities that have great potential for local hyperthermia monitoring, as it is non-ionizing, convenient and has relatively simple signal processing requirement compared to magnetic resonance imaging and computed tomography. In a two-dimensional ultrasound imaging system, changes in tissue microstructure during local hyperthermia treatment are observed in terms of pixel value analysis extracted from the ultrasound image itself. Although 2D ultrasound has shown to be the most widely used system for monitoring hyperthermia in ultrasound imaging family, 1D ultrasound on the other hand could offer a real-time monitoring and the method enables quantitative measurement to be conducted faster and with simpler measurement instrument. Therefore, this paper proposes a new local hyperthermia monitoring method that is based on one-dimensional ultrasound. Specifically, the study investigates the effect of ultrasound attenuation in normal and pathological breast tissue when the temperature in tissue is varied between 37 and 65 °C during local hyperthermia treatment. Besides that, the total protein content measurement was also conducted to investigate the relationship between attenuation and tissue denaturation level at different temperature ranges. The tissues were grouped according to their histology results, namely normal tissue with large predominance of cells (NPC), cancer tissue with large predominance of cells (CPC) and cancer with high collagen fiber content (CHF). The result shows that the attenuation coefficient of ultrasound measured following the local hyperthermia treatment increases with the increment of collagen fiber content in tissue as the CHF attenuated ultrasound at the highest rate, followed by NPC and CPC. Additionally, the attenuation increment is more pronounced at the temperature over 55 °C. This describes that the ultrasound wave experienced more energy loss when it propagates through a heated tissue as the tissue structure changes due to protein coagulation effect. Additionally, a significant increase in the sensitivity of attenuation to protein denaturation is also observed with the highest sensitivity obtained in monitoring NPC. Overall, it is concluded that one-dimensional ultrasound can be used as a monitoring method of local hyperthermia since its attenuation is very sensitive to the changes in tissue microstructure during hyperthermia.

  5. Comparison Between 2D and 3D Simulations of Rate Dependent Friction Using DEM

    NASA Astrophysics Data System (ADS)

    Wang, C.; Elsworth, D.

    2017-12-01

    Rate-state dependent constitutive laws of frictional evolution have been successful in representing many of the first- and second- order components of earthquake rupture. Although this constitutive law has been successfully applied in numerical models, difficulty remains in efficient implementation of this constitutive law in computationally-expensive granular mechanics simulations using discrete element methods (DEM). This study introduces a novel approach in implementing a rate-dependent constitutive relation of contact friction into DEM. This is essentially an implementation of a slip-weakening constitutive law onto local particle contacts without sacrificing computational efficiency. This implementation allows the analysis of slip stability of simulated fault gouge materials. Velocity-stepping experiments are reported on both uniform and textured distributions of quartz and talc as 3D analogs of gouge mixtures. Distinct local slip stability parameters (a-b) are assigned to the quartz and talc, respectively. We separately vary talc content from 0 to 100% in the uniform mixtures and talc layer thickness from 1 to 20 particles in the textured mixtures. Applied shear displacements are cycled through velocities of 1μm/s and 10μm/s. Frictional evolution data are collected and compared to 2D simulation results. We show that dimensionality significantly impacts the evolution of friction. 3D simulation results are more representative of laboratory observed behavior and numerical noise is shown at a magnitude of 0.01 in terms of friction coefficient. Stability parameters (a-b) can be straightforwardly obtained from analyzing velocity steps, and are different from locally assigned (a-b) values. Sensitivity studies on normal stress, shear velocity, particle size, local (a-b) values, and characteristic slip distance (Dc) show that the implementation is sensitive to local (a-b) values and relations between (Dc) and particle size.

  6. Quantitative estimation of localization errors of 3d transition metal pseudopotentials in diffusion Monte Carlo

    DOE PAGES

    Dzubak, Allison L.; Krogel, Jaron T.; Reboredo, Fernando A.

    2017-07-10

    The necessarily approximate evaluation of non-local pseudopotentials in diffusion Monte Carlo (DMC) introduces localization errors. In this paper, we estimate these errors for two families of non-local pseudopotentials for the first-row transition metal atoms Sc–Zn using an extrapolation scheme and multideterminant wavefunctions. Sensitivities of the error in the DMC energies to the Jastrow factor are used to estimate the quality of two sets of pseudopotentials with respect to locality error reduction. The locality approximation and T-moves scheme are also compared for accuracy of total energies. After estimating the removal of the locality and T-moves errors, we present the range ofmore » fixed-node energies between a single determinant description and a full valence multideterminant complete active space expansion. The results for these pseudopotentials agree with previous findings that the locality approximation is less sensitive to changes in the Jastrow than T-moves yielding more accurate total energies, however not necessarily more accurate energy differences. For both the locality approximation and T-moves, we find decreasing Jastrow sensitivity moving left to right across the series Sc–Zn. The recently generated pseudopotentials of Krogel et al. reduce the magnitude of the locality error compared with the pseudopotentials of Burkatzki et al. by an average estimated 40% using the locality approximation. The estimated locality error is equivalent for both sets of pseudopotentials when T-moves is used. Finally, for the Sc–Zn atomic series with these pseudopotentials, and using up to three-body Jastrow factors, our results suggest that the fixed-node error is dominant over the locality error when a single determinant is used.« less

  7. Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) for a 3-D Flexible Wing

    NASA Technical Reports Server (NTRS)

    Gumbert, Clyde R.; Hou, Gene J.-W.

    2001-01-01

    The formulation and implementation of an optimization method called Simultaneous Aerodynamic Analysis and Design Optimization (SAADO) are extended from single discipline analysis (aerodynamics only) to multidisciplinary analysis - in this case, static aero-structural analysis - and applied to a simple 3-D wing problem. The method aims to reduce the computational expense incurred in performing shape optimization using state-of-the-art Computational Fluid Dynamics (CFD) flow analysis, Finite Element Method (FEM) structural analysis and sensitivity analysis tools. Results for this small problem show that the method reaches the same local optimum as conventional optimization. However, unlike its application to the win,, (single discipline analysis), the method. as I implemented here, may not show significant reduction in the computational cost. Similar reductions were seen in the two-design-variable (DV) problem results but not in the 8-DV results given here.

  8. Adaptation of an urban land surface model to a tropical suburban area: Offline evaluation, sensitivity analysis, and optimization of TEB/ISBA (SURFEX)

    NASA Astrophysics Data System (ADS)

    Harshan, Suraj

    The main objective of the present thesis is the improvement of the TEB/ISBA (SURFEX) urban land surface model (ULSM) through comprehensive evaluation, sensitivity analysis, and optimization experiments using energy balance and radiative and air temperature data observed during 11 months at a tropical sub-urban site in Singapore. Overall the performance of the model is satisfactory, with a small underestimation of net radiation and an overestimation of sensible heat flux. Weaknesses in predicting the latent heat flux are apparent with smaller model values during daytime and the model also significantly underpredicts both the daytime peak and nighttime storage heat. Surface temperatures of all facets are generally overpredicted. Significant variation exists in the model behaviour between dry and wet seasons. The vegetation parametrization used in the model is inadequate to represent the moisture dynamics, producing unrealistically low latent heat fluxes during a particularly dry period. The comprehensive evaluation of the USLM shows the need for accurate estimation of input parameter values for present site. Since obtaining many of these parameters through empirical methods is not feasible, the present study employed a two step approach aimed at providing information about the most sensitive parameters and an optimized parameter set from model calibration. Two well established sensitivity analysis methods (global: Sobol and local: Morris) and a state-of-the-art multiobjective evolutionary algorithm (Borg) were employed for sensitivity analysis and parameter estimation. Experiments were carried out for three different weather periods. The analysis indicates that roof related parameters are the most important ones in controlling the behaviour of the sensible heat flux and net radiation flux, with roof and road albedo as the most influential parameters. Soil moisture initialization parameters are important in controlling the latent heat flux. The built (town) fraction has a significant influence on all fluxes considered. Comparison between the Sobol and Morris methods shows similar sensitivities, indicating the robustness of the present analysis and that the Morris method can be employed as a computationally cheaper alternative of Sobol's method. Optimization as well as the sensitivity experiments for the three periods (dry, wet and mixed), show a noticeable difference in parameter sensitivity and parameter convergence, indicating inadequacies in model formulation. Existence of a significant proportion of less sensitive parameters might be indicating an over-parametrized model. Borg MOEA showed great promise in optimizing the input parameters set. The optimized model modified using the site specific values for thermal roughness length parametrization shows an improvement in the performances of outgoing longwave radiation flux, overall surface temperature, heat storage flux and sensible heat flux.

  9. Validity of multislice computerized tomography for diagnosis of maxillofacial fractures using an independent workstation.

    PubMed

    Dos Santos, Denise Takehana; Costa e Silva, Adriana Paula Andrade; Vannier, Michael Walter; Cavalcanti, Marcelo Gusmão Paraiso

    2004-12-01

    The purpose of this study was to demonstrate the sensitivity and specificity of multislice computerized tomography (CT) for diagnosis of maxillofacial fractures following specific protocols using an independent workstation. The study population consisted of 56 patients with maxillofacial fractures who were submitted to a multislice CT. The original data were transferred to an independent workstation using volumetric imaging software to generate axial images and simultaneous multiplanar (MPR) and 3-dimensional (3D-CT) volume rendering reconstructed images. The images were then processed and interpreted by 2 examiners using the following protocols independently of each other: axial, MPR/axial, 3D-CT images, and the association of axial/MPR/3D images. The clinical/surgical findings were considered the gold standard corroborating the diagnosis of the fractures and their anatomic localization. The statistical analysis was carried out using validity and chi-squared tests. The association of axial/MPR/3D images indicated a higher sensitivity (range 95.8%) and specificity (range 99%) than the other methods regarding the analysis of all regions. CT imaging demonstrated high specificity and sensitivity for maxillofacial fractures. The association of axial/MPR/3D-CT images added important information in relationship to other CT protocols.

  10. Improved spatial regression analysis of diffusion tensor imaging for lesion detection during longitudinal progression of multiple sclerosis in individual subjects

    NASA Astrophysics Data System (ADS)

    Liu, Bilan; Qiu, Xing; Zhu, Tong; Tian, Wei; Hu, Rui; Ekholm, Sven; Schifitto, Giovanni; Zhong, Jianhui

    2016-03-01

    Subject-specific longitudinal DTI study is vital for investigation of pathological changes of lesions and disease evolution. Spatial Regression Analysis of Diffusion tensor imaging (SPREAD) is a non-parametric permutation-based statistical framework that combines spatial regression and resampling techniques to achieve effective detection of localized longitudinal diffusion changes within the whole brain at individual level without a priori hypotheses. However, boundary blurring and dislocation limit its sensitivity, especially towards detecting lesions of irregular shapes. In the present study, we propose an improved SPREAD (dubbed improved SPREAD, or iSPREAD) method by incorporating a three-dimensional (3D) nonlinear anisotropic diffusion filtering method, which provides edge-preserving image smoothing through a nonlinear scale space approach. The statistical inference based on iSPREAD was evaluated and compared with the original SPREAD method using both simulated and in vivo human brain data. Results demonstrated that the sensitivity and accuracy of the SPREAD method has been improved substantially by adapting nonlinear anisotropic filtering. iSPREAD identifies subject-specific longitudinal changes in the brain with improved sensitivity, accuracy, and enhanced statistical power, especially when the spatial correlation is heterogeneous among neighboring image pixels in DTI.

  11. Market surveillance on non-halal additives incorporated in surimi based products using polymerase chain reaction (PCR)-southern hybridization analysis

    NASA Astrophysics Data System (ADS)

    Aravindran, S.; Sahilah, A. M.; Aminah, A.

    2014-09-01

    Halal surveillance on halal ingredients incorporated in surimi based products were studied using polymerase chain reaction (PCR)-southern hybridization on chip analysis. The primers used in this technique were targeted on mitochondria DNA (mtDNA) of cytochrome b (cyt b) gene sequence which able to differentiate 7 type (beef, chicken, duck, goat, buffalo, lamb and pork) of species on a single chip. 17 (n = 17*3) different brands of surimi-based product were purchased randomly from Selangor local market in January 2013. Of 17 brands, 3 (n = 3*3) brands were positive for chicken DNA, 1 (n = 1*3) brand was positive for goat DNA, and the remainder 13 brands (n = 13*3) have no DNA species detected. The sensitivity of PCR-southern hybridization primers to detect each meat species was 0.1 ng. In the present study, it is evidence that PCR-Southern Hybridization analysis offered a reliable result due to its highly specific and sensitive properties in detecting non-halal additive such as plasma protein incorporation in surimi-based product.

  12. SEM probe of IC radiation sensitivity

    NASA Technical Reports Server (NTRS)

    Gauthier, M. K.; Stanley, A. G.

    1979-01-01

    Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

  13. No Association between Cortical Gyrification or Intrinsic Curvature and Attention-deficit/Hyperactivity Disorder in Adolescents and Young Adults.

    PubMed

    Forde, Natalie J; Ronan, Lisa; Zwiers, Marcel P; Alexander-Bloch, Aaron F; Faraone, Stephen V; Oosterlaan, Jaap; Heslenfeld, Dirk J; Hartman, Catharina A; Buitelaar, Jan K; Hoekstra, Pieter J

    2017-01-01

    Magnetic resonance imaging (MRI) studies have highlighted subcortical, cortical, and structural connectivity abnormalities associated with attention-deficit/hyperactivity disorder (ADHD). Gyrification investigations of the cortex have been inconsistent and largely negative, potentially due to a lack of sensitivity of the previously used morphological parameters. The innovative approach of applying intrinsic curvature analysis, which is predictive of gyrification pattern, to the cortical surface applied herein allowed us greater sensitivity to determine whether the structural connectivity abnormalities thus far identified at a centimeter scale also occur at a millimeter scale within the cortical surface. This could help identify neurodevelopmental processes that contribute to ADHD. Structural MRI datasets from the NeuroIMAGE project were used [ n = 306 ADHD, n = 164 controls, and n = 148 healthy siblings of individuals with ADHD (age in years, mean(sd); 17.2 (3.4), 16.8 (3.2), and 17.7 (3.8), respectively)]. Reconstructions of the cortical surfaces were computed with FreeSurfer. Intrinsic curvature (taken as a marker of millimeter-scale surface connectivity) and local gyrification index were calculated for each point on the surface (vertex) with Caret and FreeSurfer, respectively. Intrinsic curvature skew and mean local gyrification index were extracted per region; frontal, parietal, temporal, occipital, cingulate, and insula. A generalized additive model was used to compare the trajectory of these measures between groups over age, with sex, scanner site, total surface area of hemisphere, and familiality accounted for. After correcting for sex, scanner site, and total surface area no group differences were found in the developmental trajectory of intrinsic curvature or local gyrification index. Despite the increased sensitivity of intrinsic curvature, compared to gyrification measures, to subtle morphological abnormalities of the cortical surface we found no milimeter-scale connectivity abnormalities associated with ADHD.

  14. Aedes communis Reactivity Is Associated with Bee Venom Hypersensitivity: An in vitro and in vivo Study.

    PubMed

    Scala, Enrico; Pirrotta, Lia; Uasuf, Carina G; Mistrello, Gianni; Amato, Stefano; Guerra, Emma Cristina; Locanto, Maria; Meneguzzi, Giorgia; Giani, Mauro; Cecchi, Lorenzo; Abeni, Damiano; Asero, Riccardo

    2018-01-01

    Mosquito bite is usually followed by a local reaction, but severe or systemic reaction may, in rare cases, occur. Allergic reactions to Aedes communis (Ac) may be underestimated due to the lack of reliable diagnostic tools. In this multicenter study, 205 individuals reporting large local reactions to Ac were enrolled and studied for cutaneous or IgE reactivity to Ac, Blattella germanica, Penaeus monodon, and Dermatophagoides pteronyssinus. Extract and molecular IgE reactivity to bees, wasps, hornets, and yellow jacket venoms were also studied in 119 patients with a clinical history of adverse reaction to Hymenoptera. Immunoblot (IB) analysis and immunoCAP IgE inhibition experiments were carried out in selected sera. Ac sensitization was recorded in 96 (46.8%) patients on SPT. Strict relationship between Ac and D. pteronyssinus, B. germanica, P. monodon, or Apis mellifera reactivity on SPT was observed. Ac IgE recognition was seen in 60/131 (45.8%) patients, 49 (81.6%) of them SPT positive, and 5/14 IB reactors. Ac IgE sensitization was associated with Tabanus spp, A. mellifera, Vespula vulgaris, and Polistes dominula reactivity. A strict relationship between Ac IgE reactivity and Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was recorded. IgE reactivity to AC was inhibited in 9/15 cases after serum absorption with the A. mellifera extract. Both SPT and IgE Ac reactivity is observed in about half of patients with a history of large local reactions to mosquito bites. The significant relationship between Ac sensitization and either extract or single bee venom components is suggestive of a "bee-mosquito syndrome" occurrence. © 2018 S. Karger AG, Basel.

  15. Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes.

    PubMed

    Bekar, Lane K; Loewen, Matthew E; Cao, Kun; Sun, Xianfeng; Leis, Jerome; Wang, Rui; Forsyth, George W; Walz, Wolfgang

    2005-03-01

    Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity.

  16. Behavioural sensitivity to binaural spatial cues in ferrets: evidence for plasticity in the duplex theory of sound localization

    PubMed Central

    Keating, Peter; Nodal, Fernando R; King, Andrew J

    2014-01-01

    For over a century, the duplex theory has guided our understanding of human sound localization in the horizontal plane. According to this theory, the auditory system uses interaural time differences (ITDs) and interaural level differences (ILDs) to localize low-frequency and high-frequency sounds, respectively. Whilst this theory successfully accounts for the localization of tones by humans, some species show very different behaviour. Ferrets are widely used for studying both clinical and fundamental aspects of spatial hearing, but it is not known whether the duplex theory applies to this species or, if so, to what extent the frequency range over which each binaural cue is used depends on acoustical or neurophysiological factors. To address these issues, we trained ferrets to lateralize tones presented over earphones and found that the frequency dependence of ITD and ILD sensitivity broadly paralleled that observed in humans. Compared with humans, however, the transition between ITD and ILD sensitivity was shifted toward higher frequencies. We found that the frequency dependence of ITD sensitivity in ferrets can partially be accounted for by acoustical factors, although neurophysiological mechanisms are also likely to be involved. Moreover, we show that binaural cue sensitivity can be shaped by experience, as training ferrets on a 1-kHz ILD task resulted in significant improvements in thresholds that were specific to the trained cue and frequency. Our results provide new insights into the factors limiting the use of different sound localization cues and highlight the importance of sensory experience in shaping the underlying neural mechanisms. PMID:24256073

  17. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients.

    PubMed

    Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

    2015-06-01

    Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37°C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Fusion of Computed Tomography and PROPELLER Diffusion-Weighted Magnetic Resonance Imaging for the Detection and Localization of Middle Ear Cholesteatoma.

    PubMed

    Locketz, Garrett D; Li, Peter M M C; Fischbein, Nancy J; Holdsworth, Samantha J; Blevins, Nikolas H

    2016-10-01

    A method to optimize imaging of cholesteatoma by combining the strengths of available modalities will improve diagnostic accuracy and help to target treatment. To assess whether fusing Periodically Rotated Overlapping Parallel Lines With Enhanced Reconstruction (PROPELLER) diffusion-weighted magnetic resonance imaging (DW-MRI) with corresponding temporal bone computed tomography (CT) images could increase cholesteatoma diagnostic and localization accuracy across 6 distinct anatomical regions of the temporal bone. Case series and preliminary technology evaluation of adults with preoperative temporal bone CT and PROPELLER DW-MRI scans who underwent surgery for clinically suggested cholesteatoma at a tertiary academic hospital. When cholesteatoma was encountered surgically, the precise location was recorded in a diagram of the middle ear and mastoid. For each patient, the 3 image data sets (CT, PROPELLER DW-MRI, and CT-MRI fusion) were reviewed in random order for the presence or absence of cholesteatoma by an investigator blinded to operative findings. If cholesteatoma was deemed present on review of each imaging modality, the location of the lesion was mapped presumptively. Image analysis was then compared with surgical findings. Twelve adults (5 women and 7 men; median [range] age, 45.5 [19-77] years) were included. The use of CT-MRI fusion had greater diagnostic sensitivity (0.88 vs 0.75), positive predictive value (0.88 vs 0.86), and negative predictive value (0.75 vs 0.60) than PROPELLER DW-MRI alone. Image fusion also showed increased overall localization accuracy when stratified across 6 distinct anatomical regions of the temporal bone (localization sensitivity and specificity, 0.76 and 0.98 for CT-MRI fusion vs 0.58 and 0.98 for PROPELLER DW-MRI). For PROPELLER DW-MRI, there were 15 true-positive, 45 true-negative, 1 false-positive, and 11 false-negative results; overall accuracy was 0.83. For CT-MRI fusion, there were 20 true-positive, 45 true-negative, 1 false-positive, and 6 false-negative results; overall accuracy was 0.90. The poor anatomical spatial resolution of DW-MRI makes precise localization of cholesteatoma within the middle ear and mastoid a diagnostic challenge. This study suggests that the bony anatomic detail obtained via CT coupled with the excellent sensitivity and specificity of PROPELLER DW-MRI for cholesteatoma can improve both preoperative identification and localization of disease over DW-MRI alone.

  19. Disulfide proteomics of rice cultured cells in response to OsRacl and probenazole-related immune signaling pathway in rice.

    PubMed

    Morino, Kazuko; Kimizu, Mayumi; Fujiwara, Masayuki

    2016-01-01

    Reactive oxygen species (ROS) production is an early event in the immune response of plants. ROS production affects the redox-based modification of cysteine residues in redox proteins, which contribute to protein functions such as enzymatic activity, protein-protein interactions, oligomerization, and intracellular localization. Thus, the sensitivity of cysteine residues to changes in the cellular redox status is critical to the immune response of plants. We used disulfide proteomics to identify immune response-related redox proteins. Total protein was extracted from rice cultured cells expressing constitutively active or dominant-negative OsRacl, which is a key regulator of the immune response in rice, and from rice cultured cells that were treated with probenazole, which is an activator of the plant immune response, in the presence of the thiol group-specific fluorescent probe monobromobimane (mBBr), which was a tag for reduced proteins in a differential display two-dimensional gel electrophoresis. The mBBr fluorescence was detected by using a charge-coupled device system, and total protein spots were detected using Coomassie brilliant blue staining. Both of the protein spots were analyzed by gel image software and identified using MS spectrometry. The possible disulfide bonds were identified using the disulfide bond prediction software. Subcellular localization and bimolecular fluorescence complementation analysis were performed in one of the identified proteins: Oryza sativa cold shock protein 2 (OsCSP2). We identified seven proteins carrying potential redox-sensitive cysteine residues. Two proteins of them were oxidized in cultured cells expressing DN-OsRac1, which indicates that these two proteins would be inactivated through the inhibition of OsRac1 signaling pathway. One of the two oxidized proteins, OsCSP2, contains 197 amino acid residues and six cysteine residues. Site-directed mutagenesis of these cysteine residues revealed that a Cys 140 mutation causes mislocalization of a green fluorescent protein fusion protein in the root cells of rice. Bimolecular fluorescence complementation analysis revealed that OsCSP2 is localized in the nucleus as a homo dimer in rice root cells. The findings of the study indicate that redox-sensitive cysteine modification would contribute to the immune response in rice.

  20. Is the Job Satisfaction Survey a good tool to measure job satisfaction amongst health workers in Nepal? Results of a validation analysis.

    PubMed

    Batura, Neha; Skordis-Worrall, Jolene; Thapa, Rita; Basnyat, Regina; Morrison, Joanna

    2016-07-27

    Job satisfaction is an important predictor of an individual's intention to leave the workplace. It is increasingly being used to consider the retention of health workers in low-income countries. However, the determinants of job satisfaction vary in different contexts, and it is important to use measurement methods that are contextually appropriate. We identified a measurement tool developed by Paul Spector, and used mixed methods to assess its validity and reliability in measuring job satisfaction among maternal and newborn health workers (MNHWs) in government facilities in rural Nepal. We administered the tool to 137 MNHWs and collected qualitative data from 78 MNHWs, and district and central level stakeholders to explore definitions of job satisfaction and factors that affected it. We calculated a job satisfaction index for all MNHWs using quantitative data and tested for validity, reliability and sensitivity. We conducted qualitative content analysis and compared the job satisfaction indices with qualitative data. Results from the internal consistency tests offer encouraging evidence of the validity, reliability and sensitivity of the tool. Overall, the job satisfaction indices reflected the qualitative data. The tool was able to distinguish levels of job satisfaction among MNHWs. However, the work environment and promotion dimensions of the tool did not adequately reflect local conditions. Further, community fit was found to impact job satisfaction but was not captured by the tool. The relatively high incidence of missing responses may suggest that responding to some statements was perceived as risky. Our findings indicate that the adapted job satisfaction survey was able to measure job satisfaction in Nepal. However, it did not include key contextual factors affecting job satisfaction of MNHWs, and as such may have been less sensitive than a more inclusive measure. The findings suggest that this tool can be used in similar settings and populations, with the addition of statements reflecting the nature of the work environment and structure of the local health system. Qualitative data on job satisfaction should be collected before using the tool in a new context, to highlight any locally relevant dimensions of job satisfaction not already captured in the standard survey.

  1. Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity.

    PubMed

    Astrada, Soledad; Fernández Massó, Julio Raúl; Vallespí, Maribel G; Bollati-Fogolín, Mariela

    2018-03-30

    CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization.

  2. Parametric Sensitivity Analysis of Precipitation at Global and Local Scales in the Community Atmosphere Model CAM5

    DOE PAGES

    Qian, Yun; Yan, Huiping; Hou, Zhangshuan; ...

    2015-04-10

    We investigate the sensitivity of precipitation characteristics (mean, extreme and diurnal cycle) to a set of uncertain parameters that influence the qualitative and quantitative behavior of the cloud and aerosol processes in the Community Atmosphere Model (CAM5). We adopt both the Latin hypercube and quasi-Monte Carlo sampling approaches to effectively explore the high-dimensional parameter space and then conduct two large sets of simulations. One set consists of 1100 simulations (cloud ensemble) perturbing 22 parameters related to cloud physics and convection, and the other set consists of 256 simulations (aerosol ensemble) focusing on 16 parameters related to aerosols and cloud microphysics.more » Results show that for the 22 parameters perturbed in the cloud ensemble, the six having the greatest influences on the global mean precipitation are identified, three of which (related to the deep convection scheme) are the primary contributors to the total variance of the phase and amplitude of the precipitation diurnal cycle over land. The extreme precipitation characteristics are sensitive to a fewer number of parameters. The precipitation does not always respond monotonically to parameter change. The influence of individual parameters does not depend on the sampling approaches or concomitant parameters selected. Generally the GLM is able to explain more of the parametric sensitivity of global precipitation than local or regional features. The total explained variance for precipitation is primarily due to contributions from the individual parameters (75-90% in total). The total variance shows a significant seasonal variability in the mid-latitude continental regions, but very small in tropical continental regions.« less

  3. Plasmon-enhanced tilted fiber Bragg gratings with oriented silver nanowire coatings

    NASA Astrophysics Data System (ADS)

    Renoirt, J.-M.; Debliquy, M.; Albert, J.; Ianoul, A.; Caucheteur, C.

    2014-05-01

    (TFBG) covered by silver nanowires aligned perpendicularly to the fiber axis. TBFGs are a convenient way to measure surrounding refractive index, as they provide intrinsic temperature-insensitivity and preserve the optical fiber structural integrity. With bare TFBGs, sensitivity is about 60 nm/RIU (refractive index unit) while when coated with a gold thin film, surface plasmon resonance can be excited leading to a sensitivity about 600 nm/RIU. In our case, we show that localized plasmon resonances can be excited on silver nanowires. These nanowires (100 nm diameter and about 2.5 µm length) were synthetized by polyol process (ethylene glycol reducing silver nitrate in the presence of poly (vinyl pyrrolidone and sodium chloride). The nanowires were aligned and deposited perpendicularly to the fiber axis on the gratings using the Langmuir-Blodgett technique in order to maximise the coupling between azimuthally polarized light modes and the localized plasmons. Excitation of surface plasmons at wavelengths around 1.5 µm occurred, leading to a dip in the polarization dependent losses of the grating. This dip is highly dependent of the surrounding refractive index, leading to a sensitivity of 650 nm/RIU, which is a 10-fold increase compared to bare gratings. We obtain results equal or slightly higher than those obtained using a gold layer on TFBGs. In spite of the comparable bulk refractometric sensitivity, the use of these oriented nanowire layers provide significantly higher contact surface area for biochemical analysis using bioreceptors, and benefit from stronger polarization selectivity between azimuthal and radially polarized modes.

  4. Local oscillator induced degradation of medium-term stability in passive atomic frequency standards

    NASA Technical Reports Server (NTRS)

    Dick, G. John; Prestage, John D.; Greenhall, Charles A.; Maleki, Lute

    1990-01-01

    As the performance of passive atomic frequency standards improves, a new limitation is encountered due to frequency fluctuations in an ancillary local oscillator (L.O.). The effect is due to time variation in the gain of the feedback which compensates L.O. frequency fluctuations. The high performance promised by new microwave and optical trapped ion standards may be severely compromised by this effect. Researchers present an analysis of this performance limitation for the case of sequentially interrogated standards. The time dependence of the sensitivity of the interrogation process to L.O. frequency fluctuations is evaluated for single-pulse and double-pulse Ramsey RF interrogation and for amplitude modulated pulses. The effect of these various time dependencies on performance of the standard is calculated for an L.O. with frequency fluctuations showing a typical 1/f spectral density. A limiting 1/sq. root gamma dependent deviation of frequency fluctuations is calculated as a function of pulse lengths, dead time, and pulse overlap. Researchers also present conceptual and hardware-oriented solutions to this problem which achieve a much more nearly constant sensitivity to L.O. fluctuations. Solutions involve use of double-pulse interrogation; alternate interrogation of multiple traps so that the dead time of one trap can be covered by operation of the other; and the use of double-pulse interrogation for two traps, so that during the time of the RF pulses, the increasing sensitivity of one trap tends to compensate for the decreasing sensitivity of the other. A solution making use of amplified-modulated pulses is also presented which shows nominally zero time variation.

  5. Characterizing Chemical Similarity with Vibrational Spectroscopy: New Insights into the Substituent Effects in Monosubstituted Benzenes.

    PubMed

    Tao, Yunwen; Zou, Wenli; Cremer, Dieter; Kraka, Elfi

    2017-10-26

    A novel approach is presented to assess chemical similarity based the local vibrational mode analysis developed by Konkoli and Cremer. The local mode frequency shifts are introduced as similarity descriptors that are sensitive to any electronic structure change. In this work, 59 different monosubstituted benzenes are compared. For a subset of 43 compounds, for which experimental data was available, the ortho-/para- and meta-directing effect in electrophilic aromatic substitution reactions could be correctly reproduced, proving the robustness of the new similarity index. For the remaining 16 compounds, the directing effect was predicted. The new approach is broadly applicable to all compounds for which either experimental or calculated vibrational frequency information is available.

  6. Observation of airplane flow fields by natural condensation effects

    NASA Technical Reports Server (NTRS)

    Campbell, James F.; Chambers, Joseph R.; Rumsey, Christopher L.

    1988-01-01

    In-flight condensation patterns can illustrate a variety of airplane flow fields, such as attached and separated flows, vortex flows, and expansion and shock waves. These patterns are a unique source of flow visualization that has not been utilized previously. Condensation patterns at full-scale Reynolds number can provide useful information for researchers experimenting in subscale tunnels. It is also shown that computed values of relative humidity in the local flow field provide an inexpensive way to analyze the qualitative features of the condensation pattern, although a more complete theoretical modeling is necessary to obtain details of the condensation process. Furthermore, the analysis revealed that relative humidity is more sensitive to changes in local static temperature than to changes in pressure.

  7. Job Superscheduler Architecture and Performance in Computational Grid Environments

    NASA Technical Reports Server (NTRS)

    Shan, Hongzhang; Oliker, Leonid; Biswas, Rupak

    2003-01-01

    Computational grids hold great promise in utilizing geographically separated heterogeneous resources to solve large-scale complex scientific problems. However, a number of major technical hurdles, including distributed resource management and effective job scheduling, stand in the way of realizing these gains. In this paper, we propose a novel grid superscheduler architecture and three distributed job migration algorithms. We also model the critical interaction between the superscheduler and autonomous local schedulers. Extensive performance comparisons with ideal, central, and local schemes using real workloads from leading computational centers are conducted in a simulation environment. Additionally, synthetic workloads are used to perform a detailed sensitivity analysis of our superscheduler. Several key metrics demonstrate that substantial performance gains can be achieved via smart superscheduling in distributed computational grids.

  8. [Multifocal visual electrophysiology in visual function evaluation].

    PubMed

    Peng, Shu-Ya; Chen, Jie-Min; Liu, Rui-Jue; Zhou, Shu; Liu, Dong-Mei; Xia, Wen-Tao

    2013-08-01

    Multifocal visual electrophysiology, consisting of multifocal electroretinography (mfERG) and multifocal visual evoked potential (mfVEP), can objectively evaluate retina function and retina-cortical conduction pathway status by stimulating many local retinal regions and obtaining each local response simultaneously. Having many advantages such as short testing time and high sensitivity, it has been widely used in clinical ophthalmology, especially in the diagnosis of retinal disease and glaucoma. It is a new objective technique in clinical forensic medicine involving visual function evaluation of ocular trauma in particular. This article summarizes the way of stimulation, the position of electrodes, the way of analysis, the visual function evaluation of mfERG and mfVEP, and discussed the value of multifocal visual electrophysiology in forensic medicine.

  9. The influence of local electric fields on photoinduced absorption in dye-sensitized solar cells.

    PubMed

    Cappel, Ute B; Feldt, Sandra M; Schöneboom, Jan; Hagfeldt, Anders; Boschloo, Gerrit

    2010-07-07

    The dye-sensitized solar cell (DSC) challenges conventional photovoltaics with its potential for low-cost production and its flexibility in terms of color and design. Transient absorption spectroscopy is widely used to unravel the working mechanism of DSCs. A surprising, unexplained feature observed in these studies is an apparent bleach of the ground-state absorption of the dye, under conditions where the dye is in the ground state. Here, we demonstrate that this feature can be attributed to a change of the local electric field affecting the absorption spectrum of the dye, an effect related to the Stark effect first reported in 1913. We present a method for measuring the effect of an externally applied electric field on the absorption of dye monolayers adsorbed on flat TiO(2) substrates. The measured signal has the shape of the first derivative of the absorption spectra of the dyes and reverses sign along with the reversion of the direction of the change in dipole moment upon excitation relative to the TiO(2) surface. A very similar signal is observed in photoinduced absorption spectra of dye-sensitized TiO(2) electrodes under solar cell conditions, demonstrating that the electric field across the dye molecules changes upon illumination. This result has important implications for the analysis of transient absorption spectra of DSCs and other molecular optoelectronic devices and challenges the interpretation of many previously published results.

  10. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Srisuttee, Ratakorn; Koh, Sang Seok; Department of Functional Genomics, University of Science and Technology, Daejeon 305-333

    Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stablymore » expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.« less

  11. The interplay between siderophore secretion and coupled iron and copper transport in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120.

    PubMed

    Nicolaisen, Kerstin; Hahn, Alexander; Valdebenito, Marianne; Moslavac, Suncana; Samborski, Anastazia; Maldener, Iris; Wilken, Corinna; Valladares, Ana; Flores, Enrique; Hantke, Klaus; Schleiff, Enrico

    2010-11-01

    Iron uptake is essential for Gram-negative bacteria including cyanobacteria. In cyanobacteria, however, the iron demand is higher than in proteobacteria due to the function of iron as a cofactor in photosynthesis and nitrogen fixation, but our understanding of iron uptake by cyanobacteria stands behind the knowledge in proteobacteria. Here, two genes involved in this process in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 were identified. ORF all4025 encodes SchE, a putative cytoplasmic membrane-localized transporter involved in TolC-dependent siderophore secretion. Inactivation of schE resulted in an enhanced sensitivity to high metal concentrations and decreased secretion of hydroxamate-type siderophores. ORF all4026 encodes a predicted outer membrane-localized TonB-dependent iron transporter, IacT. Inactivation of iacT resulted in decreased sensitivity to elevated iron and copper levels. Expression of iacT from the artificial trc promoter (P(trc)) resulted in sensitization against tested metals. Further analysis showed that iron and copper effects are synergistic because a decreased supply of iron induced a significant decrease of copper levels in the iacT insertion mutant but an increase of those levels in the strain carrying P(trc)-iacT. Our results unravel a link between iron and copper homeostasis in Anabaena sp. PCC 7120. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Direct magnetic field estimation based on echo planar raw data.

    PubMed

    Testud, Frederik; Splitthoff, Daniel Nicolas; Speck, Oliver; Hennig, Jürgen; Zaitsev, Maxim

    2010-07-01

    Gradient recalled echo echo planar imaging is widely used in functional magnetic resonance imaging. The fast data acquisition is, however, very sensitive to field inhomogeneities which manifest themselves as artifacts in the images. Typically used correction methods have the common deficit that the data for the correction are acquired only once at the beginning of the experiment, assuming the field inhomogeneity distribution B(0) does not change over the course of the experiment. In this paper, methods to extract the magnetic field distribution from the acquired k-space data or from the reconstructed phase image of a gradient echo planar sequence are compared and extended. A common derivation for the presented approaches provides a solid theoretical basis, enables a fair comparison and demonstrates the equivalence of the k-space and the image phase based approaches. The image phase analysis is extended here to calculate the local gradient in the readout direction and improvements are introduced to the echo shift analysis, referred to here as "k-space filtering analysis." The described methods are compared to experimentally acquired B(0) maps in phantoms and in vivo. The k-space filtering analysis presented in this work demonstrated to be the most sensitive method to detect field inhomogeneities.

  13. An ATP sensitive light addressable biosensor for extracellular monitoring of single taste receptor cell.

    PubMed

    Wu, Chunsheng; Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping

    2012-12-01

    Adenosine triphosphate (ATP) is considered as the key neurotransmitter in taste buds for taste signal transmission and processing. Measurements of ATP secreted from single taste receptor cell (TRC) with high sensitivity and specificity are essential for investigating mechanisms underlying taste cell-to-cell communications. In this study, we presented an aptamer-based biosensor for the detection of ATP locally secreted from single TRC. ATP sensitive DNA aptamer was used as recognition element and its DNA competitor was served as signal transduction element that was covalently immobilized on the surface of light addressable potentiometric sensor (LAPS). Due to the light addressable capability of LAPS, local ATP secretion from single TRC can be detected by monitoring the working potential shifts of LAPS. The results show this biosensor can detect ATP with high sensitivity and specificity. It is demonstrated this biosensor can effectively detect the local ATP secretion from single TRC responding to tastant mixture. This biosensor could provide a promising new tool for the research of taste cell-to-cell communications as well as for the detection of local ATP secretion from other types of ATP secreting individual cells.

  14. Genetic Architecture of Aluminum Tolerance in Rice (Oryza sativa) Determined through Genome-Wide Association Analysis and QTL Mapping

    PubMed Central

    Famoso, Adam N.; Zhao, Keyan; Clark, Randy T.; Tung, Chih-Wei; Wright, Mark H.; Bustamante, Carlos; Kochian, Leon V.; McCouch, Susan R.

    2011-01-01

    Aluminum (Al) toxicity is a primary limitation to crop productivity on acid soils, and rice has been demonstrated to be significantly more Al tolerant than other cereal crops. However, the mechanisms of rice Al tolerance are largely unknown, and no genes underlying natural variation have been reported. We screened 383 diverse rice accessions, conducted a genome-wide association (GWA) study, and conducted QTL mapping in two bi-parental populations using three estimates of Al tolerance based on root growth. Subpopulation structure explained 57% of the phenotypic variation, and the mean Al tolerance in Japonica was twice that of Indica. Forty-eight regions associated with Al tolerance were identified by GWA analysis, most of which were subpopulation-specific. Four of these regions co-localized with a priori candidate genes, and two highly significant regions co-localized with previously identified QTLs. Three regions corresponding to induced Al-sensitive rice mutants (ART1, STAR2, Nrat1) were identified through bi-parental QTL mapping or GWA to be involved in natural variation for Al tolerance. Haplotype analysis around the Nrat1 gene identified susceptible and tolerant haplotypes explaining 40% of the Al tolerance variation within the aus subpopulation, and sequence analysis of Nrat1 identified a trio of non-synonymous mutations predictive of Al sensitivity in our diversity panel. GWA analysis discovered more phenotype–genotype associations and provided higher resolution, but QTL mapping identified critical rare and/or subpopulation-specific alleles not detected by GWA analysis. Mapping using Indica/Japonica populations identified QTLs associated with transgressive variation where alleles from a susceptible aus or indica parent enhanced Al tolerance in a tolerant Japonica background. This work supports the hypothesis that selectively introgressing alleles across subpopulations is an efficient approach for trait enhancement in plant breeding programs and demonstrates the fundamental importance of subpopulation in interpreting and manipulating the genetics of complex traits in rice. PMID:21829395

  15. Translation and cross-cultural adaptation of a family booklet on comfort care in dementia: sensitive topics revised before implementation.

    PubMed

    van der Steen, Jenny T; Hertogh, Cees M P M; de Graas, Tjomme; Nakanishi, Miharu; Toscani, Franco; Arcand, Marcel

    2013-02-01

    Families of patients with dementia may need support in difficult end-of-life decision making. Such guidance may be culturally sensitive. To support families in Canada, a booklet was developed to aid decision making on palliative care issues. For reasons of cost effectiveness and promising effects, we prepared for its implementation in Italy, the Netherlands and Japan. Local teams translated and adapted the booklet to local ethical, legal and medical standards where needed, retaining guidance on palliative care. Using qualitative content analyses, we grouped and compared adaptations to understand culturally sensitive aspects. Three themes emerged: (1) relationships among patient, physician and other professionals-the authority of the physician was more explicit in adapted versions; (2) patient rights and family position-adding detail about local regulations; and (3) typology of treatments and decisions. Considerations underlying palliative care decisions were detailed (Dutch and Italian versions), and the Japanese version frequently referred to professional and legal standards, and life-prolongation was a competing goal. Text on artificial feeding or fluids and euthanasia was revised extensively. Providing artificial feeding and fluids and discussing euthanasia may be particularly sensitive topics, and guidance on these subjects needs careful consideration of ethical aspects and possible adaptations to local standards and practice. The findings may promote cross-national debate on sensitive, core issues regarding end-of-life care in dementia.

  16. In situ fluorescence imaging of localized corrosion with a pH-sensitive imaging fiber

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Panova, A.A.; Pantano, P.; Walt, D.R.

    1997-12-01

    A fiber optic pH-sensor capable of both visualizing corrosion sites and measuring local chemical concentrations is applied to real-time corrosion monitoring. The imaging fiber`s distal face containing an immobilized pH-sensitive fluorescent dye is brought into contact with metal surfaces submerged in aqueous buffers and fluorescence images are acquired as a function of time. The observed changes in fluorescence due to increases in pH at cathodic sites and decreases in pH at anodic sites are indicative of localized corrosion rates.

  17. Local active information storage as a tool to understand distributed neural information processing

    PubMed Central

    Wibral, Michael; Lizier, Joseph T.; Vögler, Sebastian; Priesemann, Viola; Galuske, Ralf

    2013-01-01

    Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for today's digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, definitions were given for the dynamics of these information processing operations on a local scale in space and time in a distributed system, and the specific concept of local active information storage was successfully applied to the analysis and optimization of artificial neural systems. However, no attempt to measure the space-time dynamics of local active information storage in neural data has been made to date. Here we measure local active information storage on a local scale in time and space in voltage sensitive dye imaging data from area 18 of the cat. We show that storage reflects neural properties such as stimulus preferences and surprise upon unexpected stimulus change, and in area 18 reflects the abstract concept of an ongoing stimulus despite the locally random nature of this stimulus. We suggest that LAIS will be a useful quantity to test theories of cortical function, such as predictive coding. PMID:24501593

  18. Surface-enhanced localized surface plasmon resonance biosensing of avian influenza DNA hybridization using subwavelength metallic nanoarrays

    NASA Astrophysics Data System (ADS)

    Kim, Shin Ae; Byun, Kyung Min; Kim, Kyujung; Jang, Sung Min; Ma, Kyungjae; Oh, Youngjin; Kim, Donghyun; Kim, Sung Guk; Shuler, Michael L.; Kim, Sung June

    2010-09-01

    We demonstrated enhanced localized surface plasmon resonance (SPR) biosensing based on subwavelength gold nanoarrays built on a thin gold film. Arrays of nanogratings (1D) and nanoholes (2D) with a period of 200 nm were fabricated by electron-beam lithography and used for the detection of avian influenza DNA hybridization. Experimental results showed that both nanoarrays provided significant sensitivity improvement and, especially, 1D nanogratings exhibited higher SPR signal amplification compared with 2D nanohole arrays. The sensitivity enhancement is associated with changes in surface-limited reaction area and strong interactions between bound molecules and localized plasmon fields. Our approach is expected to improve both the sensitivity and sensing resolution and can be applicable to label-free detection of DNA without amplification by polymerase chain reaction.

  19. Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

    PubMed

    Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

    2017-03-20

    As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

  20. Weather Research and Forecasting Model Sensitivity Comparisons for Warm Season Convective Initiation

    NASA Technical Reports Server (NTRS)

    Watson, Leela R.

    2007-01-01

    This report describes the work done by the Applied Meteorology Unit (AMU) in assessing the success of different model configurations in predicting warm season convection over East-Central Florida. The Weather Research and Forecasting Environmental Modeling System (WRF EMS) software allows users to choose among two dynamical cores - the Advanced Research WRF (ARW) and the Non-hydrostatic Mesoscale Model (NMM). There are also data assimilation analysis packages available for the initialization of the WRF model - the Local Analysis and Prediction System (LAPS) and the Advanced Regional Prediction System (ARPS) Data Analysis System (ADAS). Besides model core and initialization options, the WRF model can be run with one- or two-way nesting. Having a series of initialization options and WRF cores, as well as many options within each core, creates challenges for local forecasters, such as determining which configuration options are best to address specific forecast concerns. This project assessed three different model intializations available to determine which configuration best predicts warm season convective initiation in East-Central Florida. The project also examined the use of one- and two-way nesting in predicting warm season convection.

  1. Economic impact of Tegaderm chlorhexidine gluconate (CHG) dressing in critically ill patients.

    PubMed

    Thokala, Praveen; Arrowsmith, Martin; Poku, Edith; Martyn-St James, Marissa; Anderson, Jeff; Foster, Steve; Elliott, Tom; Whitehouse, Tony

    2016-09-01

    To estimate the economic impact of a Tegaderm TM chlorhexidine gluconate (CHG) gel dressing compared with a standard intravenous (i.v.) dressing (defined as non-antimicrobial transparent film dressing), used for insertion site care of short-term central venous and arterial catheters (intravascular catheters) in adult critical care patients using a cost-consequence model populated with data from published sources. A decision analytical cost-consequence model was developed which assigned each patient with an indwelling intravascular catheter and a standard dressing, a baseline risk of associated dermatitis, local infection at the catheter insertion site and catheter-related bloodstream infections (CRBSI), estimated from published secondary sources. The risks of these events for patients with a Tegaderm CHG were estimated by applying the effectiveness parameters from the clinical review to the baseline risks. Costs were accrued through costs of intervention (i.e. Tegaderm CHG or standard intravenous dressing) and hospital treatment costs depended on whether the patients had local dermatitis, local infection or CRBSI. Total costs were estimated as mean values of 10,000 probabilistic sensitivity analysis (PSA) runs. Tegaderm CHG resulted in an average cost-saving of £77 per patient in an intensive care unit. Tegaderm CHG also has a 98.5% probability of being cost-saving compared to standard i.v. dressings. The analyses suggest that Tegaderm CHG is a cost-saving strategy to reduce CRBSI and the results were robust to sensitivity analyses.

  2. Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

    PubMed

    Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

    2017-04-16

    An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

  3. Can currently available non-animal methods detect pre and pro-haptens relevant for skin sensitization?

    PubMed

    Patlewicz, Grace; Casati, Silvia; Basketter, David A; Asturiol, David; Roberts, David W; Lepoittevin, Jean-Pierre; Worth, Andrew P; Aschberger, Karin

    2016-12-01

    Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal tests such as the Local Lymph Node Assay (LLNA). In recent years, regulations in the cosmetics and chemicals sectors have provided strong impetus to develop non-animal alternatives. Three test methods have undergone OECD validation: the direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human Cell Line Activation Test (h-CLAT). Whilst these methods perform relatively well in predicting LLNA results, a concern raised is their ability to predict chemicals that need activation to be sensitizing (pre- or pro-haptens). This current study reviewed an EURL ECVAM dataset of 127 substances for which information was available in the LLNA and three non-animal test methods. Twenty eight of the sensitizers needed to be activated, with the majority being pre-haptens. These were correctly identified by 1 or more of the test methods. Six substances were categorized exclusively as pro-haptens, but were correctly identified by at least one of the cell-based assays. The analysis here showed that skin metabolism was not likely to be a major consideration for assessing sensitization potential and that sensitizers requiring activation could be identified correctly using one or more of the current non-animal methods. Published by Elsevier Inc.

  4. The sensitivity and significance analysis of parameters in the model of pH regulation on lactic acid production by Lactobacillus bulgaricus.

    PubMed

    Liu, Ke; Zeng, Xiangmiao; Qiao, Lei; Li, Xisheng; Yang, Yubo; Dai, Cuihong; Hou, Aiju; Xu, Dechang

    2014-01-01

    The excessive production of lactic acid by L. bulgaricus during yogurt storage is a phenomenon we are always tried to prevent. The methods used in industry either control the post-acidification inefficiently or kill the probiotics in yogurt. Genetic methods of changing the activity of one enzyme related to lactic acid metabolism make the bacteria short of energy to growth, although they are efficient ways in controlling lactic acid production. A model of pH-induced promoter regulation on the production of lactic acid by L. bulgaricus was built. The modelled lactic acid metabolism without pH-induced promoter regulation fitted well with wild type L. bulgaricus (R2LAC = 0.943, R2LA = 0.942). Both the local sensitivity analysis and Sobol sensitivity analysis indicated parameters Tmax, GR, KLR, S, V0, V1 and dLR were sensitive. In order to guide the future biology experiments, three adjustable parameters, KLR, V0 and V1, were chosen for further simulations. V0 had little effect on lactic acid production if the pH-induced promoter could be well induced when pH decreased to its threshold. KLR and V1 both exhibited great influence on the producing of lactic acid. The proposed method of introducing a pH-induced promoter to regulate a repressor gene could restrain the synthesis of lactic acid if an appropriate strength of promoter and/or an appropriate strength of ribosome binding sequence (RBS) in lacR gene has been designed.

  5. Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint.

    PubMed

    Moncada, S; Ferreira, S H; Vane, J R

    1975-04-01

    A method has been developed to measure the analgesic action of aspirin-like drugs in knee joints of anaesthetized dogs. Bradykinin, injected into the joint cavity, induced a reflex rise in blood pressure which was dose-dependent; this was used as a measure of nociceptive activity. The joint cavity became more sensitive to bradykinin as the experiment proceeded, or when a low concentration of prostaglandin E1 or E2 was infused locally. The increase in sensitivity with time was prevented by local injection of aspirin or indomethacin, but that induced by exogenous prostaglandin infusion was not. Injections of carrageenin into dog knee joints increased the prostaglandin E2 content of synovial fluid by up to 160 ng per joint; indomethacin prevented this increase. These experiments support our previous conclusion that local biosynthesis of a prostaglandin (induced by mild trauma) sensitizes pain receptors to mechanical or chemical stimuli. Aspirin-like drugs are analgesic because they prevent prostaglandin biosynthesis, thereby preventing this sensitization.

  6. Binaural sensitivity changes between cortical on and off responses

    PubMed Central

    Dahmen, Johannes C.; King, Andrew J.; Schnupp, Jan W. H.

    2011-01-01

    Neurons exhibiting on and off responses with different frequency tuning have previously been described in the primary auditory cortex (A1) of anesthetized and awake animals, but it is unknown whether other tuning properties, including sensitivity to binaural localization cues, also differ between on and off responses. We measured the sensitivity of A1 neurons in anesthetized ferrets to 1) interaural level differences (ILDs), using unmodulated broadband noise with varying ILDs and average binaural levels, and 2) interaural time delays (ITDs), using sinusoidally amplitude-modulated broadband noise with varying envelope ITDs. We also assessed fine-structure ITD sensitivity and frequency tuning, using pure-tone stimuli. Neurons most commonly responded to stimulus onset only, but purely off responses and on-off responses were also recorded. Of the units exhibiting significant binaural sensitivity nearly one-quarter showed binaural sensitivity in both on and off responses, but in almost all (∼97%) of these units the binaural tuning of the on responses differed significantly from that seen in the off responses. Moreover, averaged, normalized ILD and ITD tuning curves calculated from all units showing significant sensitivity to binaural cues indicated that on and off responses displayed different sensitivity patterns across the population. A principal component analysis of ITD response functions suggested a continuous cortical distribution of binaural sensitivity, rather than discrete response classes. Rather than reflecting a release from inhibition without any functional significance, we propose that binaural off responses may be important to cortical encoding of sound-source location. PMID:21562191

  7. Multiple heteroatom substitution to graphene nanoribbon

    PubMed Central

    Meyer, Ernst

    2018-01-01

    Substituting heteroatoms into nanostructured graphene elements, such as graphene nanoribbons, offers the possibility for atomic engineering of electronic properties. To characterize these substitutions, functionalized atomic force microscopy (AFM)—a tool to directly resolve chemical structures—is one of the most promising tools, yet the chemical analysis of heteroatoms has been rarely performed. We synthesized multiple heteroatom-substituted graphene nanoribbons and showed that AFM can directly resolve elemental differences and can be correlated to the van der Waals radii, as well as the modulated local electron density caused by the substitution. This elemental-sensitive measurement takes an important step in the analysis of functionalized two-dimensional carbon materials. PMID:29662955

  8. An insight into the formation of severe ozone episodes: modeling the 21/03/01 event in the ESCOMPTE region

    NASA Astrophysics Data System (ADS)

    Lasry, Fanny; Coll, Isabelle; Buisson, Emmanuel

    2005-03-01

    High ozone concentrations are observed more and more frequently in the lower troposphere. The development of such polluted episodes is linked to a complex set of chemical, physical and dynamical parameters that interact with each other. To improve air quality, it is necessary to understand and quantify the role of all these processes on the intensity of ozone formation. The ESCOMPTE program, especially dedicated to the numerical simulation of photochemical episodes, offers an ideal frame to investigate details of the roles of many of these processes through 3D modeling. This paper presents the analysis, with a 3D eulerian model, of a severe and local episode of ozone pollution that occurred on the 21st of March 2001 in the ESCOMPTE region. This episode is particularly interesting due to the intensity of the observed ozone peaks (450 μg/m 3 during 15 mn) but also because it did not occur in summer but at the beginning of spring. As part of the premodeling work of the ESCOMPTE program, this study focuses on the sensitivity of the simulated ozone peaks to various chemical and physical phenomena (long-range transport, industrial emissions, local dynamic phenomena…) to determine their influence on the rise of high local photooxidant concentrations and to better picture the photochemistry of the ESCOMPTE region. Through sensitivity tests to dynamical calculation resolution and emissions, this paper shows how the combination of sea and pond breezes with emissions of reactive VOCs can generate local intense ozone peaks.

  9. Influence of local production and vertical transport on the organic aerosol budget over Paris

    NASA Astrophysics Data System (ADS)

    Janssen, R. H. H.; Tsimpidi, A. P.; Karydis, V. A.; Pozzer, A.; Lelieveld, J.; Crippa, M.; Prévôt, A. S. H.; Ait-Helal, W.; Borbon, A.; Sauvage, S.; Locoge, N.

    2017-08-01

    We performed a case study of the organic aerosol (OA) budget during the MEGAPOLI campaign during summer 2009 in Paris. We combined aerosol mass spectrometer, gas phase chemistry, and atmospheric boundary layer (ABL) data and applied the MXL/MESSy column model. We find that during daytime, vertical mixing due to ABL growth has opposing effects on secondary organic aerosol (SOA) and primary organic aerosol (POA) concentrations. POA concentrations are mainly governed by dilution due to boundary layer expansion and transport of POA-depleted air from aloft, while SOA concentrations are enhanced by entrainment of SOA-rich air from the residual layer (RL). Further, local emissions and photochemical production control the diurnal cycle of SOA. SOA from intermediate volatility organic compounds constitutes about half of the locally formed SOA mass. Other processes that previously have been shown to influence the urban OA budget, such as aging of semivolatile and intermediate volatility organic compounds (S/IVOC), dry deposition of S/IVOCs, and IVOC emissions, are found to have minor influences on OA. Our model results show that the modern carbon content of the OA is driven by vertical and long-range transport, with a minor contribution from local cooking emissions. SOA from regional sources and resulting from aging and long-lived precursors can lead to high SOA concentrations above the ABL, which can strongly influence ground-based observations through downward transport. Sensitivity analysis shows that modeled SOA concentrations in the ABL are equally sensitive to ABL dynamics as to SOA concentrations transported from the RL.

  10. Emotion modulates activity in the 'what' but not 'where' auditory processing pathway.

    PubMed

    Kryklywy, James H; Macpherson, Ewan A; Greening, Steven G; Mitchell, Derek G V

    2013-11-15

    Auditory cortices can be separated into dissociable processing pathways similar to those observed in the visual domain. Emotional stimuli elicit enhanced neural activation within sensory cortices when compared to neutral stimuli. This effect is particularly notable in the ventral visual stream. Little is known, however, about how emotion interacts with dorsal processing streams, and essentially nothing is known about the impact of emotion on auditory stimulus localization. In the current study, we used fMRI in concert with individualized auditory virtual environments to investigate the effect of emotion during an auditory stimulus localization task. Surprisingly, participants were significantly slower to localize emotional relative to neutral sounds. A separate localizer scan was performed to isolate neural regions sensitive to stimulus location independent of emotion. When applied to the main experimental task, a significant main effect of location, but not emotion, was found in this ROI. A whole-brain analysis of the data revealed that posterior-medial regions of auditory cortex were modulated by sound location; however, additional anterior-lateral areas of auditory cortex demonstrated enhanced neural activity to emotional compared to neutral stimuli. The latter region resembled areas described in dual pathway models of auditory processing as the 'what' processing stream, prompting a follow-up task to generate an identity-sensitive ROI (the 'what' pathway) independent of location and emotion. Within this region, significant main effects of location and emotion were identified, as well as a significant interaction. These results suggest that emotion modulates activity in the 'what,' but not the 'where,' auditory processing pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Analgesia for total knee arthroplasty: a meta-analysis comparing local infiltration and femoral nerve block.

    PubMed

    Mei, ShuYa; Jin, ShuQing; Chen, ZhiXia; Ding, XiBing; Zhao, Xiang; Li, Quan

    2015-09-01

    Patients frequently experience postoperative pain after a total knee arthroplasty; such pain is always challenging to treat and may delay the patient's recovery. It is unclear whether local infiltration or a femoral nerve block offers a better analgesic effect after total knee arthroplasty.We performed a systematic review and meta-analysis of randomized controlled trials to compare local infiltration with a femoral nerve block in patients who underwent a primary unilateral total knee arthroplasty. We searched Pubmed, EMBASE, and the Cochrane Library through December 2014. Two reviewers scanned abstracts and extracted data. The data collected included numeric rating scale values for pain at rest and pain upon movement and opioid consumption in the first 24 hours. Mean differences with 95% confidence intervals were calculated for each end point. A sensitivity analysis was conducted to evaluate potential sources of heterogeneity.While the numeric rating scale values for pain upon movement (MD-0.62; 95%CI: -1.13 to -0.12; p=0.02) in the first 24 hours differed significantly between the patients who received local infiltration and those who received a femoral nerve block, there were no differences in the numeric rating scale results for pain at rest (MD-0.42; 95%CI:-1.32 to 0.47; p=0.35) or opioid consumption (MD 2.92; 95%CI:-1.32 to 7.16; p=0.18) in the first 24 hours.Local infiltration and femoral nerve block showed no significant differences in pain intensity at rest or opioid consumption after total knee arthroplasty, but the femoral nerve block was associated with reduced pain upon movement.

  12. Analgesia for total knee arthroplasty: a meta-analysis comparing local infiltration and femoral nerve block

    PubMed Central

    Mei, ShuYa; Jin, ShuQing; Chen, ZhiXia; Ding, XiBing; Zhao, Xiang; Li, Quan

    2015-01-01

    Patients frequently experience postoperative pain after a total knee arthroplasty; such pain is always challenging to treat and may delay the patient's recovery. It is unclear whether local infiltration or a femoral nerve block offers a better analgesic effect after total knee arthroplasty. We performed a systematic review and meta-analysis of randomized controlled trials to compare local infiltration with a femoral nerve block in patients who underwent a primary unilateral total knee arthroplasty. We searched Pubmed, EMBASE, and the Cochrane Library through December 2014. Two reviewers scanned abstracts and extracted data. The data collected included numeric rating scale values for pain at rest and pain upon movement and opioid consumption in the first 24 hours. Mean differences with 95% confidence intervals were calculated for each end point. A sensitivity analysis was conducted to evaluate potential sources of heterogeneity. While the numeric rating scale values for pain upon movement (MD-0.62; 95%CI: -1.13 to -0.12; p=0.02) in the first 24 hours differed significantly between the patients who received local infiltration and those who received a femoral nerve block, there were no differences in the numeric rating scale results for pain at rest (MD-0.42; 95%CI:-1.32 to 0.47; p=0.35) or opioid consumption (MD 2.92; 95%CI:-1.32 to 7.16; p=0.18) in the first 24 hours. Local infiltration and femoral nerve block showed no significant differences in pain intensity at rest or opioid consumption after total knee arthroplasty, but the femoral nerve block was associated with reduced pain upon movement. PMID:26375568

  13. Accelerator mass spectrometry of small biological samples.

    PubMed

    Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran

    2008-12-01

    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of microg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A (12)C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

  14. Probing the pH sensitivity of R-phycoerythrin: investigations of active conformational and functional variation.

    PubMed

    Liu, Lu-Ning; Su, Hai-Nan; Yan, Shi-Gan; Shao, Si-Mi; Xie, Bin-Bin; Chen, Xiu-Lan; Zhang, Xi-Ying; Zhou, Bai-Cheng; Zhang, Yu-Zhong

    2009-07-01

    Crystal structures of phycobiliproteins have provided valuable information regarding the conformations and amino acid organizations of peptides and chromophores, and enable us to investigate their structural and functional relationships with respect to environmental variations. In this work, we explored the pH-induced conformational and functional dynamics of R-phycoerythrin (R-PE) by means of absorption, fluorescence and circular dichroism spectra, together with analysis of its crystal structure. R-PE presents stronger functional stability in the pH range of 3.5-10 compared to the structural stability. Beyond this range, pronounced functional and structural changes occur. Crystal structure analysis shows that the tertiary structure of R-PE is fixed by several key anchoring points of the protein. With this specific association, the fundamental structure of R-PE is stabilized to present physiological spectroscopic properties, while local variations in protein peptides are also allowed in response to environmental disturbances. The functional stability and relative structural sensitivity of R-PE allow environmental adaptation.

  15. Analysis of yeast prp20 mutations and functional complementation by the human homologue RCC1, a protein involved in the control of chromosome condensation.

    PubMed

    Fleischmann, M; Clark, M W; Forrester, W; Wickens, M; Nishimoto, T; Aebi, M

    1991-07-01

    Mutations in the PRP20 gene of yeast show a pleiotropic phenotype, in which both mRNA metabolism and nuclear structure are affected. srm1 mutants, defective in the same gene, influence the signal transduction pathway for the pheromone response. The yeast PRP20/SRM1 protein is highly homologous to the RCC1 protein of man, hamster and frog. In mammalian cells, this protein is a negative regulator for initiation of chromosome condensation. We report the analysis of two, independently isolated, recessive temperature-sensitive prp20 mutants. They have identical G to A transitions, leading to the alteration of a highly conserved glycine residue to glutamic acid. By immunofluorescence microscopy the PRP20 protein was localized in the nucleus. Expression of the RCC1 protein can complement the temperature-sensitive phenotype of prp20 mutants, demonstrating the functional similarity of the yeast and mammalian proteins.

  16. Cost-Effectiveness Analysis of a Capitated Patient Navigation Program for Medicare Beneficiaries with Lung Cancer.

    PubMed

    Shih, Ya-Chen Tina; Chien, Chun-Ru; Moguel, Rocio; Hernandez, Mike; Hajek, Richard A; Jones, Lovell A

    2016-04-01

    To assess the cost-effectiveness of implementing a patient navigation (PN) program with capitated payment for Medicare beneficiaries diagnosed with lung cancer. Cost-effectiveness analysis. A Markov model to capture the disease progression of lung cancer and characterize clinical benefits of PN services as timeliness of treatment and care coordination. Taking a payer's perspective, we estimated the lifetime costs, life years (LYs), and quality-adjusted life years (QALYs) and addressed uncertainties in one-way and probabilistic sensitivity analyses. Model inputs were extracted from the literature, supplemented with data from a Centers for Medicare and Medicaid Services demonstration project. Compared to usual care, PN services incurred higher costs but also yielded better outcomes. The incremental cost and effectiveness was $9,145 and 0.47 QALYs, respectively, resulting in an incremental cost-effectiveness ratio of $19,312/QALY. One-way sensitivity analysis indicated that findings were most sensitive to a parameter capturing PN survival benefit for local-stage patients. CE-acceptability curve showed the probability that the PN program was cost-effective was 0.80 and 0.91 at a societal willingness-to-pay of $50,000 and $100,000/QALY, respectively. Instituting a capitated PN program is cost-effective for lung cancer patients in Medicare. Future research should evaluate whether the same conclusion holds in other cancers. © Health Research and Educational Trust.

  17. iTOUGH2 v7.1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    FINSTERLE, STEFAN; JUNG, YOOJIN; KOWALSKY, MICHAEL

    2016-09-15

    iTOUGH2 (inverse TOUGH2) provides inverse modeling capabilities for TOUGH2, a simulator for multi-dimensional, multi-phase, multi-component, non-isothermal flow and transport in fractured porous media. iTOUGH2 performs sensitivity analyses, data-worth analyses, parameter estimation, and uncertainty propagation analyses in geosciences and reservoir engineering and other application areas. iTOUGH2 supports a number of different combinations of fluids and components (equation-of-state (EOS) modules). In addition, the optimization routines implemented in iTOUGH2 can also be used for sensitivity analysis, automatic model calibration, and uncertainty quantification of any external code that uses text-based input and output files using the PEST protocol. iTOUGH2 solves the inverse problem bymore » minimizing a non-linear objective function of the weighted differences between model output and the corresponding observations. Multiple minimization algorithms (derivative-free, gradient-based, and second-order; local and global) are available. iTOUGH2 also performs Latin Hypercube Monte Carlo simulations for uncertainty propagation analyses. A detailed residual and error analysis is provided. This upgrade includes (a) global sensitivity analysis methods, (b) dynamic memory allocation (c) additional input features and output analyses, (d) increased forward simulation capabilities, (e) parallel execution on multicore PCs and Linux clusters, and (f) bug fixes. More details can be found at http://esd.lbl.gov/iTOUGH2.« less

  18. Optimal management of colorectal liver metastases in older patients: a decision analysis

    PubMed Central

    Yang, Simon; Alibhai, Shabbir MH; Kennedy, Erin D; El-Sedfy, Abraham; Dixon, Matthew; Coburn, Natalie; Kiss, Alex; Law, Calvin HL

    2014-01-01

    Background Comparative trials evaluating management strategies for colorectal cancer liver metastases (CLM) are lacking, especially for older patients. This study developed a decision-analytic model to quantify outcomes associated with treatment strategies for CLM in older patients. Methods A Markov-decision model was built to examine the effect on life expectancy (LE) and quality-adjusted life expectancy (QALE) for best supportive care (BSC), systemic chemotherapy (SC), radiofrequency ablation (RFA) and hepatic resection (HR). The baseline patient cohort assumptions included healthy 70-year-old CLM patients after a primary cancer resection. Event and transition probabilities and utilities were derived from a literature review. Deterministic and probabilistic sensitivity analyses were performed on all study parameters. Results In base case analysis, BSC, SC, RFA and HR yielded LEs of 11.9, 23.1, 34.8 and 37.0 months, and QALEs of 7.8, 13.2, 22.0 and 25.0 months, respectively. Model results were sensitive to age, comorbidity, length of model simulation and utility after HR. Probabilistic sensitivity analysis showed increasing preference for RFA over HR with increasing patient age. Conclusions HR may be optimal for healthy 70-year-old patients with CLM. In older patients with comorbidities, RFA may provide better LE and QALE. Treatment decisions in older cancer patients should account for patient age, comorbidities, local expertise and individual values. PMID:24961482

  19. Treelets Binary Feature Retrieval for Fast Keypoint Recognition.

    PubMed

    Zhu, Jianke; Wu, Chenxia; Chen, Chun; Cai, Deng

    2015-10-01

    Fast keypoint recognition is essential to many vision tasks. In contrast to the classification-based approaches, we directly formulate the keypoint recognition as an image patch retrieval problem, which enjoys the merit of finding the matched keypoint and its pose simultaneously. To effectively extract the binary features from each patch surrounding the keypoint, we make use of treelets transform that can group the highly correlated data together and reduce the noise through the local analysis. Treelets is a multiresolution analysis tool, which provides an orthogonal basis to reflect the geometry of the noise-free data. To facilitate the real-world applications, we have proposed two novel approaches. One is the convolutional treelets that capture the image patch information locally and globally while reducing the computational cost. The other is the higher-order treelets that reflect the relationship between the rows and columns within image patch. An efficient sub-signature-based locality sensitive hashing scheme is employed for fast approximate nearest neighbor search in patch retrieval. Experimental evaluations on both synthetic data and the real-world Oxford dataset have shown that our proposed treelets binary feature retrieval methods outperform the state-of-the-art feature descriptors and classification-based approaches.

  20. Population structure of the Korean gizzard shad, Konosirus punctatus (Clupeiformes, Clupeidae) using multivariate morphometric analysis

    NASA Astrophysics Data System (ADS)

    Myoung, Se Hun; Kim, Jin-Koo

    2016-03-01

    The gizzard shad, Konosirus punctatus, is one of the most important fish species in Korea, China, Japan and Taiwan, and therefore the implementation of an appropriate population structure analysis is both necessary and fitting. In order to clarify the current distribution range for the two lineages of the Korean gizzard shad (Myoung and Kim 2014), we conducted a multivariate morphometric analysis by locality and lineage. We analyzed 17 morphometric and 5 meristic characters of 173 individuals, which were sampled from eight localities in the East Sea, the Yellow Sea and the Korean Strait. Unlike population genetics studies, the canonical discriminant analysis (CDA) results showed that the two morphotypes were clearly segregated by the center value "0" of CAN1, of which morphotype A occurred from the Yellow Sea to the western Korean Strait with negative values, and morphotype B occurred from the East Sea to the eastern Korean Strait with positive values even though there exists an admixture zone in the eastern Korean Strait. Further studies using more sensitive markers such as microsatellite DNA are required in order to define the true relationship between the two lineages.

  1. A novel versatile microbiosensor for local hydrogen detection by means of scanning photoelectrochemical microscopy.

    PubMed

    Zhao, Fangyuan; Conzuelo, Felipe; Hartmann, Volker; Li, Huaiguang; Stapf, Stefanie; Nowaczyk, Marc M; Rögner, Matthias; Plumeré, Nicolas; Lubitz, Wolfgang; Schuhmann, Wolfgang

    2017-08-15

    The development of a versatile microbiosensor for hydrogen detection is reported. Carbon-based microelectrodes were modified with a [NiFe]-hydrogenase embedded in a viologen-modified redox hydrogel for the fabrication of a sensitive hydrogen biosensor By integrating the microbiosensor in a scanning photoelectrochemical microscope, it was capable of serving simultaneously as local light source to initiate photo(bio)electrochemical reactions while acting as sensitive biosensor for the detection of hydrogen. A hydrogen evolution biocatalyst based on photosystem 1-platinum nanoparticle biocomplexes embedded into a specifically designed redox polymer was used as a model for proving the capability of the developed hydrogen biosensor for the detection of hydrogen upon localized illumination. The versatility and sensitivity of the proposed microbiosensor as probe tip allows simplification of the set-up used for the evaluation of complex electrochemical processes and the rapid investigation of local photoelectrocatalytic activity of biocatalysts towards light-induced hydrogen evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Local Populations of Arabidopsis thaliana Show Clear Relationship between Photoperiodic Sensitivity of Flowering Time and Altitude

    PubMed Central

    Lewandowska-Sabat, Anna M.; Fjellheim, Siri; Olsen, Jorunn E.; Rognli, Odd A.

    2017-01-01

    Adaptation of plants to local conditions that vary substantially within their geographic range is essential for seasonal timing of flowering, a major determinant of plant reproductive success. This study investigates photoperiodic responses in natural populations of Arabidopsis thaliana from high northern latitudes and their significance for local adaptation. Thirty lineages from ten local A. thaliana populations, representing different locations across an altitudinal gradient (2–850 m a.s.l.) in Norway, were grown under uniform controlled conditions, and used to screen for responses to five different photoperiods. We studied relationships between variation in photoperiodic sensitivity of flowering time, altitude, and climatic factors associated with the sites of origin. We found that variation in response to photoperiod is significantly correlated with altitude and climatic variables associated with the sites of origin of the populations. Populations originating from lower altitudes showed stronger photoperiodic sensitivity than populations from higher altitudes. Our results indicate that the altitudinal climatic gradient generates clinal variation in adaptive traits in A. thaliana. PMID:28659966

  3. Molecule-Specific Imaging Analysis of Carcinogens in Breast Cancer Cells Using Time-of-Flight Secondary Ion Mass Spectrometry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Quong, J N; Knize, M G; Kulp, K S

    2003-08-19

    Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) is used to study the localization of heterocyclic amines in MCF7 line of human breast cancer cells. The detection sensitivities of a model rodent mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were determined. Following an established criteria for the determination of status of freeze-fracture cells, the distribution of PhIP in the MCF7 cells are reported.

  4. Using global sensitivity analysis to understand higher order interactions in complex models: an application of GSA on the Revised Universal Soil Loss Equation (RUSLE) to quantify model sensitivity and implications for ecosystem services management in Costa Rica

    NASA Astrophysics Data System (ADS)

    Fremier, A. K.; Estrada Carmona, N.; Harper, E.; DeClerck, F.

    2011-12-01

    Appropriate application of complex models to estimate system behavior requires understanding the influence of model structure and parameter estimates on model output. To date, most researchers perform local sensitivity analyses, rather than global, because of computational time and quantity of data produced. Local sensitivity analyses are limited in quantifying the higher order interactions among parameters, which could lead to incomplete analysis of model behavior. To address this concern, we performed a GSA on a commonly applied equation for soil loss - the Revised Universal Soil Loss Equation. USLE is an empirical model built on plot-scale data from the USA and the Revised version (RUSLE) includes improved equations for wider conditions, with 25 parameters grouped into six factors to estimate long-term plot and watershed scale soil loss. Despite RUSLE's widespread application, a complete sensitivity analysis has yet to be performed. In this research, we applied a GSA to plot and watershed scale data from the US and Costa Rica to parameterize the RUSLE in an effort to understand the relative importance of model factors and parameters across wide environmental space. We analyzed the GSA results using Random Forest, a statistical approach to evaluate parameter importance accounting for the higher order interactions, and used Classification and Regression Trees to show the dominant trends in complex interactions. In all GSA calculations the management of cover crops (C factor) ranks the highest among factors (compared to rain-runoff erosivity, topography, support practices, and soil erodibility). This is counter to previous sensitivity analyses where the topographic factor was determined to be the most important. The GSA finding is consistent across multiple model runs, including data from the US, Costa Rica, and a synthetic dataset of the widest theoretical space. The three most important parameters were: Mass density of live and dead roots found in the upper inch of soil (C factor), slope angle (L and S factor), and percentage of land area covered by surface cover (C factor). Our findings give further support to the importance of vegetation as a vital ecosystem service provider - soil loss reduction. Concurrent, progress is already been made in Costa Rica, where dam managers are moving forward on a Payment for Ecosystem Services scheme to help keep private lands forested and to improve crop management through targeted investments. Use of complex watershed models, such as RUSLE can help managers quantify the effect of specific land use changes. Moreover, effective land management of vegetation has other important benefits, such as bundled ecosystem services (e.g. pollination, habitat connectivity, etc) and improvements of communities' livelihoods.

  5. Influence of Residual Tumor Volume and Radiation Dose Coverage in Outcomes for Clival Chordoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechukwu R.

    2016-05-01

    Purpose: The purpose of this study was to evaluate factors associated with tumor control in clival chordomas. Methods and Materials: A retrospective review of 39 patients treated with surgery and proton therapy for clival chordomas between 2004 and 2014 was performed. The median prescribed dose was 77.4 Gy (relative biological effectiveness [RBE]); range was 70.2-79.2 Gy (RBE). Minimum and median doses to gross tumor volume (GTV), radiation dose received by 1 cm{sup 3} of GTV (D1cm{sup 3}), and the equivalent uniform dose were calculated. Receiver operating characteristics curves evaluated the predictive sensitivity and specificity for local failure of potential cutpoint values for GTVmore » and D1cm{sup 3}. Results: After a median follow-up of 51 months, the 5-year estimate of local control (LC) was 69.6% (95% confidence interval [CI] 50.0%-89.2%), and overall survival (OS) was 81.4% (95% CI: 65.3%-97.5%). Tumor histology, GTV at the time of radiation, and prescribed radiation dose were significantly associated with local control on multivariate analysis, whereas D1cm{sup 3} was associated with overall survival. Compared to those patients whose conditions remained controlled, patients experiencing tumor failure had statistically significant larger GTVs and lower D1cm{sup 3}, and prescribed and median doses to GTV. A subset of 21 patients with GTV of ≤20 cm{sup 3} and D1cm{sup 3} of >67 Gy (RBE) had a median follow-up of 47 months. The 5-year estimate of local control in this subset was 81.1% (95% CI: 61.7%-100%; P=.004, overall comparison by GTV ≤20 cm{sup 3} stratified by D1cm{sup 3}). A D1cm{sup 3} of 74.5 Gy (RBE) had 80% sensitivity for local control and 60% specificity, whereas a GTV of 9.3 cm{sup 3} had 80% sensitivity for local control and 66.7% specificity. Conclusions: Local control of clival chordomas was associated with both smaller size of residual tumor and more complete high-dose coverage of residual tumor. Multidisciplinary care should seek maximal safe surgical resection, particularly to facilitate delivery of high-dose radiation therapy in proximity to critical structures. A D1cm{sup 3} ≥74.5 Gy (RBE) represents a proposed treatment planning objective.« less

  6. [Feasibility analysis of sentinel lymph node biopsy in patients with breast cancer after local lumpectomy].

    PubMed

    Wang, J; Wang, X; Wang, W Y; Liu, J Q; Xing, Z Y; Wang, X

    2016-07-01

    To explore the feasibility, safety and clinical application value of sentinel lymph node biopsy(SLNB)in patients with breast cancer after local lumpectomy. Clinical data of 195 patients who previously received local lumpectomy from January 2005 to April 2015 were retrospectively analyzed. All the patients with pathologic stage T1-2N0M0 (T1-2N0M0) breast cancer underwent SLNB. Methylene blue, carbon nanoparticles suspension, technetium-99m-labeled dextran, or in combination were used in the SLNB. The interval from lumpectomy to SLNB was 1-91 days(mean, 18.3 days)and the maximum diameter of tumors before first operation was 0.2-4.5 cm (mean, 1.8 cm). The sentinel lymph node was successfully found in all the cases and the detection rate was 100%. 42 patients received axillary lymph node dissection (ALND), 19 patients had pathologically positive sentinel lymph node, with an accuracy rate of 97.6%, sensitivity of 95.0%, false negative rate of 5.0%, and specificity of 100%, and the false positive rate was 0. Logistic regression analysis suggested that the age of patients was significantly associated with sentinel lymph node metastasis after local lumpectomy. For early breast cancer and after breast tumor biopsy, the influence of local lumpectomy on detection rate and accuracy of sentinel lymph node is not significant. Sentinel lymph node biopsy with appropriately chosen tracing technique may still provide a high detection rate and accuracy.

  7. The air's got to be far cleaner here: a discursive analysis of place-identity threat.

    PubMed

    Hugh-Jones, Siobhan; Madill, Anna

    2009-12-01

    That talk is never disinterested complicates the relationship between the environment and the claims people make about it. Talk about place, and one's self in it, is particularly complex when the environment poses risk or is otherwise problematized. This study, a secondary analysis of interview data, seeks to extend discursive work on place-identity by examining the ways in which 14 residents of a small English village talk about themselves and their locale. The locale accommodates an active quarry, and many residents had lodged complaints to the quarry about dust, noise and vibrations from blasting. Attention to the interactional context of the interviews illustrates the ways in which (simply) interviewing people about their locale can threaten self- and place-identity. When asked about life in the village, interviewees oriented to two main dilemmas in protecting self- and place-identity: (1) how to justify continued residence in a challenging environment and (2) how to complain about the locale whilst maintaining positive place-identity. Discursive responses to these dilemmas drew upon typical identity processes, such as self- and place distinctiveness and the formulation of out-groups, as well as upon constructions of localized power-sharing and morally obligated tolerance of risk. We suggest that research on problematical places, and of environmental risk, needs to be sensitized to how it may constitute a threat to self- and place-identity, and how this may mediate formulations self and place, as well as of environmental risk.

  8. A Web-based environmental decision support system (WEDSS) for environmental planning and watershed management

    NASA Astrophysics Data System (ADS)

    Sugumaran, Ramanathan; Meyer, James C.; Davis, Jim

    2004-10-01

    Local governments often struggle to balance competing demands for residential, commercial and industrial development with imperatives to minimize environmental degradation. In order to effectively manage this development process on a sustainable basis, local planners and government agencies are increasingly seeking better tools and techniques. In this paper, we describe the development of a Web-Based Environmental Decision Support System (WEDSS), which helps to prioritize local watersheds in terms of environmental sensitivity using multiple criteria identified by planners and local government staff in the city of Columbia, and Boone County, Missouri. The development of the system involved three steps, the first was to establish the relevant environmental criteria and develop data layers for each criterion, then a spatial model was developed for analysis, and lastly a Web-based interface with analysis tools was developed using client-server technology. The WEDSS is an example of a way to run spatial models over the Web and represents a significant increase in capability over other WWW-based GIS applications that focus on database querying and map display. The WEDSS seeks to aid in the development of agreement regarding specific local areas deserving increased protection and the public policies to be pursued in minimizing the environmental impact of future development. The tool is also intended to assist ongoing public information and education efforts concerning watershed management and water quality issues for the City of Columbia, Missouri and adjacent developing areas within Boone County, Missouri.

  9. Optical Fibers Would Sense Local Strains

    NASA Technical Reports Server (NTRS)

    Egalon, Claudio O.; Rogowski, Robert S.

    1994-01-01

    Proposed fiber-optic transducers measure local strains. Includes lead-in and lead-out lengths producing no changes in phase shifts, plus short sensing length in which phase shift is sensitive to strain. Phase shifts in single-mode fibers vary with strains. In alternative version, multiple portions of optical fiber sensitive to strains characteristic of specific vibrational mode of object. Same principle also used with two-mode fiber.

  10. Multi-resolutional shape features via non-Euclidean wavelets: Applications to statistical analysis of cortical thickness

    PubMed Central

    Kim, Won Hwa; Singh, Vikas; Chung, Moo K.; Hinrichs, Chris; Pachauri, Deepti; Okonkwo, Ozioma C.; Johnson, Sterling C.

    2014-01-01

    Statistical analysis on arbitrary surface meshes such as the cortical surface is an important approach to understanding brain diseases such as Alzheimer’s disease (AD). Surface analysis may be able to identify specific cortical patterns that relate to certain disease characteristics or exhibit differences between groups. Our goal in this paper is to make group analysis of signals on surfaces more sensitive. To do this, we derive multi-scale shape descriptors that characterize the signal around each mesh vertex, i.e., its local context, at varying levels of resolution. In order to define such a shape descriptor, we make use of recent results from harmonic analysis that extend traditional continuous wavelet theory from the Euclidean to a non-Euclidean setting (i.e., a graph, mesh or network). Using this descriptor, we conduct experiments on two different datasets, the Alzheimer’s Disease NeuroImaging Initiative (ADNI) data and images acquired at the Wisconsin Alzheimer’s Disease Research Center (W-ADRC), focusing on individuals labeled as having Alzheimer’s disease (AD), mild cognitive impairment (MCI) and healthy controls. In particular, we contrast traditional univariate methods with our multi-resolution approach which show increased sensitivity and improved statistical power to detect a group-level effects. We also provide an open source implementation. PMID:24614060

  11. The role of SISCOM in preoperative evaluation for patients with epilepsy surgery: A meta-analysis.

    PubMed

    Chen, Tong; Guo, Liang

    2016-10-01

    To assess the specific value of subtraction ictal and inter-ictal SPECT co-registered to MRI (SISCOM) in identifying the epileptogenic zone (EZ) and predicting postoperative outcomes in epileptic surgical patients. A meta-analysis of studies published from January 1995 to June 2015 was conducted through a comprehensive literature search, and 11 studies were included. R software was first used to calculate a pooled positive rate, concordant rate and positive predictive value (PPV) for good outcomes. Stata software was then used to explore the relationship between SISCOM localization and surgical outcomes, including a subgroup analysis for extra-temporal lobe epilepsy. The unweighted positive and concordant rates of SISCOM were 85.9% and 65.3%, respectively. In 142 MRI-negative patients, the SISCOM positive rate was 83.8%. The pooled PPV of 178 surgical patients with concordant SISCOM was 56%. In the meta-analysis of 275 surgical patients, the seizure-free odds ratio was 3.28-times higher in concordant than in non-concordant SISCOM patients [95%CI (1.90, 5.67)]. For extra-temporal lobe epilepsy, the seizure-free odds ratio was 2.44-times higher in concordant than in non-concordant SISCOM patients [95%CI (1.34, 4.43)]. Our data indicate that SISCOM has moderate sensitivity in localizing the epileptogenic zone and can provide complementary information when MRI is negative. Furthermore, SISCOM localization concordant with the gold standard demonstrates slightly higher predictive value for good surgical outcomes. Further research is required to explore the influence of SISCOM localization results in temporal lobe versus extra-temporal lobe epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. Space station data system analysis/architecture study. Task 3: Trade studies, DR-5, volume 1

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The primary objective of Task 3 is to provide additional analysis and insight necessary to support key design/programmatic decision for options quantification and selection for system definition. This includes: (1) the identification of key trade study topics; (2) the definition of a trade study procedure for each topic (issues to be resolved, key inputs, criteria/weighting, methodology); (3) conduct tradeoff and sensitivity analysis; and (4) the review/verification of results within the context of evolving system design and definition. The trade study topics addressed in this volume include space autonomy and function automation, software transportability, system network topology, communications standardization, onboard local area networking, distributed operating system, software configuration management, and the software development environment facility.

  13. Diagnostic value of CT-localizer and axial low-dose computed tomography for the detection of drug body packing.

    PubMed

    Aissa, Joel; Kohlmeier, Antonia; Rubbert, Christian; Hohn, Ulrich; Blondin, Dirk; Schleich, Christoph; Kröpil, Patric; Boos, Johannes; Antoch, Gerald; Miese, Falk

    2016-01-01

    The purpose of this study was to assess the diagnostic performance of CT-localizers in the detection of intracorporal containers. This study was approved by the research ethics committee of our clinic. From March 2012 to March 2013, 108 subjects were referred to our institute with suspected body packing. The CT-localizer and the axial CT-images were compared by two blinded observers retrospectively. Presence of body packs was assessed in consensus. Sensitivity and specificity, PPV and NPV of the CT-localizer were calculated. Packets were detected in the CT-localizer of 19 suspects. In 28 of 108 cases packs were detected in axial CT-images. Sensitivity of CT-localizer for detection of packs was 0.68, and specificity was 1.00. There were no cases rated as false positive. The PPV was 1.0 and the NPV was 0.89. The omission of the axial CT-images would have led to a mean radiation dose reduction of 1.94 ± 0.5 mSv. The value of CT-localizers lies in their high PPV. Localizers are limited by low sensitivity, compared to axial CT-images in screening of potential body packers. However, in positive cases their high PPV may possibly allow to omit the complete axial abdominal CT to achieve even lower radiation exposure. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  14. Highly sensitive measurement of whole blood chromium by inductively coupled plasma mass spectrometry.

    PubMed

    Cieslak, Wendy; Pap, Kathleen; Bunch, Dustin R; Reineks, Edmunds; Jackson, Raymond; Steinle, Roxanne; Wang, Sihe

    2013-02-01

    Chromium (Cr), a trace metal element, is implicated in diabetes and cardiovascular disease. A hypochromic state has been associated with poor blood glucose control and unfavorable lipid metabolism. Sensitive and accurate measurement of blood chromium is very important to assess the chromium nutritional status. However, interferents in biological matrices and contamination make the sensitive analysis challenging. The primary goal of this study was to develop a highly sensitive method for quantification of total Cr in whole blood by inductively coupled plasma mass spectrometry (ICP-MS) and to validate the reference interval in a local healthy population. This method was developed on an ICP-MS with a collision/reaction cell. Interference was minimized using both kinetic energy discrimination between the quadrupole and hexapole and a selective collision gas (helium). Reference interval was validated in whole blood samples (n=51) collected in trace element free EDTA tubes from healthy adults (12 males, 39 females), aged 19-64 years (38.8±12.6), after a minimum of 8 h fasting. Blood samples were aliquoted into cryogenic vials and stored at -70 °C until analysis. The assay linearity was 3.42 to 1446.59 nmol/L with an accuracy of 87.7 to 99.8%. The high sensitivity was achieved by minimization of interference through selective kinetic energy discrimination and selective collision using helium. The reference interval for total Cr using a non-parametric method was verified to be 3.92 to 7.48 nmol/L. This validated ICP-MS methodology is highly sensitive and selective for measuring total Cr in whole blood. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Published by Elsevier Inc. All rights reserved.

  15. Parallel magnetic resonance imaging using coils with localized sensitivities.

    PubMed

    Goldfarb, James W; Holland, Agnes E

    2004-09-01

    The purpose of this study was to present clinical examples and illustrate the inefficiencies of a conventional reconstruction using a commercially available phased array coil with localized sensitivities. Five patients were imaged at 1.5 T using a cardiac-synchronized gadolinium-enhanced acquisition and a commercially available four-element phased array coil. Four unique sets of images were reconstructed from the acquired k-space data: (a) sum-of-squares image using four elements of the coil; localized sum-of-squares images from the (b) anterior coils and (c) posterior coils and a (c) local reconstruction. Images were analyzed for artifacts and usable field-of-view. Conventional image reconstruction produced images with fold-over artifacts in all cases spanning a portion of the image (mean 90 mm; range 36-126 mm). The local reconstruction removed fold-over artifacts and resulted in an effective increase in the field-of-view (mean 50%; range 20-70%). Commercially available phased array coils do not always have overlapping sensitivities. Fold-over artifacts can be removed using an alternate reconstruction method. When assessing the advantages of parallel imaging techniques, gains achieved using techniques such as SENSE and SMASH should be gauged against the acquisition time of the localized method rather than the conventional sum-of-squares method.

  16. Evaluation of a National Call Center and a Local Alerts System for Detection of New Cases of Ebola Virus Disease - Guinea, 2014-2015.

    PubMed

    Lee, Christopher T; Bulterys, Marc; Martel, Lise D; Dahl, Benjamin A

    2016-03-11

    The epidemic of Ebola virus disease (Ebola) in West Africa began in Guinea in late 2013 (1), and on August 8, 2014, the World Health Organization (WHO) declared the epidemic a Public Health Emergency of International Concern (2). Guinea was declared Ebola-free on December 29, 2015, and is under a 90 day period of enhanced surveillance, following 3,351 confirmed and 453 probable cases of Ebola and 2,536 deaths (3). Passive surveillance for Ebola in Guinea has been conducted principally through the use of a telephone alert system. Community members and health facilities report deaths and suspected Ebola cases to local alert numbers operated by prefecture health departments or to a national toll-free call center. The national call center additionally functions as a source of public health information by responding to questions from the public about Ebola. To evaluate the sensitivity of the two systems and compare the sensitivity of the national call center with the local alerts system, the CDC country team performed probabilistic record linkage of the combined prefecture alerts database, as well as the national call center database, with the national viral hemorrhagic fever (VHF) database; the VHF database contains records of all known confirmed Ebola cases. Among 17,309 alert calls analyzed from the national call center, 71 were linked to 1,838 confirmed Ebola cases in the VHF database, yielding a sensitivity of 3.9%. The sensitivity of the national call center was highest in the capital city of Conakry (11.4%) and lower in other prefectures. In comparison, the local alerts system had a sensitivity of 51.1%. Local public health infrastructure plays an important role in surveillance in an epidemic setting.

  17. Mass detection, localization and estimation for wind turbine blades based on statistical pattern recognition

    NASA Astrophysics Data System (ADS)

    Colone, L.; Hovgaard, M. K.; Glavind, L.; Brincker, R.

    2018-07-01

    A method for mass change detection on wind turbine blades using natural frequencies is presented. The approach is based on two statistical tests. The first test decides if there is a significant mass change and the second test is a statistical group classification based on Linear Discriminant Analysis. The frequencies are identified by means of Operational Modal Analysis using natural excitation. Based on the assumption of Gaussianity of the frequencies, a multi-class statistical model is developed by combining finite element model sensitivities in 10 classes of change location on the blade, the smallest area being 1/5 of the span. The method is experimentally validated for a full scale wind turbine blade in a test setup and loaded by natural wind. Mass change from natural causes was imitated with sand bags and the algorithm was observed to perform well with an experimental detection rate of 1, localization rate of 0.88 and mass estimation rate of 0.72.

  18. Localization of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene (TNT) in poplar and switchgrass plants using phosphor imager autoradiography.

    PubMed

    Brentner, Laura B; Mukherji, Sachiyo T; Walsh, Susan A; Schnoor, Jerald L

    2010-02-01

    Phosphor imager autoradiography is a technique for rapid, sensitive analysis of the localization of xenobiotics in plant tissues. Use of this technique is relatively new to research in the field of plant science, and the potential for enhancing visualization and understanding of plant uptake and transport of xenobiotics remains largely untapped. Phosphor imager autoradiography is used to investigate the uptake and translocation of the explosives 1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene within Populus deltoides x nigra DN34 (poplar) and Panicum vigratum Alamo (switchgrass). In both plant types, TNT and/or TNT-metabolites remain predominantly in root tissues while RDX and/or RDX-metabolites are readily translocated to leaf tissues. Phosphor imager autoradiography is further investigated for use in semi-quantitative analysis of uptake of TNT by switchgrass. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  19. Decreasing spatial variability in precipitation extremes in southwestern China and the local/large-scale influencing factors

    NASA Astrophysics Data System (ADS)

    Liu, Meixian; Xu, Xianli; Sun, Alex

    2015-07-01

    Climate extremes can cause devastating damage to human society and ecosystems. Recent studies have drawn many conclusions about trends in climate extremes, but few have focused on quantitative analysis of their spatial variability and underlying mechanisms. By using the techniques of overlapping moving windows, the Mann-Kendall trend test, correlation, and stepwise regression, this study examined the spatial-temporal variation of precipitation extremes and investigated the potential key factors influencing this variation in southwestern (SW) China, a globally important biodiversity hot spot and climate-sensitive region. Results showed that the changing trends of precipitation extremes were not spatially uniform, but the spatial variability of these precipitation extremes decreased from 1959 to 2012. Further analysis found that atmospheric circulations rather than local factors (land cover, topographic conditions, etc.) were the main cause of such precipitation extremes. This study suggests that droughts or floods may become more homogenously widespread throughout SW China. Hence, region-wide assessments and coordination are needed to help mitigate the economic and ecological impacts.

  20. Improving the durability of the optical fiber sensor based on strain transfer analysis

    NASA Astrophysics Data System (ADS)

    Wang, Huaping; Jiang, Lizhong; Xiang, Ping

    2018-05-01

    To realize the reliable and long-term strain detection, the durability of optical fiber sensors has attracted more and more attention. The packaging technique has been considered as an effective method, which can enhance the survival ratios of optical fiber sensors to resist the harsh construction and service environment in civil engineering. To monitor the internal strain of structures, the embedded installation is adopted. Due to the different material properties between host material and the protective layer, the monitored structure embedded with sensors can be regarded as a typical model containing inclusions. Interfacial characteristic between the sensor and host material exists obviously, and the contacted interface is prone to debonding failure induced by the large interfacial shear stress. To recognize the local interfacial debonding damage and extend the effective life cycle of the embedded sensor, strain transfer analysis of a general three-layered sensing model is conducted to investigate the failure mechanism. The perturbation of the embedded sensor on the local strain field of host material is discussed. Based on the theoretical analysis, the distribution of the interfacial shear stress along the sensing length is characterized and adopted for the diagnosis of local interfacial debonding, and the sensitive parameters influencing the interfacial shear stress are also investigated. The research in this paper explores the interfacial debonding failure mechanism of embedded sensors based on the strain transfer analysis and provides theoretical basis for enhancing the interfacial bonding properties and improving the durability of embedded optical fiber sensors.

  1. Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kobayashi, Hikaru; Nobeyama, Yoshimasa, E-mail: nobederm@jikei.ac.jp; Nakagawa, Hidemi

    2015-08-21

    Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. Amore » proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells. Results: Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β. - Highlights: • We search melanoma-suppressive molecules induced by IFN-β. • IFN-β induces a high amount of CXCL10 from lymphatic endothelial cells. • CXCL10 induction level in melanoma cells is correlated with the sensitivity to IFN-β. • CXCL10 reduces proliferation in IFN-β-sensitive cells as well as resistant cells. • CXCR3-B is down-regulated by IFN-β exclusively in IFN-β-resistant cells.« less

  2. Impact of local and non-local sources of pollution on background US Ozone: synergy of a low-earth orbiting and geostationary sounder constellation

    NASA Astrophysics Data System (ADS)

    Bowman, K. W.; Lee, M.

    2015-12-01

    Dramatic changes in the global distribution of emissions over the last decade have fundamentally altered source-receptor pollution impacts. A new generation of low-earth orbiting (LEO) sounders complimented by geostationary sounders over North America, Europe, and Asia providing a unique opportunity to quantify the current and future trajectory of emissions and their impact on global pollution. We examine the potential of this constellation of air quality sounders to quantify the role of local and non-local sources of pollution on background ozone in the US. Based upon an adjoint sensitivity method, we quantify the role synoptic scale transport of non-US pollution on US background ozone over months representative of different source-receptor relationships. This analysis allows us distinguish emission trajectories from megacities, e.g. Beijing, or regions, e.g., western China, from natural trends on downwind ozone. We subsequently explore how a combination of LEO and GEO observations could help quantify the balance of local emissions against changes in distant sources . These results show how this unprecedented new international ozone observing system can monitor the changing structure of emissions and their impact on global pollution.

  3. Scanning thermo-ionic microscopy for probing local electrochemistry at the nanoscale

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eshghinejad, Ahmadreza; Nasr Esfahani, Ehsan; Wang, Peiqi

    2016-05-28

    Conventional electrochemical characterization techniques based on voltage and current measurements only probe faradaic and capacitive rates in aggregate. In this work we develop a scanning thermo-ionic microscopy (STIM) to probe local electrochemistry at the nanoscale, based on imaging of Vegard strain induced by thermal oscillation. It is demonstrated from both theoretical analysis and experimental validation that the second harmonic response of thermally induced cantilever vibration, associated with thermal expansion, is present in all solids, whereas the fourth harmonic response, caused by local transport of mobile species, is only present in ionic materials. The origin of STIM response is further confirmedmore » by its reduced amplitude with respect to increased contact force, due to the coupling of stress to concentration of ionic species and/or electronic defects. The technique has been applied to probe Sm-doped Ceria and LiFePO{sub 4}, both of which exhibit higher concentrations of mobile species near grain boundaries. The STIM gives us a powerful method to study local electrochemistry with high sensitivity and spatial resolution for a wide range of ionic systems, as well as ability to map local thermomechanical response.« less

  4. Electric field dependent local structure of (KxNa1-x) 0.5B i0.5Ti O3

    NASA Astrophysics Data System (ADS)

    Goetzee-Barral, A. J.; Usher, T.-M.; Stevenson, T. J.; Jones, J. L.; Levin, I.; Brown, A. P.; Bell, A. J.

    2017-07-01

    The in situ x-ray pair-distribution function (PDF) characterization technique has been used to study the behavior of (KxNa1-x) 0.5B i0.5Ti O3 , as a function of electric field. As opposed to conventional x-ray Bragg diffraction techniques, PDF is sensitive to local atomic displacements, detecting local structural changes at the angstrom to nanometer scale. Several field-dependent ordering mechanisms can be observed in x =0.15 , 0.18 and at the morphotropic phase boundary composition x =0.20 . X-ray total scattering shows suppression of diffuse scattering with increasing electric-field amplitude, indicative of an increase in structural ordering. Analysis of PDF peaks in the 3-4-Å range shows ordering of Bi-Ti distances parallel to the applied electric field, illustrated by peak amplitude redistribution parallel and perpendicular to the electric-field vector. A transition from <110 > to <112 > -type off-center displacements of Bi relative to the neighboring Ti atoms is observable with increasing x . Analysis of PDF peak shift with electric field shows the effects of Bi-Ti redistribution and onset of piezoelectric lattice strain. The combination of these field-induced ordering mechanisms is consistent with local redistribution of Bi-Ti distances associated with domain reorientation and an overall increase in order of atomic displacements.

  5. Electric field dependent local structure of ( K x N a 1 - x ) 0.5 B i 0.5 Ti O 3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Goetzee-Barral, A. J.; Usher, T. -M.; Stevenson, T. J.

    The in situ x-ray pair-distribution function (PDF) characterization technique has been used to study the behavior of (K xNa 1–x) 0.5Bi 0.5TiO 3, as a function of electric field. As opposed to conventional x-ray Bragg diffraction techniques, PDF is sensitive to local atomic displacements, detecting local structural changes at the angstrom to nanometer scale. Several field-dependent ordering mechanisms can be observed in x = 0.15, 0.18 and at the morphotropic phase boundary composition x = 0.20. X-ray total scattering shows suppression of diffuse scattering with increasing electric-field amplitude, indicative of an increase in structural ordering. Analysis of PDF peaks inmore » the 3–4-Å range shows ordering of Bi-Ti distances parallel to the applied electric field, illustrated by peak amplitude redistribution parallel and perpendicular to the electric-field vector. A transition from < 110 > to < 112 >-type off-center displacements of Bi relative to the neighboring Ti atoms is observable with increasing x. Analysis of PDF peak shift with electric field shows the effects of Bi-Ti redistribution and onset of piezoelectric lattice strain. Furthermore, the combination of these field-induced ordering mechanisms is consistent with local redistribution of Bi-Ti distances associated with domain reorientation and an overall increase in order of atomic displacements.« less

  6. Electric field dependent local structure of ( K x N a 1 - x ) 0.5 B i 0.5 Ti O 3

    DOE PAGES

    Goetzee-Barral, A. J.; Usher, T. -M.; Stevenson, T. J.; ...

    2017-07-31

    The in situ x-ray pair-distribution function (PDF) characterization technique has been used to study the behavior of (K xNa 1–x) 0.5Bi 0.5TiO 3, as a function of electric field. As opposed to conventional x-ray Bragg diffraction techniques, PDF is sensitive to local atomic displacements, detecting local structural changes at the angstrom to nanometer scale. Several field-dependent ordering mechanisms can be observed in x = 0.15, 0.18 and at the morphotropic phase boundary composition x = 0.20. X-ray total scattering shows suppression of diffuse scattering with increasing electric-field amplitude, indicative of an increase in structural ordering. Analysis of PDF peaks inmore » the 3–4-Å range shows ordering of Bi-Ti distances parallel to the applied electric field, illustrated by peak amplitude redistribution parallel and perpendicular to the electric-field vector. A transition from < 110 > to < 112 >-type off-center displacements of Bi relative to the neighboring Ti atoms is observable with increasing x. Analysis of PDF peak shift with electric field shows the effects of Bi-Ti redistribution and onset of piezoelectric lattice strain. Furthermore, the combination of these field-induced ordering mechanisms is consistent with local redistribution of Bi-Ti distances associated with domain reorientation and an overall increase in order of atomic displacements.« less

  7. Sensitivity Analysis on Remote Sensing Evapotranspiration Algorithm of Surface Energy Balance for Land

    NASA Astrophysics Data System (ADS)

    Wang, J.; Samms, T.; Meier, C.; Simmons, L.; Miller, D.; Bathke, D.

    2005-12-01

    Spatial evapotranspiration (ET) is usually estimated by Surface Energy Balance Algorithm for Land. The average accuracy of the algorithm is 85% on daily basis and 95% on seasonable basis. However, the accuracy of the algorithm varies from 67% to 95% on instantaneous ET estimates and, as reported in 18 studies, 70% to 98% on 1 to 10-day ET estimates. There is a need to understand the sensitivity of the ET calculation with respect to the algorithm variables and equations. With an increased understanding, information can be developed to improve the algorithm, and to better identify the key variables and equations. A Modified Surface Energy Balance Algorithm for Land (MSEBAL) was developed and validated with data from a pecan orchard and an alfalfa field. The MSEBAL uses ground reflectance and temperature data from ASTER sensors along with humidity, wind speed, and solar radiation data from a local weather station. MSEBAL outputs hourly and daily ET with 90 m by 90 m resolution. A sensitivity analysis was conducted for MSEBAL on ET calculation. In order to observe the sensitivity of the calculation to a particular variable, the value of that variable was changed while holding the magnitudes of the other variables. The key variables and equations to which the ET calculation most sensitive were determined in this study. href='http://weather.nmsu.edu/pecans/SEBALFolder/San%20Francisco%20AGU%20meeting/ASensitivityAnalysisonMSE">http://weather.nmsu.edu/pecans/SEBALFolder/San%20Francisco%20AGU%20meeting/ASensitivityAnalysisonMSE

  8. Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.

    PubMed

    Vogl, Thomas; Eisenblätter, Michel; Völler, Tom; Zenker, Stefanie; Hermann, Sven; van Lent, Peter; Faust, Andreas; Geyer, Christiane; Petersen, Beatrix; Roebrock, Kirsten; Schäfers, Michael; Bremer, Christoph; Roth, Johannes

    2014-08-06

    Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.

  9. Multiple-wavelength neutron holography with pulsed neutrons

    PubMed Central

    Hayashi, Kouichi; Ohoyama, Kenji; Happo, Naohisa; Matsushita, Tomohiro; Hosokawa, Shinya; Harada, Masahide; Inamura, Yasuhiro; Nitani, Hiroaki; Shishido, Toetsu; Yubuta, Kunio

    2017-01-01

    Local structures around impurities in solids provide important information for understanding the mechanisms of material functions, because most of them are controlled by dopants. For this purpose, the x-ray absorption fine structure method, which provides radial distribution functions around specific elements, is most widely used. However, a similar method using neutron techniques has not yet been developed. If one can establish a method of local structural analysis with neutrons, then a new frontier of materials science can be explored owing to the specific nature of neutron scattering—that is, its high sensitivity to light elements and magnetic moments. Multiple-wavelength neutron holography using the time-of-flight technique with pulsed neutrons has great potential to realize this. We demonstrated multiple-wavelength neutron holography using a Eu-doped CaF2 single crystal and obtained a clear three-dimensional atomic image around trivalent Eu substituted for divalent Ca, revealing an interesting feature of the local structure that allows it to maintain charge neutrality. The new holography technique is expected to provide new information on local structures using the neutron technique. PMID:28835917

  10. Multiple-wavelength neutron holography with pulsed neutrons.

    PubMed

    Hayashi, Kouichi; Ohoyama, Kenji; Happo, Naohisa; Matsushita, Tomohiro; Hosokawa, Shinya; Harada, Masahide; Inamura, Yasuhiro; Nitani, Hiroaki; Shishido, Toetsu; Yubuta, Kunio

    2017-08-01

    Local structures around impurities in solids provide important information for understanding the mechanisms of material functions, because most of them are controlled by dopants. For this purpose, the x-ray absorption fine structure method, which provides radial distribution functions around specific elements, is most widely used. However, a similar method using neutron techniques has not yet been developed. If one can establish a method of local structural analysis with neutrons, then a new frontier of materials science can be explored owing to the specific nature of neutron scattering-that is, its high sensitivity to light elements and magnetic moments. Multiple-wavelength neutron holography using the time-of-flight technique with pulsed neutrons has great potential to realize this. We demonstrated multiple-wavelength neutron holography using a Eu-doped CaF 2 single crystal and obtained a clear three-dimensional atomic image around trivalent Eu substituted for divalent Ca, revealing an interesting feature of the local structure that allows it to maintain charge neutrality. The new holography technique is expected to provide new information on local structures using the neutron technique.

  11. Relevant Feature Set Estimation with a Knock-out Strategy and Random Forests

    PubMed Central

    Ganz, Melanie; Greve, Douglas N.; Fischl, Bruce; Konukoglu, Ender

    2015-01-01

    Group analysis of neuroimaging data is a vital tool for identifying anatomical and functional variations related to diseases as well as normal biological processes. The analyses are often performed on a large number of highly correlated measurements using a relatively smaller number of samples. Despite the correlation structure, the most widely used approach is to analyze the data using univariate methods followed by post-hoc corrections that try to account for the data’s multivariate nature. Although widely used, this approach may fail to recover from the adverse effects of the initial analysis when local effects are not strong. Multivariate pattern analysis (MVPA) is a powerful alternative to the univariate approach for identifying relevant variations. Jointly analyzing all the measures, MVPA techniques can detect global effects even when individual local effects are too weak to detect with univariate analysis. Current approaches are successful in identifying variations that yield highly predictive and compact models. However, they suffer from lessened sensitivity and instabilities in identification of relevant variations. Furthermore, current methods’ user-defined parameters are often unintuitive and difficult to determine. In this article, we propose a novel MVPA method for group analysis of high-dimensional data that overcomes the drawbacks of the current techniques. Our approach explicitly aims to identify all relevant variations using a “knock-out” strategy and the Random Forest algorithm. In evaluations with synthetic datasets the proposed method achieved substantially higher sensitivity and accuracy than the state-of-the-art MVPA methods, and outperformed the univariate approach when the effect size is low. In experiments with real datasets the proposed method identified regions beyond the univariate approach, while other MVPA methods failed to replicate the univariate results. More importantly, in a reproducibility study with the well-known ADNI dataset the proposed method yielded higher stability and power than the univariate approach. PMID:26272728

  12. Texture Analysis and Machine Learning for Detecting Myocardial Infarction in Noncontrast Low-Dose Computed Tomography: Unveiling the Invisible.

    PubMed

    Mannil, Manoj; von Spiczak, Jochen; Manka, Robert; Alkadhi, Hatem

    2018-06-01

    The aim of this study was to test whether texture analysis and machine learning enable the detection of myocardial infarction (MI) on non-contrast-enhanced low radiation dose cardiac computed tomography (CCT) images. In this institutional review board-approved retrospective study, we included non-contrast-enhanced electrocardiography-gated low radiation dose CCT image data (effective dose, 0.5 mSv) acquired for the purpose of calcium scoring of 27 patients with acute MI (9 female patients; mean age, 60 ± 12 years), 30 patients with chronic MI (8 female patients; mean age, 68 ± 13 years), and in 30 subjects (9 female patients; mean age, 44 ± 6 years) without cardiac abnormality, hereafter termed controls. Texture analysis of the left ventricle was performed using free-hand regions of interest, and texture features were classified twice (Model I: controls versus acute MI versus chronic MI; Model II: controls versus acute and chronic MI). For both classifications, 6 commonly used machine learning classifiers were used: decision tree C4.5 (J48), k-nearest neighbors, locally weighted learning, RandomForest, sequential minimal optimization, and an artificial neural network employing deep learning. In addition, 2 blinded, independent readers visually assessed noncontrast CCT images for the presence or absence of MI. In Model I, best classification results were obtained using the k-nearest neighbors classifier (sensitivity, 69%; specificity, 85%; false-positive rate, 0.15). In Model II, the best classification results were found with the locally weighted learning classification (sensitivity, 86%; specificity, 81%; false-positive rate, 0.19) with an area under the curve from receiver operating characteristics analysis of 0.78. In comparison, both readers were not able to identify MI in any of the noncontrast, low radiation dose CCT images. This study indicates the ability of texture analysis and machine learning in detecting MI on noncontrast low radiation dose CCT images being not visible for the radiologists' eye.

  13. Development of high-sensitive, reproducible colloidal surface-enhanced Raman spectroscopy active substrate using silver nanocubes for potential biosensing applications

    NASA Astrophysics Data System (ADS)

    Hasna, Kudilatt; Lakshmi, Kiran; Ezhuthachan Jayaraj, Madambi Kunjukuttan; Kumar, Kumaran Rajeev; Matham, Murukeshan Vadakke

    2016-04-01

    Surface-enhanced Raman spectroscopy (SERS) has emerged as one of the thrust research areas that could find potential applications in bio and chemical sensing. We developed colloidal SERS active substrate with excellent sensitivity and high reproducibility using silver nanocube (AgNC) synthesized via the solvothermal method. Finite-difference time-domain simulation was carried out in detail to visualize dipole generation in the nanocube during localized surface plasmon resonance and to locate the respective hot spots in AgNC responsible for the huge Raman enhancement. The prediction is verified by the SERS analysis of the synthesized nanocubes using Rhodamine 6G molecule. An excellent sensitivity with a detection limit of 10-17 M and a very high enhancement factor of 1.2×108 confirms the "hot spots" in the nanocube. SERS activity is also carried out for crystal violet and for food adulterant Sudan I molecule. Finally, label-free DNA detection is performed to demonstrate the versatility of SERS as a potential biosensor.

  14. Thermal biology mediates responses of amphibians and reptiles to habitat modification.

    PubMed

    Nowakowski, A Justin; Watling, James I; Thompson, Michelle E; Brusch, George A; Catenazzi, Alessandro; Whitfield, Steven M; Kurz, David J; Suárez-Mayorga, Ángela; Aponte-Gutiérrez, Andrés; Donnelly, Maureen A; Todd, Brian D

    2018-03-01

    Human activities often replace native forests with warmer, modified habitats that represent novel thermal environments for biodiversity. Reducing biodiversity loss hinges upon identifying which species are most sensitive to the environmental conditions that result from habitat modification. Drawing on case studies and a meta-analysis, we examined whether observed and modelled thermal traits, including heat tolerances, variation in body temperatures, and evaporative water loss, explained variation in sensitivity of ectotherms to habitat modification. Low heat tolerances of lizards and amphibians and high evaporative water loss of amphibians were associated with increased sensitivity to habitat modification, often explaining more variation than non-thermal traits. Heat tolerances alone explained 24-66% (mean = 38%) of the variation in species responses, and these trends were largely consistent across geographic locations and spatial scales. As habitat modification alters local microclimates, the thermal biology of species will likely play a key role in the reassembly of terrestrial communities. © 2018 John Wiley & Sons Ltd/CNRS.

  15. Comparison of large-scale structures and velocities in the local universe

    NASA Technical Reports Server (NTRS)

    Yahil, Amos

    1994-01-01

    Comparison of the large-scale density and velocity fields in the local universe shows detailed agreement, strengthening the standard paradigm of the gravitational origin of these structures. Quantitative analysis can determine the cosmological density parameter, Omega, and biasing factor, b; there is virtually no sensitivity in any local analyses to the cosmologial constant, lambda. Comparison of the dipole anisotropy of the cosmic microwave background with the acceleration due to the Infrared Astronomy Satellite (IRAS) galaxies puts the linear growth factor in the range beta approximately equals Omega (exp 0.6)/b = 0.6(+0.7/-0.3) (95% confidence). A direct comparison of the density and velocity fields of nearby galaxies gives beta = 1.3 (+0.7/-0.6), and from nonlinear analysis the weaker limit (Omega greater than 0.45 for b greater than 0.5 (again 95% confidence). A tighter limit (Omega greater than 0.3 (4-6 sigma)), is obtained by a reconstruction of the probability distribution function of the initial fluctuations from which the structures observed today arose. The last two methods depend critically on the smooth velocity field determined from the observed velocities of nearby galaxies by the POTENT method. A new analysis of these velocities, with more than three times the data used to obtain the above quoted results, is now underway and promises to tighten the uncertainties considerably, as well as reduce systematic bias.

  16. Data in support of the detection of genetically modified organisms (GMOs) in food and feed samples.

    PubMed

    Alasaad, Noor; Alzubi, Hussein; Kader, Ahmad Abdul

    2016-06-01

    Food and feed samples were randomly collected from different sources, including local and imported materials from the Syrian local market. These included maize, barley, soybean, fresh food samples and raw material. GMO detection was conducted by PCR and nested PCR-based techniques using specific primers for the most used foreign DNA commonly used in genetic transformation procedures, i.e., 35S promoter, T-nos, epsps, cryIA(b) gene and nptII gene. The results revealed for the first time in Syria the presence of GM foods and feeds with glyphosate-resistant trait of P35S promoter and NOS terminator in the imported soybean samples with high frequency (5 out of the 6 imported soybean samples). While, tests showed negative results for the local samples. Also, tests revealed existence of GMOs in two imported maize samples detecting the presence of 35S promoter and nos terminator. Nested PCR results using two sets of primers confirmed our data. The methods applied in the brief data are based on DNA analysis by Polymerase Chain Reaction (PCR). This technique is specific, practical, reproducible and sensitive enough to detect up to 0.1% GMO in food and/or feedstuffs. Furthermore, all of the techniques mentioned are economic and can be applied in Syria and other developing countries. For all these reasons, the DNA-based analysis methods were chosen and preferred over protein-based analysis.

  17. Estrogen-anchored pH-sensitive liposomes as nanomodule designed for site-specific delivery of doxorubicin in breast cancer therapy.

    PubMed

    Paliwal, Shivani R; Paliwal, Rishi; Pal, Harish C; Saxena, Ajeet K; Sharma, Pradyumana R; Gupta, Prem N; Agrawal, Govind P; Vyas, Suresh P

    2012-01-01

    The present investigation reports the development of nanoengineered estrogen receptor (ER) targeted pH-sensitive liposome for the site-specific intracellular delivery of doxorubicin (DOX) for breast cancer therapy. Estrone, a bioligand, was anchored on the surface of pH-sensitive liposome for drug targeting to ERs. The estrone-anchored pH-sensitive liposomes (ES-pH-sensitive-SL) showed fusogenic potential at acidic pH (5.5). In vitro cytotoxicity studies carried out on ER-positive MCF-7 breast carcinoma cells revealed that ES-pH-sensitive-SL formulation was more cytotoxic than non-pH-sensitive targeted liposomes (ES-SL). The flow cytometry analysis confirmed significant enhanced uptake (p < 0.05) of ES-pH-sensitive-SL by MCF-7 cells. Intracellular delivery and nuclear localization of the DOX was confirmed by fluorescence microscopy. The mechanism for higher cytotoxicity shown by estrone-anchored pH-sensitive liposomal-DOX was elucidated using reactive oxygen species (ROS) determination. The in vivo biodistribution studies and antitumor activities of formulations were evaluated on tumor bearing female Balb/c mice followed by intravenous administration. The ES-pH-sensitive-SL efficiently suppressed the breast tumor growth in comparison to both ES-SL and free DOX. Serum enzyme activities such as LDH and CPK levels were assayed for the evaluation of DOX induced cardiotoxicity. The ES-pH-sensitive-SL accelerated the intracellular trafficking of encapsulated DOX, thus increasing the therapeutic efficacy. The findings support that estrone-anchored pH-sensitive liposomes could be one of the promising nanocarriers for the targeted intracellular delivery of anticancer agents to breast cancer with reduced systemic side effects.

  18. Generalization of the slip line field theory for temperature sensitive visco-plastic materials

    NASA Astrophysics Data System (ADS)

    Paesold, Martin; Peters, Max; Regenauer-Lieb, Klaus; Veveakis, Manolis; Bassom, Andrew

    2015-04-01

    Geological processes can be a combination of various effects such as heat production or consumption, chemical reactions or fluid flow. These individual effects are coupled to each other via feedbacks and the mathematical analysis becomes challenging due to these interdependencies. Here, we concentrate solely on thermo-mechanical coupling and a main result of this work is that the coupling can depend on material parameters and boundary conditions and the coupling is more or less pronounced depending on theses parameters. The transitions from weak to strong coupling can be studied in the context of a bifurcation analysis. classically, Material instabilities in solids are approached as material bifurcations of a rate-independent, isothermal, elasto-plastic solid. However, previous research has shown that temperature and deformation rate are important factors and are fully coupled with the mechanical deformation. Early experiments in steel revealed a distinct pattern of localized heat dissipation and plastic deformation known as heat lines. Further, earth materials, soils, rocks and ceramics are known to be greatly influenced by temperature with strain localization being strongly affected by thermal loading. In this work, we provide a theoretical framework for the evolution of plastic deformation for such coupled systems, with a two-pronged approach to the prediction of localized failure. First, slip line field theory is employed to predict the geometry of the failure patterns and second, failure criteria are derived from an energy bifurcation analysis. The bifurcation analysis is concerned with the local energy balance of a material and compares the effects of heat diffusion terms and heat production terms where the heat production is due to mechanical processes. Commonly, the heat is produced locally along the slip lines and if the heat production outweighs diffusion the material is locally weakened which eventually leads to failure. The effect of diffusion and heat production is captured by a dimensionless quantity, the Gruntfest number, and only if the Gruntfest number is larger than a critical value localized failure occurs. This critical Gruntfest number depends on boundary conditions such as temperature or pressure and hence this critical value gives rise to localization criteria. We find that the results of this approach agree with earlier contributions to the theory of plasticity but gives the advantage of a unified framework which might prove useful in numerical schemes for visco-plasticity.

  19. Local symmetric distortion boosted photon up-conversion and thermometric sensitivity in lanthanum oxide nanospheres.

    PubMed

    Suo, Hao; Zhao, Xiaoqi; Zhang, Zhiyu; Shi, Rui; Wu, Yanfang; Xiang, Jinmeng; Guo, Chongfeng

    2018-05-17

    It is essential to simultaneously boost the luminescence intensity and thermometric sensitivity of up-converted optical thermometers towards potential biomedical sensing applications. Herein, the effects of local site symmetry on the up-conversion (UC) emission and thermal sensing ability in trigonal-phased La2O3:Er3+/Yb3+ nanospheres were qualitatively explored using cubic-phased Lu2O3 and Y2O3 with a similar shape and phonon energy as contrasts. Under 980 nm light excitation, much stronger UC emissions were detected in La2O3 samples than that in cubic Lu2O3 and Y2O3 samples, and the possible mechanisms were elaborately proposed using Eu3+ as a luminescent probe. Thermo-responsive emission intensity from 2H11/2/4S3/2 levels was monitored to evaluate the absolute sensitivity of three samples, which strongly depends on the dopant-induced local site symmetric distortions according to the Judd-Ofelt theory. The potentiality of La2O3:Er3+/Yb3+ for sub-tissue thermometry was also validated by ex vivo experiments. Results open a promising avenue for realizing highly sensitive thermometry with a large signal-to-noise ratio in sub-tissues via finely tailoring the local site symmetry.

  20. Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

    PubMed

    Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

    2013-05-01

    Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

  1. Plasmonic Imaging of Electrochemical Reactions of Single Nanoparticles.

    PubMed

    Fang, Yimin; Wang, Hui; Yu, Hui; Liu, Xianwei; Wang, Wei; Chen, Hong-Yuan; Tao, N J

    2016-11-15

    Electrochemical reactions are involved in many natural phenomena, and are responsible for various applications, including energy conversion and storage, material processing and protection, and chemical detection and analysis. An electrochemical reaction is accompanied by electron transfer between a chemical species and an electrode. For this reason, it has been studied by measuring current, charge, or related electrical quantities. This approach has led to the development of various electrochemical methods, which have played an essential role in the understanding and applications of electrochemistry. While powerful, most of the traditional methods lack spatial and temporal resolutions desired for studying heterogeneous electrochemical reactions on electrode surfaces and in nanoscale materials. To overcome the limitations, scanning probe microscopes have been invented to map local electrochemical reactions with nanometer resolution. Examples include the scanning electrochemical microscope and scanning electrochemical cell microscope, which directly image local electrochemical reaction current using a scanning electrode or pipet. The use of a scanning probe in these microscopes provides high spatial resolution, but at the expense of temporal resolution and throughput. This Account discusses an alternative approach to study electrochemical reactions. Instead of measuring electron transfer electrically, it detects the accompanying changes in the reactant and product concentrations on the electrode surface optically via surface plasmon resonance (SPR). SPR is highly surface sensitive, and it provides quantitative information on the surface concentrations of reactants and products vs time and electrode potential, from which local reaction kinetics can be analyzed and quantified. The plasmonic approach allows imaging of local electrochemical reactions with high temporal resolution and sensitivity, making it attractive for studying electrochemical reactions in biological systems and nanoscale materials with high throughput. The plasmonic approach has two imaging modes: electrochemical current imaging and interfacial impedance imaging. The former images local electrochemical current associated with electrochemical reactions (faradic current), and the latter maps local interfacial impedance, including nonfaradic contributions (e.g., double layer charging). The plasmonic imaging technique can perform voltammetry (cyclic or square wave) in an analogous manner to the traditional electrochemical methods. It can also be integrated with bright field, dark field, and fluorescence imaging capabilities in one optical setup to provide additional capabilities. To date the plasmonic imaging technique has found various applications, including mapping of heterogeneous surface reactions, analysis of trace substances, detection of catalytic reactions, and measurement of graphene quantum capacitance. The plasmonic and other emerging optical imaging techniques (e.g., dark field and fluorescence microscopy), together with the scanning probe-based electrochemical imaging and single nanoparticle analysis techniques, provide new capabilities for one to study single nanoparticle electrochemistry with unprecedented spatial and temporal resolutions. In this Account, we focus on imaging of electrochemical reactions at single nanoparticles.

  2. Molecular assembly and subcellular distribution of ATP-sensitive potassium channel proteins in rat hearts.

    PubMed

    Kuniyasu, Akihiko; Kaneko, Kazuyoshi; Kawahara, Kohichi; Nakayama, Hitoshi

    2003-09-25

    Cardiac ATP-sensitive K(+) (K(ATP)) channels are proposed to contribute to cardio-protection and ischemic preconditioning. Although mRNAs for all subunits of K(ATP) channels (Kir6.0 and sulfonylurea receptors SURs) were detected in hearts, subcellular localization of their proteins and the subunit combination are not well elucidated. We address these questions in rat hearts, using anti-peptide antibodies raised against each subunit. By immunoblot analysis, all of the subunits were detected in microsomal fractions including sarcolemmal membranes, while they were not detected in mitochondrial fractions at all. Immunoprecipitation and sucrose gradient sedimentation of the digitonin-solubilized microsomes indicated that Kir6.2 exclusively assembled with SUR2A. The molecular mass of the Kir6.2-SUR2A complex estimated by sucrose sedimentation was 1150 kDa, significantly larger than the calculated value for (Kir6.2)(4)-(SUR2A)(4), suggesting a potential formation of micellar complex with digitonin but no indication of hybrid channel formation under the conditions. These findings provide additional information on the structural and functional relationships of cardiac K(ATP) channel proteins involving subcellular localization and roles for cardioprotection and ischemic preconditioning.

  3. Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor

    PubMed Central

    Görner, Wolfram; Durchschlag, Erich; Wolf, Julia; Brown, Elizabeth L.; Ammerer, Gustav; Ruis, Helmut; Schüller, Christoph

    2002-01-01

    In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP-dependent protein kinase (cAPK). Genetic analysis suggests that Msn2-NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2-NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full-length Msn2. The Msn2-NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose-sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short-term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5-dependent nuclear export and/or retention mechanism. PMID:11782433

  4. Characterization of the Spatial Structure of Local Functional Connectivity Using Multidistance Average Correlation Measures.

    PubMed

    Macià, Dídac; Pujol, Jesus; Blanco-Hinojo, Laura; Martínez-Vilavella, Gerard; Martín-Santos, Rocío; Deus, Joan

    2018-06-01

    There is ample evidence from basic research in neuroscience of the importance of local corticocortical networks. Millimetric resolution is achievable with current functional magnetic resonance imaging (fMRI) scanners and sequences, and consequently a number of "local" activity similarity measures have been defined to describe patterns of segregation and integration at this spatial scale. We have introduced the use of IsoDistant Average Correlation (IDAC), easily defined as the average fMRI temporal correlation of a given voxel with other voxels placed at increasingly separated isodistant intervals, to characterize the curve of local fMRI signal similarities. IDAC curves can be statistically compared using parametric multivariate statistics. Furthermore, by using red-green-blue color coding to display jointly IDAC values belonging to three different distance lags, IDAC curves can also be displayed as multidistance IDAC maps. We applied IDAC analysis to a sample of 41 subjects scanned under two different conditions, a resting state and an auditory-visual continuous stimulation. Multidistance IDAC mapping was able to discriminate between gross anatomofunctional cortical areas and, moreover, was sensitive to modulation between the two brain conditions in areas known to activate and deactivate during audiovisual tasks. Unlike previous fMRI local similarity measures already in use, our approach draws special attention to the continuous smooth pattern of local functional connectivity.

  5. Degeneracy in NLP and the development of results motivated by its presence

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fiacco, A.; Liu, J.

    We study notions of nondegeneracy and several levels of increasing degeneracy from the perspective of the local behavior of a local solution of a nonlinear program when problem parameters are slightly perturbed. This overview may be viewed as a structured survey of sensitivity and stability results: the focus is on progressive levels of degeneracy. We note connections of nondegeneracy with the convergence of algorithms and observe the striking parallel between the effects of nondegeneracy and degeneracy on optimality conditions, stability analysis and algorithmic convergence behavior. Although our orientation here is primarily interpretive and noncritical, we conclude that more effort ismore » needed to unify optimality, stability and convergence theory and more results are needed in all three areas for radically degenerate problems.« less

  6. DPYD, TYMS, TYMP, TK1, and TK2 Genetic Expressions as Response Markers in Locally Advanced Rectal Cancer Patients Treated with Fluoropyrimidine-Based Chemoradiotherapy

    PubMed Central

    Wu, Chan-Han; Huang, Chun-Ming; Chung, Fu-Yen; Huang, Ching-Wen; Tsai, Hsiang-Lin; Chen, Chin-Fan; Wang, Jaw-Yuan

    2013-01-01

    This study is to investigate multiple chemotherapeutic agent- and radiation-related genetic biomarkers in locally advanced rectal cancer (LARC) patients following fluoropyrimidine-based concurrent chemoradiotherapy (CCRT) for response prediction. We initially selected 6 fluoropyrimidine metabolism-related genes (DPYD, ORPT, TYMS, TYMP, TK1, and TK2) and 3 radiotherapy response-related genes (GLUT1, HIF-1 α, and HIF-2 α) as targets for gene expression identification in 60 LARC cancer specimens. Subsequently, a high-sensitivity weighted enzymatic chip array was designed and constructed to predict responses following CCRT. After CCRT, 39 of 60 (65%) LARC patients were classified as responders (pathological tumor regression grade 2 ~ 4). Using a panel of multiple genetic biomarkers (chip), including DPYD, TYMS, TYMP, TK1, and TK2, at a cutoff value for 3 positive genes, a sensitivity of 89.7% and a specificity of 81% were obtained (AUC: 0.915; 95% CI: 0.840–0.991). Negative chip results were significantly correlated to poor CCRT responses (TRG 0-1) (P = 0.014, hazard ratio: 22.704, 95% CI: 3.055–235.448 in multivariate analysis). Disease-free survival analysis showed significantly better survival rate in patients with positive chip results (P = 0.0001). We suggest that a chip including DPYD, TYMS, TYMP, TK1, and TK2 genes is a potential tool to predict response in LARC following fluoropyrimidine-based CCRT. PMID:24455740

  7. THE CHANDRA SURVEY OF THE COSMOS FIELD. II. SOURCE DETECTION AND PHOTOMETRY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Puccetti, S.; Vignali, C.; Cappelluti, N.

    2009-12-01

    The Chandra COSMOS Survey (C-COSMOS) is a large, 1.8 Ms, Chandra program that covers the central contiguous {approx}0.92 deg{sup 2} of the COSMOS field. C-COSMOS is the result of a complex tiling, with every position being observed in up to six overlapping pointings (four overlapping pointings in most of the central {approx}0.45 deg{sup 2} area with the best exposure, and two overlapping pointings in most of the surrounding area, covering an additional {approx}0.47 deg{sup 2}). Therefore, the full exploitation of the C-COSMOS data requires a dedicated and accurate analysis focused on three main issues: (1) maximizing the sensitivity when themore » point-spread function (PSF) changes strongly among different observations of the same source (from {approx}1 arcsec up to {approx}10 arcsec half-power radius); (2) resolving close pairs; and (3) obtaining the best source localization and count rate. We present here our treatment of four key analysis items: source detection, localization, photometry, and survey sensitivity. Our final procedure consists of a two step procedure: (1) a wavelet detection algorithm to find source candidates and (2) a maximum likelihood PSF fitting algorithm to evaluate the source count rates and the probability that each source candidate is a fluctuation of the background. We discuss the main characteristics of this procedure, which was the result of detailed comparisons between different detection algorithms and photometry tools, calibrated with extensive and dedicated simulations.« less

  8. The local, remote, and global consequences of climate feedbacks

    NASA Astrophysics Data System (ADS)

    Feldl, Nicole

    Climate feedbacks offer a powerful framework for revealing the energetic pathways by which the system adjusts to an imposed forcing, such as an increase in atmospheric CO2. We investigate how local atmospheric feedbacks, such as those associated with Arctic sea ice and the Walker circulation, affect both global climate sensitivity and spatial patterns of warming. Emphasis is placed on a general circulation model with idealized boundary conditions, for the clarity it provides. For this aquaplanet simulation, we account for rapid tropospheric adjustments to CO2 and explicitly diagnose feedbacks (using radiative kernels) and forcing for this precise model set-up. In particular, a detailed closure of the energy budget within a clean experimental set-up allows us to consider nonlinear interactions between feedbacks. The inclusion of a tropical Walker circulation is found to prime the Hadley Circulation for a larger deceleration under CO2 doubling, by altering subtropical stratus decks and the meridional feedback gradient. We perform targeted experiments to isolate the atmospheric processes responsible for the variability in climate sensitivity, with implications for high-sensitivity paleoclimates. The local climate response is characterized in terms of the meridional structure of feedbacks, atmospheric heat transport, nonlinearities, and forcing. Our results display a combination of positive subtropical feedbacks and polar amplified warming. These two factors imply a critical role for transport and nonlinear effects, with the latter acting to substantially reduce global climate sensitivity. At the hemispheric scale, a rich picture emerges: anomalous divergence of heat flux away from positive feedbacks in the subtropics; clear-sky nonlinearities that reinforce the pattern of tropical cooling and high-latitude warming tendencies; and strong ice-line feedbacks that drive further amplification of polar warming. These results have implications for regional climate predictability, by providing an indication of how spatial patterns in feedbacks combine to affect both the local and nonlocal climate response, and how constraining uncertainty in those feedbacks may constrain the climate response. We also consider how competing definitions of feedbacks influence interpretation of climate sensitivity. While climate feedbacks represent a convenient breakdown of the energy balance, their widespread appeal has led to a profusion of definitions, and to variations upon the traditional decomposition. We demonstrate that a locally defined feedback framework does provide several advantages from the perspective of regional climate predictability. Namely, it enables a partial temperature change analysis which quantifies contributions to spatial patterns of warming; it also ensures feedbacks are not biased at high latitudes due to polar amplification. Alternative approaches to characterizing feedbacks can also isolate and illuminate different atmospheric processes. In particular, comparison of two versions of the water vapor feedback, one focused on specific humidity and the other on relative humidity, allows for an elegant dissection of the relative importance of thermodynamical and dynamical changes in a warmer world.

  9. Characterization, localization and function of pertussis toxin-sensitive G proteins in the nervous systems of Aplysia and Loligo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vogel, S.S.

    1989-01-01

    The author has characterized pertussis toxin-sensitive G proteins in the nervous systems of the gastropod mollusc Aplysia and the cephalopod Loligo using ({sup 32}P)ADP-ribosylation and immunoblotting with G protein specific antisera. As in vertebrates, this class of G protein is associated with membranes and enriched in nervous tissue in Aplysia. Analysis of dissected Aplysia ganglia reveal that it is enriched in neuropil, a region containing most of the central nervous system synapses. Because both Aplysia and Loligo synaptosomes are enriched in pertussis toxin-sensitive G proteins, it is likely that they are found in synaptic terminals. Fractionation of Aplysia synaptosomes intomore » membrane and vesicle fractions reveals that, although the majority of G protein is recovered in the plasma membrane fraction, a small proportion is recovered in the vesicle fraction. He shows that G proteins are on intracellular membranes by ADP-ribosylating extruded axoplasm with pertussis toxin. A plausible explanation for vesicular localization of G protein in axoplasm is that G proteins are transported to terminals on vesicles. He has shown, using ligature experiments with Aplysia connectives and temperature block experiments in the giant axon of Loligo, that G proteins move by anterograde fast axonal transport. Injection of pertussis toxin into the identified Aplysia neuron L10 blocks histamine-induced presynaptic inhibition of transmitter release. This suggests that pertussis toxin sensitive G proteins play a role in modulating transmitter release at synaptic terminals. In the giant synapse of Loligo, he presents preliminary data that demonstrates that the activation of G proteins in the presynaptic terminal results in decreased transmitter release.« less

  10. Assessment of the presence of mucosal human papillomaviruses in malignant melanomas using combined fluorescent in situ hybridization and chemiluminescent immunohistochemistry.

    PubMed

    Ambretti, S; Venturoli, S; Mirasoli, M; La Placa, M; Bonvicini, F; Cricca, M; Zerbini, M; Roda, A; Musiani, M

    2007-01-01

    The vast majority of studies aimed at detecting human papillomavirus (HPV) DNA in skin cancer have used sensitive polymerase chain reaction (PCR) methods but the PCR technique, despite its high sensitivity, is not suitable to ascertain whether (i) the presence of HPV can be related only to few cells harbouring the virus, (ii) the presence of HPV is due to a tumour surface contamination and (iii) the presence of HPV is localized in cancer cells, rather than in normal keratinocytes present in the tumour biopsy. In a recent work we have found mucosal high-risk (HR) HPV genotypes in primary melanoma by PCR. To localize mucosal HR-HPV nucleic acids and tumoural melanocytic marker in the same sections of primary melanoma samples in order to understand the relationship between HPVs and melanoma cells. We have developed a very sensitive method that combines an enzyme-amplified fluorescent in situ hybridization (ISH) for the detection of HPV nucleic acids (types 16 and 18) with a chemiluminescent immunohistochemistry (IHC) method for the detection of the tumoural melanocytic marker HMB-45 sequentially in the same section. Digital images of fluorescent ISH and chemiluminescent IHC were separately recorded, assigned different colours and merged using specific software for image analysis. The combined fluorescent ISH and chemiluminescent IHC demonstrated a sharp colocalization (in the range 60-80%) of HPV nucleic acids and melanoma marker inside the same sections of melanoma biopsies, with a strong specificity and sensitivity. The strong colocalization of mucosal HR-HPV nucleic acids and HMB-45 melanocytic marker emphasized that viral nucleic acids were specifically present in melanoma cells and supported a possible active role of HPV in malignant melanoma.

  11. Imaging of tumor hypermetabolism with near-infrared fluorescence contrast agents

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Zheng, Gang; Zhang, Zhihong; Blessington, Dana; Intes, Xavier; Achilefu, Samuel I.; Chance, Britton

    2004-08-01

    We have developed a high sensitivity near-infrared (NIR) optical imaging system for non-invasive cancer detection through molecular labeled fluorescent contrast agents. Near-infrared (NIR) imaging can probe tissue deeply thus possess the potential for non-invasively detection of breast or lymph node cancer. Recent developments in molecular beacons can selectively label various pre-cancer/cancer signatures and provide high tumor to background contrast. To increase the sensitivity in detecting fluorescent photons and the accuracy of localization, phase cancellation (in- and anti-phase) device is employed. This frequency-domain system utilizes the interference-like pattern of diffuse photon density wave to achieve high detection sensitivity and localization accuracy for the fluorescent heterogeneity embedded inside the scattering media. The opto-electronic system consists of the laser sources, fiber optics, interference filter to select the fluorescent photons and the high sensitivity photon detector (photomultiplier tube). The source-detector pair scans the tissue surface in multiple directions and the two-dimensional localization image can be obtained using goniometric reconstruction. In vivo measurements with tumor-bearing mouse model using the novel Cypate-mono-2-deoxy-glucose (Cypate-2-D-Glucosamide) fluorescent contrast agent, which targets the enhanced tumor glycolysis, demonstrated the feasibility on detection of 2 cm deep subsurface tumor in the tissue-like medium, with a localization accuracy within 2 ~ 3 mm. This instrument has the potential for tumor diagnosis and imaging, and the accuracy of the localization suggests that this system could help to guide the clinical fine-needle biopsy. This portable device would be complementary to X-ray mammogram and provide add-on information on early diagnosis and localization of early breast tumor.

  12. Long-lived room temperature deep-red/near-IR emissive intraligand triplet excited state (3IL) of naphthalimide in cyclometalated platinum(II) complexes and its application in upconversion.

    PubMed

    Wu, Wenting; Guo, Huimin; Wu, Wanhua; Ji, Shaomin; Zhao, Jianzhang

    2011-11-21

    [C(^)NPt(acac)] (C(^)N = cyclometalating ligand; acac = acetylacetonato) complexes in which the naphthalimide (NI) moiety is directly cyclometalated (NI as the C donor of the C-Pt bond) were synthesized. With 4-pyrazolylnaphthalimide, isomers with five-membered (Pt-2) and six-membered (Pt-3) chelate rings were obtained. With 4-pyridinylnaphthalimide, only the complex with a five-membered chelate ring (Pt-4) was isolated. A model complex with 1-phenylpyrazole as the C(^)N ligand was prepared (Pt-1). Strong absorption of visible light (ε = 21,900 M(-1) cm(-1) at 443 nm for Pt-3) and room temperature (RT) phosphorescence at 630 nm (Pt-2 and Pt-3) or 674 nm (Pt-4) were observed. Long-lived phosphorescences were observed for Pt-2 (τ(P) = 12.8 μs) and Pt-3 (τ(P) = 61.9 μs). Pt-1 is nonphosphorescent at RT in solution because of the acac-localized T(1) excited state [based on density functional theory (DFT) calculations and spin density analysis], but a structured emission band centered at 415 nm was observed at 77 K. Time-resolved transient absorption spectra and spin density analysis indicated a NI-localized intraligand triplet excited state ((3)IL) for complexes Pt-2, Pt-3, and Pt-4. DFT calculations on the transient absorption spectra (T(1) → T(n) transitions, n > 1) also support the (3)IL assignment of the T(1) excited states of Pt-2, Pt-3, and Pt-4. The complexes were used as triplet sensitizers for triplet-triplet-annihilation (TTA) based upconversion, and the results show that Pt-3 is an efficient sensitizer with an upconversion quantum yield of up to 14.1%, despite its low phosphorescence quantum yield of 5.2%. Thus, we propose that the sensitizer molecules at the triplet excited state that are otherwise nonphosphorescent were involved in the TTA upconversion process, indicating that weakly phosphorescent or nonphosphorescent transition-metal complexes can be used as triplet sensitizers for TTA upconversion.

  13. Local indicators of geocoding accuracy (LIGA): theory and application

    PubMed Central

    Jacquez, Geoffrey M; Rommel, Robert

    2009-01-01

    Background Although sources of positional error in geographic locations (e.g. geocoding error) used for describing and modeling spatial patterns are widely acknowledged, research on how such error impacts the statistical results has been limited. In this paper we explore techniques for quantifying the perturbability of spatial weights to different specifications of positional error. Results We find that a family of curves describes the relationship between perturbability and positional error, and use these curves to evaluate sensitivity of alternative spatial weight specifications to positional error both globally (when all locations are considered simultaneously) and locally (to identify those locations that would benefit most from increased geocoding accuracy). We evaluate the approach in simulation studies, and demonstrate it using a case-control study of bladder cancer in south-eastern Michigan. Conclusion Three results are significant. First, the shape of the probability distributions of positional error (e.g. circular, elliptical, cross) has little impact on the perturbability of spatial weights, which instead depends on the mean positional error. Second, our methodology allows researchers to evaluate the sensitivity of spatial statistics to positional accuracy for specific geographies. This has substantial practical implications since it makes possible routine sensitivity analysis of spatial statistics to positional error arising in geocoded street addresses, global positioning systems, LIDAR and other geographic data. Third, those locations with high perturbability (most sensitive to positional error) and high leverage (that contribute the most to the spatial weight being considered) will benefit the most from increased positional accuracy. These are rapidly identified using a new visualization tool we call the LIGA scatterplot. Herein lies a paradox for spatial analysis: For a given level of positional error increasing sample density to more accurately follow the underlying population distribution increases perturbability and introduces error into the spatial weights matrix. In some studies positional error may not impact the statistical results, and in others it might invalidate the results. We therefore must understand the relationships between positional accuracy and the perturbability of the spatial weights in order to have confidence in a study's results. PMID:19863795

  14. Good research practices for measuring drug costs in cost-effectiveness analyses: an international perspective: the ISPOR Drug Cost Task Force report--Part VI.

    PubMed

    Shi, Lizheng; Hodges, Meredith; Drummond, Michael; Ahn, Jeonghoon; Li, Shu Chuen; Hu, Shanlian; Augustovski, Federico; Hay, Joel W; Smeeding, Jim

    2010-01-01

    The pharmacoeconomic guidelines available in the literature or promulgated in many countries are either vague or silent about how drug costs should be established or measured so an international comparison of cost-effectiveness analysis (CEA) results can be made. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs done from an internationally comparative perspective. Members of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) subgroup from several countries were experienced developers or users of CEA models, and worked in academia, industry, and as advisors to governments. They solicited comments on drafts from a core group of 174 external reviewers and more broadly, from the members of the ISPOR at the ISPOR 12th Annual International meeting and via the ISPOR Web site. Drug units should be standardized in terms of volume of active ingredient, regardless of packaging and dosing strength variations across countries. Drug costs should be measured in local currency per unit of active ingredient and should be converted to other currencies using sensitivity analyses of purchasing power parities (PPP) and exchange rates, whichever is more appropriate. When using drug prices from different years, the consumer price index for the local currency should be applied before the PPP and/or exchange rate conversion. CEA researchers conducting international pharmacoeconomic analysis should tailor the appropriate measure of drug costs to the international perspective, to maintain clarity and transparency on drug cost measurement in the context of international drug comparison and report the sensitivity of CEA results to reasonable cost conversions.

  15. Primary treatments for clinically localized prostate cancer: a comprehensive lifetime cost-utility analysis

    PubMed Central

    Cooperberg, Matthew R.; Ramakrishna, Naren R.; Duff, Steven B.; Hughes, Kathleen E.; Sadownik, Sara; Smith, Joseph A.; Tewari, Ashutosh K.

    2012-01-01

    Objectives To characterize the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (dose-escalated 3-dimensional conformal radiation, intensity-modulated radiation, brachytherapy, or combination), using a comprehensive, lifetime decision analytic model. Patients and Methods A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes following primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. Patients could experience remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the U.S. payer perspective, with incorporation of patient costs in a sensitivity analysis. Results Differences in quality-adjusted life years across modalities were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6 to 10.5 for intermediate-risk patients, and 7.8 to 9.3 for high-risk patients. There were no statistically significant differences among surgical modalities, which tended to be more effective than radiation modalities, with the exception of combination external beam + brachytherapy for high-risk disease. Radiation modalities were consistently more expensive than surgical modalities; costs ranged from $19,901 (robot-assisted prostatectomy for low-risk disease) to $50,276 (combination radiation for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Conclusions Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions regarding strategies to improve efficiency of treatment selection for localized prostate cancer. PMID:23279038

  16. Graph Theoretical Analysis of Functional Brain Networks: Test-Retest Evaluation on Short- and Long-Term Resting-State Functional MRI Data

    PubMed Central

    Wang, Jin-Hui; Zuo, Xi-Nian; Gohel, Suril; Milham, Michael P.; Biswal, Bharat B.; He, Yong

    2011-01-01

    Graph-based computational network analysis has proven a powerful tool to quantitatively characterize functional architectures of the brain. However, the test-retest (TRT) reliability of graph metrics of functional networks has not been systematically examined. Here, we investigated TRT reliability of topological metrics of functional brain networks derived from resting-state functional magnetic resonance imaging data. Specifically, we evaluated both short-term (<1 hour apart) and long-term (>5 months apart) TRT reliability for 12 global and 6 local nodal network metrics. We found that reliability of global network metrics was overall low, threshold-sensitive and dependent on several factors of scanning time interval (TI, long-term>short-term), network membership (NM, networks excluding negative correlations>networks including negative correlations) and network type (NT, binarized networks>weighted networks). The dependence was modulated by another factor of node definition (ND) strategy. The local nodal reliability exhibited large variability across nodal metrics and a spatially heterogeneous distribution. Nodal degree was the most reliable metric and varied the least across the factors above. Hub regions in association and limbic/paralimbic cortices showed moderate TRT reliability. Importantly, nodal reliability was robust to above-mentioned four factors. Simulation analysis revealed that global network metrics were extremely sensitive (but varying degrees) to noise in functional connectivity and weighted networks generated numerically more reliable results in compared with binarized networks. For nodal network metrics, they showed high resistance to noise in functional connectivity and no NT related differences were found in the resistance. These findings provide important implications on how to choose reliable analytical schemes and network metrics of interest. PMID:21818285

  17. Impact evaluation of environmental factors on respiratory function of asthma patients living in urban territory.

    PubMed

    Veremchuk, Lyudmila V; Tsarouhas, Konstantinos; Vitkina, Tatyana I; Mineeva, Elena E; Gvozdenko, Tatyana A; Antonyuk, Marina V; Rakitskii, Valeri N; Sidletskaya, Karolina A; Tsatsakis, Aristidis M; Golokhvast, Kirill S

    2018-04-01

    Environmental pollution, local climatic conditions and their association with the prevalence and exacerbation of asthma are topics of intense current medical investigation. Air pollution in the area of Vladivostock was estimated both by the index of emission volumes of "air gaseous components" (nitrogen oxide and nitrogen dioxide, formaldehyde, hydrogen sulfide, carbon monoxide) in urban atmosphere and by mass spectrometric analysis of precipitates in snow samples. A total of 172 local asthma patients (101 controlled-asthma patients-CAP and 71 non-controlled asthma patients - nCAP) were evaluated with the use of spirometry and body plethysmography. Airway obstruction reversibility was evaluated with the use of an inhaled bronchodilator. Using discriminant analysis the association of environmental parameters with clinical indices of asthma patients is explored and thresholds of impact are established. CAP presented high sensitivity to large-size suspended air particles and to several of the studied climatic parameters. Discriminant analysis showed high values of Wilks' lambda index (α = 0.69-0.81), which implies limited influence of environmental factors on the respiratory parameters of CAP. nCAP were more sensitive and susceptible to the majority of the environmental factors studied, including air suspended toxic metals particles (Cr, Zn and Ni). Air suspended particles showed higher tendency for pathogenicity in nCAP population than in the CAP, with a wider range of particle sizes being involved. Dust fractions ranging from 0 to 1 μm and from 50 to 100 μm were additionally implicated compared to CAP group. Considerably lowest thresholds levels of impact are calculated for nCAP. Copyright © 2017. Published by Elsevier Ltd.

  18. Participation of the nitric oxide-cyclic GMP-ATP-sensitive K(+) channel pathway in the antinociceptive action of ketorolac.

    PubMed

    Lázaro-Ibáñez, G G; Torres-López, J E; Granados-Soto, V

    2001-08-24

    The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K(+) channels in the antinociceptive effect of ketorolac was assessed using the formalin test in the rat. Local administration of ketorolac in a formalin-injured paw produced a dose-dependent antinociceptive effect due to a local action, as drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with N(G)-L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) or glibenclamide (an ATP-sensitive K(+) channel blocker) prevented ketorolac-induced antinociception. However, pretreatment with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was inactive by itself, but increased the effect of ketorolac. The present results suggest that the antinociceptive effect of ketorolac involves activation of the NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K(+) channels at the peripheral level.

  19. Elucidation of the role of biological factors and device design in cerebral NIRS using an in vivo hematoma model based on high-intensity focused ultrasound

    NASA Astrophysics Data System (ADS)

    Wang, Jianting; Huang, Stanley; Myers, Matthew; Chen, Yu; Welle, Cristin; Pfefer, Joshua

    2016-03-01

    Near-Infrared Spectroscopy (NIRS) is an emerging medical countermeasure for rapid, field detection of hematomas caused by traumatic brain injury (TBI). Bench and animal tests to determine NIRS sensitivity and specificity are needed. However, current animal models involving non-invasively induced, localized neural damage are limited. We investigated an in vivo murine hematoma model in which cerebral hemorrhage was induced noninvasively by high-intensity focused ultrasound (HIFU) with calibrated positioning and parameters. To characterize the morphology of induced hematomas, we used skull-intact histological evaluation. A multi-wavelength fiber-optic NIRS system with three source-detector separation distances was used to detect hematoma A 1.1 MHz transducer produced consistent small-to-medium hematoma localized to a single hemisphere, along with bruising of the scalp, with a low mortality rate. A 220 kHz transducer produced larger, more diffuse hematomas, with higher variability in size and a correspondingly higher mortality rate. No skin bruising or blood accumulation between the skin and skull was observed following injury application with the 220 kHz transducer. Histological analysis showed higher sensitivity for larger hematomas (>4x4 mm2). NIRS optical density change after HIFU was able to detect all hematomas, with sensitivity dependent on wavelength and separation distance. While improvements in methods for validating cerebral blood distribution are needed, the HIFU hematoma model provided useful insights that will inform development of biologically relevant, performance test methods for cerebral NIRS systems.

  20. Cross-scale analysis of cluster correspondence using different operational neighborhoods

    NASA Astrophysics Data System (ADS)

    Lu, Yongmei; Thill, Jean-Claude

    2008-09-01

    Cluster correspondence analysis examines the spatial autocorrelation of multi-location events at the local scale. This paper argues that patterns of cluster correspondence are highly sensitive to the definition of operational neighborhoods that form the spatial units of analysis. A subset of multi-location events is examined for cluster correspondence if they are associated with the same operational neighborhood. This paper discusses the construction of operational neighborhoods for cluster correspondence analysis based on the spatial properties of the underlying zoning system and the scales at which the zones are aggregated into neighborhoods. Impacts of this construction on the degree of cluster correspondence are also analyzed. Empirical analyses of cluster correspondence between paired vehicle theft and recovery locations are conducted on different zoning methods and across a series of geographic scales and the dynamics of cluster correspondence patterns are discussed.

  1. Immunophenotyping does not improve predictivity of the local lymph node assay in mice.

    PubMed

    Strauss, Volker; Kolle, Susanne N; Honarvar, Naveed; Dammann, Martina; Groeters, Sibylle; Faulhammer, Frank; Landsiedel, Robert; van Ravenzwaay, Bennard

    2015-04-01

    The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry-based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I-A(κ) and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non-irritating sensitizers and non-sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Who contracts for primary care?

    PubMed

    Lewis, R; Gillam, S; Gosden, T; Sheaff, R

    1999-12-01

    The implications of the 1997 NHS (Primary Care) Act have been largely overlooked in the rush to establish Primary Care Groups. Allowing health authorities to develop local contracts for primary care has far-reaching implications and is an important departure from the national system of negotiation that has characterized general practice to date. This paper describes a content analysis of a sample of Personal Medical Services (PMS) pilot contracts. In the first year little attention has been given to achieving cost savings or greater efficiency and few contracts promote clinical guidelines. The difficulties of specifying services sensitive to local health needs are highlighted and the national Statement of Fees and Allowances (the 'Red Book') may not be swiftly supplanted. However, the pilots have introduced innovations such as salaried general practitioners, nurse-led services and NHS trust-managed care. The development of local contracts provides a valuable learning experience for general practitioners and health authorities in advance of the establishment of Primary Care Trusts.

  3. Understanding and mimicking the dual optimality of the fly ear

    NASA Astrophysics Data System (ADS)

    Liu, Haijun; Currano, Luke; Gee, Danny; Helms, Tristan; Yu, Miao

    2013-08-01

    The fly Ormia ochracea has the remarkable ability, given an eardrum separation of only 520 μm, to pinpoint the 5 kHz chirp of its cricket host. Previous research showed that the two eardrums are mechanically coupled, which amplifies the directional cues. We have now performed a mechanics and optimization analysis which reveals that the right coupling strength is key: it results in simultaneously optimized directional sensitivity and directional cue linearity at 5 kHz. We next demonstrated that this dual optimality is replicable in a synthetic device and can be tailored for a desired frequency. Finally, we demonstrated a miniature sensor endowed with this dual-optimality at 8 kHz with unparalleled sound localization. This work provides a quantitative and mechanistic explanation for the fly's sound-localization ability from a new perspective, and it provides a framework for the development of fly-ear inspired sensors to overcoming a previously-insurmountable size constraint in engineered sound-localization systems.

  4. Six components observations of local earthquakes during the 2016 Central Italy seismic sequence

    NASA Astrophysics Data System (ADS)

    Simonelli, A.; Bernauer, F.; Chow, B.; Braun, T.; Wassermann, J. M.; Igel, H.

    2017-12-01

    For many years the seismological community has looked for a reliable, sensitive, broadband three-component portable rotational sensor. In this preliminary study, we show the possibility of measuring and extracting relevant seismological information from local earthquakes. We employ portable three-component rotational sensors, insensitive to translations, which operate on optical interferometry principles (Sagnac effect). Multiple sensors recording redundantly add significance to the measurements.During the Central Italy seismic sequence in November 2016, we deployed two portable fiber-optic gyroscopes (BlueSeis3A from iXBlue and LCG demonstrator from LITEF) and a broadband seismometer in Colfiorito, Italy. We present here the six-component observations, with analysis of rotational (three redundant components) and translational (three components) ground motions, generated by earthquakes at local distances. For each seismic event, we compare coherence between rotational sensors and estimate a back azimuth consistent with theoretical values. We also estimate Love and Rayleigh wave phase velocities in the 5 to 10 Hz frequency range.

  5. Advanced materials for improving biosensing performances of propagating and localized plasmonic transducers

    NASA Astrophysics Data System (ADS)

    Manera, M. G.; Colombelli, A.; Convertino, A.; Rella, S.; De Lorenzis, E.; Taurino, A.; Malitesta, C.; Rella, R.

    2015-05-01

    Among all transduction methodologies reported in the field of solid state optical chemical sensors, the attention has been focused onto the optical sensing characterization by using propagating and localized surface plasmon resonance (SPR) techniques. The research in this field is always oriented in the improvement of the sensing features in terms of sensitivity and limits of detection. To this purpose different strategies have been proposed to realize advanced materials for high sensitive plasmonic devices. In this work nanostructured silica nanowires decorated by gold nanoparticles and active magneto-plasmonic transductors are considered as new biosensing transductors useful to increase the performance of sensitive devices.

  6. [Sensitivity of meningococci to the antagonistic activity of nasopharyngeal microflora and antibiotics].

    PubMed

    Bochkov, I A; Larina, L I

    1977-12-01

    Comparative study of the meningococcus sensitivity of various serological groups with different localization in the human organism to the antagonistic activity of normal microbes of the nasopharynx and the antibiotics it was found that strains isolated from the cerebrospinal fluid of patients suffering from cerebrospinal meningitis, chiefly of serological group A, had the greatest resistance to the antagonists. Taking into consideration the leading epidemiological role of the cultures belonging to the serological group A in the USSR, it can be supposed that meningococcus sensitivity to the nasopharyngeal antagonists was of significance for the manifestation of their pathogenic properties. No association of the antibiotic sensitivity of the same strains with reference to a definite serological group or the site of the microbe localization was revealed.

  7. Automatic detection of DNA double strand breaks after irradiation using an γH2AX assay.

    PubMed

    Hohmann, Tim; Kessler, Jacqueline; Grabiec, Urszula; Bache, Matthias; Vordermark, Dyrk; Dehghani, Faramarz

    2018-05-01

    Radiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations. Therefore, we present a method to automatically analyze the number of foci inside nuclei, facilitating and quickening the analysis of DSBs with high reliability in fluorescent images. First nuclei were detected in fluorescent images. Afterwards, the nuclei were analyzed independently from each other with a local thresholding algorithm. This approach allowed accounting for different levels of noise and detection of the foci inside the respective nucleus, using Hough transformation searching for circles. The presented algorithm was able to correctly classify most foci in cases of "high" and "average" image quality (sensitivity>0.8) with a low rate of false positive detections (positive predictive value (PPV)>0.98). In cases of "low" image quality the approach had a decreased sensitivity (0.7-0.9), depending on the manual control counter. The PPV remained high (PPV>0.91). Compared to other automatic approaches the presented algorithm had a higher sensitivity and PPV. The used automatic foci detection algorithm was capable of detecting foci with high sensitivity and PPV. Thus it can be used for automatic analysis of images of varying quality.

  8. High-Speed Real-Time Resting-State fMRI Using Multi-Slab Echo-Volumar Imaging

    PubMed Central

    Posse, Stefan; Ackley, Elena; Mutihac, Radu; Zhang, Tongsheng; Hummatov, Ruslan; Akhtari, Massoud; Chohan, Muhammad; Fisch, Bruce; Yonas, Howard

    2013-01-01

    We recently demonstrated that ultra-high-speed real-time fMRI using multi-slab echo-volumar imaging (MEVI) significantly increases sensitivity for mapping task-related activation and resting-state networks (RSNs) compared to echo-planar imaging (Posse et al., 2012). In the present study we characterize the sensitivity of MEVI for mapping RSN connectivity dynamics, comparing independent component analysis (ICA) and a novel seed-based connectivity analysis (SBCA) that combines sliding-window correlation analysis with meta-statistics. This SBCA approach is shown to minimize the effects of confounds, such as movement, and CSF and white matter signal changes, and enables real-time monitoring of RSN dynamics at time scales of tens of seconds. We demonstrate highly sensitive mapping of eloquent cortex in the vicinity of brain tumors and arterio-venous malformations, and detection of abnormal resting-state connectivity in epilepsy. In patients with motor impairment, resting-state fMRI provided focal localization of sensorimotor cortex compared with more diffuse activation in task-based fMRI. The fast acquisition speed of MEVI enabled segregation of cardiac-related signal pulsation using ICA, which revealed distinct regional differences in pulsation amplitude and waveform, elevated signal pulsation in patients with arterio-venous malformations and a trend toward reduced pulsatility in gray matter of patients compared with healthy controls. Mapping cardiac pulsation in cortical gray matter may carry important functional information that distinguishes healthy from diseased tissue vasculature. This novel fMRI methodology is particularly promising for mapping eloquent cortex in patients with neurological disease, having variable degree of cooperation in task-based fMRI. In conclusion, ultra-high-real-time speed fMRI enhances the sensitivity of mapping the dynamics of resting-state connectivity and cerebro-vascular pulsatility for clinical and neuroscience research applications. PMID:23986677

  9. ASPASIA: A toolkit for evaluating the effects of biological interventions on SBML model behaviour.

    PubMed

    Evans, Stephanie; Alden, Kieran; Cucurull-Sanchez, Lourdes; Larminie, Christopher; Coles, Mark C; Kullberg, Marika C; Timmis, Jon

    2017-02-01

    A calibrated computational model reflects behaviours that are expected or observed in a complex system, providing a baseline upon which sensitivity analysis techniques can be used to analyse pathways that may impact model responses. However, calibration of a model where a behaviour depends on an intervention introduced after a defined time point is difficult, as model responses may be dependent on the conditions at the time the intervention is applied. We present ASPASIA (Automated Simulation Parameter Alteration and SensItivity Analysis), a cross-platform, open-source Java toolkit that addresses a key deficiency in software tools for understanding the impact an intervention has on system behaviour for models specified in Systems Biology Markup Language (SBML). ASPASIA can generate and modify models using SBML solver output as an initial parameter set, allowing interventions to be applied once a steady state has been reached. Additionally, multiple SBML models can be generated where a subset of parameter values are perturbed using local and global sensitivity analysis techniques, revealing the model's sensitivity to the intervention. To illustrate the capabilities of ASPASIA, we demonstrate how this tool has generated novel hypotheses regarding the mechanisms by which Th17-cell plasticity may be controlled in vivo. By using ASPASIA in conjunction with an SBML model of Th17-cell polarisation, we predict that promotion of the Th1-associated transcription factor T-bet, rather than inhibition of the Th17-associated transcription factor RORγt, is sufficient to drive switching of Th17 cells towards an IFN-γ-producing phenotype. Our approach can be applied to all SBML-encoded models to predict the effect that intervention strategies have on system behaviour. ASPASIA, released under the Artistic License (2.0), can be downloaded from http://www.york.ac.uk/ycil/software.

  10. Total Scattering and Pair Distribution Function Analysis in Modelling Disorder in PZN

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Whitfield, Ross E.; Goossens, Darren J; Welberry, T. R.

    2016-01-01

    The ability of the pair distribution function (PDF) analysis of total scattering (TS) from a powder to determine the local ordering in ferroelectric PZN (PbZn 1/3Nb 2/3O 3) has been explored by comparison with a model established using single-crystal diffuse scattering (SCDS). While X-ray PDF analysis is discussed, the focus is on neutron diffraction results because of the greater extent of the data and the sensitivity of the neutron to oxygen atoms, the behaviour of which is important in PZN. The PDF was shown to be sensitive to many effects not apparent in the average crystal structure, including variations inmore » the B-site—O separation distances and the fact that (110) Pb 2+ displacements are most likely. A qualitative comparison between SCDS and the PDF shows that some features apparent in SCDS were not apparent in the PDF. These tended to pertain to short-range correlations in the structure, rather than to interatomic separations. For example, in SCDS the short-range alternation of the B-site cations was quite apparent in diffuse scattering at (½ ½ ½), whereas it was not apparent in the PDF.« less

  11. Funding a smoking cessation program for Crohn's disease: an economic evaluation.

    PubMed

    Coward, Stephanie; Heitman, Steven J; Clement, Fiona; Negron, Maria; Panaccione, Remo; Ghosh, Subrata; Barkema, Herman W; Seow, Cynthia; Leung, Yvette P Y; Kaplan, Gilaad G

    2015-03-01

    Patients with Crohn's disease (CD) who smoke are at a higher risk of flaring and requiring surgery. Cost-effectiveness studies of funding smoking cessation programs are lacking. Thus, we performed a cost-utility analysis of funding smoking cessation programs for CD. A cost-utility analysis was performed comparing five smoking cessation strategies: No Program, Counseling, Nicotine Replacement Therapy (NRT), NRT+Counseling, and Varenicline. The time horizon for the Markov model was 5 years. The health states included medical remission (azathioprine or antitumor necrosis factor (anti-TNF), dose escalation of an anti-TNF, second anti-TNF, surgery, and death. Probabilities were taken from peer-reviewed literature, and costs (CAN$) for surgery, medications, and smoking cessation programs were estimated locally. The primary outcome was the cost per quality-adjusted life year (QALY) gained associated with each smoking cessation strategy. Threshold, three-way sensitivity, probabilistic sensitivity analysis (PSA), and budget impact analysis (BIA) were carried out. All strategies dominated No Program. Strategies from most to least cost effective were as follows: Varenicline (cost: $55,614, QALY: 3.70), NRT+Counseling (cost: $58,878, QALY: 3.69), NRT (cost: $59,540, QALY: 3.69), Counseling (cost: $61,029, QALY: 3.68), and No Program (cost: $63,601, QALY: 3.67). Three-way sensitivity analysis demonstrated that No Program was only more cost effective when every strategy's cost exceeded approximately 10 times their estimated costs. The PSA showed that No Program was the most cost-effective <1% of the time. The BIA showed that any strategy saved the health-care system money over No Program. Health-care systems should consider funding smoking cessation programs for CD, as they improve health outcomes and reduce costs.

  12. Economic Evaluation of First-Line Treatments for Metastatic Renal Cell Carcinoma: A Cost-Effectiveness Analysis in A Health Resource–Limited Setting

    PubMed Central

    Wu, Bin; Dong, Baijun; Xu, Yuejuan; Zhang, Qiang; Shen, Jinfang; Chen, Huafeng; Xue, Wei

    2012-01-01

    Background To estimate, from the perspective of the Chinese healthcare system, the economic outcomes of five different first-line strategies among patients with metastatic renal cell carcinoma (mRCC). Methods and Findings A decision-analytic model was developed to simulate the lifetime disease course associated with renal cell carcinoma. The health and economic outcomes of five first-line strategies (interferon-alfa, interleukin-2, interleukin-2 plus interferon-alfa, sunitinib and bevacizumab plus interferon-alfa) were estimated and assessed by indirect comparison. The clinical and utility data were taken from published studies. The cost data were estimated from local charge data and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the sunitinib patient assistant program (SPAP) was evaluated via scenario analysis. The base-case analysis showed that the sunitinib strategy yielded the maximum health benefits: 2.71 life years and 1.40 quality-adjusted life-years (QALY). The marginal cost-effectiveness (cost per additional QALY) gained via the sunitinib strategy compared with the conventional strategy was $220,384 (without SPAP, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated) and $16,993 (with SPAP, interferon-alfa, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated). In general, the results were sensitive to the hazard ratio of progression-free survival. The probabilistic sensitivity analysis demonstrated that the sunitinib strategy with SPAP was the most cost-effective approach when the willingness-to-pay threshold was over $16,000. Conclusions Our analysis suggests that traditional cytokine therapy is the cost-effective option in the Chinese healthcare setting. In some relatively developed regions, sunitinib with SPAP may be a favorable cost-effective alternative for mRCC. PMID:22412884

  13. Economic evaluation of first-line treatments for metastatic renal cell carcinoma: a cost-effectiveness analysis in a health resource-limited setting.

    PubMed

    Wu, Bin; Dong, Baijun; Xu, Yuejuan; Zhang, Qiang; Shen, Jinfang; Chen, Huafeng; Xue, Wei

    2012-01-01

    To estimate, from the perspective of the Chinese healthcare system, the economic outcomes of five different first-line strategies among patients with metastatic renal cell carcinoma (mRCC). A decision-analytic model was developed to simulate the lifetime disease course associated with renal cell carcinoma. The health and economic outcomes of five first-line strategies (interferon-alfa, interleukin-2, interleukin-2 plus interferon-alfa, sunitinib and bevacizumab plus interferon-alfa) were estimated and assessed by indirect comparison. The clinical and utility data were taken from published studies. The cost data were estimated from local charge data and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the sunitinib patient assistant program (SPAP) was evaluated via scenario analysis. The base-case analysis showed that the sunitinib strategy yielded the maximum health benefits: 2.71 life years and 1.40 quality-adjusted life-years (QALY). The marginal cost-effectiveness (cost per additional QALY) gained via the sunitinib strategy compared with the conventional strategy was $220,384 (without SPAP, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated) and $16,993 (with SPAP, interferon-alfa, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated). In general, the results were sensitive to the hazard ratio of progression-free survival. The probabilistic sensitivity analysis demonstrated that the sunitinib strategy with SPAP was the most cost-effective approach when the willingness-to-pay threshold was over $16,000. Our analysis suggests that traditional cytokine therapy is the cost-effective option in the Chinese healthcare setting. In some relatively developed regions, sunitinib with SPAP may be a favorable cost-effective alternative for mRCC.

  14. Assessing the effect of extrinsic incubation period (EIP) prolongation in controlling dengue transmission with wolbachia-infected mosquito intervention

    NASA Astrophysics Data System (ADS)

    Putri, Y. E.; Rozi, S.; Tasman, H.; Aldila, D.

    2017-03-01

    A mathematical model of dengue disease transmission with involving Extrinsic Incubation Period (EIP) effect as a consequence of wolbachia introduction into mossquito population will be discussed in this article. Mathematical model analysis to find equilibrium points, basic reproductive ratio (ℛ0), and criteria of endemic occurrence which depend on some parameters were performed. From analytical result, we find that ℛ0 hold an important role to determine the existence and local stability of equilibrium points. From sensitivity analysis of ℛ0 and numerical simulation, we conclude that prolongation of EIP with wolbachia intervention succeed to reduce number of infected human and mosquito significantly.

  15. Intracellular applications of fluorescence correlation spectroscopy: prospects for neuroscience.

    PubMed

    Kim, Sally A; Schwille, Petra

    2003-10-01

    Based on time-averaging fluctuation analysis of small fluorescent molecular ensembles in equilibrium, fluorescence correlation spectroscopy has recently been applied to investigate processes in the intracellular milieu. The exquisite sensitivity of fluorescence correlation spectroscopy provides access to a multitude of measurement parameters (rates of diffusion, local concentration, states of aggregation and molecular interactions) in real time with fast temporal and high spatial resolution. The introduction of dual-color cross-correlation, imaging, two-photon excitation, and coincidence analysis coupled with fluorescence correlation spectroscopy has expanded the utility of the technique to encompass a wide range of promising applications in living cells that may provide unprecedented insight into understanding the molecular mechanisms of intracellular neurobiological processes.

  16. Parameter sensitivity and identifiability for a biogeochemical model of hypoxia in the northern Gulf of Mexico

    EPA Science Inventory

    Local sensitivity analyses and identifiable parameter subsets were used to describe numerical constraints of a hypoxia model for bottom waters of the northern Gulf of Mexico. The sensitivity of state variables differed considerably with parameter changes, although most variables ...

  17. Ellipsoidal analysis of coordination polyhedra

    PubMed Central

    Cumby, James; Attfield, J. Paul

    2017-01-01

    The idea of the coordination polyhedron is essential to understanding chemical structure. Simple polyhedra in crystalline compounds are often deformed due to structural complexity or electronic instabilities so distortion analysis methods are useful. Here we demonstrate that analysis of the minimum bounding ellipsoid of a coordination polyhedron provides a general method for studying distortion, yielding parameters that are sensitive to various orders in metal oxide examples. Ellipsoidal analysis leads to discovery of a general switching of polyhedral distortions at symmetry-disallowed transitions in perovskites that may evidence underlying coordination bistability, and reveals a weak off-centre ‘d5 effect' for Fe3+ ions that could be exploited in multiferroics. Separating electronic distortions from intrinsic deformations within the low temperature superstructure of magnetite provides new insights into the charge and trimeron orders. Ellipsoidal analysis can be useful for exploring local structure in many materials such as coordination complexes and frameworks, organometallics and organic molecules. PMID:28146146

  18. Nanoscale deformation analysis with high-resolution transmission electron microscopy and digital image correlation

    DOE PAGES

    Wang, Xueju; Pan, Zhipeng; Fan, Feifei; ...

    2015-09-10

    We present an application of the digital image correlation (DIC) method to high-resolution transmission electron microscopy (HRTEM) images for nanoscale deformation analysis. The combination of DIC and HRTEM offers both the ultrahigh spatial resolution and high displacement detection sensitivity that are not possible with other microscope-based DIC techniques. We demonstrate the accuracy and utility of the HRTEM-DIC technique through displacement and strain analysis on amorphous silicon. Two types of error sources resulting from the transmission electron microscopy (TEM) image noise and electromagnetic-lens distortions are quantitatively investigated via rigid-body translation experiments. The local and global DIC approaches are applied for themore » analysis of diffusion- and reaction-induced deformation fields in electrochemically lithiated amorphous silicon. As a result, the DIC technique coupled with HRTEM provides a new avenue for the deformation analysis of materials at the nanometer length scales.« less

  19. OPTIMA: sensitive and accurate whole-genome alignment of error-prone genomic maps by combinatorial indexing and technology-agnostic statistical analysis.

    PubMed

    Verzotto, Davide; M Teo, Audrey S; Hillmer, Axel M; Nagarajan, Niranjan

    2016-01-01

    Resolution of complex repeat structures and rearrangements in the assembly and analysis of large eukaryotic genomes is often aided by a combination of high-throughput sequencing and genome-mapping technologies (for example, optical restriction mapping). In particular, mapping technologies can generate sparse maps of large DNA fragments (150 kilo base pairs (kbp) to 2 Mbp) and thus provide a unique source of information for disambiguating complex rearrangements in cancer genomes. Despite their utility, combining high-throughput sequencing and mapping technologies has been challenging because of the lack of efficient and sensitive map-alignment algorithms for robustly aligning error-prone maps to sequences. We introduce a novel seed-and-extend glocal (short for global-local) alignment method, OPTIMA (and a sliding-window extension for overlap alignment, OPTIMA-Overlap), which is the first to create indexes for continuous-valued mapping data while accounting for mapping errors. We also present a novel statistical model, agnostic with respect to technology-dependent error rates, for conservatively evaluating the significance of alignments without relying on expensive permutation-based tests. We show that OPTIMA and OPTIMA-Overlap outperform other state-of-the-art approaches (1.6-2 times more sensitive) and are more efficient (170-200 %) and precise in their alignments (nearly 99 % precision). These advantages are independent of the quality of the data, suggesting that our indexing approach and statistical evaluation are robust, provide improved sensitivity and guarantee high precision.

  20. Epoxy resin monomers with reduced skin sensitizing potency.

    PubMed

    O'Boyle, Niamh M; Niklasson, Ida B; Tehrani-Bagha, Ali R; Delaine, Tamara; Holmberg, Krister; Luthman, Kristina; Karlberg, Ann-Therese

    2014-06-16

    Epoxy resin monomers (ERMs), especially diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to commonly cause skin allergy. This research describes a number of alternative ERMs, designed with the aim of reducing the skin sensitizing potency while maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, and assessed for sensitizing potency using the in vivo murine local lymph node assay (LLNA). All six epoxy resin monomers had decreased sensitizing potencies compared to those of DGEBA and DGEBF. With respect to the LLNA EC3 value, the best of the alternative monomers had a value approximately 2.5 times higher than those of DGEBA and DGEBF. The diepoxides were reacted with triethylenetetramine, and the polymers formed were tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. Four out of the six alternative ERMs gave polymers with a thermal stability comparable to that obtained with DGEBA and DGEBF. The use of improved epoxy resin monomers with less skin sensitizing effects is a direct way to tackle the problem of contact allergy to epoxy resin systems, particularly in occupational settings, resulting in a reduction in the incidence of allergic contact dermatitis.

  1. Implementation of a WRF-CMAQ Air Quality Modeling System in Bogotá, Colombia

    NASA Astrophysics Data System (ADS)

    Nedbor-Gross, R.; Henderson, B. H.; Pachon, J. E.; Davis, J. R.; Baublitz, C. B.; Rincón, A.

    2014-12-01

    Due to a continuous economic growth Bogotá, Colombia has experienced air pollution issues in recent years. The local environmental authority has implemented several strategies to curb air pollution that have resulted in the decrease of PM10 concentrations since 2010. However, more activities are necessary in order to meet international air quality standards in the city. The University of Florida Air Quality and Climate group is collaborating with the Universidad de La Salle to prioritize regulatory strategies for Bogotá using air pollution simulations. To simulate pollution, we developed a modeling platform that combines the Weather Research and Forecasting Model (WRF), local emissions, and the Community Multi-scale Air Quality model (CMAQ). This platform is the first of its kind to be implemented in the megacity of Bogota, Colombia. The presentation will discuss development and evaluation of the air quality modeling system, highlight initial results characterizing photochemical conditions in Bogotá, and characterize air pollution under proposed regulatory strategies. The WRF model has been configured and applied to Bogotá, which resides in a tropical climate with complex mountainous topography. Developing the configuration included incorporation of local topography and land-use data, a physics sensitivity analysis, review, and systematic evaluation. The threshold, however, was set based on synthesis of model performance under less mountainous conditions. We will evaluate the impact that differences in autocorrelation contribute to the non-ideal performance. Air pollution predictions are currently under way. CMAQ has been configured with WRF meteorology, global boundary conditions from GEOS-Chem, and a locally produced emission inventory. Preliminary results from simulations show promising performance of CMAQ in Bogota. Anticipated results include a systematic performance evaluation of ozone and PM10, characterization of photochemical sensitivity, and air quality predictions under proposed regulatory scenarios.

  2. HLA-A, -B, and -DR zero-mismatched kidneys shipped to the University of Wisconsin, Madison, 1993-2006: superior graft survival despite longer preservation time.

    PubMed

    Burlingham, William J; Muñoz del Rio, Alejandro; Lorentzen, David; Sollinger, Hans W; Pirsch, John D; Jankowska-Gan, Ewa; D'Alessandro, Anthony

    2010-08-15

    To determine the impact at a single center of the United Network for Organ Sharing-mandated sharing program for human leukocyte antigen (HLA)-A/-B/-DR 0-mismatched (0MM) kidneys, we analyzed the results of 264 kidney transplants from 0MM distant donors between 1993 and 2006, with a follow-up through January 31, 2007. We compared these results with that of concurrent kidneys transplanted from HLA more than 0MM local donors and with shipped more than 0MM kidneys from "payback" donors. Despite a significantly longer preservation time, we found an 11% increase in 8-year graft survival (63% vs. 52%; P<0.003) of 0MM shipped versus locally procured, >0MM donor kidneys. Graft survival of 0MM shipped kidneys at 8 years was significantly better in nonsensitized (<20% panel reactive antibodies; 68% vs. 55%; P<0.0005) but not in sensitized (>or=20% panel reactive antibodies) recipients, who showed an early (2 years) but short-lived benefit. The benefit of receiving a HLA-A, -B, and -DR 0MM shipped kidney remained strong and statistically significant (0.71 relative risk of graft loss vs. local; P<0.02) when adjusted for 22 potentially confounding variables in a Cox proportional hazards analysis. The recent change in United Network for Organ Sharing policy restricting mandated sharing of 0MM kidneys to sensitized and pediatric recipients will give greater flexibility to the local organ procurement organization in allocating organs. However, the survival benefit to nonsensitized patients is real and long lasting and will be lost.

  3. Building Training Curricula for Accelerating the Use of NOAA Climate Products and Tools

    NASA Astrophysics Data System (ADS)

    Timofeyeva-Livezey, M. M.; Meyers, J. C.; Stevermer, A.; Abshire, W. E.; Beller-Simms, N.; Herring, D.

    2016-12-01

    The National Oceanic and Atmospheric Administration (NOAA) plays a leading role in U.S. intergovernmental efforts on the Climate Data Initiative and the Climate Resilience Toolkit (CRT). CRT (http://toolkit.climate.gov/) is a valuable resource that provides tools, information, and subject matter expertise to decision makers in various sectors, such as agriculture, water resources and transportation, to help them build resilience to our changing climate. In order to make best use of the toolkit and all the resources within it, a training component is critical. The training section helps building users' understanding of the data, science, and impacts of climate variability and change. CRT identifies five steps in building resilience that includes use of appropriate tools to support decision makers depending on their needs. One tool that can be potentially integrated into CRT is NOAA's Local Climate Analysis Tool (LCAT), which provides access to trusted NOAA data and scientifically-sound analysis techniques for doing regional and local climate studies on climate variability and climate change. However, in order for LCAT to be used effectively, we have found an iterative learning approach using specific examples to train users. For example, for LCAT application in analysis of water resources, we use existing CRT case studies for Arizona and Florida water supply users. The Florida example demonstrates primary sensitivity to climate variability impacts, whereas the Arizona example takes into account longer- term climate change. The types of analyses included in LCAT are time series analysis of local climate and the estimated rate of change in the local climate. It also provides a composite analysis to evaluate the relationship between local climate and climate variability events such as El Niño Southern Oscillation, the Pacific North American Index, and other modes of climate variability. This paper will describe the development of a training module for use of LCAT and its integration into CRT. An iterative approach was used that incorporates specific examples of decision making while working with subject matter experts within the water supply community. The recommended strategy is to use a "stepping stone" learning structure to build users knowledge of best practices for use of LCAT.

  4. SU-F-T-294: The Analysis of Gamma Criteria for Delta4 Dosimetry Using Statistical Process Control

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cho, S; Ahn, S; Kim, J

    Purpose: To evaluate the sensitivity of gamma criteria for patient-specific volumetric modulated arc therapy(VMAT) quality assurance of the Delta{sup 4} dosimetry program using the statistical process control(SPC) methodology. Methods: The authors selected 20 patient-specific VMAT QA cases which were undertaken MapCHECK and ArcCHECK with gamma pass rate better than 97%. The QAs data were collected Delta4 Phantom+ and Elekta Agility six megavolts without using an angle incrementer. The gamma index(GI) were calculated in 2D planes with normalizing deviation to local dose(local gamma). The sensitivity of the GI methodology using criterion of 3%/3mm, 3%/2mm and 2%/3mm was analyzed with using processmore » acceptability indices. We used local confidence(LC) level, the upper control limit(UCL) and lower control limit(LCL) of I-MR chart for process capability index(Cp) and a process acceptability index (Cpk). Results: The lower local confidence levels of 3%/3mm, 3%/2mm and 2%/3mm were 92.0%, 83.6% and 78.8% respectively. All of the calculated Cp and Cpk values that used LC level were under 1.0 in this study. The calculated LCLs of I-MR charts were 89.5%, 79.0% and 70.5% respectively. These values were higher than 1.0 which means good quality of QA. For the generally used lower limit of 90%, we acquired over 1.3 of Cp value for the gamma index of 3%/3mm and lower than 1.0 in the rest of GI. Conclusion: We applied SPC methodology to evaluate the sensitivity of gamma criteria and could see the lower control limits of VMAT QA for the Delta 4 dosimetry and could see that Delta 4 phantom+ dosimetry more affected by the position error and the I-MR chart derived values are more suitable for establishing lower limits. Acknowledgement: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (No. 2015R1D1A1A01060463)« less

  5. Non-localization and localization ROC analyses using clinically based scoring

    NASA Astrophysics Data System (ADS)

    Paquerault, Sophie; Samuelson, Frank W.; Myers, Kyle J.; Smith, Robert C.

    2009-02-01

    We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance. The data utilized in this investigation were derived from a multi-reader multi-case observer study involving one hundred mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low- and high-intensity signal sets. The study setting allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) lower than the average reader. Seven readers were asked to review each set in the unaided and CAD-aided reading modes, mark and rate their findings. Using this data, we studied the effect on study conclusion of three clinically-based receiver operating characteristic (ROC) scoring definitions. These scoring definitions included both location-specific and non-location-specific rules. The results showed agreement in the estimated impact of CAD on the overall reader performance. In the study setting where CAD sensitivity is superior to the average reader, the mean difference in AUC between the CAD-aided read and unaided read was 0.049 (95%CIs: -0.027; 0.130) for the image scoring definition that is based on non-location-specific rules, and 0.104 (95%CIs: 0.036; 0.174) and 0.090 (95%CIs: 0.031; 0.155) for image scoring definitions that are based on location-specific rules. The increases in AUC were statistically significant for the location-specific scoring definitions. It was further observed that the variance on these estimates was reduced when using the location-specific scoring definitions compared to that using a non-location-specific scoring definition. In the study setting where CAD sensitivity is equivalent or lower than the average reader, the mean differences in AUC are slightly above 0.01 for all image scoring definitions. These increases in AUC were not statistical significant for any of the image scoring definitions. The results on the variance analysis differed from those observed in the other study setting. This investigation furthers our understanding of the relationships between non-localization-specific and localization-specific ROC assessment methodologies and their relevance to clinical practice.

  6. Evaluation Methodology between Globalization and Localization Features Approaches for Skin Cancer Lesions Classification

    NASA Astrophysics Data System (ADS)

    Ahmed, H. M.; Al-azawi, R. J.; Abdulhameed, A. A.

    2018-05-01

    Huge efforts have been put in the developing of diagnostic methods to skin cancer disease. In this paper, two different approaches have been addressed for detection the skin cancer in dermoscopy images. The first approach uses a global method that uses global features for classifying skin lesions, whereas the second approach uses a local method that uses local features for classifying skin lesions. The aim of this paper is selecting the best approach for skin lesion classification. The dataset has been used in this paper consist of 200 dermoscopy images from Pedro Hispano Hospital (PH2). The achieved results are; sensitivity about 96%, specificity about 100%, precision about 100%, and accuracy about 97% for globalization approach while, sensitivity about 100%, specificity about 100%, precision about 100%, and accuracy about 100% for Localization Approach, these results showed that the localization approach achieved acceptable accuracy and better than globalization approach for skin cancer lesions classification.

  7. Brain shaving: adaptive detection for brain PET data

    NASA Astrophysics Data System (ADS)

    Grecchi, Elisabetta; Doyle, Orla M.; Bertoldo, Alessandra; Pavese, Nicola; Turkheimer, Federico E.

    2014-05-01

    The intricacy of brain biology is such that the variation of imaging end-points in health and disease exhibits an unpredictable range of spatial distributions from the extremely localized to the very diffuse. This represents a challenge for the two standard approaches to analysis, the mass univariate and the multivariate that exhibit either strong specificity but not as good sensitivity (the former) or poor specificity and comparatively better sensitivity (the latter). In this work, we develop an analytical methodology for positron emission tomography that operates an extraction (‘shaving’) of coherent patterns of signal variation while maintaining control of the type I error. The methodology operates two rotations on the image data, one local using the wavelet transform and one global using the singular value decomposition. The control of specificity is obtained by using the gap statistic that selects, within each eigenvector, a subset of significantly coherent elements. Face-validity of the algorithm is demonstrated using a paradigmatic data-set with two radiotracers, [11C]-raclopride and [11C]-(R)-PK11195, measured on the same Huntington's disease patients, a disorder with a genetic based diagnosis. The algorithm is able to detect the two well-known separate but connected processes of dopamine neuronal loss (localized in the basal ganglia) and neuroinflammation (diffusive around the whole brain). These processes are at the two extremes of the distributional envelope, one being very sparse and the latter being perfectly Gaussian and they are not adequately detected by the univariate and the multivariate approaches.

  8. Evaluation of four seagrass species as early warning indicators for nitrogen overloading: Implications for eutrophic evaluation and ecosystem management.

    PubMed

    Yang, Xiaolong; Zhang, Peidong; Li, Wentao; Hu, Chengye; Zhang, Xiumei; He, Pingguo

    2018-04-23

    Seagrasses are major coastal primary producers and are widely distributed on coasts worldwide. Seagrasses show sensitivity to environmental stress due to their high phenotypic plasticity, and therefore, we evaluated the use of constituent elements in four dominant seagrass species as early warning indicators for nitrogen eutrophication of coastal regions. A meta-analysis was conducted with published data to develop a global benchmark for the selected indicator, which was used to evaluate nitrogen loading at a global scale. A case study at three bays was subsequently conducted to test for local-scale differences in leaf C/N ratios in four seagrasses. Additionally, morphological and physiological metrics of seagrasses were measured from the three locations under varied nitrogen levels to develop further assessment indexes. The benchmark and local study showed that leaf C/N ratios of Zostera marina were sensitive to nitrogen discharge, which could be a highly valuable early warning indicator on a global scale. Moreover, the threshold value of seagrass leaf C/N was determined according to the benchmark to differentiate eutrophic and low nitrogen levels at a local scale. Of the eight phenotypic metrics measured, leaf width, total chlorophyll (a + b), chlorophyll ratio (a/b), and starch in the rhizome were the most effective at discriminating between the three locations and could also be promising indicators for monitoring eutrophication. Copyright © 2018. Published by Elsevier B.V.

  9. Sensitivity analysis of urban flood flows to hydraulic controls

    NASA Astrophysics Data System (ADS)

    Chen, Shangzhi; Garambois, Pierre-André; Finaud-Guyot, Pascal; Dellinger, Guilhem; Terfous, Abdelali; Ghenaim, Abdallah

    2017-04-01

    Flooding represents one of the most significant natural hazards on each continent and particularly in highly populated areas. Improving the accuracy and robustness of prediction systems has become a priority. However, in situ measurements of floods remain difficult while a better understanding of flood flow spatiotemporal dynamics along with dataset for model validations appear essential. The present contribution is based on a unique experimental device at the scale 1/200, able to produce urban flooding with flood flows corresponding to frequent to rare return periods. The influence of 1D Saint Venant and 2D Shallow water model input parameters on simulated flows is assessed using global sensitivity analysis (GSA). The tested parameters are: global and local boundary conditions (water heights and discharge), spatially uniform or distributed friction coefficient and or porosity respectively tested in various ranges centered around their nominal values - calibrated thanks to accurate experimental data and related uncertainties. For various experimental configurations a variance decomposition method (ANOVA) is used to calculate spatially distributed Sobol' sensitivity indices (Si's). The sensitivity of water depth to input parameters on two main streets of the experimental device is presented here. Results show that the closer from the downstream boundary condition on water height, the higher the Sobol' index as predicted by hydraulic theory for subcritical flow, while interestingly the sensitivity to friction decreases. The sensitivity indices of all lateral inflows, representing crossroads in 1D, are also quantified in this study along with their asymptotic trends along flow distance. The relationship between lateral discharge magnitude and resulting sensitivity index of water depth is investigated. Concerning simulations with distributed friction coefficients, crossroad friction is shown to have much higher influence on upstream water depth profile than street friction coefficients. This methodology could be applied to any urban flood configuration in order to better understand flow dynamics and repartition but also guide model calibration in the light of flow controls.

  10. A theoretical investigation into the strength of N-NO2 bonds, ring strain and electrostatic potential upon formation of intermolecular H-bonds between HF and the nitro group in nitrogen heterocyclic rings C n H2n N-NO2 (n = 2-5), RDX and HMX.

    PubMed

    Wang, Bao-Guo; Ren, Fu-de; Shi, Wen-Jing

    2015-11-01

    Changes in N-NO2 bond strength, ring strain energy and electrostatic potential upon formation of intermolecular H-bonds between HF and the nitro group in nitrogen heterocyclic rings C n H2n N-NO2 (n = 2-5), RDX and HMX were investigated using DFT-B3LYP and MP2(full) methods with the 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. Analysis of electron density shifts was also carried out. The results indicate that H-bonding energy correlates well with the increment of ring strain energy. Upon complex formation, the strength of the N-NO2 trigger-bond is enhanced, suggesting reduced sensitivity, while judged by the increased ring strain energy, sensitivity is increased. However, some features of the molecular surface electrostatic potential, such as a local maximum above the N-NO2 bond and ring, σ + (2) and electrostatic balance parameter ν, remain essentially unchanged upon complex formation, and only a small change in the impact sensitivity h 50 is suggested. It is not sufficient to determine sensitivity solely on the basis of trigger bond or ring strain; as a global feature of a molecule, the molecular surface electrostatic potential is available to help judge the change of sensitivity in H-bonded complexes. Graphical Abstract The strengthened N-NO2 bond suggests reduced sensitivity, while it is reverse by theincreased ring strain energy upon the complex formation. However, the molecular surfaceelectrostatic potential (V S) shows the little change of h 50. The V S should be taken into accountin the analysis of explosive sensitivity in the H-bonded complex.

  11. Analysis of the polar amplification pattern of global warming on an aquaplanet in "ghost forcing" experiments with no ice-albedo feedbacks

    NASA Astrophysics Data System (ADS)

    Alexeev, V. A.; Langen, P. L.

    2004-05-01

    Non-ice-albedo feedback mechanisms leading to polar amplification, as reported by Alexeev (2003), are explored in three aquaplanet climate model systems of different complexity. We analyze this pattern using three different "ghost forcing" experiments (Hansen et al, 1997). In the first one we uniformly add 4W/m2 to the oceanic mixed layer in order to roughly simulate a 2xCO2 forcing at the surface. The second forcing, of the same magnitude, is applied only within the tropics and the third forcing is applied only polewards of 30 degrees (north and south). It turns out that our systems' equilibrium responses are linear with respect to these forcings. Surprisingly, the response to the tropical-only forcing is essentially non-local with quite significant warming at higher latitudes. The response to the high-latitude-only forcing is more local and has higher amplitude near the poles. Our explanation of the polar amplification obtained in the uniform forcing experiment is therefore two-fold. Firstly, the tropics are much more difficult to warm because of the higher sensitivity of the surface budget to SST changes at higher temperatures. Secondly, any extra heat deposited in the tropics is not easily radiated to outer space because of the high opaqueness of the tropical atmosphere. The energy, most of which is latent, needs to be redistributed by transports to the extra-tropics. Consequently, the tropical "ghost forcing" results in an essentially non-local response, while the extra-tropical one yields a more localized response, because the energy in the atmosphere cannot propagate effectively equator-wards from high latitudes. The paper deals with these mechanisms in three climate model systems with no ice-albedo feedback - an EBM and two different GCMs - one with cloud feedbacks and the other with cloud feedbacks excluded. References. Alexeev, V.A., (2003) Sensitivity to CO2 doubling of an atmospheric GCM coupled to an oceanic mixed layer: a linear analysis. Climate Dynamics, 20: p.775-787. Hansen, J., Sato M, and R. Ruedy, (1997) Radiative forcing and climate response, JGR, 102, No. D6, 6831-6864.

  12. Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT.

    PubMed

    Hinson, Andrew M; Lee, David R; Hobbs, Bradley A; Fitzgerald, Ryan T; Bodenner, Donald L; Stack, Brendan C

    2015-11-01

    To evaluate 4-dimensional (4D) computed tomography (CT) for the localization of parathyroid adenomas previously considered nonlocalizing on ultrasound and single-photon emission CT with CT scanning (SPECT-CT). To measure radiation exposure associated with 4D-CT and compared it with SPECT-CT. Case series with chart review. University tertiary hospital. Nineteen adults with primary hyperparathyroidism who underwent preoperative 4D CT from November 2013 through July 2014 after nonlocalizing preoperative ultrasound and technetium-99m SPECT-CT scans. Sensitivity, specificity, predictive values, and accuracy of 4D CT were evaluated. Nineteen patients (16 women and 3 men) were included with a mean age of 66 years (range, 39-80 years). Mean preoperative parathyroid hormone level was 108.5 pg/mL (range, 59.3-220.9 pg/mL), and mean weight of the excised gland was 350 mg (range, 83-797 mg). 4D CT sensitivity and specificity for localization to the patient's correct side of the neck were 84.2% and 81.8%, respectively; accuracy was 82.9%. The sensitivity for localizing adenomas to the correct quadrant was 76.5% and 91.5%, respectively; accuracy was 88.2%. 4D CT radiation exposure was significantly less than the radiation associated with SPECT-CT (13.8 vs 18.4 mSv, P = 0.04). 4D CT localizes parathyroid adenomas with relatively high sensitivity and specificity and allows for the localization of some adenomas not observed on other sestamibi-based scans. 4D CT was also associated with less radiation exposure when compared with SPECT-CT based on our study protocol. 4D CT may be considered as first- or second-line imaging for localizing parathyroid adenomas in the setting of primary hyperparathyroidism. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  13. Solar energy system economic evaluation for Seeco Lincoln, Lincoln, Nebraska

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The economic analysis of the solar energy system that was installed at Lincoln, Nebraska is developed for this and four other sites typical of a wide range of environmental and economic conditions in the continental United States. This analysis is accomplished based on the technical and economic models in the f chart design procedure with inputs based on the characteristics of the installed system and local conditions. The results are expressed in terms of the economic parameters of present worth of system cost over projected twenty year life: life cycle savings, year of positive savings and year of payback for the optimized solar energy system at each of the analysis sites. The sensitivity of the economic evaluation to uncertainties in constituent system and economic variables is also investigated.

  14. Scanning laser polarimetry using variable corneal compensation in the detection of glaucoma with localized visual field defects.

    PubMed

    Kook, Michael S; Cho, Hyun-soo; Seong, Mincheol; Choi, Jaewan

    2005-11-01

    To evaluate the ability of scanning laser polarimetry parameters and a novel deviation map algorithm to discriminate between healthy and early glaucomatous eyes with localized visual field (VF) defects confined to one hemifield. Prospective case-control study. Seventy glaucomatous eyes with localized VF defects and 66 normal controls. A Humphrey field analyzer 24-2 full-threshold test and scanning laser polarimetry with variable corneal compensation were used. We assessed the sensitivity and specificity of scanning laser polarimetry parameters, sensitivity and cutoff values for scanning laser polarimetry deviation map algorithms at different specificity values (80%, 90%, and 95%) in the detection of glaucoma, and correlations between the algorithms of scanning laser polarimetry and of the pattern deviation derived from Humphrey field analyzer testing. There were significant differences between the glaucoma group and normal subjects in the mean parametric values of the temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average, inferior average, and TSNIT standard deviation (SD) (P<0.05). The sensitivity and specificity of each scanning laser polarimetry variable was as follows: TSNIT, 44.3% (95% confidence interval [CI], 39.8%-49.8%) and 100% (95.4%-100%); superior average, 30% (25.5%-34.5%) and 97% (93.5%-100%); inferior average, 45.7% (42.2%-49.2%) and 100% (95.8%-100%); and TSNIT SD, 30% (25.9%-34.1%) and 97% (93.2%-100%), respectively (when abnormal was defined as P<0.05). Based on nerve fiber indicator cutoff values of > or =30 and > or =51 to indicate glaucoma, sensitivities were 54.3% (50.1%-58.5%) and 10% (6.4%-13.6%), and specificities were 97% (93.2%-100%) and 100% (95.8%-100%), respectively. The range of areas under the receiver operating characteristic curves using the scanning laser polarimetry deviation map algorithm was 0.790 to 0.879. Overall sensitivities combining each probability scale and severity score at 80%, 90%, and 95% specificities were 90.0% (95% CI, 86.4%-93.6%), 71.4% (67.4%-75.4%), and 60.0% (56.2%-63.8%), respectively. There was a statistically significant correlation between the scanning laser polarimetry severity score and the VF severity score (R2 = 0.360, P<0.001). Scanning laser polarimetry parameters may not be sufficiently sensitive to detect glaucomatous patients with localized VF damage. Our algorithm using the scanning laser polarimetry deviation map may enhance the understanding of scanning laser polarimetry printouts in terms of the locality, deviation size, and severity of localized retinal nerve fiber layer defects in eyes with localized VF loss.

  15. Psychological Factors Predict Local and Referred Experimental Muscle Pain: A Cluster Analysis in Healthy Adults

    PubMed Central

    Lee, Jennifer E.; Watson, David; Frey-Law, Laura A.

    2012-01-01

    Background Recent studies suggest an underlying three- or four-factor structure explains the conceptual overlap and distinctiveness of several negative emotionality and pain-related constructs. However, the validity of these latent factors for predicting pain has not been examined. Methods A cohort of 189 (99F; 90M) healthy volunteers completed eight self-report negative emotionality and pain-related measures (Eysenck Personality Questionnaire-Revised; Positive and Negative Affect Schedule; State-Trait Anxiety Inventory; Pain Catastrophizing Scale; Fear of Pain Questionnaire; Somatosensory Amplification Scale; Anxiety Sensitivity Index; Whiteley Index). Using principal axis factoring, three primary latent factors were extracted: General Distress; Catastrophic Thinking; and Pain-Related Fear. Using these factors, individuals clustered into three subgroups of high, moderate, and low negative emotionality responses. Experimental pain was induced via intramuscular acidic infusion into the anterior tibialis muscle, producing local (infusion site) and/or referred (anterior ankle) pain and hyperalgesia. Results Pain outcomes differed between clusters (multivariate analysis of variance and multinomial regression), with individuals in the highest negative emotionality cluster reporting the greatest local pain (p = 0.05), mechanical hyperalgesia (pressure pain thresholds; p = 0.009) and greater odds (2.21 OR) of experiencing referred pain compared to the lowest negative emotionality cluster. Conclusion Our results provide support for three latent psychological factors explaining the majority of the variance between several pain-related psychological measures, and that individuals in the high negative emotionality subgroup are at increased risk for (1) acute local muscle pain; (2) local hyperalgesia; and (3) referred pain using a standardized nociceptive input. PMID:23165778

  16. Obesity in Korean pre-adolescent school children: comparison of various anthropometric measurements based on bioelectrical impedance analysis.

    PubMed

    Yoo, S; Lee, S-Y; Kim, K-N; Sung, E

    2006-07-01

    To examine the relationships between body mass index (BMI), percentage-weight-for-height (PWH) and percentage body fat (PBF), and to compare their validity based on PBF with the BMI criteria of International Obesity Task Force (IOTF) for childhood obesity in Korean pre-adolescent school children. Statistical comparative analysis for anthropometric measures. Korean pre-adolescent children (438 boys and 454 girls, aged 8-12 years, mean BMI 19.5+/-3.4 kg/m2). Body mass index and PWH were calculated as body size indices from height and weight. Hand-to-foot bioelectrical impedance analysis (BIA) was performed to obtain PBF values, with obese children defined as PBF above 35%. Sensitivity and specificity were displayed with the gold standard of PBF, and receiver operating characteristic (ROC) curves were used to assess the performance of BMI and PWH in detecting obesity. The prevalence of obesity varied by the criteria: 18.8% by Korean BMI standards for 95 percentile, 11% by the IOTF-BMI 30 kg/m2 and 29.4% by Korean PWH cutoffs. Body mass index and PWH were significantly correlated with PBF after adjusting for age, 0.910 (P<0.01) and 0.915 (P<0.01), respectively. The sensitivity and specificity of the PWH cutoffs were 0.909 and 0.882, respectively. The local BMI 95 percentiles had lower sensitivity (0.714) and specificity (0.790). The IOTF-BMI definition showed much lower sensitivity (0.457) and higher specificity (0.990). The BMI cutoffs corresponding with the highest accuracy were smaller than IOTF-BMI 30 kg/m2 for all age groups in both boys and girls. The prevalence of obesity among Korean pre-adolescent children widely varied according to the diagnostic criteria applied. Universally recommended cutoffs for children by IOTF showed the lowest sensitivity among the criteria used, and may therefore underestimate obesity in this population.

  17. PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

    PubMed

    Testa, A C; Ferrandina, G; Moro, F; Pasciuto, T; Moruzzi, M C; De Blasis, I; Mascilini, F; Foti, E; Autorino, R; Collarino, A; Gui, B; Zannoni, G F; Gambacorta, M A; Valentini, A L; Rufini, V; Scambia, G

    2018-05-01

    Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response. There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm 3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%). Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  18. LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies.

    PubMed

    Hoffmann, Sebastian

    2015-01-01

    The development of non-animal skin sensitization test methods and strategies is quickly progressing. Either individually or in combination, the predictive capacity is usually described in comparison to local lymph node assay (LLNA) results. In this process the important lesson from other endpoints, such as skin or eye irritation, to account for variability reference test results - here the LLNA - has not yet been fully acknowledged. In order to provide assessors as well as method and strategy developers with appropriate estimates, we investigated the variability of EC3 values from repeated substance testing using the publicly available NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) LLNA database. Repeat experiments for more than 60 substances were analyzed - once taking the vehicle into account and once combining data over all vehicles. In general, variability was higher when different vehicles were used. In terms of skin sensitization potential, i.e., discriminating sensitizer from non-sensitizers, the false positive rate ranged from 14-20%, while the false negative rate was 4-5%. In terms of skin sensitization potency, the rate to assign a substance to the next higher or next lower potency class was approx.10-15%. In addition, general estimates for EC3 variability are provided that can be used for modelling purposes. With our analysis we stress the importance of considering the LLNA variability in the assessment of skin sensitization test methods and strategies and provide estimates thereof.

  19. Digital-Direct-RT-PCR: a sensitive and specific method for quantification of CTC in patients with cervical carcinoma.

    PubMed

    Pfitzner, Claudia; Schröder, Isabel; Scheungraber, Cornelia; Dogan, Askin; Runnebaum, Ingo Bernhard; Dürst, Matthias; Häfner, Norman

    2014-02-05

    The detection of circulating tumour cells (CTC) in cancer patients may be useful for therapy monitoring and prediction of relapse. A sensitive assay based on HPV-oncogene transcripts which are highly specific for cervical cancer cells was established. The Digital-Direct-RT-PCR (DD-RT-PCR) combines Ficoll-separation, ThinPrep-fixation and one-step RT-PCR in a low-throughput digital-PCR format enabling the direct analysis and detection of individual CTC without RNA isolation. Experimental samples demonstrated a sensitivity of one HPV-positive cell in 500,000 HPV-negative cells. Spike-in experiments with down to 5 HPV-positive cells per millilitre EDTA-blood resulted in concordant positive results by PCR and immunocytochemistry. Blood samples from 3 of 10 CxCa patients each contained a single HPV-oncogene transcript expressing CTC among 5 to 15*10(5) MNBC. Only 1 of 7 patients with local but 2 of 3 women with systemic disease had CTC. This highly sensitive DD-RT-PCR for the detection of CTC may also be applied to other tumour entities which express tumour-specific transcripts.

  20. Environmental Electrometry with Luminescent Carbon Nanotubes.

    PubMed

    Noé, Jonathan C; Nutz, Manuel; Reschauer, Jonathan; Morell, Nicolas; Tsioutsios, Ioannis; Reserbat-Plantey, Antoine; Watanabe, Kenji; Taniguchi, Takashi; Bachtold, Adrian; Högele, Alexander

    2018-06-25

    We demonstrate that localized excitons in luminescent carbon nanotubes can be utilized to study electrostatic fluctuations in the nanotube environment with sensitivity down to the elementary charge. By monitoring the temporal evolution of the cryogenic photoluminescence from individual carbon nanotubes grown on silicon oxide and hexagonal boron nitride, we characterize the dynamics of charge trap defects for both dielectric supports. We find a one order of magnitude reduction in the photoluminescence spectral wandering for nanotubes on extended atomically flat terraces of hexagonal boron nitride. For nanotubes on hexagonal boron nitride with pronounced spectral fluctuations, our analysis suggests proximity to terrace ridges where charge fluctuators agglomerate to exhibit areal densities exceeding those of silicon oxide. Our results establish carbon nanotubes as sensitive probes of environmental charge fluctuations and highlight their potential for applications in electrometric nanodevices with all-optical readout.

  1. A single-index threshold Cox proportional hazard model for identifying a treatment-sensitive subset based on multiple biomarkers.

    PubMed

    He, Ye; Lin, Huazhen; Tu, Dongsheng

    2018-06-04

    In this paper, we introduce a single-index threshold Cox proportional hazard model to select and combine biomarkers to identify patients who may be sensitive to a specific treatment. A penalized smoothed partial likelihood is proposed to estimate the parameters in the model. A simple, efficient, and unified algorithm is presented to maximize this likelihood function. The estimators based on this likelihood function are shown to be consistent and asymptotically normal. Under mild conditions, the proposed estimators also achieve the oracle property. The proposed approach is evaluated through simulation analyses and application to the analysis of data from two clinical trials, one involving patients with locally advanced or metastatic pancreatic cancer and one involving patients with resectable lung cancer. Copyright © 2018 John Wiley & Sons, Ltd.

  2. Seismic Constraints on Interior Solar Convection

    NASA Technical Reports Server (NTRS)

    Hanasoge, Shravan M.; Duvall, Thomas L.; DeRosa, Marc L.

    2010-01-01

    We constrain the velocity spectral distribution of global-scale solar convective cells at depth using techniques of local helioseismology. We calibrate the sensitivity of helioseismic waves to large-scale convective cells in the interior by analyzing simulations of waves propagating through a velocity snapshot of global solar convection via methods of time-distance helioseismology. Applying identical analysis techniques to observations of the Sun, we are able to bound from above the magnitudes of solar convective cells as a function of spatial convective scale. We find that convection at a depth of r/R(solar) = 0.95 with spatial extent l < 30, where l is the spherical harmonic degree, comprise weak flow systems, on the order of 15 m/s or less. Convective features deeper than r/R(solar) = 0.95 are more difficult to image due to the rapidly decreasing sensitivity of helioseismic waves.

  3. Applied Meteorology Unit (AMU) Quarterly Report Third Quarter FY-08

    NASA Technical Reports Server (NTRS)

    Bauman, William; Crawford, Winifred; Barrett, Joe; Watson, Leela; Dreher, Joseph

    2008-01-01

    This report summarizes the Applied Meteorology Unit (AMU) activities for the third quarter of Fiscal Year 2008 (April - June 2008). Tasks reported on are: Peak Wind Tool for User Launch Commit Criteria (LCC), Anvil Forecast Tool in AWIPS Phase II, Completion of the Edward Air Force Base (EAFB) Statistical Guidance Wind Tool, Volume Averaged Height Integ rated Radar Reflectivity (VAHIRR), Impact of Local Sensors, Radar Scan Strategies for the PAFB WSR-74C Replacement, VAHIRR Cost Benefit Analysis, and WRF Wind Sensitivity Study at Edwards Air Force Base

  4. Uncertainty quantification for PZT bimorph actuators

    NASA Astrophysics Data System (ADS)

    Bravo, Nikolas; Smith, Ralph C.; Crews, John

    2018-03-01

    In this paper, we discuss the development of a high fidelity model for a PZT bimorph actuator used for micro-air vehicles, which includes the Robobee. We developed a high-fidelity model for the actuator using the homogenized energy model (HEM) framework, which quantifies the nonlinear, hysteretic, and rate-dependent behavior inherent to PZT in dynamic operating regimes. We then discussed an inverse problem on the model. We included local and global sensitivity analysis of the parameters in the high-fidelity model. Finally, we will discuss the results of Bayesian inference and uncertainty quantification on the HEM.

  5. Numerical and analytical investigation of the chimera state excitation conditions in the Kuramoto-Sakaguchi oscillator network

    NASA Astrophysics Data System (ADS)

    Frolov, Nikita S.; Goremyko, Mikhail V.; Makarov, Vladimir V.; Maksimenko, Vladimir A.; Hramov, Alexander E.

    2017-03-01

    In this paper we study the conditions of chimera states excitation in ensemble of non-locally coupled Kuramoto-Sakaguchi (KS) oscillators. In the framework of current research we analyze the dynamics of the homogeneous network containing identical oscillators. We show the chimera state formation process is sensitive to the parameters of coupling kernel and to the KS network initial state. To perform the analysis we have used the Ott-Antonsen (OA) ansatz to consider the behavior of infinitely large KS network.

  6. LuciPHOr: Algorithm for Phosphorylation Site Localization with False Localization Rate Estimation Using Modified Target-Decoy Approach*

    PubMed Central

    Fermin, Damian; Walmsley, Scott J.; Gingras, Anne-Claude; Choi, Hyungwon; Nesvizhskii, Alexey I.

    2013-01-01

    The localization of phosphorylation sites in peptide sequences is a challenging problem in large-scale phosphoproteomics analysis. The intense neutral loss peaks and the coexistence of multiple serine/threonine and/or tyrosine residues are limiting factors for objectively scoring site patterns across thousands of peptides. Various computational approaches for phosphorylation site localization have been proposed, including Ascore, Mascot Delta score, and ProteinProspector, yet few address direct estimation of the false localization rate (FLR) in each experiment. Here we propose LuciPHOr, a modified target-decoy-based approach that uses mass accuracy and peak intensities for site localization scoring and FLR estimation. Accurate estimation of the FLR is a difficult task at the individual-site level because the degree of uncertainty in localization varies significantly across different peptides. LuciPHOr carries out simultaneous localization on all candidate sites in each peptide and estimates the FLR based on the target-decoy framework, where decoy phosphopeptides generated by placing artificial phosphorylation(s) on non-candidate residues compete with the non-decoy phosphopeptides. LuciPHOr also reports approximate site-level confidence scores for all candidate sites as a means to localize additional sites from multiphosphorylated peptides in which localization can be partially achieved. Unlike the existing tools, LuciPHOr is compatible with any search engine output processed through the Trans-Proteomic Pipeline. We evaluated the performance of LuciPHOr in terms of the sensitivity and accuracy of FLR estimates using two synthetic phosphopeptide libraries and a phosphoproteomic dataset generated from complex mouse brain samples. PMID:23918812

  7. Selecting sustainable alternatives for cruise ships in Venice using multi-criteria decision analysis.

    PubMed

    Pesce, Marco; Terzi, Stefano; Al-Jawasreh, Raid Issa Mahmoud; Bommarito, Claudia; Calgaro, Loris; Fogarin, Stefano; Russo, Elisabetta; Marcomini, Antonio; Linkov, Igor

    2018-06-14

    The rapid growth of cruise ship tourism increases the use of historic port cities as strategic hubs for cruise ship operators. Benefits derived from increased tourism for the municipality and cruise ships are often at odds with the environmental and social impacts associated with continued historical port use. This study illustrates the use of Multi-Criteria Decision Analysis (MCDA) for weighing of various criteria and metrics related to the environment, economy, and social sustainability for the selection of a sustainable cruise line route. Specifically, MCDA methodology was employed in Venice, Italy to illustrate its application. First, the four most representative navigational route projects among those presented to local authorities were assessed based on social, economic, and environmental considerations. Second, a pool of experts representing the local authority, private port businesses, and cruise line industry were consulted to evaluate the validity and weight assignments for the selected criteria. Finally, a sensitivity analysis was employed to assess the robustness of the recommendations using an evaluation of weight changes and their effects on the ranking of alternative navigational routes. The results were presented and discussed in a multi-stakeholder meeting to further the route selection process. Published by Elsevier B.V.

  8. Scanning electron microscope fractography in failure analysis of steels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wouters, R.; Froyen, L.

    1996-04-01

    For many failure cases, macroscopic examination of the fracture surface permits discrimination of fatigue fractures from overload fractures. For clarifying fatigue fractures, the practical significance of microfractography is limited to an investigation of the crack initiation areas. Scanning electron microscopy is successfully used in tracing local material abnormalities that act as fatigue crack initiators. The task for the scanning electron microscope, however, is much more substantial in failure analysis of overload fractures, especially for steels. By revealing specific fractographic characteristics, complemented by information about the material and the loading conditions, scanning electron microscopy provides a strong indication of the probablemore » cause of failure. A complete dimple fracture is indicative of acceptable bulk material properties; overloading, by subdimensioning or excessive external loading, has to be verified. The presence of cleavage fracture makes the material properties questionable if external conditions causing embrittlement are absent. Intergranular brittle fracture requires verification of grain-boundary weakening conditions--a sensitized structure, whether or not combined with a local stress state or a specific environment. The role of scanning electron microscopy in failure analysis is illustrated by case histories of the aforementioned fracture types.« less

  9. District nursing workforce planning: a review of the methods.

    PubMed

    Reid, Bernie; Kane, Kay; Curran, Carol

    2008-11-01

    District nursing services in Northern Ireland face increasing demands and challenges which may be responded to by effective and efficient workforce planning and development. The aim of this paper is to critically analyse district nursing workforce planning and development methods, in an attempt to find a suitable method for Northern Ireland. A systematic analysis of the literature reveals four methods: professional judgement; population-based health needs; caseload analysis and dependency-acuity. Each method has strengths and weaknesses. Professional judgement offers a 'belt and braces' approach but lacks sensitivity to fluctuating patient numbers. Population-based health needs methods develop staffing algorithms that reflect deprivation and geographical spread, but are poorly understood by district nurses. Caseload analysis promotes equitable workloads but poorly performing district nursing localities may continue if benchmarking processes only consider local data. Dependency-acuity methods provide a means of equalizing and prioritizing workload but are prone to district nurses overstating factors in patient dependency or understating carers' capability. In summary a mixed method approach is advocated to evaluate and adjust the size and mix of district nursing teams using empirically determined patient dependency and activity-based variables based on the population's health needs.

  10. Sequence-dependent modelling of local DNA bending phenomena: curvature prediction and vibrational analysis.

    PubMed

    Vlahovicek, K; Munteanu, M G; Pongor, S

    1999-01-01

    Bending is a local conformational micropolymorphism of DNA in which the original B-DNA structure is only distorted but not extensively modified. Bending can be predicted by simple static geometry models as well as by a recently developed elastic model that incorporate sequence dependent anisotropic bendability (SDAB). The SDAB model qualitatively explains phenomena including affinity of protein binding, kinking, as well as sequence-dependent vibrational properties of DNA. The vibrational properties of DNA segments can be studied by finite element analysis of a model subjected to an initial bending moment. The frequency spectrum is obtained by applying Fourier analysis to the displacement values in the time domain. This analysis shows that the spectrum of the bending vibrations quite sensitively depends on the sequence, for example the spectrum of a curved sequence is characteristically different from the spectrum of straight sequence motifs of identical basepair composition. Curvature distributions are genome-specific, and pronounced differences are found between protein-coding and regulatory regions, respectively, that is, sites of extreme curvature and/or bendability are less frequent in protein-coding regions. A WWW server is set up for the prediction of curvature and generation of 3D models from DNA sequences (http:@www.icgeb.trieste.it/dna).

  11. Chloroplast microsatellites reveal colonization and metapopulation dynamics in the Canary Island pine

    PubMed Central

    Navascués, Miguel; Vaxevanidou, Zafeiro; González-Martínez, Santiago C; Climent, José; Gil, Luis; Emerson, Brent C

    2006-01-01

    Chloroplast microsatellites are becoming increasingly popular markers for population genetic studies in plants, but there has been little focus on their potential for demographic inference. In this work the utility of chloroplast microsatellites for the study of population expansions was explored. First, we investigated the power of mismatch distribution analysis and the FS test with coalescent simulations of different demographic scenarios. We then applied those methods to empirical data obtained for the Canary Island pine (Pinus canariensis). The results of the simulations showed that chloroplast microsatellites are sensitive to sudden population growth. The power of the FS test and accuracy of demographic parameter estimates, such as the time of expansion, were reduced proportionally to the level of homoplasy within the data. The analysis of Canary Island pine chloroplast microsatellite data indicated population expansions for almost all sample localities. Demographic expansions at the island level can be explained by the colonisation of the archipelago by the pine, while population expansions of different ages in different localities within an island appear to be the result of local extinctions and recolonisation dynamics. Comparable mitochondrial DNA sequence data from a parasite of P. canariensis, the weevil Brachyderes rugatus, supports this scenario, suggesting a key role for volcanism in the evolution of pine forest communities in the Canary Islands. PMID:16911194

  12. Recent Advances in the Measurement of Arsenic, Cadmium, and Mercury in Rice and Other Foods

    PubMed Central

    Punshon, Tracy

    2015-01-01

    Trace element analysis of foods is of increasing importance because of raised consumer awareness and the need to evaluate and establish regulatory guidelines for toxic trace metals and metalloids. This paper reviews recent advances in the analysis of trace elements in food, including challenges, state-of-the art methods, and use of spatially resolved techniques for localizing the distribution of As and Hg within rice grains. Total elemental analysis of foods is relatively well-established but the push for ever lower detection limits requires that methods be robust from potential matrix interferences which can be particularly severe for food. Inductively coupled plasma mass spectrometry (ICP-MS) is the method of choice, allowing for multi-element and highly sensitive analyses. For arsenic, speciation analysis is necessary because the inorganic forms are more likely to be subject to regulatory limits. Chromatographic techniques coupled to ICP-MS are most often used for arsenic speciation and a range of methods now exist for a variety of different arsenic species in different food matrices. Speciation and spatial analysis of foods, especially rice, can also be achieved with synchrotron techniques. Sensitive analytical techniques and methodological advances provide robust methods for the assessment of several metals in animal and plant-based foods, in particular for arsenic, cadmium and mercury in rice and arsenic speciation in foodstuffs. PMID:25938012

  13. iTOUGH2 V6.5

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Finsterle, Stefan A.

    2010-11-01

    iTOUGH2 (inverse TOUGH2) provides inverse modeling capabilities for TOUGH2, a simulator for multi-dimensional , multi-phase, multi-component, non-isothermal flow and transport in fractured porous media. It performs sensitivity analysis, parameter estimation, and uncertainty propagation, analysis in geosciences and reservoir engineering and other application areas. It supports a number of different combination of fluids and components [equation-of-state (EOS) modules]. In addition, the optimization routines implemented in iTOUGH2 can also be used or sensitivity analysis, automatic model calibration, and uncertainty quantification of any external code that uses text-based input and output files. This link is achieved by means of the PEST application programmingmore » interface. iTOUGH2 solves the inverse problem by minimizing a non-linear objective function of the weighted differences between model output and the corresponding observations. Multiple minimization algorithms (derivative fee, gradient-based and second-order; local and global) are available. iTOUGH2 also performs Latin Hypercube Monte Carlos simulation for uncertainty propagation analysis. A detailed residual and error analysis is provided. This upgrade includes new EOS modules (specifically EOS7c, ECO2N and TMVOC), hysteretic relative permeability and capillary pressure functions and the PEST API. More details can be found at http://esd.lbl.gov/iTOUGH2 and the publications cited there. Hardware Req.: Multi-platform; Related/auxiliary software PVM (if running in parallel).« less

  14. A Cost-Effectiveness Analysis of Clopidogrel for Patients with Non-ST-Segment Elevation Acute Coronary Syndrome in China.

    PubMed

    Cui, Ming; Tu, Chen Chen; Chen, Er Zhen; Wang, Xiao Li; Tan, Seng Chuen; Chen, Can

    2016-09-01

    There are a number of economic evaluation studies of clopidogrel for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) published from the perspective of multiple countries in recent years. However, relevant research is quite limited in China. We aimed to estimate the long-term cost effectiveness for up to 1-year treatment with clopidogrel plus acetylsalicylic acid (ASA) versus ASA alone for NSTEACS from the public payer perspective in China. This analysis used a Markov model to simulate a cohort of patients for quality-adjusted life years (QALYs) gained and incremental cost for lifetime horizon. Based on the primary event rates, adherence rate, and mortality derived from the CURE trial, hazard functions obtained from published literature were used to extrapolate the overall survival to lifetime horizon. Resource utilization, hospitalization, medication costs, and utility values were estimated from official reports, published literature, and analysis of the patient-level insurance data in China. To assess the impact of parameters' uncertainty on cost-effectiveness results, one-way sensitivity analyses were undertaken for key parameters, and probabilistic sensitivity analysis (PSA) was conducted using the Monte Carlo simulation. The therapy of clopidogrel plus ASA is a cost-effective option in comparison with ASA alone for the treatment of NSTEACS in China, leading to 0.0548 life years (LYs) and 0.0518 QALYs gained per patient. From the public payer perspective in China, clopidogrel plus ASA is associated with an incremental cost of 43,340 China Yuan (CNY) per QALY gained and 41,030 CNY per LY gained (discounting at 3.5% per year). PSA results demonstrated that 88% of simulations were lower than the cost-effectiveness threshold of 150,721 CYN per QALY gained. Based on the one-way sensitivity analysis, results are most sensitive to price of clopidogrel, but remain well below this threshold. This analysis suggests that treatment with clopidogrel plus ASA for up to 1 year for patients with NSTEACS is cost effective in the local context of China from a public payers' perspective. Sanofi China.

  15. The additional lateralizing and localizing value of the postictal EEG in frontal lobe epilepsy.

    PubMed

    Whitehead, Kimberley; Gollwitzer, Stephanie; Millward, Helen; Wehner, Tim; Scott, Catherine; Diehl, Beate

    2016-03-01

    The aim of this study was to describe the additional lateralizing and localizing value of the postictal EEG in frontal lobe epilepsy (FLE). The ictal EEG in FLE is frequently challenging to localize. We identified patients investigated for epilepsy surgery with unilateral FLE based on consistent semiology, a clear lesion and/or with frontal onset on intracranial EEG. A one hour section of postictal EEG was analyzed by two raters for new or activated EEG features and it was assessed whether these features offered additional information when compared to the ictal EEG. Postictal features assessed included asymmetrical return of the posterior dominant rhythm and potentiated lateralized or regional frontal slowing, spikes or sharp waves. Thirty-eight patients were included who had a combined total of ninety-six seizures. 47/96 (49%) postictal periods contained correctly lateralizing or localizing information. The sensitivity for asymmetrical return of the posterior dominant rhythm was 24%. The sensitivity for regional frontal slow and frontal spikes was 23% and 20% respectively. Further analysis showed that in 14/38 (39%) patients, at least one seizure with an unhelpful ictal EEG was followed by postictal EEG features that added new localizing or lateralizing information. A subgroup of 11 patients who were ⩾1 year seizure-free (ILAE class 1) and thus classified as having a 'gold-standard' FLE diagnosis were analyzed separately and it was found that 14/30 of their seizures (47%) had extra postictal information. The new postictal information was always concordant with the ultimate diagnosis, except for asymmetric postictal return of background activity ipsilateral to the epileptogenic zone in three patients. This study shows that a close examination of the postictal EEG can offer additional information which can contribute to the identification of a potentially resectable epileptogenic zone. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. How sensitive are estimates of carbon fixation in agricultural models to input data?

    PubMed Central

    2012-01-01

    Background Process based vegetation models are central to understand the hydrological and carbon cycle. To achieve useful results at regional to global scales, such models require various input data from a wide range of earth observations. Since the geographical extent of these datasets varies from local to global scale, data quality and validity is of major interest when they are chosen for use. It is important to assess the effect of different input datasets in terms of quality to model outputs. In this article, we reflect on both: the uncertainty in input data and the reliability of model results. For our case study analysis we selected the Marchfeld region in Austria. We used independent meteorological datasets from the Central Institute for Meteorology and Geodynamics and the European Centre for Medium-Range Weather Forecasts (ECMWF). Land cover / land use information was taken from the GLC2000 and the CORINE 2000 products. Results For our case study analysis we selected two different process based models: the Environmental Policy Integrated Climate (EPIC) and the Biosphere Energy Transfer Hydrology (BETHY/DLR) model. Both process models show a congruent pattern to changes in input data. The annual variability of NPP reaches 36% for BETHY/DLR and 39% for EPIC when changing major input datasets. However, EPIC is less sensitive to meteorological input data than BETHY/DLR. The ECMWF maximum temperatures show a systematic pattern. Temperatures above 20°C are overestimated, whereas temperatures below 20°C are underestimated, resulting in an overall underestimation of NPP in both models. Besides, BETHY/DLR is sensitive to the choice and accuracy of the land cover product. Discussion This study shows that the impact of input data uncertainty on modelling results need to be assessed: whenever the models are applied under new conditions, local data should be used for both input and result comparison. PMID:22296931

  17. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine

    2006-04-01

    Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Onlymore » MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.« less

  18. The local lymph node assay and skin sensitization testing.

    PubMed

    Kimber, Ian; Dearman, Rebecca J

    2010-01-01

    The mouse local lymph node assay (LLNA) is a method for the identification and characterization of skin sensitization hazards. In this context the method can be used both to identify contact allergens, and also determine the relative skin sensitizing potency as a basis for derivation of effective risk assessments.The assay is based on measurement of proliferative responses by draining lymph node cells induced following topical exposure of mice to test chemicals. Such responses are known to be causally and quantitatively associated with the acquisition of skin sensitization and therefore provide a relevant marker for characterization of contact allergic potential.The LLNA has been the subject of exhaustive evaluation and validation exercises and has been assigned Organization for Economic Cooperation and Development (OECD) test guideline 429. Herein we describe the conduct and interpretation of the LLNA.

  19. Identifying and counting point defects in carbon nanotubes.

    PubMed

    Fan, Yuwei; Goldsmith, Brett R; Collins, Philip G

    2005-12-01

    The prevailing conception of carbon nanotubes and particularly single-walled carbon nanotubes (SWNTs) continues to be one of perfectly crystalline wires. Here, we demonstrate a selective electrochemical method that labels point defects and makes them easily visible for quantitative analysis. High-quality SWNTs are confirmed to contain one defect per 4 microm on average, with a distribution weighted towards areas of SWNT curvature. Although this defect density compares favourably to high-quality, silicon single-crystals, the presence of a single defect can have tremendous electronic effects in one-dimensional conductors such as SWNTs. We demonstrate a one-to-one correspondence between chemically active point defects and sites of local electronic sensitivity in SWNT circuits, confirming the expectation that individual defects may be critical to understanding and controlling variability, noise and chemical sensitivity in SWNT electronic devices. By varying the SWNT synthesis technique, we further show that the defect spacing can be varied over orders of magnitude. The ability to detect and analyse point defects, especially at very low concentrations, indicates the promise of this technique for quantitative process analysis, especially in nanoelectronics development.

  20. Lorentz-Symmetry Test at Planck-Scale Suppression With a Spin-Polarized 133Cs Cold Atom Clock.

    PubMed

    Pihan-Le Bars, H; Guerlin, C; Lasseri, R-D; Ebran, J-P; Bailey, Q G; Bize, S; Khan, E; Wolf, P

    2018-06-01

    We present the results of a local Lorentz invariance (LLI) test performed with the 133 Cs cold atom clock FO2, hosted at SYRTE. Such a test, relating the frequency shift between 133 Cs hyperfine Zeeman substates with the Lorentz violating coefficients of the standard model extension (SME), has already been realized by Wolf et al. and led to state-of-the-art constraints on several SME proton coefficients. In this second analysis, we used an improved model, based on a second-order Lorentz transformation and a self-consistent relativistic mean field nuclear model, which enables us to extend the scope of the analysis from purely proton to both proton and neutron coefficients. We have also become sensitive to the isotropic coefficient , another SME coefficient that was not constrained by Wolf et al. The resulting limits on SME coefficients improve by up to 13 orders of magnitude the present maximal sensitivities for laboratory tests and reach the generally expected suppression scales at which signatures of Lorentz violation could appear.

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