Aeroservoelastic Model Validation and Test Data Analysis of the F/A-18 Active Aeroelastic Wing

NASA Technical Reports Server (NTRS)

Brenner, Martin J.; Prazenica, Richard J.

2003-01-01

Model validation and flight test data analysis require careful consideration of the effects of uncertainty, noise, and nonlinearity. Uncertainty prevails in the data analysis techniques and results in a composite model uncertainty from unmodeled dynamics, assumptions and mechanics of the estimation procedures, noise, and nonlinearity. A fundamental requirement for reliable and robust model development is an attempt to account for each of these sources of error, in particular, for model validation, robust stability prediction, and flight control system development. This paper is concerned with data processing procedures for uncertainty reduction in model validation for stability estimation and nonlinear identification. F/A-18 Active Aeroelastic Wing (AAW) aircraft data is used to demonstrate signal representation effects on uncertain model development, stability estimation, and nonlinear identification. Data is decomposed using adaptive orthonormal best-basis and wavelet-basis signal decompositions for signal denoising into linear and nonlinear identification algorithms. Nonlinear identification from a wavelet-based Volterra kernel procedure is used to extract nonlinear dynamics from aeroelastic responses, and to assist model development and uncertainty reduction for model validation and stability prediction by removing a class of nonlinearity from the uncertainty.

Model Validation | Center for Cancer Research

Cancer.gov

Research Investigation and Animal Model Validation This activity is also under development and thus far has included increasing pathology resources, delivering pathology services, as well as using imaging and surgical methods to develop and refine animal models in collaboration with other CCR investigators.

Passion: Does one scale fit all? Construct validity of two-factor passion scale and psychometric invariance over different activities and languages.

PubMed

Marsh, Herbert W; Vallerand, Robert J; Lafrenière, Marc-André K; Parker, Philip; Morin, Alexandre J S; Carbonneau, Noémie; Jowett, Sophia; Bureau, Julien S; Fernet, Claude; Guay, Frédéric; Salah Abduljabbar, Adel; Paquet, Yvan

2013-09-01

The passion scale, based on the dualistic model of passion, measures 2 distinct types of passion: Harmonious and obsessive passions are predictive of adaptive and less adaptive outcomes, respectively. In a substantive-methodological synergy, we evaluate the construct validity (factor structure, reliability, convergent and discriminant validity) of Passion Scale responses (N = 3,571). The exploratory structural equation model fit to the data was substantially better than the confirmatory factor analysis solution, and resulted in better differentiated (less correlated) factors. Results from a 13-model taxonomy of measurement invariance supported complete invariance (factor loadings, factor correlations, item uniquenesses, item intercepts, and latent means) over language (French vs. English; the instrument was originally devised in French, then translated into English) and gender. Strong measurement partial invariance over 5 passion activity groups (leisure, sport, social, work, education) indicates that the same set of items is appropriate for assessing passion across a wide variety of activities--a previously untested, implicit assumption that greatly enhances practical utility. Support was found for the convergent and discriminant validity of the harmonious and obsessive passion scales, based on a set of validity correlates: life satisfaction, rumination, conflict, time investment, activity liking and valuation, and perceiving the activity as a passion.

Solar Sail Models and Test Measurements Correspondence for Validation Requirements Definition

NASA Technical Reports Server (NTRS)

Ewing, Anthony; Adams, Charles

2004-01-01

Solar sails are being developed as a mission-enabling technology in support of future NASA science missions. Current efforts have advanced solar sail technology sufficient to justify a flight validation program. A primary objective of this activity is to test and validate solar sail models that are currently under development so that they may be used with confidence in future science mission development (e.g., scalable to larger sails). Both system and model validation requirements must be defined early in the program to guide design cycles and to ensure that relevant and sufficient test data will be obtained to conduct model validation to the level required. A process of model identification, model input/output documentation, model sensitivity analyses, and test measurement correspondence is required so that decisions can be made to satisfy validation requirements within program constraints.

Model Validation Status Review

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

E.L. Hardin

The primary objective for the Model Validation Status Review was to perform a one-time evaluation of model validation associated with the analysis/model reports (AMRs) containing model input to total-system performance assessment (TSPA) for the Yucca Mountain site recommendation (SR). This review was performed in response to Corrective Action Request BSC-01-C-01 (Clark 2001, Krisha 2001) pursuant to Quality Assurance review findings of an adverse trend in model validation deficiency. The review findings in this report provide the following information which defines the extent of model validation deficiency and the corrective action needed: (1) AMRs that contain or support models are identified,more » and conversely, for each model the supporting documentation is identified. (2) The use for each model is determined based on whether the output is used directly for TSPA-SR, or for screening (exclusion) of features, events, and processes (FEPs), and the nature of the model output. (3) Two approaches are used to evaluate the extent to which the validation for each model is compliant with AP-3.10Q (Analyses and Models). The approaches differ in regard to whether model validation is achieved within individual AMRs as originally intended, or whether model validation could be readily achieved by incorporating information from other sources. (4) Recommendations are presented for changes to the AMRs, and additional model development activities or data collection, that will remedy model validation review findings, in support of licensing activities. The Model Validation Status Review emphasized those AMRs that support TSPA-SR (CRWMS M&O 2000bl and 2000bm). A series of workshops and teleconferences was held to discuss and integrate the review findings. The review encompassed 125 AMRs (Table 1) plus certain other supporting documents and data needed to assess model validity. The AMRs were grouped in 21 model areas representing the modeling of processes affecting the natural and engineered barriers, plus the TSPA model itself Description of the model areas is provided in Section 3, and the documents reviewed are described in Section 4. The responsible manager for the Model Validation Status Review was the Chief Science Officer (CSO) for Bechtel-SAIC Co. (BSC). The team lead was assigned by the CSO. A total of 32 technical specialists were engaged to evaluate model validation status in the 21 model areas. The technical specialists were generally independent of the work reviewed, meeting technical qualifications as discussed in Section 5.« less

Development and Validation of a Computational Model for Androgen Receptor Activity

PubMed Central

2016-01-01

Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference. The in vitro HTS assays probed perturbations of the AR pathway at multiple points (receptor binding, coregulator recruitment, gene transcription, and protein production) and multiple cell types. Confirmatory in vitro antagonist assay data and cytotoxicity information were used as additional flags for potential nonspecific activity. Validating such alternative testing strategies requires high-quality reference data. We compiled 158 putative androgen-active and -inactive chemicals from a combination of international test method validation efforts and semiautomated systematic literature reviews. Detailed in vitro assay information and results were compiled into a single database using a standardized ontology. Reference chemical concentrations that activated or inhibited AR pathway activity were identified to establish a range of potencies with reproducible reference chemical results. Comparison with existing Tier 1 AR binding data from the U.S. EPA Endocrine Disruptor Screening Program revealed that the model identified binders at relevant test concentrations (<100 μM) and was more sensitive to antagonist activity. The AR pathway model based on the ToxCast/Tox21 assays had balanced accuracies of 95.2% for agonist (n = 29) and 97.5% for antagonist (n = 28) reference chemicals. Out of 1855 chemicals screened in the AR pathway model, 220 chemicals demonstrated AR agonist or antagonist activity and an additional 174 chemicals were predicted to have potential weak AR pathway activity. PMID:27933809

Validation of a common data model for active safety surveillance research

PubMed Central

Ryan, Patrick B; Reich, Christian G; Hartzema, Abraham G; Stang, Paul E

2011-01-01

Objective Systematic analysis of observational medical databases for active safety surveillance is hindered by the variation in data models and coding systems. Data analysts often find robust clinical data models difficult to understand and ill suited to support their analytic approaches. Further, some models do not facilitate the computations required for systematic analysis across many interventions and outcomes for large datasets. Translating the data from these idiosyncratic data models to a common data model (CDM) could facilitate both the analysts' understanding and the suitability for large-scale systematic analysis. In addition to facilitating analysis, a suitable CDM has to faithfully represent the source observational database. Before beginning to use the Observational Medical Outcomes Partnership (OMOP) CDM and a related dictionary of standardized terminologies for a study of large-scale systematic active safety surveillance, the authors validated the model's suitability for this use by example. Validation by example To validate the OMOP CDM, the model was instantiated into a relational database, data from 10 different observational healthcare databases were loaded into separate instances, a comprehensive array of analytic methods that operate on the data model was created, and these methods were executed against the databases to measure performance. Conclusion There was acceptable representation of the data from 10 observational databases in the OMOP CDM using the standardized terminologies selected, and a range of analytic methods was developed and executed with sufficient performance to be useful for active safety surveillance. PMID:22037893

The CMEMS-Med-MFC-Biogeochemistry operational system: implementation of NRT and Multi-Year validation tools

NASA Astrophysics Data System (ADS)

Salon, Stefano; Cossarini, Gianpiero; Bolzon, Giorgio; Teruzzi, Anna

2017-04-01

The Mediterranean Monitoring and Forecasting Centre (Med-MFC) is one of the regional production centres of the EU Copernicus Marine Environment Monitoring Service (CMEMS). Med-MFC manages a suite of numerical model systems for the operational delivery of the CMEMS products, providing continuous monitoring and forecasting of the Mediterranean marine environment. The CMEMS products of fundamental biogeochemical variables (chlorophyll, nitrate, phosphate, oxygen, phytoplankton biomass, primary productivity, pH, pCO2) are organised as gridded datasets and are available at the marine.copernicus.eu web portal. Quantitative estimates of CMEMS products accuracy are prerequisites to release reliable information to intermediate users, end users and to other downstream services. In particular, validation activities aim to deliver accuracy information of the model products and to serve as a long term monitoring of the performance of the modelling systems. The quality assessment of model output is implemented using a multiple-stages approach, basically inspired to the classic "GODAE 4 Classes" metrics and criteria (consistency, quality, performance and benefit). Firstly, pre-operational runs qualify the operational model system against historical data, also providing a verification of the improvements of the new model system release with respect to the previous version. Then, the near real time (NRT) validation aims at delivering a sustained on-line skill assessment of the model analysis and forecast, relying on the NRT available relevant observations (e.g. in situ, Bio Argo and satellite observations). NRT validation results are operated on weekly basis and published on the MEDEAF web portal (www.medeaf.inogs.it). On a quarterly basis, the integration of the NRT validation activities delivers a comprehensive view of the accuracy of model forecast through the official CMEMS validation webpage. Multi-Year production (e.g. reanalysis runs) follows a similar procedure, and the validation is achieved using the same metrics on available historical observations (e.g. the World Ocean Atlas 2013 dataset). Results of the validation activities show that the comparison of the different variables of the CMEMS products with experimental data is feasible at different levels (i.e. either as skill assessment of the short-term forecast and as model consistency through different system versions) and at different spatial and temporal scales. In particular, the accuracy of some variables (chlorophyll, nitrate, oxygen) can be provided at weekly scale and sub-mesoscale, others (carbonate system, phosphate) at quarterly/annual and sub-basin scale, and others (phytoplankton biomass, primary production) only at the level of consistency of model functioning (e.g. literature- or climatology-based). In spite of a wide literature on model validation has been produced so far, maintaining a validation framework in the biogeochemical operational contest that fulfils GODAE criteria is still a challenge. Recent results of the validation activities and new potential validation framework at the Med-MFC will be presented in our contribution.

Quantitative structure-activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods.

PubMed

Ahmadi, Mehdi; Shahlaei, Mohsen

2015-01-01

P2X7 antagonist activity for a set of 49 molecules of the P2X7 receptor antagonists, derivatives of purine, was modeled with the aid of chemometric and artificial intelligence techniques. The activity of these compounds was estimated by means of combination of principal component analysis (PCA), as a well-known data reduction method, genetic algorithm (GA), as a variable selection technique, and artificial neural network (ANN), as a non-linear modeling method. First, a linear regression, combined with PCA, (principal component regression) was operated to model the structure-activity relationships, and afterwards a combination of PCA and ANN algorithm was employed to accurately predict the biological activity of the P2X7 antagonist. PCA preserves as much of the information as possible contained in the original data set. Seven most important PC's to the studied activity were selected as the inputs of ANN box by an efficient variable selection method, GA. The best computational neural network model was a fully-connected, feed-forward model with 7-7-1 architecture. The developed ANN model was fully evaluated by different validation techniques, including internal and external validation, and chemical applicability domain. All validations showed that the constructed quantitative structure-activity relationship model suggested is robust and satisfactory.

Quantitative structure–activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods

PubMed Central

Ahmadi, Mehdi; Shahlaei, Mohsen

2015-01-01

P2X7 antagonist activity for a set of 49 molecules of the P2X7 receptor antagonists, derivatives of purine, was modeled with the aid of chemometric and artificial intelligence techniques. The activity of these compounds was estimated by means of combination of principal component analysis (PCA), as a well-known data reduction method, genetic algorithm (GA), as a variable selection technique, and artificial neural network (ANN), as a non-linear modeling method. First, a linear regression, combined with PCA, (principal component regression) was operated to model the structure–activity relationships, and afterwards a combination of PCA and ANN algorithm was employed to accurately predict the biological activity of the P2X7 antagonist. PCA preserves as much of the information as possible contained in the original data set. Seven most important PC's to the studied activity were selected as the inputs of ANN box by an efficient variable selection method, GA. The best computational neural network model was a fully-connected, feed-forward model with 7−7−1 architecture. The developed ANN model was fully evaluated by different validation techniques, including internal and external validation, and chemical applicability domain. All validations showed that the constructed quantitative structure–activity relationship model suggested is robust and satisfactory. PMID:26600858

Transtheoretical Model Constructs for Physical Activity Behavior are Invariant across Time among Ethnically Diverse Adults in Hawaii

PubMed Central

Nigg, Claudio R; Motl, Robert W; Horwath, Caroline; Dishman, Rod K

2012-01-01

Objectives Physical activity (PA) research applying the Transtheoretical Model (TTM) to examine group differences and/or change over time requires preliminary evidence of factorial validity and invariance. The current study examined the factorial validity and longitudinal invariance of TTM constructs recently revised for PA. Method Participants from an ethnically diverse sample in Hawaii (N=700) completed questionnaires capturing each TTM construct. Results Factorial validity was confirmed for each construct using confirmatory factor analysis with full-information maximum likelihood. Longitudinal invariance was evidenced across a shorter (3-month) and longer (6-month) time period via nested model comparisons. Conclusions The questionnaires for each validated TTM construct are provided, and can now be generalized across similar subgroups and time points. Further validation of the provided measures is suggested in additional populations and across extended time points. PMID:22778669

A new method for assessing content validity in model-based creation and iteration of eHealth interventions.

PubMed

Kassam-Adams, Nancy; Marsac, Meghan L; Kohser, Kristen L; Kenardy, Justin A; March, Sonja; Winston, Flaura K

2015-04-15

The advent of eHealth interventions to address psychological concerns and health behaviors has created new opportunities, including the ability to optimize the effectiveness of intervention activities and then deliver these activities consistently to a large number of individuals in need. Given that eHealth interventions grounded in a well-delineated theoretical model for change are more likely to be effective and that eHealth interventions can be costly to develop, assuring the match of final intervention content and activities to the underlying model is a key step. We propose to apply the concept of "content validity" as a crucial checkpoint to evaluate the extent to which proposed intervention activities in an eHealth intervention program are valid (eg, relevant and likely to be effective) for the specific mechanism of change that each is intended to target and the intended target population for the intervention. The aims of this paper are to define content validity as it applies to model-based eHealth intervention development, to present a feasible method for assessing content validity in this context, and to describe the implementation of this new method during the development of a Web-based intervention for children. We designed a practical 5-step method for assessing content validity in eHealth interventions that includes defining key intervention targets, delineating intervention activity-target pairings, identifying experts and using a survey tool to gather expert ratings of the relevance of each activity to its intended target, its likely effectiveness in achieving the intended target, and its appropriateness with a specific intended audience, and then using quantitative and qualitative results to identify intervention activities that may need modification. We applied this method during our development of the Coping Coach Web-based intervention for school-age children. In the evaluation of Coping Coach content validity, 15 experts from five countries rated each of 15 intervention activity-target pairings. Based on quantitative indices, content validity was excellent for relevance and good for likely effectiveness and age-appropriateness. Two intervention activities had item-level indicators that suggested the need for further review and potential revision by the development team. This project demonstrated that assessment of content validity can be straightforward and feasible to implement and that results of this assessment provide useful information for ongoing development and iterations of new eHealth interventions, complementing other sources of information (eg, user feedback, effectiveness evaluations). This approach can be utilized at one or more points during the development process to guide ongoing optimization of eHealth interventions.

Surrogate screening models for the low physical activity criterion of frailty.

PubMed

Eckel, Sandrah P; Bandeen-Roche, Karen; Chaves, Paulo H M; Fried, Linda P; Louis, Thomas A

2011-06-01

Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women's Health and Aging Study (WHAS). Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by "relative influence" in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

Community-wide validation of geospace model local K-index predictions to support model transition to operations

NASA Astrophysics Data System (ADS)

Glocer, A.; Rastätter, L.; Kuznetsova, M.; Pulkkinen, A.; Singer, H. J.; Balch, C.; Weimer, D.; Welling, D.; Wiltberger, M.; Raeder, J.; Weigel, R. S.; McCollough, J.; Wing, S.

2016-07-01

We present the latest result of a community-wide space weather model validation effort coordinated among the Community Coordinated Modeling Center (CCMC), NOAA Space Weather Prediction Center (SWPC), model developers, and the broader science community. Validation of geospace models is a critical activity for both building confidence in the science results produced by the models and in assessing the suitability of the models for transition to operations. Indeed, a primary motivation of this work is supporting NOAA/SWPC's effort to select a model or models to be transitioned into operations. Our validation efforts focus on the ability of the models to reproduce a regional index of geomagnetic disturbance, the local K-index. Our analysis includes six events representing a range of geomagnetic activity conditions and six geomagnetic observatories representing midlatitude and high-latitude locations. Contingency tables, skill scores, and distribution metrics are used for the quantitative analysis of model performance. We consider model performance on an event-by-event basis, aggregated over events, at specific station locations, and separated into high-latitude and midlatitude domains. A summary of results is presented in this report, and an online tool for detailed analysis is available at the CCMC.

Community-Wide Validation of Geospace Model Local K-Index Predictions to Support Model Transition to Operations

NASA Technical Reports Server (NTRS)

Glocer, A.; Rastaetter, L.; Kuznetsova, M.; Pulkkinen, A.; Singer, H. J.; Balch, C.; Weimer, D.; Welling, D.; Wiltberger, M.; Raeder, J.;

An Empirical Comparison of Different Models of Active Aging in Canada: The International Mobility in Aging Study

PubMed Central

Ahmed, Tamer; Filiatrault, Johanne; Yu, Hsiu-Ting; Zunzunegui, Maria Victoria

2017-01-01

Abstract Purpose: Active aging is a concept that lacks consensus. The WHO defines it as a holistic concept that encompasses the overall health, participation, and security of older adults. Fernández-Ballesteros and colleagues propose a similar concept but omit security and include mood and cognitive function. To date, researchers attempting to validate conceptual models of active aging have obtained mixed results. The goal of this study was to examine the validity of existing models of active aging with epidemiological data from Canada. Methods: The WHO model of active aging and the psychological model of active aging developed by Fernández-Ballesteros and colleagues were tested with confirmatory factor analysis. The data used included 799 community-dwelling older adults between 65 and 74 years old, recruited from the patient lists of family physicians in Saint-Hyacinthe, Quebec and Kingston, Ontario. Results: Neither model could be validated in the sample of Canadian older adults. Although a concept of healthy aging can be modeled adequately, social participation and security did not fit a latent factor model. A simple binary index indicated that 27% of older adults in the sample did not meet the active aging criteria proposed by the WHO. Implications: Our results suggest that active aging might represent a human rights policy orientation rather than an empirical measurement tool to guide research among older adult populations. Binary indexes of active aging may serve to highlight what remains to be improved about the health, participation, and security of growing populations of older adults. PMID:26350153

Control Oriented Modeling and Validation of Aeroservoelastic Systems

NASA Technical Reports Server (NTRS)

Crowder, Marianne; deCallafon, Raymond (Principal Investigator)

2002-01-01

Lightweight aircraft design emphasizes the reduction of structural weight to maximize aircraft efficiency and agility at the cost of increasing the likelihood of structural dynamic instabilities. To ensure flight safety, extensive flight testing and active structural servo control strategies are required to explore and expand the boundary of the flight envelope. Aeroservoelastic (ASE) models can provide online flight monitoring of dynamic instabilities to reduce flight time testing and increase flight safety. The success of ASE models is determined by the ability to take into account varying flight conditions and the possibility to perform flight monitoring under the presence of active structural servo control strategies. In this continued study, these aspects are addressed by developing specific methodologies and algorithms for control relevant robust identification and model validation of aeroservoelastic structures. The closed-loop model robust identification and model validation are based on a fractional model approach where the model uncertainties are characterized in a closed-loop relevant way.

Bridging the gap between computation and clinical biology: validation of cable theory in humans

PubMed Central

Finlay, Malcolm C.; Xu, Lei; Taggart, Peter; Hanson, Ben; Lambiase, Pier D.

2013-01-01

Introduction: Computerized simulations of cardiac activity have significantly contributed to our understanding of cardiac electrophysiology, but techniques of simulations based on patient-acquired data remain in their infancy. We sought to integrate data acquired from human electrophysiological studies into patient-specific models, and validated this approach by testing whether electrophysiological responses to sequential premature stimuli could be predicted in a quantitatively accurate manner. Methods: Eleven patients with structurally normal hearts underwent electrophysiological studies. Semi-automated analysis was used to reconstruct activation and repolarization dynamics for each electrode. This S2 extrastimuli data was used to inform individualized models of cardiac conduction, including a novel derivation of conduction velocity restitution. Activation dynamics of multiple premature extrastimuli were then predicted from this model and compared against measured patient data as well as data derived from the ten-Tusscher cell-ionic model. Results: Activation dynamics following a premature S3 were significantly different from those after an S2. Patient specific models demonstrated accurate prediction of the S3 activation wave, (Pearson's R2 = 0.90, median error 4%). Examination of the modeled conduction dynamics allowed inferences into the spatial dispersion of activation delay. Further validation was performed against data from the ten-Tusscher cell-ionic model, with our model accurately recapitulating predictions of repolarization times (R2 = 0.99). Conclusions: Simulations based on clinically acquired data can be used to successfully predict complex activation patterns following sequential extrastimuli. Such modeling techniques may be useful as a method of incorporation of clinical data into predictive models. PMID:24027527

Does Rational Selection of Training and Test Sets Improve the Outcome of QSAR Modeling?

EPA Science Inventory

Prior to using a quantitative structure activity relationship (QSAR) model for external predictions, its predictive power should be established and validated. In the absence of a true external dataset, the best way to validate the predictive ability of a model is to perform its s...

QSAR modeling of GPCR ligands: methodologies and examples of applications.

PubMed

Tropsha, A; Wang, S X

2006-01-01

GPCR ligands represent not only one of the major classes of current drugs but the major continuing source of novel potent pharmaceutical agents. Because 3D structures of GPCRs as determined by experimental techniques are still unavailable, ligand-based drug discovery methods remain the major computational molecular modeling approaches to the analysis of growing data sets of tested GPCR ligands. This paper presents an overview of modern Quantitative Structure Activity Relationship (QSAR) modeling. We discuss the critical issue of model validation and the strategy for applying the successfully validated QSAR models to virtual screening of available chemical databases. We present several examples of applications of validated QSAR modeling approaches to GPCR ligands. We conclude with the comments on exciting developments in the QSAR modeling of GPCR ligands that focus on the study of emerging data sets of compounds with dual or even multiple activities against two or more of GPCRs.

LIVVkit 2: An extensible land ice verification and validation toolkit for comparing observations and models?

NASA Astrophysics Data System (ADS)

Kennedy, J. H.; Bennett, A. R.; Evans, K. J.; Fyke, J. G.; Vargo, L.; Price, S. F.; Hoffman, M. J.

2016-12-01

Accurate representation of ice sheets and glaciers are essential for robust predictions of arctic climate within Earth System models. Verification and Validation (V&V) is a set of techniques used to quantify the correctness and accuracy of a model, which builds developer/modeler confidence, and can be used to enhance the credibility of the model. Fundamentally, V&V is a continuous process because each model change requires a new round of V&V testing. The Community Ice Sheet Model (CISM) development community is actively developing LIVVkit, the Land Ice Verification and Validation toolkit, which is designed to easily integrate into an ice-sheet model's development workflow (on both personal and high-performance computers) to provide continuous V&V testing.LIVVkit is a robust and extensible python package for V&V, which has components for both software V&V (construction and use) and model V&V (mathematics and physics). The model Verification component is used, for example, to verify model results against community intercomparisons such as ISMIP-HOM. The model validation component is used, for example, to generate a series of diagnostic plots showing the differences between model results against observations for variables such as thickness, surface elevation, basal topography, surface velocity, surface mass balance, etc. Because many different ice-sheet models are under active development, new validation datasets are becoming available, and new methods of analysing these models are actively being researched, LIVVkit includes a framework to easily extend the model V&V analyses by ice-sheet modelers. This allows modelers and developers to develop evaluations of parameters, implement changes, and quickly see how those changes effect the ice-sheet model and earth system model (when coupled). Furthermore, LIVVkit outputs a portable hierarchical website allowing evaluations to be easily shared, published, and analysed throughout the arctic and Earth system communities.

Summary of EASM Turbulence Models in CFL3D With Validation Test Cases

NASA Technical Reports Server (NTRS)

Rumsey, Christopher L.; Gatski, Thomas B.

2003-01-01

This paper summarizes the Explicit Algebraic Stress Model in k-omega form (EASM-ko) and in k-epsilon form (EASM-ke) in the Reynolds-averaged Navier-Stokes code CFL3D. These models have been actively used over the last several years in CFL3D, and have undergone some minor modifications during that time. Details of the equations and method for coding the latest versions of the models are given, and numerous validation cases are presented. This paper serves as a validation archive for these models.

Validation of the Activities of Community Transportation model for individuals with cognitive impairments.

PubMed

Sohlberg, McKay Moore; Fickas, Stephen; Lemoncello, Rik; Hung, Pei-Fang

2009-01-01

To develop a theoretical, functional model of community navigation for individuals with cognitive impairments: the Activities of Community Transportation (ACTs). Iterative design using qualitative methods (i.e. document review, focus groups and observations). Four agencies providing travel training to adults with cognitive impairments in the USA participated in the validation study. A thorough document review and series of focus groups led to the development of a comprehensive model (ACTs Wheels) delineating the requisite steps and skills for community navigation. The model was validated and updated based on observations of 395 actual trips by travellers with navigational challenges from the four participating agencies. Results revealed that the 'ACTs Wheel' models were complete and comprehensive. The 'ACTs Wheels' represent a comprehensive model of the steps needed to navigate to destinations using paratransit and fixed-route public transportation systems for travellers with cognitive impairments. Suggestions are made for future investigations of community transportation for this population.

An Empirical Comparison of Different Models of Active Aging in Canada: The International Mobility in Aging Study.

PubMed

Bélanger, Emmanuelle; Ahmed, Tamer; Filiatrault, Johanne; Yu, Hsiu-Ting; Zunzunegui, Maria Victoria

2017-04-01

Active aging is a concept that lacks consensus. The WHO defines it as a holistic concept that encompasses the overall health, participation, and security of older adults. Fernández-Ballesteros and colleagues propose a similar concept but omit security and include mood and cognitive function. To date, researchers attempting to validate conceptual models of active aging have obtained mixed results. The goal of this study was to examine the validity of existing models of active aging with epidemiological data from Canada. The WHO model of active aging and the psychological model of active aging developed by Fernández-Ballesteros and colleagues were tested with confirmatory factor analysis. The data used included 799 community-dwelling older adults between 65 and 74 years old, recruited from the patient lists of family physicians in Saint-Hyacinthe, Quebec and Kingston, Ontario. Neither model could be validated in the sample of Canadian older adults. Although a concept of healthy aging can be modeled adequately, social participation and security did not fit a latent factor model. A simple binary index indicated that 27% of older adults in the sample did not meet the active aging criteria proposed by the WHO. Our results suggest that active aging might represent a human rights policy orientation rather than an empirical measurement tool to guide research among older adult populations. Binary indexes of active aging may serve to highlight what remains to be improved about the health, participation, and security of growing populations of older adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prediction of muscle activation for an eye movement with finite element modeling.

PubMed

Karami, Abbas; Eghtesad, Mohammad; Haghpanah, Seyyed Arash

2017-10-01

In this paper, a 3D finite element (FE) modeling is employed in order to predict extraocular muscles' activation and investigate force coordination in various motions of the eye orbit. A continuum constitutive hyperelastic model is employed for material description in dynamic modeling of the extraocular muscles (EOMs). Two significant features of this model are accurate mass modeling with FE method and stimulating EOMs for motion through muscle activation parameter. In order to validate the eye model, a forward dynamics simulation of the eye motion is carried out by variation of the muscle activation. Furthermore, to realize muscle activation prediction in various eye motions, two different tracking-based inverse controllers are proposed. The performance of these two inverse controllers is investigated according to their resulted muscle force magnitude and muscle force coordination. The simulation results are compared with the available experimental data and the well-known existing neurological laws. The comparison authenticates both the validation and the prediction results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated Disposal Facility FY 2016: ILAW Verification and Validation of the eSTOMP Simulator

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

Freedman, Vicky L.; Bacon, Diana H.; Fang, Yilin

2016-05-13

This document describes two sets of simulations carried out to further verify and validate the eSTOMP simulator. In this report, a distinction is made between verification and validation, and the focus is on verifying eSTOMP through a series of published benchmarks on cementitious wastes, and validating eSTOMP based on a lysimeter experiment for the glassified waste. These activities are carried out within the context of a scientific view of validation that asserts that models can only be invalidated, and that model validation (and verification) is a subjective assessment.

The effect of leverage and/or influential on structure-activity relationships.

PubMed

Bolboacă, Sorana D; Jäntschi, Lorentz

2013-05-01

In the spirit of reporting valid and reliable Quantitative Structure-Activity Relationship (QSAR) models, the aim of our research was to assess how the leverage (analysis with Hat matrix, h(i)) and the influential (analysis with Cook's distance, D(i)) of QSAR models may reflect the models reliability and their characteristics. The datasets included in this research were collected from previously published papers. Seven datasets which accomplished the imposed inclusion criteria were analyzed. Three models were obtained for each dataset (full-model, h(i)-model and D(i)-model) and several statistical validation criteria were applied to the models. In 5 out of 7 sets the correlation coefficient increased when compounds with either h(i) or D(i) higher than the threshold were removed. Withdrawn compounds varied from 2 to 4 for h(i)-models and from 1 to 13 for D(i)-models. Validation statistics showed that D(i)-models possess systematically better agreement than both full-models and h(i)-models. Removal of influential compounds from training set significantly improves the model and is recommended to be conducted in the process of quantitative structure-activity relationships developing. Cook's distance approach should be combined with hat matrix analysis in order to identify the compounds candidates for removal.

Developing Guided Inquiry-Based Student Lab Worksheet for Laboratory Knowledge Course

NASA Astrophysics Data System (ADS)

Rahmi, Y. L.; Novriyanti, E.; Ardi, A.; Rifandi, R.

2018-04-01

The course of laboratory knowledge is an introductory course for biology students to follow various lectures practicing in the biology laboratory. Learning activities of laboratory knowledge course at this time in the Biology Department, Universitas Negeri Padang has not been completed by supporting learning media such as student lab worksheet. Guided inquiry learning model is one of the learning models that can be integrated into laboratory activity. The study aimed to produce student lab worksheet based on guided inquiry for laboratory knowledge course and to determine the validity of lab worksheet. The research was conducted using research and developmet (R&D) model. The instruments used in data collection in this research were questionnaire for student needed analysis and questionnaire to measure the student lab worksheet validity. The data obtained was quantitative from several validators. The validators consist of three lecturers. The percentage of a student lab worksheet validity was 94.18 which can be categorized was very good.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

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

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

2D-QSAR and 3D-QSAR Analyses for EGFR Inhibitors

PubMed Central

Zhao, Manman; Zheng, Linfeng; Qiu, Chun

2017-01-01

Epidermal growth factor receptor (EGFR) is an important target for cancer therapy. In this study, EGFR inhibitors were investigated to build a two-dimensional quantitative structure-activity relationship (2D-QSAR) model and a three-dimensional quantitative structure-activity relationship (3D-QSAR) model. In the 2D-QSAR model, the support vector machine (SVM) classifier combined with the feature selection method was applied to predict whether a compound was an EGFR inhibitor. As a result, the prediction accuracy of the 2D-QSAR model was 98.99% by using tenfold cross-validation test and 97.67% by using independent set test. Then, in the 3D-QSAR model, the model with q2 = 0.565 (cross-validated correlation coefficient) and r2 = 0.888 (non-cross-validated correlation coefficient) was built to predict the activity of EGFR inhibitors. The mean absolute error (MAE) of the training set and test set was 0.308 log units and 0.526 log units, respectively. In addition, molecular docking was also employed to investigate the interaction between EGFR inhibitors and EGFR. PMID:28630865

Some guidance on preparing validation plans for the DART Full System Models.

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

Gray, Genetha Anne; Hough, Patricia Diane; Hills, Richard Guy

2009-03-01

Planning is an important part of computational model verification and validation (V&V) and the requisite planning document is vital for effectively executing the plan. The document provides a means of communicating intent to the typically large group of people, from program management to analysts to test engineers, who must work together to complete the validation activities. This report provides guidelines for writing a validation plan. It describes the components of such a plan and includes important references and resources. While the initial target audience is the DART Full System Model teams in the nuclear weapons program, the guidelines are generallymore » applicable to other modeling efforts. Our goal in writing this document is to provide a framework for consistency in validation plans across weapon systems, different types of models, and different scenarios. Specific details contained in any given validation plan will vary according to application requirements and available resources.« less

Concurrent and convergent validity of the mobility- and multidimensional-hierarchical disability categorization models with physical performance in community older adults.

PubMed

Hu, Ming-Hsia; Yeh, Chih-Jun; Chen, Tou-Rong; Wang, Ching-Yi

2014-01-01

A valid, time-efficient and easy-to-use instrument is important for busy clinical settings, large scale surveys, or community screening use. The purpose of this study was to validate the mobility hierarchical disability categorization model (an abbreviated model) by investigating its concurrent validity with the multidimensional hierarchical disability categorization model (a comprehensive model) and triangulating both models with physical performance measures in older adults. 604 community-dwelling older adults of at least 60 years in age volunteered to participate. Self-reported function on mobility, instrumental activities of daily living (IADL) and activities of daily living (ADL) domains were recorded and then the disability status determined based on both the multidimensional hierarchical categorization model and the mobility hierarchical categorization model. The physical performance measures, consisting of grip strength and usual and fastest gait speeds (UGS, FGS), were collected on the same day. Both categorization models showed high correlation (γs = 0.92, p < 0.001) and agreement (kappa = 0.61, p < 0.0001). Physical performance measures demonstrated significant different group means among the disability subgroups based on both categorization models. The results of multiple regression analysis indicated that both models individually explain similar amount of variance on all physical performances, with adjustments for age, sex, and number of comorbidities. Our results found that the mobility hierarchical disability categorization model is a valid and time efficient tool for large survey or screening use.

Insight into the structural requirements of proton pump inhibitors based on CoMFA and CoMSIA studies.

PubMed

Nayana, M Ravi Shashi; Sekhar, Y Nataraja; Nandyala, Haritha; Muttineni, Ravikumar; Bairy, Santosh Kumar; Singh, Kriti; Mahmood, S K

2008-10-01

In the present study, a series of 179 quinoline and quinazoline heterocyclic analogues exhibiting inhibitory activity against Gastric (H+/K+)-ATPase were investigated using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) methods. Both the models exhibited good correlation between the calculated 3D-QSAR fields and the observed biological activity for the respective training set compounds. The most optimal CoMFA and CoMSIA models yielded significant leave-one-out cross-validation coefficient, q(2) of 0.777, 0.744 and conventional cross-validation coefficient, r(2) of 0.927, 0.914 respectively. The predictive ability of generated models was tested on a set of 52 compounds having broad range of activity. CoMFA and CoMSIA yielded predicted activities for test set compounds with r(pred)(2) of 0.893 and 0.917 respectively. These validation tests not only revealed the robustness of the models but also demonstrated that for our models r(pred)(2) based on the mean activity of test set compounds can accurately estimate external predictivity. The factors affecting activity were analyzed carefully according to standard coefficient contour maps of steric, electrostatic, hydrophobic, acceptor and donor fields derived from the CoMFA and CoMSIA. These contour plots identified several key features which explain the wide range of activities. The results obtained from models offer important structural insight into designing novel peptic-ulcer inhibitors prior to their synthesis.

FIRE Science Results 1989

NASA Technical Reports Server (NTRS)

Mcdougal, David S. (Editor)

1990-01-01

FIRE (First ISCCP Regional Experiment) is a U.S. cloud-radiation research program formed in 1984 to increase the basic understanding of cirrus and marine stratocumulus cloud systems, to develop realistic parameterizations for these systems, and to validate and improve ISCCP cloud product retrievals. Presentations of results culminating the first 5 years of FIRE research activities were highlighted. The 1986 Cirrus Intensive Field Observations (IFO), the 1987 Marine Stratocumulus IFO, the Extended Time Observations (ETO), and modeling activities are described. Collaborative efforts involving the comparison of multiple data sets, incorporation of data measurements into modeling activities, validation of ISCCP cloud parameters, and development of parameterization schemes for General Circulation Models (GCMs) are described.

Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors.

PubMed

Nargotra, Amit; Sharma, Sujata; Koul, Jawahir Lal; Sangwan, Pyare Lal; Khan, Inshad Ali; Kumar, Ashwani; Taneja, Subhash Chander; Koul, Surrinder

2009-10-01

Quantitative structure activity relationship (QSAR) analysis of piperine analogs as inhibitors of efflux pump NorA from Staphylococcus aureus has been performed in order to obtain a highly accurate model enabling prediction of inhibition of S. aureus NorA of new chemical entities from natural sources as well as synthetic ones. Algorithm based on genetic function approximation method of variable selection in Cerius2 was used to generate the model. Among several types of descriptors viz., topological, spatial, thermodynamic, information content and E-state indices that were considered in generating the QSAR model, three descriptors such as partial negative surface area of the compounds, area of the molecular shadow in the XZ plane and heat of formation of the molecules resulted in a statistically significant model with r(2)=0.962 and cross-validation parameter q(2)=0.917. The validation of the QSAR models was done by cross-validation, leave-25%-out and external test set prediction. The theoretical approach indicates that the increase in the exposed partial negative surface area increases the inhibitory activity of the compound against NorA whereas the area of the molecular shadow in the XZ plane is inversely proportional to the inhibitory activity. This model also explains the relationship of the heat of formation of the compound with the inhibitory activity. The model is not only able to predict the activity of new compounds but also explains the important regions in the molecules in quantitative manner.

Shoulder model validation and joint contact forces during wheelchair activities.

PubMed

Morrow, Melissa M B; Kaufman, Kenton R; An, Kai-Nan

2010-09-17

Chronic shoulder impingement is a common problem for manual wheelchair users. The loading associated with performing manual wheelchair activities of daily living is substantial and often at a high frequency. Musculoskeletal modeling and optimization techniques can be used to estimate the joint contact forces occurring at the shoulder to assess the soft tissue loading during an activity and to possibly identify activities and strategies that place manual wheelchair users at risk for shoulder injuries. The purpose of this study was to validate an upper extremity musculoskeletal model and apply the model to wheelchair activities for analysis of the estimated joint contact forces. Upper extremity kinematics and handrim wheelchair kinetics were measured over three conditions: level propulsion, ramp propulsion, and a weight relief lift. The experimental data were used as input to a subject-specific musculoskeletal model utilizing optimization to predict joint contact forces of the shoulder during all conditions. The model was validated using a mean absolute error calculation. Model results confirmed that ramp propulsion and weight relief lifts place the shoulder under significantly higher joint contact loading than level propulsion. In addition, they exhibit large superior contact forces that could contribute to impingement. This study highlights the potential impingement risk associated with both the ramp and weight relief lift activities. Level propulsion was shown to have a low relative risk of causing injury, but with consideration of the frequency with which propulsion is performed, this observation is not conclusive.

Space Weather Models and Their Validation and Verification at the CCMC

NASA Technical Reports Server (NTRS)

Hesse, Michael

2010-01-01

The Community Coordinated l\\lodeling Center (CCMC) is a US multi-agency activity with a dual mission. With equal emphasis, CCMC strives to provide science support to the international space research community through the execution of advanced space plasma simulations, and it endeavors to support the space weather needs of the CS and partners. Space weather support involves a broad spectrum, from designing robust forecasting systems and transitioning them to forecasters, to providing space weather updates and forecasts to NASA's robotic mission operators. All of these activities have to rely on validation and verification of models and their products, so users and forecasters have the means to assign confidence levels to the space weather information. In this presentation, we provide an overview of space weather models resident at CCMC, as well as of validation and verification activities undertaken at CCMC or through the use of CCMC services.

Active imaging system performance model for target acquisition

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Teaney, Brian; Nguyen, Quang; Jacobs, Eddie L.; Halford, Carl E.; Tofsted, David H.

2007-04-01

The U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate has developed a laser-range-gated imaging system performance model for the detection, recognition, and identification of vehicle targets. The model is based on the established US Army RDECOM CERDEC NVESD sensor performance models of the human system response through an imaging system. The Java-based model, called NVLRG, accounts for the effect of active illumination, atmospheric attenuation, and turbulence effects relevant to LRG imagers, such as speckle and scintillation, and for the critical sensor and display components. This model can be used to assess the performance of recently proposed active SWIR systems through various trade studies. This paper will describe the NVLRG model in detail, discuss the validation of recent model components, present initial trade study results, and outline plans to validate and calibrate the end-to-end model with field data through human perception testing.

Rational selection of training and test sets for the development of validated QSAR models

NASA Astrophysics Data System (ADS)

Golbraikh, Alexander; Shen, Min; Xiao, Zhiyan; Xiao, Yun-De; Lee, Kuo-Hsiung; Tropsha, Alexander

2003-02-01

Quantitative Structure-Activity Relationship (QSAR) models are used increasingly to screen chemical databases and/or virtual chemical libraries for potentially bioactive molecules. These developments emphasize the importance of rigorous model validation to ensure that the models have acceptable predictive power. Using k nearest neighbors ( kNN) variable selection QSAR method for the analysis of several datasets, we have demonstrated recently that the widely accepted leave-one-out (LOO) cross-validated R2 (q2) is an inadequate characteristic to assess the predictive ability of the models [Golbraikh, A., Tropsha, A. Beware of q2! J. Mol. Graphics Mod. 20, 269-276, (2002)]. Herein, we provide additional evidence that there exists no correlation between the values of q 2 for the training set and accuracy of prediction ( R 2) for the test set and argue that this observation is a general property of any QSAR model developed with LOO cross-validation. We suggest that external validation using rationally selected training and test sets provides a means to establish a reliable QSAR model. We propose several approaches to the division of experimental datasets into training and test sets and apply them in QSAR studies of 48 functionalized amino acid anticonvulsants and a series of 157 epipodophyllotoxin derivatives with antitumor activity. We formulate a set of general criteria for the evaluation of predictive power of QSAR models.

Description of a Website Resource for Turbulence Modeling Verification and Validation

NASA Technical Reports Server (NTRS)

Rumsey, Christopher L.; Smith, Brian R.; Huang, George P.

2010-01-01

The activities of the Turbulence Model Benchmarking Working Group - which is a subcommittee of the American Institute of Aeronautics and Astronautics (AIAA) Fluid Dynamics Technical Committee - are described. The group s main purpose is to establish a web-based repository for Reynolds-averaged Navier-Stokes turbulence model documentation, including verification and validation cases. This turbulence modeling resource has been established based on feedback from a survey on what is needed to achieve consistency and repeatability in turbulence model implementation and usage, and to document and disseminate information on new turbulence models or improvements to existing models. The various components of the website are described in detail: description of turbulence models, turbulence model readiness rating system, verification cases, validation cases, validation databases, and turbulence manufactured solutions. An outline of future plans of the working group is also provided.

Testing a self-determination theory model of children's physical activity motivation: a cross-sectional study.

PubMed

Sebire, Simon J; Jago, Russell; Fox, Kenneth R; Edwards, Mark J; Thompson, Janice L

2013-09-26

Understanding children's physical activity motivation, its antecedents and associations with behavior is important and can be advanced by using self-determination theory. However, research among youth is largely restricted to adolescents and studies of motivation within certain contexts (e.g., physical education). There are no measures of self-determination theory constructs (physical activity motivation or psychological need satisfaction) for use among children and no previous studies have tested a self-determination theory-based model of children's physical activity motivation. The purpose of this study was to test the reliability and validity of scores derived from scales adapted to measure self-determination theory constructs among children and test a motivational model predicting accelerometer-derived physical activity. Cross-sectional data from 462 children aged 7 to 11 years from 20 primary schools in Bristol, UK were analysed. Confirmatory factor analysis was used to examine the construct validity of adapted behavioral regulation and psychological need satisfaction scales. Structural equation modelling was used to test cross-sectional associations between psychological need satisfaction, motivation types and physical activity assessed by accelerometer. The construct validity and reliability of the motivation and psychological need satisfaction measures were supported. Structural equation modelling provided evidence for a motivational model in which psychological need satisfaction was positively associated with intrinsic and identified motivation types and intrinsic motivation was positively associated with children's minutes in moderate-to-vigorous physical activity. The study provides evidence for the psychometric properties of measures of motivation aligned with self-determination theory among children. Children's motivation that is based on enjoyment and inherent satisfaction of physical activity is associated with their objectively-assessed physical activity and such motivation is positively associated with perceptions of psychological need satisfaction. These psychological factors represent potential malleable targets for interventions to increase children's physical activity.

Validation of MCNP NPP Activation Simulations for Decommissioning Studies by Analysis of NPP Neutron Activation Foil Measurement Campaigns

NASA Astrophysics Data System (ADS)

Volmert, Ben; Pantelias, Manuel; Mutnuru, R. K.; Neukaeter, Erwin; Bitterli, Beat

2016-02-01

In this paper, an overview of the Swiss Nuclear Power Plant (NPP) activation methodology is presented and the work towards its validation by in-situ NPP foil irradiation campaigns is outlined. Nuclear Research and consultancy Group (NRG) in The Netherlands has been given the task of performing the corresponding neutron metrology. For this purpose, small Aluminium boxes containing a set of circular-shaped neutron activation foils have been prepared. After being irradiated for one complete reactor cycle, the sets have been successfully retrieved, followed by gamma-spectrometric measurements of the individual foils at NRG. Along with the individual activities of the foils, the reaction rates and thermal, intermediate and fast neutron fluence rates at the foil locations have been determined. These determinations include appropriate corrections for gamma self-absorption and neutron self-shielding as well as corresponding measurement uncertainties. The comparison of the NPP Monte Carlo calculations with the results of the foil measurements is done by using an individual generic MCNP model functioning as an interface and allowing the simulation of individual foil activation by predetermined neutron spectra. To summarize, the comparison between calculation and measurement serve as a sound validation of the Swiss NPP activation methodology by demonstrating a satisfying agreement between measurement and calculation. Finally, the validation offers a chance for further improvements of the existing NPP models by ensuing calibration and/or modelling optimizations for key components and structures.

ADVANCED UTILITY SIMULATION MODEL, REPORT OF SENSITIVITY TESTING, CALIBRATION, AND MODEL OUTPUT COMPARISONS (VERSION 3.0)

EPA Science Inventory

The report gives results of activities relating to the Advanced Utility Simulation Model (AUSM): sensitivity testing. comparison with a mature electric utility model, and calibration to historical emissions. The activities were aimed at demonstrating AUSM's validity over input va...

QSAR Analysis of 2-Amino or 2-Methyl-1-Substituted Benzimidazoles Against Pseudomonas aeruginosa

PubMed Central

Podunavac-Kuzmanović, Sanja O.; Cvetković, Dragoljub D.; Barna, Dijana J.

2009-01-01

A set of benzimidazole derivatives were tested for their inhibitory activities against the Gram-negative bacterium Pseudomonas aeruginosa and minimum inhibitory concentrations were determined for all the compounds. Quantitative structure activity relationship (QSAR) analysis was applied to fourteen of the abovementioned derivatives using a combination of various physicochemical, steric, electronic, and structural molecular descriptors. A multiple linear regression (MLR) procedure was used to model the relationships between molecular descriptors and the antibacterial activity of the benzimidazole derivatives. The stepwise regression method was used to derive the most significant models as a calibration model for predicting the inhibitory activity of this class of molecules. The best QSAR models were further validated by a leave one out technique as well as by the calculation of statistical parameters for the established theoretical models. To confirm the predictive power of the models, an external set of molecules was used. High agreement between experimental and predicted inhibitory values, obtained in the validation procedure, indicated the good quality of the derived QSAR models. PMID:19468332

AdViSHE: A Validation-Assessment Tool of Health-Economic Models for Decision Makers and Model Users.

PubMed

Vemer, P; Corro Ramos, I; van Voorn, G A K; Al, M J; Feenstra, T L

2016-04-01

A trade-off exists between building confidence in health-economic (HE) decision models and the use of scarce resources. We aimed to create a practical tool providing model users with a structured view into the validation status of HE decision models, to address this trade-off. A Delphi panel was organized, and was completed by a workshop during an international conference. The proposed tool was constructed iteratively based on comments from, and the discussion amongst, panellists. During the Delphi process, comments were solicited on the importance and feasibility of possible validation techniques for modellers, their relevance for decision makers, and the overall structure and formulation in the tool. The panel consisted of 47 experts in HE modelling and HE decision making from various professional and international backgrounds. In addition, 50 discussants actively engaged in the discussion at the conference workshop and returned 19 questionnaires with additional comments. The final version consists of 13 items covering all relevant aspects of HE decision models: the conceptual model, the input data, the implemented software program, and the model outcomes. Assessment of the Validation Status of Health-Economic decision models (AdViSHE) is a validation-assessment tool in which model developers report in a systematic way both on validation efforts performed and on their outcomes. Subsequently, model users can establish whether confidence in the model is justified or whether additional validation efforts should be undertaken. In this way, AdViSHE enhances transparency of the validation status of HE models and supports efficient model validation.

Aeroservoelastic wind-tunnel investigations using the Active Flexible Wing Model: Status and recent accomplishments

NASA Technical Reports Server (NTRS)

Noll, Thomas E.; Perry, Boyd, III; Tiffany, Sherwood H.; Cole, Stanley R.; Buttrill, Carey S.; Adams, William M., Jr.; Houck, Jacob A.; Srinathkumar, S.; Mukhopadhyay, Vivek; Pototzky, Anthony S.

1989-01-01

The status of the joint NASA/Rockwell Active Flexible Wing Wind-Tunnel Test Program is described. The objectives are to develop and validate the analysis, design, and test methodologies required to apply multifunction active control technology for improving aircraft performance and stability. Major tasks include designing digital multi-input/multi-output flutter-suppression and rolling-maneuver-load alleviation concepts for a flexible full-span wind-tunnel model, obtaining an experimental data base for the basic model and each control concept and providing comparisons between experimental and analytical results to validate the methodologies. The opportunity is provided to improve real-time simulation techniques and to gain practical experience with digital control law implementation procedures.

Validation workflow for a clinical Bayesian network model in multidisciplinary decision making in head and neck oncology treatment.

PubMed

Cypko, Mario A; Stoehr, Matthaeus; Kozniewski, Marcin; Druzdzel, Marek J; Dietz, Andreas; Berliner, Leonard; Lemke, Heinz U

2017-11-01

Oncological treatment is being increasingly complex, and therefore, decision making in multidisciplinary teams is becoming the key activity in the clinical pathways. The increased complexity is related to the number and variability of possible treatment decisions that may be relevant to a patient. In this paper, we describe validation of a multidisciplinary cancer treatment decision in the clinical domain of head and neck oncology. Probabilistic graphical models and corresponding inference algorithms, in the form of Bayesian networks, can support complex decision-making processes by providing a mathematically reproducible and transparent advice. The quality of BN-based advice depends on the quality of the model. Therefore, it is vital to validate the model before it is applied in practice. For an example BN subnetwork of laryngeal cancer with 303 variables, we evaluated 66 patient records. To validate the model on this dataset, a validation workflow was applied in combination with quantitative and qualitative analyses. In the subsequent analyses, we observed four sources of imprecise predictions: incorrect data, incomplete patient data, outvoting relevant observations, and incorrect model. Finally, the four problems were solved by modifying the data and the model. The presented validation effort is related to the model complexity. For simpler models, the validation workflow is the same, although it may require fewer validation methods. The validation success is related to the model's well-founded knowledge base. The remaining laryngeal cancer model may disclose additional sources of imprecise predictions.

Assessment of Cognitively Stimulating Activity in a Spanish Population.

PubMed

Morales Ortiz, Manuel; Fernández, Aaron

2018-05-01

Theoretical models of active ageing and cognitive reserve emphasize the importance of leading an active life to delay age-related cognitive deterioration and maintain good levels of well-being and personal satisfaction in the elderly. The objective of this research was to construct a scale to measure cognitively stimulating activities (CSA) in the Spanish language. The sample consisted of a total of 453 older persons. The scale was constructed from a list of 28 items and validated using structural equation models. The scale obtained showed a negative correlation with age and a positive correlation with education and physical activity. Using hierarchical regression models, CSAs were found to have a significant effect on attention when controlling for the effect of age and education. Likewise, a significant interaction between age and CSA was found on the measure of episodic memory. The validated CSA scale will enable the relationships between changes in cognitive functions and stimulating activities to be studied.

A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

PubMed

Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

2016-02-13

Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides. Copyright © 2015 Elsevier B.V. All rights reserved.

Predicting human skin absorption of chemicals: development of a novel quantitative structure activity relationship.

PubMed

Luo, Wen; Medrek, Sarah; Misra, Jatin; Nohynek, Gerhard J

2007-02-01

The objective of this study was to construct and validate a quantitative structure-activity relationship model for skin absorption. Such models are valuable tools for screening and prioritization in safety and efficacy evaluation, and risk assessment of drugs and chemicals. A database of 340 chemicals with percutaneous absorption was assembled. Two models were derived from the training set consisting 306 chemicals (90/10 random split). In addition to the experimental K(ow) values, over 300 2D and 3D atomic and molecular descriptors were analyzed using MDL's QsarIS computer program. Subsequently, the models were validated using both internal (leave-one-out) and external validation (test set) procedures. Using the stepwise regression analysis, three molecular descriptors were determined to have significant statistical correlation with K(p) (R2 = 0.8225): logK(ow), X0 (quantification of both molecular size and the degree of skeletal branching), and SsssCH (count of aromatic carbon groups). In conclusion, two models to estimate skin absorption were developed. When compared to other skin absorption QSAR models in the literature, our model incorporated more chemicals and explored a large number of descriptors. Additionally, our models are reasonably predictive and have met both internal and external statistical validations.

Use of Daily Phone Diary to study religiosity and mood: Convergent validity

PubMed Central

Szczesniak, Rhonda D.; Zou, Yuanshu; Dimitriou, Sophia M.; Quittner, Alexandra L.; Grossoehme, Daniel H.

2017-01-01

Studies of religious/spiritual behavior frequently rely on self-reported questionnaire data, which is susceptible to bias. The Daily Phone Diary (DPD) was developed to minimize bias in reporting activities and behavior across a 24-hour period. A cross-sectional study of 126 parents of children with cystic fibrosis was used to establish the validity of the DPD to study religious/spiritual behaviors. Longitudinal models were used to determine the odds of improved mood during religious/spiritual activities. Convergent validity was found. Participants had increased odds of improved mood during religious/spiritual activities compared to non-religious/spiritual activities. Associations with gender and religious affiliations were found. The DPD is a valid tool for studying religious/spiritual activities and opens novel avenues for chaplaincy research and the development of chaplaincy interventions incorporating these findings. PMID:27869567

Validation of a "Kane's Dynamics" Model for the Active Rack Isolation System

NASA Technical Reports Server (NTRS)

Beech, Geoffrey S.; Hampton, R. David

2000-01-01

Many microgravity space-science experiments require vibratory acceleration levels unachievable without active isolation. The Boeing Corporation's Active Rack Isolation System (ARIS) employs a novel combination of magnetic actuation and mechanical linkages, to address these isolation requirements on the International Space Station (ISS). ARIS provides isolation at the rack (international Standard Payload Rack, or ISPR) level. Effective model-based vibration isolation requires (1) an isolation device, (2) an adequate dynamic (i.e., mathematical) model of that isolator, and (3) a suitable, corresponding controller, ARIS provides the ISS response to the first requirement. In November 1999, the authors presented a response to the second ("A 'Kane's Dynamics' model for the Active Rack Isolation System", Hampton and Beech) intended to facilitate an optimal-controls approach to the third. This paper documents the validation of that high-fidelity dynamic model of ARIS. As before, this model contains the full actuator dynamics, however, the umbilical models are not included in this presentation. The validation of this dynamics model was achieved by utilizing two Commercial Off the Shelf (COTS) software tools: Deneb's ENVISION, and Online Dynamics' AUTOLEV. ENVISION is a robotics software package developed for the automotive industry that employs 3-dimensional (3-D) Computer Aided Design (CAD) models to facilitate both forward and inverse kinematics analyses. AUTOLEV is a DOS based interpreter that is designed in general to solve vector based mathematical problems and specifically to solve Dynamics problems using Kane's method.

Quantitative studies on structure-DPPH• scavenging activity relationships of food phenolic acids.

PubMed

Jing, Pu; Zhao, Shu-Juan; Jian, Wen-Jie; Qian, Bing-Jun; Dong, Ying; Pang, Jie

2012-11-01

Phenolic acids are potent antioxidants, yet the quantitative structure-activity relationships of phenolic acids remain unclear. The purpose of this study was to establish 3D-QSAR models able to predict phenolic acids with high DPPH• scavenging activity and understand their structure-activity relationships. The model has been established by using a training set of compounds with cross-validated q2 = 0.638/0.855, non-cross-validated r2 = 0.984/0.986, standard error of estimate = 0.236/0.216, and F = 139.126/208.320 for the best CoMFA/CoMSIA models. The predictive ability of the models was validated with the correlation coefficient r2(pred) = 0.971/0.996 (>0.6) for each model. Additionally, the contour map results suggested that structural characteristics of phenolics acids favorable for the high DPPH• scavenging activity might include: (1) bulky and/or electron-donating substituent groups on the phenol ring; (2) electron-donating groups at the meta-position and/or hydrophobic groups at the meta-/ortho-position; (3) hydrogen-bond donor/electron-donating groups at the ortho-position. The results have been confirmed based on structural analyses of phenolic acids and their DPPH• scavenging data from eight recent publications. The findings may provide deeper insight into the antioxidant mechanisms and provide useful information for selecting phenolic acids for free radical scavenging properties.

QSAR models for anti-malarial activity of 4-aminoquinolines.

PubMed

Masand, Vijay H; Toropov, Andrey A; Toropova, Alla P; Mahajan, Devidas T

2014-03-01

In the present study, predictive quantitative structure - activity relationship (QSAR) models for anti-malarial activity of 4-aminoquinolines have been developed. CORAL, which is freely available on internet (http://www.insilico.eu/coral), has been used as a tool of QSAR analysis to establish statistically robust QSAR model of anti-malarial activity of 4-aminoquinolines. Six random splits into the visible sub-system of the training and invisible subsystem of validation were examined. Statistical qualities for these splits vary, but in all these cases, statistical quality of prediction for anti-malarial activity was quite good. The optimal SMILES-based descriptor was used to derive the single descriptor based QSAR model for a data set of 112 aminoquinolones. All the splits had r(2)> 0.85 and r(2)> 0.78 for subtraining and validation sets, respectively. The three parametric multilinear regression (MLR) QSAR model has Q(2) = 0.83, R(2) = 0.84 and F = 190.39. The anti-malarial activity has strong correlation with presence/absence of nitrogen and oxygen at a topological distance of six.

Lessons learned from recent geomagnetic disturbance model validation activities

NASA Astrophysics Data System (ADS)

Pulkkinen, A. A.; Welling, D. T.

2017-12-01

Due to concerns pertaining to geomagnetically induced current impact on ground-based infrastructure, there has been significantly elevated interest in applying models for local geomagnetic disturbance or "delta-B" predictions. Correspondingly there has been elevated need for testing the quality of the delta-B predictions generated by the modern empirical and physics-based models. To address this need, community-wide activities were launched under the GEM Challenge framework and one culmination of the activities was the validation and selection of models that were transitioned into operations at NOAA SWPC. The community-wide delta-B action is continued under the CCMC-facilitated International Forum for Space Weather Capabilities Assessment and its "Ground Magnetic Perturbations: dBdt, delta-B, GICs, FACs" working group. The new delta-B working group builds on the past experiences and expands the collaborations to cover the entire international space weather community. In this paper, we discuss the key lessons learned from the past delta-B validation exercises and lay out the path forward for building on those experience under the new delta-B working group.

Application of Quantitative Structure–Activity Relationship Models of 5-HT1A Receptor Binding to Virtual Screening Identifies Novel and Potent 5-HT1A Ligands

PubMed Central

2015-01-01

The 5-hydroxytryptamine 1A (5-HT1A) serotonin receptor has been an attractive target for treating mood and anxiety disorders such as schizophrenia. We have developed binary classification quantitative structure–activity relationship (QSAR) models of 5-HT1A receptor binding activity using data retrieved from the PDSP Ki database. The prediction accuracy of these models was estimated by external 5-fold cross-validation as well as using an additional validation set comprising 66 structurally distinct compounds from the World of Molecular Bioactivity database. These validated models were then used to mine three major types of chemical screening libraries, i.e., drug-like libraries, GPCR targeted libraries, and diversity libraries, to identify novel computational hits. The five best hits from each class of libraries were chosen for further experimental testing in radioligand binding assays, and nine of the 15 hits were confirmed to be active experimentally with binding affinity better than 10 μM. The most active compound, Lysergol, from the diversity library showed very high binding affinity (Ki) of 2.3 nM against 5-HT1A receptor. The novel 5-HT1A actives identified with the QSAR-based virtual screening approach could be potentially developed as novel anxiolytics or potential antischizophrenic drugs. PMID:24410373

[New questionnaire to assess self-efficacy toward physical activity in children].

PubMed

Aedo, Angeles; Avila, Héctor

2009-10-01

To design a questionnaire for assessment of self-efficacy toward physical activity in school children, as well as to measure its construct validity, test-retest reliability, and internal consistency. A four-stage multimethod approach was used: (1) bibliographic research followed by exploratory study and the formulation of questions and responses based on a dichotomous scale of 14 items; (2) validation of the content by a panel of experts; (3) application of the preliminary version of the questionnaire to a sample of 900 school-aged children in Mexico City; and (4) determination of the construct validity, test-retest reliability, and internal consistency (Cronbach's alpha). Three factors were identified that explain 64.15% of the variance: the search for positive alternatives to physical activity, ability to deal with possible barriers to exercising, and expectations of skill or competence. The model was validated using the goodness of fit, and the result of 65% less than 0.05 indicated that the estimated factor model fit the data. Cronbach's consistency alpha was 0.733; test-retest reliability was 0.867. The scale designed has adequate reliability and validity. These results are a good indicator of self-efficacy toward physical activity in school children, which is important when developing programs intended to promote such behavior in this age group.

Assessing the validity and reliability of family factors on physical activity: A case study in Turkey.

PubMed

Steenson, Sharalyn; Özcebe, Hilal; Arslan, Umut; Konşuk Ünlü, Hande; Araz, Özgür M; Yardim, Mahmut; Üner, Sarp; Bilir, Nazmi; Huang, Terry T-K

2018-01-01

Childhood obesity rates have been rising rapidly in developing countries. A better understanding of the risk factors and social context is necessary to inform public health interventions and policies. This paper describes the validation of several measurement scales for use in Turkey, which relate to child and parent perceptions of physical activity (PA) and enablers and barriers of physical activity in the home environment. The aim of this study was to assess the validity and reliability of several measurement scales in Turkey using a population sample across three socio-economic strata in the Turkish capital, Ankara. Surveys were conducted in Grade 4 children (mean age = 9.7 years for boys; 9.9 years for girls), and their parents, across 6 randomly selected schools, stratified by SES (n = 641 students, 483 parents). Construct validity of the scales was evaluated through exploratory and confirmatory factor analysis. Internal consistency of scales and test-retest reliability were assessed by Cronbach's alpha and intra-class correlation. The scales as a whole were found to have acceptable-to-good model fit statistics (PA Barriers: RMSEA = 0.076, SRMR = 0.0577, AGFI = 0.901; PA Outcome Expectancies: RMSEA = 0.054, SRMR = 0.0545, AGFI = 0.916, and PA Home Environment: RMSEA = 0.038, SRMR = 0.0233, AGFI = 0.976). The PA Barriers subscales showed good internal consistency and poor to fair test-retest reliability (personal α = 0.79, ICC = 0.29, environmental α = 0.73, ICC = 0.59). The PA Outcome Expectancies subscales showed good internal consistency and test-retest reliability (negative α = 0.77, ICC = 0.56; positive α = 0.74, ICC = 0.49). Only the PA Home Environment subscale on support for PA was validated in the final confirmatory model; it showed moderate internal consistency and test-retest reliability (α = 0.61, ICC = 0.48). This study is the first to validate measures of perceptions of physical activity and the physical activity home environment in Turkey. Our results support the originally hypothesized two-factor structures for Physical Activity Barriers and Physical Activity Outcome Expectancies. However, we found the one-factor rather than two-factor structure for Physical Activity Home Environment had the best model fit. This study provides general support for the use of these scales in Turkey in terms of validity, but test-retest reliability warrants further research.

Validation of design procedure and performance modeling of a heat and fluid transport field experiment in the unsaturated zone

NASA Astrophysics Data System (ADS)

Nir, A.; Doughty, C.; Tsang, C. F.

Validation methods which developed in the context of deterministic concepts of past generations often cannot be directly applied to environmental problems, which may be characterized by limited reproducibility of results and highly complex models. Instead, validation is interpreted here as a series of activities, including both theoretical and experimental tests, designed to enhance our confidence in the capability of a proposed model to describe some aspect of reality. We examine the validation process applied to a project concerned with heat and fluid transport in porous media, in which mathematical modeling, simulation, and results of field experiments are evaluated in order to determine the feasibility of a system for seasonal thermal energy storage in shallow unsaturated soils. Technical details of the field experiments are not included, but appear in previous publications. Validation activities are divided into three stages. The first stage, carried out prior to the field experiments, is concerned with modeling the relevant physical processes, optimization of the heat-exchanger configuration and the shape of the storage volume, and multi-year simulation. Subjects requiring further theoretical and experimental study are identified at this stage. The second stage encompasses the planning and evaluation of the initial field experiment. Simulations are made to determine the experimental time scale and optimal sensor locations. Soil thermal parameters and temperature boundary conditions are estimated using an inverse method. Then results of the experiment are compared with model predictions using different parameter values and modeling approximations. In the third stage, results of an experiment performed under different boundary conditions are compared to predictions made by the models developed in the second stage. Various aspects of this theoretical and experimental field study are described as examples of the verification and validation procedure. There is no attempt to validate a specific model, but several models of increasing complexity are compared with experimental results. The outcome is interpreted as a demonstration of the paradigm proposed by van der Heijde, 26 that different constituencies have different objectives for the validation process and therefore their acceptance criteria differ also.

Calibration and validation of an activated sludge model for greenhouse gases no. 1 (ASMG1): prediction of temperature-dependent N₂O emission dynamics.

PubMed

Guo, Lisha; Vanrolleghem, Peter A

2014-02-01

An activated sludge model for greenhouse gases no. 1 was calibrated with data from a wastewater treatment plant (WWTP) without control systems and validated with data from three similar plants equipped with control systems. Special about the calibration/validation approach adopted in this paper is that the data are obtained from simulations with a mathematical model that is widely accepted to describe effluent quality and operating costs of actual WWTPs, the Benchmark Simulation Model No. 2 (BSM2). The calibration also aimed at fitting the model to typical observed nitrous oxide (N₂O) emission data, i.e., a yearly average of 0.5% of the influent total nitrogen load emitted as N₂O-N. Model validation was performed by challenging the model in configurations with different control strategies. The kinetic term describing the dissolved oxygen effect on the denitrification by ammonia-oxidizing bacteria (AOB) was modified into a Haldane term. Both original and Haldane-modified models passed calibration and validation. Even though their yearly averaged values were similar, the two models presented different dynamic N₂O emissions under cold temperature conditions and control. Therefore, data collected in such situations can potentially permit model discrimination. Observed seasonal trends in N₂O emissions are simulated well with both original and Haldane-modified models. A mechanistic explanation based on the temperature-dependent interaction between heterotrophic and autotrophic N₂O pathways was provided. Finally, while adding the AOB denitrification pathway to a model with only heterotrophic N₂O production showed little impact on effluent quality and operating cost criteria, it clearly affected N2O emission productions.

QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity.

PubMed

Sousa, Inês J; Ferreira, Maria-José U; Molnár, Joseph; Fernandes, Miguel X

2013-02-14

Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatrophane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure-activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to determine which structural modifications can be performed to improve their activity. Using experimental biological data at two concentrations (4 and 40 μg/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for biological activities at compound concentrations of 4 and 40 μg/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R²(pred) values of 0.765 and 0.534 for biological activities at compound concentrations of 4 and 40 μg/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40 μg/ml concentrations, respectively. For the same concentrations, the obtained R²(pred) values for jatrophanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability. Copyright © 2012 Elsevier B.V. All rights reserved.

Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles.

PubMed

Johnson, Will L; Jindrich, Devin L; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2011-12-01

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb, which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model, we investigated the suitability of a lumped-parameter model for the prediction of muscle activation during dynamic tasks. Using the validated model, we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury.

Application of a Rat Hindlimb Model: A Prediction of Force Spaces Reachable Through Stimulation of Nerve Fascicles

PubMed Central

Johnson, Will L.; Jindrich, Devin L.; Zhong, Hui; Roy, Roland R.

2011-01-01

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model we investigated the suitability of a lumped-parameter model for prediction of muscle activation during dynamic tasks. Using the validated model we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury. PMID:21244999

Cervical Spine Injuries: A Whole-Body Musculoskeletal Model for the Analysis of Spinal Loading.

PubMed

Cazzola, Dario; Holsgrove, Timothy P; Preatoni, Ezio; Gill, Harinderjit S; Trewartha, Grant

2017-01-01

Cervical spine trauma from sport or traffic collisions can have devastating consequences for individuals and a high societal cost. The precise mechanisms of such injuries are still unknown as investigation is hampered by the difficulty in experimentally replicating the conditions under which these injuries occur. We harness the benefits of computer simulation to report on the creation and validation of i) a generic musculoskeletal model (MASI) for the analyses of cervical spine loading in healthy subjects, and ii) a population-specific version of the model (Rugby Model), for investigating cervical spine injury mechanisms during rugby activities. The musculoskeletal models were created in OpenSim, and validated against in vivo data of a healthy subject and a rugby player performing neck and upper limb movements. The novel aspects of the Rugby Model comprise i) population-specific inertial properties and muscle parameters representing rugby forward players, and ii) a custom scapula-clavicular joint that allows the application of multiple external loads. We confirm the utility of the developed generic and population-specific models via verification steps and validation of kinematics, joint moments and neuromuscular activations during rugby scrummaging and neck functional movements, which achieve results comparable with in vivo and in vitro data. The Rugby Model was validated and used for the first time to provide insight into anatomical loading and cervical spine injury mechanisms related to rugby, whilst the MASI introduces a new computational tool to allow investigation of spinal injuries arising from other sporting activities, transport, and ergonomic applications. The models used in this study are freely available at simtk.org and allow to integrate in silico analyses with experimental approaches in injury prevention.

Cervical Spine Injuries: A Whole-Body Musculoskeletal Model for the Analysis of Spinal Loading

PubMed Central

Holsgrove, Timothy P.; Preatoni, Ezio; Gill, Harinderjit S.; Trewartha, Grant

2017-01-01

Cervical spine trauma from sport or traffic collisions can have devastating consequences for individuals and a high societal cost. The precise mechanisms of such injuries are still unknown as investigation is hampered by the difficulty in experimentally replicating the conditions under which these injuries occur. We harness the benefits of computer simulation to report on the creation and validation of i) a generic musculoskeletal model (MASI) for the analyses of cervical spine loading in healthy subjects, and ii) a population-specific version of the model (Rugby Model), for investigating cervical spine injury mechanisms during rugby activities. The musculoskeletal models were created in OpenSim, and validated against in vivo data of a healthy subject and a rugby player performing neck and upper limb movements. The novel aspects of the Rugby Model comprise i) population-specific inertial properties and muscle parameters representing rugby forward players, and ii) a custom scapula-clavicular joint that allows the application of multiple external loads. We confirm the utility of the developed generic and population-specific models via verification steps and validation of kinematics, joint moments and neuromuscular activations during rugby scrummaging and neck functional movements, which achieve results comparable with in vivo and in vitro data. The Rugby Model was validated and used for the first time to provide insight into anatomical loading and cervical spine injury mechanisms related to rugby, whilst the MASI introduces a new computational tool to allow investigation of spinal injuries arising from other sporting activities, transport, and ergonomic applications. The models used in this study are freely available at simtk.org and allow to integrate in silico analyses with experimental approaches in injury prevention. PMID:28052130

Developing Enhanced Blood–Brain Barrier Permeability Models: Integrating External Bio-Assay Data in QSAR Modeling

PubMed Central

Wang, Wenyi; Kim, Marlene T.; Sedykh, Alexander

2015-01-01

Purpose Experimental Blood–Brain Barrier (BBB) permeability models for drug molecules are expensive and time-consuming. As alternative methods, several traditional Quantitative Structure-Activity Relationship (QSAR) models have been developed previously. In this study, we aimed to improve the predictivity of traditional QSAR BBB permeability models by employing relevant public bio-assay data in the modeling process. Methods We compiled a BBB permeability database consisting of 439 unique compounds from various resources. The database was split into a modeling set of 341 compounds and a validation set of 98 compounds. Consensus QSAR modeling workflow was employed on the modeling set to develop various QSAR models. A five-fold cross-validation approach was used to validate the developed models, and the resulting models were used to predict the external validation set compounds. Furthermore, we used previously published membrane transporter models to generate relevant transporter profiles for target compounds. The transporter profiles were used as additional biological descriptors to develop hybrid QSAR BBB models. Results The consensus QSAR models have R2=0.638 for fivefold cross-validation and R2=0.504 for external validation. The consensus model developed by pooling chemical and transporter descriptors showed better predictivity (R2=0.646 for five-fold cross-validation and R2=0.526 for external validation). Moreover, several external bio-assays that correlate with BBB permeability were identified using our automatic profiling tool. Conclusions The BBB permeability models developed in this study can be useful for early evaluation of new compounds (e.g., new drug candidates). The combination of chemical and biological descriptors shows a promising direction to improve the current traditional QSAR models. PMID:25862462

Combined expectancies: electrophysiological evidence for the adjustment of expectancy effects

PubMed Central

Mattler, Uwe; van der Lugt, Arie; Münte, Thomas F

2006-01-01

Background When subjects use cues to prepare for a likely stimulus or a likely response, reaction times are facilitated by valid cues but prolonged by invalid cues. In studies on combined expectancy effects, two cues can independently give information regarding two dimensions of the forthcoming task. In certain situations, cueing effects on one dimension are reduced when the cue on the other dimension is invalid. According to the Adjusted Expectancy Model, cues affect different processing levels and a mechanism is presumed which is sensitive to the validity of early level cues and leads to online adjustment of expectancy effects at later levels. To examine the predictions of this model cueing of stimulus modality was combined with response cueing. Results Behavioral measures showed the interaction of cueing effects. Electrophysiological measures of the lateralized readiness potential (LRP) and the N200 amplitude confirmed the predictions of the model. The LRP showed larger effects of response cues on response activation when modality cues were valid rather than invalid. N200 amplitude was largest with valid modality cues and invalid response cues, medium with invalid modality cues, and smallest with two valid cues. Conclusion Findings support the view that the validity of early level expectancies modulates the effects of late level expectancies, which included response activation and response conflict in the present study. PMID:16674805

Testing a self-determination theory model of children’s physical activity motivation: a cross-sectional study

PubMed Central

2013-01-01

Background Understanding children’s physical activity motivation, its antecedents and associations with behavior is important and can be advanced by using self-determination theory. However, research among youth is largely restricted to adolescents and studies of motivation within certain contexts (e.g., physical education). There are no measures of self-determination theory constructs (physical activity motivation or psychological need satisfaction) for use among children and no previous studies have tested a self-determination theory-based model of children’s physical activity motivation. The purpose of this study was to test the reliability and validity of scores derived from scales adapted to measure self-determination theory constructs among children and test a motivational model predicting accelerometer-derived physical activity. Methods Cross-sectional data from 462 children aged 7 to 11 years from 20 primary schools in Bristol, UK were analysed. Confirmatory factor analysis was used to examine the construct validity of adapted behavioral regulation and psychological need satisfaction scales. Structural equation modelling was used to test cross-sectional associations between psychological need satisfaction, motivation types and physical activity assessed by accelerometer. Results The construct validity and reliability of the motivation and psychological need satisfaction measures were supported. Structural equation modelling provided evidence for a motivational model in which psychological need satisfaction was positively associated with intrinsic and identified motivation types and intrinsic motivation was positively associated with children’s minutes in moderate-to-vigorous physical activity. Conclusions The study provides evidence for the psychometric properties of measures of motivation aligned with self-determination theory among children. Children’s motivation that is based on enjoyment and inherent satisfaction of physical activity is associated with their objectively-assessed physical activity and such motivation is positively associated with perceptions of psychological need satisfaction. These psychological factors represent potential malleable targets for interventions to increase children’s physical activity. PMID:24067078

Measurement of Function Post Hip Fracture: Testing a Comprehensive Measurement Model of Physical Function

PubMed Central

Gruber-Baldini, Ann L.; Hicks, Gregory; Ostir, Glen; Klinedinst, N. Jennifer; Orwig, Denise; Magaziner, Jay

2015-01-01

Background Measurement of physical function post hip fracture has been conceptualized using multiple different measures. Purpose This study tested a comprehensive measurement model of physical function. Design This was a descriptive secondary data analysis including 168 men and 171 women post hip fracture. Methods Using structural equation modeling, a measurement model of physical function which included grip strength, activities of daily living, instrumental activities of daily living and performance was tested for fit at 2 and 12 months post hip fracture and among male and female participants and validity of the measurement model of physical function was evaluated based on how well the model explained physical activity, exercise and social activities post hip fracture. Findings The measurement model of physical function fit the data. The amount of variance the model or individual factors of the model explained varied depending on the activity. Conclusion Decisions about the ideal way in which to measure physical function should be based on outcomes considered and participant Clinical Implications The measurement model of physical function is a reliable and valid method to comprehensively measure physical function across the hip fracture recovery trajectory. Practical but useful assessment of function should be considered and monitored over the recovery trajectory post hip fracture. PMID:26492866

Antenna gain of actively compensated free-space optical communication systems under strong turbulence conditions.

PubMed

Juarez, Juan C; Brown, David M; Young, David W

2014-05-19

Current Strehl ratio models for actively compensated free-space optical communications terminals do not accurately predict system performance under strong turbulence conditions as they are based on weak turbulence theory. For evaluation of compensated systems, we present an approach for simulating the Strehl ratio with both low-order (tip/tilt) and higher-order (adaptive optics) correction. Our simulation results are then compared to the published models and their range of turbulence validity is assessed. Finally, we propose a new Strehl ratio model and antenna gain equation that are valid for general turbulence conditions independent of the degree of compensation.

Computational Steroidogenesis Model To Predict Biochemical Responses to Endocrine Active Chemicals: Model Development and Cross Validation

EPA Science Inventory

Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

Skill assessment of the coupled physical-biogeochemical operational Mediterranean Forecasting System

NASA Astrophysics Data System (ADS)

Cossarini, Gianpiero; Clementi, Emanuela; Salon, Stefano; Grandi, Alessandro; Bolzon, Giorgio; Solidoro, Cosimo

2016-04-01

The Mediterranean Monitoring and Forecasting Centre (Med-MFC) is one of the regional production centres of the European Marine Environment Monitoring Service (CMEMS-Copernicus). Med-MFC operatively manages a suite of numerical model systems (3DVAR-NEMO-WW3 and 3DVAR-OGSTM-BFM) that provides gridded datasets of physical and biogeochemical variables for the Mediterranean marine environment with a horizontal resolution of about 6.5 km. At the present stage, the operational Med-MFC produces ten-day forecast: daily for physical parameters and bi-weekly for biogeochemical variables. The validation of the coupled model system and the estimate of the accuracy of model products are key issues to ensure reliable information to the users and the downstream services. Product quality activities at Med-MFC consist of two levels of validation and skill analysis procedures. Pre-operational qualification activities focus on testing the improvement of the quality of a new release of the model system and relays on past simulation and historical data. Then, near real time (NRT) validation activities aim at the routinely and on-line skill assessment of the model forecast and relays on the NRT available observations. Med-MFC validation framework uses both independent (i.e. Bio-Argo float data, in-situ mooring and vessel data of oxygen, nutrients and chlorophyll, moored buoys, tide-gauges and ADCP of temperature, salinity, sea level and velocity) and semi-independent data (i.e. data already used for assimilation, such as satellite chlorophyll, Satellite SLA and SST and in situ vertical profiles of temperature and salinity from XBT, Argo and Gliders) We give evidence that different variables (e.g. CMEMS-products) can be validated at different levels (i.e. at the forecast level or at the level of model consistency) and at different spatial and temporal scales. The fundamental physical parameters temperature, salinity and sea level are routinely validated on daily, weekly and quarterly base at regional and sub-regional scale and along specific vertical layers (temperature and salinity); while velocity fields are daily validated against in situ coastal moorings. Since the velocity skill cannot be accurately assessed through coastal measurements due to the actual model horizontal resolution (~6.5 km), new validation metrics and procedures are under investigation. Chlorophyll is the only biogeochemical variable that can be validated routinely at the temporal and spatial scale of the weekly forecast, while nutrients and oxygen predictions can be validated locally or at sub-basin and seasonal scales. For the other biogeochemical variables (i.e. primary production, carbonate system variables) only the accuracy of the average dynamics and model consistency can be evaluated. Then, we discuss the limiting factors of the present validation framework, and the quality and extension of the observing system that would be needed for improving the reliability of the physical and biogeochemical Mediterranean forecast services.

Investigation on Quantitative Structure Activity Relationships of a Series of Inducible Nitric Oxide.

PubMed

Sharma, Mukesh C; Sharma, S

2016-12-01

A series of 2-dihydro-4-quinazolin with potent highly selective inhibitors of inducible nitric oxide synthase activities was subjected to quantitative structure activity relationships (QSAR) analysis. Statistically significant equations with high correlation coefficient (r 2  = 0.8219) were developed. The k-nearest neighbor model has showed good cross-validated correlation coefficient and external validation values of 0.7866 and 0.7133, respectively. The selected electrostatic field descriptors the presence of blue ball around R1 and R4 in the quinazolinamine moiety showed electronegative groups favorable for nitric oxide synthase activity. The QSAR models may lead to the structural requirements of inducible nitric oxide compounds and help in the design of new compounds.

Modeling and Validation of a Navy A6-Intruder Actively Controlled Landing Gear System

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Daugherty, Robert H.; Martinson, Veloria J.

1999-01-01

Concepts for long-range air travel are characterized by airframe designs with long, slender, relatively flexible fuselages. One aspect often overlooked is ground-induced vibration of these aircraft. This paper presents an analytical and experimental study of reducing ground-induced aircraft vibration loads by using actively controlled landing gear. A facility has been developed to test various active landing gear control concepts and their performance, The facility uses a Navy A6 Intruder landing gear fitted with an auxiliary hydraulic supply electronically controlled by servo valves. An analytical model of the gear is presented, including modifications to actuate the gear externally, and test data are used to validate the model. The control design is described and closed-loop test and analysis comparisons are presented.

Validation of a Scalable Solar Sailcraft

NASA Technical Reports Server (NTRS)

Murphy, D. M.

2006-01-01

The NASA In-Space Propulsion (ISP) program sponsored intensive solar sail technology and systems design, development, and hardware demonstration activities over the past 3 years. Efforts to validate a scalable solar sail system by functional demonstration in relevant environments, together with test-analysis correlation activities on a scalable solar sail system have recently been successfully completed. A review of the program, with descriptions of the design, results of testing, and analytical model validations of component and assembly functional, strength, stiffness, shape, and dynamic behavior are discussed. The scaled performance of the validated system is projected to demonstrate the applicability to flight demonstration and important NASA road-map missions.

Confirmatory factorial analysis of the children´s attraction to physical activity scale (capa).

PubMed

Seabra, A C; Maia, J A; Parker, M; Seabra, A; Brustad, R; Fonseca, A M

2015-03-27

Attraction to physical activity (PA) is an important contributor to children´s intrinsic motivation to engage in games, and sports. Previous studies have supported the utility of the children´s attraction to PA scale (CAPA) (Brustad, 1996) but the validity of this measure for use in Portugal has not been established. The purpose of this study was to cross-validate the shorter version of the CAPA scale in the Portuguese cultural context. A sample of 342 children (8--10 years of age) was used. Confirmatory factor analyses using EQS software ( version 6.1) tested t hree competing measurement models: a single--factor model, a five factor model, and a second order factor model. The single--factor model and the second order model showed a poor fit to the data. It was found that a five-factor model similar to the original one revealed good fit to the data (S--B χ 2 (67) =94.27,p=0.02; NNFI=0.93; CFI=0.95; RMSEA=0.04; 90%CI=0.02;0.05). The results indicated that the CAPA scale is valid and appropriate for use in the Portuguese cultural context. The availability of a valid scale to evaluate attraction to PA at schools should provide improved opportunities for better assessment and understanding of children´s involvement in PA.

Predictors of validity and reliability of a physical activity record in adolescents

PubMed Central

2013-01-01

Background Poor to moderate validity of self-reported physical activity instruments is commonly observed in young people in low- and middle-income countries. However, the reasons for such low validity have not been examined in detail. We tested the validity of a self-administered daily physical activity record in adolescents and assessed if personal characteristics or the convenience level of reporting physical activity modified the validity estimates. Methods The study comprised a total of 302 adolescents from an urban and rural area in Ecuador. Validity was evaluated by comparing the record with accelerometer recordings for seven consecutive days. Test-retest reliability was examined by comparing registrations from two records administered three weeks apart. Time spent on sedentary (SED), low (LPA), moderate (MPA) and vigorous (VPA) intensity physical activity was estimated. Bland Altman plots were used to evaluate measurement agreement. We assessed if age, sex, urban or rural setting, anthropometry and convenience of completing the record explained differences in validity estimates using a linear mixed model. Results Although the record provided higher estimates for SED and VPA and lower estimates for LPA and MPA compared to the accelerometer, it showed an overall fair measurement agreement for validity. There was modest reliability for assessing physical activity in each intensity level. Validity was associated with adolescents’ personal characteristics: sex (SED: P = 0.007; LPA: P = 0.001; VPA: P = 0.009) and setting (LPA: P = 0.000; MPA: P = 0.047). Reliability was associated with the convenience of completing the physical activity record for LPA (low convenience: P = 0.014; high convenience: P = 0.045). Conclusions The physical activity record provided acceptable estimates for reliability and validity on a group level. Sex and setting were associated with validity estimates, whereas convenience to fill out the record was associated with better reliability estimates for LPA. This tendency of improved reliability estimates for adolescents reporting higher convenience merits further consideration. PMID:24289296

Design, synthesis and screening studies of potent thiazol-2-amine derivatives as fibroblast growth factor receptor 1 inhibitors.

PubMed

Kumar, B V S Suneel; Lakshmi, Narasu; Kumar, M Ravi; Rambabu, Gundla; Manjashetty, Thimmappa H; Arunasree, Kalle M; Sriram, Dharmarajan; Ramkumar, Kavya; Neamati, Nouri; Dayam, Raveendra; Sarma, J A R P

2014-01-01

Fibroblast growth factor receptor 1 (FGFR1) a tyrosine kinase receptor, plays important roles in angiogenesis, embryonic development, cell proliferation, cell differentiation, and wound healing. The FGFR isoforms and their receptors (FGFRs) considered as a potential targets and under intense research to design potential anticancer agents. Fibroblast growth factors (FGF's) and its growth factor receptors (FGFR) plays vital role in one of the critical pathway in monitoring angiogenesis. In the current study, quantitative pharmacophore models were generated and validated using known FGFR1 inhibitors. The pharmacophore models were generated using a set of 28 compounds (training). The top pharmacophore model was selected and validated using a set of 126 compounds (test set) and also using external validation. The validated pharmacophore was considered as a virtual screening query to screen a database of 400,000 virtual molecules and pharmacophore model retrieved 2800 hits. The retrieved hits were subsequently filtered based on the fit value. The selected hits were subjected for docking studies to observe the binding modes of the retrieved hits and also to reduce the false positives. One of the potential hits (thiazole-2-amine derivative) was selected based the pharmacophore fit value, dock score, and synthetic feasibility. A few analogues of the thiazole-2-amine derivative were synthesized. These compounds were screened for FGFR1 activity and anti-proliferative studies. The top active compound showed 56.87% inhibition of FGFR1 activity at 50 µM and also showed good cellular activity. Further optimization of thiazole-2-amine derivatives is in progress.

Revealing interaction mode between HIV-1 protease and mannitol analog inhibitor.

PubMed

Yan, Guan-Wen; Chen, Yue; Li, Yixue; Chen, Hai-Feng

2012-06-01

HIV protease is a key enzyme to play a key role in the HIV-1 replication cycle and control the maturation from HIV viruses to an infectious virion. HIV-1 protease has become an important target for anti-HIV-1 drug development. Here, we used molecular dynamics simulation to study the binding mode between mannitol derivatives and HIV-1 protease. The results suggest that the most active compound (M35) has more stable hydrogen bonds and stable native contacts than the less active one (M17). These mannitol derivatives might have similar interaction mode with HIV-1 protease. Then, 3D-QSAR was used to construct quantitative structure-activity models. The cross-validated q(2) values are found as 0.728 and 0.611 for CoMFA and CoMSIA, respectively. And the non-cross-validated r(2) values are 0.973 and 0.950. Nine test set compounds validate the model. The results show that this model possesses better prediction ability than the previous work. This model can be used to design new chemical entities and make quantitative prediction of the bioactivities for HIV-1 protease inhibitors before resorting to in vitro and in vivo experiment. © 2012 John Wiley & Sons A/S.

Validation of models to estimate the fumigant and larvicidal activity of Eucalyptus essential oils against Aedes aegypti (Diptera: Culicidae).

PubMed

Lucia, Alejandro; Juan, Laura W; Zerba, Eduardo N; Harrand, Leonel; Marcó, Martín; Masuh, Hector M

2012-05-01

The aim of this work is to validate the pre-existing models that relate the larvicidal and adulticidal activities of the Eucalyptus essential oils on Aedes aegypti. Previous works at our laboratory described that the larvicidal activity of Eucalyptus essential oils can be estimated from the relative concentration of two main components (p-cymene and 1,8-cineole) and that the adulticidal effectiveness can be explained, to a great extent, by the presence of large amounts of the component 1,8-cineole in it. In general, the results show that the higher adulticidal effect of essential oils the lower their larvicidal activity. Fresh leaves was harvested and distilled. Once the essential oil was obtained, the chemical composition was analysed, evaluating the biological activity of 15 species of the genus Eucalyptus (Eucalyptus badjensis Beuzev and Welch, Eucalyptus badjensis × nitens, Eucalyptus benthamii var Benthamii Maiden and Cambage, Eucalyptus benthamii var dorrigoensis Maiden and Cambage, Eucalyptus botryoides Smith, Eucalyptus dalrympleana Maiden, Eucalyptus fastigata Deane and Maiden, Eucalyptus nobilis L.A.S. Johnson and K.D.Hill, Eucalyptus polybractea R. Baker, Eucalyptus radiata ssp radiata Sieber ex Spreng, Eucalyptus resinifera Smith, Eucalyptus robertsonii Blakely, Eucalyptus robusta Smith, Eucalyptus rubida Deane and Maiden, Eucalyptus smithii R. Baker). Essential oils of these plant species were used for the validation of equations from preexistent models, in which observed and estimated values of the biological activity were compared. The regression analysis showed a strong validation of the models, re-stating the trends previously observed. The models were expressed as follows: A, fumigant activity [KT(50(min)) = 10.65-0.076 × 1,8-cineole (%)](p < 0.01; F, 397; R (2), 0.79); B, larval mortality (%)((40 ppm)) = 103.85 + 0.482 × p-cymene (%) - 0.363 × α-pinene (%) - 1.07 × 1,8-cineole (%) (p < 0.01; F, 300; R (2), 0.90). These results confirmed the importance of the mayor components in the biological activity of Eucalyptus essential oils on A. aegypti. However, it is worth mentioning that two or three species differ in the data estimated by the models, and these biological activity results coincide with the presence of minor differential components in the essential oils. According to what was previously mentioned, it can be inferred that the model is able to estimate very closely the biological activity of essential oils of Eucalyptus on A. aegypti.

Towards practical application of sensors for monitoring animal health; design and validation of a model to detect ketosis.

PubMed

Steensels, Machteld; Maltz, Ephraim; Bahr, Claudia; Berckmans, Daniel; Antler, Aharon; Halachmi, Ilan

2017-05-01

The objective of this study was to design and validate a mathematical model to detect post-calving ketosis. The validation was conducted in four commercial dairy farms in Israel, on a total of 706 multiparous Holstein dairy cows: 203 cows clinically diagnosed with ketosis and 503 healthy cows. A logistic binary regression model was developed, where the dependent variable is categorical (healthy/diseased) and a set of explanatory variables were measured with existing commercial sensors: rumination duration, activity and milk yield of each individual cow. In a first validation step (within-farm), the model was calibrated on the database of each farm separately. Two thirds of the sick cows and an equal number of healthy cows were randomly selected for model validation. The remaining one third of the cows, which did not participate in the model validation, were used for model calibration. In order to overcome the random selection effect, this procedure was repeated 100 times. In a second (between-farms) validation step, the model was calibrated on one farm and validated on another farm. Within-farm accuracy, ranging from 74 to 79%, was higher than between-farm accuracy, ranging from 49 to 72%, in all farms. The within-farm sensitivities ranged from 78 to 90%, and specificities ranged from 71 to 74%. The between-farms sensitivities ranged from 65 to 95%. The developed model can be improved in future research, by employing other variables that can be added; or by exploring other models to achieve greater sensitivity and specificity.

Investigation of remote sensing techniques of measuring soil moisture

NASA Technical Reports Server (NTRS)

Newton, R. W. (Principal Investigator); Blanchard, A. J.; Nieber, J. L.; Lascano, R.; Tsang, L.; Vanbavel, C. H. M.

1981-01-01

Major activities described include development and evaluation of theoretical models that describe both active and passive microwave sensing of soil moisture, the evaluation of these models for their applicability, the execution of a controlled field experiment during which passive microwave measurements were acquired to validate these models, and evaluation of previously acquired aircraft microwave measurements. The development of a root zone soil water and soil temperature profile model and the calibration and evaluation of gamma ray attenuation probes for measuring soil moisture profiles are considered. The analysis of spatial variability of soil information as related to remote sensing is discussed as well as the implementation of an instrumented field site for acquisition of soil moisture and meteorologic information for use in validating the soil water profile and soil temperature profile models.

Quantification and modeling of mechanical degradation in lithium-ion batteries based on nanoscale imaging.

PubMed

Müller, Simon; Pietsch, Patrick; Brandt, Ben-Elias; Baade, Paul; De Andrade, Vincent; De Carlo, Francesco; Wood, Vanessa

2018-06-14

Capacity fade in lithium-ion battery electrodes can result from a degradation mechanism in which the carbon black-binder network detaches from the active material. Here we present two approaches to visualize and quantify this detachment and use the experimental results to develop and validate a model that considers how the active particle size, the viscoelastic parameters of the composite electrode, the adhesion between the active particle and the carbon black-binder domain, and the solid electrolyte interphase growth rate impact detachment and capacity fade. Using carbon-silicon composite electrodes as a model system, we demonstrate X-ray nano-tomography and backscatter scanning electron microscopy with sufficient resolution and contrast to segment the pore space, active particles, and carbon black-binder domain and quantify delamination as a function of cycle number. The validated model is further used to discuss how detachment and capacity fade in high-capacity materials can be minimized through materials engineering.

Quantitative Structure-Activity Relationship of Insecticidal Activity of Benzyl Ether Diamidine Derivatives

NASA Astrophysics Data System (ADS)

Zhai, Mengting; Chen, Yan; Li, Jing; Zhou, Jun

2017-12-01

The molecular electrongativity distance vector (MEDV-13) was used to describe the molecular structure of benzyl ether diamidine derivatives in this paper, Based on MEDV-13, The three-parameter (M 3, M 15, M 47) QSAR model of insecticidal activity (pIC 50) for 60 benzyl ether diamidine derivatives was constructed by leaps-and-bounds regression (LBR) . The traditional correlation coefficient (R) and the cross-validation correlation coefficient (R CV ) were 0.975 and 0.971, respectively. The robustness of the regression model was validated by Jackknife method, the correlation coefficient R were between 0.971 and 0.983. Meanwhile, the independent variables in the model were tested to be no autocorrelation. The regression results indicate that the model has good robust and predictive capabilities. The research would provide theoretical guidance for the development of new generation of anti African trypanosomiasis drugs with efficiency and low toxicity.

New mechanistically based model for predicting reduction of biosolids waste by ozonation of return activated sludge.

PubMed

Isazadeh, Siavash; Feng, Min; Urbina Rivas, Luis Enrique; Frigon, Dominic

2014-04-15

Two pilot-scale activated sludge reactors were operated for 98 days to provide the necessary data to develop and validate a new mathematical model predicting the reduction of biosolids production by ozonation of the return activated sludge (RAS). Three ozone doses were tested during the study. In addition to the pilot-scale study, laboratory-scale experiments were conducted with mixed liquor suspended solids and with pure cultures to parameterize the biomass inactivation process during exposure to ozone. The experiments revealed that biomass inactivation occurred even at the lowest doses, but that it was not associated with extensive COD solubilization. For validation, the model was used to simulate the temporal dynamics of the pilot-scale operational data. Increasing the description accuracy of the inactivation process improved the precision of the model in predicting the operational data. Copyright © 2014 Elsevier B.V. All rights reserved.

Validation of lumbar spine loading from a musculoskeletal model including the lower limbs and lumbar spine.

PubMed

Actis, Jason A; Honegger, Jasmin D; Gates, Deanna H; Petrella, Anthony J; Nolasco, Luis A; Silverman, Anne K

2018-02-08

Low back mechanics are important to quantify to study injury, pain and disability. As in vivo forces are difficult to measure directly, modeling approaches are commonly used to estimate these forces. Validation of model estimates is critical to gain confidence in modeling results across populations of interest, such as people with lower-limb amputation. Motion capture, ground reaction force and electromyographic data were collected from ten participants without an amputation (five male/five female) and five participants with a unilateral transtibial amputation (four male/one female) during trunk-pelvis range of motion trials in flexion/extension, lateral bending and axial rotation. A musculoskeletal model with a detailed lumbar spine and the legs including 294 muscles was used to predict L4-L5 loading and muscle activations using static optimization. Model estimates of L4-L5 intervertebral joint loading were compared to measured intradiscal pressures from the literature and muscle activations were compared to electromyographic signals. Model loading estimates were only significantly different from experimental measurements during trunk extension for males without an amputation and for people with an amputation, which may suggest a greater portion of L4-L5 axial load transfer through the facet joints, as facet loads are not captured by intradiscal pressure transducers. Pressure estimates between the model and previous work were not significantly different for flexion, lateral bending or axial rotation. Timing of model-estimated muscle activations compared well with electromyographic activity of the lumbar paraspinals and upper erector spinae. Validated estimates of low back loading can increase the applicability of musculoskeletal models to clinical diagnosis and treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Model-based verification and validation of the SMAP uplink processes

NASA Astrophysics Data System (ADS)

Khan, M. O.; Dubos, G. F.; Tirona, J.; Standley, S.

Model-Based Systems Engineering (MBSE) is being used increasingly within the spacecraft design community because of its benefits when compared to document-based approaches. As the complexity of projects expands dramatically with continually increasing computational power and technology infusion, the time and effort needed for verification and validation (V& V) increases geometrically. Using simulation to perform design validation with system-level models earlier in the life cycle stands to bridge the gap between design of the system (based on system-level requirements) and verifying those requirements/validating the system as a whole. This case study stands as an example of how a project can validate a system-level design earlier in the project life cycle than traditional V& V processes by using simulation on a system model. Specifically, this paper describes how simulation was added to a system model of the Soil Moisture Active-Passive (SMAP) mission's uplink process. Also discussed are the advantages and disadvantages of the methods employed and the lessons learned; which are intended to benefit future model-based and simulation-based development efforts.

Coupling of the Models of Human Physiology and Thermal Comfort

NASA Astrophysics Data System (ADS)

Pokorny, J.; Jicha, M.

2013-04-01

A coupled model of human physiology and thermal comfort was developed in Dymola/Modelica. A coupling combines a modified Tanabe model of human physiology and thermal comfort model developed by Zhang. The Coupled model allows predicting the thermal sensation and comfort of both local and overall from local boundary conditions representing ambient and personal factors. The aim of this study was to compare prediction of the Coupled model with the Fiala model prediction and experimental data. Validation data were taken from the literature, mainly from the validation manual of software Theseus-FE [1]. In the paper validation of the model for very light physical activities (1 met) indoor environment with temperatures from 12 °C up to 48 °C is presented. The Coupled model predicts mean skin temperature for cold, neutral and warm environment well. However prediction of core temperature in cold environment is inaccurate and very affected by ambient temperature. Evaluation of thermal comfort in warm environment is supplemented by skin wettedness prediction. The Coupled model is designed for non-uniform and transient environmental conditions; it is also suitable simulation of thermal comfort in vehicles cabins. The usage of the model is limited for very light physical activities up to 1.2 met only.

Irma 5.2 multi-sensor signature prediction model

NASA Astrophysics Data System (ADS)

Savage, James; Coker, Charles; Thai, Bea; Aboutalib, Omar; Chow, Anthony; Yamaoka, Neil; Kim, Charles

2007-04-01

The Irma synthetic signature prediction code is being developed by the Munitions Directorate of the Air Force Research Laboratory (AFRL/MN) to facilitate the research and development of multi-sensor systems. There are over 130 users within the Department of Defense, NASA, Department of Transportation, academia, and industry. Irma began as a high-resolution, physics-based Infrared (IR) target and background signature model for tactical weapon applications and has grown to include: a laser (or active) channel (1990), improved scene generator to support correlated frame-to-frame imagery (1992), and passive IR/millimeter wave (MMW) channel for a co-registered active/passive IR/MMW model (1994). Irma version 5.0 was released in 2000 and encompassed several upgrades to both the physical models and software; host support was expanded to Windows, Linux, Solaris, and SGI Irix platforms. In 2005, version 5.1 was released after an extensive verification and validation of an upgraded and reengineered active channel. Since 2005, the reengineering effort has focused on the Irma passive channel. Field measurements for the validation effort include the unpolarized data collection. Irma 5.2 is scheduled for release in the summer of 2007. This paper will report the validation test results of the Irma passive models and discuss the new features in Irma 5.2.

Active transportation and demand management (ATDM) trajectory-level validation state of the practice review.

DOT National Transportation Integrated Search

2016-04-15

This state of the practice review is a literature and industry review of existing vehicle trajectory datasets, vehicle trajectory collection methods, and traffic simulation model validation techniques. This report has the following four sections and ...

Derivation of a 3D pharmacophore model for the angiotensin-II site one receptor

NASA Astrophysics Data System (ADS)

Prendergast, Kristine; Adams, Kym; Greenlee, William J.; Nachbar, Robert B.; Patchett, Arthur A.; Underwood, Dennis J.

1994-10-01

A systematic search has been used to derive a hypothesis for the receptor-bound conformation of A-II antagonists at the AT1 receptor. The validity of the pharmacophore hypothesis has been tested using CoMFA, which included 50 diverse A-II antagonists, spanning four orders of magnitude in activity. The resulting cross-validated R2 of 0.64 (conventional R2 of 0.76) is indicative of a good predictive model of activity, and has been used to estimate potency for a variety of non-peptidyl antagonists. The structural model for the non-peptide has been compared with respect to the natural substrate, A-II, by generating peptide to non-peptide overlays.

Utilisation of real-scale renewable energy test facility for validation of generic wind turbine and wind power plant controller models

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

Zeni, Lorenzo; Hesselbæk, Bo; Bech, John

This article presents an example of application of a modern test facility conceived for experiments regarding the integration of renewable energy in the power system. The capabilities of the test facility are used to validate dynamic simulation models of wind power plants and their controllers. The models are based on standard and generic blocks. The successful validation of events related to the control of active power (control phenomena in <10 Hz range, including frequency control and power oscillation damping) is described, demonstrating the capabilities of the test facility and drawing the track for future work and improvements.

Neuroreceptor Activation by Vibration-Assisted Tunneling

PubMed Central

Hoehn, Ross D.; Nichols, David; Neven, Hartmut; Kais, Sabre

2015-01-01

G protein-coupled receptors (GPCRs) constitute a large family of receptor proteins that sense molecular signals on the exterior of a cell and activate signal transduction pathways within the cell. Modeling how an agonist activates such a receptor is fundamental for an understanding of a wide variety of physiological processes and it is of tremendous value for pharmacology and drug design. Inelastic electron tunneling spectroscopy (IETS) has been proposed as a model for the mechanism by which olfactory GPCRs are activated by a bound agonist. We apply this hyothesis to GPCRs within the mammalian nervous system using quantum chemical modeling. We found that non-endogenous agonists of the serotonin receptor share a particular IET spectral aspect both amongst each other and with the serotonin molecule: a peak whose intensity scales with the known agonist potencies. We propose an experiential validation of this model by utilizing lysergic acid dimethylamide (DAM-57), an ergot derivative, and its deuterated isotopologues; we also provide theoretical predictions for comparison to experiment. If validated our theory may provide new avenues for guided drug design and elevate methods of in silico potency/activity prediction. PMID:25909758

Validity of "sputtering and re-condensation" model in active screen cage plasma nitriding process

NASA Astrophysics Data System (ADS)

Saeed, A.; Khan, A. W.; Jan, F.; Abrar, M.; Khalid, M.; Zakaullah, M.

2013-05-01

The validity of "sputtering and re-condensation" model in active screen plasma nitriding for nitrogen mass transfer mechanism is investigated. The dominant species including NH, Fe-I, N2+, N-I and N2 along with Hα and Hβ lines are observed in the optical emission spectroscopy (OES) analysis. Active screen cage and dc plasma nitriding of AISI 316 stainless steel as function of treatment time is also investigated. The structure and phases composition of the nitrided layer is studied by X-ray diffraction (XRD). Surface morphology is studied by scanning electron microscopy (SEM) and hardness profile is obtained by Vicker's microhardness tester. Increasing trend in microhardness is observed in both cases but the increase in active screen plasma nitriding is about 3 times greater than that achieved by dc plasma nitriding. On the basis of metallurgical and OES observations the use of "sputtering and re-condensation" model in active screen plasma nitriding is tested.

[Multi-mathematical modelings for compatibility optimization of Jiangzhi granules].

PubMed

Yang, Ming; Zhang, Li; Ge, Yingli; Lu, Yanliu; Ji, Guang

2011-12-01

To investigate into the method of "multi activity index evaluation and combination optimized of mult-component" for Chinese herbal formulas. According to the scheme of uniform experimental design, efficacy experiment, multi index evaluation, least absolute shrinkage, selection operator (LASSO) modeling, evolutionary optimization algorithm, validation experiment, we optimized the combination of Jiangzhi granules based on the activity indexes of blood serum ALT, ALT, AST, TG, TC, HDL, LDL and TG level of liver tissues, ratio of liver tissue to body. Analytic hierarchy process (AHP) combining with criteria importance through intercriteria correlation (CRITIC) for multi activity index evaluation was more reasonable and objective, it reflected the information of activity index's order and objective sample data. LASSO algorithm modeling could accurately reflect the relationship between different combination of Jiangzhi granule and the activity comprehensive indexes. The optimized combination of Jiangzhi granule showed better values of the activity comprehensive indexed than the original formula after the validation experiment. AHP combining with CRITIC can be used for multi activity index evaluation and LASSO algorithm, it is suitable for combination optimized of Chinese herbal formulas.

Enhancing students' learning in problem based learning: validation of a self-assessment scale for active learning and critical thinking.

PubMed

Khoiriyah, Umatul; Roberts, Chris; Jorm, Christine; Van der Vleuten, C P M

2015-08-26

Problem based learning (PBL) is a powerful learning activity but fidelity to intended models may slip and student engagement wane, negatively impacting learning processes, and outcomes. One potential solution to solve this degradation is by encouraging self-assessment in the PBL tutorial. Self-assessment is a central component of the self-regulation of student learning behaviours. There are few measures to investigate self-assessment relevant to PBL processes. We developed a Self-assessment Scale on Active Learning and Critical Thinking (SSACT) to address this gap. We wished to demonstrated evidence of its validity in the context of PBL by exploring its internal structure. We used a mixed methods approach to scale development. We developed scale items from a qualitative investigation, literature review, and consideration of previous existing tools used for study of the PBL process. Expert review panels evaluated its content; a process of validation subsequently reduced the pool of items. We used structural equation modelling to undertake a confirmatory factor analysis (CFA) of the SSACT and coefficient alpha. The 14 item SSACT consisted of two domains "active learning" and "critical thinking." The factorial validity of SSACT was evidenced by all items loading significantly on their expected factors, a good model fit for the data, and good stability across two independent samples. Each subscale had good internal reliability (>0.8) and strongly correlated with each other. The SSACT has sufficient evidence of its validity to support its use in the PBL process to encourage students to self-assess. The implementation of the SSACT may assist students to improve the quality of their learning in achieving PBL goals such as critical thinking and self-directed learning.

Decoding Spontaneous Emotional States in the Human Brain

PubMed Central

Kragel, Philip A.; Knodt, Annchen R.; Hariri, Ahmad R.; LaBar, Kevin S.

2016-01-01

Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems. PMID:27627738

Three-dimensional quantitative structure-activity relationship studies on c-Src inhibitors based on different docking methods.

PubMed

Bairy, Santhosh Kumar; Suneel Kumar, B V S; Bhalla, Joseph Uday Tej; Pramod, A B; Ravikumar, Muttineni

2009-04-01

c-Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on quinazolin derivatives inhibiting c-Src kinase. Molecular field analysis (MFA) models with four different alignment techniques, namely, GLIDE, GOLD, LIGANDFIT and Least squares based methods were developed. glide based MFA model showed better results (Leave one out cross validation correlation coefficient r(2)(cv) = 0.923 and non-cross validation correlation coefficient r(2)= 0.958) when compared with other models. These results help us to understand the nature of descriptors required for activity of these compounds and thereby provide guidelines to design novel and potent c-Src kinase inhibitors.

Toward accurate and valid estimates of greenhouse gas reductions from bikeway projects.

DOT National Transportation Integrated Search

2016-07-31

We sought to accurately and validly model emissions generating and activities, including changes in traveler behavior and thus GHG : emissions in the wake of bikeway projects. We wanted the results to be applicable to practice and policy in Californi...

Development and Validation of a Computational Model for Androgen Receptor Activity

EPA Science Inventory

Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can mo...

The use of docking-based comparative intermolecular contacts analysis to identify optimal docking conditions within glucokinase and to discover of new GK activators

NASA Astrophysics Data System (ADS)

Taha, Mutasem O.; Habash, Maha; Khanfar, Mohammad A.

2014-05-01

Glucokinase (GK) is involved in normal glucose homeostasis and therefore it is a valid target for drug design and discovery efforts. GK activators (GKAs) have excellent potential as treatments of hyperglycemia and diabetes. The combined recent interest in GKAs, together with docking limitations and shortages of docking validation methods prompted us to use our new 3D-QSAR analysis, namely, docking-based comparative intermolecular contacts analysis (dbCICA), to validate docking configurations performed on a group of GKAs within GK binding site. dbCICA assesses the consistency of docking by assessing the correlation between ligands' affinities and their contacts with binding site spots. Optimal dbCICA models were validated by receiver operating characteristic curve analysis and comparative molecular field analysis. dbCICA models were also converted into valid pharmacophores that were used as search queries to mine 3D structural databases for new GKAs. The search yielded several potent bioactivators that experimentally increased GK bioactivity up to 7.5-folds at 10 μM.

The Influence of Neck Muscle Activation on Head and Neck Injuries of Occupants in Frontal Impacts.

PubMed

Li, Fan; Lu, Ronggui; Hu, Wei; Li, Honggeng; Hu, Shiping; Hu, Jiangzhong; Wang, Haibin; Xie, He

2018-01-01

The aim of the present paper was to study the influence of neck muscle activation on head and neck injuries of vehicle occupants in frontal impacts. A mixed dummy-human finite element model was developed to simulate a frontal impact. The head-neck part of a Hybrid III dummy model was replaced by a well-validated head-neck FE model with passive and active muscle characteristics. The mixed dummy-human FE model was validated by 15 G frontal volunteer tests conducted in the Naval Biodynamics Laboratory. The effects of neck muscle activation on the head dynamic responses and neck injuries of occupants in three frontal impact intensities, low speed (10 km/h), medium speed (30 km/h), and high speed (50 km/h), were studied. The results showed that the mixed dummy-human FE model has good biofidelity. The activation of neck muscles can not only lower the head resultant acceleration under different impact intensities and the head angular acceleration in medium- and high-speed impacts, thereby reducing the risks of head injury, but also protect the neck from injury in low-speed impacts.

Physiological time model of Scirpophaga incertulas (Lepidoptera: Pyralidae) in rice in Guandong Province, People's Republic of China.

PubMed

Stevenson, Douglass E; Feng, Ge; Zhang, Runjie; Harris, Marvin K

2005-08-01

Scirpophaga incertulas (Walker) (Lepidoptera: Pyralidae) is autochthonous and monophagous on rice, Oryza spp., which favors the development of a physiological time model using degree-days (degrees C) to establish a well defined window during which adults will be present in fields. Model development of S. incertulas adult flight phenology used climatic data and historical field observations of S. incertulas from 1962 through 1988. Analysis of variance was used to evaluate 5,203 prospective models with starting dates ranging from 1 January (day 1) to 30 April (day 121) and base temperatures ranging from -3 through 18.5 degrees C. From six candidate models, which shared the lowest standard deviation of prediction error, a model with a base temperature of 10 degrees C starting on 19 January was selected for validation. Validation with linear regression evaluated the differences between predicted and observed events and showed the model consistently predicted phenological events of 10 to 90% cumulative flight activity within a 3.5-d prediction interval regarded as acceptable for pest management decision making. The degree-day phenology model developed here is expected to find field application in Guandong Province. Expansion to other areas of rice production will require field validation. We expect the degree-day characterization of the activity period will remain essentially intact, but the start day may vary based on climate and geographic location. The development and validation of the phenology model of the S. incertulas by using procedures originally developed for pecan nut casebearer, Acrobasis nuxvorella Neunzig, shows the fungibility of this approach to developing prediction models for other insects.

Experimental Errors in QSAR Modeling Sets: What We Can Do and What We Cannot Do.

PubMed

Zhao, Linlin; Wang, Wenyi; Sedykh, Alexander; Zhu, Hao

2017-06-30

Numerous chemical data sets have become available for quantitative structure-activity relationship (QSAR) modeling studies. However, the quality of different data sources may be different based on the nature of experimental protocols. Therefore, potential experimental errors in the modeling sets may lead to the development of poor QSAR models and further affect the predictions of new compounds. In this study, we explored the relationship between the ratio of questionable data in the modeling sets, which was obtained by simulating experimental errors, and the QSAR modeling performance. To this end, we used eight data sets (four continuous endpoints and four categorical endpoints) that have been extensively curated both in-house and by our collaborators to create over 1800 various QSAR models. Each data set was duplicated to create several new modeling sets with different ratios of simulated experimental errors (i.e., randomizing the activities of part of the compounds) in the modeling process. A fivefold cross-validation process was used to evaluate the modeling performance, which deteriorates when the ratio of experimental errors increases. All of the resulting models were also used to predict external sets of new compounds, which were excluded at the beginning of the modeling process. The modeling results showed that the compounds with relatively large prediction errors in cross-validation processes are likely to be those with simulated experimental errors. However, after removing a certain number of compounds with large prediction errors in the cross-validation process, the external predictions of new compounds did not show improvement. Our conclusion is that the QSAR predictions, especially consensus predictions, can identify compounds with potential experimental errors. But removing those compounds by the cross-validation procedure is not a reasonable means to improve model predictivity due to overfitting.

Experimental Errors in QSAR Modeling Sets: What We Can Do and What We Cannot Do

PubMed Central

2017-01-01

Numerous chemical data sets have become available for quantitative structure–activity relationship (QSAR) modeling studies. However, the quality of different data sources may be different based on the nature of experimental protocols. Therefore, potential experimental errors in the modeling sets may lead to the development of poor QSAR models and further affect the predictions of new compounds. In this study, we explored the relationship between the ratio of questionable data in the modeling sets, which was obtained by simulating experimental errors, and the QSAR modeling performance. To this end, we used eight data sets (four continuous endpoints and four categorical endpoints) that have been extensively curated both in-house and by our collaborators to create over 1800 various QSAR models. Each data set was duplicated to create several new modeling sets with different ratios of simulated experimental errors (i.e., randomizing the activities of part of the compounds) in the modeling process. A fivefold cross-validation process was used to evaluate the modeling performance, which deteriorates when the ratio of experimental errors increases. All of the resulting models were also used to predict external sets of new compounds, which were excluded at the beginning of the modeling process. The modeling results showed that the compounds with relatively large prediction errors in cross-validation processes are likely to be those with simulated experimental errors. However, after removing a certain number of compounds with large prediction errors in the cross-validation process, the external predictions of new compounds did not show improvement. Our conclusion is that the QSAR predictions, especially consensus predictions, can identify compounds with potential experimental errors. But removing those compounds by the cross-validation procedure is not a reasonable means to improve model predictivity due to overfitting. PMID:28691113

Assessing the Validity of a Stage Measure on Physical Activity in a Population-Based Sample of Individuals with Type 1 or Type 2 Diabetes

ERIC Educational Resources Information Center

Plotnikoff, Ronald C.; Lippke, Sonia; Reinbold-Matthews, Melissa; Courneya, Kerry S.; Karunamuni, Nandini; Sigal, Ronald J.; Birkett, Nicholas

2007-01-01

This study was designed to test the validity of a transtheoretical model's physical activity (PA) stage measure with intention and different intensities of behavior in a large population-based sample of adults living with diabetes (Type 1 diabetes, n = 697; Type 2 diabetes, n = 1,614) and examine different age groups. The overall…

Study of the validity of a job-exposure matrix for the job strain model factors: an update and a study of changes over time.

PubMed

Niedhammer, Isabelle; Milner, Allison; LaMontagne, Anthony D; Chastang, Jean-François

2018-03-08

The objectives of the study were to construct a job-exposure matrix (JEM) for psychosocial work factors of the job strain model, to evaluate its validity, and to compare the results over time. The study was based on national representative data of the French working population with samples of 46,962 employees (2010 SUMER survey) and 24,486 employees (2003 SUMER survey). Psychosocial work factors included the job strain model factors (Job Content Questionnaire): psychological demands, decision latitude, social support, job strain and iso-strain. Job title was defined by three variables: occupation and economic activity coded using standard classifications, and company size. A JEM was constructed using a segmentation method (Classification and Regression Tree-CART) and cross-validation. The best quality JEM was found using occupation and company size for social support. For decision latitude and psychological demands, there was not much difference using occupation and company size with or without economic activity. The validity of the JEM estimates was higher for decision latitude, job strain and iso-strain, and lower for social support and psychological demands. Differential changes over time were observed for psychosocial work factors according to occupation, economic activity and company size. This study demonstrated that company size in addition to occupation may improve the validity of JEMs for psychosocial work factors. These matrices may be time-dependent and may need to be updated over time. More research is needed to assess the validity of JEMs given that these matrices may be able to provide exposure assessments to study a range of health outcomes.

Validity of hip-mounted uniaxial accelerometry with heart-rate monitoring vs. triaxial accelerometry in the assessment of free-living energy expenditure in young children: the IDEFICS Validation Study.

PubMed

Ojiambo, Robert; Konstabel, Kenn; Veidebaum, Toomas; Reilly, John; Verbestel, Vera; Huybrechts, Inge; Sioen, Isabelle; Casajús, José A; Moreno, Luis A; Vicente-Rodriguez, German; Bammann, Karin; Tubic, Bojan M; Marild, Staffan; Westerterp, Klaas; Pitsiladis, Yannis P

2012-11-01

One of the aims of Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) validation study is to validate field measures of physical activity (PA) and energy expenditure (EE) in young children. This study compared the validity of uniaxial accelerometry with heart-rate (HR) monitoring vs. triaxial accelerometry against doubly labeled water (DLW) criterion method for assessment of free-living EE in young children. Forty-nine European children (25 female, 24 male) aged 4-10 yr (mean age: 6.9 ± 1.5 yr) were assessed by uniaxial ActiTrainer with HR, uniaxial 3DNX, and triaxial 3DNX accelerometry. Total energy expenditure (TEE) was estimated using DLW over a 1-wk period. The longitudinal axis of both devices and triaxial 3DNX counts per minute (CPM) were significantly (P < 0.05) associated with physical activity level (PAL; r = 0.51 ActiTrainer, r = 0.49 uniaxial-3DNX, and r = 0.42 triaxial Σ3DNX). Eight-six percent of the variance in TEE could be predicted by a model combining body mass (partial r(2) = 71%; P < 0.05), CPM-ActiTrainer (partial r(2) = 11%; P < 0.05), and difference between HR at moderate and sedentary activities (ModHR - SedHR) (partial r(2) = 4%; P < 0.05). The SE of TEE estimate for ActiTrainer and 3DNX models ranged from 0.44 to 0.74 MJ/days or ∼7-11% of the average TEE. The SE of activity-induced energy expenditure (AEE) model estimates ranged from 0.38 to 0.57 MJ/day or 24-26% of the average AEE. It is concluded that the comparative validity of hip-mounted uniaxial and triaxial accelerometers for assessing PA and EE is similar.

Multivariate analysis of PRISMA optimized TLC image for predicting antioxidant activity and identification of contributing compounds from Pereskia bleo.

PubMed

Sharif, K M; Rahman, M M; Azmir, J; Khatib, A; Sabina, E; Shamsudin, S H; Zaidul, I S M

2015-12-01

Multivariate analysis of thin-layer chromatography (TLC) images was modeled to predict antioxidant activity of Pereskia bleo leaves and to identify the contributing compounds of the activity. TLC was developed in optimized mobile phase using the 'PRISMA' optimization method and the image was then converted to wavelet signals and imported for multivariate analysis. An orthogonal partial least square (OPLS) model was developed consisting of a wavelet-converted TLC image and 2,2-diphynyl-picrylhydrazyl free radical scavenging activity of 24 different preparations of P. bleo as the x- and y-variables, respectively. The quality of the constructed OPLS model (1 + 1 + 0) with one predictive and one orthogonal component was evaluated by internal and external validity tests. The validated model was then used to identify the contributing spot from the TLC plate that was then analyzed by GC-MS after trimethylsilyl derivatization. Glycerol and amine compounds were mainly found to contribute to the antioxidant activity of the sample. An alternative method to predict the antioxidant activity of a new sample of P. bleo leaves has been developed. Copyright © 2015 John Wiley & Sons, Ltd.

An Overview of NASA's IM&S Verification and Validation Process Plan and Specification for Space Exploration

NASA Technical Reports Server (NTRS)

Gravitz, Robert M.; Hale, Joseph

2006-01-01

NASA's Exploration Systems Mission Directorate (ESMD) is implementing a management approach for modeling and simulation (M&S) that will provide decision-makers information on the model's fidelity, credibility, and quality. This information will allow the decision-maker to understand the risks involved in using a model's results in the decision-making process. This presentation will discuss NASA's approach for verification and validation (V&V) of its models or simulations supporting space exploration. This presentation will describe NASA's V&V process and the associated M&S verification and validation (V&V) activities required to support the decision-making process. The M&S V&V Plan and V&V Report templates for ESMD will also be illustrated.

Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure.

PubMed

Zhu, Hao; Martin, Todd M; Ye, Lin; Sedykh, Alexander; Young, Douglas M; Tropsha, Alexander

2009-12-01

Few quantitative structure-activity relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity end points. In this study, a comprehensive data set of 7385 compounds with their most conservative lethal dose (LD(50)) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire data set was selected that included all 3472 compounds used in TOPKAT's training set. The remaining 3913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R(2) of linear regression between actual and predicted LD(50) values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R(2) ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD(50) for every compound using all five models. The consensus models afforded higher prediction accuracy for the external validation data set with the higher coverage as compared to individual constituent models. The validated consensus LD(50) models developed in this study can be used as reliable computational predictors of in vivo acute toxicity.

The localization of focal heart activity via body surface potential measurements: tests in a heterogeneous torso phantom

NASA Astrophysics Data System (ADS)

Wetterling, F.; Liehr, M.; Schimpf, P.; Liu, H.; Haueisen, J.

2009-09-01

The non-invasive localization of focal heart activity via body surface potential measurements (BSPM) could greatly benefit the understanding and treatment of arrhythmic heart diseases. However, the in vivo validation of source localization algorithms is rather difficult with currently available measurement techniques. In this study, we used a physical torso phantom composed of different conductive compartments and seven dipoles, which were placed in the anatomical position of the human heart in order to assess the performance of the Recursively Applied and Projected Multiple Signal Classification (RAP-MUSIC) algorithm. Electric potentials were measured on the torso surface for single dipoles with and without further uncorrelated or correlated dipole activity. The localization error averaged 11 ± 5 mm over 22 dipoles, which shows the ability of RAP-MUSIC to distinguish an uncorrelated dipole from surrounding sources activity. For the first time, real computational modelling errors could be included within the validation procedure due to the physically modelled heterogeneities. In conclusion, the introduced heterogeneous torso phantom can be used to validate state-of-the-art algorithms under nearly realistic measurement conditions.

Relations Between Autonomous Motivation and Leisure-Time Physical Activity Participation: The Mediating Role of Self-Regulation Techniques.

PubMed

Nurmi, Johanna; Hagger, Martin S; Haukkala, Ari; Araújo-Soares, Vera; Hankonen, Nelli

2016-04-01

This study tested the predictive validity of a multitheory process model in which the effect of autonomous motivation from self-determination theory on physical activity participation is mediated by the adoption of self-regulatory techniques based on control theory. Finnish adolescents (N = 411, aged 17-19) completed a prospective survey including validated measures of the predictors and physical activity, at baseline and after one month (N = 177). A subsample used an accelerometer to objectively measure physical activity and further validate the physical activity self-report assessment tool (n = 44). Autonomous motivation statistically significantly predicted action planning, coping planning, and self-monitoring. Coping planning and self-monitoring mediated the effect of autonomous motivation on physical activity, although self-monitoring was the most prominent. Controlled motivation had no effect on self-regulation techniques or physical activity. Developing interventions that support autonomous motivation for physical activity may foster increased engagement in self-regulation techniques and positively affect physical activity behavior.

Model-Based Verification and Validation of the SMAP Uplink Processes

NASA Technical Reports Server (NTRS)

Khan, M. Omair; Dubos, Gregory F.; Tirona, Joseph; Standley, Shaun

2013-01-01

This case study stands as an example of how a project can validate a system-level design earlier in the project life cycle than traditional V&V processes by using simulation on a system model. Specifically, this paper describes how simulation was added to a system model of the Soil Moisture Active-Passive (SMAP) mission's uplink process.Also discussed are the advantages and disadvantages of the methods employed and the lessons learned; which are intended to benefit future model-based and simulation-based V&V development efforts.

Innovative learning model for improving students’ argumentation skill and concept understanding on science

NASA Astrophysics Data System (ADS)

Nafsiati Astuti, Rini

2018-04-01

Argumentation skill is the ability to compose and maintain arguments consisting of claims, supports for evidence, and strengthened-reasons. Argumentation is an important skill student needs to face the challenges of globalization in the 21st century. It is not an ability that can be developed by itself along with the physical development of human, but it must be developed under nerve like process, giving stimulus so as to require a person to be able to argue. Therefore, teachers should develop students’ skill of arguing in science learning in the classroom. The purpose of this study is to obtain an innovative learning model that are valid in terms of content and construct in improving the skills of argumentation and concept understanding of junior high school students. The assessment of content validity and construct validity was done through Focus Group Discussion (FGD), using the content and construct validation sheet, book model, learning video, and a set of learning aids for one meeting. Assessment results from 3 (three) experts showed that the learning model developed in the category was valid. The validity itself shows that the developed learning model has met the content requirement, the student needs, state of the art, strong theoretical and empirical foundation and construct validity, which has a connection of syntax stages and components of learning model so that it can be applied in the classroom activities

Design of Novel Chemotherapeutic Agents Targeting Checkpoint Kinase 1 Using 3D-QSAR Modeling and Molecular Docking Methods.

PubMed

Balupuri, Anand; Balasubramanian, Pavithra K; Cho, Seung J

2016-01-01

Checkpoint kinase 1 (Chk1) has emerged as a potential therapeutic target for design and development of novel anticancer drugs. Herein, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses on a series of diazacarbazoles to design potent Chk1 inhibitors. 3D-QSAR models were developed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Docking studies were performed using AutoDock. The best CoMFA and CoMSIA models exhibited cross-validated correlation coefficient (q2) values of 0.631 and 0.585, and non-cross-validated correlation coefficient (r2) values of 0.933 and 0.900, respectively. CoMFA and CoMSIA models showed reasonable external predictabilities (r2 pred) of 0.672 and 0.513, respectively. A satisfactory performance in the various internal and external validation techniques indicated the reliability and robustness of the best model. Docking studies were performed to explore the binding mode of inhibitors inside the active site of Chk1. Molecular docking revealed that hydrogen bond interactions with Lys38, Glu85 and Cys87 are essential for Chk1 inhibitory activity. The binding interaction patterns observed during docking studies were complementary to 3D-QSAR results. Information obtained from the contour map analysis was utilized to design novel potent Chk1 inhibitors. Their activities and binding affinities were predicted using the derived model and docking studies. Designed inhibitors were proposed as potential candidates for experimental synthesis.

Is the Acute NMDA Receptor Hypofunction a Valid Model of Schizophrenia?

PubMed Central

Adell, Albert; Jiménez-Sánchez, Laura; López-Gil, Xavier; Romón, Tamara

2012-01-01

Several genetic, neurodevelopmental, and pharmacological animal models of schizophrenia have been established. This short review examines the validity of one of the most used pharmacological model of the illness, ie, the acute administration of N-methyl-D-aspartate (NMDA) receptor antagonists in rodents. In some cases, data on chronic or prenatal NMDA receptor antagonist exposure have been introduced for comparison. The face validity of acute NMDA receptor blockade is granted inasmuch as hyperlocomotion and stereotypies induced by phencyclidine, ketamine, and MK-801 are regarded as a surrogate for the positive symptoms of schizophrenia. In addition, the loss of parvalbumin-containing cells (which is one of the most compelling finding in postmortem schizophrenia brain) following NMDA receptor blockade adds construct validity to this model. However, the lack of changes in glutamic acid decarboxylase (GAD67) is at variance with human studies. It is possible that changes in GAD67 are more reflective of the neurodevelopmental condition of schizophrenia. Finally, the model also has predictive validity, in that its behavioral and transmitter activation in rodents are responsive to antipsychotic treatment. Overall, although not devoid of drawbacks, the acute administration of NMDA receptor antagonists can be considered as a good model of schizophrenia bearing a satisfactory degree of validity. PMID:21965469

Intrinsic Motivation and Engagement as "Active Ingredients" in Garden-Based Education: Examining Models and Measures Derived from Self-Determination Theory

ERIC Educational Resources Information Center

Skinner, Ellen A.; Chi, Una

2012-01-01

Building on self-determination theory, this study presents a model of intrinsic motivation and engagement as "active ingredients" in garden-based education. The model was used to create reliable and valid measures of key constructs, and to guide the empirical exploration of motivational processes in garden-based learning. Teacher- and…

Design and experimental validation of a flutter suppression controller for the active flexible wing

NASA Technical Reports Server (NTRS)

Waszak, Martin R.; Srinathkumar, S.

1992-01-01

The synthesis and experimental validation of an active flutter suppression controller for the Active Flexible Wing wind tunnel model is presented. The design is accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and extensive simulation based analysis. The design approach uses a fundamental understanding of the flutter mechanism to formulate a simple controller structure to meet stringent design specifications. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite modeling errors in predicted flutter dynamic pressure and flutter frequency. The flutter suppression controller was also successfully operated in combination with another controller to perform flutter suppression during rapid rolling maneuvers.

A quantitative structure-activity relationship to predict efficacy of granular activated carbon adsorption to control emerging contaminants.

PubMed

Kennicutt, A R; Morkowchuk, L; Krein, M; Breneman, C M; Kilduff, J E

2016-08-01

A quantitative structure-activity relationship was developed to predict the efficacy of carbon adsorption as a control technology for endocrine-disrupting compounds, pharmaceuticals, and components of personal care products, as a tool for water quality professionals to protect public health. Here, we expand previous work to investigate a broad spectrum of molecular descriptors including subdivided surface areas, adjacency and distance matrix descriptors, electrostatic partial charges, potential energy descriptors, conformation-dependent charge descriptors, and Transferable Atom Equivalent (TAE) descriptors that characterize the regional electronic properties of molecules. We compare the efficacy of linear (Partial Least Squares) and non-linear (Support Vector Machine) machine learning methods to describe a broad chemical space and produce a user-friendly model. We employ cross-validation, y-scrambling, and external validation for quality control. The recommended Support Vector Machine model trained on 95 compounds having 23 descriptors offered a good balance between good performance statistics, low error, and low probability of over-fitting while describing a wide range of chemical features. The cross-validated model using a log-uptake (qe) response calculated at an aqueous equilibrium concentration (Ce) of 1 μM described the training dataset with an r(2) of 0.932, had a cross-validated r(2) of 0.833, and an average residual of 0.14 log units.

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

PubMed Central

Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A.; Hopkinson, Nicholas S.; Polkey, Michael I.; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I.; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A.; Karlsson, Niklas

2015-01-01

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity. Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. PMID:26022965

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease.

PubMed

Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A; Hopkinson, Nicholas S; Polkey, Michael I; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A; Karlsson, Niklas; Garcia-Aymerich, Judith

2015-10-01

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. Copyright ©ERS 2015.

Model-Based Design of Air Traffic Controller-Automation Interaction

NASA Technical Reports Server (NTRS)

Romahn, Stephan; Callantine, Todd J.; Palmer, Everett A.; Null, Cynthia H. (Technical Monitor)

1998-01-01

A model of controller and automation activities was used to design the controller-automation interactions necessary to implement a new terminal area air traffic management concept. The model was then used to design a controller interface that provides the requisite information and functionality. Using data from a preliminary study, the Crew Activity Tracking System (CATS) was used to help validate the model as a computational tool for describing controller performance.

Multiple QSAR models, pharmacophore pattern and molecular docking analysis for anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues

NASA Astrophysics Data System (ADS)

Masand, Vijay H.; El-Sayed, Nahed N. E.; Bambole, Mukesh U.; Quazi, Syed A.

2018-04-01

Multiple discrete quantitative structure-activity relationships (QSARs) models were constructed for the anticancer activity of α, β-unsaturated carbonyl-based compounds, oxime and oxime ether analogues with a variety of substituents like sbnd Br, sbnd OH, -OMe, etc. at different positions. A big pool of descriptors was considered for QSAR model building. Genetic algorithm (GA), available in QSARINS-Chem, was executed to choose optimum number and set of descriptors to create the multi-linear regression equations for a dataset of sixty-nine compounds. The newly developed five parametric models were subjected to exhaustive internal and external validation along with Y-scrambling using QSARINS-Chem, according to the OECD principles for QSAR model validation. The models were built using easily interpretable descriptors and accepted after confirming statistically robustness with high external predictive ability. The five parametric models were found to have R2 = 0.80 to 0.86, R2ex = 0.75 to 0.84, and CCCex = 0.85 to 0.90. The models indicate that frequency of nitrogen and oxygen atoms separated by five bonds from each other and internal electronic environment of the molecule have correlation with the anticancer activity.

Influence of thermodynamic parameter in Lanosterol 14alpha-demethylase inhibitory activity as antifungal agents: a QSAR approach.

PubMed

Vasanthanathan, Poongavanam; Lakshmi, Manickavasagam; Arockia Babu, Marianesan; Kaskhedikar, Sathish Gopalrao

2006-06-01

A quantitative structure activity relationship, Hansch approach was applied on twenty compounds of chromene derivatives as Lanosterol 14alpha-demethylase inhibitory activity against eight fungal organisms. Various physicochemical descriptors and reported minimum inhibitory concentration values of different fungal organisms were used as independent variables and dependent variable respectively. The best models for eight different fungal organisms were first validated by leave-one-out cross validation procedure. It was revealed that thermodynamic parameters were found to have overall significant correlationship with anti fungal activity and these studies provide an insight to design new molecules.

Reduced density gradient as a novel approach for estimating QSAR descriptors, and its application to 1, 4-dihydropyridine derivatives with potential antihypertensive effects.

PubMed

Jardínez, Christiaan; Vela, Alberto; Cruz-Borbolla, Julián; Alvarez-Mendez, Rodrigo J; Alvarado-Rodríguez, José G

2016-12-01

The relationship between the chemical structure and biological activity (log IC 50 ) of 40 derivatives of 1,4-dihydropyridines (DHPs) was studied using density functional theory (DFT) and multiple linear regression analysis methods. With the aim of improving the quantitative structure-activity relationship (QSAR) model, the reduced density gradient s( r) of the optimized equilibrium geometries was used as a descriptor to include weak non-covalent interactions. The QSAR model highlights the correlation between the log IC 50 with highest molecular orbital energy (E HOMO ), molecular volume (V), partition coefficient (log P), non-covalent interactions NCI(H4-G) and the dual descriptor [Δf(r)]. The model yielded values of R 2 =79.57 and Q 2 =69.67 that were validated with the next four internal analytical validations DK=0.076, DQ=-0.006, R P =0.056, and R N =0.000, and the external validation Q 2 boot =64.26. The QSAR model found can be used to estimate biological activity with high reliability in new compounds based on a DHP series. Graphical abstract The good correlation between the log IC 50 with the NCI (H4-G) estimated by the reduced density gradient approach of the DHP derivatives.

Mind the Noise When Identifying Computational Models of Cognition from Brain Activity.

PubMed

Kolossa, Antonio; Kopp, Bruno

2016-01-01

The aim of this study was to analyze how measurement error affects the validity of modeling studies in computational neuroscience. A synthetic validity test was created using simulated P300 event-related potentials as an example. The model space comprised four computational models of single-trial P300 amplitude fluctuations which differed in terms of complexity and dependency. The single-trial fluctuation of simulated P300 amplitudes was computed on the basis of one of the models, at various levels of measurement error and at various numbers of data points. Bayesian model selection was performed based on exceedance probabilities. At very low numbers of data points, the least complex model generally outperformed the data-generating model. Invalid model identification also occurred at low levels of data quality and under low numbers of data points if the winning model's predictors were closely correlated with the predictors from the data-generating model. Given sufficient data quality and numbers of data points, the data-generating model could be correctly identified, even against models which were very similar to the data-generating model. Thus, a number of variables affects the validity of computational modeling studies, and data quality and numbers of data points are among the main factors relevant to the issue. Further, the nature of the model space (i.e., model complexity, model dependency) should not be neglected. This study provided quantitative results which show the importance of ensuring the validity of computational modeling via adequately prepared studies. The accomplishment of synthetic validity tests is recommended for future applications. Beyond that, we propose to render the demonstration of sufficient validity via adequate simulations mandatory to computational modeling studies.

An animal model of panic vulnerability with chronic disinhibition of the dorsomedial/perifornical hypothalamus

PubMed Central

Johnson, Philip L.; Shekhar, Anantha

2013-01-01

Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as sodium lactate infusions or hypercapnia induction. Here we review a model of panic vulnerability in rats involving chronic inhibition of GABAergic tone in the dorsomedial/ perifornical hypothalamic (DMH/PeF) region that produces enhanced anxiety and freezing responses in fearful situations, as well as a vulnerability to displaying acute panic-like increases in cardioexcitation, respiration activity and “flight” associated behavior following subthreshold interoceptive stimuli that do not elicit panic responses in control rats. This model of panic vulnerability was developed over 15 years ago and has provided an excellent preclinical model with robust face, predictive and construct validity. The model recapitulates many of the phenotypics features of panic attacks associated with human panic disorder (face validity) including greater sensitivity to panicogenic stimuli demonstrated by sudden onset of anxiety and autonomic activation following an administration of a sub-threshold (i.e., do not usually induce panic in healthy subjects) stimulus such as sodium lactate, CO2, or yohimbine. The construct validity is supported by several key findings; DMH/PeF neurons regulate behavioral and autonomic components of a normal adaptive panic response, as well as being implicated in eliciting panic-like responses in humans. Additionally, Patients with PD have deficits in central GABA activity and pharmacological restoration of central GABA activity prevents panic attacks, consistent with this model. The model’s predictive validity is demonstrated by not only showing panic responses to several panic-inducing agents that elicit panic in patients with PD, but also by the positive therapeutic responses to clinically used agents such as alprazolam and antidepressants that attenuate panic attacks in patients. More importantly, this model has been utilized to discover novel drugs such as group II metabotropic glutamate agonists and a new class of translocator protein enhancers of GABA, both of which subsequently showed anti-panic properties in clinical trials. All of these data suggest that this preparation provides a strong preclinical model of some forms of human panic disorders. PMID:22484112

Issues and approach to develop validated analysis tools for hypersonic flows: One perspective

NASA Technical Reports Server (NTRS)

Deiwert, George S.

1993-01-01

Critical issues concerning the modeling of low density hypervelocity flows where thermochemical nonequilibrium effects are pronounced are discussed. Emphasis is on the development of validated analysis tools, and the activity in the NASA Ames Research Center's Aerothermodynamics Branch is described. Inherent in the process is a strong synergism between ground test and real gas computational fluid dynamics (CFD). Approaches to develop and/or enhance phenomenological models and incorporate them into computational flowfield simulation codes are discussed. These models were partially validated with experimental data for flows where the gas temperature is raised (compressive flows). Expanding flows, where temperatures drop, however, exhibit somewhat different behavior. Experimental data for these expanding flow conditions is sparse and reliance must be made on intuition and guidance from computational chemistry to model transport processes under these conditions. Ground based experimental studies used to provide necessary data for model development and validation are described. Included are the performance characteristics of high enthalpy flow facilities, such as shock tubes and ballistic ranges.

Issues and approach to develop validated analysis tools for hypersonic flows: One perspective

NASA Technical Reports Server (NTRS)

Deiwert, George S.

1992-01-01

Critical issues concerning the modeling of low-density hypervelocity flows where thermochemical nonequilibrium effects are pronounced are discussed. Emphasis is on the development of validated analysis tools. A description of the activity in the Ames Research Center's Aerothermodynamics Branch is also given. Inherent in the process is a strong synergism between ground test and real-gas computational fluid dynamics (CFD). Approaches to develop and/or enhance phenomenological models and incorporate them into computational flow-field simulation codes are discussed. These models have been partially validated with experimental data for flows where the gas temperature is raised (compressive flows). Expanding flows, where temperatures drop, however, exhibit somewhat different behavior. Experimental data for these expanding flow conditions are sparse; reliance must be made on intuition and guidance from computational chemistry to model transport processes under these conditions. Ground-based experimental studies used to provide necessary data for model development and validation are described. Included are the performance characteristics of high-enthalpy flow facilities, such as shock tubes and ballistic ranges.

Towards policy relevant environmental modeling: contextual validity and pragmatic models

USGS Publications Warehouse

Miles, Scott B.

2000-01-01

"What makes for a good model?" In various forms, this question is a question that, undoubtedly, many people, businesses, and institutions ponder with regards to their particular domain of modeling. One particular domain that is wrestling with this question is the multidisciplinary field of environmental modeling. Examples of environmental models range from models of contaminated ground water flow to the economic impact of natural disasters, such as earthquakes. One of the distinguishing claims of the field is the relevancy of environmental modeling to policy and environment-related decision-making in general. A pervasive view by both scientists and decision-makers is that a "good" model is one that is an accurate predictor. Thus, determining whether a model is "accurate" or "correct" is done by comparing model output to empirical observations. The expected outcome of this process, usually referred to as "validation" or "ground truthing," is a stamp on the model in question of "valid" or "not valid" that serves to indicate whether or not the model will be reliable before it is put into service in a decision-making context. In this paper, I begin by elaborating on the prevailing view of model validation and why this view must change. Drawing from concepts coming out of the studies of science and technology, I go on to propose a contextual view of validity that can overcome the problems associated with "ground truthing" models as an indicator of model goodness. The problem of how we talk about and determine model validity has much to do about how we perceive the utility of environmental models. In the remainder of the paper, I argue that we should adopt ideas of pragmatism in judging what makes for a good model and, in turn, developing good models. From such a perspective of model goodness, good environmental models should facilitate communication, convey—not bury or "eliminate"—uncertainties, and, thus, afford the active building of consensus decisions, instead of promoting passive or self-righteous decisions.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Description and Validation of a Dynamical Systems Model of Presynaptic Serotonin Function: Genetic Variation, Brain Activation and Impulsivity

PubMed Central

Stoltenberg, Scott F.; Nag, Parthasarathi

2010-01-01

Despite more than a decade of empirical work on the role of genetic polymorphisms in the serotonin system on behavior, the details across levels of analysis are not well understood. We describe a mathematical model of the genetic control of presynaptic serotonergic function that is based on control theory, implemented using systems of differential equations, and focused on better characterizing pathways from genes to behavior. We present the results of model validation tests that include the comparison of simulation outcomes with empirical data on genetic effects on brain response to affective stimuli and on impulsivity. Patterns of simulated neural firing were consistent with recent findings of additive effects of serotonin transporter and tryptophan hydroxylase-2 polymorphisms on brain activation. In addition, simulated levels of cerebral spinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) were negatively correlated with Barratt Impulsiveness Scale (Version 11) Total scores in college students (r = −.22, p = .002, N = 187), which is consistent with the well-established negative correlation between CSF 5-HIAA and impulsivity. The results of the validation tests suggest that the model captures important aspects of the genetic control of presynaptic serotonergic function and behavior via brain activation. The proposed model can be: (1) extended to include other system components, neurotransmitter systems, behaviors and environmental influences; (2) used to generate testable hypotheses. PMID:20111992

Tritium environmental transport studies at TFTR

NASA Astrophysics Data System (ADS)

Ritter, P. D.; Dolan, T. J.; Longhurst, G. R.

1993-06-01

Environmental tritium concentrations will be measured near the Tokamak Fusion Test Reactor (TFTR) to help validate dynamic models of tritium transport in the environment. For model validation the database must contain sequential measurements of tritium concentrations in key environmental compartments. Since complete containment of tritium is an operational goal, the supplementary monitoring program should be able to glean useful data from an unscheduled acute release. Portable air samplers will be used to take samples automatically every 4 hours for a week after an acute release, thus obtaining the time resolution needed for code validation. Samples of soil, vegetation, and foodstuffs will be gathered daily at the same locations as the active air monitors. The database may help validate the plant/soil/air part of tritium transport models and enhance environmental tritium transport understanding for the International Thermonuclear Experimental Reactor (ITER).

Noise and diffusion of a vibrated self-propelled granular particle

NASA Astrophysics Data System (ADS)

Walsh, Lee; Wagner, Caleb G.; Schlossberg, Sarah; Olson, Christopher; Baskaran, Aparna; Menon, Narayanan

Granular materials are an important physical realization of active matter. In vibration-fluidized granular matter, both diffusion and self-propulsion derive from the same collisional forcing, unlike many other active systems where there is a clean separation between the origin of single-particle mobility and the coupling to noise. Here we present experimental studies of single-particle motion in a vibrated granular monolayer, along with theoretical analysis that compares grain motion at short and long time scales to the assumptions and predictions, respectively, of the active Brownian particle (ABP) model. The results demonstrate that despite the unique relation between noise and propulsion, granular media do show the generic features predicted by the ABP model and indicate that this is a valid framework to predict collective phenomena. Additionally, our scheme of analysis for validating the inputs and outputs of the model can be applied to other granular and non-granular systems.

NASA GPM GV Science Implementation

NASA Technical Reports Server (NTRS)

Petersen, W. A.

2009-01-01

Pre-launch algorithm development & post-launch product evaluation: The GPM GV paradigm moves beyond traditional direct validation/comparison activities by incorporating improved algorithm physics & model applications (end-to-end validation) in the validation process. Three approaches: 1) National Network (surface): Operational networks to identify and resolve first order discrepancies (e.g., bias) between satellite and ground-based precipitation estimates. 2) Physical Process (vertical column): Cloud system and microphysical studies geared toward testing and refinement of physically-based retrieval algorithms. 3) Integrated (4-dimensional): Integration of satellite precipitation products into coupled prediction models to evaluate strengths/limitations of satellite precipitation producers.

Developing Capture Mechanisms and High-Fidelity Dynamic Models for the MXER Tether System

NASA Technical Reports Server (NTRS)

Canfield, Steven L.

2007-01-01

A team consisting of collaborators from Tennessee Technological University (TTU), Marshall Space Flight Center, BD Systems, and the University of Delaware (herein called the TTU team) conducted specific research and development activities in MXER tether systems during the base period of May 15, 2004 through September 30, 2006 under contract number NNM04AB13C. The team addressed two primary topics related to the MXER tether system: 1) Development of validated high-fidelity dynamic models of an elastic rotating tether and 2) development of feasible mechanisms to enable reliable rendezvous and capture. This contractor report will describe in detail the activities that were performed during the base period of this cycle-2 MXER tether activity and will summarize the results of this funded activity. The primary deliverables of this project were the quad trap, a robust capture mechanism proposed, developed, tested, and demonstrated with a high degree of feasibility and the detailed development of a validated high-fidelity elastic tether dynamic model provided through multiple formulations.

Collaborative development of predictive toxicology applications

PubMed Central

2010-01-01

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals. The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation. Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH-relevant endpoints: ToxPredict which predicts and reports on toxicities for endpoints for an input chemical structure, and ToxCreate which builds and validates a predictive toxicity model based on an input toxicology dataset. Because of the extensible nature of the standardised Framework design, barriers of interoperability between applications and content are removed, as the user may combine data, models and validation from multiple sources in a dependable and time-effective way. PMID:20807436

Collaborative development of predictive toxicology applications.

PubMed

Hardy, Barry; Douglas, Nicki; Helma, Christoph; Rautenberg, Micha; Jeliazkova, Nina; Jeliazkov, Vedrin; Nikolova, Ivelina; Benigni, Romualdo; Tcheremenskaia, Olga; Kramer, Stefan; Girschick, Tobias; Buchwald, Fabian; Wicker, Joerg; Karwath, Andreas; Gütlein, Martin; Maunz, Andreas; Sarimveis, Haralambos; Melagraki, Georgia; Afantitis, Antreas; Sopasakis, Pantelis; Gallagher, David; Poroikov, Vladimir; Filimonov, Dmitry; Zakharov, Alexey; Lagunin, Alexey; Gloriozova, Tatyana; Novikov, Sergey; Skvortsova, Natalia; Druzhilovsky, Dmitry; Chawla, Sunil; Ghosh, Indira; Ray, Surajit; Patel, Hitesh; Escher, Sylvia

2010-08-31

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals.The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation.Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH-relevant endpoints: ToxPredict which predicts and reports on toxicities for endpoints for an input chemical structure, and ToxCreate which builds and validates a predictive toxicity model based on an input toxicology dataset. Because of the extensible nature of the standardised Framework design, barriers of interoperability between applications and content are removed, as the user may combine data, models and validation from multiple sources in a dependable and time-effective way.

Active Aeroelastic Wing Aerodynamic Model Development and Validation for a Modified F/A-18A Airplane

NASA Technical Reports Server (NTRS)

Cumming, Stephen B.; Diebler, Corey G.

2005-01-01

A new aerodynamic model has been developed and validated for a modified F/A-18A airplane used for the Active Aeroelastic Wing (AAW) research program. The goal of the program was to demonstrate the advantages of using the inherent flexibility of an aircraft to enhance its performance. The research airplane was an F/A-18A with wings modified to reduce stiffness and a new control system to increase control authority. There have been two flight phases. Data gathered from the first flight phase were used to create the new aerodynamic model. A maximum-likelihood output-error parameter estimation technique was used to obtain stability and control derivatives. The derivatives were incorporated into the National Aeronautics and Space Administration F-18 simulation, validated, and used to develop new AAW control laws. The second phase of flights was used to evaluate the handling qualities of the AAW airplane and the control law design process, and to further test the accuracy of the new model. The flight test envelope covered Mach numbers between 0.85 and 1.30 and dynamic pressures from 600 to 1250 pound-force per square foot. The results presented in this report demonstrate that a thorough parameter identification analysis can be used to improve upon models that were developed using other means. This report describes the parameter estimation technique used, details the validation techniques, discusses differences between previously existing F/A-18 models, and presents results from the second phase of research flights.

Validation of persuasive messages for the promotion of physical activity among people with coronary heart disease.

PubMed

Mendez, Roberto Della Rosa; Rodrigues, Roberta Cunha Matheus; Spana, Thaís Moreira; Cornélio, Marília Estevam; Gallani, Maria Cecília Bueno Jayme; Pérez-Nebra, Amalia Raquel

2012-01-01

to validate the content of persuasive messages for promoting walking among patients with coronary heart disease (CHD). The messages were constructed to strengthen or change patients' attitudes to walking. the selection of persuasive arguments was based on behavioral beliefs (determinants of attitude) related to walking. The messages were constructed based in the Elaboration Likelihood Model and were submitted to content validation. the data was analyzed with the content validity index and by the importance which the patients attributed to the messages' persuasive arguments. Positive behavioral beliefs (i.e. positive and negative reinforcement) and self-efficacy were the appeals which the patients considered important. The messages with validation evidence will be tested in an intervention study for the promotion of the practice of physical activity among patients with CHD.

Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling.

PubMed

Jacobsen, Annika; Heijmans, Nika; Verkaar, Folkert; Smit, Martine J; Heringa, Jaap; van Amerongen, Renée; Feenstra, K Anton

2016-01-01

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulation) and hyperactive (GSK3 inhibition) signaling by comparing our simulation and experimental data. We used this experimentally validated model to get further insights into the effect of the negative feedback regulator AXIN2 upon WNT stimulation and observed an attenuated β-catenin stabilization. We furthermore simulated the effect of APC inactivating mutations, yielding a stabilization of β-catenin levels comparable to the Wnt-pathway activities observed in colorectal and breast cancer. Our model can be used for further investigation and viable predictions of the role of Wnt/β-catenin signaling in oncogenesis and development.

Construction and Experimental Validation of a Petri Net Model of Wnt/β-Catenin Signaling

PubMed Central

Heijmans, Nika; Verkaar, Folkert; Smit, Martine J.; Heringa, Jaap

2016-01-01

The Wnt/β-catenin signaling pathway is important for multiple developmental processes and tissue maintenance in adults. Consequently, deregulated signaling is involved in a range of human diseases including cancer and developmental defects. A better understanding of the intricate regulatory mechanism and effect of physiological (active) and pathophysiological (hyperactive) WNT signaling is important for predicting treatment response and developing novel therapies. The constitutively expressed CTNNB1 (commonly and hereafter referred to as β-catenin) is degraded by a destruction complex, composed of amongst others AXIN1 and GSK3. The destruction complex is inhibited during active WNT signaling, leading to β-catenin stabilization and induction of β-catenin/TCF target genes. In this study we investigated the mechanism and effect of β-catenin stabilization during active and hyperactive WNT signaling in a combined in silico and in vitro approach. We constructed a Petri net model of Wnt/β-catenin signaling including main players from the plasma membrane (WNT ligands and receptors), cytoplasmic effectors and the downstream negative feedback target gene AXIN2. We validated that our model can be used to simulate both active (WNT stimulation) and hyperactive (GSK3 inhibition) signaling by comparing our simulation and experimental data. We used this experimentally validated model to get further insights into the effect of the negative feedback regulator AXIN2 upon WNT stimulation and observed an attenuated β-catenin stabilization. We furthermore simulated the effect of APC inactivating mutations, yielding a stabilization of β-catenin levels comparable to the Wnt-pathway activities observed in colorectal and breast cancer. Our model can be used for further investigation and viable predictions of the role of Wnt/β-catenin signaling in oncogenesis and development. PMID:27218469

3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase

NASA Astrophysics Data System (ADS)

Li, Wenlian; Si, Hongzong; Li, Yang; Ge, Cuizhu; Song, Fucheng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

2016-08-01

Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion and hepatitis C virus (HCV) infection is a global health threat. The HCV NS5B polymerase, an RNA dependent RNA polymerase (RdRp) and an essential role in the replication of the virus, has no functional equivalent in mammalian cells. So the research and development of efficient NS5B polymerase inhibitors provides a great strategy for antiviral therapy against HCV. A combined three-dimensional quantitative structure-activity relationship (QSAR) modeling was accomplished to profoundly understand the structure-activity correlation of a train of indole-based inhibitors of the HCV NS5B polymerase to against HCV. A comparative molecular similarity indices analysis (COMSIA) model as the foundation of the maximum common substructure alignment was developed. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient q2 was 0.627 and non-cross-validated r2 value was 0.943. In addition, the results of internal validations of bootstrapping and Y-randomization confirmed the rationality and good predictive ability of the model, as well as external validation (the external predictive correlation coefficient rext2 = 0.629). The information obtained from the COMSIA contour maps enables the interpretation of their structure-activity relationship. Furthermore, the molecular docking study of the compounds for 3TYV as the protein target revealed important interactions between active compounds and amino acids, and several new potential inhibitors with higher activity predicted were designed basis on our analyses and supported by the simulation of molecular docking. Meanwhile, the OSIRIS Property Explorer was introduced to help select more satisfactory compounds. The satisfactory results from this study may lay a reliable theoretical base for drug development of hepatitis C virus NS5B polymerase inhibitors.

Predictive Ability of Pender's Health Promotion Model for Physical Activity and Exercise in People with Spinal Cord Injuries: A Hierarchical Regression Analysis

ERIC Educational Resources Information Center

Keegan, John P.; Chan, Fong; Ditchman, Nicole; Chiu, Chung-Yi

2012-01-01

The main objective of this study was to validate Pender's Health Promotion Model (HPM) as a motivational model for exercise/physical activity self-management for people with spinal cord injuries (SCIs). Quantitative descriptive research design using hierarchical regression analysis (HRA) was used. A total of 126 individuals with SCI were recruited…

Validation of the Physical Activity Questionnaire for Older Children (PAQ-C) among Chinese Children.

PubMed

Wang, Jing Jing; Baranowski, Tom; Lau, Wc Patrick; Chen, Tzu An; Pitkethly, Amanda Jane

2016-03-01

This study initially validates the Chinese version of the Physical Activity Questionnaire for Older Children (PAQ-C), which has been identified as a potentially valid instrument to assess moderate-to-vigorous physical activity (MVPA) in children among diverse racial groups. The psychometric properties of the PAQ-C with 742 Hong Kong Chinese children were assessed with the scale's internal consistency, reliability, test-retest reliability, confirmatory factory analysis (CFA) in the overall sample, and multistep invariance tests across gender groups as well as convergent validity with body mass index (BMI), and an accelerometry-based MVPA. The Cronbach alpha coefficient (α=0.79), composite reliability value (ρ=0.81), and the intraclass correlation coefficient (α=0.82) indicate the satisfactory reliability of the PAQ-C score. The CFA indicated data fit a single factor model, suggesting that the PAQ-C measures only one construct, on MVPA over the previous 7 days. The multiple-group CFAs suggested that the factor loadings and variances and covariances of the PAQ-C measurement model were invariant across gender groups. The PAQ-C score was related to accelerometry-based MVPA (r=0.33) and inversely related to BMI (r=-0.18). This study demonstrates the reliability and validity of the PAQ-C in Chinese children. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

The PDB_REDO server for macromolecular structure model optimization.

PubMed

Joosten, Robbie P; Long, Fei; Murshudov, Garib N; Perrakis, Anastassis

2014-07-01

The refinement and validation of a crystallographic structure model is the last step before the coordinates and the associated data are submitted to the Protein Data Bank (PDB). The success of the refinement procedure is typically assessed by validating the models against geometrical criteria and the diffraction data, and is an important step in ensuring the quality of the PDB public archive [Read et al. (2011 ▶), Structure, 19, 1395-1412]. The PDB_REDO procedure aims for 'constructive validation', aspiring to consistent and optimal refinement parameterization and pro-active model rebuilding, not only correcting errors but striving for optimal interpretation of the electron density. A web server for PDB_REDO has been implemented, allowing thorough, consistent and fully automated optimization of the refinement procedure in REFMAC and partial model rebuilding. The goal of the web server is to help practicing crystallo-graphers to improve their model prior to submission to the PDB. For this, additional steps were implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g. testing of resolution limits and k-fold cross-validation for small test sets, and as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS and ligand validation as implemented in YASARA. Innovative ways to present the refinement and validation results to the user are also described, which together with auto-generated Coot scripts can guide users to subsequent model inspection and improvement. It is demonstrated that using the server can lead to substantial improvement of structure models before they are submitted to the PDB.

Structural exploration for the refinement of anticancer matrix metalloproteinase-2 inhibitor designing approaches through robust validated multi-QSARs

NASA Astrophysics Data System (ADS)

Adhikari, Nilanjan; Amin, Sk. Abdul; Saha, Achintya; Jha, Tarun

2018-03-01

Matrix metalloproteinase-2 (MMP-2) is a promising pharmacological target for designing potential anticancer drugs. MMP-2 plays critical functions in apoptosis by cleaving the DNA repair enzyme namely poly (ADP-ribose) polymerase (PARP). Moreover, MMP-2 expression triggers the vascular endothelial growth factor (VEGF) having a positive influence on tumor size, invasion, and angiogenesis. Therefore, it is an urgent need to develop potential MMP-2 inhibitors without any toxicity but better pharmacokinetic property. In this article, robust validated multi-quantitative structure-activity relationship (QSAR) modeling approaches were attempted on a dataset of 222 MMP-2 inhibitors to explore the important structural and pharmacophoric requirements for higher MMP-2 inhibition. Different validated regression and classification-based QSARs, pharmacophore mapping and 3D-QSAR techniques were performed. These results were challenged and subjected to further validation to explain 24 in house MMP-2 inhibitors to judge the reliability of these models further. All these models were individually validated internally as well as externally and were supported and validated by each other. These results were further justified by molecular docking analysis. Modeling techniques adopted here not only helps to explore the necessary structural and pharmacophoric requirements but also for the overall validation and refinement techniques for designing potential MMP-2 inhibitors.

Perception of competence in middle school physical education: instrument development and validation.

PubMed

Scrabis-Fletcher, Kristin; Silverman, Stephen

2010-03-01

Perception of Competence (POC) has been studied extensively in physical activity (PA) research with similar instruments adapted for physical education (PE) research. Such instruments do not account for the unique PE learning environment. Therefore, an instrument was developed and the scores validated to measure POC in middle school PE. A multiphase design was used consisting of an intensive theoretical review, elicitation study, prepilot study, pilot study, content validation study, and final validation study (N=1281). Data analysis included a multistep iterative process to identify the best model fit. A three-factor model for POC was tested and resulted in root mean square error of approximation = .09, root mean square residual = .07, goodness offit index = .90, and adjusted goodness offit index = .86 values in the acceptable range (Hu & Bentler, 1999). A two-factor model was also tested and resulted in a good fit (two-factor fit indexes values = .05, .03, .98, .97, respectively). The results of this study suggest that an instrument using a three- or two-factor model provides reliable and valid scores ofPOC measurement in middle school PE.

Updating and prospective validation of a prognostic model for high sickness absence.

PubMed

Roelen, C A M; Heymans, M W; Twisk, J W R; van Rhenen, W; Pallesen, S; Bjorvatn, B; Moen, B E; Magerøy, N

2015-01-01

To further develop and validate a Dutch prognostic model for high sickness absence (SA). Three-wave longitudinal cohort study of 2,059 Norwegian nurses. The Dutch prognostic model was used to predict high SA among Norwegian nurses at wave 2. Subsequently, the model was updated by adding person-related (age, gender, marital status, children at home, and coping strategies), health-related (BMI, physical activity, smoking, and caffeine and alcohol intake), and work-related (job satisfaction, job demands, decision latitude, social support at work, and both work-to-family and family-to-work spillover) variables. The updated model was then prospectively validated for predictions at wave 3. 1,557 (77 %) nurses had complete data at wave 2 and 1,342 (65 %) at wave 3. The risk of high SA was under-estimated by the Dutch model, but discrimination between high-risk and low-risk nurses was fair after re-calibration to the Norwegian data. Gender, marital status, BMI, physical activity, smoking, alcohol intake, job satisfaction, job demands, decision latitude, support at the workplace, and work-to-family spillover were identified as potential predictors of high SA. However, these predictors did not improve the model's discriminative ability, which remained fair at wave 3. The prognostic model correctly identifies 73 % of Norwegian nurses at risk of high SA, although additional predictors are needed before the model can be used to screen working populations for risk of high SA.

Validation metrics for turbulent plasma transport

DOE PAGES

Holland, C.

2016-06-22

Developing accurate models of plasma dynamics is essential for confident predictive modeling of current and future fusion devices. In modern computer science and engineering, formal verification and validation processes are used to assess model accuracy and establish confidence in the predictive capabilities of a given model. This paper provides an overview of the key guiding principles and best practices for the development of validation metrics, illustrated using examples from investigations of turbulent transport in magnetically confined plasmas. Particular emphasis is given to the importance of uncertainty quantification and its inclusion within the metrics, and the need for utilizing synthetic diagnosticsmore » to enable quantitatively meaningful comparisons between simulation and experiment. As a starting point, the structure of commonly used global transport model metrics and their limitations is reviewed. An alternate approach is then presented, which focuses upon comparisons of predicted local fluxes, fluctuations, and equilibrium gradients against observation. Furthermore, the utility of metrics based upon these comparisons is demonstrated by applying them to gyrokinetic predictions of turbulent transport in a variety of discharges performed on the DIII-D tokamak, as part of a multi-year transport model validation activity.« less

Validation metrics for turbulent plasma transport

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

Holland, C.

Developing accurate models of plasma dynamics is essential for confident predictive modeling of current and future fusion devices. In modern computer science and engineering, formal verification and validation processes are used to assess model accuracy and establish confidence in the predictive capabilities of a given model. This paper provides an overview of the key guiding principles and best practices for the development of validation metrics, illustrated using examples from investigations of turbulent transport in magnetically confined plasmas. Particular emphasis is given to the importance of uncertainty quantification and its inclusion within the metrics, and the need for utilizing synthetic diagnosticsmore » to enable quantitatively meaningful comparisons between simulation and experiment. As a starting point, the structure of commonly used global transport model metrics and their limitations is reviewed. An alternate approach is then presented, which focuses upon comparisons of predicted local fluxes, fluctuations, and equilibrium gradients against observation. Furthermore, the utility of metrics based upon these comparisons is demonstrated by applying them to gyrokinetic predictions of turbulent transport in a variety of discharges performed on the DIII-D tokamak, as part of a multi-year transport model validation activity.« less

Designing an activity-based costing model for a non-admitted prisoner healthcare setting.

PubMed

Cai, Xiao; Moore, Elizabeth; McNamara, Martin

2013-09-01

To design and deliver an activity-based costing model within a non-admitted prisoner healthcare setting. Key phases from the NSW Health clinical redesign methodology were utilised: diagnostic, solution design and implementation. The diagnostic phase utilised a range of strategies to identify issues requiring attention in the development of the costing model. The solution design phase conceptualised distinct 'building blocks' of activity and cost based on the speciality of clinicians providing care. These building blocks enabled the classification of activity and comparisons of costs between similar facilities. The implementation phase validated the model. The project generated an activity-based costing model based on actual activity performed, gained acceptability among clinicians and managers, and provided the basis for ongoing efficiency and benchmarking efforts.

Validation of the Malay version of the Inventory of Functional Status after Childbirth questionnaire.

PubMed

Noor, Norhayati Mohd; Aziz, Aniza Abd; Mostapa, Mohd Rosmizaki; Awang, Zainudin

2015-01-01

This study was designed to examine the psychometric properties of Malay version of the Inventory of Functional Status after Childbirth (IFSAC). A cross-sectional study. A total of 108 postpartum mothers attending Obstetrics and Gynaecology Clinic, in a tertiary teaching hospital in Malaysia, were involved. Construct validity and internal consistency were performed after the translation, content validity, and face validity process. The data were analyzed using Analysis of Moment Structure version 18 and Statistical Packages for the Social Sciences version 20. The final model consists of four constructs, namely, infant care, personal care, household activities, and social and community activities, with 18 items demonstrating acceptable factor loadings, domain to domain correlation, and best fit (Chi-squared/degree of freedom = 1.678; Tucker-Lewis index = 0.923; comparative fit index = 0.936; and root mean square error of approximation = 0.080). Composite reliability and average variance extracted of the domains ranged from 0.659 to 0.921 and from 0.499 to 0.628, respectively. The study suggested that the four-factor model with 18 items of the Malay version of IFSAC was acceptable to be used to measure functional status after childbirth because it is valid, reliable, and simple.

Hands-On and Minds-On Modeling Activities to Improve Students' Conceptions of Microscopic Friction

NASA Astrophysics Data System (ADS)

Corpuz, Edgar G.; Rebello, N. Sanjay

2007-11-01

In this paper we discuss the development and validation of hands-on and minds-on modeling activities geared towards improving students' understanding of microscopic friction. We will also present our investigation on the relative effectiveness of the use of the developed instructional material with two lecture formats—traditional and videotaped lectures. Results imply that through a series of carefully designed hands-on and minds-on modeling activities, it is possible to facilitate the refinement of students' ideas of microscopic friction.

Flutter suppression for the Active Flexible Wing - Control system design and experimental validation

NASA Technical Reports Server (NTRS)

Waszak, M. R.; Srinathkumar, S.

1992-01-01

The synthesis and experimental validation of a control law for an active flutter suppression system for the Active Flexible Wing wind-tunnel model is presented. The design was accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and with extensive use of simulation-based analysis. The design approach relied on a fundamental understanding of the flutter mechanism to formulate understanding of the flutter mechanism to formulate a simple control law structure. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite errors in the design model. The flutter suppression controller was also successfully operated in combination with a rolling maneuver controller to perform flutter suppression during rapid rolling maneuvers.

Integrating Model-Based Transmission Reduction into a multi-tier architecture

NASA Astrophysics Data System (ADS)

Straub, J.

A multi-tier architecture consists of numerous craft as part of the system, orbital, aerial, and surface tiers. Each tier is able to collect progressively greater levels of information. Generally, craft from lower-level tiers are deployed to a target of interest based on its identification by a higher-level craft. While the architecture promotes significant amounts of science being performed in parallel, this may overwhelm the computational and transmission capabilities of higher-tier craft and links (particularly the deep space link back to Earth). Because of this, a new paradigm in in-situ data processing is required. Model-based transmission reduction (MBTR) is such a paradigm. Under MBTR, each node (whether a single spacecraft in orbit of the Earth or another planet or a member of a multi-tier network) is given an a priori model of the phenomenon that it is assigned to study. It performs activities to validate this model. If the model is found to be erroneous, corrective changes are identified, assessed to ensure their significance for being passed on, and prioritized for transmission. A limited amount of verification data is sent with each MBTR assertion message to allow those that might rely on the data to validate the correct operation of the spacecraft and MBTR engine onboard. Integrating MBTR with a multi-tier framework creates an MBTR hierarchy. Higher levels of the MBTR hierarchy task lower levels with data collection and assessment tasks that are required to validate or correct elements of its model. A model of the expected conditions is sent to the lower level craft; which then engages its own MBTR engine to validate or correct the model. This may include tasking a yet lower level of craft to perform activities. When the MBTR engine at a given level receives all of its component data (whether directly collected or from delegation), it randomly chooses some to validate (by reprocessing the validation data), performs analysis and sends its own results (v- lidation and/or changes of model elements and supporting validation data) to its upstream node. This constrains data transmission to only significant (either because it includes a change or is validation data critical for assessing overall performance) information and reduces the processing requirements (by not having to process insignificant data) at higher-level nodes. This paper presents a framework for multi-tier MBTR and two demonstration mission concepts: an Earth sensornet and a mission to Mars. These multi-tier MBTR concepts are compared to a traditional mission approach.

Combined active and passive microwave remote sensing of soil moisture for vegetated surfaces at L-band

USDA-ARS?s Scientific Manuscript database

The distorted Born approximation (DBA) combined with the numerical solutions of Maxwell equations (NMM3D) has been used for the radar backscattering model for the SMAP mission. The models for vegetated surfaces such as wheat, grass, soybean and corn have been validated with the Soil Moisture Active ...

QSAR studies on triazole derivatives as sglt inhibitors via CoMFA and CoMSIA

NASA Astrophysics Data System (ADS)

Zhi, Hui; Zheng, Junxia; Chang, Yiqun; Li, Qingguo; Liao, Guochao; Wang, Qi; Sun, Pinghua

2015-10-01

Forty-six sodium-dependent glucose cotransporters-2 (SGLT-2) inhibitors with hypoglycemic activity were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set of 39 compounds were used to build up the models, which were then evaluated by a series of internal and external cross-validation techniques. A test set of 7 compounds was used for the external validation. The CoMFA model predicted a q2 value of 0.792 and an r2 value of 0.985. The best CoMSIA model predicted a q2 value of 0.633 and an r2 value of 0.895 based on a combination of steric, electrostatic, hydrophobic and hydrogen-bond acceptor effects. The predictive correlation coefficients (rpred2) of CoMFA and CoMSIA models were 0.872 and 0.839, respectively. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active sglt inhibitors, and on the basis of the models 8 new sglt inhibitors were designed and predicted.

GEANT4 benchmark with MCNPX and PHITS for activation of concrete

NASA Astrophysics Data System (ADS)

Tesse, Robin; Stichelbaut, Frédéric; Pauly, Nicolas; Dubus, Alain; Derrien, Jonathan

2018-02-01

The activation of concrete is a real problem from the point of view of waste management. Because of the complexity of the issue, Monte Carlo (MC) codes have become an essential tool to its study. But various codes or even nuclear models exist in MC. MCNPX and PHITS have already been validated for shielding studies but GEANT4 is also a suitable solution. In these codes, different models can be considered for a concrete activation study. The Bertini model is not the best model for spallation while BIC and INCL model agrees well with previous results in literature.

Development and Validation of the Total HUman Model for Safety (THUMS) Toward Further Understanding of Occupant Injury Mechanisms in Precrash and During Crash.

PubMed

Iwamoto, Masami; Nakahira, Yuko; Kimpara, Hideyuki

2015-01-01

Active safety devices such as automatic emergency brake (AEB) and precrash seat belt have the potential to accomplish further reduction in the number of the fatalities due to automotive accidents. However, their effectiveness should be investigated by more accurate estimations of their interaction with human bodies. Computational human body models are suitable for investigation, especially considering muscular tone effects on occupant motions and injury outcomes. However, the conventional modeling approaches such as multibody models and detailed finite element (FE) models have advantages and disadvantages in computational costs and injury predictions considering muscular tone effects. The objective of this study is to develop and validate a human body FE model with whole body muscles, which can be used for the detailed investigation of interaction between human bodies and vehicular structures including some safety devices precrash and during a crash with relatively low computational costs. In this study, we developed a human body FE model called THUMS (Total HUman Model for Safety) with a body size of 50th percentile adult male (AM50) and a sitting posture. The model has anatomical structures of bones, ligaments, muscles, brain, and internal organs. The total number of elements is 281,260, which would realize relatively low computational costs. Deformable material models were assigned to all body parts. The muscle-tendon complexes were modeled by truss elements with Hill-type muscle material and seat belt elements with tension-only material. The THUMS was validated against 35 series of cadaver or volunteer test data on frontal, lateral, and rear impacts. Model validations for 15 series of cadaver test data associated with frontal impacts are presented in this article. The THUMS with a vehicle sled model was applied to investigate effects of muscle activations on occupant kinematics and injury outcomes in specific frontal impact situations with AEB. In the validations using 5 series of cadaver test data, force-time curves predicted by the THUMS were quantitatively evaluated using correlation and analysis (CORA), which showed good or acceptable agreement with cadaver test data in most cases. The investigation of muscular effects showed that muscle activation levels and timing had significant effects on occupant kinematics and injury outcomes. Although further studies on accident injury reconstruction are needed, the THUMS has the potential for predictions of occupant kinematics and injury outcomes considering muscular tone effects with relatively low computational costs.

Validity evidence for the adaptation of the State Mindfulness Scale for Physical Activity (SMS-PA) in Spanish youth.

PubMed

Ullrich-French, Sarah; González Hernández, Juan; Hidalgo Montesinos, María D

2017-02-01

Mindfulness is an increasingly popular construct with promise in enhancing multiple positive health outcomes. Physical activity is an important behavior for enhancing overall health, but no Spanish language scale exists to test how mindfulness during physical activity may facilitate physical activity motivation or behavior. This study examined the validity of a Spanish adaption of a new scale, the State Mindfulness Scale for Physical Activity, to assess mindfulness during a specific experience of physical activity. Spanish youths (N = 502) completed a cross-sectional survey of state mindfulness during physical activity and physical activity motivation regulations based on Self-Determination Theory. A high-order model fit the data well and supports the use of one general state mindfulness factor or the use of separate subscales of mindfulness of mental (e.g., thoughts, emotions) and body (physical movement, muscles) aspects of the experience. Internal consistency reliability was good for the general scale and both sub-scales. The pattern of correlations with motivation regulations provides further support for construct validity with significant and positive correlations with self-determined forms of motivation and significant and negative correlations with external regulation and amotivation. Initial validity evidence is promising for the use of the adapted measure.

Dependence and physical exercise: Spanish validation of the Exercise Dependence Scale-Revised (EDS-R).

PubMed

Sicilia, Alvaro; González-Cutre, David

2011-05-01

The purpose of this study was to validate the Spanish version of the Exercise Dependence Scale-Revised (EDS-R). To achieve this goal, a sample of 531 sport center users was used and the psychometric properties of the EDS-R were examined through different analyses. The results supported both the first-order seven-factor model and the higher-order model (seven first-order factors and one second-order factor). The structure of both models was invariant across age. Correlations among the subscales indicated a related factor model, supporting construct validity of the scale. Alpha values over .70 (except for Reduction in Other Activities) and suitable levels of temporal stability were obtained. Users practicing more than three days per week had higher scores in all subscales than the group practicing with a frequency of three days or fewer. The findings of this study provided reliability and validity for the EDS-R in a Spanish context.

Revision of empirical electric field modeling in the inner magnetosphere using Cluster data

NASA Astrophysics Data System (ADS)

Matsui, H.; Torbert, R. B.; Spence, H. E.; Khotyaintsev, Yu. V.; Lindqvist, P.-A.

2013-07-01

Using Cluster data from the Electron Drift (EDI) and the Electric Field and Wave (EFW) instruments, we revise our empirically-based, inner-magnetospheric electric field (UNH-IMEF) model at 22.662 mV/m; Kp<1, 1≤Kp<2, 2≤Kp<3, 3≤Kp<4, 4≤Kp<5, and Kp≥4+. Patterns consist of one set of data and processing for smaller activities, and another for higher activities. As activity increases, the skewed potential contour related to the partial ring current appears on the nightside. With the revised analysis, we find that the skewed potential contours get clearer and potential contours get denser on the nightside and morningside. Since the fluctuating components are not negligible, standard deviations from the modeled values are included in the model. In this study, we perform validation of the derived model more extensively. We find experimentally that the skewed contours are located close to the last closed equipotential, consistent with previous theories. This gives physical context to our model and serves as one validation effort. As another validation effort, the derived results are compared with other models/measurements. From these comparisons, we conclude that our model has some clear advantages over the others.

Load Composition Model Workflow (BPA TIP-371 Deliverable 1A)

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

Chassin, David P.; Cezar, Gustavo V.

This project is funded under Bonneville Power Administration (BPA) Strategic Partnership Project (SPP) 17-005 between BPA and SLAC National Accelerator Laboratory. The project in a BPA Technology Improvement Project (TIP) that builds on and validates the Composite Load Model developed by the Western Electric Coordinating Council's (WECC) Load Modeling Task Force (LMTF). The composite load model is used by the WECC Modeling and Validation Work Group to study the stability and security of the western electricity interconnection. The work includes development of load composition data sets, collection of load disturbance data, and model development and validation. This work supports reliablemore » and economic operation of the power system. This report was produced for Deliverable 1A of the BPA TIP-371 Project entitled \\TIP 371: Advancing the Load Composition Model". The deliverable documents the proposed work ow for the Composite Load Model, which provides the basis for the instrumentation, data acquisition, analysis and data dissemination activities addressed by later phases of the project.« less

Modelling and attenuation feasibility of the aeroelastic response of active helicopter rotor systems during the engagement/disengagement phase of maritime operation

NASA Astrophysics Data System (ADS)

Khouli, F.

An aeroelastic phenomenon, known as blade sailing, encountered during maritime operation of helicopters is identified as being a factor that limits the tactical flexibility of helicopter operation in some sea conditions. The hazards associated with this phenomenon and its complexity, owing to the number of factors contributing to its occurrence, led previous investigators to conclude that advanced and validated simulation tools are best suited to investigate it. A research gap is identified in terms of scaled experimental investigation of this phenomenon and practical engineering solutions to alleviate its negative impact on maritime helicopter operation. The feasibility of a proposed strategy to alleviate it required addressing a gap in modelling thin-walled composite active beams/rotor blades. The modelling is performed by extending a mathematically-consistent and asymptotic reduction strategy of the 3-D elastic problem to account for embedded active materials. The derived active cross-sectional theory is validated using 2-D finite element results for closed and open cross-sections. The geometrically-exact intrinsic formulation of active maritime rotor systems is demonstrated to yield compact and symbolic governing equations. The intrinsic feature is shown to allow a classical and proven solution scheme to be successfully applied to obtain time history solutions. A Froude-scaled experimental rotor was designed, built, and tested in a scaled ship airwake environment and representative ship motion. Based on experimental and simulations data, conclusions are drawn regarding the influence of the maritime operation environment and the rotor operation parameters on the blade sailing phenomenon. The experimental data is also used to successfully validate the developed simulation tools. The feasibility of an open-loop control strategy based on the integral active twist concept to counter blade sailing is established in a Mach-scaled maritime operation environment. Recommendations are proposed to improve the strategy and further establish its validity in a full-scale maritime operation environment.

QSAR modeling: where have you been? Where are you going to?

PubMed

Cherkasov, Artem; Muratov, Eugene N; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-06-26

Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making.

QSAR Modeling: Where have you been? Where are you going to?

PubMed Central

Cherkasov, Artem; Muratov, Eugene N.; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I.; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C.; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E.; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-01-01

Quantitative Structure-Activity Relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss: (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists towards collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making. PMID:24351051

Development of probabilistic thinking-oriented learning tools for probability materials at junior high school students

NASA Astrophysics Data System (ADS)

Sari, Dwi Ivayana; Hermanto, Didik

2017-08-01

This research is a developmental research of probabilistic thinking-oriented learning tools for probability materials at ninth grade students. This study is aimed to produce a good probabilistic thinking-oriented learning tools. The subjects were IX-A students of MTs Model Bangkalan. The stages of this development research used 4-D development model which has been modified into define, design and develop. Teaching learning tools consist of lesson plan, students' worksheet, learning teaching media and students' achievement test. The research instrument used was a sheet of learning tools validation, a sheet of teachers' activities, a sheet of students' activities, students' response questionnaire and students' achievement test. The result of those instruments were analyzed descriptively to answer research objectives. The result was teaching learning tools in which oriented to probabilistic thinking of probability at ninth grade students which has been valid. Since teaching and learning tools have been revised based on validation, and after experiment in class produced that teachers' ability in managing class was effective, students' activities were good, students' responses to the learning tools were positive and the validity, sensitivity and reliability category toward achievement test. In summary, this teaching learning tools can be used by teacher to teach probability for develop students' probabilistic thinking.

Cross-cultural adaptation and construct validity of the Korean version of a physical activity measure for community-dwelling elderly.

PubMed

Choi, Bongsam

2018-01-01

[Purpose] This study aimed to cross-cultural adapt and validate the Korean version of an physical activity measure (K-PAM) for community-dwelling elderly. [Subjects and Methods] One hundred and thirty eight community-dwelling elderlies, 32 males and 106 female, participated in the study. All participants were asked to fill out a fifty-one item questionnaire measuring perceived difficulty in the activities of daily living (ADL) for the elderly. One-parameter model of item response theory (Rasch analysis) was applied to determine the construct validity and to inspect item-level psychometric properties of 51 ADL items of the K-PAM. [Results] Person separation reliability (analogous to Cronbach's alpha) for internal consistency was ranging 0.93 to 0.94. A total of 16 items was misfit to the Rasch model. After misfit item deletion, 35 ADL items of the K-PAM were placed in an empirically meaningful hierarchy from easy to hard. The item-person map analysis delineated that the item difficulty was well matched for the elderlies with moderate and low ability except for high ceilings. [Conclusion] Cross-cultural adapted K-PAM was shown to be sufficient for establishing construct validity and stable psychometric properties confirmed by person separation reliability and fit statistics.

Social Validity of a Positive Behavior Interventions and Support Model

ERIC Educational Resources Information Center

Miramontes, Nancy Y.; Marchant, Michelle; Heath, Melissa Allen; Fischer, Lane

2011-01-01

As more schools turn to positive behavior interventions and support (PBIS) to address students' academic and behavioral problems, there is an increased need to adequately evaluate these programs for social relevance. The present study used social validation measures to evaluate a statewide PBIS initiative. Active consumers of the program were…

Imidazole derivatives as angiotensin II AT1 receptor blockers: Benchmarks, drug-like calculations and quantitative structure-activity relationships modeling

NASA Astrophysics Data System (ADS)

Alloui, Mebarka; Belaidi, Salah; Othmani, Hasna; Jaidane, Nejm-Eddine; Hochlaf, Majdi

2018-03-01

We performed benchmark studies on the molecular geometry, electron properties and vibrational analysis of imidazole using semi-empirical, density functional theory and post Hartree-Fock methods. These studies validated the use of AM1 for the treatment of larger systems. Then, we treated the structural, physical and chemical relationships for a series of imidazole derivatives acting as angiotensin II AT1 receptor blockers using AM1. QSAR studies were done for these imidazole derivatives using a combination of various physicochemical descriptors. A multiple linear regression procedure was used to design the relationships between molecular descriptor and the activity of imidazole derivatives. Results validate the derived QSAR model.

VERIFICATION AND VALIDATION OF THE SPARC MODEL

EPA Science Inventory

Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values--that is, the physical and chemical constants that govern reactivity. Although empirical structure-activity relationships that allow estimation of some ...

From Vivaldi to Beatles and back: predicting lateralized brain responses to music.

PubMed

Alluri, Vinoo; Toiviainen, Petri; Lund, Torben E; Wallentin, Mikkel; Vuust, Peter; Nandi, Asoke K; Ristaniemi, Tapani; Brattico, Elvira

2013-12-01

We aimed at predicting the temporal evolution of brain activity in naturalistic music listening conditions using a combination of neuroimaging and acoustic feature extraction. Participants were scanned using functional Magnetic Resonance Imaging (fMRI) while listening to two musical medleys, including pieces from various genres with and without lyrics. Regression models were built to predict voxel-wise brain activations which were then tested in a cross-validation setting in order to evaluate the robustness of the hence created models across stimuli. To further assess the generalizability of the models we extended the cross-validation procedure by including another dataset, which comprised continuous fMRI responses of musically trained participants to an Argentinean tango. Individual models for the two musical medleys revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions could be predicted. Notably, activations in the medial orbitofrontal region and the anterior cingulate cortex, relevant for self-referential appraisal and aesthetic judgments, could be predicted successfully. Cross-validation across musical stimuli and participant pools helped identify a region of the right superior temporal gyrus, encompassing the planum polare and the Heschl's gyrus, as the core structure that processed complex acoustic features of musical pieces from various genres, with or without lyrics. Models based on purely instrumental music were able to predict activation in the bilateral auditory cortices, parietal, somatosensory, and left hemispheric primary and supplementary motor areas. The presence of lyrics on the other hand weakened the prediction of activations in the left superior temporal gyrus. Our results suggest spontaneous emotion-related processing during naturalistic listening to music and provide supportive evidence for the hemispheric specialization for categorical sounds with realistic stimuli. We herewith introduce a powerful means to predict brain responses to music, speech, or soundscapes across a large variety of contexts. © 2013.

Predicting free-living energy expenditure using a miniaturized ear-worn sensor: an evaluation against doubly labeled water.

PubMed

Bouarfa, Loubna; Atallah, Louis; Kwasnicki, Richard Mark; Pettitt, Claire; Frost, Gary; Yang, Guang-Zhong

2014-02-01

Accurate estimation of daily total energy expenditure (EE)is a prerequisite for assisted weight management and assessing certain health conditions. The use of wearable sensors for predicting free-living EE is challenged by consistent sensor placement, user compliance, and estimation methods used. This paper examines whether a single ear-worn accelerometer can be used for EE estimation under free-living conditions.An EE prediction model as first derived and validated in a controlled setting using healthy subjects involving different physical activities. Ten different activities were assessed showing a tenfold cross validation error of 0.24. Furthermore, the EE prediction model shows a mean absolute deviation(MAD) below 1.2 metabolic equivalent of tasks. The same model was applied to a free-living setting with a different population for further validation. The results were compared against those derived from doubly labeled water. In free-living settings, the predicted daily EE has a correlation of 0.74, p 0.008, and a MAD of 272 kcal day. These results demonstrate that laboratory-derived prediction models can be used to predict EE under free-living conditions [corrected].

Evaluation of the US DOE's conceptual model of hydrothermal activity at Yucca Mountain, Nevada

NASA Astrophysics Data System (ADS)

Dublyansky, Y. V.

2014-08-01

A unique conceptual model describing the conductive heating of rocks in the thick unsaturated zone of Yucca Mountain, Nevada by a silicic pluton emplaced several kilometers away is accepted by the US Department of Energy (DOE) as an explanation of the elevated depositional temperatures measured in fluid inclusions in secondary fluorite and calcite. Acceptance of this model allowed the DOE to keep from considering hydrothermal activity in the performance assessment of the proposed high-level nuclear waste disposal facility. The evaluation presented in this paper shows that no computational modeling results have yet produced a satisfactory match with the empirical benchmark data, specifically with age and fluid inclusion data that indicate high temperatures (up to ca. 80 °C) in the unsaturated zone of Yucca Mountain. Auxiliary sub-models complementing the DOE model, as well as observations at a natural analog site, have also been evaluated. Summarily, the model cannot be considered as validated. Due to the lack of validation, the reliance on this model must be discontinued and the appropriateness of decisions which rely on this model must be re-evaluated.

A process-oriented measure of habit strength for moderate-to-vigorous physical activity

PubMed Central

Grove, J. Robert; Zillich, Irja; Medic, Nikola

2014-01-01

Purpose: Habitual action is an important aspect of health behaviour, but the relevance of various habit strength indicators continues to be debated. This study focused specifically on moderate-to-vigorous physical activity (MVPA) and evaluated the construct validity of a framework emphasizing patterned action, stimulus-response bonding, automaticity, and negative consequences for nonperformance as indicators of habit strength for this form of exercise. Methods: Upper-level undergraduates (N = 124) provided demographic information and responded to questionnaire items assessing historical MVPA involvement, current MVPA involvement, and the four proposed habit strength dimensions. Factor analyses were used to examine the latent structure of the habit strength indicators, and the model's construct validity was evaluated via an examination of relationships with repetition history and current behaviour. Results: At a measurement level, findings indicated that the proposed four-component model possessed psychometric integrity as a coherent set of factors. Criterion-related validity was also demonstrated via significant changes in three of the four factors as a function of past involvement in MVPA and significant correlations with the frequency, duration, and intensity of current MVPA. Conclusions: These findings support the construct validity of this exercise habit strength model and suggest that it could provide a template for future research on how MVPA habits are developed and maintained. PMID:25750789

A process-oriented measure of habit strength for moderate-to-vigorous physical activity.

PubMed

Grove, J Robert; Zillich, Irja; Medic, Nikola

2014-01-01

Purpose : Habitual action is an important aspect of health behaviour, but the relevance of various habit strength indicators continues to be debated. This study focused specifically on moderate-to-vigorous physical activity (MVPA) and evaluated the construct validity of a framework emphasizing patterned action, stimulus-response bonding, automaticity, and negative consequences for nonperformance as indicators of habit strength for this form of exercise. Methods : Upper-level undergraduates ( N  = 124) provided demographic information and responded to questionnaire items assessing historical MVPA involvement, current MVPA involvement, and the four proposed habit strength dimensions. Factor analyses were used to examine the latent structure of the habit strength indicators, and the model's construct validity was evaluated via an examination of relationships with repetition history and current behaviour. Results : At a measurement level, findings indicated that the proposed four-component model possessed psychometric integrity as a coherent set of factors. Criterion-related validity was also demonstrated via significant changes in three of the four factors as a function of past involvement in MVPA and significant correlations with the frequency, duration, and intensity of current MVPA. Conclusions : These findings support the construct validity of this exercise habit strength model and suggest that it could provide a template for future research on how MVPA habits are developed and maintained.

Reconstructing liver shape and position from MR image slices using an active shape model

NASA Astrophysics Data System (ADS)

Fenchel, Matthias; Thesen, Stefan; Schilling, Andreas

2008-03-01

We present an algorithm for fully automatic reconstruction of 3D position, orientation and shape of the human liver from a sparsely covering set of n 2D MR slice images. Reconstructing the shape of an organ from slice images can be used for scan planning, for surgical planning or other purposes where 3D anatomical knowledge has to be inferred from sparse slices. The algorithm is based on adapting an active shape model of the liver surface to a given set of slice images. The active shape model is created from a training set of liver segmentations from a group of volunteers. The training set is set up with semi-manual segmentations of T1-weighted volumetric MR images. Searching for the optimal shape model that best fits to the image data is done by maximizing a similarity measure based on local appearance at the surface. Two different algorithms for the active shape model search are proposed and compared: both algorithms seek to maximize the a-posteriori probability of the grey level appearance around the surface while constraining the surface to the space of valid shapes. The first algorithm works by using grey value profile statistics in normal direction. The second algorithm uses average and variance images to calculate the local surface appearance on the fly. Both algorithms are validated by fitting the active shape model to abdominal 2D slice images and comparing the shapes, which have been reconstructed, to the manual segmentations and to the results of active shape model searches from 3D image data. The results turn out to be promising and competitive to active shape model segmentations from 3D data.

Chemical Sensor Array Response Modeling Using Quantitative Structure-Activity Relationships Technique

NASA Astrophysics Data System (ADS)

Shevade, Abhijit V.; Ryan, Margaret A.; Homer, Margie L.; Zhou, Hanying; Manfreda, Allison M.; Lara, Liana M.; Yen, Shiao-Pin S.; Jewell, April D.; Manatt, Kenneth S.; Kisor, Adam K.

We have developed a Quantitative Structure-Activity Relationships (QSAR) based approach to correlate the response of chemical sensors in an array with molecular descriptors. A novel molecular descriptor set has been developed; this set combines descriptors of sensing film-analyte interactions, representing sensor response, with a basic analyte descriptor set commonly used in QSAR studies. The descriptors are obtained using a combination of molecular modeling tools and empirical and semi-empirical Quantitative Structure-Property Relationships (QSPR) methods. The sensors under investigation are polymer-carbon sensing films which have been exposed to analyte vapors at parts-per-million (ppm) concentrations; response is measured as change in film resistance. Statistically validated QSAR models have been developed using Genetic Function Approximations (GFA) for a sensor array for a given training data set. The applicability of the sensor response models has been tested by using it to predict the sensor activities for test analytes not considered in the training set for the model development. The validated QSAR sensor response models show good predictive ability. The QSAR approach is a promising computational tool for sensing materials evaluation and selection. It can also be used to predict response of an existing sensing film to new target analytes.

Prediction of functional aerobic capacity without exercise testing

NASA Technical Reports Server (NTRS)

Jackson, A. S.; Blair, S. N.; Mahar, M. T.; Wier, L. T.; Ross, R. M.; Stuteville, J. E.

1990-01-01

The purpose of this study was to develop functional aerobic capacity prediction models without using exercise tests (N-Ex) and to compare the accuracy with Astrand single-stage submaximal prediction methods. The data of 2,009 subjects (9.7% female) were randomly divided into validation (N = 1,543) and cross-validation (N = 466) samples. The validation sample was used to develop two N-Ex models to estimate VO2peak. Gender, age, body composition, and self-report activity were used to develop two N-Ex prediction models. One model estimated percent fat from skinfolds (N-Ex %fat) and the other used body mass index (N-Ex BMI) to represent body composition. The multiple correlations for the developed models were R = 0.81 (SE = 5.3 ml.kg-1.min-1) and R = 0.78 (SE = 5.6 ml.kg-1.min-1). This accuracy was confirmed when applied to the cross-validation sample. The N-Ex models were more accurate than what was obtained from VO2peak estimated from the Astrand prediction models. The SEs of the Astrand models ranged from 5.5-9.7 ml.kg-1.min-1. The N-Ex models were cross-validated on 59 men on hypertensive medication and 71 men who were found to have a positive exercise ECG. The SEs of the N-Ex models ranged from 4.6-5.4 ml.kg-1.min-1 with these subjects.(ABSTRACT TRUNCATED AT 250 WORDS).

Validated simulator for space debris removal with nets and other flexible tethers applications

NASA Astrophysics Data System (ADS)

Gołębiowski, Wojciech; Michalczyk, Rafał; Dyrek, Michał; Battista, Umberto; Wormnes, Kjetil

2016-12-01

In the context of active debris removal technologies and preparation activities for the e.Deorbit mission, a simulator for net-shaped elastic bodies dynamics and their interactions with rigid bodies, has been developed. Its main application is to aid net design and test scenarios for space debris deorbitation. The simulator can model all the phases of the debris capturing process: net launch, flight and wrapping around the target. It handles coupled simulation of rigid and flexible bodies dynamics. Flexible bodies were implemented using Cosserat rods model. It allows to simulate flexible threads or wires with elasticity and damping for stretching, bending and torsion. Threads may be combined into structures of any topology, so the software is able to simulate nets, pure tethers, tether bundles, cages, trusses, etc. Full contact dynamics was implemented. Programmatic interaction with simulation is possible - i.e. for control implementation. The underlying model has been experimentally validated and due to significant gravity influence, experiment had to be performed in microgravity conditions. Validation experiment for parabolic flight was a downscaled process of Envisat capturing. The prepacked net was launched towards the satellite model, it expanded, hit the model and wrapped around it. The whole process was recorded with 2 fast stereographic camera sets for full 3D trajectory reconstruction. The trajectories were used to compare net dynamics to respective simulations and then to validate the simulation tool. The experiments were performed on board of a Falcon-20 aircraft, operated by National Research Council in Ottawa, Canada. Validation results show that model reflects phenomenon physics accurately enough, so it may be used for scenario evaluation and mission design purposes. The functionalities of the simulator are described in detail in the paper, as well as its underlying model, sample cases and methodology behind validation. Results are presented and typical use cases are discussed showing that the software may be used to design throw nets for space debris capturing, but also to simulate deorbitation process, chaser control system or general interactions between rigid and elastic bodies - all in convenient and efficient way. The presented work was led by SKA Polska under the ESA contract, within the CleanSpace initiative.

Operations Assessment of Launch Vehicle Architectures using Activity Based Cost Models

NASA Technical Reports Server (NTRS)

Ruiz-Torres, Alex J.; McCleskey, Carey

2000-01-01

The growing emphasis on affordability for space transportation systems requires the assessment of new space vehicles for all life cycle activities, from design and development, through manufacturing and operations. This paper addresses the operational assessment of launch vehicles, focusing on modeling the ground support requirements of a vehicle architecture, and estimating the resulting costs and flight rate. This paper proposes the use of Activity Based Costing (ABC) modeling for this assessment. The model uses expert knowledge to determine the activities, the activity times and the activity costs based on vehicle design characteristics. The approach provides several advantages to current approaches to vehicle architecture assessment including easier validation and allowing vehicle designers to understand the cost and cycle time drivers.

Midazolam as an active placebo in 3 fentanyl-validated nociceptive pain models.

PubMed

Prosenz, Julian; Gustorff, Burkhard

2017-07-01

The use of inactive placebos in early translational trials of potentially analgesic compounds is discouraged because of the side-effect profiles of centrally acting analgesics. Therefore, benzodiazepines are used, although their use has not been validated in this context. Whether benzodiazepines confound the results of acute pain tests is unknown. Midazolam (0.06 mg/kg) as an active placebo was investigated in 3 nociceptive models that included contact heat, electrical pain, and pressure pain thresholds in 24 healthy volunteers. Fentanyl (1 μg/kg) served as an internal validator in this randomized, placebo (saline) controlled, 3-way cross-over trial. The primary outcome parameter (contact heat pain) was analyzed using a one-way, repeated measures analysis of variance and Tukey's post test. Midazolam did not reduce pain ([numeric rating scale], 0-100) in a statistically significant manner compared with placebo for the contact heat (mean difference -1.7, 95% confidence interval -10.6 to 7.3; P = 0.89) or electrical pain (4.3, -5.1 to 13.7; P = 0.51) test, nor did it raise the pressure pain thresholds (-28 kPa, -122; 64 kPa, P = 0.73). The width of the confidence intervals suggested that there were no clinically meaningful analgesic effects compared with the placebo. In contrast, the analgesic efficacy of fentanyl was effectively demonstrated in all 3 models (P < 0.01 vs midazolam and placebo). The findings of this study show that midazolam can be used as an active placebo in analgesic drug trials. Furthermore, the proposed models were simple to implement and very effective in detecting analgesia. The test battery can be used in translational trials for new compounds and comes with an active placebo and an optional active comparator.

Validation of Accelerometer-Based Energy Expenditure Prediction Models in Structured and Simulated Free-Living Settings

ERIC Educational Resources Information Center

Montoye, Alexander H. K.; Conger, Scott A.; Connolly, Christopher P.; Imboden, Mary T.; Nelson, M. Benjamin; Bock, Josh M.; Kaminsky, Leonard A.

2017-01-01

This study compared accuracy of energy expenditure (EE) prediction models from accelerometer data collected in structured and simulated free-living settings. Twenty-four adults (mean age 45.8 years, 50% female) performed two sessions of 11 to 21 activities, wearing four ActiGraph GT9X Link activity monitors (right hip, ankle, both wrists) and a…

A New Structure-Activity Relationship (SAR) Model for Predicting Drug-Induced Liver Injury, Based on Statistical and Expert-Based Structural Alerts

PubMed Central

Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Benfenati, Emilio

2016-01-01

The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model. To extract structural alerts (SAs) related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC) on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81, 63, and 68%, specificity 89, 33, and 33%, sensitivity 93, 88, and 80% and MCC 0.63, 0.27, and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model's architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform. PMID:27920722

Modeling temporal sequences of cognitive state changes based on a combination of EEG-engagement, EEG-workload, and heart rate metrics

PubMed Central

Stikic, Maja; Berka, Chris; Levendowski, Daniel J.; Rubio, Roberto F.; Tan, Veasna; Korszen, Stephanie; Barba, Douglas; Wurzer, David

2014-01-01

The objective of this study was to investigate the feasibility of physiological metrics such as ECG-derived heart rate and EEG-derived cognitive workload and engagement as potential predictors of performance on different training tasks. An unsupervised approach based on self-organizing neural network (NN) was utilized to model cognitive state changes over time. The feature vector comprised EEG-engagement, EEG-workload, and heart rate metrics, all self-normalized to account for individual differences. During the competitive training process, a linear topology was developed where the feature vectors similar to each other activated the same NN nodes. The NN model was trained and auto-validated on combat marksmanship training data from 51 participants that were required to make “deadly force decisions” in challenging combat scenarios. The trained NN model was cross validated using 10-fold cross-validation. It was also validated on a golf study in which additional 22 participants were asked to complete 10 sessions of 10 putts each. Temporal sequences of the activated nodes for both studies followed the same pattern of changes, demonstrating the generalization capabilities of the approach. Most node transition changes were local, but important events typically caused significant changes in the physiological metrics, as evidenced by larger state changes. This was investigated by calculating a transition score as the sum of subsequent state transitions between the activated NN nodes. Correlation analysis demonstrated statistically significant correlations between the transition scores and subjects' performances in both studies. This paper explored the hypothesis that temporal sequences of physiological changes comprise the discriminative patterns for performance prediction. These physiological markers could be utilized in future training improvement systems (e.g., through neurofeedback), and applied across a variety of training environments. PMID:25414629

Isolation of 4,5-O-Dicaffeoylquinic Acid as a Pigmentation Inhibitor Occurring in Artemisia capillaris Thunberg and Its Validation In Vivo.

PubMed

Tabassum, Nadia; Lee, Ji-Hyung; Yim, Soon-Ho; Batkhuu, Galzad Javzan; Jung, Da-Woon; Williams, Darren R

2016-01-01

There is a continual need to develop novel and effective melanogenesis inhibitors for the prevention of hyperpigmentation disorders. The plant Artemisia capillaris Thunberg (Oriental Wormwood) was screened for antipigmentation activity using murine cultured cells (B16-F10 malignant melanocytes). Activity-based fractionation using HPLC and NMR analyses identified the compound 4,5-O-dicaffeoylquinic acid as an active component in this plant. 4,5-O-Dicaffeoylquinic acid significantly reduced melanin synthesis and tyrosinase activity in a dose-dependent manner in the melanocytes. In addition, 4,5-O-dicaffeoylquinic acid treatment reduced the expression of tyrosinase-related protein-1. Significantly, we could validate the antipigmentation activity of this compound in vivo, using a zebrafish model. Moreover, 4,5-O-dicaffeoylquinic acid did not show toxicity in this animal model. Our discovery of 4,5-O-dicaffeoylquinic acid as an inhibitor of pigmentation that is active in vivo shows that this compound can be developed as an active component for formulations to treat pigmentation disorders.

The PDB_REDO server for macromolecular structure model optimization

PubMed Central

Joosten, Robbie P.; Long, Fei; Murshudov, Garib N.; Perrakis, Anastassis

2014-01-01

The refinement and validation of a crystallographic structure model is the last step before the coordinates and the associated data are submitted to the Protein Data Bank (PDB). The success of the refinement procedure is typically assessed by validating the models against geometrical criteria and the diffraction data, and is an important step in ensuring the quality of the PDB public archive [Read et al. (2011 ▶), Structure, 19, 1395–1412]. The PDB_REDO procedure aims for ‘constructive validation’, aspiring to consistent and optimal refinement parameterization and pro-active model rebuilding, not only correcting errors but striving for optimal interpretation of the electron density. A web server for PDB_REDO has been implemented, allowing thorough, consistent and fully automated optimization of the refinement procedure in REFMAC and partial model rebuilding. The goal of the web server is to help practicing crystallo­graphers to improve their model prior to submission to the PDB. For this, additional steps were implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g. testing of resolution limits and k-fold cross-validation for small test sets, and as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS and ligand validation as implemented in YASARA. Innovative ways to present the refinement and validation results to the user are also described, which together with auto-generated Coot scripts can guide users to subsequent model inspection and improvement. It is demonstrated that using the server can lead to substantial improvement of structure models before they are submitted to the PDB. PMID:25075342

Radiation Measurements Performed with Active Detectors Relevant for Human Space Exploration

PubMed Central

Narici, Livio; Berger, Thomas; Matthiä, Daniel; Reitz, Günther

2015-01-01

A reliable radiation risk assessment in space is a mandatory step for the development of countermeasures and long-duration mission planning in human spaceflight. Research in radiobiology provides information about possible risks linked to radiation. In addition, for a meaningful risk evaluation, the radiation exposure has to be assessed to a sufficient level of accuracy. Consequently, both the radiation models predicting the risks and the measurements used to validate such models must have an equivalent precision. Corresponding measurements can be performed both with passive and active devices. The former is easier to handle, cheaper, lighter, and smaller but they measure neither the time dependence of the radiation environment nor some of the details useful for a comprehensive radiation risk assessment. Active detectors provide most of these details and have been extensively used in the International Space Station. To easily access such an amount of data, a single point access is becoming essential. This review presents an ongoing work on the development of a tool that allows obtaining information about all relevant measurements performed with active detectors providing reliable inputs for radiation model validation. PMID:26697408

Radiation Measurements Performed with Active Detectors Relevant for Human Space Exploration.

PubMed

Narici, Livio; Berger, Thomas; Matthiä, Daniel; Reitz, Günther

2015-01-01

A reliable radiation risk assessment in space is a mandatory step for the development of countermeasures and long-duration mission planning in human spaceflight. Research in radiobiology provides information about possible risks linked to radiation. In addition, for a meaningful risk evaluation, the radiation exposure has to be assessed to a sufficient level of accuracy. Consequently, both the radiation models predicting the risks and the measurements used to validate such models must have an equivalent precision. Corresponding measurements can be performed both with passive and active devices. The former is easier to handle, cheaper, lighter, and smaller but they measure neither the time dependence of the radiation environment nor some of the details useful for a comprehensive radiation risk assessment. Active detectors provide most of these details and have been extensively used in the International Space Station. To easily access such an amount of data, a single point access is becoming essential. This review presents an ongoing work on the development of a tool that allows obtaining information about all relevant measurements performed with active detectors providing reliable inputs for radiation model validation.

Development of a human body finite element model with multiple muscles and their controller for estimating occupant motions and impact responses in frontal crash situations.

PubMed

Iwamoto, Masami; Nakahira, Yuko; Kimpara, Hideyuki; Sugiyama, Takahiko; Min, Kyuengbo

2012-10-01

A few reports suggest differences in injury outcomes between cadaver tests and real-world accidents under almost similar conditions. This study hypothesized that muscle activity could primarily cause the differences, and then developed a human body finite element (FE) model with individual muscles. Each muscle was modeled as a hybrid model of bar elements with active properties and solid elements with passive properties. The model without muscle activation was firstly validated against five series of cadaver test data on impact responses in the anterior-posterior direction. The model with muscle activation levels estimated based on electromyography (EMG) data was secondly validated against four series of volunteer test data on bracing effects for stiffness and thickness of an upper arm muscle, and braced driver's responses under a static environment and a brake deceleration. A muscle controller using reinforcement learning (RL), which is a mathematical model of learning process in the basal ganglia associated with human postural controls, were newly proposed to estimate muscle activity in various occupant conditions including inattentive and attentive conditions. Control of individual muscles predicted by RL reproduced more human like head-neck motions than conventional control of two groups of agonist and antagonist muscles. The model and the controller demonstrated that head-neck motions of an occupant under an impact deceleration of frontal crash were different in between a bracing condition with maximal braking force and an occupant condition predicted by RL. The model and the controller have the potential to investigate muscular effects in various occupant conditions during frontal crashes.

Psychometric evaluation of the PainCAS Interference with Daily Activities, Psychological/Emotional Distress, and Pain scales.

PubMed

McCaffrey, Stacey A; Black, Ryan A; Butler, Stephen F

2018-03-01

The PainCAS is a web-based clinical tool for assessing and tracking pain and opioid risk in chronic pain patients. Despite evidence for its utility within the clinical setting, the PainCAS scales have never been subject to psychometric evaluation. The current study is the first to evaluate the psychometric properties of the PainCAS Interference with Daily Activities, Psychological/Emotional Distress, and Pain scales. Patients (N = 4797) from treatment centers and hospitals in 16 different states completed the PainCAS as part of routine clinical assessment. A subsample (n = 73) from two hospital-based treatment centers also completed comparator measures. Rasch Rating Scale Models were employed to evaluate the Interference with Daily Activities and Psychological/Emotional Distress scales, and empirical evaluation included assessment of dimensionality, discrimination, item fit, reliability, information, and person-to-item targeting. Additionally, convergent and discriminant validity were evaluated through classical test theory approaches. Convergent validity of the Pain scales was evaluated through correlations with corresponding comparator items. One Interference with Daily Activities item was removed due to poor functioning and discrimination. The retained items from the Interference with Daily Activities and Psychological/Emotional Distress scales conformed to unidimensional Rasch measurement models, yielding satisfactory item fit, reliability, precision, and coverage. Further, results provided support for the convergent and discriminant validity of these two scales. Convergent validity between the PainCAS Pain and BPI Pain items was also strong. Taken together, results provide strong psychometric support for these PainCAS Pain scales. Strengths and limitations of the current study are discussed.

Development and Validation of a Musculoskeletal Model of the Fully Articulated Thoracolumbar Spine and Rib Cage

PubMed Central

Bruno, Alexander G.; Bouxsein, Mary L.; Anderson, Dennis E.

2015-01-01

We developed and validated a fully articulated model of the thoracolumbar spine in opensim that includes the individual vertebrae, ribs, and sternum. To ensure trunk muscles in the model accurately represent muscles in vivo, we used a novel approach to adjust muscle cross-sectional area (CSA) and position using computed tomography (CT) scans of the trunk sampled from a community-based cohort. Model predictions of vertebral compressive loading and trunk muscle tension were highly correlated to previous in vivo measures of intradiscal pressure (IDP), vertebral loading from telemeterized implants and trunk muscle myoelectric activity recorded by electromyography (EMG). PMID:25901907

Modeling and dynamic simulation of astronaut's upper limb motions considering counter torques generated by the space suit.

PubMed

Li, Jingwen; Ye, Qing; Ding, Li; Liao, Qianfang

2017-07-01

Extravehicular activity (EVA) is an inevitable task for astronauts to maintain proper functions of both the spacecraft and the space station. Both experimental research in a microgravity simulator (e.g. neutral buoyancy tank, zero-g aircraft or a drop tower/tube) and mathematical modeling were used to study EVA to provide guidance for the training on Earth and task design in space. Modeling has become more and more promising because of its efficiency. Based on the task analysis, almost 90% of EVA activity is accomplished through upper limb motions. Therefore, focusing on upper limb models of the body and space suit is valuable to this effort. In previous modeling studies, some multi-rigid-body systems were developed to simplify the human musculoskeletal system, and the space suit was mostly considered as a part of the astronaut body. With the aim to improve the reality of the models, we developed an astronauts' upper limb model, including a torque model and a muscle-force model, with the counter torques from the space suit being considered as a boundary condition. Inverse kinematics and the Maggi-Kane's method was applied to calculate the joint angles, joint torques and muscle force given that the terminal trajectory of upper limb motion was known. Also, we validated the muscle-force model using electromyogram (EMG) data collected in a validation experiment. Muscle force calculated from our model presented a similar trend with the EMG data, supporting the effectiveness and feasibility of the muscle-force model we established, and also, partially validating the joint model in kinematics aspect.

Three-dimensional quantitative structure-activity relationship studies on novel series of benzotriazine based compounds acting as Src inhibitors using CoMFA and CoMSIA.

PubMed

Gueto, Carlos; Ruiz, José L; Torres, Juan E; Méndez, Jefferson; Vivas-Reyes, Ricardo

2008-03-01

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of benzotriazine derivatives, as Src inhibitors. Ligand molecular superimposition on the template structure was performed by database alignment method. The statistically significant model was established of 72 molecules, which were validated by a test set of six compounds. The CoMFA model yielded a q(2)=0.526, non cross-validated R(2) of 0.781, F value of 88.132, bootstrapped R(2) of 0.831, standard error of prediction=0.587, and standard error of estimate=0.351 while the CoMSIA model yielded the best predictive model with a q(2)=0.647, non cross-validated R(2) of 0.895, F value of 115.906, bootstrapped R(2) of 0.953, standard error of prediction=0.519, and standard error of estimate=0.178. The contour maps obtained from 3D-QSAR studies were appraised for activity trends for the molecules analyzed. Results indicate that small steric volumes in the hydrophobic region, electron-withdrawing groups next to the aryl linker region, and atoms close to the solvent accessible region increase the Src inhibitory activity of the compounds. In fact, adding substituents at positions 5, 6, and 8 of the benzotriazine nucleus were generated new compounds having a higher predicted activity. The data generated from the present study will further help to design novel, potent, and selective Src inhibitors as anticancer therapeutic agents.

Gene-environment interactions and construct validity in preclinical models of psychiatric disorders.

PubMed

Burrows, Emma L; McOmish, Caitlin E; Hannan, Anthony J

2011-08-01

The contributions of genetic risk factors to susceptibility for brain disorders are often so closely intertwined with environmental factors that studying genes in isolation cannot provide the full picture of pathogenesis. With recent advances in our understanding of psychiatric genetics and environmental modifiers we are now in a position to develop more accurate animal models of psychiatric disorders which exemplify the complex interaction of genes and environment. Here, we consider some of the insights that have emerged from studying the relationship between defined genetic alterations and environmental factors in rodent models. A key issue in such animal models is the optimization of construct validity, at both genetic and environmental levels. Standard housing of laboratory mice and rats generally includes ad libitum food access and limited opportunity for physical exercise, leading to metabolic dysfunction under control conditions, and thus reducing validity of animal models with respect to clinical populations. A related issue, of specific relevance to neuroscientists, is that most standard-housed rodents have limited opportunity for sensory and cognitive stimulation, which in turn provides reduced incentive for complex motor activity. Decades of research using environmental enrichment has demonstrated beneficial effects on brain and behavior in both wild-type and genetically modified rodent models, relative to standard-housed littermate controls. One interpretation of such studies is that environmentally enriched animals more closely approximate average human levels of cognitive and sensorimotor stimulation, whereas the standard housing currently used in most laboratories models a more sedentary state of reduced mental and physical activity and abnormal stress levels. The use of such standard housing as a single environmental variable may limit the capacity for preclinical models to translate into successful clinical trials. Therefore, there is a need to optimize 'environmental construct validity' in animal models, while maintaining comparability between laboratories, so as to ensure optimal scientific and medical outcomes. Utilizing more sophisticated models to elucidate the relative contributions of genetic and environmental factors will allow for improved construct, face and predictive validity, thus facilitating the identification of novel therapeutic targets. Copyright © 2010 Elsevier Inc. All rights reserved.

Validity of Students Worksheet Based Problem-Based Learning for 9th Grade Junior High School in living organism Inheritance and Food Biotechnology.

NASA Astrophysics Data System (ADS)

Jefriadi, J.; Ahda, Y.; Sumarmin, R.

2018-04-01

Based on preliminary research of students worksheet used by teachers has several disadvantages such as students worksheet arranged directly drove learners conduct an investigation without preceded by directing learners to a problem or provide stimulation, student's worksheet not provide a concrete imageand presentation activities on the students worksheet not refer to any one learning models curicullum recommended. To address problems Reviews these students then developed a worksheet based on problem-based learning. This is a research development that using Ploom models. The phases are preliminary research, development and assessment. The instruments used in data collection that includes pieces of observation/interviews, instrument self-evaluation, instruments validity. The results of the validation expert on student worksheets get a valid result the average value 80,1%. Validity of students worksheet based problem-based learning for 9th grade junior high school in living organism inheritance and food biotechnology get valid category.

Implementation and validation of the extended Hill-type muscle model with robust routing capabilities in LS-DYNA for active human body models.

PubMed

Kleinbach, Christian; Martynenko, Oleksandr; Promies, Janik; Haeufle, Daniel F B; Fehr, Jörg; Schmitt, Syn

2017-09-02

In the state of the art finite element AHBMs for car crash analysis in the LS-DYNA software material named *MAT_MUSCLE (*MAT_156) is used for active muscles modeling. It has three elements in parallel configuration, which has several major drawbacks: restraint approximation of the physical reality, complicated parameterization and absence of the integrated activation dynamics. This study presents implementation of the extended four element Hill-type muscle model with serial damping and eccentric force-velocity relation including [Formula: see text] dependent activation dynamics and internal method for physiological muscle routing. Proposed model was implemented into the general-purpose finite element (FE) simulation software LSDYNA as a user material for truss elements. This material model is verified and validated with three different sets of mammalian experimental data, taken from the literature. It is compared to the *MAT_MUSCLE (*MAT_156) Hill-type muscle model already existing in LS-DYNA, which is currently used in finite element human body models (HBMs). An application example with an arm model extracted from the FE ViVA OpenHBM is given, taking into account physiological muscle paths. The simulation results show better material model accuracy, calculation robustness and improved muscle routing capability compared to *MAT_156. The FORTRAN source code for the user material subroutine dyn21.f and the muscle parameters for all simulations, conducted in the study, are given at https://zenodo.org/record/826209 under an open source license. This enables a quick application of the proposed material model in LS-DYNA, especially in active human body models (AHBMs) for applications in automotive safety.

The Role of Integrated Modeling in the Design and Verification of the James Webb Space Telescope

NASA Technical Reports Server (NTRS)

Mosier, Gary E.; Howard, Joseph M.; Johnston, John D.; Parrish, Keith A.; Hyde, T. Tupper; McGinnis, Mark A.; Bluth, Marcel; Kim, Kevin; Ha, Kong Q.

2004-01-01

The James Web Space Telescope (JWST) is a large, infrared-optimized space telescope scheduled for launch in 2011. System-level verification of critical optical performance requirements will rely on integrated modeling to a considerable degree. In turn, requirements for accuracy of the models are significant. The size of the lightweight observatory structure, coupled with the need to test at cryogenic temperatures, effectively precludes validation of the models and verification of optical performance with a single test in 1-g. Rather, a complex series of steps are planned by which the components of the end-to-end models are validated at various levels of subassembly, and the ultimate verification of optical performance is by analysis using the assembled models. This paper describes the critical optical performance requirements driving the integrated modeling activity, shows how the error budget is used to allocate and track contributions to total performance, and presents examples of integrated modeling methods and results that support the preliminary observatory design. Finally, the concepts for model validation and the role of integrated modeling in the ultimate verification of observatory are described.

Cross-validation of an employee safety climate model in Malaysia.

PubMed

Bahari, Siti Fatimah; Clarke, Sharon

2013-06-01

Whilst substantial research has investigated the nature of safety climate, and its importance as a leading indicator of organisational safety, much of this research has been conducted with Western industrial samples. The current study focuses on the cross-validation of a safety climate model in the non-Western industrial context of Malaysian manufacturing. The first-order factorial validity of Cheyne et al.'s (1998) [Cheyne, A., Cox, S., Oliver, A., Tomas, J.M., 1998. Modelling safety climate in the prediction of levels of safety activity. Work and Stress, 12(3), 255-271] model was tested, using confirmatory factor analysis, in a Malaysian sample. Results showed that the model fit indices were below accepted levels, indicating that the original Cheyne et al. (1998) safety climate model was not supported. An alternative three-factor model was developed using exploratory factor analysis. Although these findings are not consistent with previously reported cross-validation studies, we argue that previous studies have focused on validation across Western samples, and that the current study demonstrates the need to take account of cultural factors in the development of safety climate models intended for use in non-Western contexts. The results have important implications for the transferability of existing safety climate models across cultures (for example, in global organisations) and highlight the need for future research to examine cross-cultural issues in relation to safety climate. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Computational identification of structural factors affecting the mutagenic potential of aromatic amines: study design and experimental validation.

PubMed

Slavov, Svetoslav H; Stoyanova-Slavova, Iva; Mattes, William; Beger, Richard D; Brüschweiler, Beat J

2018-07-01

A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13 C and 15 N NMR chemical shifts augmented with through-space interatomic distances was used to model the mutagenicity of 554 primary and 419 secondary aromatic amines. A robust modeling strategy supported by extensive validation including randomized training/hold-out test set pairs, validation sets, "blind" external test sets as well as experimental validation was applied to avoid over-parameterization and build Organization for Economic Cooperation and Development (OECD 2004) compliant models. Based on an experimental validation set of 23 chemicals tested in a two-strain Salmonella typhimurium Ames assay, 3D-SDAR was able to achieve performance comparable to 5-strain (Ames) predictions by Lhasa Limited's Derek and Sarah Nexus for the same set. Furthermore, mapping of the most frequently occurring bins on the primary and secondary aromatic amine structures allowed the identification of molecular features that were associated either positively or negatively with mutagenicity. Prominent structural features found to enhance the mutagenic potential included: nitrobenzene moieties, conjugated π-systems, nitrothiophene groups, and aromatic hydroxylamine moieties. 3D-SDAR was also able to capture "true" negative contributions that are particularly difficult to detect through alternative methods. These include sulphonamide, acetamide, and other functional groups, which not only lack contributions to the overall mutagenic potential, but are known to actively lower it, if present in the chemical structures of what otherwise would be potential mutagens.

Optimization of CMCase production from sorghum straw by Aspergillus terreus SUK-1 under solid substrate fermentation using response surface methodology

NASA Astrophysics Data System (ADS)

Tibin, El Mubarak Musa; Al-Shorgani, Najeeb Kaid Naseer; Abuelhassan, Nawal Noureldaim; Hamid, Aidil Abdul; Kalil, Mohd Sahaid; Yusoff, Wan Mohtar Wan

2013-11-01

The cellulase production using sorghum straw as substrate by fungal culture of Aspergillus terreus SUK-1 was investigated in solid substrate fermentation (SSF). The optimum CMCase was achieved by testing most effective fermentation parameters which were: incubation temperature, pH and moisture content using Response Surface Methodology (RSM) based on Central Composite Design (CCD). The carboxymethyl cellulase activity (CMCase) was measured as the defining factor. The results were analysed by analysis of variance (ANOVA) and the regression quadratic model was obtained. The model was found to be significant (p<0.05) and the effect of temperature (25-40°C) and pH (4-7) was found to be not significant on CMCase activity whereas the moisture content was significant in the SSF conditions employed. The high yield of predicted CMCase activity (0.2 U/ml) was obtained under the optimized conditions (temperature 40 □C, pH 5.4 and moisture content of 80%). The model was validated by applying the optimized conditions and it was found that the model was valid.

Youth Oriented Activity Trackers: Comprehensive Laboratory- and Field-Based Validation

PubMed Central

2017-01-01

Background Commercial activity trackers are growing in popularity among adults and some are beginning to be marketed to children. There is, however, a paucity of independent research examining the validity of these devices to detect physical activity of different intensity levels. Objectives The purpose of this study was to determine the validity of the output from 3 commercial youth-oriented activity trackers in 3 phases: (1) orbital shaker, (2) structured indoor activities, and (3) 4 days of free-living activity. Methods Four units of each activity tracker (Movband [MB], Sqord [SQ], and Zamzee [ZZ]) were tested in an orbital shaker for 5-minutes at three frequencies (1.3, 1.9, and 2.5 Hz). Participants for Phase 2 (N=14) and Phase 3 (N=16) were 6-12 year old children (50% male). For Phase 2, participants completed 9 structured activities while wearing each tracker, the ActiGraph GT3X+ (AG) research accelerometer, and a portable indirect calorimetry system to assess energy expenditure (EE). For Phase 3, participants wore all 4 devices for 4 consecutive days. Correlation coefficients, linear models, and non-parametric statistics evaluated the criterion and construct validity of the activity tracker output. Results Output from all devices was significantly associated with oscillation frequency (r=.92-.99). During Phase 2, MB and ZZ only differentiated sedentary from light intensity (P<.01), whereas the SQ significantly differentiated among all intensity categories (all comparisons P<.01), similar to AG and EE. During Phase 3, AG counts were significantly associated with activity tracker output (r=.76, .86, and .59 for the MB, SQ, and ZZ, respectively). Conclusions Across study phases, the SQ demonstrated stronger validity than the MB and ZZ. The validity of youth-oriented activity trackers may directly impact their effectiveness as behavior modification tools, demonstrating a need for more research on such devices. PMID:28724509

Three-Step Validation of Exercise Behavior Processes of Change in an Adolescent Sample

ERIC Educational Resources Information Center

Rhodes, Ryan E.; Berry, Tanya; Naylor, Patti-Jean; Higgins, S. Joan Wharf

2004-01-01

Though the processes of change are conceived as the core constructs of the transtheoretical model (TTM), few researchers have examined their construct validity in the physical activity domain. Further, only 1 study was designed to investigate the processes of change in an adolescent sample. The purpose of this study was to examine the exercise…

Validation metrics for turbulent plasma transport

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

Holland, C., E-mail: chholland@ucsd.edu

Developing accurate models of plasma dynamics is essential for confident predictive modeling of current and future fusion devices. In modern computer science and engineering, formal verification and validation processes are used to assess model accuracy and establish confidence in the predictive capabilities of a given model. This paper provides an overview of the key guiding principles and best practices for the development of validation metrics, illustrated using examples from investigations of turbulent transport in magnetically confined plasmas. Particular emphasis is given to the importance of uncertainty quantification and its inclusion within the metrics, and the need for utilizing synthetic diagnosticsmore » to enable quantitatively meaningful comparisons between simulation and experiment. As a starting point, the structure of commonly used global transport model metrics and their limitations is reviewed. An alternate approach is then presented, which focuses upon comparisons of predicted local fluxes, fluctuations, and equilibrium gradients against observation. The utility of metrics based upon these comparisons is demonstrated by applying them to gyrokinetic predictions of turbulent transport in a variety of discharges performed on the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)], as part of a multi-year transport model validation activity.« less

Organizational member involvement in physical activity coalitions across the United States: development and testing of a novel survey instrument for assessing coalition functioning.

PubMed

Bornstein, Daniel B; Pate, Russell R; Beets, Michael W; Saunders, Ruth P; Blair, Steven N

2015-06-01

Coalitions are often composed of member organizations. Member involvement is thought to be associated with coalition success. No instrument currently exists for evaluating organizational member involvement in physical activity coalitions. This study aimed to develop a survey instrument for evaluating organizational member involvement in physical activity coalitions. The study was carried out in three phases: (a) developing a draft survey, (b) assessing the content validity of the draft survey, and (c) assessing the underlying factor structure, reliability, and validity of the survey. A cross-sectional design was employed. In Phase 1, a team of experts in survey development produced a draft survey. In Phase 2, the content validity of the draft survey was evaluated by a panel of individuals with expertise in physical activity coalitions. In Phase 3, the survey was administered to 120 individuals on local-, state-, and national-level physical activity coalitions. Responses were subjected to an exploratory factor analysis in order to determine the survey's underlying factor structure, reliability, and validity. Phases 1 and 2yielded a survey instrument with demonstrated content validity. Phase 3 yielded a three-factor model with three subscales: Strategic Alignment, Organizational Alignment, and Providing Input. Each subscale demonstrated high internal consistency reliability and construct validity. The survey instrument developed here demonstrated sound psychometric properties and provides new insight into organizational member involvement in physical activity coalitions. This instrument may be an important tool in developing a more complete picture of coalition functioning in physical activity coalitions specifically and health-based coalitions overall. © 2014 Society for Public Health Education.

Validation of the Malay Version of the Inventory of Functional Status after Childbirth Questionnaire

PubMed Central

Noor, Norhayati Mohd; Aziz, Aniza Abd.; Mostapa, Mohd Rosmizaki; Awang, Zainudin

2015-01-01

Objective. This study was designed to examine the psychometric properties of Malay version of the Inventory of Functional Status after Childbirth (IFSAC). Design. A cross-sectional study. Materials and Methods. A total of 108 postpartum mothers attending Obstetrics and Gynaecology Clinic, in a tertiary teaching hospital in Malaysia, were involved. Construct validity and internal consistency were performed after the translation, content validity, and face validity process. The data were analyzed using Analysis of Moment Structure version 18 and Statistical Packages for the Social Sciences version 20. Results. The final model consists of four constructs, namely, infant care, personal care, household activities, and social and community activities, with 18 items demonstrating acceptable factor loadings, domain to domain correlation, and best fit (Chi-squared/degree of freedom = 1.678; Tucker-Lewis index = 0.923; comparative fit index = 0.936; and root mean square error of approximation = 0.080). Composite reliability and average variance extracted of the domains ranged from 0.659 to 0.921 and from 0.499 to 0.628, respectively. Conclusion. The study suggested that the four-factor model with 18 items of the Malay version of IFSAC was acceptable to be used to measure functional status after childbirth because it is valid, reliable, and simple. PMID:25667932

Measuring emotions during epistemic activities: the Epistemically-Related Emotion Scales.

PubMed

Pekrun, Reinhard; Vogl, Elisabeth; Muis, Krista R; Sinatra, Gale M

2017-09-01

Measurement instruments assessing multiple emotions during epistemic activities are largely lacking. We describe the construction and validation of the Epistemically-Related Emotion Scales, which measure surprise, curiosity, enjoyment, confusion, anxiety, frustration, and boredom occurring during epistemic cognitive activities. The instrument was tested in a multinational study of emotions during learning from conflicting texts (N = 438 university students from the United States, Canada, and Germany). The findings document the reliability, internal validity, and external validity of the instrument. A seven-factor model best fit the data, suggesting that epistemically-related emotions should be conceptualised in terms of discrete emotion categories, and the scales showed metric invariance across the North American and German samples. Furthermore, emotion scores changed over time as a function of conflicting task information and related significantly to perceived task value and use of cognitive and metacognitive learning strategies.

An Evaluation of Blood Cholinesterase Testing Methods for Military Health

DTIC Science & Technology

2008-05-01

activity found that only one device has been validated for ChE testing in the field: the Model 400 Test-mate™ ChE kit by EQM Research, Inc. (Cincinnati...OH). Suggested future modifications to the Model 400 Test-mate™ ChE kit include displaying/recording of acetyl-ChE activity uncorrected for...cholinesterase activity , that are routinely monitored by the Department of Defense (DoD). Within DoD, definitive cholinesterase testing is conducted by

The 2014 Sandia Verification and Validation Challenge: Problem statement

DOE PAGES

Hu, Kenneth; Orient, George

2016-01-18

This paper presents a case study in utilizing information from experiments, models, and verification and validation (V&V) to support a decision. It consists of a simple system with data and models provided, plus a safety requirement to assess. The goal is to pose a problem that is flexible enough to allow challengers to demonstrate a variety of approaches, but constrained enough to focus attention on a theme. This was accomplished by providing a good deal of background information in addition to the data, models, and code, but directing the participants' activities with specific deliverables. In this challenge, the theme ismore » how to gather and present evidence about the quality of model predictions, in order to support a decision. This case study formed the basis of the 2014 Sandia V&V Challenge Workshop and this resulting special edition of the ASME Journal of Verification, Validation, and Uncertainty Quantification.« less

Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder.

PubMed

Fuchs, Eberhard

2005-03-01

Animal models are invaluable in preclinical research on human psychopathology. Valid animal models to study the pathophysiology of depression and specific biological and behavioral responses to antidepressant drug treatments are of prime interest. In order to improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation seen in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews. Coexistence of two males in visual and olfactory contact leads to a stable dominant/subordinate relationship, with the subordinates showing obvious changes in behavioral, neuroendocrine, and central nervous activity that are similar to the signs and symptoms observed during episodes of depression in patients. To discover whether this model, besides its "face validity" for depression, also has "predictive validity," we treated subordinate animals with the tricyclic antidepressant clomipramine and found a time-dependent recovery of both endocrine function and normal behavior. In contrast, the anxiolytic diazepam was ineffective. Chronic psychosocial stress in male tree shrews significantly decreased hippocampal volume and the proliferation rate of the granule precursor cells in the dentate gyrus. These stress-induced changes can be prevented by treating the animals with clomipramine, tianeptine, or the selective neurokinin receptor antagonist L-760,735. In addition to its apparent face and predictive validity, the tree shrew model also has a "molecular validity" due to the degradation routes of psychotropic compounds and gene sequences of receptors are very similar to those in humans. Although further research is required to validate this model fully, it provides an adequate and interesting non-rodent experimental paradigm for preclinical research on depression.

Prediction of energy expenditure and physical activity in preschoolers

USDA-ARS?s Scientific Manuscript database

Accurate, nonintrusive, and feasible methods are needed to predict energy expenditure (EE) and physical activity (PA) levels in preschoolers. Herein, we validated cross-sectional time series (CSTS) and multivariate adaptive regression splines (MARS) models based on accelerometry and heart rate (HR) ...

Forecasting volcanic ash dispersal and coeval resuspension during the April-May 2015 Calbuco eruption

NASA Astrophysics Data System (ADS)

Reckziegel, F.; Bustos, E.; Mingari, L.; Báez, W.; Villarosa, G.; Folch, A.; Collini, E.; Viramonte, J.; Romero, J.; Osores, S.

2016-07-01

Atmospheric dispersion of volcanic ash from explosive eruptions or from subsequent fallout deposit resuspension causes a range of impacts and disruptions on human activities and ecosystems. The April-May 2015 Calbuco eruption in Chile involved eruption and resuspension activities. We overview the chronology, effects, and products resulting from these events, in order to validate an operational forecast strategy for tephra dispersal. The modelling strategy builds on coupling the meteorological Weather Research and Forecasting (WRF/ARW) model with the FALL3D dispersal model for eruptive and resuspension processes. The eruption modelling considers two distinct particle granulometries, a preliminary first guess distribution used operationally when no field data was available yet, and a refined distribution based on field measurements. Volcanological inputs were inferred from eruption reports and results from an Argentina-Chilean ash sample data network, which performed in-situ sampling during the eruption. In order to validate the modelling strategy, results were compared with satellite retrievals and ground deposit measurements. Results indicate that the WRF-FALL3D modelling system can provide reasonable forecasts in both eruption and resuspension modes, particularly when the adjusted granulometry is considered. The study also highlights the importance of having dedicated datasets of active volcanoes furnishing first-guess model inputs during the early stages of an eruption.

Validation and Verification of Operational Land Analysis Activities at the Air Force Weather Agency

NASA Technical Reports Server (NTRS)

Shaw, Michael; Kumar, Sujay V.; Peters-Lidard, Christa D.; Cetola, Jeffrey

2012-01-01

The NASA developed Land Information System (LIS) is the Air Force Weather Agency's (AFWA) operational Land Data Assimilation System (LDAS) combining real time precipitation observations and analyses, global forecast model data, vegetation, terrain, and soil parameters with the community Noah land surface model, along with other hydrology module options, to generate profile analyses of global soil moisture, soil temperature, and other important land surface characteristics. (1) A range of satellite data products and surface observations used to generate the land analysis products (2) Global, 1/4 deg spatial resolution (3) Model analysis generated at 3 hours. AFWA recognizes the importance of operational benchmarking and uncertainty characterization for land surface modeling and is developing standard methods, software, and metrics to verify and/or validate LIS output products. To facilitate this and other needs for land analysis activities at AFWA, the Model Evaluation Toolkit (MET) -- a joint product of the National Center for Atmospheric Research Developmental Testbed Center (NCAR DTC), AFWA, and the user community -- and the Land surface Verification Toolkit (LVT), developed at the Goddard Space Flight Center (GSFC), have been adapted to operational benchmarking needs of AFWA's land characterization activities.

Synthesis, activity and pharmacophore development for isatin-β-thiosemicarbazones with selective activity towards multidrug resistant cellsa

PubMed Central

Hall, Matthew D.; Salam, Noeris K.; Hellawell, Jennifer L.; Fales, Henry M.; Kensler, Caroline B.; Ludwig, Joseph A.; Szakacs, Gergely; Hibbs, David E.; Gottesman, Michael M.

2009-01-01

We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β-thiosemicarbazones from our initial study have been validated, and a range of analogs synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1-selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone, and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicty of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity, and aid in directing the search for the mechanism of action of 1. PMID:19397322

A Gibbs Energy Minimization Approach for Modeling of Chemical Reactions in a Basic Oxygen Furnace

NASA Astrophysics Data System (ADS)

Kruskopf, Ari; Visuri, Ville-Valtteri

2017-12-01

In modern steelmaking, the decarburization of hot metal is converted into steel primarily in converter processes, such as the basic oxygen furnace. The objective of this work was to develop a new mathematical model for top blown steel converter, which accounts for the complex reaction equilibria in the impact zone, also known as the hot spot, as well as the associated mass and heat transport. An in-house computer code of the model has been developed in Matlab. The main assumption of the model is that all reactions take place in a specified reaction zone. The mass transfer between the reaction volume, bulk slag, and metal determine the reaction rates for the species. The thermodynamic equilibrium is calculated using the partitioning of Gibbs energy (PGE) method. The activity model for the liquid metal is the unified interaction parameter model and for the liquid slag the modified quasichemical model (MQM). The MQM was validated by calculating iso-activity lines for the liquid slag components. The PGE method together with the MQM was validated by calculating liquidus lines for solid components. The results were compared with measurements from literature. The full chemical reaction model was validated by comparing the metal and slag compositions to measurements from industrial scale converter. The predictions were found to be in good agreement with the measured values. Furthermore, the accuracy of the model was found to compare favorably with the models proposed in the literature. The real-time capability of the proposed model was confirmed in test calculations.

Modeling the target acquisition performance of active imaging systems

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Jacobs, Eddie L.; Halford, Carl E.; Vollmerhausen, Richard; Tofsted, David H.

2007-04-01

Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

Modeling the target acquisition performance of active imaging systems.

PubMed

Espinola, Richard L; Jacobs, Eddie L; Halford, Carl E; Vollmerhausen, Richard; Tofsted, David H

2007-04-02

Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

HPLC-Based Activity Profiling for GABAA Receptor Modulators in Extracts: Validation of an Approach Utilizing a Larval Zebrafish Locomotor Assay.

PubMed

Moradi-Afrapoli, Fahimeh; Ebrahimi, Samad Nejad; Smiesko, Martin; Hamburger, Matthias

2017-05-26

Gamma-aminobutyric acid type A (GABA A ) receptors are major inhibitory neurotransmitter receptors in the central nervous system and a target for numerous clinically important drugs used to treat anxiety, insomnia, and epilepsy. A series of allosteric GABA A receptor agonists was identified previously with the aid of HPLC-based activity profiling, whereby activity was tracked with an electrophysiological assay in Xenopus laevis oocytes. To accelerate the discovery process, an approach has been established for HPLC-based profiling using a larval zebrafish (Danio rerio) seizure model induced by pentylenetetrazol (PTZ), a pro-convulsant GABA A receptor antagonist. The assay was validated with the aid of representative GABAergic plant compounds and extracts. Various parameters that are relevant for the quality of results obtained, including PTZ concentration, the number of larvae, the incubation time, and the data analysis protocol, were optimized. The assay was then translated into an HPLC profiling protocol, and active compounds were tracked in extracts of Valeriana officinalis and Magnolia officinalis. For selected compounds the effects in the zebrafish larvae model were compared with data from in silico blood-brain barrier (BBB) permeability predictions, to validate the use for discovery of BBB-permeable natural products.

Multi-day activity scheduling reactions to planned activities and future events in a dynamic model of activity-travel behavior

NASA Astrophysics Data System (ADS)

Nijland, Linda; Arentze, Theo; Timmermans, Harry

2014-01-01

Modeling multi-day planning has received scarce attention in activity-based transport demand modeling so far. However, new dynamic activity-based approaches are being developed at the current moment. The frequency and inflexibility of planned activities and events in activity schedules of individuals indicate the importance of incorporating those pre-planned activities in the new generation of dynamic travel demand models. Elaborating and combining previous work on event-driven activity generation, the aim of this paper is to develop and illustrate an extension of a need-based model of activity generation that takes into account possible influences of pre-planned activities and events. This paper describes the theory and shows the results of simulations of the extension. The simulation was conducted for six different activities, and the parameter values used were consistent with an earlier estimation study. The results show that the model works well and that the influences of the parameters are consistent, logical, and have clear interpretations. These findings offer further evidence of face and construct validity to the suggested modeling approach.

Discovering new PI3Kα inhibitors with a strategy of combining ligand-based and structure-based virtual screening

NASA Astrophysics Data System (ADS)

Yu, Miao; Gu, Qiong; Xu, Jun

2018-02-01

PI3Kα is a promising drug target for cancer chemotherapy. In this paper, we report a strategy of combing ligand-based and structure-based virtual screening to identify new PI3Kα inhibitors. First, naïve Bayesian (NB) learning models and a 3D-QSAR pharmacophore model were built based upon known PI3Kα inhibitors. Then, the SPECS library was screened by the best NB model. This resulted in virtual hits, which were validated by matching the structures against the pharmacophore models. The pharmacophore matched hits were then docked into PI3Kα crystal structures to form ligand-receptor complexes, which are further validated by the Glide-XP program to result in structural validated hits. The structural validated hits were examined by PI3Kα inhibitory assay. With this screening protocol, ten PI3Kα inhibitors with new scaffolds were discovered with IC50 values ranging 0.44-31.25 μM. The binding affinities for the most active compounds 33 and 74 were estimated through molecular dynamics simulations and MM-PBSA analyses.

How much detail is needed in modeling a transcranial magnetic stimulation figure-8 coil: Measurements and brain simulations

PubMed Central

Mandija, Stefano; Sommer, Iris E. C.; van den Berg, Cornelis A. T.; Neggers, Sebastiaan F. W.

2017-01-01

Background Despite TMS wide adoption, its spatial and temporal patterns of neuronal effects are not well understood. Although progress has been made in predicting induced currents in the brain using realistic finite element models (FEM), there is little consensus on how a magnetic field of a typical TMS coil should be modeled. Empirical validation of such models is limited and subject to several limitations. Methods We evaluate and empirically validate models of a figure-of-eight TMS coil that are commonly used in published modeling studies, of increasing complexity: simple circular coil model; coil with in-plane spiral winding turns; and finally one with stacked spiral winding turns. We will assess the electric fields induced by all 3 coil models in the motor cortex using a computer FEM model. Biot-Savart models of discretized wires were used to approximate the 3 coil models of increasing complexity. We use a tailored MR based phase mapping technique to get a full 3D validation of the incident magnetic field induced in a cylindrical phantom by our TMS coil. FEM based simulations on a meshed 3D brain model consisting of five tissues types were performed, using two orthogonal coil orientations. Results Substantial differences in the induced currents are observed, both theoretically and empirically, between highly idealized coils and coils with correctly modeled spiral winding turns. Thickness of the coil winding turns affect minimally the induced electric field, and it does not influence the predicted activation. Conclusion TMS coil models used in FEM simulations should include in-plane coil geometry in order to make reliable predictions of the incident field. Modeling the in-plane coil geometry is important to correctly simulate the induced electric field and to correctly make reliable predictions of neuronal activation PMID:28640923

Two-Speed Gearbox Dynamic Simulation Predictions and Test Validation

NASA Technical Reports Server (NTRS)

Lewicki, David G.; DeSmidt, Hans; Smith, Edward C.; Bauman, Steven W.

2010-01-01

Dynamic simulations and experimental validation tests were performed on a two-stage, two-speed gearbox as part of the drive system research activities of the NASA Fundamental Aeronautics Subsonics Rotary Wing Project. The gearbox was driven by two electromagnetic motors and had two electromagnetic, multi-disk clutches to control output speed. A dynamic model of the system was created which included a direct current electric motor with proportional-integral-derivative (PID) speed control, a two-speed gearbox with dual electromagnetically actuated clutches, and an eddy current dynamometer. A six degree-of-freedom model of the gearbox accounted for the system torsional dynamics and included gear, clutch, shaft, and load inertias as well as shaft flexibilities and a dry clutch stick-slip friction model. Experimental validation tests were performed on the gearbox in the NASA Glenn gear noise test facility. Gearbox output speed and torque as well as drive motor speed and current were compared to those from the analytical predictions. The experiments correlate very well with the predictions, thus validating the dynamic simulation methodologies.

Engineering uses of physics-based ground motion simulations

USGS Publications Warehouse

Baker, Jack W.; Luco, Nicolas; Abrahamson, Norman A.; Graves, Robert W.; Maechling, Phillip J.; Olsen, Kim B.

2014-01-01

This paper summarizes validation methodologies focused on enabling ground motion simulations to be used with confidence in engineering applications such as seismic hazard analysis and dynmaic analysis of structural and geotechnical systems. Numberical simullation of ground motion from large erthquakes, utilizing physics-based models of earthquake rupture and wave propagation, is an area of active research in the earth science community. Refinement and validatoin of these models require collaboration between earthquake scientists and engineering users, and testing/rating methodolgies for simulated ground motions to be used with confidence in engineering applications. This paper provides an introduction to this field and an overview of current research activities being coordinated by the Souther California Earthquake Center (SCEC). These activities are related both to advancing the science and computational infrastructure needed to produce ground motion simulations, as well as to engineering validation procedures. Current research areas and anticipated future achievements are also discussed.

A combined ligand-based and target-based drug design approach for G-protein coupled receptors: application to salvinorin A, a selective kappa opioid receptor agonist

NASA Astrophysics Data System (ADS)

Singh, Nidhi; Chevé, Gwénaël; Ferguson, David M.; McCurdy, Christopher R.

2006-08-01

Combined ligand-based and target-based drug design approaches provide a synergistic advantage over either method individually. Therefore, we set out to develop a powerful virtual screening model to identify novel molecular scaffolds as potential leads for the human KOP (hKOP) receptor employing a combined approach. Utilizing a set of recently reported derivatives of salvinorin A, a structurally unique KOP receptor agonist, a pharmacophore model was developed that consisted of two hydrogen bond acceptor and three hydrophobic features. The model was cross-validated by randomizing the data using the CatScramble technique. Further validation was carried out using a test set that performed well in classifying active and inactive molecules correctly. Simultaneously, a bovine rhodopsin based "agonist-bound" hKOP receptor model was also generated. The model provided more accurate information about the putative binding site of salvinorin A based ligands. Several protein structure-checking programs were used to validate the model. In addition, this model was in agreement with the mutation experiments carried out on KOP receptor. The predictive ability of the model was evaluated by docking a set of known KOP receptor agonists into the active site of this model. The docked scores correlated reasonably well with experimental p K i values. It is hypothesized that the integration of these two independently generated models would enable a swift and reliable identification of new lead compounds that could reduce time and cost of hit finding within the drug discovery and development process, particularly in the case of GPCRs.

Validity Assessment of 5 Day Repeated Forced-Swim Stress to Model Human Depression in Young-Adult C57BL/6J and BALB/cJ Mice

PubMed Central

Zheng, Jia; Goodyear, Laurie J.

2016-01-01

The development of animal models with construct, face, and predictive validity to accurately model human depression has been a major challenge. One proposed rodent model is the 5 d repeated forced swim stress (5d-RFSS) paradigm, which progressively increases floating during individual swim sessions. The onset and persistence of this floating behavior has been anthropomorphically characterized as a measure of depression. This interpretation has been under debate because a progressive increase in floating over time may reflect an adaptive learned behavioral response promoting survival, and not depression (Molendijk and de Kloet, 2015). To assess construct and face validity, we applied 5d-RFSS to C57BL/6J and BALB/cJ mice, two mouse strains commonly used in neuropsychiatric research, and measured a combination of emotional, homeostatic, and psychomotor symptoms indicative of a depressive-like state. We also compared the efficacy of 5d-RFSS and chronic social defeat stress (CSDS), a validated depression model, to induce a depressive-like state in C57BL/6J mice. In both strains, 5d-RFSS progressively increased floating behavior that persisted for at least 4 weeks. 5d-RFSS did not alter sucrose preference, body weight, appetite, locomotor activity, anxiety-like behavior, or immobility behavior during a tail-suspension test compared with nonstressed controls. In contrast, CSDS altered several of these parameters, suggesting a depressive-like state. Finally, predictive validity was assessed using voluntary wheel running (VWR), a known antidepressant intervention. Four weeks of VWR after 5d-RFSS normalized floating behavior toward nonstressed levels. These observations suggest that 5d-RFSS has no construct or face validity but might have predictive validity to model human depression. PMID:28058270

Validity Assessment of 5 Day Repeated Forced-Swim Stress to Model Human Depression in Young-Adult C57BL/6J and BALB/cJ Mice.

PubMed

Mul, Joram D; Zheng, Jia; Goodyear, Laurie J

2016-01-01

The development of animal models with construct, face, and predictive validity to accurately model human depression has been a major challenge. One proposed rodent model is the 5 d repeated forced swim stress (5d-RFSS) paradigm, which progressively increases floating during individual swim sessions. The onset and persistence of this floating behavior has been anthropomorphically characterized as a measure of depression. This interpretation has been under debate because a progressive increase in floating over time may reflect an adaptive learned behavioral response promoting survival, and not depression (Molendijk and de Kloet, 2015). To assess construct and face validity, we applied 5d-RFSS to C57BL/6J and BALB/cJ mice, two mouse strains commonly used in neuropsychiatric research, and measured a combination of emotional, homeostatic, and psychomotor symptoms indicative of a depressive-like state. We also compared the efficacy of 5d-RFSS and chronic social defeat stress (CSDS), a validated depression model, to induce a depressive-like state in C57BL/6J mice. In both strains, 5d-RFSS progressively increased floating behavior that persisted for at least 4 weeks. 5d-RFSS did not alter sucrose preference, body weight, appetite, locomotor activity, anxiety-like behavior, or immobility behavior during a tail-suspension test compared with nonstressed controls. In contrast, CSDS altered several of these parameters, suggesting a depressive-like state. Finally, predictive validity was assessed using voluntary wheel running (VWR), a known antidepressant intervention. Four weeks of VWR after 5d-RFSS normalized floating behavior toward nonstressed levels. These observations suggest that 5d-RFSS has no construct or face validity but might have predictive validity to model human depression.

Development of a parent‐reported questionnaire evaluating upper limb activity limitation in children with cerebral palsy

PubMed Central

Preston, N.; Levesley, M.; Mon‐Williams, M.; O'Connor, R.J.

2017-01-01

Abstract Background and purpose Upper limb activity measures for children with cerebral palsy have a number of limitations, for example, lack of validity and poor responsiveness. To overcome these limitations, we developed the Children's Arm Rehabilitation Measure (ChARM), a parent‐reported questionnaire validated for children with cerebral palsy aged 5–16 years. This paper describes both the development of the ChARM items and response categories and its psychometric testing and further refinement using the Rasch measurement model. Methods To generate valid items for the ChARM, we collected goals of therapy specifically developed by therapists, children with cerebral palsy, and their parents for improving activity limitation of the upper limb. The activities, which were the focus of these goals, formed the basis for the items. Therapists typically break an activity into natural stages for the purpose of improving activity performance, and these natural orders of achievement formed each item's response options. Items underwent face validity testing with health care professionals, parents of children with cerebral palsy, academics, and lay persons. A Rasch analysis was performed on ChARM questionnaires completed by the parents of 170 children with cerebral palsy from 12 hospital paediatric services. The ChARM was amended, and the procedure repeated on 148 ChARMs (from children's mean age: 10 years and 1 month; range: 4 years and 8 months to 16 years and 11 months; 85 males; Manual Ability Classification System Levels I = 9, II = 26, III = 48, IV = 45, and V = 18). Results The final 19‐item unidimensional questionnaire displayed fit to the Rasch model (chi‐square p = .18), excellent reliability (person separation index = 0.95, α = 0.95), and no floor or ceiling effects. Items showed no response bias for gender, distribution of impairment, age, or learning disability. Discussion The ChARM is a psychometrically sound measure of upper limb activity validated for children with cerebral palsy aged 5–16 years. The ChARM is freely available for use to clinicians and nonprofit organisations. PMID:28112465

Development of predictive pharmacophore model for in silico screening, and 3D QSAR CoMFA and CoMSIA studies for lead optimization, for designing of potent tumor necrosis factor alpha converting enzyme inhibitors

NASA Astrophysics Data System (ADS)

Murumkar, Prashant Revan; Zambre, Vishal Prakash; Yadav, Mange Ram

2010-02-01

A chemical feature-based pharmacophore model was developed for Tumor Necrosis Factor-α converting enzyme (TACE) inhibitors. A five point pharmacophore model having two hydrogen bond acceptors (A), one hydrogen bond donor (D) and two aromatic rings (R) with discrete geometries as pharmacophoric features was developed. The pharmacophore model so generated was then utilized for in silico screening of a database. The pharmacophore model so developed was validated by using four compounds having proven TACE inhibitory activity which were grafted into the database. These compounds mapped well onto the five listed pharmacophoric features. This validated pharmacophore model was also used for alignment of molecules in CoMFA and CoMSIA analysis. The contour maps of the CoMFA/CoMSIA models were utilized to provide structural insight for activity improvement of potential novel TACE inhibitors. The pharmacophore model so developed could be used for in silico screening of any commercial/in house database for identification of TACE inhibiting lead compounds, and the leads so identified could be optimized using the developed CoMSIA model. The present work highlights the tremendous potential of the two mutually complementary ligand-based drug designing techniques (i.e. pharmacophore mapping and 3D-QSAR analysis) using TACE inhibitors as prototype biologically active molecules.

Application of the Monte Carlo method to estimate doses due to neutron activation of different materials in a nuclear reactor

NASA Astrophysics Data System (ADS)

Ródenas, José

2017-11-01

All materials exposed to some neutron flux can be activated independently of the kind of the neutron source. In this study, a nuclear reactor has been considered as neutron source. In particular, the activation of control rods in a BWR is studied to obtain the doses produced around the storage pool for irradiated fuel of the plant when control rods are withdrawn from the reactor and installed into this pool. It is very important to calculate these doses because they can affect to plant workers in the area. The MCNP code based on the Monte Carlo method has been applied to simulate activation reactions produced in the control rods inserted into the reactor. Obtained activities are introduced as input into another MC model to estimate doses produced by them. The comparison of simulation results with experimental measurements allows the validation of developed models. The developed MC models have been also applied to simulate the activation of other materials, such as components of a stainless steel sample introduced into a training reactors. These models, once validated, can be applied to other situations and materials where a neutron flux can be found, not only nuclear reactors. For instance, activation analysis with an Am-Be source, neutrography techniques in both medical applications and non-destructive analysis of materials, civil engineering applications using a Troxler, analysis of materials in decommissioning of nuclear power plants, etc.

Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists

NASA Astrophysics Data System (ADS)

Ji, Yongjun; Shu, Mao; Lin, Yong; Wang, Yuanqiang; Wang, Rui; Hu, Yong; Lin, Zhihua

2013-08-01

The beta chemokine receptor 5 (CCR5) is an attractive target for pharmaceutical industry in the HIV-1, inflammation and cancer therapeutic areas. In this study, we have developed quantitative structure activity relationship (QSAR) models for a series of 41 azacycles CCR5 antagonists using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and Topomer CoMFA methods. The cross-validated coefficient q2 values of 3D-QASR (CoMFA, CoMSIA, and Topomer CoMFA) methods were 0.630, 0.758, and 0.852, respectively, the non-cross-validated R2 values were 0.979, 0.978, and 0.990, respectively. Docking studies were also employed to determine the most probable binding mode. 3D contour maps and docking results suggested that bulky groups and electron-withdrawing groups on the core part would decrease antiviral activity. Furthermore, docking results indicated that H-bonds and π bonds were favorable for antiviral activities. Finally, a set of novel derivatives with predicted activities were designed.

A clinical reasoning model focused on clients' behaviour change with reference to physiotherapists: its multiphase development and validation.

PubMed

Elvén, Maria; Hochwälder, Jacek; Dean, Elizabeth; Söderlund, Anne

2015-05-01

A biopsychosocial approach and behaviour change strategies have long been proposed to serve as a basis for addressing current multifaceted health problems. This emphasis has implications for clinical reasoning of health professionals. This study's aim was to develop and validate a conceptual model to guide physiotherapists' clinical reasoning focused on clients' behaviour change. Phase 1 consisted of the exploration of existing research and the research team's experiences and knowledge. Phases 2a and 2b consisted of validation and refinement of the model based on input from physiotherapy students in two focus groups (n = 5 per group) and from experts in behavioural medicine (n = 9). Phase 1 generated theoretical and evidence bases for the first version of a model. Phases 2a and 2b established the validity and value of the model. The final model described clinical reasoning focused on clients' behaviour change as a cognitive, reflective, collaborative and iterative process with multiple interrelated levels that included input from the client and physiotherapist, a functional behavioural analysis of the activity-related target behaviour and the selection of strategies for behaviour change. This unique model, theory- and evidence-informed, has been developed to help physiotherapists to apply clinical reasoning systematically in the process of behaviour change with their clients.

Validation of reactive gases and aerosols in the MACC global analysis and forecast system

NASA Astrophysics Data System (ADS)

Eskes, H.; Huijnen, V.; Arola, A.; Benedictow, A.; Blechschmidt, A.-M.; Botek, E.; Boucher, O.; Bouarar, I.; Chabrillat, S.; Cuevas, E.; Engelen, R.; Flentje, H.; Gaudel, A.; Griesfeller, J.; Jones, L.; Kapsomenakis, J.; Katragkou, E.; Kinne, S.; Langerock, B.; Razinger, M.; Richter, A.; Schultz, M.; Schulz, M.; Sudarchikova, N.; Thouret, V.; Vrekoussis, M.; Wagner, A.; Zerefos, C.

2015-02-01

The European MACC (Monitoring Atmospheric Composition and Climate) project is preparing the operational Copernicus Atmosphere Monitoring Service (CAMS), one of the services of the European Copernicus Programme on Earth observation and environmental services. MACC uses data assimilation to combine in-situ and remote sensing observations with global and regional models of atmospheric reactive gases, aerosols and greenhouse gases, and is based on the Integrated Forecast System of the ECMWF. The global component of the MACC service has a dedicated validation activity to document the quality of the atmospheric composition products. In this paper we discuss the approach to validation that has been developed over the past three years. Topics discussed are the validation requirements, the operational aspects, the measurement data sets used, the structure of the validation reports, the models and assimilation systems validated, the procedure to introduce new upgrades, and the scoring methods. One specific target of the MACC system concerns forecasting special events with high pollution concentrations. Such events receive extra attention in the validation process. Finally, a summary is provided of the results from the validation of the latest set of daily global analysis and forecast products from the MACC system reported in November 2014.

Psychometric properties of the Social Cognitive Theory questionnaire for physical activity in a sample of Iranian adolescent girl students.

PubMed

Ardestani, M S; Niknami, S; Hidarnia, A; Hajizadeh, E

2016-08-18

This research examined the validity and reliability of a researcher-developed questionnaire based on Social Cognitive Theory (SCT) to assess the physical activity behaviour of Iranian adolescent girls (SCT-PAIAGS). Psychometric properties of the SCT-PAIAGS were assessed by determining its face validity, content and construct validity as well as its reliability. In order to evaluate factor structure, cross-sectional research was conducted on 400 high-school girls in Tehran. Content validity index, content validity ratio and impact score for the SCT-PAIAGS varied between 0.97-1, 0.91-1 and 4.6-4.9 respectively. Confirmatory factor analysis approved a six-factor structure comprising self-efficacy, self-regulation, family support, friend support, outcome expectancy and self-efficacy to overcoming impediments. Factor loadings, t-values and fit indices showed that the SCT model was fitted to the data. Cronbach's α-coefficient ranged from 0.78 to 0.85 and intraclass correlation coefficient from 0.73 to 0.90.

Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents.

PubMed

Patel, Preeti; Singh, Avineesh; Patel, Vijay K; Jain, Deepak K; Veerasamy, Ravichandran; Rajak, Harish

2016-01-01

Histone deacetylase (HDAC) inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. To identify the important pharmacophoric features and correlate 3Dchemical structure with biological activity using 3D-QSAR and Pharmacophore modeling studies. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with wellassigned HDAC inhibitory activity were used for 3D-QSAR model development. Best 3D-QSAR model, which is a five partial least square (PLS) factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811), cross-validated coefficient rcv 2=0.9807 and R2 pred=0.7147 with low standard deviation (0.0952). Additionally, the selected pharmacophore model DDRRR.419 was used as a 3D query for virtual screening against the ZINC database. In the virtual screening workflow, docking studies (HTVS, SP and XP) were carried out by selecting multiple receptors (PDB ID: 1T69, 1T64, 4LXZ, 4LY1, 3MAX, 2VQQ, 3C10, 1W22). Finally, six compounds were obtained based on high scoring function (dock score -11.2278-10.2222 kcal/mol) and diverse structures. The structure activity correlation was established using virtual screening, docking, energetic based pharmacophore modelling, pharmacophore, atom based 3D QSAR models and their validation. The outcomes of these studies could be further employed for the design of novel HDAC inhibitors for anticancer activity.

Fiber Optic Wing Shape Sensing on NASA's Ikhana UAV

NASA Technical Reports Server (NTRS)

Richards, Lance; Parker, Allen R.; Ko, William L.; Piazza, Anthony

2008-01-01

This document discusses the development of fiber optic wing shape sensing on NASA's Ikhana vehicle. The Dryden Flight Research Center's Aerostructures Branch initiated fiber-optic instrumentation development efforts in the mid-1990s. Motivated by a failure to control wing dihedral resulting in a mishap with the Helios aircraft, new wing displacement techniques were developed. Research objectives for Ikhana included validating fiber optic sensor measurements and real-time wing shape sensing predictions; the validation of fiber optic mathematical models and design tools; assessing technical viability and, if applicable, developing methodology and approaches to incorporate wing shape measurements within the vehicle flight control system; and, developing and flight validating approaches to perform active wing shape control using conventional control surfaces and active material concepts.

Electrothermal Equivalent Three-Dimensional Finite-Element Model of a Single Neuron.

PubMed

Cinelli, Ilaria; Destrade, Michel; Duffy, Maeve; McHugh, Peter

2018-06-01

We propose a novel approach for modelling the interdependence of electrical and mechanical phenomena in nervous cells, by using electrothermal equivalences in finite element (FE) analysis so that existing thermomechanical tools can be applied. First, the equivalence between electrical and thermal properties of the nerve materials is established, and results of a pure heat conduction analysis performed in Abaqus CAE Software 6.13-3 are validated with analytical solutions for a range of steady and transient conditions. This validation includes the definition of equivalent active membrane properties that enable prediction of the action potential. Then, as a step toward fully coupled models, electromechanical coupling is implemented through the definition of equivalent piezoelectric properties of the nerve membrane using the thermal expansion coefficient, enabling prediction of the mechanical response of the nerve to the action potential. Results of the coupled electromechanical model are validated with previously published experimental results of deformation for squid giant axon, crab nerve fibre, and garfish olfactory nerve fibre. A simplified coupled electromechanical modelling approach is established through an electrothermal equivalent FE model of a nervous cell for biomedical applications. One of the key findings is the mechanical characterization of the neural activity in a coupled electromechanical domain, which provides insights into the electromechanical behaviour of nervous cells, such as thinning of the membrane. This is a first step toward modelling three-dimensional electromechanical alteration induced by trauma at nerve bundle, tissue, and organ levels.

Short-Term Forecasts Using NU-WRF for the Winter Olympics 2018

NASA Technical Reports Server (NTRS)

Srikishen, Jayanthi; Case, Jonathan L.; Petersen, Walter A.; Iguchi, Takamichi; Tao, Wei-Kuo; Zavodsky, Bradley T.; Molthan, Andrew

2017-01-01

The NASA Unified-Weather Research and Forecasting model (NU-WRF) will be included for testing and evaluation in the forecast demonstration project (FDP) of the International Collaborative Experiment -PyeongChang 2018 Olympic and Paralympic (ICE-POP) Winter Games. An international array of radar and supporting ground based observations together with various forecast and now-cast models will be operational during ICE-POP. In conjunction with personnel from NASA's Goddard Space Flight Center, the NASA Short-term Prediction Research and Transition (SPoRT) Center is developing benchmark simulations for a real-time NU-WRF configuration to run during the FDP. ICE-POP observational datasets will be used to validate model simulations and investigate improved model physics and performance for prediction of snow events during the research phase (RDP) of the project The NU-WRF model simulations will also support NASA Global Precipitation Measurement (GPM) Mission ground-validation physical and direct validation activities in relation to verifying, testing and improving satellite-based snowfall retrieval algorithms over complex terrain.

Evaluation of CASL boiling model for DNB performance in full scale 5x5 fuel bundle with spacer grids

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

Kim, Seung Jun

As one of main tasks for FY17 CASL-THM activity, Evaluation study on applicability of the CASL baseline boiling model for 5x5 DNB application is conducted and the predictive capability of the DNB analysis is reported here. While the baseline CASL-boiling model (GEN- 1A) approach has been successfully implemented and validated with a single pipe application in the previous year’s task, the extended DNB validation for realistic sub-channels with detailed spacer grid configurations are tasked in FY17. The focus area of the current study is to demonstrate the robustness and feasibility of the CASL baseline boiling model for DNB performance inmore » a full 5x5 fuel bundle application. A quantitative evaluation of the DNB predictive capability is performed by comparing with corresponding experimental measurements (i.e. reference for the model validation). The reference data are provided from the Westinghouse Electricity Company (WEC). Two different grid configurations tested here include Non-Mixing Vane Grid (NMVG), and Mixing Vane Grid (MVG). Thorough validation studies with two sub-channel configurations are performed at a wide range of realistic PWR operational conditions.« less

Refining Time-Activity Classification of Human Subjects Using the Global Positioning System.

PubMed

Hu, Maogui; Li, Wei; Li, Lianfa; Houston, Douglas; Wu, Jun

2016-01-01

Detailed spatial location information is important in accurately estimating personal exposure to air pollution. Global Position System (GPS) has been widely used in tracking personal paths and activities. Previous researchers have developed time-activity classification models based on GPS data, most of them were developed for specific regions. An adaptive model for time-location classification can be widely applied to air pollution studies that use GPS to track individual level time-activity patterns. Time-activity data were collected for seven days using GPS loggers and accelerometers from thirteen adult participants from Southern California under free living conditions. We developed an automated model based on random forests to classify major time-activity patterns (i.e. indoor, outdoor-static, outdoor-walking, and in-vehicle travel). Sensitivity analysis was conducted to examine the contribution of the accelerometer data and the supplemental spatial data (i.e. roadway and tax parcel data) to the accuracy of time-activity classification. Our model was evaluated using both leave-one-fold-out and leave-one-subject-out methods. Maximum speeds in averaging time intervals of 7 and 5 minutes, and distance to primary highways with limited access were found to be the three most important variables in the classification model. Leave-one-fold-out cross-validation showed an overall accuracy of 99.71%. Sensitivities varied from 84.62% (outdoor walking) to 99.90% (indoor). Specificities varied from 96.33% (indoor) to 99.98% (outdoor static). The exclusion of accelerometer and ambient light sensor variables caused a slight loss in sensitivity for outdoor walking, but little loss in overall accuracy. However, leave-one-subject-out cross-validation showed considerable loss in sensitivity for outdoor static and outdoor walking conditions. The random forests classification model can achieve high accuracy for the four major time-activity categories. The model also performed well with just GPS, road and tax parcel data. However, caution is warranted when generalizing the model developed from a small number of subjects to other populations.

Pharmacokinetic and pharmacodynamic model for analysis of adalimumab administered for Crohn's disease.

PubMed

Kimura, Koji; Yoshida, Atsushi; Takayanagi, Risa; Yamada, Yasuhiko

2018-05-23

Adalimumab (ADA) is used as a therapeutic agent for Crohn's disease (CD). Although that dosage regimen has been established through clinical trial experience, it has not been analyzed theoretically. In the present study, we analyzed of sequential changes of the Crohn's disease activity index (CDAI) after repeated administrations of ADA using a pharmacokinetic and pharmacodynamic model. In addition, we analyzed the validity of the dosage regimen, and potential efficacy gained by increasing the dose and reducing the interval of administration. The sequential changes in CDAI values obtained with our model were in good agreement with observed CDAI values, which was considered to show the validity of our analysis. We considered that our results showed the importance of the loading dose of ADA to obtain remission in an early stage of active CD. In addition, we showed that patients who have an incomplete response to ADA can obtain similar efficacy from increasing the dose and reducing the dose interval. In conclusion, our results showed that the present model may be applied to predict the CDAI values of ADA for CD. They indicated the validity of the dosage regimen, as well as the efficacy of increasing the dose and reducing the dose interval. This article is protected by copyright. All rights reserved.

Using Model Replication to Improve the Reliability of Agent-Based Models

NASA Astrophysics Data System (ADS)

Zhong, Wei; Kim, Yushim

The basic presupposition of model replication activities for a computational model such as an agent-based model (ABM) is that, as a robust and reliable tool, it must be replicable in other computing settings. This assumption has recently gained attention in the community of artificial society and simulation due to the challenges of model verification and validation. Illustrating the replication of an ABM representing fraudulent behavior in a public service delivery system originally developed in the Java-based MASON toolkit for NetLogo by a different author, this paper exemplifies how model replication exercises provide unique opportunities for model verification and validation process. At the same time, it helps accumulate best practices and patterns of model replication and contributes to the agenda of developing a standard methodological protocol for agent-based social simulation.

QSAR study of curcumine derivatives as HIV-1 integrase inhibitors.

PubMed

Gupta, Pawan; Sharma, Anju; Garg, Prabha; Roy, Nilanjan

2013-03-01

A QSAR study was performed on curcumine derivatives as HIV-1 integrase inhibitors using multiple linear regression. The statistically significant model was developed with squared correlation coefficients (r(2)) 0.891 and cross validated r(2) (r(2) cv) 0.825. The developed model revealed that electronic, shape, size, geometry, substitution's information and hydrophilicity were important atomic properties for determining the inhibitory activity of these molecules. The model was also tested successfully for external validation (r(2) pred = 0.849) as well as Tropsha's test for model predictability. Furthermore, the domain analysis was carried out to evaluate the prediction reliability of external set molecules. The model was statistically robust and had good predictive power which can be successfully utilized for screening of new molecules.

3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide

PubMed Central

Li, Shun-Lai; He, Mao-Yu; Du, Hong-Guang

2011-01-01

The active metabolite of the novel immunosuppressive agent leflunomide has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite. The statistical results, cross-validated rCV2 (0.664) and non cross-validated r2 (0.687), show a good predictive ability. The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme. PMID:21686163

Updates on CCMC Activities and GSFC Space Weather Services

NASA Technical Reports Server (NTRS)

Zhengm Y.; Hesse, M.; Kuznetsova, M.; Pulkkinen, A.; Rastaetter, L.; Maddox, M.; Taktakishvili, A.; Berrios, D.; Chulaki, A.; Lee, H.;

Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

DTIC Science & Technology

2015-11-01

evaluated one synthetic oxytocin agonist, Compound 39, and one oxytocin metabolite, for efficacy against social deficits in BALB/cByJ mice, and we are...currently evaluating a second oxytocin metabolite for prosocial effects. Overall, we have successfully validated three mouse models as preclinical...to, first, prioritize synthetic compounds that activate the oxytocin receptor using cell-based assays, and secondly, evaluate the therapeutic efficacy

Evaluation of the Klobuchar model in TaiWan

NASA Astrophysics Data System (ADS)

Li, Jinghua; Wan, Qingtao; Ma, Guanyi; Zhang, Jie; Wang, Xiaolan; Fan, Jiangtao

2017-09-01

Ionospheric delay is the mainly error source in Global Navigation Satellite System (GNSS). Ionospheric model is one of the ways to correct the ionospheric delay. The single-frequency GNSS users modify the ionospheric delay by receiving the correction parameters broadcasted by satellites. Klobuchar model is widely used in Global Positioning System (GPS) and COMPASS because it is simple and convenient for real-time calculation. This model is established on the observations mainly from Europe and USA. It does not describe the equatorial anomaly region. South of China is located near the north crest of the equatorial anomaly, where the ionosphere has complex spatial and temporal variation. The assessment on the validation of Klobuchar model in this area is important to improve this model. Eleven years (2003-2014) data from one GPS receiver located at Taoyuan Taiwan (121°E, 25°N) are used to assess the validation of Klobuchar model in Taiwan. Total electron content (TEC) from the dual-frequency GPS observations is calculated and used as the reference, and TEC based on the Klobuchar model is compared with the reference. The residual is defined as the difference between the TEC from Klobuchar model and the reference. It is a parameter to reflect the absolute correction of the model. RMS correction percentage presents the validation of the model relative to the observations. The residuals' long-term variation, the RMS correction percentage, and their changes with the latitudes are analyzed respectively to access the model. In some months the RMS correction did not reach the goal of 50% purposed by Klobuchar, especially in the winter of the low solar activity years and at nighttime. RMS correction did not depend on the 11-years solar activity, neither the latitudes. Different from RMS correction, the residuals changed with the solar activity, similar to the variation of TEC. The residuals were large in the daytime, during the equinox seasons and in the high solar activity years; they are small at night, during the solstice seasons, and in the low activity years. During 1300-1500 BJT in the high solar activity years, the mean bias was negative, implying the model underestimated TEC on average. The maximum mean bias was 33TECU in April 2014, and the maximum underestimation reached 97TECU in October 2011. During 0000-0200 BJT, the residuals had small mean bias, small variation range and small standard deviation. It suggested that the model could describe the TEC of the ionosphere better than that in the daytime. Besides the variation with the solar activity, the residuals also vary with the latitudes. The means bias reached the maximum at 20-22°N, corresponding to the north crest of the equatorial anomaly. At this latitude, the maximum mean bias was 47TECU lower than the observation in the high activity years, and 12TECU lower in the low activity years. The minimum variation range appeared at 30-32°N in high and low activity years. But the minimum mean bias was at different latitudes in the high and low activity years. In the high activity years, it appeared at 30-32°N, and in the low years it was at 24-26°N. For an ideal model, the residuals should have small mean bias and small variation range. Further study is needed to learn the distribution of the residuals and to improve the model.

Vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors: development and validation of predictive 3-D QSAR models through extensive ligand- and structure-based approaches

NASA Astrophysics Data System (ADS)

Ragno, Rino; Ballante, Flavio; Pirolli, Adele; Wickersham, Richard B.; Patsilinakos, Alexandros; Hesse, Stéphanie; Perspicace, Enrico; Kirsch, Gilbert

2015-08-01

Vascular endothelial growth factor receptor-2, (VEGFR-2), is a key element in angiogenesis, the process by which new blood vessels are formed, and is thus an important pharmaceutical target. Here, 3-D quantitative structure-activity relationship (3-D QSAR) were used to build a quantitative screening and pharmacophore model of the VEGFR-2 receptors for design of inhibitors with improved activities. Most of available experimental data information has been used as training set to derive optimized and fully cross-validated eight mono-probe and a multi-probe quantitative models. Notable is the use of 262 molecules, aligned following both structure-based and ligand-based protocols, as external test set confirming the 3-D QSAR models' predictive capability and their usefulness in design new VEGFR-2 inhibitors. From a survey on literature, this is the first generation of a wide-ranging computational medicinal chemistry application on VEGFR2 inhibitors.

Explanation Generation, Not Explanation Expectancy, Improves Metacomprehension Accuracy

ERIC Educational Resources Information Center

Fukaya, Tatsushi

2013-01-01

The ability to monitor the status of one's own understanding is important to accomplish academic tasks proficiently. Previous studies have shown that comprehension monitoring (metacomprehension accuracy) is generally poor, but improves when readers engage in activities that access valid cues reflecting their situation model (activities such as…

3D-QSAR studies on the inhibitory activity of trimethoprim analogues against Escherichia coli dihydrofolate reductase.

PubMed

Vijayaraj, Ramadoss; Devi, Mekapothula Lakshmi Vasavi; Subramanian, Venkatesan; Chattaraj, Pratim Kumar

2012-06-01

Three-dimensional quantitative structure activity relationship (3D-QSAR) study has been carried out on the Escherichia coli DHFR inhibitors 2,4-diamino-5-(substituted-benzyl)pyrimidine derivatives to understand the structural features responsible for the improved potency. To construct highly predictive 3D-QSAR models, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used. The predicted models show statistically significant cross-validated and non-cross-validated correlation coefficient of r2 CV and r2 nCV, respectively. The final 3D-QSAR models were validated using structurally diverse test set compounds. Analysis of the contour maps generated from CoMFA and CoMSIA methods reveals that the substitution of electronegative groups at the first and second position along with electropositive group at the third position of R2 substitution significantly increases the potency of the derivatives. The results obtained from the CoMFA and CoMSIA study delineate the substituents on the trimethoprim analogues responsible for the enhanced potency and also provide valuable directions for the design of new trimethoprim analogues with improved affinity. © 2012 John Wiley & Sons A/S.

Active Inference and Learning in the Cerebellum.

PubMed

Friston, Karl; Herreros, Ivan

2016-09-01

This letter offers a computational account of Pavlovian conditioning in the cerebellum based on active inference and predictive coding. Using eyeblink conditioning as a canonical paradigm, we formulate a minimal generative model that can account for spontaneous blinking, startle responses, and (delay or trace) conditioning. We then establish the face validity of the model using simulated responses to unconditioned and conditioned stimuli to reproduce the sorts of behavior that are observed empirically. The scheme's anatomical validity is then addressed by associating variables in the predictive coding scheme with nuclei and neuronal populations to match the (extrinsic and intrinsic) connectivity of the cerebellar (eyeblink conditioning) system. Finally, we try to establish predictive validity by reproducing selective failures of delay conditioning, trace conditioning, and extinction using (simulated and reversible) focal lesions. Although rather metaphorical, the ensuing scheme can account for a remarkable range of anatomical and neurophysiological aspects of cerebellar circuitry-and the specificity of lesion-deficit mappings that have been established experimentally. From a computational perspective, this work shows how conditioning or learning can be formulated in terms of minimizing variational free energy (or maximizing Bayesian model evidence) using exactly the same principles that underlie predictive coding in perception.

The Canadian Assessment of Physical Literacy: methods for children in grades 4 to 6 (8 to 12 years).

PubMed

Longmuir, Patricia E; Boyer, Charles; Lloyd, Meghann; Yang, Yan; Boiarskaia, Elena; Zhu, Weimo; Tremblay, Mark S

2015-08-11

Physical literacy is described as the motivation, confidence, physical competence, knowledge and understanding to value and engage in a physically active lifestyle. As such, it is expected that those who have greater physical literacy would be more likely to obtain the health benefits offered by habitual physical activity. A theoretical model and assessment battery, the Canadian Assessment of Physical Literacy (CAPL), for the assessment of childhood physical literacy had been proposed in theory but validity data were lacking. The purpose of this study was to explore validity evidence for the CAPL among children in grades 4 to 6. CAPL validity was evaluated through three analyses that utilized cross-sectional data obtained through local schools in Eastern Ontario, Canada. A confirmatory factor analysis compared the data to the theoretical model. Patterns of association between self-reported age and gender and the CAPL total and domain scores were examined using regression models. Teacher ratings of participants' knowledge, attitude and physical activity competence were compared to assessment results. The CAPL was completed by 963 children (55 % female) in grades 4, 5 and 6. Children were 8 to 12 years of age (mean 10.1 years), with 85 % of children approached agreeing to participate. A confirmatory factor analysis using data from 489 children with complete raw scores supported a model with four domains: engagement in physical activity (active and sedentary), physical competence (fitness and motor skill), motivation and confidence, and knowledge and understanding. Raw domain scores followed expected patterns for age and gender, providing evidence for their validity. Interpretive categories, developed from age and gender adjusted normative data, were not associated with age indicating that the CAPL is suitable for use across this age range. Children's gender was associated with the physical competence, motivation and engagement in physical activity domain scores, indicating that further research is required regarding the gender adjustment of the raw CAPL scores. CAPL domain and total scores were statistically significantly associated with teacher ratings of the child's motivation, attitudes, fitness, skill and overall physical activity. CAPL offers a comprehensive assessment of engagement in physical activity, physical competence, motivation and confidence, and knowledge and understanding as components of childhood (grades 4 to 6, 8 to 12 years) physical literacy. Monitoring of these measures enhances our understanding of children's physical literacy, and assists with the identification of areas where additional supports are required.

Multisample cross-validation of a model of childhood posttraumatic stress disorder symptomatology.

PubMed

Anthony, Jason L; Lonigan, Christopher J; Vernberg, Eric M; Greca, Annette M La; Silverman, Wendy K; Prinstein, Mitchell J

2005-12-01

This study is the latest advancement of our research aimed at best characterizing children's posttraumatic stress reactions. In a previous study, we compared existing nosologic and empirical models of PTSD dimensionality and determined the superior model was a hierarchical one with three symptom clusters (Intrusion/Active Avoidance, Numbing/Passive Avoidance, and Arousal; Anthony, Lonigan, & Hecht, 1999). In this study, we cross-validate this model in two populations. Participants were 396 fifth graders who were exposed to either Hurricane Andrew or Hurricane Hugo. Multisample confirmatory factor analysis demonstrated the model's factorial invariance across populations who experienced traumatic events that differed in severity. These results show the model's robustness to characterize children's posttraumatic stress reactions. Implications for diagnosis, classification criteria, and an empirically supported theory of PTSD are discussed.

Simulation of the effect of hydrogen bonds on water activity of glucose and dextran using the Veytsman model.

PubMed

De Vito, Francesca; Veytsman, Boris; Painter, Paul; Kokini, Jozef L

2015-03-06

Carbohydrates exhibit either van der Waals and ionic interactions or strong hydrogen bonding interactions. The prominence and large number of hydrogen bonds results in major contributions to phase behavior. A thermodynamic framework that accounts for hydrogen bonding interactions is therefore necessary. We have developed an extension of the thermodynamic model based on the Veytsman association theory to predict the contribution of hydrogen bonds to the behavior of glucose-water and dextran-water systems and we have calculated the free energy of mixing and its derivative leading to chemical potential and water activity. We compared our calculations with experimental data of water activity for glucose and dextran and found excellent agreement far superior to the Flory-Huggins theory. The validation of our calculations using experimental data demonstrated the validity of the Veytsman model in properly accounting for the hydrogen bonding interactions and successfully predicting water activity of glucose and dextran. Our calculations of the concentration of hydrogen bonds using the Veytsman model were instrumental in our ability to explain the difference between glucose and dextran and the role that hydrogen bonds play in contributing to these differences. The miscibility predictions showed that the Veytsman model is also able to correctly describe the phase behavior of glucose and dextran. Copyright © 2014 Elsevier Ltd. All rights reserved.

OC5 Project Phase II: Validation of Global Loads of the DeepCwind Floating Semisubmersible Wind Turbine

DOE PAGES

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.; ...

2017-10-01

This paper summarizes the findings from Phase II of the Offshore Code Comparison, Collaboration, Continued, with Correlation project. The project is run under the International Energy Agency Wind Research Task 30, and is focused on validating the tools used for modeling offshore wind systems through the comparison of simulated responses of select system designs to physical test data. Validation activities such as these lead to improvement of offshore wind modeling tools, which will enable the development of more innovative and cost-effective offshore wind designs. For Phase II of the project, numerical models of the DeepCwind floating semisubmersible wind system weremore » validated using measurement data from a 1/50th-scale validation campaign performed at the Maritime Research Institute Netherlands offshore wave basin. Validation of the models was performed by comparing the calculated ultimate and fatigue loads for eight different wave-only and combined wind/wave test cases against the measured data, after calibration was performed using free-decay, wind-only, and wave-only tests. The results show a decent estimation of both the ultimate and fatigue loads for the simulated results, but with a fairly consistent underestimation in the tower and upwind mooring line loads that can be attributed to an underestimation of wave-excitation forces outside the linear wave-excitation region, and the presence of broadband frequency excitation in the experimental measurements from wind. Participant results showed varied agreement with the experimental measurements based on the modeling approach used. Modeling attributes that enabled better agreement included: the use of a dynamic mooring model; wave stretching, or some other hydrodynamic modeling approach that excites frequencies outside the linear wave region; nonlinear wave kinematics models; and unsteady aerodynamics models. Also, it was observed that a Morison-only hydrodynamic modeling approach could create excessive pitch excitation and resulting tower loads in some frequency bands.« less

OC5 Project Phase II: Validation of Global Loads of the DeepCwind Floating Semisubmersible Wind Turbine

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

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.

This paper summarizes the findings from Phase II of the Offshore Code Comparison, Collaboration, Continued, with Correlation project. The project is run under the International Energy Agency Wind Research Task 30, and is focused on validating the tools used for modeling offshore wind systems through the comparison of simulated responses of select system designs to physical test data. Validation activities such as these lead to improvement of offshore wind modeling tools, which will enable the development of more innovative and cost-effective offshore wind designs. For Phase II of the project, numerical models of the DeepCwind floating semisubmersible wind system weremore » validated using measurement data from a 1/50th-scale validation campaign performed at the Maritime Research Institute Netherlands offshore wave basin. Validation of the models was performed by comparing the calculated ultimate and fatigue loads for eight different wave-only and combined wind/wave test cases against the measured data, after calibration was performed using free-decay, wind-only, and wave-only tests. The results show a decent estimation of both the ultimate and fatigue loads for the simulated results, but with a fairly consistent underestimation in the tower and upwind mooring line loads that can be attributed to an underestimation of wave-excitation forces outside the linear wave-excitation region, and the presence of broadband frequency excitation in the experimental measurements from wind. Participant results showed varied agreement with the experimental measurements based on the modeling approach used. Modeling attributes that enabled better agreement included: the use of a dynamic mooring model; wave stretching, or some other hydrodynamic modeling approach that excites frequencies outside the linear wave region; nonlinear wave kinematics models; and unsteady aerodynamics models. Also, it was observed that a Morison-only hydrodynamic modeling approach could create excessive pitch excitation and resulting tower loads in some frequency bands.« less

Space Weather Products at the Community Coordinated Modeling Center

NASA Technical Reports Server (NTRS)

Hesse, Michael; Kuznetsova, M.; Pulkkinen, A.; Maddox, M.; Rastaetter, L.; Berrios, D.; MacNeice, P.

2010-01-01

The Community Coordinated Modeling Center (CCMC) is a US inter-agency activity aiming at research in support of the generation of advanced space weather models. As one of its main functions, the CCMC provides to researchers the use of space science models, even if they are not model owners themselves. The second CCMC activity is to support Space Weather forecasting at national Space Weather Forecasting Centers. This second activity involves model evaluations, model transitions to operations, and the development of space weather forecasting tools. Owing to the pace of development in the science community, new model capabilities emerge frequently. Consequently, space weather products and tools involve not only increased validity, but often entirely new capabilities. This presentation will review the present state of space weather tools as well as point out emerging future capabilities.

QSAR modeling for anti-human African trypanosomiasis activity of substituted 2-Phenylimidazopyridines

NASA Astrophysics Data System (ADS)

Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.

2017-02-01

In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

Preterm labor--modeling the uterine electrical activity from cellular level to surface recording.

PubMed

Rihana, S; Marque, C

2008-01-01

Uterine electrical activity is correlated to the appearance of uterine contractions. forceful contractions appear at the end of term. Therefore, understanding the genesis and the propagation of uterine electrical activity may provide an efficient tool to diagnose preterm labor. Moreover, the control of uterine excitability seems to have important consequences in the control of preterm labor. Modeling the electrical activity in uterine tissue is thus an important step in understanding physiological uterine contractile mechanisms and to permit uterine EMG simulation. Our model presented in this paper, incorporates ion channel models at the cell level, the reaction diffusion equations at the tissue level and the spatiotemporal integration at the uterine EMG reconstructed level. This model validates some key physiological observation hypotheses concerning uterine excitability and propagation.

Notes on modeling and simulation

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

Redondo, Antonio

These notes present a high-level overview of how modeling and simulation are carried out by practitioners. The discussion is of a general nature; no specific techniques are examined but the activities associated with all modeling and simulation approaches are briefly addressed. There is also a discussion of validation and verification and, at the end, a section on why modeling and simulation are useful.

A novel integrated framework and improved methodology of computer-aided drug design.

PubMed

Chen, Calvin Yu-Chian

2013-01-01

Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated. Hence, we developed a drug design modeling framework that integrates multiple approaches, including machine learning based quantitative structure-activity relationship (QSAR) analysis, 3D-QSAR, Bayesian network, pharmacophore modeling, and structure-based docking algorithm. Restrictions for each model were defined for improved individual and overall accuracy. An integration method was applied to join the results from each model to minimize bias and errors. In addition, the integrated model adopts both static and dynamic analysis to validate the intermolecular stabilities of the receptor-ligand conformation. The proposed protocol was applied to identifying HER2 inhibitors from traditional Chinese medicine (TCM) as an example for validating our new protocol. Eight potent leads were identified from six TCM sources. A joint validation system comprised of comparative molecular field analysis, comparative molecular similarity indices analysis, and molecular dynamics simulation further characterized the candidates into three potential binding conformations and validated the binding stability of each protein-ligand complex. The ligand pathway was also performed to predict the ligand "in" and "exit" from the binding site. In summary, we propose a novel systematic CADD methodology for the identification, analysis, and characterization of drug-like candidates.

Modeling and control of active twist aircraft

NASA Astrophysics Data System (ADS)

Cramer, Nicholas Bryan

The Wright Brothers marked the beginning of powered flight in 1903 using an active twist mechanism as their means of controlling roll. As time passed due to advances in other technologies that transformed aviation the active twist mechanism was no longer used. With the recent advances in material science and manufacturability, the possibility of the practical use of active twist technologies has emerged. In this dissertation, the advantages and disadvantages of active twist techniques are investigated through the development of an aeroelastic modeling method intended for informing the designs of such technologies and wind tunnel testing to confirm the capabilities of the active twist technologies and validate the model. Control principles for the enabling structural technologies are also proposed while the potential gains of dynamic, active twist are analyzed.

Using the EZ-Diffusion Model to Score a Single-Category Implicit Association Test of Physical Activity

PubMed Central

Rebar, Amanda L.; Ram, Nilam; Conroy, David E.

2014-01-01

Objective The Single-Category Implicit Association Test (SC-IAT) has been used as a method for assessing automatic evaluations of physical activity, but measurement artifact or consciously-held attitudes could be confounding the outcome scores of these measures. The objective of these two studies was to address these measurement concerns by testing the validity of a novel SC-IAT scoring technique. Design Study 1 was a cross-sectional study, and study 2 was a prospective study. Method In study 1, undergraduate students (N = 104) completed SC-IATs for physical activity, flowers, and sedentary behavior. In study 2, undergraduate students (N = 91) completed a SC-IAT for physical activity, self-reported affective and instrumental attitudes toward physical activity, physical activity intentions, and wore an accelerometer for two weeks. The EZ-diffusion model was used to decompose the SC-IAT into three process component scores including the information processing efficiency score. Results In study 1, a series of structural equation model comparisons revealed that the information processing score did not share variability across distinct SC-IATs, suggesting it does not represent systematic measurement artifact. In study 2, the information processing efficiency score was shown to be unrelated to self-reported affective and instrumental attitudes toward physical activity, and positively related to physical activity behavior, above and beyond the traditional D-score of the SC-IAT. Conclusions The information processing efficiency score is a valid measure of automatic evaluations of physical activity. PMID:25484621

A multi-site cognitive task analysis for biomedical query mediation.

PubMed

Hruby, Gregory W; Rasmussen, Luke V; Hanauer, David; Patel, Vimla L; Cimino, James J; Weng, Chunhua

2016-09-01

To apply cognitive task analyses of the Biomedical query mediation (BQM) processes for EHR data retrieval at multiple sites towards the development of a generic BQM process model. We conducted semi-structured interviews with eleven data analysts from five academic institutions and one government agency, and performed cognitive task analyses on their BQM processes. A coding schema was developed through iterative refinement and used to annotate the interview transcripts. The annotated dataset was used to reconstruct and verify each BQM process and to develop a harmonized BQM process model. A survey was conducted to evaluate the face and content validity of this harmonized model. The harmonized process model is hierarchical, encompassing tasks, activities, and steps. The face validity evaluation concluded the model to be representative of the BQM process. In the content validity evaluation, out of the 27 tasks for BQM, 19 meet the threshold for semi-valid, including 3 fully valid: "Identify potential index phenotype," "If needed, request EHR database access rights," and "Perform query and present output to medical researcher", and 8 are invalid. We aligned the goals of the tasks within the BQM model with the five components of the reference interview. The similarity between the process of BQM and the reference interview is promising and suggests the BQM tasks are powerful for eliciting implicit information needs. We contribute a BQM process model based on a multi-site study. This model promises to inform the standardization of the BQM process towards improved communication efficiency and accuracy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Multi-Site Cognitive Task Analysis for Biomedical Query Mediation

PubMed Central

Hruby, Gregory W.; Rasmussen, Luke V.; Hanauer, David; Patel, Vimla; Cimino, James J.; Weng, Chunhua

2016-01-01

Objective To apply cognitive task analyses of the Biomedical query mediation (BQM) processes for EHR data retrieval at multiple sites towards the development of a generic BQM process model. Materials and Methods We conducted semi-structured interviews with eleven data analysts from five academic institutions and one government agency, and performed cognitive task analyses on their BQM processes. A coding schema was developed through iterative refinement and used to annotate the interview transcripts. The annotated dataset was used to reconstruct and verify each BQM process and to develop a harmonized BQM process model. A survey was conducted to evaluate the face and content validity of this harmonized model. Results The harmonized process model is hierarchical, encompassing tasks, activities, and steps. The face validity evaluation concluded the model to be representative of the BQM process. In the content validity evaluation, out of the 27 tasks for BQM, 19 meet the threshold for semi-valid, including 3 fully valid: “Identify potential index phenotype,” “If needed, request EHR database access rights,” and “Perform query and present output to medical researcher”, and 8 are invalid. Discussion We aligned the goals of the tasks within the BQM model with the five components of the reference interview. The similarity between the process of BQM and the reference interview is promising and suggests the BQM tasks are powerful for eliciting implicit information needs. Conclusions We contribute a BQM process model based on a multi-site study. This model promises to inform the standardization of the BQM process towards improved communication efficiency and accuracy. PMID:27435950

Flight Testing an Iced Business Jet for Flight Simulation Model Validation

NASA Technical Reports Server (NTRS)

Ratvasky, Thomas P.; Barnhart, Billy P.; Lee, Sam; Cooper, Jon

2007-01-01

A flight test of a business jet aircraft with various ice accretions was performed to obtain data to validate flight simulation models developed through wind tunnel tests. Three types of ice accretions were tested: pre-activation roughness, runback shapes that form downstream of the thermal wing ice protection system, and a wing ice protection system failure shape. The high fidelity flight simulation models of this business jet aircraft were validated using a software tool called "Overdrive." Through comparisons of flight-extracted aerodynamic forces and moments to simulation-predicted forces and moments, the simulation models were successfully validated. Only minor adjustments in the simulation database were required to obtain adequate match, signifying the process used to develop the simulation models was successful. The simulation models were implemented in the NASA Ice Contamination Effects Flight Training Device (ICEFTD) to enable company pilots to evaluate flight characteristics of the simulation models. By and large, the pilots confirmed good similarities in the flight characteristics when compared to the real airplane. However, pilots noted pitch up tendencies at stall with the flaps extended that were not representative of the airplane and identified some differences in pilot forces. The elevator hinge moment model and implementation of the control forces on the ICEFTD were identified as a driver in the pitch ups and control force issues, and will be an area for future work.

Covariation of depressive mood and spontaneous physical activity in major depressive disorder: toward continuous monitoring of depressive mood.

PubMed

Kim, Jinhyuk; Nakamura, Toru; Kikuchi, Hiroe; Yoshiuchi, Kazuhiro; Sasaki, Tsukasa; Yamamoto, Yoshiharu

2015-07-01

The objective evaluation of depressive mood is considered to be useful for the diagnosis and treatment of depressive disorders. Thus, we investigated psychobehavioral correlates, particularly the statistical associations between momentary depressive mood and behavioral dynamics measured objectively, in patients with major depressive disorder (MDD) and healthy subjects. Patients with MDD ( n = 14) and healthy subjects ( n = 43) wore a watch-type computer device and rated their momentary symptoms using ecological momentary assessment. Spontaneous physical activity in daily life, referred to as locomotor activity, was also continuously measured by an activity monitor built into the device. A multilevel modeling approach was used to model the associations between changes in depressive mood scores and the local statistics of locomotor activity simultaneously measured. We further examined the cross validity of such associations across groups. The statistical model established indicated that worsening of the depressive mood was associated with the increased intermittency of locomotor activity, as characterized by a lower mean and higher skewness. The model was cross validated across groups, suggesting that the same psychobehavioral correlates are shared by both healthy subjects and patients, although the latter had significantly higher mean levels of depressive mood scores. Our findings suggest the presence of robust as well as common associations between momentary depressive mood and behavioral dynamics in healthy individuals and patients with depression, which may lead to the continuous monitoring of the pathogenic processes (from healthy states) and pathological states of MDD.

Comprehensive manual handling limits for lowering, pushing, pulling and carrying activities.

PubMed

Shoaf, C; Genaidy, A; Karwowski, W; Waters, T; Christensen, D

1997-11-01

The objective of this study was to develop a set of mathematical models for manual lowering, pushing, pulling and carrying activities that would result in establishing load capacity limits to protect the lower back against occupational low-back disorders. In order to establish safe guidelines, a three-stage process was used. First, psychophysical data was used to generate the models' discounting factors and recommended load capacities. Second, biomechanical analysis was used to refine the recommended load capacities. Third, physiological criteria were used to validate the models' discounting factors. Both task and personal factors were considered in the models' development. When compared to the results from prior psychophysical research for these activities, the developed load capacity values are lower than previously established limits. The results of this study allowed the authors to validate the hypothesis proposed and tested by Karwowski (1983) that states that the combination of physiological and biomechanical stresses should lead to the overall measure of task acceptability or the psychophysical stress. This study also found that some of the discounting factors for the task frequency parameters recommended in the prior psychophysical research should not be used as several of the high frequency factors violated physiological limits.

Generating large-scale estimates from sparse, in-situ networks: multi-scale soil moisture modeling at ARS watersheds for NASA’s soil moisture active passive (SMAP) calibration/validation mission

USDA-ARS?s Scientific Manuscript database

NASA’s SMAP satellite, launched in November of 2014, produces estimates of average volumetric soil moisture at 3, 9, and 36-kilometer scales. The calibration and validation process of these estimates requires the generation of an identically-scaled soil moisture product from existing in-situ networ...

Ensemble Methods for Classification of Physical Activities from Wrist Accelerometry.

PubMed

Chowdhury, Alok Kumar; Tjondronegoro, Dian; Chandran, Vinod; Trost, Stewart G

2017-09-01

To investigate whether the use of ensemble learning algorithms improve physical activity recognition accuracy compared to the single classifier algorithms, and to compare the classification accuracy achieved by three conventional ensemble machine learning methods (bagging, boosting, random forest) and a custom ensemble model comprising four algorithms commonly used for activity recognition (binary decision tree, k nearest neighbor, support vector machine, and neural network). The study used three independent data sets that included wrist-worn accelerometer data. For each data set, a four-step classification framework consisting of data preprocessing, feature extraction, normalization and feature selection, and classifier training and testing was implemented. For the custom ensemble, decisions from the single classifiers were aggregated using three decision fusion methods: weighted majority vote, naïve Bayes combination, and behavior knowledge space combination. Classifiers were cross-validated using leave-one subject out cross-validation and compared on the basis of average F1 scores. In all three data sets, ensemble learning methods consistently outperformed the individual classifiers. Among the conventional ensemble methods, random forest models provided consistently high activity recognition; however, the custom ensemble model using weighted majority voting demonstrated the highest classification accuracy in two of the three data sets. Combining multiple individual classifiers using conventional or custom ensemble learning methods can improve activity recognition accuracy from wrist-worn accelerometer data.

Development and evaluation of social cognitive measures related to adolescent physical activity.

PubMed

Dewar, Deborah L; Lubans, David Revalds; Morgan, Philip James; Plotnikoff, Ronald C

2013-05-01

This study aimed to develop and evaluate the construct validity and reliability of modernized social cognitive measures relating to physical activity behaviors in adolescents. An instrument was developed based on constructs from Bandura's Social Cognitive Theory and included the following scales: self-efficacy, situation (perceived physical environment), social support, behavioral strategies, and outcome expectations and expectancies. The questionnaire was administered in a sample of 171 adolescents (age = 13.6 ± 1.2 years, females = 61%). Confirmatory factor analysis was employed to examine model-fit for each scale using multiple indices, including chi-square index, comparative-fit index (CFI), goodness-of-fit index (GFI), and the root mean square error of approximation (RMSEA). Reliability properties were also examined (ICC and Cronbach's alpha). Each scale represented a statistically sound measure: fit indices indicated each model to be an adequate-to-exact fit to the data; internal consistency was acceptable to good (α = 0.63-0.79); rank order repeatability was strong (ICC = 0.82-0.91). Results support the validity and reliability of social cognitive scales relating to physical activity among adolescents. As such, the developed scales have utility for the identification of potential social cognitive correlates of youth physical activity, mediators of physical activity behavior changes and the testing of theoretical models based on Social Cognitive Theory.

Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background.

PubMed

Farkas, József; Kovács, László Á; Gáspár, László; Nafz, Anna; Gaszner, Tamás; Ujvári, Balázs; Kormos, Viktória; Csernus, Valér; Hashimoto, Hitoshi; Reglődi, Dóra; Gaszner, Balázs

2017-06-23

Major depression is a common cause of chronic disability. Despite decades of efforts, no equivocally accepted animal model is available for studying depression. We tested the validity of a new model based on the three-hit concept of vulnerability and resilience. Genetic predisposition (hit 1, mutation of pituitary adenylate cyclase-activating polypeptide, PACAP gene), early-life adversity (hit 2, 180-min maternal deprivation, MD180) and chronic variable mild stress (hit 3, CVMS) were combined. Physical, endocrinological, behavioral and functional morphological tools were used to validate the model. Body- and adrenal weight changes as well as corticosterone titers proved that CVMS was effective. Forced swim test indicated increased depression in CVMS PACAP heterozygous (Hz) mice with MD180 history, accompanied by elevated anxiety level in marble burying test. Corticotropin-releasing factor neurons in the oval division of the bed nucleus of the stria terminalis showed increased FosB expression, which was refractive to CVMS exposure in wild-type and Hz mice. Urocortin1 neurons became over-active in CMVS-exposed PACAP knock out (KO) mice with MD180 history, suggesting the contribution of centrally projecting Edinger-Westphal nucleus to the reduced depression and anxiety level of stressed KO mice. Serotoninergic neurons of the dorsal raphe nucleus lost their adaptation ability to CVMS in MD180 mice. In conclusion, the construct and face validity criteria suggest that MD180 PACAP HZ mice on CD1 background upon CVMS may be used as a reliable model for the three-hit theory. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Sulfonamide-containing PTP 1B inhibitors: Docking studies, synthesis and model validation

NASA Astrophysics Data System (ADS)

Niu, Enli; Gan, Qiang; Chen, Xi; Feng, Changgen

2017-01-01

PTP 1B plays an important role in regulating insulin signaling pathway and is regarded as a valid target for curing diabetes and obesity. In this paper, two novel sulfonamide-containing PTP 1B inhibitors were designed, synthesized in mild condition, and characterized by FT-IR, 1H NMR, 13C NMR and elemental analysis. The single crystal of compounds 7 and 8 were obtained and their structures were determined by X-ray single crystal diffraction analysis. In addition, their inhibitory activity were predicted by genetic algorithm, and carried on in vitro enzyme activity test. Of which compound 8 showed good inhibitory activity, in consistent with docking studies.

Hybrid optimal descriptors as a tool to predict skin sensitization in accordance to OECD principles.

PubMed

Toropova, Alla P; Toropov, Andrey A

2017-06-05

Skin sensitization (allergic contact dermatitis) is a widespread problem arising from the contact of chemicals with the skin. The detection of molecular features with undesired effect for skin is complex task owing to unclear biochemical mechanisms and unclearness of conditions of action of chemicals to skin. The development of computational methods for estimation of this endpoint in order to reduce animal testing is recommended (Cosmetics Directive EC regulation 1907/2006; EU Regulation, Regulation, 1223/2009). The CORAL software (http://www.insilico.eu/coral) gives good predictive models for the skin sensitization. Simplified molecular input-line entry system (SMILES) together with molecular graph are used to represent the molecular structure for these models. So-called hybrid optimal descriptors are used to establish quantitative structure-activity relationships (QSARs). The aim of this study is the estimation of the predictive potential of the hybrid descriptors. Three different distributions into the training (≈70%), calibration (≈15%), and validation (≈15%) sets are studied. QSAR for these three distributions are built up with using the Monte Carlo technique. The statistical characteristics of these models for external validation set are used as a measure of predictive potential of these models. The best model, according to the above criterion, is characterized by n validation =29, r 2 validation =0.8596, RMSE validation =0.489. Mechanistic interpretation and domain of applicability for these models are defined. Copyright © 2017 Elsevier B.V. All rights reserved.

OC5 Project Phase Ib: Validation of hydrodynamic loading on a fixed, flexible cylinder for offshore wind applications

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

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.

This paper summarizes the findings from Phase Ib of the Offshore Code Comparison, Collaboration, Continued with Correlation (OC5) project. OC5 is a project run under the International Energy Agency (IEA) Wind Research Task 30, and is focused on validating the tools used for modelling offshore wind systems through the comparison of simulated responses of select offshore wind systems (and components) to physical test data. For Phase Ib of the project, simulated hydrodynamic loads on a flexible cylinder fixed to a sloped bed were validated against test measurements made in the shallow water basin at the Danish Hydraulic Institute (DHI) withmore » support from the Technical University of Denmark (DTU). The first phase of OC5 examined two simple cylinder structures (Phase Ia and Ib) to focus on validation of hydrodynamic models used in the various tools before moving on to more complex offshore wind systems and the associated coupled physics. As a result, verification and validation activities such as these lead to improvement of offshore wind modelling tools, which will enable the development of more innovative and cost-effective offshore wind designs.« less

OC5 Project Phase Ib: Validation of hydrodynamic loading on a fixed, flexible cylinder for offshore wind applications

DOE PAGES

Robertson, Amy N.; Wendt, Fabian; Jonkman, Jason M.; ...

2016-10-13

This paper summarizes the findings from Phase Ib of the Offshore Code Comparison, Collaboration, Continued with Correlation (OC5) project. OC5 is a project run under the International Energy Agency (IEA) Wind Research Task 30, and is focused on validating the tools used for modelling offshore wind systems through the comparison of simulated responses of select offshore wind systems (and components) to physical test data. For Phase Ib of the project, simulated hydrodynamic loads on a flexible cylinder fixed to a sloped bed were validated against test measurements made in the shallow water basin at the Danish Hydraulic Institute (DHI) withmore » support from the Technical University of Denmark (DTU). The first phase of OC5 examined two simple cylinder structures (Phase Ia and Ib) to focus on validation of hydrodynamic models used in the various tools before moving on to more complex offshore wind systems and the associated coupled physics. As a result, verification and validation activities such as these lead to improvement of offshore wind modelling tools, which will enable the development of more innovative and cost-effective offshore wind designs.« less

Classification and regression tree analysis of acute-on-chronic hepatitis B liver failure: Seeing the forest for the trees.

PubMed

Shi, K-Q; Zhou, Y-Y; Yan, H-D; Li, H; Wu, F-L; Xie, Y-Y; Braddock, M; Lin, X-Y; Zheng, M-H

2017-02-01

At present, there is no ideal model for predicting the short-term outcome of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBLF were screened in the study, which were recognized as derivation cohort and validation cohort, respectively. CART analysis was applied to predict the 3-month mortality of patients with ACHBLF. The accuracy of the CART model was tested using the area under the receiver operating characteristic curve, which was compared with the model for end-stage liver disease (MELD) score and a new logistic regression model. CART analysis identified four variables as prognostic factors of ACHBLF: total bilirubin, age, serum sodium and INR, and three distinct risk groups: low risk (4.2%), intermediate risk (30.2%-53.2%) and high risk (81.4%-96.9%). The new logistic regression model was constructed with four independent factors, including age, total bilirubin, serum sodium and prothrombin activity by multivariate logistic regression analysis. The performances of the CART model (0.896), similar to the logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667, P<.001). The results were confirmed in the validation cohort. We have developed and validated a novel CART model superior to MELD for predicting three-month mortality of patients with ACHBLF. Thus, the CART model could facilitate medical decision-making and provide clinicians with a validated practical bedside tool for ACHBLF risk stratification. © 2016 John Wiley & Sons Ltd.

Cheminformatics-aided pharmacovigilance: application to Stevens-Johnson Syndrome

PubMed Central

Low, Yen S; Caster, Ola; Bergvall, Tomas; Fourches, Denis; Zang, Xiaoling; Norén, G Niklas; Rusyn, Ivan; Edwards, Ralph

2016-01-01

Objective Quantitative Structure-Activity Relationship (QSAR) models can predict adverse drug reactions (ADRs), and thus provide early warnings of potential hazards. Timely identification of potential safety concerns could protect patients and aid early diagnosis of ADRs among the exposed. Our objective was to determine whether global spontaneous reporting patterns might allow chemical substructures associated with Stevens-Johnson Syndrome (SJS) to be identified and utilized for ADR prediction by QSAR models. Materials and Methods Using a reference set of 364 drugs having positive or negative reporting correlations with SJS in the VigiBase global repository of individual case safety reports (Uppsala Monitoring Center, Uppsala, Sweden), chemical descriptors were computed from drug molecular structures. Random Forest and Support Vector Machines methods were used to develop QSAR models, which were validated by external 5-fold cross validation. Models were employed for virtual screening of DrugBank to predict SJS actives and inactives, which were corroborated using knowledge bases like VigiBase, ChemoText, and MicroMedex (Truven Health Analytics Inc, Ann Arbor, Michigan). Results We developed QSAR models that could accurately predict if drugs were associated with SJS (area under the curve of 75%–81%). Our 10 most active and inactive predictions were substantiated by SJS reports (or lack thereof) in the literature. Discussion Interpretation of QSAR models in terms of significant chemical descriptors suggested novel SJS structural alerts. Conclusions We have demonstrated that QSAR models can accurately identify SJS active and inactive drugs. Requiring chemical structures only, QSAR models provide effective computational means to flag potentially harmful drugs for subsequent targeted surveillance and pharmacoepidemiologic investigations. PMID:26499102

Atom and receptor based 3D QSAR models for generating new conformations from pyrazolopyrimidine as IL-2 inducible tyrosine kinase inhibitors.

PubMed

Ul-Haq, Zaheer; Effendi, Juweria Shahrukh; Ashraf, Sajda; Bkhaitan, Majdi M

2017-06-01

In the current study, quantitative three-dimensional structure-activity-relationship (3D-QSAR) method was performed to design a model for new chemical entities by utilizing pyrazolopyrimidines. Their inhibiting activity on receptor IL-2 Itk correlates descriptors based on topology and hydrophobicity. The best model developed by ligand-based (atom-based) approach has correlation-coefficient of r 2 : 0.987 and cross-validated squared correlation-coefficient of q 2 : 0.541 with an external prediction capability of r 2 : 0.944. Whereas the best selected model developed by structured-based (receptor-based) approach has correlation-coefficient of r 2 : 0.987, cross-validated squared correlation-coefficient of q 2 : 0.637 with an external predictive ability of r 2 : 0.941. The statistical parameters prove that structure-based gave a better model to design new chemical scaffolds. The results achieved indicated that hydrophobicity at R 1 location play a vital role in the inhibitory activity and introduction of appropriately bulky and strongly hydrophobic-groups at position 3 of the terminal phenyl-group which is highly significant to enhance the activity. Six new pyrazolopyrimidine derivatives were designed. Docking simulation study was carried out and their inhibitory activity was predicted by the best structure based model with predictive activity of ranging from 8.43 to 8.85 log unit. The interacting residues PHE435, ASP500, LYS391, GLU436, MET438, CYS442, ILE369, VAL377 of PDB 4HCT were studied with respect to type of bonding with the new compounds. This study was aimed to search out more potent inhibitors of IL-2 Itk. Copyright © 2017 Elsevier Inc. All rights reserved.

Finding Furfural Hydrogenation Catalysts via Predictive Modelling

PubMed Central

Strassberger, Zea; Mooijman, Maurice; Ruijter, Eelco; Alberts, Albert H; Maldonado, Ana G; Orru, Romano V A; Rothenberg, Gadi

2010-01-01

Abstract We combine multicomponent reactions, catalytic performance studies and predictive modelling to find transfer hydrogenation catalysts. An initial set of 18 ruthenium-carbene complexes were synthesized and screened in the transfer hydrogenation of furfural to furfurol with isopropyl alcohol complexes gave varied yields, from 62% up to >99.9%, with no obvious structure/activity correlations. Control experiments proved that the carbene ligand remains coordinated to the ruthenium centre throughout the reaction. Deuterium-labelling studies showed a secondary isotope effect (kH:kD=1.5). Further mechanistic studies showed that this transfer hydrogenation follows the so-called monohydride pathway. Using these data, we built a predictive model for 13 of the catalysts, based on 2D and 3D molecular descriptors. We tested and validated the model using the remaining five catalysts (cross-validation, R2=0.913). Then, with this model, the conversion and selectivity were predicted for four completely new ruthenium-carbene complexes. These four catalysts were then synthesized and tested. The results were within 3% of the model’s predictions, demonstrating the validity and value of predictive modelling in catalyst optimization. PMID:23193388

Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.

PubMed

Gener, Petra; Gouveia, Luis Pleno; Sabat, Guillem Romero; de Sousa Rafael, Diana Fernandes; Fort, Núria Bergadà; Arranja, Alexandra; Fernández, Yolanda; Prieto, Rafael Miñana; Ortega, Joan Sayos; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

2015-11-01

To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[(d,l-lactide-co-glycolide)-co-PEG] (PLGA-co-PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase. Copyright © 2015 Elsevier Inc. All rights reserved.

Driver kinematic and muscle responses in braking events with standard and reversible pre-tensioned restraints: validation data for human models.

PubMed

Osth, Jonas; Olafsdóttir, Jóna Marín; Davidsson, Johan; Brolin, Karin

2013-11-01

The objectives of this study are to generate validation data for human models intended for simulation of occupant kinematics in a pre-crash phase, and to evaluate the effect of an integrated safety system on driver kinematics and muscle responses. Eleven male and nine female volunteers, driving a passenger car on ordinary roads, performed maximum voluntary braking; they were also subjected to autonomous braking events with both standard and reversible pre-tensioned restraints. Kinematic data was acquired through film analysis, and surface electromyography (EMG) was recorded bilaterally for muscles in the neck, the upper extremities, and lumbar region. Maximum voluntary contractions (MVCs) were carried out in a driving posture for normalization of the EMG. Seat belt positions, interaction forces, and seat indentions were measured. During normal driving, all muscle activity was below 5% of MVC for females and 9% for males. The range of activity during steady state braking for males and females was 13-44% in the cervical and lumbar extensors, while antagonistic muscles showed a co-contraction of 2.3-19%. Seat belt pre-tension affects both the kinematic and muscle responses of drivers. In autonomous braking with standard restraints, muscle activation occurred in response to the inertial load. With pre-tensioned seat belts, EMG onset occurred earlier; between 71 ms and 176 ms after belt pre-tension. The EMG onset times decreased with repeated trials and were shorter for females than for males. With the results from this study, further improvement and validation of human models that incorporate active musculature will be made possible.

A comprehensive validation toolbox for regional ocean models - Outline, implementation and application to the Baltic Sea

NASA Astrophysics Data System (ADS)

Jandt, Simon; Laagemaa, Priidik; Janssen, Frank

2014-05-01

The systematic and objective comparison between output from a numerical ocean model and a set of observations, called validation in the context of this presentation, is a beneficial activity at several stages, starting from early steps in model development and ending at the quality control of model based products delivered to customers. Even though the importance of this kind of validation work is widely acknowledged it is often not among the most popular tasks in ocean modelling. In order to ease the validation work a comprehensive toolbox has been developed in the framework of the MyOcean-2 project. The objective of this toolbox is to carry out validation integrating different data sources, e.g. time-series at stations, vertical profiles, surface fields or along track satellite data, with one single program call. The validation toolbox, implemented in MATLAB, features all parts of the validation process - ranging from read-in procedures of datasets to the graphical and numerical output of statistical metrics of the comparison. The basic idea is to have only one well-defined validation schedule for all applications, in which all parts of the validation process are executed. Each part, e.g. read-in procedures, forms a module in which all available functions of this particular part are collected. The interface between the functions, the module and the validation schedule is highly standardized. Functions of a module are set up for certain validation tasks, new functions can be implemented into the appropriate module without affecting the functionality of the toolbox. The functions are assigned for each validation task in user specific settings, which are externally stored in so-called namelists and gather all information of the used datasets as well as paths and metadata. In the framework of the MyOcean-2 project the toolbox is frequently used to validate the forecast products of the Baltic Sea Marine Forecasting Centre. Hereby the performance of any new product version is compared with the previous version. Although, the toolbox is mainly tested for the Baltic Sea yet, it can easily be adapted to different datasets and parameters, regardless of the geographic region. In this presentation the usability of the toolbox is demonstrated along with several results of the validation process.

Modeling Relationships among Learning, Attitude, Self-Perception, and Science Achievement for Grade 8 Saudi Students

ERIC Educational Resources Information Center

Tighezza, M'Hamed

2014-01-01

The purpose of the present study was to examine the validity of modeling science achievement in terms of 3 social psychological variables (school connectedness, science attitude, and active learning) and 2 self-perception variables (self-confidence and science value). Two models were tested: full mediation and partial mediation. In the…

Using School Lotteries to Evaluate the Value-Added Model

ERIC Educational Resources Information Center

Deutsch, Jonah

2013-01-01

There has been an active debate in the literature over the validity of value-added models. In this study, the author tests the central assumption of value-added models that school assignment is random relative to expected test scores conditional on prior test scores, demographic variables, and other controls. He uses a Chicago charter school's…

Simulation and optimization of ammonia removal at low temperature for a double channel oxidation ditch based on fully coupled activated sludge model (FCASM): a full-scale study.

PubMed

Yang, Min; Sun, Peide; Wang, Ruyi; Han, Jingyi; Wang, Jianqiao; Song, Yingqi; Cai, Jing; Tang, Xiudi

2013-09-01

An optimal operating condition for ammonia removal at low temperature, based on fully coupled activated sludge model (FCASM), was determined in a full-scale oxidation ditch process wastewater treatment plant (WWTP). The FCASM-based mechanisms model was calibrated and validated with the data measured on site. Several important kinetic parameters of the modified model were tested through respirometry experiment. Validated model was used to evaluate the relationship between ammonia removal and operating parameters, such as temperature (T), dissolved oxygen (DO), solid retention time (SRT) and hydraulic retention time of oxidation ditch (HRT). The simulated results showed that low temperature have a negative effect on the ammonia removal. Through orthogonal simulation tests of the last three factors and combination with the analysis of variance, the optimal operating mode acquired of DO, SRT, HRT for the WWTP at low temperature were 3.5 mg L(-1), 15 d and 14 h, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Validating and improving a zero-dimensional stack voltage model of the Vanadium Redox Flow Battery

NASA Astrophysics Data System (ADS)

König, S.; Suriyah, M. R.; Leibfried, T.

2018-02-01

Simple, computationally efficient battery models can contribute significantly to the development of flow batteries. However, validation studies for these models on an industrial-scale stack level are rarely published. We first extensively present a simple stack voltage model for the Vanadium Redox Flow Battery. For modeling the concentration overpotential, we derive mass transfer coefficients from experimental results presented in the 1990s. The calculated mass transfer coefficient of the positive half-cell is 63% larger than of the negative half-cell, which is not considered in models published to date. Further, we advance the concentration overpotential model by introducing an apparent electrochemically active electrode surface which differs from the geometric electrode area. We use the apparent surface as fitting parameter for adapting the model to experimental results of a flow battery manufacturer. For adapting the model, we propose a method for determining the agreement between model and reality quantitatively. To protect the manufacturer's intellectual property, we introduce a normalization method for presenting the results. For the studied stack, the apparent electrochemically active surface of the electrode is 41% larger than its geometrical area. Hence, the current density in the diffusion layer is 29% smaller than previously reported for a zero-dimensional model.

Performing Verification and Validation in Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1999-01-01

The implementation of reuse-based software engineering not only introduces new activities to the software development process, such as domain analysis and domain modeling, it also impacts other aspects of software engineering. Other areas of software engineering that are affected include Configuration Management, Testing, Quality Control, and Verification and Validation (V&V). Activities in each of these areas must be adapted to address the entire domain or product line rather than a specific application system. This paper discusses changes and enhancements to the V&V process, in order to adapt V&V to reuse-based software engineering.

Cognitive and neural correlates of depression-like behaviour in socially defeated mice: an animal model of depression with cognitive dysfunction.

PubMed

Yu, Tao; Guo, Ming; Garza, Jacob; Rendon, Samantha; Sun, Xue-Li; Zhang, Wei; Lu, Xin-Yun

2011-04-01

Human depression is associated with cognitive deficits. It is critical to have valid animal models in order to investigate mechanisms and treatment strategies for these associated conditions. The goal of this study was to determine the association of cognitive dysfunction with depression-like behaviour in an animal model of depression and investigate the neural circuits underlying the behaviour. Mice that were exposed to social defeat for 14 d developed depression-like behaviour, i.e. anhedonia and social avoidance as indicated by reduced sucrose preference and decreased social interaction. The assessment of cognitive performance of defeated mice demonstrated impaired working memory in the T-maze continuous alternation task and enhanced fear memory in the contextual and cued fear-conditioning tests. In contrast, reference learning and memory in the Morris water maze test were intact in defeated mice. Neuronal activation following chronic social defeat was investigated by c-fosin-situ hybridization. Defeated mice exhibited preferential neural activity in the prefrontal cortex, cingulate cortex, hippocampal formation, septum, amygdala, and hypothalamic nuclei. Taken together, our results suggest that the chronic social defeat mouse model could serve as a valid animal model to study depression with cognitive impairments. The patterns of neuronal activation provide a neural basis for social defeat-induced changes in behaviour.

Comparing Thermal Process Validation Methods for Salmonella Inactivation on Almond Kernels.

PubMed

Jeong, Sanghyup; Marks, Bradley P; James, Michael K

2017-01-01

Ongoing regulatory changes are increasing the need for reliable process validation methods for pathogen reduction processes involving low-moisture products; however, the reliability of various validation methods has not been evaluated. Therefore, the objective was to quantify accuracy and repeatability of four validation methods (two biologically based and two based on time-temperature models) for thermal pasteurization of almonds. Almond kernels were inoculated with Salmonella Enteritidis phage type 30 or Enterococcus faecium (NRRL B-2354) at ~10 8 CFU/g, equilibrated to 0.24, 0.45, 0.58, or 0.78 water activity (a w ), and then heated in a pilot-scale, moist-air impingement oven (dry bulb 121, 149, or 177°C; dew point <33.0, 69.4, 81.6, or 90.6°C; v air = 2.7 m/s) to a target lethality of ~4 log. Almond surface temperatures were measured in two ways, and those temperatures were used to calculate Salmonella inactivation using a traditional (D, z) model and a modified model accounting for process humidity. Among the process validation methods, both methods based on time-temperature models had better repeatability, with replication errors approximately half those of the surrogate ( E. faecium ). Additionally, the modified model yielded the lowest root mean squared error in predicting Salmonella inactivation (1.1 to 1.5 log CFU/g); in contrast, E. faecium yielded a root mean squared error of 1.2 to 1.6 log CFU/g, and the traditional model yielded an unacceptably high error (3.4 to 4.4 log CFU/g). Importantly, the surrogate and modified model both yielded lethality predictions that were statistically equivalent (α = 0.05) to actual Salmonella lethality. The results demonstrate the importance of methodology, a w , and process humidity when validating thermal pasteurization processes for low-moisture foods, which should help processors select and interpret validation methods to ensure product safety.

The Cerebral Basis for Language Learner Strategies: A Near-Infrared Spectroscopy Study

ERIC Educational Resources Information Center

Takeuchi, Osamu; Ikeda, Maiko; Mizumoto, Atsushi

2012-01-01

In this paper, we validate Macaro's (2006) model of strategy use among language learners by assessing the amount of neural activity around the prefrontal cortex, the supposed locus of working memory (WM). We also examine whether WM activation during first language (L1) strategy deployment is lower than WM activation during second language (L2)…

ATRIAL NATRIURETIC FACTOR RECEPTOR GUANYLATE CYCLASE SIGNALING: NEW ATP- REGULATED TRANSDUCTION MOTIF

PubMed Central

Duda, Teresa; Bharill, Shashank; Wojtas, Ireneusz; Yadav, Prem; Gryczynski, Ignacy; Gryczynski, Zygmunt; Sharma, Rameshwar K.

2010-01-01

ANF-RGC$ membrane guanylate cyclase is the receptor for the hypotensive peptide hormones, atrial natriuretic factor (ANF) and type B natriuretic peptide (BNP). It is a single transmembrane spanning protein. Binding the hormone to the extracellular domain activates its intracellular catalytic domain. This results in accelerated production of cyclic GMP, a second messenger in controlling blood pressure, cardiac vasculature and fluid secretion. ATP is the obligatory transducer of the ANF signal. It works through its ATP regulated module, ARM, which is juxtaposed to the C-terminal side of the transmembrane domain. Upon interaction, ATP induces a cascade of temporal and spatial changes in the ARM, which, finally, result in activation of the catalytic module. Although the exact nature and the details of these changes are not known, some of these have been stereographed in the simulated three-dimensional model of the ARM and validated biochemically. Through comprehensive techniques ofsteady-state, time-resolved tryptophan fluorescence and Forster Resonance Energy Transfer (FRET), site-directed and deletion-mutagenesis, and reconstitution, the present study validates and explains themechanism of the model-based predicted transduction role of the ARM’s structural motif, 669WTAPELL675. This motif is critical in the ATP-dependent ANF signaling. Molecular modeling shows that ATP binding exposes the 669WTAPELL675 motif, the exposure, in turn, facilitates its interaction and activation of the catalytic module. These principles of the model have been experimentally validated. This knowledge brings us a step closer to our understanding of the mechanism by which the ATP-dependent spatial changes within the ARM cause ANF signaling of ANF-RGC. PMID:19137266

Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.

PubMed

Gomes, Anna; van der Wijk, Lars; Proost, Johannes H; Sinha, Bhanu; Touw, Daan J

2017-01-01

Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients.

Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models

PubMed Central

van der Wijk, Lars; Proost, Johannes H.; Sinha, Bhanu; Touw, Daan J.

2017-01-01

Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients. PMID:28475651

Analysis of dose rates received around the storage pool for irradiated control rods in a BWR nuclear power plant.

PubMed

Ródenas, J; Abarca, A; Gallardo, S

2011-08-01

BWR control rods are activated by neutron reactions in the reactor. The dose produced by this activity can affect workers in the area surrounding the storage pool, where activated rods are stored. Monte Carlo (MC) models for neutron activation and dose assessment around the storage pool have been developed and validated. In this work, the MC models are applied to verify the expected reduction of dose when the irradiated control rod is hanged in an inverted position into the pool. 2010 Elsevier Ltd. All rights reserved.

Numerical Modelling of Femur Fracture and Experimental Validation Using Bone Simulant.

PubMed

Marco, Miguel; Giner, Eugenio; Larraínzar-Garijo, Ricardo; Caeiro, José Ramón; Miguélez, María Henar

2017-10-01

Bone fracture pattern prediction is still a challenge and an active field of research. The main goal of this article is to present a combined methodology (experimental and numerical) for femur fracture onset analysis. Experimental work includes the characterization of the mechanical properties and fracture testing on a bone simulant. The numerical work focuses on the development of a model whose material properties are provided by the characterization tests. The fracture location and the early stages of the crack propagation are modelled using the extended finite element method and the model is validated by fracture tests developed in the experimental work. It is shown that the accuracy of the numerical results strongly depends on a proper bone behaviour characterization.

Computational Modeling and Validation for Hypersonic Inlets

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.

1996-01-01

Hypersonic inlet research activity at NASA is reviewed. The basis for the paper is the experimental tests performed with three inlets: the NASA Lewis Research Center Mach 5, the McDonnell Douglas Mach 12, and the NASA Langley Mach 18. Both three-dimensional PNS and NS codes have been used to compute the flow within the three inlets. Modeling assumptions in the codes involve the turbulence model, the nature of the boundary layer, shock wave-boundary layer interaction, and the flow spilled to the outside of the inlet. Use of the codes and the experimental data are helping to develop a clearer understanding of the inlet flow physics and to focus on the modeling improvements required in order to arrive at validated codes.

The importance of measuring growth in response to intervention models: Testing a core assumption✩

PubMed Central

Schatschneider, Christopher; Wagner, Richard K.; Crawford, Elizabeth C.

2011-01-01

A core assumption of response to instruction or intervention (RTI) models is the importance of measuring growth in achievement over time in response to effective instruction or intervention. Many RTI models actively monitor growth for identifying individuals who need different levels of intervention. A large-scale (N=23,438), two-year longitudinal study of first grade children was carried out to compare the predictive validity of measures of achievement status, growth in achievement, and their combination for predicting future reading achievement. The results indicate that under typical conditions, measures of growth do not make a contribution to prediction that is independent of measures of achievement status. These results question the validity of a core assumption of RTI models. PMID:22224065

On vital aid: the why, what and how of validation

PubMed Central

Kleywegt, Gerard J.

2009-01-01

Limitations to the data and subjectivity in the structure-determination process may cause errors in macromolecular crystal structures. Appropriate validation techniques may be used to reveal problems in structures, ideally before they are analysed, published or deposited. Additionally, such tech­niques may be used a posteriori to assess the (relative) merits of a model by potential users. Weak validation methods and statistics assess how well a model reproduces the information that was used in its construction (i.e. experimental data and prior knowledge). Strong methods and statistics, on the other hand, test how well a model predicts data or information that were not used in the structure-determination process. These may be data that were excluded from the process on purpose, general knowledge about macromolecular structure, information about the biological role and biochemical activity of the molecule under study or its mutants or complexes and predictions that are based on the model and that can be tested experimentally. PMID:19171968

Validation and pharmacological characterisation of MK-801-induced locomotor hyperactivity in BALB/C mice as an assay for detection of novel antipsychotics.

PubMed

Bradford, Andrea M; Savage, Kevin M; Jones, Declan N C; Kalinichev, Mikhail

2010-10-01

We evaluated locomotor hyperactivity induced in BALB/C mice by an N-methyl-D-aspartate receptor antagonist MK-801 as an assay for the detection of antipsychotic drugs. We assessed the effects of antipsychotic drugs to validate the assay (study 1), selective dopamine and serotonin ligands for pharmacological characterisation of the model (study 2) and a number of compounds with efficacy in models of schizophrenia to understand the predictive validity of the model (study 3). Adult males (n  = 9/group) were pretreated with a test compound, habituated to locomotor activity cages before receiving MK-801 (0.32 mg/kg) and activity recorded for a further 75 or 120 min. In study 1, we tested haloperidol, clozapine, olanzapine, risperidone, ziprasidone, aripiprazole, sertindole and quetiapine. In study 2, we tested SCH23390 (D(1) antagonist), sulpiride (D(2)/D(3) antagonist), raclopride (D(2)/D(3) antagonist), SB-277011 (D(3) antagonist), L-745,870 (D(4) antagonist), WAY100635 (5-HT(1A) antagonist), 8-OH-DPAT (5-HT(1A) agonist), ketanserin (5-HT(2A)/5-HT(2C) antagonist) and SB-242084 (5-HT(2C) antagonist). In study 3, we tested xanomeline (M(1)/M(4) receptor agonist), LY379268 (mGluR2/3 receptor agonist), diazepam (GABA(A) modulator) and thioperamide (H(3) receptor antagonist). All antipsychotics suppressed MK-801-induced hyperactivity in a dose-dependent and specific manner. The effects of antipsychotics appear to be mediated via dopamine D(1), D(2) and 5-HT(2) receptors. Xanomeline, LY379268 and diazepam were active in this assay while thioperamide was not. MK-801-induced hyperactivity in BALB/C mice model of positive symptoms has shown predictive validity with novel compounds acing at M(1)/M(4), mGluR2/3 and GABA(A) receptors and can be used as a screening assay for detection of novel pharmacotherapies targeting those receptors.

Validity of a scale of neighbourhood informal social control relevant to pre-schoolers' physical activity: A cross-sectional study.

PubMed

Cerin, Ester; Suen, Yi Nam; Barnett, Anthony; Huang, Wendy Y J; Mellecker, Robin R

2017-12-01

Childhood physical activity (PA) is important for health across the lifespan. Time pre-schoolers spend outdoors, which has been associated with more PA, is likely influenced by parents' perception of neighbourhood informal social control relevant to pre-schoolers' PA, defined as the willingness of neighbours to intervene to ensure social order and a safe community environment for young children's active play. To advance measurement of this construct, we assessed factorial and construct validities of the PA-related neighbourhood informal social control scale for parents of pre-schoolers (PANISC-PP). In 2013-2014, Hong Kong primary caregivers (n=394) of 3-5 year-old children completed a socio-demographic questionnaire, the preliminary version of the PANISC-PP, and self-report measures of theoretical neighbourhood correlates of PA-related neighbourhood informal social control (perceived signs of physical and social disorder, community cohesion, perceived stranger danger, risk of unintentional injury and traffic safety). The fit of the data to an a priori measurement model of the PANISC-PP was examined using confirmatory factor analyses. As the a priori model showed inadequate fit to the data, the factor structure was re-specified based on theoretical considerations. The final measurement models of the PANISC-PP showed acceptable fit to the data and consisted of three correlated latent factors: "General informal supervision", "Civic engagement for the creation of a better neighbourhood environment" and "Educating and assisting neighbourhood children". The internal reliability of the subscales was good (Cronbach's α values 0.82-0.89). Generalised additive mixed models indicated that all subscales were positively associated with community cohesion and scores on the subscale "Educating and assisting neighbourhood children" were related in the expected direction to all indicators of traffic and personal safety, supporting construct validity of the PANISC-PP. This study suggests that the PANISC-PP is a reliable and valid instrument for assessing parents' perceived neighbourhood informal social control related to pre-schoolers' PA.

Validation of WBMOD in the Southeast Asian region

NASA Astrophysics Data System (ADS)

Cervera, M. A.; Thomas, R. M.; Groves, K. M.; Ramli, A. G.; Effendy

2001-01-01

The scintillation modeling code WBMOD, developed at North West Research, provides a global description of scintillation occurrence. However, the model has had limited calibration globally. Thus its performance in localized regions such as Australia-Southeast Asia is required to be evaluated. The Defence Science and Technology Organisation, Australia, in conjunction with Indonesian National Institute of Aeronautics and Space (LAPAN), Defence Science and Technology Centre, Malaysia, Air Force Research laboratory, United States, and IPS Radio and Space Services of Australia, has commissioned a network of GPS receivers to measure scintillation from sites in the region. One of the objectives of this deployment is to carry out a validation of WBMOD in the region. This paper describes the network of GPS receivers used to record the scintillation data. The details of the procedure used to validate WBMOD are given and results of the validation are presented for data collected during 1998 and 1999 from two sites, one situated in the southern anomaly region and the other situated near the geomagnetic equator. We found good overall agreement between WBMOD and the observations for low sunspot numbers at both sites, although some differences were noted, the major one being that the scintillation activity predicted by WBMOD tended to cut off too early in the night. At higher levels of sunspot activity, while WBMOD agreed with the observations in the southern anomaly region, we found that it significantly underestimated the level of scintillation activity at the geomagnetic equator.

The Isolation and Characterization of Human Prostate Cancer Stem Cells

DTIC Science & Technology

2012-02-01

established cell lines and primary patient samples) with human prostate fibroblasts hold promise as models of tumor initiation/cancer stem cell activity...We continue to optimize and validate our in vitro model of prostate cancer initiation to facilitate cancer stem cell discovery as well as drug targeting.

Relative Chemical Binding Affinities for Trout and Human Estrogen Receptor Using Different Competitive Binding Assays

EPA Science Inventory

Rainbow trout-based assays for estrogenicity are currently being used for development of predictive models based upon quantitative structure activity relationships. A predictive model based on a single species raises the question of whether this information is valid for other spe...

Modeling the Effects of Conservation Tillage on Water Quality at the Field Scale

USDA-ARS?s Scientific Manuscript database

The development and application of predictive tools to quantitatively assess the effects of tillage and related management activities should be carefully tested against high quality field data. This study reports on: 1) the calibration and validation of the Root Zone Water Quality Model (RZWQM) to a...

Fractal active contour model for segmenting the boundary of man-made target in nature scenes

NASA Astrophysics Data System (ADS)

Li, Min; Tang, Yandong; Wang, Lidi; Shi, Zelin

2006-02-01

In this paper, a novel geometric active contour model based on the fractal dimension feature to extract the boundary of man-made target in nature scenes is presented. In order to suppress the nature clutters, an adaptive weighting function is defined using the fractal dimension feature. Then the weighting function is introduced into the geodesic active contour model to detect the boundary of man-made target. Curve driven by our proposed model can evolve gradually from the initial position to the boundary of man-made target without being disturbed by nature clutters, even if the initial curve is far away from the true boundary. Experimental results validate the effectiveness and feasibility of our model.

Cooling Technology for Large Space Telescopes

NASA Technical Reports Server (NTRS)

DiPirro, Michael; Cleveland, Paul; Durand, Dale; Klavins, Andy; Muheim, Daniella; Paine, Christopher; Petach, Mike; Tenerelli, Domenick; Tolomeo, Jason; Walyus, Keith

2007-01-01

NASA's New Millennium Program funded an effort to develop a system cooling technology, which is applicable to all future infrared, sub-millimeter and millimeter cryogenic space telescopes. In particular, this technology is necessary for the proposed large space telescope Single Aperture Far-Infrared Telescope (SAFIR) mission. This technology will also enhance the performance and lower the risk and cost for other cryogenic missions. The new paradigm for cooling to low temperatures will involve passive cooling using lightweight deployable membranes that serve both as sunshields and V-groove radiators, in combination with active cooling using mechanical coolers operating down to 4 K. The Cooling Technology for Large Space Telescopes (LST) mission planned to develop and demonstrate a multi-layered sunshield, which is actively cooled by a multi-stage mechanical cryocooler, and further the models and analyses critical to scaling to future missions. The outer four layers of the sunshield cool passively by radiation, while the innermost layer is actively cooled to enable the sunshield to decrease the incident solar irradiance by a factor of more than one million. The cryocooler cools the inner layer of the sunshield to 20 K, and provides cooling to 6 K at a telescope mounting plate. The technology readiness level (TRL) of 7 will be achieved by the active cooling technology following the technology validation flight in Low Earth Orbit. In accordance with the New Millennium charter, tests and modeling are tightly integrated to advance the technology and the flight design for "ST-class" missions. Commercial off-the-shelf engineering analysis products are used to develop validated modeling capabilities to allow the techniques and results from LST to apply to a wide variety of future missions. The LST mission plans to "rewrite the book" on cryo-thermal testing and modeling techniques, and validate modeling techniques to scale to future space telescopes such as SAFIR.

Validation of reactive gases and aerosols in the MACC global analysis and forecast system

NASA Astrophysics Data System (ADS)

Eskes, H.; Huijnen, V.; Arola, A.; Benedictow, A.; Blechschmidt, A.-M.; Botek, E.; Boucher, O.; Bouarar, I.; Chabrillat, S.; Cuevas, E.; Engelen, R.; Flentje, H.; Gaudel, A.; Griesfeller, J.; Jones, L.; Kapsomenakis, J.; Katragkou, E.; Kinne, S.; Langerock, B.; Razinger, M.; Richter, A.; Schultz, M.; Schulz, M.; Sudarchikova, N.; Thouret, V.; Vrekoussis, M.; Wagner, A.; Zerefos, C.

2015-11-01

The European MACC (Monitoring Atmospheric Composition and Climate) project is preparing the operational Copernicus Atmosphere Monitoring Service (CAMS), one of the services of the European Copernicus Programme on Earth observation and environmental services. MACC uses data assimilation to combine in situ and remote sensing observations with global and regional models of atmospheric reactive gases, aerosols, and greenhouse gases, and is based on the Integrated Forecasting System of the European Centre for Medium-Range Weather Forecasts (ECMWF). The global component of the MACC service has a dedicated validation activity to document the quality of the atmospheric composition products. In this paper we discuss the approach to validation that has been developed over the past 3 years. Topics discussed are the validation requirements, the operational aspects, the measurement data sets used, the structure of the validation reports, the models and assimilation systems validated, the procedure to introduce new upgrades, and the scoring methods. One specific target of the MACC system concerns forecasting special events with high-pollution concentrations. Such events receive extra attention in the validation process. Finally, a summary is provided of the results from the validation of the latest set of daily global analysis and forecast products from the MACC system reported in November 2014.

Dynamic modeling of sludge compaction and consolidation processes in wastewater secondary settling tanks.

PubMed

Abusam, A; Keesman, K J

2009-01-01

The double exponential settling model is the widely accepted model for wastewater secondary settling tanks. However, this model does not estimate accurately solids concentrations in the settler underflow stream, mainly because sludge compression and consolidation processes are not considered. In activated sludge systems, accurate estimation of the solids in the underflow stream will facilitate the calibration process and can lead to correct estimates of particularly kinetic parameters related to biomass growth. Using principles of compaction and consolidation, as in soil mechanics, a dynamic model of the sludge consolidation processes taking place in the secondary settling tanks is developed and incorporated to the commonly used double exponential settling model. The modified double exponential model is calibrated and validated using data obtained from a full-scale wastewater treatment plant. Good agreement between predicted and measured data confirmed the validity of the modified model.

Summary of BISON Development and Validation Activities - NEAMS FY16 Report

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

Williamson, R. L.; Pastore, G.; Gamble, K. A.

This summary report contains an overview of work performed under the work package en- titled “FY2016 NEAMS INL-Engineering Scale Fuel Performance (BISON)” A first chapter identifies the specific FY-16 milestones, providing a basic description of the associated work and references to related detailed documentation. Where applicable, a representative technical result is provided. A second chapter summarizes major additional accomplishments, which in- clude: 1) publication of a journal article on solution verification and validation of BISON for LWR fuel, 2) publication of a journal article on 3D Missing Pellet Surface (MPS) analysis of BWR fuel, 3) use of BISON to designmore » a unique 3D MPS validation experiment for future in- stallation in the Halden research reactor, 4) participation in an OECD benchmark on Pellet Clad Mechanical Interaction (PCMI), 5) participation in an OECD benchmark on Reactivity Insertion Accident (RIA) analysis, 6) participation in an OECD activity on uncertainity quantification and sensitivity analysis in nuclear fuel modeling and 7) major improvements to BISON’s fission gas behavior models. A final chapter outlines FY-17 future work.« less

Fault Detection for Automotive Shock Absorber

NASA Astrophysics Data System (ADS)

Hernandez-Alcantara, Diana; Morales-Menendez, Ruben; Amezquita-Brooks, Luis

2015-11-01

Fault detection for automotive semi-active shock absorbers is a challenge due to the non-linear dynamics and the strong influence of the disturbances such as the road profile. First obstacle for this task, is the modeling of the fault, which has been shown to be of multiplicative nature. Many of the most widespread fault detection schemes consider additive faults. Two model-based fault algorithms for semiactive shock absorber are compared: an observer-based approach and a parameter identification approach. The performance of these schemes is validated and compared using a commercial vehicle model that was experimentally validated. Early results shows that a parameter identification approach is more accurate, whereas an observer-based approach is less sensible to parametric uncertainty.

Fixed gain and adaptive techniques for rotorcraft vibration control

NASA Technical Reports Server (NTRS)

Roy, R. H.; Saberi, H. A.; Walker, R. A.

1985-01-01

The results of an analysis effort performed to demonstrate the feasibility of employing approximate dynamical models and frequency shaped cost functional control law desgin techniques for helicopter vibration suppression are presented. Both fixed gain and adaptive control designs based on linear second order dynamical models were implemented in a detailed Rotor Systems Research Aircraft (RSRA) simulation to validate these active vibration suppression control laws. Approximate models of fuselage flexibility were included in the RSRA simulation in order to more accurately characterize the structural dynamics. The results for both the fixed gain and adaptive approaches are promising and provide a foundation for pursuing further validation in more extensive simulation studies and in wind tunnel and/or flight tests.

Self-reported competency--validation of the Norwegian version of the patient competency rating scale for traumatic brain injury.

PubMed

Sveen, Unni; Andelic, Nada; Bautz-Holter, Erik; Røe, Cecilie

2015-01-01

To evaluate the psychometric properties of the Norwegian version of the Patient Competency Rating Scale (PCRS) in patients with traumatic brain injury (TBI) at 12 months post-injury. Demographic and injury-related data were registered upon admission to the hospital in 148 TBI patients with mild, moderate, or severe TBI. At 12 months post-injury, competency in activities and global functioning were measured using the PCRS patient version and the Glasgow Outcome Scale-Extended (GOSE). Descriptive reliability statistics, factor analysis and Rasch modeling were applied to explore the psychometric properties of the PCRS. External validity was evaluated using the GOSE. The PCRS can be divided into three subscales that reflect interpersonal/emotional, cognitive, and activities of daily living competency. The three-factor solution explained 56.6% of the variance in functioning. The internal consistency was very good, with a Cronbach's α of 0.95. Item 30, "controlling my laughter", did not load above 0.40 on any factors and did not fit the Rasch model. The external validity of the subscales was acceptable, with correlations between 0.50 and 0.52 with the GOSE. The Norwegian version of the PCRS is reliable, has an acceptable construct and external validity, and can be recommended for use during the later phases of TBI.

Space Weather Models at the CCMC And Their Capabilities

NASA Technical Reports Server (NTRS)

Hesse, Michael; Rastatter, Lutz; MacNeice, Peter; Kuznetsova, Masha

2007-01-01

The Community Coordinated Modeling Center (CCMC) is a US inter-agency activity aiming at research in support of the generation of advanced space weather models. As one of its main functions, the CCMC provides to researchers the use of space science models, even if they are not model owners themselves. The second focus of CCMC activities is on validation and verification of space weather models, and on the transition of appropriate models to space weather forecast centers. As part of the latter activity, the CCMC develops real-time simulation systems that stress models through routine execution. A by-product of these real-time calculations is the ability to derive model products, which may be useful for space weather operators. In this presentation, we will provide an overview of the community-provided, space weather-relevant, model suite, which resides at CCMC. We will discuss current capabilities, and analyze expected future developments of space weather related modeling.

A Comparison of Energy Expenditure Estimation of Several Physical Activity Monitors

PubMed Central

Dannecker, Kathryn L.; Sazonova, Nadezhda A.; Melanson, Edward L.; Sazonov, Edward S.; Browning, Raymond C.

2013-01-01

Accurately and precisely estimating free-living energy expenditure (EE) is important for monitoring energy balance and quantifying physical activity. Recently, single and multi-sensor devices have been developed that can classify physical activities, potentially resulting in improved estimates of EE. PURPOSE To determine the validity of EE estimation of a footwear-based physical activity monitor and to compare this validity against a variety of research and consumer physical activity monitors. METHODS Nineteen healthy young adults (10 male, 9 female), completed a four-hour stay in a room calorimeter. Participants wore a footwear-based physical activity monitor, as well as Actical, Actigraph, IDEEA, DirectLife and Fitbit devices. Each individual performed a series of postures/activities. We developed models to estimate EE from the footwear-based device, and we used the manufacturer's software to estimate EE for all other devices. RESULTS Estimated EE using the shoe-based device was not significantly different than measured EE (476(20) vs. 478(18) kcal) (Mean (SE)), respectively, and had a root mean square error (RMSE) of (29.6 kcal (6.2%)). The IDEEA and DirectLlife estimates of EE were not significantly different than the measured EE but the Actigraph and Fitbit devices significantly underestimated EE. Root mean square errors were 93.5 (19%), 62.1 kcal (14%), 88.2 kcal (18%), 136.6 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for Actical, DirectLife, IDEEA, Actigraph and Fitbit respectively. CONCLUSIONS The shoe based physical activity monitor provides a valid estimate of EE while the other physical activity monitors tested have a wide range of validity when estimating EE. Our results also demonstrate that estimating EE based on classification of physical activities can be more accurate and precise than estimating EE based on total physical activity. PMID:23669877

Predictions of BuChE inhibitors using support vector machine and naive Bayesian classification techniques in drug discovery.

PubMed

Fang, Jiansong; Yang, Ranyao; Gao, Li; Zhou, Dan; Yang, Shengqian; Liu, Ai-Lin; Du, Guan-hua

2013-11-25

Butyrylcholinesterase (BuChE, EC 3.1.1.8) is an important pharmacological target for Alzheimer's disease (AD) treatment. However, the currently available BuChE inhibitor screening assays are expensive, labor-intensive, and compound-dependent. It is necessary to develop robust in silico methods to predict the activities of BuChE inhibitors for the lead identification. In this investigation, support vector machine (SVM) models and naive Bayesian models were built to discriminate BuChE inhibitors (BuChEIs) from the noninhibitors. Each molecule was initially represented in 1870 structural descriptors (1235 from ADRIANA.Code, 334 from MOE, and 301 from Discovery studio). Correlation analysis and stepwise variable selection method were applied to figure out activity-related descriptors for prediction models. Additionally, structural fingerprint descriptors were added to improve the predictive ability of models, which were measured by cross-validation, a test set validation with 1001 compounds and an external test set validation with 317 diverse chemicals. The best two models gave Matthews correlation coefficient of 0.9551 and 0.9550 for the test set and 0.9132 and 0.9221 for the external test set. To demonstrate the practical applicability of the models in virtual screening, we screened an in-house data set with 3601 compounds, and 30 compounds were selected for further bioactivity assay. The assay results showed that 10 out of 30 compounds exerted significant BuChE inhibitory activities with IC50 values ranging from 0.32 to 22.22 μM, at which three new scaffolds as BuChE inhibitors were identified for the first time. To our best knowledge, this is the first report on BuChE inhibitors using machine learning approaches. The models generated from SVM and naive Bayesian approaches successfully predicted BuChE inhibitors. The study proved the feasibility of a new method for predicting bioactivities of ligands and discovering novel lead compounds.

A Model-based Approach to Controlling the ST-5 Constellation Lights-Out Using the GMSEC Message Bus and Simulink

NASA Technical Reports Server (NTRS)

Witt, Kenneth J.; Stanley, Jason; Shendock, Robert; Mandl, Daniel

2005-01-01

Space Technology 5 (ST-5) is a three-satellite constellation, technology validation mission under the New Millennium Program at NASA to be launched in March 2006. One of the key technologies to be validated is a lights-out, model-based operations approach to be used for one week to control the ST-5 constellation with no manual intervention. The ground architecture features the GSFC Mission Services Evolution Center (GMSEC) middleware, which allows easy plugging in of software components and a standardized messaging protocol over a software bus. A predictive modeling tool built on MatLab's Simulink software package makes use of the GMSEC standard messaging protocol to interface to the Advanced Mission Planning System (AMPS) Scenario Scheduler which controls all activities, resource allocation and real-time re-profiling of constellation resources when non-nominal events occur. The key features of this system, which we refer to as the ST-5 Simulink system, are as follows: Original daily plan is checked to make sure that predicted resources needed are available by comparing the plan against the model. As the plan is run in real-time, the system re-profiles future activities in real-time if planned activities do not occur in the predicted timeframe or fashion. Alert messages are sent out on the GMSEC bus by the system if future predicted problems are detected. This will allow the Scenario Scheduler to correct the situation before the problem happens. The predictive model is evolved automatically over time via telemetry updates thus reducing the cost of implementing and maintaining the models by an order of magnitude from previous efforts at GSFC such as the model-based system built for MAP in the mid-1990's. This paper will describe the key features, lessons learned and implications for future missions once this system is successfully validated on-orbit in 2006.

Steps in the design, development and formative evaluation of obesity prevention-related behavior change trials.

PubMed

Baranowski, Tom; Cerin, Ester; Baranowski, Janice

2009-01-21

Obesity prevention interventions through dietary and physical activity change have generally not been effective. Limitations on possible program effectiveness are herein identified at every step in the mediating variable model, a generic conceptual framework for understanding how interventions may promote behavior change. To minimize these problems, and thereby enhance likely intervention effectiveness, four sequential types of formative studies are proposed: targeted behavior validation, targeted mediator validation, intervention procedure validation, and pilot feasibility intervention. Implementing these studies would establish the relationships at each step in the mediating variable model, thereby maximizing the likelihood that an intervention would work and its effects would be detected. Building consensus among researchers, funding agencies, and journal editors on distinct intervention development studies should avoid identified limitations and move the field forward.

Steps in the design, development and formative evaluation of obesity prevention-related behavior change trials

PubMed Central

Baranowski, Tom; Cerin, Ester; Baranowski, Janice

2009-01-01

Obesity prevention interventions through dietary and physical activity change have generally not been effective. Limitations on possible program effectiveness are herein identified at every step in the mediating variable model, a generic conceptual framework for understanding how interventions may promote behavior change. To minimize these problems, and thereby enhance likely intervention effectiveness, four sequential types of formative studies are proposed: targeted behavior validation, targeted mediator validation, intervention procedure validation, and pilot feasibility intervention. Implementing these studies would establish the relationships at each step in the mediating variable model, thereby maximizing the likelihood that an intervention would work and its effects would be detected. Building consensus among researchers, funding agencies, and journal editors on distinct intervention development studies should avoid identified limitations and move the field forward. PMID:19159476

Distributed Trust Management for Validating SLA Choreographies

NASA Astrophysics Data System (ADS)

Haq, Irfan Ul; Alnemr, Rehab; Paschke, Adrian; Schikuta, Erich; Boley, Harold; Meinel, Christoph

For business workflow automation in a service-enriched environment such as a grid or a cloud, services scattered across heterogeneous Virtual Organizations (VOs) can be aggregated in a producer-consumer manner, building hierarchical structures of added value. In order to preserve the supply chain, the Service Level Agreements (SLAs) corresponding to the underlying choreography of services should also be incrementally aggregated. This cross-VO hierarchical SLA aggregation requires validation, for which a distributed trust system becomes a prerequisite. Elaborating our previous work on rule-based SLA validation, we propose a hybrid distributed trust model. This new model is based on Public Key Infrastructure (PKI) and reputation-based trust systems. It helps preventing SLA violations by identifying violation-prone services at service selection stage and actively contributes in breach management at the time of penalty enforcement.

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

PubMed Central

Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun

2016-01-01

The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening. PMID:27102549

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery.

PubMed

Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun

2016-04-22

The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening.

Validation of Community Models: 2. Development of a Baseline, Using the Wang-Sheeley-Arge Model

NASA Technical Reports Server (NTRS)

MacNeice, Peter

2009-01-01

This paper is the second in a series providing independent validation of community models of the outer corona and inner heliosphere. Here I present a comprehensive validation of the Wang-Sheeley-Arge (WSA) model. These results will serve as a baseline against which to compare the next generation of comparable forecasting models. The WSA model is used by a number of agencies to predict Solar wind conditions at Earth up to 4 days into the future. Given its importance to both the research and forecasting communities, it is essential that its performance be measured systematically and independently. I offer just such an independent and systematic validation. I report skill scores for the model's predictions of wind speed and interplanetary magnetic field (IMF) polarity for a large set of Carrington rotations. The model was run in all its routinely used configurations. It ingests synoptic line of sight magnetograms. For this study I generated model results for monthly magnetograms from multiple observatories, spanning the Carrington rotation range from 1650 to 2074. I compare the influence of the different magnetogram sources and performance at quiet and active times. I also consider the ability of the WSA model to forecast both sharp transitions in wind speed from slow to fast wind and reversals in the polarity of the radial component of the IMF. These results will serve as a baseline against which to compare future versions of the model as well as the current and future generation of magnetohydrodynamic models under development for forecasting use.

Validating soil denitrification models based on laboratory N_{2} and N_{2}O fluxes and underlying processes derived by stable isotope approaches

NASA Astrophysics Data System (ADS)

Well, Reinhard; Böttcher, Jürgen; Butterbach-Bahl, Klaus; Dannenmann, Michael; Deppe, Marianna; Dittert, Klaus; Dörsch, Peter; Horn, Marcus; Ippisch, Olaf; Mikutta, Robert; Müller, Carsten; Müller, Christoph; Senbayram, Mehmet; Vogel, Hans-Jörg; Wrage-Mönnig, Nicole

2016-04-01

Robust denitrification data suitable to validate soil N2 fluxes in denitrification models are scarce due to methodical limitations and the extreme spatio-temporal heterogeneity of denitrification in soils. Numerical models have become essential tools to predict denitrification at different scales. Model performance could either be tested for total gaseous flux (NO + N2O + N2), individual denitrification products (e.g. N2O and/or NO) or for the effect of denitrification factors (e.g. C-availability, respiration, diffusivity, anaerobic volume, etc.). While there are numerous examples for validating N2O fluxes, there are neither robust field data of N2 fluxes nor sufficiently resolved measurements of control factors used as state variables in the models. To the best of our knowledge there has been only one published validation of modelled soil N2 flux by now, using a laboratory data set to validate an ecosystem model. Hence there is a need for validation data at both, the mesocosm and the field scale including validation of individual denitrification controls. Here we present the concept for collecting model validation data which is be part of the DFG-research unit "Denitrification in Agricultural Soils: Integrated Control and Modelling at Various Scales (DASIM)" starting this year. We will use novel approaches including analysis of stable isotopes, microbial communities, pores structure and organic matter fractions to provide denitrification data sets comprising as much detail on activity and regulation as possible as a basis to validate existing and calibrate new denitrification models that are applied and/or developed by DASIM subprojects. The basic idea is to simulate "field-like" conditions as far as possible in an automated mesocosm system without plants in order to mimic processes in the soil parts not significantly influenced by the rhizosphere (rhizosphere soils are studied by other DASIM projects). Hence, to allow model testing in a wide range of conditions, denitrification control factors will be varied in the initial settings (pore volume, plant residues, mineral N, pH) but also over time, where moisture, temperature, and mineral N will be manipulated according to typical time patterns in the field. This will be realized by including precipitation events, fertilization (via irrigation), drainage (via water potential) and temperature in the course of incubations. Moreover, oxygen concentration will be varied to simulate anaerobic events. These data will be used to calibrate the newly to develop DASIM models as well as existing denitrification models. One goal of DASIM is to create a public data base as a joint basis for model testing by denitrification modellers. Therefore we invite contributions of suitable data-sets from the scientific community. Requirements will be briefly outlined.

Derivation and validation of a multivariate model to predict mortality from pulmonary embolism with cancer: the POMPE-C tool

PubMed Central

Roy, Pierre-Marie; Than, Martin P.; Hernandez, Jackeline; Courtney, D. Mark; Jones, Alan E.; Penazola, Andrea; Pollack, Charles V.

2012-01-01

Background Clinical guidelines recommend risk stratification of patients with acute pulmonary embolism (PE). Active cancer increases risk of PE and worsens prognosis, but also causes incidental PE that may be discovered during cancer staging. No quantitative decision instrument has been derived specifically for patients with active cancer and PE. Methods Classification and regression technique was used to reduce 25 variables prospectively collected from 408 patients with AC and PE. Selected variables were transformed into a logistic regression model, termed POMPE-C, and compared with the pulmonary embolism severity index (PESI) score to predict the outcome variable of death within 30 days. Validation was performed in an independent sample of 182 patients with active cancer and PE. Results POMPE-C included eight predictors: body mass, heart rate >100, respiratory rate, SaO2%, respiratory distress, altered mental status, do not resuscitate status, and unilateral limb swelling. In the derivation set, the area under the ROC curve for POMPE-C was 0.84 (95% CI: 0.82-0.87), significantly greater than PESI (0.68, 0.60-0.76). In the validation sample, POMPE-C had an AUC of 0.86 (0.78-0.93). No patient with POMPE-C estimate ≤5% died within 30 days (0/50, 0-7%), whereas 10/13 (77%, 46-95%) with POMPE-C estimate >50% died within 30 days. Conclusion In patients with active cancer and PE, POMPE-C demonstrated good prognostic accuracy for 30 day mortality and better performance than PESI. If validated in a large sample, POMPE-C may provide a quantitative basis to decide treatment options for PE discovered during cancer staging and with advanced cancer. PMID:22475313

"ELIP-MARC" Activities via TPS of Cooperative Learning to Improve Student's Mathematical Reasoning

ERIC Educational Resources Information Center

Ulya, Wisulah Titah; Purwanto; Parta, I. Nengah; Mulyati, Sri

2017-01-01

The purpose of this study is to describe and generate interaction model of learning through "Elip-Marc" activity via "TPS" cooperative learning in order to improve student's mathematical reasoning who have valid, practical and effective criteria. "Elip-Marc" is an acronym of eliciting, inserting, pressing,…

Pilot utilization plan for satellite data-based service for agriculture in Poland

NASA Astrophysics Data System (ADS)

Gatkowska, Martyna; Paradowski, Karol; Wróbel, Karolina

2017-10-01

The paper aims at demonstrating the assumptions and achievements of the Pilot Utilization Plan Activities performed within the Project ASAP "Advanced Sustainable Agricultural Production", co-financed by European Space Agency under the ARTES IAP Programme. Within the course of the project, the Pilot Utilization Plan (PilUP) activities are performed in order to develop the remote sensing based models, and further calibrate and validate them in order to achieve the accuracy, which meets the requirements of paying customers. The completion of the first PilUP resulted in development of the following models based of Landsat 8 and Sentinel 2 satellite data: model of homogenous polygons demarcation on the basis of comparison of electromagnetic scanning results and bare soil spectral reflectance, model of problematic areas indication and model for yield potential, delivered on the basis of NDVI map developed 1 month before harvest and the map of yield/collected yield derived from Users participating in PilUP. The second edition of the PilUP is being conducted between March 2017 until the end of 2017. This edition includes farmers and insurance companies. The following activities are planned: development of model for delimitation of loses due to unfavorable wintering of winter crops and validation of the model with in-situ data collected by the insurance companies in-field investigators, further enhancement of the model for homogenous polygons delimitation and primary indication of soil productivity and testing of the applicability and viability of map of problematic areas with the farmers.

A passive and active microwave-vector radiative transfer (PAM-VRT) model

NASA Astrophysics Data System (ADS)

Yang, Jun; Min, Qilong

2015-11-01

A passive and active microwave vector radiative transfer (PAM-VRT) package has been developed. This fast and accurate forward microwave model, with flexible and versatile input and output components, self-consistently and realistically simulates measurements/radiation of passive and active microwave sensors. The core PAM-VRT, microwave radiative transfer model, consists of five modules: gas absorption (two line-by-line databases and four fast models); hydrometeor property of water droplets and ice (spherical and nonspherical) particles; surface emissivity (from Community Radiative Transfer Model (CRTM)); vector radiative transfer of successive order of scattering (VSOS); and passive and active microwave simulation. The PAM-VRT package has been validated against other existing models, demonstrating good accuracy. The PAM-VRT not only can be used to simulate or assimilate measurements of existing microwave sensors, but also can be used to simulate observation results at some new microwave sensors.

An Overview of Prognosis Health Management Research at Glenn Research Center for Gas Turbine Engine Structures With Special Emphasis on Deformation and Damage Modeling

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Goldberg, Robert K.; Lerch, Bradley A.; Saleeb, Atef F.

2009-01-01

Herein a general, multimechanism, physics-based viscoelastoplastic model is presented in the context of an integrated diagnosis and prognosis methodology which is proposed for structural health monitoring, with particular applicability to gas turbine engine structures. In this methodology, diagnostics and prognostics will be linked through state awareness variable(s). Key technologies which comprise the proposed integrated approach include (1) diagnostic/detection methodology, (2) prognosis/lifing methodology, (3) diagnostic/prognosis linkage, (4) experimental validation, and (5) material data information management system. A specific prognosis lifing methodology, experimental characterization and validation and data information management are the focal point of current activities being pursued within this integrated approach. The prognostic lifing methodology is based on an advanced multimechanism viscoelastoplastic model which accounts for both stiffness and/or strength reduction damage variables. Methods to characterize both the reversible and irreversible portions of the model are discussed. Once the multiscale model is validated the intent is to link it to appropriate diagnostic methods to provide a full-featured structural health monitoring system.

An Overview of Prognosis Health Management Research at GRC for Gas Turbine Engine Structures With Special Emphasis on Deformation and Damage Modeling

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Goldberg, Robert K.; Lerch, Bradley A.; Saleeb, Atef F.

2009-01-01

Herein a general, multimechanism, physics-based viscoelastoplastic model is presented in the context of an integrated diagnosis and prognosis methodology which is proposed for structural health monitoring, with particular applicability to gas turbine engine structures. In this methodology, diagnostics and prognostics will be linked through state awareness variable(s). Key technologies which comprise the proposed integrated approach include 1) diagnostic/detection methodology, 2) prognosis/lifing methodology, 3) diagnostic/prognosis linkage, 4) experimental validation and 5) material data information management system. A specific prognosis lifing methodology, experimental characterization and validation and data information management are the focal point of current activities being pursued within this integrated approach. The prognostic lifing methodology is based on an advanced multi-mechanism viscoelastoplastic model which accounts for both stiffness and/or strength reduction damage variables. Methods to characterize both the reversible and irreversible portions of the model are discussed. Once the multiscale model is validated the intent is to link it to appropriate diagnostic methods to provide a full-featured structural health monitoring system.

A combined LS-SVM & MLR QSAR workflow for predicting the inhibition of CXCR3 receptor by quinazolinone analogs.

PubMed

Afantitis, Antreas; Melagraki, Georgia; Sarimveis, Haralambos; Koutentis, Panayiotis A; Igglessi-Markopoulou, Olga; Kollias, George

2010-05-01

A novel QSAR workflow is constructed that combines MLR with LS-SVM classification techniques for the identification of quinazolinone analogs as "active" or "non-active" CXCR3 antagonists. The accuracy of the LS-SVM classification technique for the training set and test was 100% and 90%, respectively. For the "active" analogs a validated MLR QSAR model estimates accurately their I-IP10 IC(50) inhibition values. The accuracy of the QSAR model (R (2) = 0.80) is illustrated using various evaluation techniques, such as leave-one-out procedure (R(LOO2)) = 0.67) and validation through an external test set (R(pred2) = 0.78). The key conclusion of this study is that the selected molecular descriptors, Highest Occupied Molecular Orbital energy (HOMO), Principal Moment of Inertia along X and Y axes PMIX and PMIZ, Polar Surface Area (PSA), Presence of triple bond (PTrplBnd), and Kier shape descriptor ((1) kappa), demonstrate discriminatory and pharmacophore abilities.

Quantifying Hydroperiod, Fire and Nutrient Effects on the Composition of Plant Communities in Marl Prairie of the Everglades: a Joint Probability Method Based Model

NASA Astrophysics Data System (ADS)

Zhai, L.

2017-12-01

Plant community can be simultaneously affected by human activities and climate changes, and quantifying and predicting this combined effect on plant community by appropriate model framework which is validated by field data is complex, but very useful to conservation management. Plant communities in the Everglades provide an unique set of conditions to develop and validate this model framework, because they are both experiencing intensive effects of human activities (such as changing hydroperiod by drainage and restoration projects, nutrients from upstream agriculture, prescribed fire, etc.) and climate changes (such as warming, changing precipitation patter, sea level rise, etc.). More importantly, previous research attention focuses on plant communities in slough ecosystem (including ridge, slough and their tree islands), very few studies consider the marl prairie ecosystem. Comparing with slough ecosystem featured by remaining consistently flooded almost year-round, marl prairie has relatively shorter hydroperiod (just in wet-season of one year). Therefore, plant communities of marl prairie may receive more impacts from hydroperiod change. In addition to hydroperiod, fire and nutrients also affect the plant communities in the marl prairie. Therefore, to quantify the combined effects of water level, fire, and nutrients on the composition of the plant communities, we are developing a joint probability method based vegetation dynamic model. Further, the model is being validated by field data about changes of vegetation assemblage along environmental gradients in the marl prairie. Our poster showed preliminary data from our current project.

A review and validation of the IMPLAN model for Pennsylvania's solid hardwood product industries

Treesearch

Bruce E. Lord; Charles H. Strauss

1993-01-01

The IMPLAN model for Pennsylvania was reviewed with respect to the industries processing the state's solid hardwood resources. Several sectors were found to be under represented in the standard sources of industrial activity. Further problems were attributed to the lack of distinction between hardwoods and softwoods in the national model. A further set of changes...

Validating the Learning Cycle Models of Business Simulation Games via Student Perceived Gains in Skills and Knowledge

ERIC Educational Resources Information Center

Tao, Yu-Hui; Yeh, C. Rosa; Hung, Kung Chin

2015-01-01

Several theoretical models have been constructed to determine the effects of buisness simulation games (BSGs) on learning performance. Although these models agree on the concept of learning-cycle effect, no empirical evidence supports the claim that the use of learning cycle activities with BSGs produces an effect on incremental gains in knowledge…

Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives.

PubMed

Ragno, Rino; Artico, Marino; De Martino, Gabriella; La Regina, Giuseppe; Coluccia, Antonio; Di Pasquali, Alessandra; Silvestri, Romano

2005-01-13

Three-dimensional quantitative structure-activity relationship (3-D QSAR) studies and docking simulations were developed on indolyl aryl sulfones (IASs), a class of novel HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (Silvestri, et al. J. Med. Chem. 2003, 46, 2482-2493) highly active against wild type and some clinically relevant resistant strains (Y181C, the double mutant K103N-Y181C, and the K103R-V179D-P225H strain, highly resistant to efavirenz). Predictive 3-D QSAR models using the combination of GRID and GOLPE programs were obtained using a receptor-based alignment by means of docking IASs into the non-nucleoside binding site (NNBS) of RT. The derived 3-D QSAR models showed conventional correlation (r(2)) and cross-validated (q(2)) coefficients values ranging from 0.79 to 0.93 and from 0.59 to 0.84, respectively. All described models were validated by an external test set compiled from previously reported pyrryl aryl sulfones (Artico, et al. J. Med. Chem. 1996, 39, 522-530). The most predictive 3-D QSAR model was then used to predict the activity of novel untested IASs. The synthesis of six designed derivatives (prediction set) allowed disclosure of new IASs endowed with high anti-HIV-1 activities.

Reliability and validity of a treatment adherence measure for child psychiatric rehabilitation.

PubMed

Williams, Nathaniel J; Green, Philip

2012-09-01

Treatment adherence, defined as the degree to which practitioners implemented prescribed program principles and activities and avoided proscribed activities, has been an area of growing interest in mental health services for children with severe emotional and behavioral disorders. This study evaluated the reliability and validity of a treatment adherence measure for child psychiatric rehabilitation (CPSR). Parents of children receiving CPSR (n = 79) or psychotherapy (n = 27) completed the Children's Psychosocial Rehabilitation Treatment Adherence Measure (CTAM) and a measure of 2-week session impact. Psychiatric rehabilitation (PSR) supervisors identified PSR practitioners with reputations for high or low adherence to the model. The CTAM's discriminant validity was assessed by using known-groups procedures and predictive validity by examining its relationship to 2-week session impact. The CTAM demonstrated excellent internal consistency (α = .92), discriminant validity (p = .002, d = .72; p = .021, d = .59), and predictive validity (B = 2.24, SE = .31, p < .001), accounting for 28% of the child-level variance in 2-week session impact. Findings suggest the CTAM is a reliable and valid measure of treatment adherence for CPSR programs with a skill-teaching focus. Providers and agencies should take steps to enhance treatment adherence because it may be an important predictor of children's short-term response to CPSR. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

A cluster expansion model for predicting activation barrier of atomic processes

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

Rehman, Tafizur; Jaipal, M.; Chatterjee, Abhijit, E-mail: achatter@iitk.ac.in

2013-06-15

We introduce a procedure based on cluster expansion models for predicting the activation barrier of atomic processes encountered while studying the dynamics of a material system using the kinetic Monte Carlo (KMC) method. Starting with an interatomic potential description, a mathematical derivation is presented to show that the local environment dependence of the activation barrier can be captured using cluster interaction models. Next, we develop a systematic procedure for training the cluster interaction model on-the-fly, which involves: (i) obtaining activation barriers for handful local environments using nudged elastic band (NEB) calculations, (ii) identifying the local environment by analyzing the NEBmore » results, and (iii) estimating the cluster interaction model parameters from the activation barrier data. Once a cluster expansion model has been trained, it is used to predict activation barriers without requiring any additional NEB calculations. Numerical studies are performed to validate the cluster expansion model by studying hop processes in Ag/Ag(100). We show that the use of cluster expansion model with KMC enables efficient generation of an accurate process rate catalog.« less

CoMFA and CoMSIA studies on C-aryl glucoside SGLT2 inhibitors as potential anti-diabetic agents.

PubMed

Vyas, V K; Bhatt, H G; Patel, P K; Jalu, J; Chintha, C; Gupta, N; Ghate, M

2013-01-01

SGLT2 has become a target of therapeutic interest in diabetes research. CoMFA and CoMSIA studies were performed on C-aryl glucoside SGLT2 inhibitors (180 analogues) as potential anti-diabetic agents. Three different alignment strategies were used for the compounds. The best CoMFA and CoMSIA models were obtained by means of Distill rigid body alignment of training and test sets, and found statistically significant with cross-validated coefficients (q²) of 0.602 and 0.618, respectively, and conventional coefficients (r²) of 0.905 and 0.902, respectively. Both models were validated by a test set of 36 compounds giving satisfactory predicted correlation coefficients (r² pred) of 0.622 and 0.584 for CoMFA and CoMSIA models, respectively. A comparison was made with earlier 3D QSAR study on SGLT2 inhibitors, which shows that our 3D QSAR models are better than earlier models to predict good inhibitory activity. CoMFA and CoMSIA models generated in this work can provide useful information to design new compounds and helped in prediction of activity prior to synthesis.

Pharmacophore modeling and virtual screening studies to design some potential histone deacetylase inhibitors as new leads.

PubMed

Vadivelan, S; Sinha, B N; Rambabu, G; Boppana, Kiran; Jagarlapudi, Sarma A R P

2008-02-01

Histone deacetylase is one of the important targets in the treatment of solid tumors and hematological cancers. A total of 20 well-defined inhibitors were used to generate Pharmacophore models using and HypoGen module of Catalyst. These 20 molecules broadly represent 3 different chemotypes. The best HypoGen model consists of four-pharmacophore features--one hydrogen bond acceptor, one hydrophobic aliphatic and two ring aromatic centers. This model was validated against 378 known HDAC inhibitors with a correlation of 0.897 as well as enrichment factor of 2.68 against a maximum value of 3. This model was further used to retrieve molecules from NCI database with 238,819 molecules. A total of 4638 molecules from a pool of 238,819 molecules were identified as hits while 297 molecules were indicated as highly active. Also, a Similarity analysis has been carried out for set of 4638 hits with respect to most active molecule of each chemotypes which validated not only the Virtual Screening potential of the model but also identified the possible new Chemotypes. This type of Similarity analysis would prove to be efficient not only for lead generation but also for lead optimization.

Molecular description of α-keto-based inhibitors of cruzain with activity against Chagas disease combining 3D-QSAR studies and molecular dynamics.

PubMed

Saraiva, Ádria P B; Miranda, Ricardo M; Valente, Renan P P; Araújo, Jéssica O; Souza, Rutelene N B; Costa, Clauber H S; Oliveira, Amanda R S; Almeida, Michell O; Figueiredo, Antonio F; Ferreira, João E V; Alves, Cláudio Nahum; Honorio, Kathia M

2018-04-22

In this work, a group of α-keto-based inhibitors of the cruzain enzyme with anti-chagas activity was selected for a three-dimensional quantitative structure-activity relationship study (3D-QSAR) combined with molecular dynamics (MD). Firstly, statistical models based on Partial Least Square (PLS) regression were developed employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) descriptors. Validation parameters (q 2 and r 2 )for the models were, respectively, 0.910 and 0.997 (CoMFA) and 0.913 and 0.992 (CoMSIA). In addition, external validation for the models using a test group revealed r 2 pred  = 0.728 (CoMFA) and 0.971 (CoMSIA). The most relevant aspect in this study was the generation of molecular fields in both favorable and unfavorable regions based on the models developed. These fields are important to interpret modifications necessary to enhance the biological activities of the inhibitors. This analysis was restricted considering the inhibitors in a fixed conformation, not interacting with their target, the cruzain enzyme. Then, MD was employed taking into account important variables such as time and temperature. MD helped describe the behavior of the inhibitors and their properties showed similar results as those generated by QSAR-3D study. © 2018 John Wiley & Sons A/S.

Guided Inquiry Facilitated Blended Learning to Improve Metacognitive and Learning Outcome of High School Students

NASA Astrophysics Data System (ADS)

Suwono, H.; Susanti, S.; Lestari, U.

2017-04-01

The learning activities that involve the students to learn actively is one of the characteristics of a qualified education. The learning strategy that involves students’ active learning is guided inquiry. Learning problems today are growing metacognitive skills and cognitive learning outcomes. It is the research and development of learning module by using 4D models of Thiagarajan. The first phase is Define, which analyses the problems and needs required by the prior preparation of the module. The second phase is Design, which formulates learning design and devices to obtain the initial draft of learning modules. The third stage is Develop, which is developing and writing module, module validation, product testing, revision, and the resulting an end-product results module development. The fourth stage is Disseminate, which is disseminating of the valid products. Modules were validated by education experts, practitioners, subject matter experts, and expert of online media. The results of the validation module indicated that the module was valid and could be used in teaching and learning. In the validation phase of testing methods, we used experiments to know the difference of metacognitive skills and learning outcomes between the control group and experimental group. The experimental design was a one group pretest-posttest design. The results of the data analysis showed that the modules could enhance metacognitive skills and learning outcomes. The advantages of this module is as follows, 1) module is accompanied by a video link on a website that contains practical activities that are appropriate to Curriculum 2013, 2) module is accompanied by a video link on a website that contains about manual laboratory activities that will be used in the classroom face-to-face, so that students are ready when doing laboratory activities, 3) this module can be online through chat to increase students’ understanding. The disadvantages of this module are the material presented in the modules is limited. It is suggested that for the better utilisation of the online activities, students should be present at every meeting of the activities, so as to make all the students participate actively. It is also suggested that school set up facilities to support blended learning.

Calibration of self-report tools for physical activity research: the Physical Activity Questionnaire (PAQ)

PubMed Central

2014-01-01

Background The utility of self-report measures of physical activity (PA) in youth can be greatly enhanced by calibrating self-report output against objectively measured PA data. This study demonstrates the potential of calibrating self-report output against objectively measured physical activity (PA) in youth by using a commonly used self-report tool called the Physical Activity Questionnaire (PAQ). Methods A total of 148 participants (grades 4 through 12) from 9 schools (during the 2009–2010 school year) wore an Actigraph accelerometer for 7 days and then completed the PAQ. Multiple linear regression modeling was used on 70% of the available sample to develop a calibration equation and this was cross validated on an independent sample of participants (30% of sample). Results A calibration model with age, gender, and PAQ scores explained 40% of the variance in values for the percentage of time in moderate-to-vigorous PA (%MVPA) measured from the accelerometers (%MVPA = 14.56 - (sex*0.98) - (0.84*age) + (1.01*PAQ)). When tested on an independent, hold-out sample, the model estimated %MVPA values that were highly correlated with the recorded accelerometer values (r = .63) and there was no significant difference between the estimated and recorded activity values (mean diff. = 25.3 ± 18.1 min; p = .17). Conclusions These results suggest that the calibrated PAQ may be a valid alternative tool to activity monitoring instruments for estimating %MVPA in groups of youth. PMID:24886625

Calibration of self-report tools for physical activity research: the Physical Activity Questionnaire (PAQ).

PubMed

Saint-Maurice, Pedro F; Welk, Gregory J; Beyler, Nicholas K; Bartee, Roderick T; Heelan, Kate A

2014-05-16

The utility of self-report measures of physical activity (PA) in youth can be greatly enhanced by calibrating self-report output against objectively measured PA data.This study demonstrates the potential of calibrating self-report output against objectively measured physical activity (PA) in youth by using a commonly used self-report tool called the Physical Activity Questionnaire (PAQ). A total of 148 participants (grades 4 through 12) from 9 schools (during the 2009-2010 school year) wore an Actigraph accelerometer for 7 days and then completed the PAQ. Multiple linear regression modeling was used on 70% of the available sample to develop a calibration equation and this was cross validated on an independent sample of participants (30% of sample). A calibration model with age, gender, and PAQ scores explained 40% of the variance in values for the percentage of time in moderate-to-vigorous PA (%MVPA) measured from the accelerometers (%MVPA = 14.56 - (sex*0.98) - (0.84*age) + (1.01*PAQ)). When tested on an independent, hold-out sample, the model estimated %MVPA values that were highly correlated with the recorded accelerometer values (r = .63) and there was no significant difference between the estimated and recorded activity values (mean diff. = 25.3 ± 18.1 min; p = .17). These results suggest that the calibrated PAQ may be a valid alternative tool to activity monitoring instruments for estimating %MVPA in groups of youth.

Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness.

PubMed

Baldwin, Matthew R; Singer, Jonathan P; Huang, Debbie; Sell, Jessica; Gonzalez, Wendy C; Pollack, Lauren R; Maurer, Mathew S; D'Ovidio, Frank F; Bacchetta, Matthew; Sonett, Joshua R; Arcasoy, Selim M; Shah, Lori; Robbins, Hilary; Hays, Steven R; Kukreja, Jasleen; Greenland, John R; Shah, Rupal J; Leard, Lorriana; Morrell, Matthew; Gries, Cynthia; Katz, Patricia P; Christie, Jason D; Diamond, Joshua M; Lederer, David J

2017-08-01

The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients. To test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument. In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors. Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3). The DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

Development of a physically-based planar inductors VHDL-AMS model for integrated power converter design

NASA Astrophysics Data System (ADS)

Ammouri, Aymen; Ben Salah, Walid; Khachroumi, Sofiane; Ben Salah, Tarek; Kourda, Ferid; Morel, Hervé

2014-05-01

Design of integrated power converters needs prototype-less approaches. Specific simulations are required for investigation and validation process. Simulation relies on active and passive device models. Models of planar devices, for instance, are still not available in power simulator tools. There is, thus, a specific limitation during the simulation process of integrated power systems. The paper focuses on the development of a physically-based planar inductor model and its validation inside a power converter during transient switching. The planar inductor model remains a complex device to model, particularly when the skin, the proximity and the parasitic capacitances effects are taken into account. Heterogeneous simulation scheme, including circuit and device models, is successfully implemented in VHDL-AMS language and simulated in Simplorer platform. The mixed simulation results has been favorably tested and compared with practical measurements. It is found that the multi-domain simulation results and measurements data are in close agreement.

Creating a Test Validated Structural Dynamic Finite Element Model of the Multi-Utility Technology Test Bed Aircraft

NASA Technical Reports Server (NTRS)

Pak, Chan-Gi; Truong, Samson S.

2014-01-01

Small modeling errors in the finite element model will eventually induce errors in the structural flexibility and mass, thus propagating into unpredictable errors in the unsteady aerodynamics and the control law design. One of the primary objectives of Multi Utility Technology Test Bed, X-56A, aircraft is the flight demonstration of active flutter suppression, and therefore in this study, the identification of the primary and secondary modes for the structural model tuning based on the flutter analysis of X-56A. The ground vibration test validated structural dynamic finite element model of the X-56A is created in this study. The structural dynamic finite element model of the X-56A is improved using a model tuning tool. In this study, two different weight configurations of the X-56A have been improved in a single optimization run.

ActivityAware: An App for Real-Time Daily Activity Level Monitoring on the Amulet Wrist-Worn Device.

PubMed

Boateng, George; Batsis, John A; Halter, Ryan; Kotz, David

2017-03-01

Physical activity helps reduce the risk of cardiovascular disease, hypertension and obesity. The ability to monitor a person's daily activity level can inform self-management of physical activity and related interventions. For older adults with obesity, the importance of regular, physical activity is critical to reduce the risk of long-term disability. In this work, we present ActivityAware , an application on the Amulet wrist-worn device that measures daily activity levels (sedentary, moderate and vigorous) of individuals, continuously and in real-time. The app implements an activity-level detection model, continuously collects acceleration data on the Amulet, classifies the current activity level, updates the day's accumulated time spent at that activity level, logs the data for later analysis, and displays the results on the screen. We developed an activity-level detection model using a Support Vector Machine (SVM). We trained our classifiers using data from a user study, where subjects performed the following physical activities: sit, stand, lay down, walk and run. With 10-fold cross validation and leave-one-subject-out (LOSO) cross validation, we obtained preliminary results that suggest accuracies up to 98%, for n=14 subjects. Testing the ActivityAware app revealed a projected battery life of up to 4 weeks before needing to recharge. The results are promising, indicating that the app may be used for activity-level monitoring, and eventually for the development of interventions that could improve the health of individuals.

An RL10A-3-3A rocket engine model using the rocket engine transient simulator (ROCETS) software

NASA Technical Reports Server (NTRS)

Binder, Michael

1993-01-01

Steady-state and transient computer models of the RL10A-3-3A rocket engine have been created using the Rocket Engine Transient Simulation (ROCETS) code. These models were created for several purposes. The RL10 engine is a critical component of past, present, and future space missions; the model will give NASA an in-house capability to simulate the performance of the engine under various operating conditions and mission profiles. The RL10 simulation activity is also an opportunity to further validate the ROCETS program. The ROCETS code is an important tool for modeling rocket engine systems at NASA Lewis. ROCETS provides a modular and general framework for simulating the steady-state and transient behavior of any desired propulsion system. Although the ROCETS code is being used in a number of different analysis and design projects within NASA, it has not been extensively validated for any system using actual test data. The RL10A-3-3A has a ten year history of test and flight applications; it should provide sufficient data to validate the ROCETS program capability. The ROCETS models of the RL10 system were created using design information provided by Pratt & Whitney, the engine manufacturer. These models are in the process of being validated using test-stand and flight data. This paper includes a brief description of the models and comparison of preliminary simulation output against flight and test-stand data.

The NETL MFiX Suite of multiphase flow models: A brief review and recent applications of MFiX-TFM to fossil energy technologies

DOE PAGES

Li, Tingwen; Rogers, William A.; Syamlal, Madhava; ...

2016-07-29

Here, the MFiX suite of multiphase computational fluid dynamics (CFD) codes is being developed at U.S. Department of Energy's National Energy Technology Laboratory (NETL). It includes several different approaches to multiphase simulation: MFiX-TFM, a two-fluid (Eulerian–Eulerian) model; MFiX-DEM, an Eulerian fluid model with a Lagrangian Discrete Element Model for the solids phase; and MFiX-PIC, Eulerian fluid model with Lagrangian particle ‘parcels’ representing particle groups. These models are undergoing continuous development and application, with verification, validation, and uncertainty quantification (VV&UQ) as integrated activities. After a brief summary of recent progress in the verification, validation and uncertainty quantification (VV&UQ), this article highlightsmore » two recent accomplishments in the application of MFiX-TFM to fossil energy technology development. First, recent application of MFiX to the pilot-scale KBR TRIG™ Transport Gasifier located at DOE's National Carbon Capture Center (NCCC) is described. Gasifier performance over a range of operating conditions was modeled and compared to NCCC operational data to validate the ability of the model to predict parametric behavior. Second, comparison of code predictions at a detailed fundamental scale is presented studying solid sorbents for the post-combustion capture of CO 2 from flue gas. Specifically designed NETL experiments are being used to validate hydrodynamics and chemical kinetics for the sorbent-based carbon capture process.« less

Recalibration and Validation of the SMAP L-Band Radiometer

NASA Technical Reports Server (NTRS)

Peng, Jinzheng; Piepmeier, Jeffrey; Le Vine, David M.; Dinnat, Emmanuel; Bindlish, Rajat; De amici, Giovanni; Mohammed, Priscilla; Misra, Sidharth; Yueh, Simon; Meissner, Thomas

2017-01-01

SMAP mission was launched on 31st January 2015 in a 6 AM 6 PM sun-synchronous orbit at 685 km altitude to measure soil moisture and freethaw globally. The passive instrument of SMAP is a fully polarimetric L-band radiometer (1.4GHz) operating with a bandwidth of 24MHz. The radiometer L1B data product version 3 has been released for public science activities. Post-launch calibration and validation activities are described in [4,5]. Validation results show that SMAP antenna temperature (TA) is 2.6 K warmer over galactic Cold Sky (CS), and land TB is 2.6 K colder comparing to SMOS land TB (compared at the top of the atmosphere) after the update of the reflectors thermal model. Due to the biases, the SMAP radiometer is under re-calibration for next data release in 2018.We present the updated calibration approaches for the SMAP radiometer product. We will discuss the various radiometer calibration parameters and part of the validation process and result.

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

PubMed

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation and clinical significance of the Childhood Myositis Assessment Scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies.

PubMed

Huber, Adam M; Feldman, Brian M; Rennebohm, Robert M; Hicks, Jeanne E; Lindsley, Carol B; Perez, Maria D; Zemel, Lawrence S; Wallace, Carol A; Ballinger, Susan H; Passo, Murray H; Reed, Ann M; Summers, Ronald M; White, Patience H; Katona, Ildy M; Miller, Frederick W; Lachenbruch, Peter A; Rider, Lisa G

2004-05-01

To examine the measurement characteristics of the Childhood Myositis Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory myopathy (juvenile IIM), and to obtain preliminary data on the clinical significance of CMAS scores. One hundred eight children with juvenile IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of physical function, strength, and disease activity. Interrater reliability, construct validity, and responsiveness of the CMAS were examined. The minimum clinically important difference (MID) and CMAS scores corresponding to various degrees of physical disability were estimated. The intraclass correlation coefficient for 26 patients assessed by 2 examiners was 0.89, indicating very good interrater reliability. The CMAS score correlated highly with the Childhood Health Assessment Questionnaire (C-HAQ) score and with findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and moderately with physician-assessed global disease activity and skin activity, parent-assessed global disease severity, and muscle magnetic resonance imaging (r(s) = -0.44 to -0.61), thereby demonstrating good construct validity. The standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in patients with at least 0.8 cm improvement on a 10-cm visual analog scale for physician-assessed global disease activity, indicating strong responsiveness. In bivariate regression models predicting physician-assessed global disease activity, MMT remained significant in models containing the CMAS (P = 0.03) while the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate, and moderate physical disability, respectively, were 48, 45, 39, and 30. The CMAS exhibits good reliability, construct validity, and responsiveness, and is therefore a valid instrument for the assessment of physical function, muscle strength, and endurance in children with juvenile IIM. Preliminary data on MID and corresponding levels of disability should aid in the clinical interpretation of CMAS scores when assessing patients with juvenile IIM.

Refining Time-Activity Classification of Human Subjects Using the Global Positioning System

PubMed Central

Hu, Maogui; Li, Wei; Li, Lianfa; Houston, Douglas; Wu, Jun

2016-01-01

Background Detailed spatial location information is important in accurately estimating personal exposure to air pollution. Global Position System (GPS) has been widely used in tracking personal paths and activities. Previous researchers have developed time-activity classification models based on GPS data, most of them were developed for specific regions. An adaptive model for time-location classification can be widely applied to air pollution studies that use GPS to track individual level time-activity patterns. Methods Time-activity data were collected for seven days using GPS loggers and accelerometers from thirteen adult participants from Southern California under free living conditions. We developed an automated model based on random forests to classify major time-activity patterns (i.e. indoor, outdoor-static, outdoor-walking, and in-vehicle travel). Sensitivity analysis was conducted to examine the contribution of the accelerometer data and the supplemental spatial data (i.e. roadway and tax parcel data) to the accuracy of time-activity classification. Our model was evaluated using both leave-one-fold-out and leave-one-subject-out methods. Results Maximum speeds in averaging time intervals of 7 and 5 minutes, and distance to primary highways with limited access were found to be the three most important variables in the classification model. Leave-one-fold-out cross-validation showed an overall accuracy of 99.71%. Sensitivities varied from 84.62% (outdoor walking) to 99.90% (indoor). Specificities varied from 96.33% (indoor) to 99.98% (outdoor static). The exclusion of accelerometer and ambient light sensor variables caused a slight loss in sensitivity for outdoor walking, but little loss in overall accuracy. However, leave-one-subject-out cross-validation showed considerable loss in sensitivity for outdoor static and outdoor walking conditions. Conclusions The random forests classification model can achieve high accuracy for the four major time-activity categories. The model also performed well with just GPS, road and tax parcel data. However, caution is warranted when generalizing the model developed from a small number of subjects to other populations. PMID:26919723

Domain-Specific QSAR Models for Identifying Potential Estrogenic Activity of Phenols (FutureTox III)

EPA Science Inventory

Computational tools can be used for efficient evaluation of untested chemicals for their ability to disrupt the endocrine system. We have employed previously developed global QSAR models that were trained and validated on the ToxCast/Tox21 ER assay data for virtual screening of a...

Active bio-based food-packaging: Diffusion and release of active substances through and from cellulose nanofiber coating toward food-packaging design.

PubMed

Lavoine, Nathalie; Guillard, Valérie; Desloges, Isabelle; Gontard, Nathalie; Bras, Julien

2016-09-20

Cellulose nanofibers (CNFs) were recently investigated for the elaboration of new functional food-packaging materials. Their nanoporous network was especially of interest for controlling the release of active species. Qualitative release studies were conducted, but quantification of the diffusion phenomenon observed when the active species are released from and through CNF coating has not yet been studied. Therefore, this work aims to model CNF-coated paper substrates as controlled release system for food-packaging using release data obtained for two model molecules, namely caffeine and chlorhexidine digluconate. The applied mathematical model - derived from Fickian diffusion - was validated for caffeine only. When the active species chemically interacts with the release device, another model is required as a non-predominantly diffusion-controlled release was observed. From caffeine modeling data, a theoretical active food-packaging material was designed. The use of CNFs as barrier coating was proved to be the ideal material configuration that best meets specifications. Copyright © 2016. Published by Elsevier Ltd.

NREL: International Activities - Bhutan Resource Maps

Science.gov Websites

modeling approach along with NREL's empirical validation methodology. The high-resolution (10-km) annual -time specific solar mapping approach developed at the U.S. State University of New York at Albany. Data

Understanding human dynamics in microblog posting activities

NASA Astrophysics Data System (ADS)

Jiang, Zhihong; Zhang, Yubao; Wang, Hui; Li, Pei

2013-02-01

Human activity patterns are an important issue in behavior dynamics research. Empirical evidence indicates that human activity patterns can be characterized by a heavy-tailed inter-event time distribution. However, most researchers give an understanding by only modeling the power-law feature of the inter-event time distribution, and those overlooked non-power-law features are likely to be nontrivial. In this work, we propose a behavior dynamics model, called the finite memory model, in which humans adaptively change their activity rates based on a finite memory of recent activities, which is driven by inherent individual interest. Theoretical analysis shows a finite memory model can properly explain various heavy-tailed inter-event time distributions, including a regular power law and some non-power-law deviations. To validate the model, we carry out an empirical study based on microblogging activity from thousands of microbloggers in the Celebrity Hall of the Sina microblog. The results show further that the model is reasonably effective. We conclude that finite memory is an effective dynamics element to describe the heavy-tailed human activity pattern.

Factorial structure of the locomotor disability scale in a sample of adults with mobility impairments in Bangladesh.

PubMed

Mahmud, Ilias; Clarke, Lynda; Nahar, Nazmun; Ploubidis, George B

2018-05-02

Disability does not only depend on individuals' health conditions but also the contextual factors in which individuals live. Therefore, disability measurement scales need to be developed or adapted to the context. Bangladesh lacks any locally developed or validated scales to measure disabilities in adults with mobility impairment. We developed a new Locomotor Disability Scale (LDS) in a previous qualitative study. The present study developed a shorter version of the scale and explored its factorial structure. We administered the LDS to 316 adults with mobility impairments, selected from outpatient and community-based settings of a rehabilitation centre in Bangladesh. We did exploratory factor analysis (EFA) to determine a shorter version of the LDS and explore its factorial structure. We retained 19 items from the original LDS following evaluation of response rate, floor/ceiling effects, inter-item correlations, and factor loadings in EFA. The Eigenvalues greater than one rule and the Scree test suggested a two-factor model of measuring locomotor disability (LD) in adults with mobility impairment. These two factors are 'mobility activity limitations' and 'functional activity limitations'. We named the higher order factor as 'locomotor disability'. This two-factor model explained over 68% of the total variance among the LD indicators. The reproduced correlation matrix indicated a good model fit with 14% non-redundant residuals with absolute values > 0.05. However, the Chi-square test indicated poor model fit (p < .001). The Bartlett's test of Sphericity confirmed patterned relationships amongst the LD indicators (p < .001). The Kaiser-Meyer-Olkin Measure (KMO) of sampling adequacy was .94 and the individual diagonal elements in the anti-correlation matrix were > .91. Among the retained 19 items, there was no correlation coefficient > .9 or a large number of correlation coefficients < .3. The communalities were high: between .495 and .882 with a mean of 0.684. As an evidence of convergent validity, we had all loadings above .5, except one. As an evidence of discriminant validity, we had no strong (> .3) cross loadings and the correlation between the two factors was .657. The 'mobility activity limitations' and 'functional activity limitations' sub-scales demonstrated excellent internal consistency (Cronbach's alpha were .954 and .937, respectively). The 19-item LDS was found to be a reliable and valid scale to measure the latent constructs mobility activity limitations and functional activity limitations among adults with mobility impairments in outpatient and community-based settings in Bangladesh.

Qualitative validation of the reduction from two reciprocally coupled neurons to one self-coupled neuron in a respiratory network model.

PubMed

Dunmyre, Justin R

2011-06-01

The pre-Bötzinger complex of the mammalian brainstem is a heterogeneous neuronal network, and individual neurons within the network have varying strengths of the persistent sodium and calcium-activated nonspecific cationic currents. Individually, these currents have been the focus of modeling efforts. Previously, Dunmyre et al. (J Comput Neurosci 1-24, 2011) proposed a model and studied the interactions of these currents within one self-coupled neuron. In this work, I consider two identical, reciprocally coupled model neurons and validate the reduction to the self-coupled case. I find that all of the dynamics of the two model neuron network and the regions of parameter space where these distinct dynamics are found are qualitatively preserved in the reduction to the self-coupled case.

Discovery of potential ZAP-70 kinase inhibitors: pharmacophore design, database screening and docking studies.

PubMed

Sanam, Ramadevi; Vadivelan, S; Tajne, Sunita; Narasu, Lakshmi; Rambabu, G; Jagarlapudi, Sarma A R P

2009-12-01

The best ZAP-70 inhibitor model consists of four-pharmacophore features, (1) one hydrogen bond acceptor, (2) one hydrogen bond donor (3) one hydrophobic aliphatic and (4) one hydrophobic aromatic features. This model was validated against 110 known ZAP-70 inhibitors with a correlation of 0.902 as well as enrichment factor of 1.61 against a maximum value of 2. This model picked 4094 hits from a database of 238,819 molecules while 358 molecules were indicated as highly active. Subsequently, docking studies were performed on the hits and novel series of potent leads were suggested based on the interactions energy between ZAP-70 and the putative inhibitors which validated not only the virtual screening potential of the model but also identified the possible new Chemotypes.

Testing the Accuracy of Data-driven MHD Simulations of Active Region Evolution and Eruption

NASA Astrophysics Data System (ADS)

Leake, J. E.; Linton, M.; Schuck, P. W.

2017-12-01

Models for the evolution of the solar coronal magnetic field are vital for understanding solar activity, yet the best measurements of the magnetic field lie at the photosphere, necessitating the recent development of coronal models which are "data-driven" at the photosphere. Using magnetohydrodynamic simulations of active region formation and our recently created validation framework we investigate the source of errors in data-driven models that use surface measurements of the magnetic field, and derived MHD quantities, to model the coronal magnetic field. The primary sources of errors in these studies are the temporal and spatial resolution of the surface measurements. We will discuss the implications of theses studies for accurately modeling the build up and release of coronal magnetic energy based on photospheric magnetic field observations.

Insight into the Structural Determinants of Imidazole Scaffold-Based Derivatives as TNF-α Release Inhibitors by in Silico Explorations

PubMed Central

Wang, Yuan; Wu, Mingwei; Ai, Chunzhi; Wang, Yonghua

2015-01-01

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity relationships (3D-QSAR) of the compounds were explored. The proposed pharmacophore model, including two hydrophobic sites, two aromatic centers, two H-bond donor atoms, two H-bond acceptor atoms, and two H-bond donor sites characterizes the necessary structural features of TNF-α release inhibitors. Both the resultant CoMFA and CoMSIA models exhibited satisfactory predictability (with Q2 (cross-validated correlation coefficient) = 0.557, R2ncv (non-cross-validated correlation coefficient) = 0.740, R2pre (predicted correlation coefficient) = 0.749 and Q2 = 0.598, R2ncv = 0.767, R2pre = 0.860, respectively). Good consistency was observed between the 3D-QSAR models and the pharmacophore model that the hydrophobic interaction and hydrogen bonds play crucial roles in the mechanism of actions. The corresponding contour maps generated by these models provide more diverse information about the key intermolecular interactions of inhibitors with the surrounding environment. All these models have extended the understanding of imidazole-based compounds in the structure-activity relationship, and are useful for rational design and screening of novel 2-thioimidazole-based TNF-α release inhibitors. PMID:26307982

Insight into the Structural Determinants of Imidazole Scaffold-Based Derivatives as TNF-α Release Inhibitors by in Silico Explorations.

PubMed

Wang, Yuan; Wu, Mingwei; Ai, Chunzhi; Wang, Yonghua

2015-08-25

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity relationships (3D-QSAR) of the compounds were explored. The proposed pharmacophore model, including two hydrophobic sites, two aromatic centers, two H-bond donor atoms, two H-bond acceptor atoms, and two H-bond donor sites characterizes the necessary structural features of TNF-α release inhibitors. Both the resultant CoMFA and CoMSIA models exhibited satisfactory predictability (with Q(2) (cross-validated correlation coefficient) = 0.557, R(2)ncv (non-cross-validated correlation coefficient) = 0.740, R(2)pre (predicted correlation coefficient) = 0.749 and Q(2) = 0.598, R(2)ncv = 0.767, R(2)pre = 0.860, respectively). Good consistency was observed between the 3D-QSAR models and the pharmacophore model that the hydrophobic interaction and hydrogen bonds play crucial roles in the mechanism of actions. The corresponding contour maps generated by these models provide more diverse information about the key intermolecular interactions of inhibitors with the surrounding environment. All these models have extended the understanding of imidazole-based compounds in the structure-activity relationship, and are useful for rational design and screening of novel 2-thioimidazole-based TNF-α release inhibitors.

Prognostics of Power Electronics, Methods and Validation Experiments

NASA Technical Reports Server (NTRS)

Kulkarni, Chetan S.; Celaya, Jose R.; Biswas, Gautam; Goebel, Kai

2012-01-01

Abstract Failure of electronic devices is a concern for future electric aircrafts that will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. As a result, investigation of precursors to failure in electronics and prediction of remaining life of electronic components is of key importance. DC-DC power converters are power electronics systems employed typically as sourcing elements for avionics equipment. Current research efforts in prognostics for these power systems focuses on the identification of failure mechanisms and the development of accelerated aging methodologies and systems to accelerate the aging process of test devices, while continuously measuring key electrical and thermal parameters. Preliminary model-based prognostics algorithms have been developed making use of empirical degradation models and physics-inspired degradation model with focus on key components like electrolytic capacitors and power MOSFETs (metal-oxide-semiconductor-field-effect-transistor). This paper presents current results on the development of validation methods for prognostics algorithms of power electrolytic capacitors. Particularly, in the use of accelerated aging systems for algorithm validation. Validation of prognostics algorithms present difficulties in practice due to the lack of run-to-failure experiments in deployed systems. By using accelerated experiments, we circumvent this problem in order to define initial validation activities.

Factorial validity of an abbreviated neighborhood environment walkability scale for seniors in the Nurses' Health Study.

PubMed

Starnes, Heather A; McDonough, Meghan H; Tamura, Kosuke; James, Peter; Laden, Francine; Troped, Philip J

2014-10-10

Using validated measures of individuals' perceptions of their neighborhood built environment is important for accurately estimating effects on physical activity. However, no studies to date have examined the factorial validity of a measure of perceived neighborhood environment among older adults in the United States. The purpose of this measurement study was to test the factorial validity of a version of the Abbreviated Neighborhood Environment Walkability Scale (NEWS-A) modified for seniors in the Nurses' Health Study (NHS). A random sample of 2,920 female nurses (mean age = 73 ± 7 years) in the NHS cohort from California, Massachusetts, and Pennsylvania completed a 36-item modified NEWS-A for seniors. Confirmatory factor analyses were conducted to test measurement models for both the modified NEWS-A for seniors and the original NEWS-A. Internal consistency within factors was examined using Cronbach's alpha. The hypothesized 7-factor measurement model was a poor fit for the modified NEWS-A for seniors. Overall, the best-fitting measurement model was the original 6-factor solution to the NEWS-A. Factors were correlated and internally consistent. This study provided support for the construct validity of the original NEWS-A for assessing perceptions of neighborhood environments in older women in the United States.

Synthetic cannabinoids: In silico prediction of the cannabinoid receptor 1 affinity by a quantitative structure-activity relationship model.

PubMed

Paulke, Alexander; Proschak, Ewgenij; Sommer, Kai; Achenbach, Janosch; Wunder, Cora; Toennes, Stefan W

2016-03-14

The number of new synthetic psychoactive compounds increase steadily. Among the group of these psychoactive compounds, the synthetic cannabinoids (SCBs) are most popular and serve as a substitute of herbal cannabis. More than 600 of these substances already exist. For some SCBs the in vitro cannabinoid receptor 1 (CB1) affinity is known, but for the majority it is unknown. A quantitative structure-activity relationship (QSAR) model was developed, which allows the determination of the SCBs affinity to CB1 (expressed as binding constant (Ki)) without reference substances. The chemically advance template search descriptor was used for vector representation of the compound structures. The similarity between two molecules was calculated using the Feature-Pair Distribution Similarity. The Ki values were calculated using the Inverse Distance Weighting method. The prediction model was validated using a cross validation procedure. The predicted Ki values of some new SCBs were in a range between 20 (considerably higher affinity to CB1 than THC) to 468 (considerably lower affinity to CB1 than THC). The present QSAR model can serve as a simple, fast and cheap tool to get a first hint of the biological activity of new synthetic cannabinoids or of other new psychoactive compounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exploiting different active silicon detectors in the International Space Station: ALTEA and DOSTEL galactic cosmic radiation (GCR) measurements

NASA Astrophysics Data System (ADS)

Narici, Livo; Berger, Thomas; Burmeister, Sönke; Di Fino, Luca; Rizzo, Alessandro; Matthiä, Daniel; Reitz, Günther

2017-08-01

The solar system exploration by humans requires to successfully deal with the radiation exposition issue. The scientific aspect of this issue is twofold: knowing the radiation environment the astronauts are going to face and linking radiation exposure to health risks. Here we focus on the first issue. It is generally agreed that the final tool to describe the radiation environment in a space habitat will be a model featuring the needed amount of details to perform a meaningful risk assessment. The model should also take into account the shield changes due to the movement of materials inside the habitat, which in turn produce changes in the radiation environment. This model will have to undergo a final validation with a radiation field of similar complexity. The International Space Station (ISS) is a space habitat that features a radiation environment inside which is similar to what will be found in habitats in deep space, if we use measurements acquired only during high latitude passages (where the effects of the Earth magnetic field are reduced). Active detectors, providing time information, that can easily select data from different orbital sections, are the ones best fulfilling the requirements for these kinds of measurements. The exploitation of the radiation measurements performed in the ISS by all the available instruments is therefore mandatory to provide the largest possible database to the scientific community, to be merged with detailed Computer Aided Design (CAD) models, in the quest for a full model validation. While some efforts in comparing results from multiple active detectors have been attempted, a thorough study of a procedure to merge data in a single data matrix in order to provide the best validation set for radiation environment models has never been attempted. The aim of this paper is to provide such a procedure, to apply it to two of the most performing active detector systems in the ISS: the Anomalous Long Term Effects in Astronauts (ALTEA) instrument and the DOSimetry TELescope (DOSTEL) detectors, applied in the frame of the DOSIS and DOSIS 3D project onboard the ISS and to present combined results exploiting the features of each of the two apparatuses.

Development and validation of clinical prediction models for mortality, functional outcome and cognitive impairment after stroke: a study protocol

PubMed Central

Fahey, Marion; Rudd, Anthony; Béjot, Yannick; Wolfe, Charles; Douiri, Abdel

2017-01-01

Introduction Stroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support. Methods 2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995–2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005–2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985–2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented. Ethics Patients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy’s and St Thomas’ NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l’Informatique et des Libertés. PMID:28821511

Development and application of a predictive model of Aspergillus candidus growth as a tool to improve shelf life of bakery products.

PubMed

Huchet, V; Pavan, S; Lochardet, A; Divanac'h, M L; Postollec, F; Thuault, D

2013-12-01

Molds are responsible for spoilage of bakery products during storage. A modeling approach to predict the effect of water activity (aw) and temperature on the appearance time of Aspergillus candidus was developed and validated on cakes. The gamma concept of Zwietering was adapted to model fungal growth, taking into account the impact of temperature and aw. We hypothesized that the same model could be used to calculate the time for mycelium to become visible (tv), by substituting the matrix parameter by tv. Cardinal values of A. candidus were determined on potato dextrose agar, and predicted tv were further validated by challenge-tests run on 51 pastries. Taking into account the aw dynamics recorded in pastries during reasonable conditions of storage, high correlation was shown between predicted and observed tv when the aw at equilibrium (after 14 days of storage) was used for modeling (Af = 1.072, Bf = 0.979). Validation studies on industrial cakes confirmed the experimental results and demonstrated the suitability of the model to predict tv in food as a function of aw and temperature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of Learning Model Based on Cognitive Conflict toward Student’s Conceptual Understanding

NASA Astrophysics Data System (ADS)

Mufit, F.; Festiyed, F.; Fauzan, A.; Lufri, L.

2018-04-01

The problems that often occur in the learning of physics is a matter of misconception and low understanding of the concept. Misconceptions do not only happen to students, but also happen to college students and teachers. The existing learning model has not had much impact on improving conceptual understanding and remedial efforts of student misconception. This study aims to see the impact of cognitive-based learning model in improving conceptual understanding and remediating student misconceptions. The research method used is Design / Develop Research. The product developed is a cognitive conflict-based learning model along with its components. This article reports on product design results, validity tests, and practicality test. The study resulted in the design of cognitive conflict-based learning model with 4 learning syntaxes, namely (1) preconception activation, (2) presentation of cognitive conflict, (3) discovery of concepts & equations, (4) Reflection. The results of validity tests by some experts on aspects of content, didactic, appearance or language, indicate very valid criteria. Product trial results also show a very practical product to use. Based on pretest and posttest results, cognitive conflict-based learning models have a good impact on improving conceptual understanding and remediating misconceptions, especially in high-ability students.

ASME V\\&V challenge problem: Surrogate-based V&V

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

Beghini, Lauren L.; Hough, Patricia D.

2015-12-18

The process of verification and validation can be resource intensive. From the computational model perspective, the resource demand typically arises from long simulation run times on multiple cores coupled with the need to characterize and propagate uncertainties. In addition, predictive computations performed for safety and reliability analyses have similar resource requirements. For this reason, there is a tradeoff between the time required to complete the requisite studies and the fidelity or accuracy of the results that can be obtained. At a high level, our approach is cast within a validation hierarchy that provides a framework in which we perform sensitivitymore » analysis, model calibration, model validation, and prediction. The evidence gathered as part of these activities is mapped into the Predictive Capability Maturity Model to assess credibility of the model used for the reliability predictions. With regard to specific technical aspects of our analysis, we employ surrogate-based methods, primarily based on polynomial chaos expansions and Gaussian processes, for model calibration, sensitivity analysis, and uncertainty quantification in order to reduce the number of simulations that must be done. The goal is to tip the tradeoff balance to improving accuracy without increasing the computational demands.« less

The Madden-Julian Oscillation and its Impact on Northern Hemisphere Weather Predictability during Wintertime

NASA Technical Reports Server (NTRS)

Jones, Charles; Waliser, Duane E.; Lau, K. M.; Stern, W.

2003-01-01

The Madden-Julian Oscillation (MJO) is known as the dominant mode of tropical intraseasonal variability and has an important role in the coupled-atmosphere system. This study used twin numerical model experiments to investigate the influence of the MJO activity on weather predictability in the midlatitudes of the Northern Hemisphere during boreal winter. The National Aeronautics and Space Administration (NASA) Goddard laboratory for the Atmospheres (GLA) general circulation model was first used in a 10-yr simulation with fixed climatological SSTs to generate a validation data set as well as to select initial conditions for active MJO periods and Null cases. Two perturbation numerical experiments were performed for the 75 cases selected [(4 MJO phases + Null phase) _ 15 initial conditions in each]. For each alternative initial condition, the model was integrated for 90 days. Mean anomaly correlations in the midlatitudes of the Northern Hemisphere (2O deg N_60 deg.N) and standardized root-mean-square errors were computed to validate forecasts and control run. The analyses of 500-hPa geopotential height, 200-hPa Streamfunction and 850-hPa zonal wind component systematically show larger predictability during periods of active MJO as opposed to quiescent episodes of the oscillation.

Psychometric properties of the Spanish version of the Passion Scale.

PubMed

Chamarro, Andrés; Penelo, Eva; Fornieles, Albert; Oberst, Ursula; Vallerand, Robert J; Fernández-Castro, Jordi

2015-01-01

Passion has been shown to be involved in psychological processes that emerge in diverse human activities like physical activity and sports, work, leisure, videogaming, pathological gambling, and interpersonal relationships. We aimed to present evidence of validity and internal consistency of the Passion Scale in Spanish based on the Dualistic Model of Passion, comprising harmonious and obsessive dimensions. The sample comprised 1,007 participants (350 females and 657 males), aged 16-65 (Md= 30.0 years). Exploratory Structural Equation Modeling (ESEM), measurement invariance and Multiple-Cause-Multiple-Indicator models (MIMIC) were used. Fit for the ESEM 2-factor solution was acceptable. Near full or partial measurement invariance across sex, type of activity, and age was supported. Relationships between both harmonious and obsessive dimensions and the external variables considered (age, sex, and criterion items) reasonably replicated those found in previous studies. Both scale scores showed adequate internal consistency (α = .81). Empirical evidence for the validity and internal consistency of the Spanish version of the Passion Scale is satisfactory and reveals that the scale is comparable to the English and French versions. Therefore, the Passion Scale can be used in research conducted in Spanish.

QSAR Modeling of Rat Acute Toxicity by Oral Exposure

PubMed Central

Zhu, Hao; Martin, Todd M.; Ye, Lin; Sedykh, Alexander; Young, Douglas M.; Tropsha, Alexander

2009-01-01

Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. In this study, a comprehensive dataset of 7,385 compounds with their most conservative lethal dose (LD50) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire dataset was selected that included all 3,472 compounds used in the TOPKAT’s training set. The remaining 3,913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R2 of linear regression between actual and predicted LD50 values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R2 ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD50 for every compound using all 5 models. The consensus models afforded higher prediction accuracy for the external validation dataset with the higher coverage as compared to individual constituent models. The validated consensus LD50 models developed in this study can be used as reliable computational predictors of in vivo acute toxicity. PMID:19845371

Does rational selection of training and test sets improve the outcome of QSAR modeling?

PubMed

Martin, Todd M; Harten, Paul; Young, Douglas M; Muratov, Eugene N; Golbraikh, Alexander; Zhu, Hao; Tropsha, Alexander

2012-10-22

Prior to using a quantitative structure activity relationship (QSAR) model for external predictions, its predictive power should be established and validated. In the absence of a true external data set, the best way to validate the predictive ability of a model is to perform its statistical external validation. In statistical external validation, the overall data set is divided into training and test sets. Commonly, this splitting is performed using random division. Rational splitting methods can divide data sets into training and test sets in an intelligent fashion. The purpose of this study was to determine whether rational division methods lead to more predictive models compared to random division. A special data splitting procedure was used to facilitate the comparison between random and rational division methods. For each toxicity end point, the overall data set was divided into a modeling set (80% of the overall set) and an external evaluation set (20% of the overall set) using random division. The modeling set was then subdivided into a training set (80% of the modeling set) and a test set (20% of the modeling set) using rational division methods and by using random division. The Kennard-Stone, minimal test set dissimilarity, and sphere exclusion algorithms were used as the rational division methods. The hierarchical clustering, random forest, and k-nearest neighbor (kNN) methods were used to develop QSAR models based on the training sets. For kNN QSAR, multiple training and test sets were generated, and multiple QSAR models were built. The results of this study indicate that models based on rational division methods generate better statistical results for the test sets than models based on random division, but the predictive power of both types of models are comparable.

CCM-C,Collins checks the middeck experiment

NASA Image and Video Library

1999-07-24

S93-E-5016 (23 July 1999) --- Astronaut Eileen M. Collins, mission commander, checks on an experiment on Columbia's middeck during Flight Day 1 activity. The experiment is called the Cell Culture Model, Configuration C. Objectives of it are to validate cell culture models for muscle, bone and endothelial cell biochemical and functional loss induced by microgravity stress; to evaluate cytoskeleton, metabolism, membrane integrity and protease activity in target cells; and to test tissue loss pharmaceuticals for efficacy. The photo was recorded with an electronic still camera (ESC).

Measuring patient activation in Italy: Translation, adaptation and validation of the Italian version of the patient activation measure 13 (PAM13-I).

PubMed

Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea; Lozza, Edoardo; Hibbard, Judith

2015-12-23

The Patient Activation Measure (PAM13) is an instrument that assesses patient knowledge, skills, and confidence for disease self-management. This cross-sectional study was aimed to validate a culturally-adapted Italian Patient Activation Measure (PAM13-I) for patients with chronic conditions. 519 chronic patients were involved in the Italian validation study and responded to PAM13-I. The PAM 13 was translated into Italian by a standardized forward-backward translation. Data quality was assessed by mean, median, item response, missing values, floor and ceiling effects, internal consistency (Cronbach's alpha and average inter-item correlation), item-rest correlations. Rasch Model and differential item functioning assessed scale properties. Mean PAM13-I score was 66.2. Rasch analysis showed that the PAM13-I is a good measure of patient activation. The level of internal consistency was good (α = 0.88). For all items, the distribution of answers was left-skewed, with a small floor effect (range 1.7-4.5 %) and a moderate ceiling effect (range 27.6-55.0 %). The Italian version formed a unidimensional, probabilistic Guttman-like scale explaining 41 % of the variance. The PAM13-I has been demonstrated to be a valid and reliable measure of patient activation and the present study suggests its applicability to the Italian-speaking chronic patient population. The measure has good psychometric properties and appears to be consistent with the developmental nature of the patient activation phenomenon, although it presents a different ranking order of the items comparing to the American version. PAM13-I can be a useful assessment tool to evaluate interventions aimed at improving patient engagement in healthcare and to train doctors in attuning their communication to the level of patients' activation. Future research could be conducted to further confirm the validity of the PAM13-I.

Bayesian Models Leveraging Bioactivity and Cytotoxicity Information for Drug Discovery

PubMed Central

Ekins, Sean; Reynolds, Robert C.; Kim, Hiyun; Koo, Mi-Sun; Ekonomidis, Marilyn; Talaue, Meliza; Paget, Steve D.; Woolhiser, Lisa K.; Lenaerts, Anne J.; Bunin, Barry A.; Connell, Nancy; Freundlich, Joel S.

2013-01-01

SUMMARY Identification of unique leads represents a significant challenge in drug discovery. This hurdle is magnified in neglected diseases such as tuberculosis. We have leveraged public high-throughput screening (HTS) data, to experimentally validate virtual screening approach employing Bayesian models built with bioactivity information (single-event model) as well as bioactivity and cytotoxicity information (dual-event model). We virtually screen a commercial library and experimentally confirm actives with hit rates exceeding typical HTS results by 1-2 orders of magnitude. The first dual-event Bayesian model identified compounds with antitubercular whole-cell activity and low mammalian cell cytotoxicity from a published set of antimalarials. The most potent hit exhibits the in vitro activity and in vitro/in vivo safety profile of a drug lead. These Bayesian models offer significant economies in time and cost to drug discovery. PMID:23521795

Validation of ISS Floating Potential Measurement Unit Electron Densities and Temperatures

NASA Technical Reports Server (NTRS)

Coffey, Victoria N.; Minow, Joseph I.; Parker, Linda N.; Bui, Them; Wright, Kenneth, Jr.; Koontz, Steven L.; Schneider, T.; Vaughn, J.; Craven, P.

2007-01-01

Validation of the Floating Potential Measurement Unit (FPMU) electron density and temperature measurements is an important step in the process of evaluating International Space Station spacecraft charging issues .including vehicle arcing and hazards to crew during extravehicular activities. The highest potentials observed on Space Station are due to the combined VxB effects on a large spacecraft and the collection of ionospheric electron and ion currents by the 160 V US solar array modules. Ionospheric electron environments are needed for input to the ISS spacecraft charging models used to predict the severity and frequency of occurrence of ISS charging hazards. Validation of these charging models requires comparing their predictions with measured FPMU values. Of course, the FPMU measurements themselves must also be validated independently for use in manned flight safety work. This presentation compares electron density and temperatures derived from the FPMU Langmuir probes and Plasma Impedance Probe against the independent density and temperature measurements from ultraviolet imagers, ground based incoherent scatter radar, and ionosonde sites.

Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities*

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

Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov; Cross, Kevin P.

Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure–activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describemore » the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. -- Highlights: ► We characterize a new in silico model to predict mutagenicity of drug impurities. ► The model predicts Salmonella mutagenicity and will be useful for safety assessment. ► We examine toxicity fingerprints and toxicophores of this Ames assay model. ► We compare these attributes to those found in drug impurities known to FDA/CDER. ► We validate the model and find it has a desired predictive performance.« less

Development of Internal System of Education Quality Assessment at a University

ERIC Educational Resources Information Center

Kalimullin, Aydar M.; Khodyreva, Elena ?.; Koinova-Zoellner, Julia

2016-01-01

The urgency of the research is determined by the need to ensure the quality of higher education an essential factor of which is development of the internal assessment system for educational activities at universities. The aim of the article is validation of the model of development of the internal assessment system for educational activities at…

A test of an expert-based bird-habitat relationship model in South Carolina

Treesearch

John C. Kilgo; David L. Gartner; Brian R. Chapman; John B. Dunnin; Kathleen E. Franzreb; Sidney A. Gauthreaux; Cathryn H. Greenberg; Douglas J. Levey; Karl V. Miller; Scott F. Pearson

2002-01-01

Wildlife-habitat relationships models are used widely by land managers to provide information on which species are likely to occur in an area of interest and may be impacted by a proposed management activity. Few such models have been tested. We used recent avian census data from the Savannah River Site, South Carolina to validate BIRDHAB, a geographic information...

Validation of a dynamic linked segment model to calculate joint moments in lifting.

PubMed

de Looze, M P; Kingma, I; Bussmann, J B; Toussaint, H M

1992-08-01

A two-dimensional dynamic linked segment model was constructed and applied to a lifting activity. Reactive forces and moments were calculated by an instantaneous approach involving the application of Newtonian mechanics to individual adjacent rigid segments in succession. The analysis started once at the feet and once at a hands/load segment. The model was validated by comparing predicted external forces and moments at the feet or at a hands/load segment to actual values, which were simultaneously measured (ground reaction force at the feet) or assumed to be zero (external moments at feet and hands/load and external forces, beside gravitation, at hands/load). In addition, results of both procedures, in terms of joint moments, including the moment at the intervertebral disc between the fifth lumbar and first sacral vertebra (L5-S1), were compared. A correlation of r = 0.88 between calculated and measured vertical ground reaction forces was found. The calculated external forces and moments at the hands showed only minor deviations from the expected zero level. The moments at L5-S1, calculated starting from feet compared to starting from hands/load, yielded a coefficient of correlation of r = 0.99. However, moments calculated from hands/load were 3.6% (averaged values) and 10.9% (peak values) higher. This difference is assumed to be due mainly to erroneous estimations of the positions of centres of gravity and joint rotation centres. The estimation of the location of L5-S1 rotation axis can affect the results significantly. Despite the numerous studies estimating the load on the low back during lifting on the basis of linked segment models, only a few attempts to validate these models have been made. This study is concerned with the validity of the presented linked segment model. The results support the model's validity. Effects of several sources of error threatening the validity are discussed. Copyright © 1992. Published by Elsevier Ltd.

Two-state model of light induced activation and thermal bleaching of photochromic glasses: theory and experiments

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

Ferrari, Jose A.; Perciante, Cesar D

2008-07-10

The behavior of photochromic glasses during activation and bleaching is investigated. A two-state phenomenological model describing light-induced activation (darkening) and thermal bleaching is presented. The proposed model is based on first-order kinetics. We demonstrate that the time behavior in the activation process (acting simultaneously with the thermal fading) can be characterized by two relaxation times that depend on the intensity of the activating light. These characteristic times are lower than the decay times of the pure thermal bleaching process. We study the temporal evolution of the glass optical density and its dependence on the activating intensity. We also present amore » series of activation and bleaching experiments that validate the proposed model. Our approach may be used to gain more insight into the transmittance behavior of photosensitive glasses, which could be potentially relevant in a broad range of applications, e.g., real-time holography and reconfigurable optical memories.« less

Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions.

PubMed

Sedykh, Alexander; Fourches, Denis; Duan, Jianmin; Hucke, Oliver; Garneau, Michel; Zhu, Hao; Bonneau, Pierre; Tropsha, Alexander

2013-04-01

Membrane transporters mediate many biological effects of chemicals and play a major role in pharmacokinetics and drug resistance. The selection of viable drug candidates among biologically active compounds requires the assessment of their transporter interaction profiles. Using public sources, we have assembled and curated the largest, to our knowledge, human intestinal transporter database (>5,000 interaction entries for >3,700 molecules). This data was used to develop thoroughly validated classification Quantitative Structure-Activity Relationship (QSAR) models of transport and/or inhibition of several major transporters including MDR1, BCRP, MRP1-4, PEPT1, ASBT, OATP2B1, OCT1, and MCT1. QSAR models have been developed with advanced machine learning techniques such as Support Vector Machines, Random Forest, and k Nearest Neighbors using Dragon and MOE chemical descriptors. These models afforded high external prediction accuracies of 71-100% estimated by 5-fold external validation, and showed hit retrieval rates with up to 20-fold enrichment in the virtual screening of DrugBank compounds. The compendium of predictive QSAR models developed in this study can be used for virtual profiling of drug candidates and/or environmental agents with the optimal transporter profiles.

Use of the Monte Carlo Method for OECD Principles-Guided QSAR Modeling of SIRT1 Inhibitors.

PubMed

Kumar, Ashwani; Chauhan, Shilpi

2017-01-01

SIRT1 inhibitors offer therapeutic potential for the treatment of a number of diseases including cancer and human immunodeficiency virus infection. A diverse series of 45 compounds with reported SIRT1 inhibitory activity has been employed for the development of quantitative structure-activity relationship (QSAR) models using the Monte Carlo optimization method. This method makes use of simplified molecular input line entry system notation of the molecular structure. The QSAR models were built up according to OECD principles. Three subsets of three splits were examined and validated by respective external sets. All the three described models have good statistical quality. The best model has the following statistical characteristics: R 2  = 0.8350, Q 2 test  = 0.7491 for the test set and R 2  = 0.9655, Q 2 ext  = 0.9261 for the validation set. In the mechanistic interpretation, structural attributes responsible for the endpoint increase and decrease are defined. Further, the design of some prospective SIRT1 inhibitors is also presented on the basis of these structural attributes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The proposal of architecture for chemical splitting to optimize QSAR models for aquatic toxicity.

PubMed

Colombo, Andrea; Benfenati, Emilio; Karelson, Mati; Maran, Uko

2008-06-01

One of the challenges in the field of quantitative structure-activity relationship (QSAR) analysis is the correct classification of a chemical compound to an appropriate model for the prediction of activity. Thus, in previous studies, compounds have been divided into distinct groups according to their mode of action or chemical class. In the current study, theoretical molecular descriptors were used to divide 568 organic substances into subsets with toxicity measured for the 96-h lethal median concentration for the Fathead minnow (Pimephales promelas). Simple constitutional descriptors such as the number of aliphatic and aromatic rings and a quantum chemical descriptor, maximum bond order of a carbon atom divide compounds into nine subsets. For each subset of compounds the automatic forward selection of descriptors was applied to construct QSAR models. Significant correlations were achieved for each subset of chemicals and all models were validated with the leave-one-out internal validation procedure (R(2)(cv) approximately 0.80). The results encourage to consider this alternative way for the prediction of toxicity using QSAR subset models without direct reference to the mechanism of toxic action or the traditional chemical classification.

Highlights of Project Accomplishments (2000-2004): Redshift Dependence of the Interaction-Activity Connection

NASA Technical Reports Server (NTRS)

Borne, Kirk D.

2004-01-01

We completed this project by developing the new galaxy-galaxy collision simulation code that we originally proposed. We included star formation heuristically, along with gas recycling and energetic feedback into the interstellar medium of the galaxies. We ran several test simulations. And we finally validated the code by running models to emulate the double-ring galaxy AM 0644-741. Most of the exotic and unique features of this collisional ring galaxy were matched by our models, thereby validating our algorithm, which may now be used by us and by the community for additional dynamic studies of galaxies. A paper has been submitted to the Astrophysical Journal describing our algorithm and the results of the AM 0644-741 modeling.

Simulation of Fusion Plasmas

ScienceCinema

Holland, Chris [UC San Diego, San Diego, California, United States

2017-12-09

The upcoming ITER experiment (www.iter.org) represents the next major milestone in realizing the promise of using nuclear fusion as a commercial energy source, by moving into the “burning plasma” regime where the dominant heat source is the internal fusion reactions. As part of its support for the ITER mission, the US fusion community is actively developing validated predictive models of the behavior of magnetically confined plasmas. In this talk, I will describe how the plasma community is using the latest high performance computing facilities to develop and refine our models of the nonlinear, multiscale plasma dynamics, and how recent advances in experimental diagnostics are allowing us to directly test and validate these models at an unprecedented level.

Modeling of quantitative relationships between physicochemical properties of active pharmaceutical ingredients and tensile strength of tablets using a boosted tree.

PubMed

Hayashi, Yoshihiro; Oishi, Takuya; Shirotori, Kaede; Marumo, Yuki; Kosugi, Atsushi; Kumada, Shungo; Hirai, Daijiro; Takayama, Kozo; Onuki, Yoshinori

2018-07-01

The aim of this study was to explore the potential of boosted tree (BT) to develop a correlation model between active pharmaceutical ingredient (API) characteristics and a tensile strength (TS) of tablets as critical quality attributes. First, we evaluated 81 kinds of API characteristics, such as particle size distribution, bulk density, tapped density, Hausner ratio, moisture content, elastic recovery, molecular weight, and partition coefficient. Next, we prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1% magnesium stearate using direct compression at 6, 8, and 10 kN, and measured TS. Then, we applied BT to our dataset to develop a correlation model. Finally, the constructed BT model was validated using k-fold cross-validation. Results showed that the BT model achieved high-performance statistics, whereas multiple regression analysis resulted in poor estimations. Sensitivity analysis of the BT model revealed that diameter of powder particles at the 10th percentile of the cumulative percentage size distribution was the most crucial factor for TS. In addition, the influences of moisture content, partition coefficients, and modal diameter were appreciably meaningful factors. This study demonstrates that BT model could provide comprehensive understanding of the latent structure underlying APIs and TS of tablets.

Quantitative prediction of ionization effect on human skin permeability.

PubMed

Baba, Hiromi; Ueno, Yusuke; Hashida, Mitsuru; Yamashita, Fumiyoshi

2017-04-30

Although skin permeability of an active ingredient can be severely affected by its ionization in a dose solution, most of the existing prediction models cannot predict such impacts. To provide reliable predictors, we curated a novel large dataset of in vitro human skin permeability coefficients for 322 entries comprising chemically diverse permeants whose ionization fractions can be calculated. Subsequently, we generated thousands of computational descriptors, including LogD (octanol-water distribution coefficient at a specific pH), and analyzed the dataset using nonlinear support vector regression (SVR) and Gaussian process regression (GPR) combined with greedy descriptor selection. The SVR model was slightly superior to the GPR model, with externally validated squared correlation coefficient, root mean square error, and mean absolute error values of 0.94, 0.29, and 0.21, respectively. These models indicate that Log D is effective for a comprehensive prediction of ionization effects on skin permeability. In addition, the proposed models satisfied the statistical criteria endorsed in recent model validation studies. These models can evaluate virtually generated compounds at any pH; therefore, they can be used for high-throughput evaluations of numerous active ingredients and optimization of their skin permeability with respect to permeant ionization. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

PubMed

Mladenović, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

2017-04-24

Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including the following: (1) definition of optimized and validated structure-based three-dimensional (3-D) quantitative structure-activity relationships (QSAR) models derived from available cocrystallized inhibitor-MAO B complexes; (2) elaboration of SAR features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61 ) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rule assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSAR training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a result of rational SB/LB 3D QSAR design; therefore, D123 (IC 50 = 0.83 nM, K i = 0.25 nM) and D124 (IC 50 = 0.97 nM, K i = 0.29 nM) are potential lead candidates as anti-Parkinson's drugs.

In-Silico Screening of Ligand Based Pharmacophore, Database Mining and Molecular Docking on 2, 5-Diaminopyrimidines Azapurines as Potential Inhibitors of Glycogen Synthase Kinase-3β.

PubMed

Mishra, Pooja; Kesar, Seema; Paliwal, Sarvesh K; Chauhan, Monika; Madan, Kirtika

2018-05-29

Glycogen synthase kinase-3β plays a significant role in the regulation of various pathological pathways relating to central nervous system (CNS). Dysregulation of Glycogen synthase kinase 3 (GSK-3) activity gives a rise to numerous neuroinflammation and neurodegenerative related disorders that affect the whole central nervous system. By the sequential application of in-silico tools, efforts have been attempted to design the novel GSK-3β inhibitors. Owing to the potential role of GSK-3β in nervous disorders, we have attempted to develop the quantitative four featured pharmacophore model comprising two hydrogen bond acceptors (HBA), one ring aromatic (RA), and one hydrophobe (HY), which were further affirmed by cost-function analysis, rm2 matrices, internal and external test set validation and Güner-Henry (GH) scoring analysis. Validated pharmacophoric model was used for virtual screening and out of 345 compounds, two potential virtual hits were finalized that were on the basis of fit value, estimated activity and Lipinski's violation. The chosen compounds were subjected to dock within the active site of GSK-3β Result: Four essential features, i.e., two hydrogen bond acceptors(HBA), one ring aromatic(RA), and one hydrophobe(HY), were subjected to build the pharmacophoric model and showed good correlation coefficient, RMSD and cost difference values of 0.91, 0.94 and 42.9 respectively and further model was validated employing cost-function analysis, rm2-matrices, internal and external test set prediction with r2 value of 0.77 and 0.84. Docked conformations showed potential interactions in between the features of the identified hits (NCI 4296, NCI 3034) and the amino acids present in the active site. In line with the overhead discussion, and through our stepwise computational approaches, we have identified novel, structurally diverse glycogen synthase kinase inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhancement of problem solving ability of high school students through learning with real engagement in active problem solving (REAPS) model on the concept of heat transfer

NASA Astrophysics Data System (ADS)

Yulindar, A.; Setiawan, A.; Liliawati, W.

2018-05-01

This study aims to influence the enhancement of problem solving ability before and after learning using Real Engagement in Active Problem Solving (REAPS) model on the concept of heat transfer. The research method used is quantitative method with 35 high school students in Pontianak as sample. The result of problem solving ability of students is obtained through the test in the form of 3 description questions. The instrument has tested the validity by the expert judgment and field testing that obtained the validity value of 0.84. Based on data analysis, the value of N-Gain is 0.43 and the enhancement of students’ problem solving ability is in medium category. This was caused of students who are less accurate in calculating the results of answers and they also have limited time in doing the questions given.

Computer simulation and performance assessment of the packet-data service of the Aeronautical Mobile Satellite Service (AMSS)

NASA Technical Reports Server (NTRS)

Ferzali, Wassim; Zacharakis, Vassilis; Upadhyay, Triveni; Weed, Dennis; Burke, Gregory

1995-01-01

The ICAO Aeronautical Mobile Communications Panel (AMCP) completed the drafting of the Aeronautical Mobile Satellite Service (AMSS) Standards and Recommended Practices (SARP's) and the associated Guidance Material and submitted these documents to ICAO Air Navigation Commission (ANC) for ratification in May 1994. This effort, encompassed an extensive, multi-national SARP's validation. As part of this activity, the US Federal Aviation Administration (FAA) sponsored an effort to validate the SARP's via computer simulation. This paper provides a description of this effort. Specifically, it describes: (1) the approach selected for the creation of a high-fidelity AMSS computer model; (2) the test traffic generation scenarios; and (3) the resultant AMSS performance assessment. More recently, the AMSS computer model was also used to provide AMSS performance statistics in support of the RTCA standardization activities. This paper describes this effort as well.

WFIRST: Coronagraph Systems Engineering and Performance Budgets

NASA Astrophysics Data System (ADS)

Poberezhskiy, Ilya; cady, eric; Frerking, Margaret A.; Kern, Brian; Nemati, Bijan; Noecker, Martin; Seo, Byoung-Joon; Zhao, Feng; Zhou, Hanying

2018-01-01

The WFIRST coronagraph instrument (CGI) will be the first in-space coronagraph using active wavefront control to directly image and characterize mature exoplanets and zodiacal disks in reflected starlight. For CGI systems engineering, including requirements development, CGI performance is predicted using a hierarchy of performance budgets to estimate various noise components — spatial and temporal flux variations — that obscure exoplanet signals in direct imaging and spectroscopy configurations. These performance budgets are validated through a robust integrated modeling and testbed model validation efforts.We present the performance budgeting framework used by WFIRST for the flow-down of coronagraph science requirements, mission constraints, and observatory interfaces to measurable instrument engineering parameters.

The Low Earth Orbit validation of a dynamic and anisotropic trapped radiation model through ISS measurements

NASA Astrophysics Data System (ADS)

Badavi, Francis F.; Nealy, John E.; Wilson, John W.

2011-10-01

The International Space Station (ISS) provides the proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the experimental validation of radiation environmental models, nuclear transport code algorithms and nuclear reaction cross sections. Indeed, prior measurements on the Space Transportation System (STS; Shuttle) have provided vital information impacting both the environmental models and the nuclear transport code development by requiring dynamic models of the Low Earth Orbit (LEO) environment. Previous studies using Computer Aided Design (CAD) models of the evolving ISS configurations with Thermo-Luminescent Detector (TLD) area monitors, demonstrated that computational dosimetry requires environmental models with accurate non-isotropic as well as dynamic behavior, detailed information on rack loading, and an accurate six degree of freedom (DOF) description of ISS trajectory and orientation. It is imperative that we understand ISS exposures dynamically for crew career planning, and insure that the regulatory requirements of keeping exposure as low as reasonably achievable (ALARA) are adequately implemented. This is especially true as ISS nears some form of completion with increasing complexity, resulting in a larger drag coefficient, and requiring operation at higher altitudes with increased exposure rates. In this paper ISS environmental model is configured for 11A (circa mid 2005), and uses non-isotropic and dynamic geomagnetic transmission and trapped proton models. ISS 11A and LEO model validations are important steps in preparation for the design and validation for the next generation manned vehicles. While the described cutoff rigidity, trapped proton and electron formalisms as coded in a package named GEORAD (GEOmagnetic RADiation) and a web interface named OLTARIS (On-line Tool for the Assessment of Radiation in Space) are applicable to the LEO, Medium Earth Orbit (MEO) and Geosynchronous Earth Orbit (GEO) at quiet solar periods, in this report, the validation of the models using available measurements are limited to STS and ISS nominal operational altitudes (300-400 km) range at LEO where the dominant fields within the vehicle are the trapped proton and attenuated Galactic Cosmic Ray (GCR) ions. The described formalism applies to trapped electron at LEO, MEO and GEO as well. Due to the scarcity of available electron measurements, the trapped electron capabilities of the GEORAD are not discussed in this report, but are accessible through OLTARIS web interface. GEORAD and OLTARIS interests are in the study of long term effects (i.e. a meaningful portion of solar cycle). Therefore, GEORAD does not incorporate any short term external field contribution due to solar activity. Finally, we apply these environmental models to selected target points within ISS 6A (circa early 2001), 7A (circa late 2001), and 11A during its passage through the South Atlantic Anomaly (SAA) to assess the validity of the environmental models at ISS altitudes.

Validation of the BASALT model for simulating off-axis hydrothermal circulation in oceanic crust

NASA Astrophysics Data System (ADS)

Farahat, Navah X.; Archer, David; Abbot, Dorian S.

2017-08-01

Fluid recharge and discharge between the deep ocean and the porous upper layer of off-axis oceanic crust tends to concentrate in small volumes of rock, such as seamounts and fractures, that are unimpeded by low-permeability sediments. Basement structure, sediment burial, heat flow, and other regional characteristics of off-axis hydrothermal systems appear to produce considerable diversity of circulation behaviors. Circulation of seawater and seawater-derived fluids controls the extent of fluid-rock interaction, resulting in significant geochemical impacts. However, the primary regional characteristics that control how seawater is distributed within upper oceanic crust are still poorly understood. In this paper we present the details of the two-dimensional (2-D) BASALT (Basement Activity Simulated At Low Temperatures) numerical model of heat and fluid transport in an off-axis hydrothermal system. This model is designed to simulate a wide range of conditions in order to explore the dominant controls on circulation. We validate the BASALT model's ability to reproduce observations by configuring it to represent a thoroughly studied transect of the Juan de Fuca Ridge eastern flank. The results demonstrate that including series of narrow, ridge-parallel fractures as subgrid features produces a realistic circulation scenario at the validation site. In future projects, a full reactive transport version of the validated BASALT model will be used to explore geochemical fluxes in a variety of off-axis hydrothermal environments.

Real external predictivity of QSAR models: how to evaluate it? Comparison of different validation criteria and proposal of using the concordance correlation coefficient.

PubMed

Chirico, Nicola; Gramatica, Paola

2011-09-26

The main utility of QSAR models is their ability to predict activities/properties for new chemicals, and this external prediction ability is evaluated by means of various validation criteria. As a measure for such evaluation the OECD guidelines have proposed the predictive squared correlation coefficient Q(2)(F1) (Shi et al.). However, other validation criteria have been proposed by other authors: the Golbraikh-Tropsha method, r(2)(m) (Roy), Q(2)(F2) (Schüürmann et al.), Q(2)(F3) (Consonni et al.). In QSAR studies these measures are usually in accordance, though this is not always the case, thus doubts can arise when contradictory results are obtained. It is likely that none of the aforementioned criteria is the best in every situation, so a comparative study using simulated data sets is proposed here, using threshold values suggested by the proponents or those widely used in QSAR modeling. In addition, a different and simple external validation measure, the concordance correlation coefficient (CCC), is proposed and compared with other criteria. Huge data sets were used to study the general behavior of validation measures, and the concordance correlation coefficient was shown to be the most restrictive. On using simulated data sets of a more realistic size, it was found that CCC was broadly in agreement, about 96% of the time, with other validation measures in accepting models as predictive, and in almost all the examples it was the most precautionary. The proposed concordance correlation coefficient also works well on real data sets, where it seems to be more stable, and helps in making decisions when the validation measures are in conflict. Since it is conceptually simple, and given its stability and restrictiveness, we propose the concordance correlation coefficient as a complementary, or alternative, more prudent measure of a QSAR model to be externally predictive.

Draft Forecasts from Real-Time Runs of Physics-Based Models - A Road to the Future

NASA Technical Reports Server (NTRS)

Hesse, Michael; Rastatter, Lutz; MacNeice, Peter; Kuznetsova, Masha

2008-01-01

The Community Coordinated Modeling Center (CCMC) is a US inter-agency activity aiming at research in support of the generation of advanced space weather models. As one of its main functions, the CCMC provides to researchers the use of space science models, even if they are not model owners themselves. The second focus of CCMC activities is on validation and verification of space weather models, and on the transition of appropriate models to space weather forecast centers. As part of the latter activity, the CCMC develops real-time simulation systems that stress models through routine execution. A by-product of these real-time calculations is the ability to derive model products, which may be useful for space weather operators. After consultations with NOAA/SEC and with AFWA, CCMC has developed a set of tools as a first step to make real-time model output useful to forecast centers. In this presentation, we will discuss the motivation for this activity, the actions taken so far, and options for future tools from model output.

Chronic Pain: Content Validation of Nursing Diagnosis in Slovakia and the Czech Republic.

PubMed

Zeleníková, Renáta; Maniaková, Lenka

2015-10-01

The main purpose of the study was to validate the defining characteristics and related factors of the nursing diagnosis "chronic pain" in Slovakia and the Czech Republic. This is a descriptive study. The validation process involved was based on Fehring's Diagnostic Content Validity Model. Three defining characteristics (reports pain, altered ability to continue previous activities, and depression) were classified as major by Slovak nurses, and one defining characteristic (reports pain) was classified as major by Czech nurses. The results of the study provide guidance in devising strategies of pain assessment and can aid in the formulation of accurate nursing diagnoses. The defining characteristic "reports pain" is important for arriving at the nursing diagnosis "chronic pain." © 2014 NANDA International, Inc.

Integrated machine learning, molecular docking and 3D-QSAR based approach for identification of potential inhibitors of trypanosomal N-myristoyltransferase.

PubMed

Singh, Nidhi; Shah, Priyanka; Dwivedi, Hemlata; Mishra, Shikha; Tripathi, Renu; Sahasrabuddhe, Amogh A; Siddiqi, Mohammad Imran

2016-11-15

N-Myristoyltransferase (NMT) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. It is a studied and validated pre-clinical drug target for fungal and parasitic infections. In the present study, a machine learning approach, docking studies and CoMFA analysis have been integrated with the objective of translation of knowledge into a pipelined workflow towards the identification of putative hits through the screening of large compound libraries. In the proposed pipeline, the reported parasitic NMT inhibitors have been used to develop predictive machine learning classification models. Simultaneously, a TbNMT complex model was generated to establish the relationship between the binding mode of the inhibitors for LmNMT and TbNMT through molecular dynamics simulation studies. A 3D-QSAR model was developed and used to predict the activity of the proposed hits in the subsequent step. The hits classified as active based on the machine learning model were assessed as the potential anti-trypanosomal NMT inhibitors through molecular docking studies, predicted activity using a QSAR model and visual inspection. In the final step, the proposed pipeline was validated through in vitro experiments. A total of seven hits have been proposed and tested in vitro for evaluation of dual inhibitory activity against Leishmania donovani and Trypanosoma brucei. Out of these five compounds showed significant inhibition against both of the organisms. The common topmost active compound SEW04173 belongs to a pyrazole carboxylate scaffold and is anticipated to enrich the chemical space with enhanced potency through optimization.

Estimation of Particulate Mass and Manganese Exposure Levels among Welders

PubMed Central

Hobson, Angela; Seixas, Noah; Sterling, David; Racette, Brad A.

2011-01-01

Background: Welders are frequently exposed to Manganese (Mn), which may increase the risk of neurological impairment. Historical exposure estimates for welding-exposed workers are needed for epidemiological studies evaluating the relationship between welding and neurological or other health outcomes. The objective of this study was to develop and validate a multivariate model to estimate quantitative levels of welding fume exposures based on welding particulate mass and Mn concentrations reported in the published literature. Methods: Articles that described welding particulate and Mn exposures during field welding activities were identified through a comprehensive literature search. Summary measures of exposure and related determinants such as year of sampling, welding process performed, type of ventilation used, degree of enclosure, base metal, and location of sampling filter were extracted from each article. The natural log of the reported arithmetic mean exposure level was used as the dependent variable in model building, while the independent variables included the exposure determinants. Cross-validation was performed to aid in model selection and to evaluate the generalizability of the models. Results: A total of 33 particulate and 27 Mn means were included in the regression analysis. The final model explained 76% of the variability in the mean exposures and included welding process and degree of enclosure as predictors. There was very little change in the explained variability and root mean squared error between the final model and its cross-validation model indicating the final model is robust given the available data. Conclusions: This model may be improved with more detailed exposure determinants; however, the relatively large amount of variance explained by the final model along with the positive generalizability results of the cross-validation increases the confidence that the estimates derived from this model can be used for estimating welder exposures in absence of individual measurement data. PMID:20870928

Applying the Health Belief Model to college students' health behavior

PubMed Central

Kim, Hak-Seon; Ahn, Joo

2012-01-01

The purpose of this research was to investigate how university students' nutrition beliefs influence their health behavioral intention. This study used an online survey engine (Qulatrics.com) to collect data from college students. Out of 253 questionnaires collected, 251 questionnaires (99.2%) were used for the statistical analysis. Confirmatory Factor Analysis (CFA) revealed that six dimensions, "Nutrition Confidence," "Susceptibility," "Severity," "Barrier," "Benefit," "Behavioral Intention to Eat Healthy Food," and "Behavioral Intention to do Physical Activity," had construct validity; Cronbach's alpha coefficient and composite reliabilities were tested for item reliability. The results validate that objective nutrition knowledge was a good predictor of college students' nutrition confidence. The results also clearly showed that two direct measures were significant predictors of behavioral intentions as hypothesized. Perceived benefit of eating healthy food and perceived barrier for eat healthy food to had significant effects on Behavioral Intentions and was a valid measurement to use to determine Behavioral Intentions. These findings can enhance the extant literature on the universal applicability of the model and serve as useful references for further investigations of the validity of the model within other health care or foodservice settings and for other health behavioral categories. PMID:23346306

Cross-Cultural Adaptation and Validation of the MPAM-R to Brazilian Portuguese and Proposal of a New Method to Calculate Factor Scores

PubMed Central

Albuquerque, Maicon R.; Lopes, Mariana C.; de Paula, Jonas J.; Faria, Larissa O.; Pereira, Eveline T.; da Costa, Varley T.

2017-01-01

In order to understand the reasons that lead individuals to practice physical activity, researchers developed the Motives for Physical Activity Measure-Revised (MPAM-R) scale. In 2010, a translation of MPAM-R to Portuguese and its validation was performed. However, psychometric measures were not acceptable. In addition, factor scores in some sports psychology scales are calculated by the mean of scores by items of the factor. Nevertheless, it seems appropriate that items with higher factor loadings, extracted by Factor Analysis, have greater weight in the factor score, as items with lower factor loadings have less weight in the factor score. The aims of the present study are to translate, validate the MPAM-R for Portuguese versions, and investigate agreement between two methods used to calculate factor scores. Three hundred volunteers who were involved in physical activity programs for at least 6 months were collected. Confirmatory Factor Analysis of the 30 items indicated that the version did not fit the model. After excluding four items, the final model with 26 items showed acceptable model fit measures by Exploratory Factor Analysis, as well as it conceptually supports the five factors as the original proposal. When two methods are compared to calculate factors scores, our results showed that only “Enjoyment” and “Appearance” factors showed agreement between methods to calculate factor scores. So, the Portuguese version of the MPAM-R can be used in a Brazilian context, and a new proposal for the calculation of the factor score seems to be promising. PMID:28293203

Binding Mode Analyses and Pharmacophore Model Development for Stilbene Derivatives as a Novel and Competitive Class of α-Glucosidase Inhibitors

PubMed Central

Kim, Jun Young; Arooj, Mahreen; Kim, Siu; Hwang, Swan; Kim, Byeong-Woo; Park, Ki Hun; Lee, Keun Woo

2014-01-01

Stilbene urea derivatives as a novel and competitive class of non-glycosidic α-glucosidase inhibitors are effective for the treatment of type II diabetes and obesity. The main purposes of our molecular modeling study are to explore the most suitable binding poses of stilbene derivatives with analyzing the binding affinity differences and finally to develop a pharmacophore model which would represents critical features responsible for α-glucosidase inhibitory activity. Three-dimensional structure of S. cerevisiae α-glucosidase was built by homology modeling method and the structure was used for the molecular docking study to find out the initial binding mode of compound 12, which is the most highly active one. The initial structure was subjected to molecular dynamics (MD) simulations for protein structure adjustment at compound 12-bound state. Based on the adjusted conformation, the more reasonable binding modes of the stilbene urea derivatives were obtained from molecular docking and MD simulations. The binding mode of the derivatives was validated by correlation analysis between experimental Ki value and interaction energy. Our results revealed that the binding modes of the potent inhibitors were engaged with important hydrogen bond, hydrophobic, and π-interactions. With the validated compound 12-bound structure obtained from combining approach of docking and MD simulation, a proper four featured pharmacophore model was generated. It was also validated by comparison of fit values with the Ki values. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from stilbene derivatives. PMID:24465730

Iterative Refinement of a Binding Pocket Model: Active Computational Steering of Lead Optimization

PubMed Central

2012-01-01

Computational approaches for binding affinity prediction are most frequently demonstrated through cross-validation within a series of molecules or through performance shown on a blinded test set. Here, we show how such a system performs in an iterative, temporal lead optimization exercise. A series of gyrase inhibitors with known synthetic order formed the set of molecules that could be selected for “synthesis.” Beginning with a small number of molecules, based only on structures and activities, a model was constructed. Compound selection was done computationally, each time making five selections based on confident predictions of high activity and five selections based on a quantitative measure of three-dimensional structural novelty. Compound selection was followed by model refinement using the new data. Iterative computational candidate selection produced rapid improvements in selected compound activity, and incorporation of explicitly novel compounds uncovered much more diverse active inhibitors than strategies lacking active novelty selection. PMID:23046104

FG7142, yohimbine, and βCCE produce anxiogenic-like effects in the elevated plus-maze but do not affect brainstem activated hippocampal theta.

PubMed

Yeung, Michelle; Lu, Lily; Hughes, Adam M; Treit, Dallas; Dickson, Clayton T

2013-12-01

The neurobiological underpinnings of anxiety are of paramount importance to selective and efficacious pharmaceutical intervention. Hippocampal theta frequency in urethane anaesthetized rats is suppressed by all known (and some previously unknown) anti-anxiety (anxiolytic) drugs. Although these findings support the predictive validity of this assay, its construct validity (i.e., whether theta frequency actually indexes anxiety per se) has not been a subject of systematic investigation. We reasoned that if anxiolytic drugs suppress hippocampal theta frequency, then drugs that increase anxiety (i.e., anxiogenic agents) should increase theta frequency, thus providing evidence of construct validity. We used three proven anxiogenic drugs--two benzodiazepine receptor inverse agonists, N-methyl-β-carboline-3-carboxamide (FG7142) and β-carboline-3-carboxylate ethyl ester (βCCE), and one α2 noradrenergic receptor antagonist, 17α-hydroxy-yohimban-16α-carboxylic acid methyl ester (yohimbine) as pharmacological probes to assess the construct validity of the theta model. Although all three anxiogenic drugs significantly increased behavioural measures of anxiety in the elevated plus-maze, none of the three increased the frequency of hippocampal theta oscillations in the neurophysiological model. As a positive control, we demonstrated that diazepam, a proven anxiolytic drug, decreased the frequency of hippocampal theta, as in all other studies using this model. Given this discrepancy between the significant effects of anxiogenic drugs in the behavioural model and the null effects of these drugs in the neurophysiological model, we conclude that the construct validity of the hippocampal theta model of anxiety is questionable. Copyright © 2013 Elsevier Ltd. All rights reserved.

Population-based validation of a German version of the Brief Resilience Scale

PubMed Central

Wenzel, Mario; Stieglitz, Rolf-Dieter; Kunzler, Angela; Bagusat, Christiana; Helmreich, Isabella; Gerlicher, Anna; Kampa, Miriam; Kubiak, Thomas; Kalisch, Raffael; Lieb, Klaus; Tüscher, Oliver

2018-01-01

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for. PMID:29438435

Validation of The Scenarios Designed For The Eu Registration of Pesticides

NASA Astrophysics Data System (ADS)

Piñeros Garcet, J. D.; de Nie, D.; Vanclooster, M.; Tiktak, A.; Klein, M.

As part of recent efforts to harmonise registration procedures for pesticides within the EU, a set of uniform principles were developed, setting out the detailed evaluation and decision making criteria for pesticide registration. The EU directive 91/414/EEC places great importance on the use of validated models to calculate Predicted Envi- ronmental Concentrations (PECs), as a basis for assessing the environmental risks and health effects. To be used in a harmonised registration process, the quality of PEC modelling needs to be assured. Quality assurance of mathematical modelling implies, amongst others, the validation of the environmental modelling scenarios. The FOrum for the CO-ordination of pesticide fate models and their USe (FOCUS), is the cur- rent platform where common modelling methodologies are designed and subjected for approval to the European authorities. In 2000, the FOCUS groundwater scenarios working group defined the procedures for realising tier 1 PEC groundwater calcula- tions for the active substances of plant protection products at the pan-european level. The procedures and guidelines were approved by the Standing Committee on Plant Health, and are now recommended for tier 1 PEC groundwater calculations in the reg-istration dossier. Yet, the working group also identified a range of uncertainties related to the validity of the present leaching scenarios. To mitigate some of these problems,the EU R&D project APECOP was designed and approved for support in the frame-work of the EU-FP5-Quality of Life Programme. One of the objectives of the project is to evaluate the appropriateness of the current Tier 1 groundwater scenarios. In this paper, we summarise the methodology and results of the scenarios validation.

Validation of The Scenarios Designed For The Eu Registration of Pesticides

NASA Astrophysics Data System (ADS)

Piñeros Garcet, J. D.; de Nie, D.; Vanclooster, M.; Tiktak, A.; Klein, M.; Jones, A.

As part of recent efforts to harmonise registration procedures for pesticides within the EU, a set of uniform principles were developed, setting out the detailed evaluation and decision making criteria for pesticide registration. The EU directive 91/414/EEC places great importance on the use of validated models to calculate Predicted Envi- ronmental Concentrations (PECs), as a basis for assessing the environmental risks and health effects. To be used in a harmonised registration process, the quality of PEC modelling needs to be assured. Quality assurance of mathematical modelling implies, amongst others, the validation of the environmental modelling scenarios. The FOrum for the CO-ordination of pesticide fate models and their USe (FOCUS), is the cur- rent platform where common modelling methodologies are designed and subjected for approval to the European authorities. In 2000, the FOCUS groundwater scenarios working group defined the procedures for realising tier 1 PEC groundwater calcula- tions for the active substances of plant protection products at the pan-european level. The procedures and guidelines were approved by the Standing Committee on Plant Health, and are now recommended for tier 1 PEC groundwater calculations in the reg- istration dossier. Yet, the working group also identified a range of uncertainties related to the validity of the present leaching scenarios. To mitigate some of these problems, the EU R&D project APECOP was designed and approved for support in the frame- work of the EU-FP5-Quality of Life Programme. One of the objectives of the project is to evaluate the appropriateness of the current Tier 1 groundwater scenarios. In this paper, we summarise the methodology and results of the scenarios validation.

Development and Validation of the Cognitive Behavioral Physical Activity Questionnaire.

PubMed

Schembre, Susan M; Durand, Casey P; Blissmer, Bryan J; Greene, Geoffrey W

2015-01-01

Develop and demonstrate preliminary validation of a brief questionnaire aimed at assessing social cognitive determinants of physical activity (PA) in a college population. Quantitative and observational. A midsized northeastern university. Convenience sample of 827 male and female college students age 18 to 24 years. International Physical Activity Questionnaire and a PA stage-of-change algorithm. A sequential process of survey development, including item generation and data reduction analyses by factor analysis, was followed with the goal of creating a parsimonious questionnaire. Structural equation modeling was used for confirmatory factor analysis and construct validation was confirmed against self-reported PA and stage of change. Validation analyses were replicated in a second, independent sample of 1032 college students. Fifteen items reflecting PA self-regulation, outcome expectations, and personal barriers explained 65% of the questionnaire data and explained 28.6% and 39.5% of the variance in total PA and moderate-to-vigorous-intensity PA, respectively. Scale scores were distinguishable across the stages of change. Findings were similar when the Cognitive Behavioral Physical Activity Questionnaire (CBPAQ) was tested in a similar and independent sample of college students (40%; R (2) moderate-to-vigorous-intensity PA = .40; p < .001). The CBPAQ successfully explains and predicts PA behavior in a college population, warranting its incorporation into future studies aiming at understanding and improving on PA behavior in college students.

Evolution of an Implementation-Ready Interprofessional Pain Assessment Reference Model

PubMed Central

Collins, Sarah A; Bavuso, Karen; Swenson, Mary; Suchecki, Christine; Mar, Perry; Rocha, Roberto A.

2017-01-01

Standards to increase consistency of comprehensive pain assessments are important for safety, quality, and analytics activities, including meeting Joint Commission requirements and learning the best management strategies and interventions for the current prescription Opioid epidemic. In this study we describe the development and validation of a Pain Assessment Reference Model ready for implementation on EHR forms and flowsheets. Our process resulted in 5 successive revisions of the reference model, which more than doubled the number of data elements to 47. The organization of the model evolved during validation sessions with panels totaling 48 subject matter experts (SMEs) to include 9 sets of data elements, with one set recommended as a minimal data set. The reference model also evolved when implemented into EHR forms and flowsheets, indicating specifications such as cascading logic that are important to inform secondary use of data. PMID:29854125

Early Activation of Ventral Hippocampus and Subiculum during Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Toyoda, Izumi; Bower, Mark R.; Leyva, Fernando

2013-01-01

Temporal lobe epilepsy is the most common form of epilepsy in adults. The pilocarpine-treated rat model is used frequently to investigate temporal lobe epilepsy. The validity of the pilocarpine model has been challenged based largely on concerns that seizures might initiate in different brain regions in rats than in patients. The present study used 32 recording electrodes per rat to evaluate spontaneous seizures in various brain regions including the septum, dorsomedial thalamus, amygdala, olfactory cortex, dorsal and ventral hippocampus, substantia nigra, entorhinal cortex, and ventral subiculum. Compared with published results from patients, seizures in rats tended to be shorter, spread faster and more extensively, generate behavioral manifestations more quickly, and produce generalized convulsions more frequently. Similarities to patients included electrographic waveform patterns at seizure onset, variability in sites of earliest seizure activity within individuals, and variability in patterns of seizure spread. Like patients, the earliest seizure activity in rats was recorded most frequently within the hippocampal formation. The ventral hippocampus and ventral subiculum displayed the earliest seizure activity. Amygdala, olfactory cortex, and septum occasionally displayed early seizure latencies, but not above chance levels. Substantia nigra and dorsomedial thalamus demonstrated consistently late seizure onsets, suggesting their unlikely involvement in seizure initiation. The results of the present study reveal similarities in onset sites of spontaneous seizures in patients with temporal lobe epilepsy and pilocarpine-treated rats that support the model's validity. PMID:23825415

Nursing diagnoses for the elderly using the International Classification for Nursing Practice and the activities of living model.

PubMed

de Medeiros, Ana Claudia Torres; da Nóbrega, Maria Miriam Lima; Rodrigues, Rosalina Aparecida Partezani; Fernandes, Maria das Graças Melo

2013-01-01

To develop nursing diagnosis statements for the elderly based on the Activities of Living Model and on the International Classification for Nursing Practice. Descriptive and exploratory study, put in practice in two stages: 1) collection of terms and concepts that are considered clinically and culturally relevant for nursing care delivered to the elderly, in order to develop a database of terms and 2) development of nursing diagnosis statements for the elderly in primary health care, based on the guidelines of the International Council of Nurses and on the database of terms for nursing practice involving the elderly. 414 terms were identified and submitted to the content validation process, with the participation of ten nursing experts, which resulted in 263 validated terms. These terms were submitted to cross mapping with the terms of the International Classification for Nursing Practice, resulting in the identification of 115 listed terms and 148 non-listed terms, which constituted the database of terms, from which 127 nursing diagnosis statements were prepared and classified into factors that affect the performance of the elderly's activities of living - 69 into biological factors, 19 into psychological, 31 into sociocultural, five into environmental, and three into political-economic factors. After clinical validation, these statements can serve as a guide for nursing consultations with elderly patients, without ignoring clinical experience, critical thinking and decision-making.

Development and Validation of a Physiologically Based Pharmacokinetic Model of Chloral Hydrate and Its Main Metabolites

DTIC Science & Technology

1995-11-01

for a computer-aided simulation of body levels of chloral hydrate in a therapeutic situation and for the estimate of toxicokinetics of its active metabolites generated during the environmental pollution scenario.

Insight into the interaction mechanism of human SGLT2 with its inhibitors: 3D-QSAR studies, homology modeling, and molecular docking and molecular dynamics simulations.

PubMed

Dong, Lili; Feng, Ruirui; Bi, Jiawei; Shen, Shengqiang; Lu, Huizhe; Zhang, Jianjun

2018-03-06

Human sodium-dependent glucose co-transporter 2 (hSGLT2) is a crucial therapeutic target in the treatment of type 2 diabetes. In this study, both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to generate three-dimensional quantitative structure-activity relationship (3D-QSAR) models. In the most accurate CoMFA-based and CoMSIA-based QSAR models, the cross-validated coefficients (r 2 cv ) were 0.646 and 0.577, respectively, while the non-cross-validated coefficients (r 2 ) were 0.997 and 0.991, respectively, indicating that both models were reliable. In addition, we constructed a homology model of hSGLT2 in the absence of a crystal structure. Molecular docking was performed to explore the bonding mode of inhibitors to the active site of hSGLT2. Molecular dynamics (MD) simulations and binding free energy calculations using MM-PBSA and MM-GBSA were carried out to further elucidate the interaction mechanism. With regards to binding affinity, we found that hydrogen-bond interactions of Asn51 and Glu75, located in the active site of hSGLT2, with compound 40 were critical. Hydrophobic and electrostatic interactions were shown to enhance activity, in agreement with the results obtained from docking and 3D-QSAR analysis. Our study results shed light on the interaction mode between inhibitors and hSGLT2 and may aid in the development of C-aryl glucoside SGLT2 inhibitors.

Deriving Tools from Real-time Runs: A New CCMC Support for SEC and AFWA

NASA Technical Reports Server (NTRS)

Hesse, Michael; Rastatter, Lutz; MacNeice, Peter; Kuznetsova, Masha

2008-01-01

The Community Coordinated Modeling Center (CCMC) is a US inter-agency activity aiming at research in support of the generation of advanced space weather models. As one of its main functions. the CCMC provides to researchers the use of space science models, even if they are not model owners themselves. The second focus of CCMC activities is on validation and verification of space weather models. and on the transition of appropriate models to space weather forecast centers. As part of the latter activity. the CCMC develops real-time simulation systems that stress models through routine execution. A by-product of these real-time calculations is the ability to derive model products, which may be useful for space weather operators. After consultations with NOA/SEC and with AFWA, CCMC has developed a set of tools as a first step to make real-time model output useful to forecast centers. In this presentation, we will discuss the motivation for this activity, the actions taken so far, and options for future tools from model output.

Agent-based modeling of noncommunicable diseases: a systematic review.

PubMed

Nianogo, Roch A; Arah, Onyebuchi A

2015-03-01

We reviewed the use of agent-based modeling (ABM), a systems science method, in understanding noncommunicable diseases (NCDs) and their public health risk factors. We systematically reviewed studies in PubMed, ScienceDirect, and Web of Sciences published from January 2003 to July 2014. We retrieved 22 relevant articles; each had an observational or interventional design. Physical activity and diet were the most-studied outcomes. Often, single agent types were modeled, and the environment was usually irrelevant to the studied outcome. Predictive validation and sensitivity analyses were most used to validate models. Although increasingly used to study NCDs, ABM remains underutilized and, where used, is suboptimally reported in public health studies. Its use in studying NCDs will benefit from clarified best practices and improved rigor to establish its usefulness and facilitate replication, interpretation, and application.

Agent-Based Modeling of Noncommunicable Diseases: A Systematic Review

PubMed Central

Arah, Onyebuchi A.

2015-01-01

We reviewed the use of agent-based modeling (ABM), a systems science method, in understanding noncommunicable diseases (NCDs) and their public health risk factors. We systematically reviewed studies in PubMed, ScienceDirect, and Web of Sciences published from January 2003 to July 2014. We retrieved 22 relevant articles; each had an observational or interventional design. Physical activity and diet were the most-studied outcomes. Often, single agent types were modeled, and the environment was usually irrelevant to the studied outcome. Predictive validation and sensitivity analyses were most used to validate models. Although increasingly used to study NCDs, ABM remains underutilized and, where used, is suboptimally reported in public health studies. Its use in studying NCDs will benefit from clarified best practices and improved rigor to establish its usefulness and facilitate replication, interpretation, and application. PMID:25602871

Web-Based Virtual Patients in Nursing Education: Development and Validation of Theory-Anchored Design and Activity Models

PubMed Central

2014-01-01

Background Research has shown that nursing students find it difficult to translate and apply their theoretical knowledge in a clinical context. Virtual patients (VPs) have been proposed as a learning activity that can support nursing students in their learning of scientific knowledge and help them integrate theory and practice. Although VPs are increasingly used in health care education, they still lack a systematic consistency that would allow their reuse outside of their original context. There is therefore a need to develop a model for the development and implementation of VPs in nursing education. Objective The aim of this study was to develop and evaluate a virtual patient model optimized to the learning and assessment needs in nursing education. Methods The process of modeling started by reviewing theoretical frameworks reported in the literature and used by practitioners when designing learning and assessment activities. The Outcome-Present State Test (OPT) model was chosen as the theoretical framework. The model was then, in an iterative manner, developed and optimized to the affordances of virtual patients. Content validation was performed with faculty both in terms of the relevance of the chosen theories but also its applicability in nursing education. The virtual patient nursing model was then instantiated in two VPs. The students’ perceived usefulness of the VPs was investigated using a questionnaire. The result was analyzed using descriptive statistics. Results A virtual patient Nursing Design Model (vpNDM) composed of three layers was developed. Layer 1 contains the patient story and ways of interacting with the data, Layer 2 includes aspects of the iterative process of clinical reasoning, and finally Layer 3 includes measurable outcomes. A virtual patient Nursing Activity Model (vpNAM) was also developed as a guide when creating VP-centric learning activities. The students perceived the global linear VPs as a relevant learning activity for the integration of theory and practice. Conclusions Virtual patients that are adapted to the nursing paradigm can support nursing students’ development of clinical reasoning skills. The proposed virtual patient nursing design and activity models will allow the systematic development of different types of virtual patients from a common model and thereby create opportunities for sharing pedagogical designs across technical solutions. PMID:24727709

Field evaluation of a random forest activity classifier for wrist-worn accelerometer data.

PubMed

Pavey, Toby G; Gilson, Nicholas D; Gomersall, Sjaan R; Clark, Bronwyn; Trost, Stewart G

2017-01-01

Wrist-worn accelerometers are convenient to wear and associated with greater wear-time compliance. Previous work has generally relied on choreographed activity trials to train and test classification models. However, validity in free-living contexts is starting to emerge. Study aims were: (1) train and test a random forest activity classifier for wrist accelerometer data; and (2) determine if models trained on laboratory data perform well under free-living conditions. Twenty-one participants (mean age=27.6±6.2) completed seven lab-based activity trials and a 24h free-living trial (N=16). Participants wore a GENEActiv monitor on the non-dominant wrist. Classification models recognising four activity classes (sedentary, stationary+, walking, and running) were trained using time and frequency domain features extracted from 10-s non-overlapping windows. Model performance was evaluated using leave-one-out-cross-validation. Models were implemented using the randomForest package within R. Classifier accuracy during the 24h free living trial was evaluated by calculating agreement with concurrently worn activPAL monitors. Overall classification accuracy for the random forest algorithm was 92.7%. Recognition accuracy for sedentary, stationary+, walking, and running was 80.1%, 95.7%, 91.7%, and 93.7%, respectively for the laboratory protocol. Agreement with the activPAL data (stepping vs. non-stepping) during the 24h free-living trial was excellent and, on average, exceeded 90%. The ICC for stepping time was 0.92 (95% CI=0.75-0.97). However, sensitivity and positive predictive values were modest. Mean bias was 10.3min/d (95% LOA=-46.0 to 25.4min/d). The random forest classifier for wrist accelerometer data yielded accurate group-level predictions under controlled conditions, but was less accurate at identifying stepping verse non-stepping behaviour in free living conditions Future studies should conduct more rigorous field-based evaluations using observation as a criterion measure. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

The derivation and validation of a simple model for predicting in-hospital mortality of acutely admitted patients to internal medicine wards.

PubMed

Sakhnini, Ali; Saliba, Walid; Schwartz, Naama; Bisharat, Naiel

2017-06-01

Limited information is available about clinical predictors of in-hospital mortality in acute unselected medical admissions. Such information could assist medical decision-making.To develop a clinical model for predicting in-hospital mortality in unselected acute medical admissions and to test the impact of secondary conditions on hospital mortality.This is an analysis of the medical records of patients admitted to internal medicine wards at one university-affiliated hospital. Data obtained from the years 2013 to 2014 were used as a derivation dataset for creating a prediction model, while data from 2015 was used as a validation dataset to test the performance of the model. For each admission, a set of clinical and epidemiological variables was obtained. The main diagnosis at hospitalization was recorded, and all additional or secondary conditions that coexisted at hospital admission or that developed during hospital stay were considered secondary conditions.The derivation and validation datasets included 7268 and 7843 patients, respectively. The in-hospital mortality rate averaged 7.2%. The following variables entered the final model; age, body mass index, mean arterial pressure on admission, prior admission within 3 months, background morbidity of heart failure and active malignancy, and chronic use of statins and antiplatelet agents. The c-statistic (ROC-AUC) of the prediction model was 80.5% without adjustment for main or secondary conditions, 84.5%, with adjustment for the main diagnosis, and 89.5% with adjustment for the main diagnosis and secondary conditions. The accuracy of the predictive model reached 81% on the validation dataset.A prediction model based on clinical data with adjustment for secondary conditions exhibited a high degree of prediction accuracy. We provide a proof of concept that there is an added value for incorporating secondary conditions while predicting probabilities of in-hospital mortality. Further improvement of the model performance and validation in other cohorts are needed to aid hospitalists in predicting health outcomes.

Validity of the Special Needs Education Assessment Tool (SNEAT), a Newly Developed Scale for Children with Disabilities.

PubMed

Kohara, Aiko; Han, ChangWan; Kwon, HaeJin; Kohzuki, Masahiro

2015-11-01

The improvement of the quality of life (QOL) of children with disabilities has been considered important. Therefore, the Special Needs Education Assessment Tool (SNEAT) was developed based on the concept of QOL to objectively evaluate the educational outcome of children with disabilities. SNEAT consists of 11 items in three domains: physical functioning, mental health, and social functioning. This study aimed to verify the reliability and construct validity of SNEAT using 93 children collected from the classes on independent activities of daily living for children with disabilities in Okinawa Prefecture between October and November 2014. Survey data were collected in a longitudinal prospective cohort study. The reliability of SNEAT was verified via the internal consistency method and the test-pretest method; both the coefficient of Cronbach's α and the intra-class correlation coefficient were over 0.7. The validity of SNEAT was also verified via one-way repeated-measures ANOVA and the latent growth curve model. The scores of all the items and domains and the total scores obtained from one-way repeated-measures ANOVA were the same as the predicted scores. SNEAT is valid based on its goodness-of-fit values obtained using the latent growth curve model, where the values of comparative fit index (0.983) and root mean square error of approximation (0.062) were within the goodness-of-fit range. These results indicate that SNEAT has high reliability and construct validity and may contribute to improve QOL of children with disabilities in the classes on independent activities of daily living for children with disabilities.

Rational design and validation of a vanilloid-sensitive TRPV2 ion channel.

PubMed

Yang, Fan; Vu, Simon; Yarov-Yarovoy, Vladimir; Zheng, Jie

2016-06-28

Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S-S498F-L505T-Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular "glue" that bridges the S4-S5 linker to the S1-S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor.

Critical validation studies of neurofeedback.

PubMed

Gruzelier, John; Egner, Tobias

2005-01-01

The field of neurofeedback training has proceeded largely without validation. In this article the authors review studies directed at validating sensory motor rhythm, beta and alpha-theta protocols for improving attention, memory, and music performance in healthy participants. Importantly, benefits were demonstrable with cognitive and neurophysiologic measures that were predicted on the basis of regression models of learning to enhance sensory motor rhythm and beta activity. The first evidence of operant control over the alpha-theta ratio is provided, together with remarkable improvements in artistic aspects of music performance equivalent to two class grades in conservatory students. These are initial steps in providing a much needed scientific basis to neurofeedback.

APG: an Active Protein-Gene network model to quantify regulatory signals in complex biological systems.

PubMed

Wang, Jiguang; Sun, Yidan; Zheng, Si; Zhang, Xiang-Sun; Zhou, Huarong; Chen, Luonan

2013-01-01

Synergistic interactions among transcription factors (TFs) and their cofactors collectively determine gene expression in complex biological systems. In this work, we develop a novel graphical model, called Active Protein-Gene (APG) network model, to quantify regulatory signals of transcription in complex biomolecular networks through integrating both TF upstream-regulation and downstream-regulation high-throughput data. Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information. We then apply this model to study spontaneous type 2 diabetic Goto-Kakizaki (GK) and Wistar control rats. Our biological experiments validate the theoretical results. In particular, SP1 is found to be a hidden TF with changed regulatory activity, and the loss of SP1 activity contributes to the increased glucose production during diabetes development. APG model provides theoretical basis to quantitatively elucidate transcriptional regulation by modelling TF combinatorial interactions and exploiting multilevel high-throughput information.

APG: an Active Protein-Gene Network Model to Quantify Regulatory Signals in Complex Biological Systems

PubMed Central

Wang, Jiguang; Sun, Yidan; Zheng, Si; Zhang, Xiang-Sun; Zhou, Huarong; Chen, Luonan

2013-01-01

Synergistic interactions among transcription factors (TFs) and their cofactors collectively determine gene expression in complex biological systems. In this work, we develop a novel graphical model, called Active Protein-Gene (APG) network model, to quantify regulatory signals of transcription in complex biomolecular networks through integrating both TF upstream-regulation and downstream-regulation high-throughput data. Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information. We then apply this model to study spontaneous type 2 diabetic Goto-Kakizaki (GK) and Wistar control rats. Our biological experiments validate the theoretical results. In particular, SP1 is found to be a hidden TF with changed regulatory activity, and the loss of SP1 activity contributes to the increased glucose production during diabetes development. APG model provides theoretical basis to quantitatively elucidate transcriptional regulation by modelling TF combinatorial interactions and exploiting multilevel high-throughput information. PMID:23346354

A Novel Model for the Entire Settling-Thickening Process in a Secondary Settling Tank.

PubMed

He, Zhijiang; Zhang, Yuankai; Wang, Hongchen; Qi, Lu; Yin, Xunfei; Zhang, Xiaojun; Wen, Yang

2016-12-01

  Sludge settling and thickening occur simultaneously in secondary settling tanks (SSTs). The ability to accurately calculate the settling and thickening capacity of activated sludge was of great importance. Despite extensive studies on the development of settling velocity models for use with SSTs, these models have not been applied due to the difficulty in calibrating the related parameters. Additionally, there have been some studies of the thickening behavior of the activated sludge in SSTs. In this study, a novel settling and thickening model for activated sludge was developed, and the model was validated using experimental data (R2 = 0.830 to 0.963, p < 0.001), which is more reasonable for the characterization of the settling and thickening behavior of the activated sludge in an SST. The application of these models requires only one critical parameter, namely, the stirred sludge volume index SSVI3.5, which is readily available in a water resource recovery facility.

QSAR modelling using combined simple competitive learning networks and RBF neural networks.

PubMed

Sheikhpour, R; Sarram, M A; Rezaeian, M; Sheikhpour, E

2018-04-01

The aim of this study was to propose a QSAR modelling approach based on the combination of simple competitive learning (SCL) networks with radial basis function (RBF) neural networks for predicting the biological activity of chemical compounds. The proposed QSAR method consisted of two phases. In the first phase, an SCL network was applied to determine the centres of an RBF neural network. In the second phase, the RBF neural network was used to predict the biological activity of various phenols and Rho kinase (ROCK) inhibitors. The predictive ability of the proposed QSAR models was evaluated and compared with other QSAR models using external validation. The results of this study showed that the proposed QSAR modelling approach leads to better performances than other models in predicting the biological activity of chemical compounds. This indicated the efficiency of simple competitive learning networks in determining the centres of RBF neural networks.

Three-dimensional quantitative structure-activity relationship CoMSIA/CoMFA and LeapFrog studies on novel series of bicyclo [4.1.0] heptanes derivatives as melanin-concentrating hormone receptor R1 antagonists.

PubMed

Morales-Bayuelo, Alejandro; Ayazo, Hernan; Vivas-Reyes, Ricardo

2010-10-01

Comparative molecular similarity indices analysis (CoMSIA) and comparative molecular field analysis (CoMFA) were performed on a series of bicyclo [4.1.0] heptanes derivatives as melanin-concentrating hormone receptor R1 antagonists (MCHR1 antagonists). Molecular superimposition of antagonists on the template structure was performed by database alignment method. The statistically significant model was established on sixty five molecules, which were validated by a test set of ten molecules. The CoMSIA model yielded the best predictive model with a q(2) = 0.639, non cross-validated R(2) of 0.953, F value of 92.802, bootstrapped R(2) of 0.971, standard error of prediction = 0.402, and standard error of estimate = 0.146 while the CoMFA model yielded a q(2) = 0.680, non cross-validated R(2) of 0.922, F value of 114.351, bootstrapped R(2) of 0.925, standard error of prediction = 0.364, and standard error of estimate = 0.180. CoMFA analysis maps were employed for generating a pseudo cavity for LeapFrog calculation. The contour maps obtained from 3D-QSAR studies were appraised for activity trends for the molecules analyzed. The results show the variability of steric and electrostatic contributions that determine the activity of the MCHR1 antagonist, with these results we proposed new antagonists that may be more potent than previously reported, these novel antagonists were designed from the addition of highly electronegative groups in the substituent di(i-C(3)H(7))N- of the bicycle [4.1.0] heptanes, using the model CoMFA which also was used for the molecular design using the technique LeapFrog. The data generated from the present study will further help to design novel, potent, and selective MCHR1 antagonists. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Development and validation of a microchip pulsed laser for ESA space altimeters

NASA Astrophysics Data System (ADS)

Couto, Bruno; Abreu, Hernâni; Gordo, Paulo; Amorim, António

2016-10-01

The development and validation of small size laser sources for space based range finding is of crucial importance to the development of miniature LIDAR devices for European space missions, particularly for planet lander probes. In this context, CENTRA-SIM is developing a passively q-switched microchip laser in the 1.5μm wavelength range. Pulses in the order of 2 ns and 100μJ were found to be suitable for range finding for small landing platforms. Both glass and crystalline Yb-Er doped active media are commonly available. Crystalline media present higher thermal conductivity and hardness, which allows for higher pumping intensities. However, glass laser media present longer laser upper-state lifetime and 99% Yb-Er transfer efficiency make phosphate glasses the typically preferred host for this type of application. In addition to this, passively q-switched microchip lasers with Yb-Er doped phosphate glass have been reported to output >100μJ pulses while their crystalline host counterparts achieve a few tens of μJ at best. Two different types of rate equation models have been found: microscopic quantities based models and macroscopic quantities based models. Based on the works of Zolotovskaya et al. and Spühler et al, we have developed a computer model that further exploits the equivalence between the two types of approaches. The simulation studies, using commercial available components allowed us to design a compact laser emitting 80μJ pulses with up to 30kW peak power and 1 to 2 ns pulse width. We considered EAT14 Yb-Er doped glass as active medium and Co2+:MgAl2O4 as saturable absorber. The active medium is pumped by a 975nm semiconductor laser focused into a 200μm spot. Measurements on an experimental test bench to validate the numerical model were carried out. Several different combinations of, saturable absorber length and output coupling were experimented.

Modeling deep brain stimulation: point source approximation versus realistic representation of the electrode

NASA Astrophysics Data System (ADS)

Zhang, Tianhe C.; Grill, Warren M.

2010-12-01

Deep brain stimulation (DBS) has emerged as an effective treatment for movement disorders; however, the fundamental mechanisms by which DBS works are not well understood. Computational models of DBS can provide insights into these fundamental mechanisms and typically require two steps: calculation of the electrical potentials generated by DBS and, subsequently, determination of the effects of the extracellular potentials on neurons. The objective of this study was to assess the validity of using a point source electrode to approximate the DBS electrode when calculating the thresholds and spatial distribution of activation of a surrounding population of model neurons in response to monopolar DBS. Extracellular potentials in a homogenous isotropic volume conductor were calculated using either a point current source or a geometrically accurate finite element model of the Medtronic DBS 3389 lead. These extracellular potentials were coupled to populations of model axons, and thresholds and spatial distributions were determined for different electrode geometries and axon orientations. Median threshold differences between DBS and point source electrodes for individual axons varied between -20.5% and 9.5% across all orientations, monopolar polarities and electrode geometries utilizing the DBS 3389 electrode. Differences in the percentage of axons activated at a given amplitude by the point source electrode and the DBS electrode were between -9.0% and 12.6% across all monopolar configurations tested. The differences in activation between the DBS and point source electrodes occurred primarily in regions close to conductor-insulator interfaces and around the insulating tip of the DBS electrode. The robustness of the point source approximation in modeling several special cases—tissue anisotropy, a long active electrode and bipolar stimulation—was also examined. Under the conditions considered, the point source was shown to be a valid approximation for predicting excitation of populations of neurons in response to DBS.

Utilizing random Forest QSAR models with optimized parameters for target identification and its application to target-fishing server.

PubMed

Lee, Kyoungyeul; Lee, Minho; Kim, Dongsup

2017-12-28

The identification of target molecules is important for understanding the mechanism of "target deconvolution" in phenotypic screening and "polypharmacology" of drugs. Because conventional methods of identifying targets require time and cost, in-silico target identification has been considered an alternative solution. One of the well-known in-silico methods of identifying targets involves structure activity relationships (SARs). SARs have advantages such as low computational cost and high feasibility; however, the data dependency in the SAR approach causes imbalance of active data and ambiguity of inactive data throughout targets. We developed a ligand-based virtual screening model comprising 1121 target SAR models built using a random forest algorithm. The performance of each target model was tested by employing the ROC curve and the mean score using an internal five-fold cross validation. Moreover, recall rates for top-k targets were calculated to assess the performance of target ranking. A benchmark model using an optimized sampling method and parameters was examined via external validation set. The result shows recall rates of 67.6% and 73.9% for top-11 (1% of the total targets) and top-33, respectively. We provide a website for users to search the top-k targets for query ligands available publicly at http://rfqsar.kaist.ac.kr . The target models that we built can be used for both predicting the activity of ligands toward each target and ranking candidate targets for a query ligand using a unified scoring scheme. The scores are additionally fitted to the probability so that users can estimate how likely a ligand-target interaction is active. The user interface of our web site is user friendly and intuitive, offering useful information and cross references.

Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations.

PubMed

Martínez-Rincón, Raúl O; Rivera-Pérez, Crisalejandra; Diambra, Luis; Noriega, Fernando G

2017-01-01

Juvenile hormone (JH) regulates development and reproductive maturation in insects. The corpora allata (CA) from female adult mosquitoes synthesize fluctuating levels of JH, which have been linked to the ovarian development and are influenced by nutritional signals. The rate of JH biosynthesis is controlled by the rate of flux of isoprenoids in the pathway, which is the outcome of a complex interplay of changes in precursor pools and enzyme levels. A comprehensive study of the changes in enzymatic activities and precursor pool sizes have been previously reported for the mosquito Aedes aegypti JH biosynthesis pathway. In the present studies, we used two different quantitative approaches to describe and predict how changes in the individual metabolic reactions in the pathway affect JH synthesis. First, we constructed generalized additive models (GAMs) that described the association between changes in specific metabolite concentrations with changes in enzymatic activities and substrate concentrations. Changes in substrate concentrations explained 50% or more of the model deviances in 7 of the 13 metabolic steps analyzed. Addition of information on enzymatic activities almost always improved the fitness of GAMs built solely based on substrate concentrations. GAMs were validated using experimental data that were not included when the model was built. In addition, a system of ordinary differential equations (ODE) was developed to describe the instantaneous changes in metabolites as a function of the levels of enzymatic catalytic activities. The results demonstrated the ability of the models to predict changes in the flux of metabolites in the JH pathway, and can be used in the future to design and validate experimental manipulations of JH synthesis.

Development of a contrast phantom for active millimeter-wave imaging systems

NASA Astrophysics Data System (ADS)

Barber, Jeffrey; Weatherall, James C.; Brauer, Carolyn S.; Smith, Barry T.

2011-06-01

As the development of active millimeter wave imaging systems continues, it is necessary to validate materials that simulate the expected response of explosives. While physics-based models have been used to develop simulants, it is desirable to image both the explosive and simulant together in a controlled fashion in order to demonstrate success. To this end, a millimeter wave contrast phantom has been created to calibrate image grayscale while controlling the configuration of the explosive and simulant such that direct comparison of their respective returns can be performed. The physics of the phantom are described, with millimeter wave images presented to show successful development of the phantom and simulant validation at GHz frequencies.

Mathematical modeling of electrical activity of uterine muscle cells.

PubMed

Rihana, Sandy; Terrien, Jeremy; Germain, Guy; Marque, Catherine

2009-06-01

The uterine electrical activity is an efficient parameter to study the uterine contractility. In order to understand the ionic mechanisms responsible for its generation, we aimed at building a mathematical model of the uterine cell electrical activity based upon the physiological mechanisms. First, based on the voltage clamp experiments found in the literature, we focus on the principal ionic channels and their cognate currents involved in the generation of this electrical activity. Second, we provide the methodology of formulations of uterine ionic currents derived from a wide range of electrophysiological data. The model is validated step by step by comparing simulated voltage-clamp results with the experimental ones. The model reproduces successfully the generation of single spikes or trains of action potentials that fit with the experimental data. It allows analyzing ionic channels implications. Likewise, the calcium-dependent conductance influences significantly the cellular oscillatory behavior.

Real-Time Performance of Mechatronic PZT Module Using Active Vibration Feedback Control.

PubMed

Aggogeri, Francesco; Borboni, Alberto; Merlo, Angelo; Pellegrini, Nicola; Ricatto, Raffaele

2016-09-25

This paper proposes an innovative mechatronic piezo-actuated module to control vibrations in modern machine tools. Vibrations represent one of the main issues that seriously compromise the quality of the workpiece. The active vibration control (AVC) device is composed of a host part integrated with sensors and actuators synchronized by a regulator; it is able to make a self-assessment and adjust to alterations in the environment. In particular, an innovative smart actuator has been designed and developed to satisfy machining requirements during active vibration control. This study presents the mechatronic model based on the kinematic and dynamic analysis of the AVC device. To ensure a real time performance, a H2-LQG controller has been developed and validated by simulations involving a machine tool, PZT actuator and controller models. The Hardware in the Loop (HIL) architecture is adopted to control and attenuate the vibrations. A set of experimental tests has been performed to validate the AVC module on a commercial machine tool. The feasibility of the real time vibration damping is demonstrated and the simulation accuracy is evaluated.

Real-Time Performance of Mechatronic PZT Module Using Active Vibration Feedback Control

PubMed Central

Aggogeri, Francesco; Borboni, Alberto; Merlo, Angelo; Pellegrini, Nicola; Ricatto, Raffaele

2016-01-01

This paper proposes an innovative mechatronic piezo-actuated module to control vibrations in modern machine tools. Vibrations represent one of the main issues that seriously compromise the quality of the workpiece. The active vibration control (AVC) device is composed of a host part integrated with sensors and actuators synchronized by a regulator; it is able to make a self-assessment and adjust to alterations in the environment. In particular, an innovative smart actuator has been designed and developed to satisfy machining requirements during active vibration control. This study presents the mechatronic model based on the kinematic and dynamic analysis of the AVC device. To ensure a real time performance, a H2-LQG controller has been developed and validated by simulations involving a machine tool, PZT actuator and controller models. The Hardware in the Loop (HIL) architecture is adopted to control and attenuate the vibrations. A set of experimental tests has been performed to validate the AVC module on a commercial machine tool. The feasibility of the real time vibration damping is demonstrated and the simulation accuracy is evaluated. PMID:27681732

Preliminary validation of computational model for neutron flux prediction of Thai Research Reactor (TRR-1/M1)

NASA Astrophysics Data System (ADS)

Sabaibang, S.; Lekchaum, S.; Tipayakul, C.

2015-05-01

This study is a part of an on-going work to develop a computational model of Thai Research Reactor (TRR-1/M1) which is capable of accurately predicting the neutron flux level and spectrum. The computational model was created by MCNPX program and the CT (Central Thimble) in-core irradiation facility was selected as the location for validation. The comparison was performed with the typical flux measurement method routinely practiced at TRR-1/M1, that is, the foil activation technique. In this technique, gold foil is irradiated for a certain period of time and the activity of the irradiated target is measured to derive the thermal neutron flux. Additionally, the flux measurement with SPND (self-powered neutron detector) was also performed for comparison. The thermal neutron flux from the MCNPX simulation was found to be 1.79×1013 neutron/cm2s while that from the foil activation measurement was 4.68×1013 neutron/cm2s. On the other hand, the thermal neutron flux from the measurement using SPND was 2.47×1013 neutron/cm2s. An assessment of the differences among the three methods was done. The difference of the MCNPX with the foil activation technique was found to be 67.8% and the difference of the MCNPX with the SPND was found to be 27.8%.

A comparison of energy expenditure estimation of several physical activity monitors.

PubMed

Dannecker, Kathryn L; Sazonova, Nadezhda A; Melanson, Edward L; Sazonov, Edward S; Browning, Raymond C

2013-11-01

Accurately and precisely estimating free-living energy expenditure (EE) is important for monitoring energy balance and quantifying physical activity. Recently, single and multisensor devices have been developed that can classify physical activities, potentially resulting in improved estimates of EE. This study aimed to determine the validity of EE estimation of a footwear-based physical activity monitor and to compare this validity against a variety of research and consumer physical activity monitors. Nineteen healthy young adults (10 men, 9 women) completed a 4-h stay in a room calorimeter. Participants wore a footwear-based physical activity monitor as well as Actical, ActiGraph, IDEEA, DirectLife, and Fitbit devices. Each individual performed a series of postures/activities. We developed models to estimate EE from the footwear-based device, and we used the manufacturer's software to estimate EE for all other devices. Estimated EE using the shoe-based device was not significantly different than measured EE (mean ± SE; 476 ± 20 vs 478 ± 18 kcal, respectively) and had a root-mean-square error of 29.6 kcal (6.2%). The IDEEA and the DirectLlife estimates of EE were not significantly different than the measured EE, but the ActiGraph and the Fitbit devices significantly underestimated EE. Root-mean-square errors were 93.5 (19%), 62.1 kcal (14%), 88.2 kcal (18%), 136.6 kcal (27%), 130.1 kcal (26%), and 143.2 kcal (28%) for Actical, DirectLife, IDEEA, ActiGraph, and Fitbit, respectively. The shoe-based physical activity monitor provides a valid estimate of EE, whereas the other physical activity monitors tested have a wide range of validity when estimating EE. Our results also demonstrate that estimating EE based on classification of physical activities can be more accurate and precise than estimating EE based on total physical activity.

A new system model for radar polarimeters

NASA Technical Reports Server (NTRS)

Freeman, Anthony

1991-01-01

The validity of the 2 x 2 receive R and transmit T model for radar polarimeter systems, first proposed by Zebker et al. (1987), is questioned. The model is found to be invalid for many practical realizations of radar polarimeters, which can lead to significant errors in the calibration of polarimetric radar images. A more general model is put forward, which addresses the system defects which cause the 2 x 2 model to break down. By measuring one simple parameter from a polarimetric active radar calibration (PARC), it is possible to transform the scattering matrix measurements made by a radar polarimeter to a format compatible with a 2 x 2 R and T matrix model. Alternatively, the PARC can be used to verify the validity of the 2 x 2 model for any polarimetric radar system. Recommendations for the use of PARCs in polarimetric calibration and to measure the orientation angle of the horizontal (H) and vertical (V) coordinate system are also presented.

A new system model for radar polarimeters

NASA Astrophysics Data System (ADS)

Freeman, Anthony

1991-09-01

The validity of the 2 x 2 receive R and transmit T model for radar polarimeter systems, first proposed by Zebker et al. (1987), is questioned. The model is found to be invalid for many practical realizations of radar polarimeters, which can lead to significant errors in the calibration of polarimetric radar images. A more general model is put forward, which addresses the system defects which cause the 2 x 2 model to break down. By measuring one simple parameter from a polarimetric active radar calibration (PARC), it is possible to transform the scattering matrix measurements made by a radar polarimeter to a format compatible with a 2 x 2 R and T matrix model. Alternatively, the PARC can be used to verify the validity of the 2 x 2 model for any polarimetric radar system. Recommendations for the use of PARCs in polarimetric calibration and to measure the orientation angle of the horizontal (H) and vertical (V) coordinate system are also presented.

Validation of the new trapped environment AE9/AP9/SPM at low Earth orbit

NASA Astrophysics Data System (ADS)

Badavi, Francis F.

2014-09-01

The completion of the international space station (ISS) in 2011 has provided the space research community an ideal proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the validation of radiation environmental models, nuclear transport codes and nuclear reaction cross sections. Indeed, prior measurements on the space transportation system (STS; shuttle) provided vital information impacting both the environmental models and the nuclear transport code developments by indicating the need for an improved dynamic model of the low Earth orbit (LEO) trapped environment. Additional studies using thermo-luminescent detector (TLD), tissue equivalent proportional counter (TEPC) area monitors, and computer aided design (CAD) model of earlier ISS configurations, confirmed STS observations that, as input, computational dosimetry requires an environmental model with dynamic and directional (anisotropic) behavior, as well as an accurate six degree of freedom (DOF) definition of the vehicle attitude and orientation along the orbit of ISS. At LEO, a vehicle encounters exposure from trapped particles and attenuated galactic cosmic rays (GCR). Within the trapped field, a challenge arises from properly estimating the amount of exposure acquired. There exist a number of models to define the intensities of the trapped particles during the solar quiet and active times. At active times, solar energetic particles (SEP) generated by solar flare or coronal mass ejection (CME) also contribute to the exposure at high northern and southern latitudes. Among the more established trapped models are the historic and popular AE8/AP8, dating back to the 1980s, the historic and less popular CRRES electron/proton, dating back to 1990s and the recently released AE9/AP9/SPM. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four solar cycles dating back to the 1970s, roughly representing 40 years of data collection. In contrast, the older AE8/AP8 and CRRES models were limited to only a few months of measurements taken during the prior solar minima and maxima. The dual goal of this paper is to first validate the AE8/AP8 and AE9/AP9/SPM trapped models against ISS dosemetric measurements for a silicon based detector, to assess the improvements in the AE9/AP9/SPM model as compared to AE8/AP8 model. The validation is done at selected target points within ISS-6A configuration during its passage through the south Atlantic anomaly (SAA). For such validation, only the isotropic spectrum of either model is needed. As a second goal, the isotropic spectra of both trapped models are re-casted into anisotropic spectra by modulating them with a measurement derived angular formalism which is applicable to trapped protons. Since at LEO electrons have minimal exposure contribution, the paper ignores the AE8 and AE9 component of the models and presents the angular validation of AP8 and AP9 against measurements from the compact environment anomaly sensor (CEASE) science instrument package, flown onboard the tri-service experiment-5 (TSX-5) satellite during the period of June 2000-July 2006. The spin stabilized satellite was flown in a 410 × 1710 km, 69° inclination orbit, allowing it to be exposed to a broad range of LEO regime. Particular emphasize is put on the validation of proton flux profiles at differential 40 MeV and integral >40 MeV, in the vicinity of SAA where protons exhibit east-west (EW) anisotropy and have a relatively narrow pitch angle distribution. Within SAA, the EW anisotropy results in different level of exposure to each side of CEASE instrument package, allowing the extraction of anisotropic proton spectra from the measurements. While the magnitude of the EW effect at LEO depends on a multitude of factors such as trapped proton energy, orientation of the spacecraft along the velocity vector and altitude of the spacecraft, for this part, the paper draws quantitative conclusions on the combined effect of proton pitch angle and EW anomaly.

GASAKe: forecasting landslide activations by a genetic-algorithms-based hydrological model

NASA Astrophysics Data System (ADS)

Terranova, O. G.; Gariano, S. L.; Iaquinta, P.; Iovine, G. G. R.

2015-07-01

GASAKe is a new hydrological model aimed at forecasting the triggering of landslides. The model is based on genetic algorithms and allows one to obtain thresholds for the prediction of slope failures using dates of landslide activations and rainfall series. It can be applied to either single landslides or a set of similar slope movements in a homogeneous environment. Calibration of the model provides families of optimal, discretized solutions (kernels) that maximize the fitness function. Starting from the kernels, the corresponding mobility functions (i.e., the predictive tools) can be obtained through convolution with the rain series. The base time of the kernel is related to the magnitude of the considered slope movement, as well as to the hydro-geological complexity of the site. Generally, shorter base times are expected for shallow slope instabilities compared to larger-scale phenomena. Once validated, the model can be applied to estimate the timing of future landslide activations in the same study area, by employing measured or forecasted rainfall series. Examples of application of GASAKe to a medium-size slope movement (the Uncino landslide at San Fili, in Calabria, southern Italy) and to a set of shallow landslides (in the Sorrento Peninsula, Campania, southern Italy) are discussed. In both cases, a successful calibration of the model has been achieved, despite unavoidable uncertainties concerning the dates of occurrence of the slope movements. In particular, for the Sorrento Peninsula case, a fitness of 0.81 has been obtained by calibrating the model against 10 dates of landslide activation; in the Uncino case, a fitness of 1 (i.e., neither missing nor false alarms) has been achieved using five activations. As for temporal validation, the experiments performed by considering further dates of activation have also proved satisfactory. In view of early-warning applications for civil protection, the capability of the model to simulate the occurrences of the Uncino landslide has been tested by means of a progressive, self-adaptive procedure. Finally, a sensitivity analysis has been performed by taking into account the main parameters of the model. The obtained results are quite promising, given the high performance of the model against different types of slope instabilities characterized by several historical activations. Nevertheless, further refinements are still needed for application to landslide risk mitigation within early-warning and decision-support systems.

GASAKe: forecasting landslide activations by a genetic-algorithms based hydrological model

NASA Astrophysics Data System (ADS)

Terranova, O. G.; Gariano, S. L.; Iaquinta, P.; Iovine, G. G. R.

2015-02-01

GASAKe is a new hydrological model aimed at forecasting the triggering of landslides. The model is based on genetic-algorithms and allows to obtaining thresholds of landslide activation from the set of historical occurrences and from the rainfall series. GASAKe can be applied to either single landslides or set of similar slope movements in a homogeneous environment. Calibration of the model is based on genetic-algorithms, and provides for families of optimal, discretized solutions (kernels) that maximize the fitness function. Starting from these latter, the corresponding mobility functions (i.e. the predictive tools) can be obtained through convolution with the rain series. The base time of the kernel is related to the magnitude of the considered slope movement, as well as to hydro-geological complexity of the site. Generally, smaller values are expected for shallow slope instabilities with respect to large-scale phenomena. Once validated, the model can be applied to estimate the timing of future landslide activations in the same study area, by employing recorded or forecasted rainfall series. Example of application of GASAKe to a medium-scale slope movement (the Uncino landslide at San Fili, in Calabria, Southern Italy) and to a set of shallow landslides (in the Sorrento Peninsula, Campania, Southern Italy) are discussed. In both cases, a successful calibration of the model has been achieved, despite unavoidable uncertainties concerning the dates of landslide occurrence. In particular, for the Sorrento Peninsula case, a fitness of 0.81 has been obtained by calibrating the model against 10 dates of landslide activation; in the Uncino case, a fitness of 1 (i.e. neither missing nor false alarms) has been achieved against 5 activations. As for temporal validation, the experiments performed by considering the extra dates of landslide activation have also proved satisfactory. In view of early-warning applications for civil protection purposes, the capability of the model to simulate the occurrences of the Uncino landslide has been tested by means of a progressive, self-adaptive procedure. Finally, a sensitivity analysis has been performed by taking into account the main parameters of the model. The obtained results are quite promising, given the high performance of the model obtained against different types of slope instabilities, characterized by several historical activations. Nevertheless, further refinements are still needed for applications to landslide risk mitigation within early-warning and decision-support systems.

Risk-Based Tailoring of the Verification, Validation, and Accreditation/Acceptance Processes (Adaptation fondee sur le risque, des processus de verification, de validation, et d’accreditation/d’acceptation)

DTIC Science & Technology

2012-04-01

Systems Concepts and Integration SET Sensors and Electronics Technology SISO Simulation Interoperability Standards Organization SIW Simulation...conjunction with 2006 Fall SIW 2006 September SISO Standards Activity Committee approved beginning IEEE balloting 2006 October IEEE Project...019 published 2008 June Edinborough, UK Held in conjunction with 2008 Euro- SIW 2008 September Laurel, MD, US Work on Composite Model 2008 December

Associations of leisure-time physical activity with balance and lower extremity strength: a validation of the neuromuscular part of the Physical Activity Pie.

PubMed

Lindström, Paula J; Suni, Jaana H; Nygård, Clas-Håkan

2009-07-01

The importance of neuromuscular-type exercise (NME) has been recognized in recent recommendations for public health. However, the knowledge on associations and dose response of different types of leisure-time physical activity (LTPA) with musculoskeletal fitness and health is incomplete. This study evaluated the validity of the NME recommendation for public health introduced by the Physical Activity Pie. Engagement in LTPA and health-related fitness were assessed in 2 consecutive studies with the same adult population age 30 to 69 years (n = 575). Cross-sectional associations between different LTPA types and motor and musculoskeletal fitness were examined by logistic-regression models. Engagement in NME was associated with good static and dynamic balance and lower extremity strength. The highest odds ratios (OR) were found between brisk NME and static balance (most vs least fit OR = 2.39, moderate vs least fit OR = 1.94) and brisk NME and leg strength (more vs least fit OR = 2.10). Some associations were also found between brisk aerobic exercise and good balance. This cross-sectional study suggests that the recommendation for NME in the Physical Activity Pie is valid in terms of balance and leg strength, the 2 major fitness factors related to mobility functioning, especially among aging adults.

Prediction-error in the context of real social relationships modulates reward system activity.

PubMed

Poore, Joshua C; Pfeifer, Jennifer H; Berkman, Elliot T; Inagaki, Tristen K; Welborn, Benjamin L; Lieberman, Matthew D

2012-01-01

The human reward system is sensitive to both social (e.g., validation) and non-social rewards (e.g., money) and is likely integral for relationship development and reputation building. However, data is sparse on the question of whether implicit social reward processing meaningfully contributes to explicit social representations such as trust and attachment security in pre-existing relationships. This event-related fMRI experiment examined reward system prediction-error activity in response to a potent social reward-social validation-and this activity's relation to both attachment security and trust in the context of real romantic relationships. During the experiment, participants' expectations for their romantic partners' positive regard of them were confirmed (validated) or violated, in either positive or negative directions. Primary analyses were conducted using predefined regions of interest, the locations of which were taken from previously published research. Results indicate that activity for mid-brain and striatal reward system regions of interest was modulated by social reward expectation violation in ways consistent with prior research on reward prediction-error. Additionally, activity in the striatum during viewing of disconfirmatory information was associated with both increases in post-scan reports of attachment anxiety and decreases in post-scan trust, a finding that follows directly from representational models of attachment and trust.

Reliability and Validity of 2 Self-Report Measures to Assess Sedentary Behavior in Older Adults.

PubMed

Gennuso, Keith P; Matthews, Charles E; Colbert, Lisa H

2015-05-01

The purpose of this study was to examine the reliability and validity of 2 currently available physical activity surveys for assessing time spent in sedentary behavior (SB) in older adults. Fifty-eight adults (≥65 years) completed the Yale Physical Activity Survey for Older Adults (YPAS) and Community Health Activities Model Program for Seniors (CHAMPS) before and after a 10-day period during which they wore an ActiGraph accelerometer (ACC). Intraclass correlation coefficients (ICC) examined test-retest reliability. Overall percent agreement and a kappa statistic examined YPAS validity. Lin's concordance correlation, Pearson correlation, and Bland-Altman analysis examined CHAMPS validity. Both surveys had moderate test-retest reliability (ICC: YPAS = 0.59 (P < .001), CHAMPS = 0.64 (P < .001)) and significantly underestimated SB time. Agreement between YPAS and ACC was low (κ = -0.0003); however, there was a linear increase (P < .01) in ACC-derived SB time across YPAS response categories. There was poor agreement between ACC-derived SB and CHAMPS (Lin's r = .005; 95% CI, -0.010 to 0.020), and no linear trend across CHAMPS quartiles (P = .53). Neither of the surveys should be used as the sole measure of SB in a study; though the YPAS has the ability to rank individuals, providing it with some merit for use in correlational SB research.

Internal validity of inter-digital web pinching as a model for perceptual diffuse noxious inhibitory controls-induced hypoalgesia in healthy humans.

PubMed

Streff, Anouk; Michaux, Gilles; Anton, Fernand

2011-01-01

Hot and ice-water immersions are commonly used for heterotopic noxious counter-stimulation (HNCS) in investigations on endogenous pain modulation. However, coincident sympathetic thermoregulatory activity does not allow to differentiate between perceptual hypoalgesia related to baroreflex sensitivity (BRS) or diffuse noxious inhibitory controls (DNIC). The present study analysed the internal validity of another supposedly less confounded tonic pain model (inter-digital web pinching; IWP) regarding its potential as DNIC trigger. We performed a randomized controlled study in 24 healthy gender-matched drug-free volunteers aged 21-54 (median 25) years. The study protocol comprised the assessment of mechanical and thermal perceptual wind-up before and after an IWP (15N) or hot water immersion trial (HIT; 47.5°C) of 2 min duration. Wind-up was induced either by 10 repetitive (1Hz) contact heat (max. 49°C; 5×5 mm thermode) or ballistic impact stimuli (0.5g at 9 m/s) on the phalanges of the non-dominant hand. Cardiovascular activity, pain experience and corrugator muscle activity were continuously monitored. Although both HNCS forms produced a similar pain experience (45% of scale), a more pronounced cardiovascular activity was observable for the HIT (P<0.01). This indicates a higher baroreceptor activity and stronger contamination of painful water immersion by BRS-related hypoalgesia. Regardless of pain modality, wind-up was significantly reduced by HNCS, although this was stronger for painful water immersion than for noxious pinching (P<0.01). The HNCS types allow a differentiation between BRS-related and DNIC-like hypoalgesia. IWP proved its validity for DNIC induction, being practically non-confounded by BRS. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Assessing Requirements Quality through Requirements Coverage

NASA Technical Reports Server (NTRS)

Rajan, Ajitha; Heimdahl, Mats; Woodham, Kurt

2008-01-01

In model-based development, the development effort is centered around a formal description of the proposed software system the model. This model is derived from some high-level requirements describing the expected behavior of the software. For validation and verification purposes, this model can then be subjected to various types of analysis, for example, completeness and consistency analysis [6], model checking [3], theorem proving [1], and test-case generation [4, 7]. This development paradigm is making rapid inroads in certain industries, e.g., automotive, avionics, space applications, and medical technology. This shift towards model-based development naturally leads to changes in the verification and validation (V&V) process. The model validation problem determining that the model accurately captures the customer's high-level requirements has received little attention and the sufficiency of the validation activities has been largely determined through ad-hoc methods. Since the model serves as the central artifact, its correctness with respect to the users needs is absolutely crucial. In our investigation, we attempt to answer the following two questions with respect to validation (1) Are the requirements sufficiently defined for the system? and (2) How well does the model implement the behaviors specified by the requirements? The second question can be addressed using formal verification. Nevertheless, the size and complexity of many industrial systems make formal verification infeasible even if we have a formal model and formalized requirements. Thus, presently, there is no objective way of answering these two questions. To this end, we propose an approach based on testing that, when given a set of formal requirements, explores the relationship between requirements-based structural test-adequacy coverage and model-based structural test-adequacy coverage. The proposed technique uses requirements coverage metrics defined in [9] on formal high-level software requirements and existing model coverage metrics such as the Modified Condition and Decision Coverage (MC/DC) used when testing highly critical software in the avionics industry [8]. Our work is related to Chockler et al. [2], but we base our work on traditional testing techniques as opposed to verification techniques.

A pharmacophore model specific to active site of CYP1A2 with a novel molecular modeling explorer and CoMFA.

PubMed

Zhang, Tao; Wei, Dong-Qing; Chou, Kuo-Chen

2012-03-01

Comparative molecular field analysis (CoMFA) is a widely used 3D-QSAR method by which we can investigate the potential relation between biological activity of compounds and their structural features. In this study, a new application of this approach is presented by combining the molecular modeling with a new developed pharmacophore model specific to CYP1A2 active site. During constructing the model, we used the molecular dynamics simulation and molecular docking method to select the sensible binding conformations for 17 CYP1A2 substrates based on the experimental data. Subsequently, the results obtained via the alignment of binding conformations of substrates were projected onto the active- site residues, upon which a simple blueprint of active site was produced. It was validated by the experimental and computational results that the model did exhibit the high degree of rationality and provide useful insights into the substrate binding. It is anticipated that our approach can be extended to investigate the protein-ligand interactions for many other enzyme-catalyzed systems as well.

Student Attitudes towards and Use of ICT in Course Study, Work and Social Activity: A Technology Acceptance Model Approach

ERIC Educational Resources Information Center

Edmunds, Rob; Thorpe, Mary; Conole, Grainne

2012-01-01

The increasing use of information and communication technology (ICT) in higher education has been explored largely in relation to student experience of coursework and university life. Students' lives and experience beyond the university have been largely unexplored. Research into student experience of ICT used a validated model--the technology…

Functional and Behavioral Product Information Representation and Consistency Validation for Collaboration in Product Lifecycle Activities

ERIC Educational Resources Information Center

Baysal, Mehmet Murat

2012-01-01

Information models that represent the function, assembly and behavior of artifacts are critical in the conceptual development of a product and its evaluation. Much research has been conducted in this area; however, existing models do not relate function, behavior and structure in a comprehensive and consistent way. In this work, NIST's Core…

Integrated modeling analysis of a novel hexapod and its application in active surface

NASA Astrophysics Data System (ADS)

Yang, Dehua; Zago, Lorenzo; Li, Hui; Lambert, Gregory; Zhou, Guohua; Li, Guoping

2011-09-01

This paper presents the concept and integrated modeling analysis of a novel mechanism, a 3-CPS/RPPS hexapod, for supporting segmented reflectors for radio telescopes and eventually segmented mirrors of optical telescopes. The concept comprises a novel type of hexapod with an original organization of actuators hence degrees of freedom, based on a swaying arm based design concept. Afterwards, with specially designed connecting joints between panels/segments, an iso-static master-slave active surface concept can be achieved for any triangular and/or hexagonal panel/segment pattern. The integrated modeling comprises all the multifold sizing and performance aspects which must be evaluated concurrently in order to optimize and validate the design and the configuration. In particular, comprehensive investigation of kinematic behavior, dynamic analysis, wave-front error and sensitivity analysis are carried out, where, frequently used tools like MATLAB/SimMechanics, CALFEM and ANSYS are used. Especially, we introduce the finite element method as a competent approach for analyses of the multi-degree of freedom mechanism. Some experimental verifications already performed validating single aspects of the integrated concept are also presented with the results obtained.

Prospective validation of pathologic complete response models in rectal cancer: Transferability and reproducibility.

PubMed

van Soest, Johan; Meldolesi, Elisa; van Stiphout, Ruud; Gatta, Roberto; Damiani, Andrea; Valentini, Vincenzo; Lambin, Philippe; Dekker, Andre

2017-09-01

Multiple models have been developed to predict pathologic complete response (pCR) in locally advanced rectal cancer patients. Unfortunately, validation of these models normally omit the implications of cohort differences on prediction model performance. In this work, we will perform a prospective validation of three pCR models, including information whether this validation will target transferability or reproducibility (cohort differences) of the given models. We applied a novel methodology, the cohort differences model, to predict whether a patient belongs to the training or to the validation cohort. If the cohort differences model performs well, it would suggest a large difference in cohort characteristics meaning we would validate the transferability of the model rather than reproducibility. We tested our method in a prospective validation of three existing models for pCR prediction in 154 patients. Our results showed a large difference between training and validation cohort for one of the three tested models [Area under the Receiver Operating Curve (AUC) cohort differences model: 0.85], signaling the validation leans towards transferability. Two out of three models had a lower AUC for validation (0.66 and 0.58), one model showed a higher AUC in the validation cohort (0.70). We have successfully applied a new methodology in the validation of three prediction models, which allows us to indicate if a validation targeted transferability (large differences between training/validation cohort) or reproducibility (small cohort differences). © 2017 American Association of Physicists in Medicine.

Deep Impact Sequence Planning Using Multi-Mission Adaptable Planning Tools With Integrated Spacecraft Models

NASA Technical Reports Server (NTRS)

Wissler, Steven S.; Maldague, Pierre; Rocca, Jennifer; Seybold, Calina

2006-01-01

The Deep Impact mission was ambitious and challenging. JPL's well proven, easily adaptable multi-mission sequence planning tools combined with integrated spacecraft subsystem models enabled a small operations team to develop, validate, and execute extremely complex sequence-based activities within very short development times. This paper focuses on the core planning tool used in the mission, APGEN. It shows how the multi-mission design and adaptability of APGEN made it possible to model spacecraft subsystems as well as ground assets throughout the lifecycle of the Deep Impact project, starting with models of initial, high-level mission objectives, and culminating in detailed predictions of spacecraft behavior during mission-critical activities.

A curved piezo-structure model: implications on active structural acoustic control.

PubMed

Henry, J K; Clark, R L

1999-09-01

Current research in Active Structural Acoustic Control (ASAC) relies heavily upon accurately capturing the application physics associated with the structure being controlled. The application of ASAC to aircraft interior noise requires a greater understanding of the dynamics of the curved panels which compose the skin of an aircraft fuselage. This paper presents a model of a simply supported curved panel with attached piezoelectric transducers. The model is validated by comparison to previous work. Further, experimental results for a simply supported curved panel test structure are presented in support of the model. The curvature is shown to affect substantially the dynamics of the panel, the integration of transducers, and the bandwidth required for structural acoustic control.

Infrared Algorithm Development for Ocean Observations with EOS/MODIS

NASA Technical Reports Server (NTRS)

Brown, Otis B.

1997-01-01

Efforts continue under this contract to develop algorithms for the computation of sea surface temperature (SST) from MODIS infrared measurements. This effort includes radiative transfer modeling, comparison of in situ and satellite observations, development and evaluation of processing and networking methodologies for algorithm computation and data accession, evaluation of surface validation approaches for IR radiances, development of experimental instrumentation, and participation in MODIS (project) related activities. Activities in this contract period have focused on radiative transfer modeling, evaluation of atmospheric correction methodologies, undertake field campaigns, analysis of field data, and participation in MODIS meetings.

Validation of Hill-Type Muscle Models in Relation to Neuromuscular Recruitment and Force–Velocity Properties: Predicting Patterns of In Vivo Muscle Force

PubMed Central

Biewener, Andrew A.; Wakeling, James M.; Lee, Sabrina S.; Arnold, Allison S.

2014-01-01

We review here the use and reliability of Hill-type muscle models to predict muscle performance under varying conditions, ranging from in situ production of isometric force to in vivo dynamics of muscle length change and force in response to activation. Muscle models are frequently used in musculoskeletal simulations of movement, particularly when applied to studies of human motor performance in which surgically implanted transducers have limited use. Musculoskeletal simulations of different animal species also are being developed to evaluate comparative and evolutionary aspects of locomotor performance. However, such models are rarely validated against direct measures of fascicle strain or recordings of muscle–tendon force. Historically, Hill-type models simplify properties of whole muscle by scaling salient properties of single fibers to whole muscles, typically accounting for a muscle’s architecture and series elasticity. Activation of the model’s single contractile element (assigned the properties of homogenous fibers) is also simplified and is often based on temporal features of myoelectric (EMG) activation recorded from the muscle. Comparison of standard one-element models with a novel two-element model and with in situ and in vivo measures of EMG, fascicle strain, and force recorded from the gastrocnemius muscles of goats shows that a two-element Hill-type model, which allows independent recruitment of slow and fast units, better predicts temporal patterns of in situ and in vivo force. Recruitment patterns of slow/fast units based on wavelet decomposition of EMG activity in frequency–time space are generally correlated with the intensity spectra of the EMG signals, the strain rates of the fascicles, and the muscle–tendon forces measured in vivo, with faster units linked to greater strain rates and to more rapid forces. Using direct measures of muscle performance to further test Hill-type models, whether traditional or more complex, remains critical for establishing their accuracy and essential for verifying their applicability to scientific and clinical studies of musculoskeletal function. PMID:24928073

Human impact parameterization in global hydrological models improves estimates of monthly discharges and hydrological extremes: a multi-model validation study

NASA Astrophysics Data System (ADS)

Veldkamp, Ted; Ward, Philip; de Moel, Hans; Aerts, Jeroen; Muller Schmied, Hannes; Portmann, Felix; Zhao, Fang; Gerten, Dieter; Masaki, Yoshimitsu; Pokhrel, Yadu; Satoh, Yusuke; Gosling, Simon; Zaherpour, Jamal; Wada, Yoshihide

2017-04-01

Human impacts on freshwater resources and hydrological features form the core of present-day water related hazards, like flooding, droughts, water scarcity, and water quality issues. Driven by the societal and scientific needs to correctly model such water related hazards a fair amount of resources has been invested over the past decades to represent human activities and their interactions with the hydrological cycle in global hydrological models (GHMs). Use of these GHMs - including the human dimension - is widespread, especially in water resources research. Evaluation or comparative assessments of the ability of such GHMs to represent real-world hydrological conditions are, unfortunately, however often limited to (near-)natural river basins. Such studies are, therefore, not able to test the model representation of human activities and its associated impact on estimates of freshwater resources or assessments of hydrological extremes. Studies that did perform a validation exercise - including the human dimension and looking into managed catchments - either focused only on one hydrological model, and/or incorporated only a few data points (i.e. river basins) for validation. To date, a comprehensive comparative analysis that evaluates whether and where incorporating the human dimension actually improves the performance of different GHMs with respect to their representation of real-world hydrological conditions and extremes is missing. The absence of such study limits the potential benchmarking of GHMs and their outcomes in hydrological hazard and risk assessments significantly, potentially hampering incorporation of GHMs and their modelling results in actual policy making and decision support with respect to water resources management. To address this issue, we evaluate in this study the performance of five state-of-the-art GHMs that include anthropogenic activities in their modelling scheme, with respect to their representation of monthly discharges and hydrological extremes. To this end, we compared their monthly discharge simulations under a naturalized and a time-dependent human impact simulation, with monthly GRDC river discharge observations of 2,412 stations over the period 1971-2010. Evaluation metrics that were used to assess the performance of the GHMs included the modified Kling-Gupta Efficiency index, and its individual parameters describing the linear correlation coefficient, the bias ratio, and the variability ratio, as well as indicators for hydrological extremes (Q90, Q10). Our results show that inclusion of anthropogenic activities in the modelling framework generally enhances the overall performance of the GHMs studied, mainly driven by bias-improvements, and to a lesser extent due to changes in modelled hydrological variability. Whilst the inclusion of anthropogenic activities takes mainly effect in the managed catchments, a significant share of the (near-)natural catchments is influenced as well. To get estimates of hydrological extremes right, especially when looking at low-flows, inclusion of human activities is paramount. Whilst high-flow estimates are mainly decreased, impact of human activities on low-flows is ambiguous, i.e. due to the relative importance of the timing of return flows and reservoir operations. Even with inclusion of the human dimension we find, nevertheless, a persistent overestimation of hydrological extremes across all models, which should be accounted for in future assessments.

Assessing participation in community-based physical activity programs in Brazil.

PubMed

Reis, Rodrigo S; Yan, Yan; Parra, Diana C; Brownson, Ross C

2014-01-01

This study aimed to develop and validate a risk prediction model to examine the characteristics that are associated with participation in community-based physical activity programs in Brazil. We used pooled data from three surveys conducted from 2007 to 2009 in state capitals of Brazil with 6166 adults. A risk prediction model was built considering program participation as an outcome. The predictive accuracy of the model was quantified through discrimination (C statistic) and calibration (Brier score) properties. Bootstrapping methods were used to validate the predictive accuracy of the final model. The final model showed sex (women: odds ratio [OR] = 3.18, 95% confidence interval [CI] = 2.14-4.71), having less than high school degree (OR = 1.71, 95% CI = 1.16-2.53), reporting a good health (OR = 1.58, 95% CI = 1.02-2.24) or very good/excellent health (OR = 1.62, 95% CI = 1.05-2.51), having any comorbidity (OR = 1.74, 95% CI = 1.26-2.39), and perceiving the environment as safe to walk at night (OR = 1.59, 95% CI = 1.18-2.15) as predictors of participation in physical activity programs. Accuracy indices were adequate (C index = 0.778, Brier score = 0.031) and similar to those obtained from bootstrapping (C index = 0.792, Brier score = 0.030). Sociodemographic and health characteristics as well as perceptions of the environment are strong predictors of participation in community-based programs in selected cities of Brazil.

The space shuttle payload planning working groups. Volume 8: Earth and ocean physics

NASA Technical Reports Server (NTRS)

1973-01-01

The findings and recommendations of the Earth and Ocean Physics working group of the space shuttle payload planning activity are presented. The requirements for the space shuttle mission are defined as: (1) precision measurement for earth and ocean physics experiments, (2) development and demonstration of new and improved sensors and analytical techniques, (3) acquisition of surface truth data for evaluation of new measurement techniques, (4) conduct of critical experiments to validate geophysical phenomena and instrumental results, and (5) development and validation of analytical/experimental models for global ocean dynamics and solid earth dynamics/earthquake prediction. Tables of data are presented to show the flight schedule estimated costs, and the mission model.

Development and validation of an instrument to assess future orientation and resilience in adolescence.

PubMed

Di Maggio, Ilaria; Ginevra, Maria Cristina; Nota, Laura; Soresi, Salvatore

2016-08-01

The study is aimed at providing the development and initial validation of the Design My Future (DMF), which may be administered in career counseling and research activities to assess adolescents' future orientation and resilience. Two studies with two independent samples of Italian adolescents were conducted to examine psychometric requisites of DMF. Specifically, in the first study, after developing items and examined the content validity, the factorial structure, reliability and discriminant validity of the DMF were tested. In the second study, the measurement invariance across gender, conducing a sequence of nested CFA models, was evaluated. Results showed good psychometric support for the instrument with Italian adolescents. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Guiding Development Based Approach Practicum Vertebrates Taxonomy Scientific Study Program for Students of Biology Education

NASA Astrophysics Data System (ADS)

Arieska, M.; Syamsurizal, S.; Sumarmin, R.

2018-04-01

Students having difficulty in identifying and describing the vertebrate animals as well as less skilled in science process as practical. Increased expertise in scientific skills, one of which is through practical activities using practical guidance based on scientific approach. This study aims to produce practical guidance vertebrate taxonomy for biology education students PGRI STKIP West Sumatra valid. This study uses a model of Plomp development consisting of three phases: the initial investigation, floating or prototype stage, and the stage of assessment. Data collection instruments used in this study is a validation sheet guiding practicum. Data were analyzed descriptively based on data obtained from the field. The result of the development of practical guidance vertebrate taxonomic validity value of 3.22 is obtained with very valid category. Research and development has produced a practical guide based vertebrate taxonomic scientific approach very valid.

Comparative docking and CoMFA analysis of curcumine derivatives as HIV-1 integrase inhibitors.

PubMed

Gupta, Pawan; Garg, Prabha; Roy, Nilanjan

2011-08-01

The docking studies and comparative molecular field analysis (CoMFA) were performed on highly active molecules of curcumine derivatives against 3' processing activity of HIV-1 integrase (IN) enzyme. The optimum CoMFA model was selected with statistically significant cross-validated r(2) value of 0.815 and non-cross validated r (2) value of 0.99. The common pharmacophore of highly active molecules was used for screening of HIV-1 IN inhibitors. The high contribution of polar interactions in pharmacophore mapping is well supported by docking and CoMFA results. The results of docking, CoMFA, and pharmacophore mapping give structural insights as well as important binding features of curcumine derivatives as HIV-1 IN inhibitors which can provide guidance for the rational design of novel HIV-1 IN inhibitors.

The Development of Multicultural Counselling Competencies (MCC) Training Module Based on MCC Matrix Model by Sue et al. (1992)

ERIC Educational Resources Information Center

Anuar, Azad Athahiri; Rozubi, Norsayyidatina Che; Abdullah, Haslee Sharil

2015-01-01

The aims of this study were to develop and validate a MCC training module for trainee counselor based on MCC matrix model by Sue et al. (1992). This module encompassed five sub modules and 11 activities developed along the concepts and components of the MCC matrix model developed by Sue, Arredondo dan McDavis (1992). The design method used in this…

A multi-source satellite data approach for modelling Lake Turkana water level: Calibration and validation using satellite altimetry data

USGS Publications Warehouse

Velpuri, N.M.; Senay, G.B.; Asante, K.O.

2012-01-01

Lake Turkana is one of the largest desert lakes in the world and is characterized by high degrees of interand intra-annual fluctuations. The hydrology and water balance of this lake have not been well understood due to its remote location and unavailability of reliable ground truth datasets. Managing surface water resources is a great challenge in areas where in-situ data are either limited or unavailable. In this study, multi-source satellite-driven data such as satellite-based rainfall estimates, modelled runoff, evapotranspiration, and a digital elevation dataset were used to model Lake Turkana water levels from 1998 to 2009. Due to the unavailability of reliable lake level data, an approach is presented to calibrate and validate the water balance model of Lake Turkana using a composite lake level product of TOPEX/Poseidon, Jason-1, and ENVISAT satellite altimetry data. Model validation results showed that the satellitedriven water balance model can satisfactorily capture the patterns and seasonal variations of the Lake Turkana water level fluctuations with a Pearson's correlation coefficient of 0.90 and a Nash-Sutcliffe Coefficient of Efficiency (NSCE) of 0.80 during the validation period (2004-2009). Model error estimates were within 10% of the natural variability of the lake. Our analysis indicated that fluctuations in Lake Turkana water levels are mainly driven by lake inflows and over-the-lake evaporation. Over-the-lake rainfall contributes only up to 30% of lake evaporative demand. During the modelling time period, Lake Turkana showed seasonal variations of 1-2m. The lake level fluctuated in the range up to 4m between the years 1998-2009. This study demonstrated the usefulness of satellite altimetry data to calibrate and validate the satellite-driven hydrological model for Lake Turkana without using any in-situ data. Furthermore, for Lake Turkana, we identified and outlined opportunities and challenges of using a calibrated satellite-driven water balance model for (i) quantitative assessment of the impact of basin developmental activities on lake levels and for (ii) forecasting lake level changes and their impact on fisheries. From this study, we suggest that globally available satellite altimetry data provide a unique opportunity for calibration and validation of hydrologic models in ungauged basins. ?? Author(s) 2012.

Thermal Diagnostics with the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory: A Validated Method for Differential Emission Measure Inversions

NASA Astrophysics Data System (ADS)

Cheung, Mark C. M.; Boerner, P.; Schrijver, C. J.; Testa, P.; Chen, F.; Peter, H.; Malanushenko, A.

2015-07-01

We present a new method for performing differential emission measure (DEM) inversions on narrow-band EUV images from the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory. The method yields positive definite DEM solutions by solving a linear program. This method has been validated against a diverse set of thermal models of varying complexity and realism. These include (1) idealized Gaussian DEM distributions, (2) 3D models of NOAA Active Region 11158 comprising quasi-steady loop atmospheres in a nonlinear force-free field, and (3) thermodynamic models from a fully compressible, 3D MHD simulation of active region (AR) corona formation following magnetic flux emergence. We then present results from the application of the method to AIA observations of Active Region 11158, comparing the region's thermal structure on two successive solar rotations. Additionally, we show how the DEM inversion method can be adapted to simultaneously invert AIA and Hinode X-ray Telescope data, and how supplementing AIA data with the latter improves the inversion result. The speed of the method allows for routine production of DEM maps, thus facilitating science studies that require tracking of the thermal structure of the solar corona in time and space.

Development of classification models for identifying "true" P-glycoprotein (P-gp) inhibitors through inhibition, ATPase activation and monolayer efflux assays.

PubMed

Rapposelli, Simona; Coi, Alessio; Imbriani, Marcello; Bianucci, Anna Maria

2012-01-01

P-glycoprotein (P-gp) is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external) validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as "true" P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function.

THERMAL DIAGNOSTICS WITH THE ATMOSPHERIC IMAGING ASSEMBLY ON BOARD THE SOLAR DYNAMICS OBSERVATORY: A VALIDATED METHOD FOR DIFFERENTIAL EMISSION MEASURE INVERSIONS

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

Cheung, Mark C. M.; Boerner, P.; Schrijver, C. J.

We present a new method for performing differential emission measure (DEM) inversions on narrow-band EUV images from the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory. The method yields positive definite DEM solutions by solving a linear program. This method has been validated against a diverse set of thermal models of varying complexity and realism. These include (1) idealized Gaussian DEM distributions, (2) 3D models of NOAA Active Region 11158 comprising quasi-steady loop atmospheres in a nonlinear force-free field, and (3) thermodynamic models from a fully compressible, 3D MHD simulation of active region (AR) corona formation following magneticmore » flux emergence. We then present results from the application of the method to AIA observations of Active Region 11158, comparing the region's thermal structure on two successive solar rotations. Additionally, we show how the DEM inversion method can be adapted to simultaneously invert AIA and Hinode X-ray Telescope data, and how supplementing AIA data with the latter improves the inversion result. The speed of the method allows for routine production of DEM maps, thus facilitating science studies that require tracking of the thermal structure of the solar corona in time and space.« less

BACT Simulation User Guide (Version 7.0)

NASA Technical Reports Server (NTRS)

Waszak, Martin R.

1997-01-01

This report documents the structure and operation of a simulation model of the Benchmark Active Control Technology (BACT) Wind-Tunnel Model. The BACT system was designed, built, and tested at NASA Langley Research Center as part of the Benchmark Models Program and was developed to perform wind-tunnel experiments to obtain benchmark quality data to validate computational fluid dynamics and computational aeroelasticity codes, to verify the accuracy of current aeroservoelasticity design and analysis tools, and to provide an active controls testbed for evaluating new and innovative control algorithms for flutter suppression and gust load alleviation. The BACT system has been especially valuable as a control system testbed.

Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy

PubMed Central

Chesi, Marta; Matthews, Geoffrey M.; Garbitt, Victoria M.; Palmer, Stephen E.; Shortt, Jake; Lefebure, Marcus; Stewart, A. Keith; Johnstone, Ricky W.

2012-01-01

The attrition rate for anticancer drugs entering clinical trials is unacceptably high. For multiple myeloma (MM), we postulate that this is because of preclinical models that overemphasize the antiproliferative activity of drugs, and clinical trials performed in refractory end-stage patients. We validate the Vk*MYC transgenic mouse as a faithful model to predict single-agent drug activity in MM with a positive predictive value of 67% (4 of 6) for clinical activity, and a negative predictive value of 86% (6 of 7) for clinical inactivity. We identify 4 novel agents that should be prioritized for evaluation in clinical trials. Transplantation of Vk*MYC tumor cells into congenic mice selected for a more aggressive disease that models end-stage drug-resistant MM and responds only to combinations of drugs with single-agent activity in untreated Vk*MYC MM. We predict that combinations of standard agents, histone deacetylase inhibitors, bromodomain inhibitors, and hypoxia-activated prodrugs will demonstrate efficacy in the treatment of relapsed MM. PMID:22451422

3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model.

PubMed

Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

2016-04-30

Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q²) value of 0.597 and correlation coefficients (r²) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q² and r² of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r²pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure-activity relationship.

PubMed

Wang, Hui; Jiang, Mingyue; Li, Shujun; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-09-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger ( A. niger ) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models ( R 2  = 0.9346 for A. niger , R 2  = 0.9590 for P. citrinum, ) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

PubMed Central

Wang, Hui; Jiang, Mingyue; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2 = 0.9346 for A. niger, R2 = 0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi. PMID:28989758

Antibacterial Activity of Imidazolium-Based Ionic Liquids Investigated by QSAR Modeling and Experimental Studies.

PubMed

Hodyna, Diana; Kovalishyn, Vasyl; Rogalsky, Sergiy; Blagodatnyi, Volodymyr; Petko, Kirill; Metelytsia, Larisa

2016-09-01

Predictive QSAR models for the inhibitors of B. subtilis and Ps. aeruginosa among imidazolium-based ionic liquids were developed using literary data. The regression QSAR models were created through Artificial Neural Network and k-nearest neighbor procedures. The classification QSAR models were constructed using WEKA-RF (random forest) method. The predictive ability of the models was tested by fivefold cross-validation; giving q(2) = 0.77-0.92 for regression models and accuracy 83-88% for classification models. Twenty synthesized samples of 1,3-dialkylimidazolium ionic liquids with predictive value of activity level of antimicrobial potential were evaluated. For all asymmetric 1,3-dialkylimidazolium ionic liquids, only compounds containing at least one radical with alkyl chain length of 12 carbon atoms showed high antibacterial activity. However, the activity of symmetric 1,3-dialkylimidazolium salts was found to have opposite relationship with the length of aliphatic radical being maximum for compounds based on 1,3-dioctylimidazolium cation. The obtained experimental results suggested that the application of classification QSAR models is more accurate for the prediction of activity of new imidazolium-based ILs as potential antibacterials. © 2016 John Wiley & Sons A/S.

Research study on neck injury lessening with active head restraint using human body FE model.

PubMed

Kitagawa, Yuichi; Yasuki, Tsuyoshi; Hasegawa, Junji

2008-12-01

The objective of this study is to examine the effectiveness of the active head restraint system in reducing neck injury risk of car occupants in low-speed rear impacts. A human body FE model "THUMS" was used to simulate head and neck kinematics of the occupant and to evaluate loading to the neck. Joint capsule strain was calculated to predict neck injury risk as well as NIC. The validity of the model was confirmed comparing its mechanical responses to those in human subjects in the literatures. Seat FE models were also prepared representing one with a fixed head restraint and the other one with an active head restraint system. The active head restraint system was designed to move the head restraint forward and upward when the lower unit was lower unit was loaded by the pelvis. Rear impact simulations were performed assuming a triangular acceleration pulse at a delta-V of 25 km/h. The model reproduced similar head and neck motions to those measured in the human volunteer test, except for active muscular responses. The calculated joint capsule strain also showed a good match with those of PMHS tests in the literature. A rear-impact simulation was conducted using the model with the fixed head restraint. The result revealed that NIC was strongly correlated with the relative acceleration between the head and the torso and that its maximum peak appeared when the head contacted the head restraint. It was also found that joint capsule strain grew in later timing synchronizing with the relative displacement. Another simulation with the active head restraint system showed that both NIC and joint capsule strain were lowered owing to the forward and upward motion of the head restraint. A close investigation of the vertebral motion indicated that the active head restraint reduced the magnitude of shear deformation in the facet joint, which contributed to the strain growth in the fixed head restraint case. Rear-impact simulations were conducted using a human body FE model, THUMS, representing an average-size male occupant. The cervical system including the facet joint capsules was incorporated to the model. The validity of the model was examined comparing its mechanical responses to those in the literature such as the whole body motion of the volunteer subject and the vertebral motion in the PMHS tests. Rear-impact simulations were conducted using the validated THUMS model and two prototype seat models; one had a fixed head restraint and the other one was equipped with an active head restraint system. The active head restraint system works moving the head restraint forward and upward when the lower unit is loaded by the pelvis. The head and neck kinematics and responses were analyzed from the simulation results. The force and acceleration rose at the pelvis first, followed by T1 and the head. The early timing of force rise and its magnitude indicated that the pelvis force was a good trigger for the active head restraint system. The results showed that the head was supported earlier in a case with the active head restraint system, and both NIC and joint capsule strain were lowered. The study also analyzed the mechanism of strain growth in the joint capsules. Relatively greater strain was observed in the direction of the facet joint surface, which was around 45 degrees inclined to the spinal column. The forward and upward motion of the active head restraint were aligned with the direction of the joint deformation and contributed to lower strain in the joint capsules. The results indicated that the active head restraint could help reduce the neck injury risk not only by supporting the head at an early timing but also through its trajectory stopping the joint deformation.