Using Portable Video Modeling Technology to Increase the Compliment Behaviors of Children with Autism During Athletic Group Play.

PubMed

Macpherson, Kevin; Charlop, Marjorie H; Miltenberger, Catherine A

2015-12-01

A multiple baseline design across participants was used to examine the effects of a portable video modeling intervention delivered in the natural environment on the verbal compliments and compliment gestures demonstrated by five children with autism. Participants were observed playing kickball with peers and adults. In baseline, participants demonstrated few compliment behaviors. During intervention, an iPad(®) was used to implement the video modeling treatment during the course of the athletic game. Viewing the video rapidly increased the verbal compliments participants gave to peers. Participants also demonstrated more response variation after watching the videos. Some generalization to an untrained activity occurred and compliment gestures also occurred. Results are discussed in terms of contributions to the literature.

Democracy under uncertainty: the wisdom of crowds and the free-rider problem in group decision making.

PubMed

Kameda, Tatsuya; Tsukasaki, Takafumi; Hastie, Reid; Berg, Nathan

2011-01-01

We introduce a game theory model of individual decisions to cooperate by contributing personal resources to group decisions versus by free riding on the contributions of other members. In contrast to most public-goods games that assume group returns are linear in individual contributions, the present model assumes decreasing marginal group production as a function of aggregate individual contributions. This diminishing marginal returns assumption is more realistic and generates starkly different predictions compared to the linear model. One important implication is that, under most conditions, there exist equilibria where some, but not all, members of a group contribute, even with completely self-interested motives. An agent-based simulation confirmed the individual and group advantages of the equilibria in which behavioral asymmetry emerges from a game structure that is a priori perfectly symmetric for all agents (all agents have the same payoff function and action space but take different actions in equilibria). A behavioral experiment demonstrated that cooperators and free riders coexist in a stable manner in groups performing with the nonlinear production function. A collateral result demonstrated that, compared to a dictatorial decision scheme guided by the best member in a group, the majority/plurality decision rules can pool information effectively and produce greater individual net welfare at equilibrium, even if free riding is not sanctioned. This is an original proof that cooperation in ad hoc decision-making groups can be understood in terms of self-interested motivations and that, despite the free-rider problem, majority/plurality decision rules can function robustly as simple, efficient social decision heuristics.

A combined experimental-modelling method for the detection and analysis of pollution in coastal zones

NASA Astrophysics Data System (ADS)

Limić, Nedzad; Valković, Vladivoj

1996-04-01

Pollution of coastal seas with toxic substances can be efficiently detected by examining toxic materials in sediment samples. These samples contain information on the overall pollution from surrounding sources such as yacht anchorages, nearby industries, sewage systems, etc. In an efficient analysis of pollution one must determine the contribution from each individual source. In this work it is demonstrated that a modelling method can be utilized for solving this latter problem. The modelling method is based on a unique interpretation of concentrations in sediments from all sampling stations. The proposed method is a synthesis consisting of the utilization of PIXE as an efficient method of pollution concentration determination and the code ANCOPOL (N. Limic and R. Benis, The computer code ANCOPOL, SimTel/msdos/geology, 1994 [1]) for the calculation of contributions from the main polluters. The efficiency and limits of the proposed method are demonstrated by discussing trace element concentrations in sediments of Punat Bay on the island of Krk in Croatia.

Attention and normalization circuits in macaque V1

PubMed Central

Sanayei, M; Herrero, J L; Distler, C; Thiele, A

2015-01-01

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. PMID:25757941

Bone marrow stem and progenitor cell contribution to neovasculogenesis is dependent on model system with SDF-1 as a permissive trigger

PubMed Central

Madlambayan, Gerard J.; Butler, Jason M.; Hosaka, Koji; Jorgensen, Marda; Fu, Dongtao; Guthrie, Steven M.; Shenoy, Anitha K.; Brank, Adam; Russell, Kathryn J.; Otero, Jaclyn; Siemann, Dietmar W.

2009-01-01

Adult bone marrow (BM) contributes to neovascularization in some but not all settings, and reasons for these discordant results have remained unexplored. We conducted novel comparative studies in which multiple neovascularization models were established in single mice to reduce variations in experimental methodology. In different combinations, BM contribution was detected in ischemic retinas and, to a lesser extent, Lewis lung carcinoma cells, whereas B16 melanomas showed little to no BM contribution. Using this spectrum of BM contribution, we demonstrate the necessity for site-specific expression of stromal-derived factor-1α (SDF-1α) and its mobilizing effects on BM. Blocking SDF-1α activity with neutralizing antibodies abrogated BM-derived neovascularization in lung cancer and retinopathy. Furthermore, secondary transplantation of single hematopoietic stem cells (HSCs) showed that HSCs are a long-term source of neovasculogenesis and that CD133+CXCR4+ myeloid progenitor cells directly participate in new blood vessel formation in response to SDF-1α. The varied BM contribution seen in different model systems is suggestive of redundant mechanisms governing postnatal neovasculogenesis and provides an explanation for contradictory results observed in the field. PMID:19717647

Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium tuberculosis: A Multiscale Computational Biology Approach

PubMed Central

Sershen, Cheryl L.; Plimpton, Steven J.; May, Elebeoba E.

2016-01-01

Mycobacterium tuberculosis associated granuloma formation can be viewed as a structural immune response that can contain and halt the spread of the pathogen. In several mammalian hosts, including non-human primates, Mtb granulomas are often hypoxic, although this has not been observed in wild type murine infection models. While a presumed consequence, the structural contribution of the granuloma to oxygen limitation and the concomitant impact on Mtb metabolic viability and persistence remains to be fully explored. We develop a multiscale computational model to test to what extent in vivo Mtb granulomas become hypoxic, and investigate the effects of hypoxia on host immune response efficacy and mycobacterial persistence. Our study integrates a physiological model of oxygen dynamics in the extracellular space of alveolar tissue, an agent-based model of cellular immune response, and a systems biology-based model of Mtb metabolic dynamics. Our theoretical studies suggest that the dynamics of granuloma organization mediates oxygen availability and illustrates the immunological contribution of this structural host response to infection outcome. Furthermore, our integrated model demonstrates the link between structural immune response and mechanistic drivers influencing Mtbs adaptation to its changing microenvironment and the qualitative infection outcome scenarios of clearance, containment, dissemination, and a newly observed theoretical outcome of transient containment. We observed hypoxic regions in the containment granuloma similar in size to granulomas found in mammalian in vivo models of Mtb infection. In the case of the containment outcome, our model uniquely demonstrates that immune response mediated hypoxic conditions help foster the shift down of bacteria through two stages of adaptation similar to thein vitro non-replicating persistence (NRP) observed in the Wayne model of Mtb dormancy. The adaptation in part contributes to the ability of Mtb to remain dormant for years after initial infection. PMID:26913242

A case study of development and application of a streamlined control and response modeling system for PM2.5 attainment assessment in China.

PubMed

Long, Shicheng; Zhu, Yun; Jang, Carey; Lin, Che-Jen; Wang, Shuxiao; Zhao, Bin; Gao, Jian; Deng, Shuang; Xie, Junping; Qiu, Xuezhen

2016-03-01

This article describes the development and application of a streamlined air control and response modeling system with a novel response surface modeling-linear coupled fitting method and a new module to provide streamlined model data for PM2.5 attainment assessment in China. This method is capable of significantly reducing the dimensions required to establish a response surface model, as well as capturing more realistic response of PM2.5 to emission changes with a limited number of model simulations. The newly developed module establishes a data link between the system and the Software for Model Attainment Test-Community Edition (SMAT-CE), and has the ability to rapidly provide model responses to emission control scenarios for SMAT-CE using a simple interface. The performance of this streamlined system is demonstrated through a case study of the Yangtze River Delta (YRD) in China. Our results show that this system is capable of reproducing the Community Multi-Scale Air Quality (CMAQ) model simulation results with maximum mean normalized error<3.5%. It is also demonstrated that primary emissions make a major contribution to ambient levels of PM2.5 in January and August (e.g., more than 50% contributed by primary emissions in Shanghai), and Shanghai needs to have regional emission control both locally and in its neighboring provinces to meet China's annual PM2.5 National Ambient Air Quality Standard. The streamlined system provides a real-time control/response assessment to identify the contributions of major emission sources to ambient PM2.5 (and potentially O3 as well) and streamline air quality data for SMAT-CE to perform attainment assessments. Copyright © 2015. Published by Elsevier B.V.

Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium tuberculosis: A Multiscale Computational Biology Approach.

PubMed

Sershen, Cheryl L; Plimpton, Steven J; May, Elebeoba E

2016-01-01

Mycobacterium tuberculosis associated granuloma formation can be viewed as a structural immune response that can contain and halt the spread of the pathogen. In several mammalian hosts, including non-human primates, Mtb granulomas are often hypoxic, although this has not been observed in wild type murine infection models. While a presumed consequence, the structural contribution of the granuloma to oxygen limitation and the concomitant impact on Mtb metabolic viability and persistence remains to be fully explored. We develop a multiscale computational model to test to what extent in vivo Mtb granulomas become hypoxic, and investigate the effects of hypoxia on host immune response efficacy and mycobacterial persistence. Our study integrates a physiological model of oxygen dynamics in the extracellular space of alveolar tissue, an agent-based model of cellular immune response, and a systems biology-based model of Mtb metabolic dynamics. Our theoretical studies suggest that the dynamics of granuloma organization mediates oxygen availability and illustrates the immunological contribution of this structural host response to infection outcome. Furthermore, our integrated model demonstrates the link between structural immune response and mechanistic drivers influencing Mtbs adaptation to its changing microenvironment and the qualitative infection outcome scenarios of clearance, containment, dissemination, and a newly observed theoretical outcome of transient containment. We observed hypoxic regions in the containment granuloma similar in size to granulomas found in mammalian in vivo models of Mtb infection. In the case of the containment outcome, our model uniquely demonstrates that immune response mediated hypoxic conditions help foster the shift down of bacteria through two stages of adaptation similar to the in vitro non-replicating persistence (NRP) observed in the Wayne model of Mtb dormancy. The adaptation in part contributes to the ability of Mtb to remain dormant for years after initial infection.

Hot Rolling Scrap Reduction through Edge Cracking and Surface Defects Control

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

Beaudoin, Armand

2016-05-29

The design of future aircraft must address the combined demands for fuel efficiency, reduced emissions and lower operating costs. One contribution to these goals is weight savings through the development of new alloys and design techniques for airframe structures. This research contributes to the light-weighting through fabrication of monolithic components from advanced aluminum alloys by making a link between alloy processing history and in-service performance. Specifically, this research demonstrates the link between growing cracks with features of the alloy microstructure that follow from thermo-mechanical processing. This is achieved through a computer model of crack deviation. The model is validated againstmore » experimental data from production scale aluminum alloy plate, and demonstration of the effect of changes in processing history on crack growth is made. The model is cast in the open-source finite element code WARP3D, which is freely downloadable and well documented. This project provides benefit along several avenues. First, the technical contribution of the computer model offers the materials engineer a critical means of providing guidance both upstream, to process tuning to achieve optimal properties, and downstream, to enhance fault tolerance. Beyond the fuel savings and emissions reduction inherent in the light-weighting of aircraft structures, improved fault tolerance addresses demands for longer inspection intervals over baseline, and a lower life cycle cost.« less

A neural hypothesis for stress-induced headache.

PubMed

Cathcart, Stuart

2009-12-01

The mechanisms by which stress contributes to CTH are not clearly understood. The commonly accepted notion of muscle hyper-reactivity to stress in CTH sufferers is not supported in the research data. We propose a neural model whereby stress acts supra-spinally to aggravate already increased pain sensitivity in CTH sufferers. Indirect support for the model comes from emerging research elucidating complex supra-spinal networks through which psychological stress may contribute to and even cause pain. Similarly, emerging research demonstrates supra-spinal pain processing abnormalities in CTH sufferers. While research with CTH sufferers offering direct support for the model is lacking at present, initial work by our group is consistent with the models predictions, particularly, that stress aggravates already increased pain sensitivity in CTH sufferers.

Modeling Creep-Fatigue-Environment Interactions in Steam Turbine Rotor Materials for Advanced Ultra-supercritical Coal Power Plants

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

Shen, Chen

2014-04-01

The goal of this project is to model creep-fatigue-environment interactions in steam turbine rotor materials for advanced ultra-supercritical (A-USC) coal power Alloy 282 plants, to develop and demonstrate computational algorithms for alloy property predictions, and to determine and model key mechanisms that contribute to the damages caused by creep-fatigue-environment interactions.

Factors that Contribute towards Improving Learning Effectiveness Using a Specific Learning Management System (LMS) at the Military Academy (MA): A Demonstration

ERIC Educational Resources Information Center

Pretorius, Andre

2010-01-01

Purpose: The purpose of this paper is to explore the factors that contribute towards learning effectiveness in e-learning courses. A review of previous studies was carried out to determine those factors that are most applicable to a tertiary teaching environment and to propose a model to assess effectiveness in online courses. The virtual learning…

Development and demonstration of smoke plume, fire emissions, and pre- and postprescribed fire fuel models on North Carolina Coastal Plain forest ecosystems

Treesearch

Robert A. Mickler; Miriam Rorig; Christopher D. Geron; Gary L. Achtemier; Andrew D. Bailey; Candice Krull; David Brownlie

2007-01-01

Wildland fuels have been accumulating in the United States during at least the past half-century due to wildland fire management practices and policies. The additional fuels contribute to intense fire behavior, increase the costs of wildland fire control, and contribute to the degradation of local and regional air quality. The management of prescribed and wildland fire...

Interpreting Space-Based Trends in Carbon Monoxide with Multiple Models

NASA Technical Reports Server (NTRS)

Strode, Sarah A.; Worden, Helen M.; Damon, Megan; Douglass, Anne R.; Duncan, Bryan N.; Emmons, Louisa K.; Lamarque, Jean-Francois; Manyin, Michael; Oman, Luke D.; Rodriguez, Jose M.;

A deep auto-encoder model for gene expression prediction.

PubMed

Xie, Rui; Wen, Jia; Quitadamo, Andrew; Cheng, Jianlin; Shi, Xinghua

2017-11-17

Gene expression is a key intermediate level that genotypes lead to a particular trait. Gene expression is affected by various factors including genotypes of genetic variants. With an aim of delineating the genetic impact on gene expression, we build a deep auto-encoder model to assess how good genetic variants will contribute to gene expression changes. This new deep learning model is a regression-based predictive model based on the MultiLayer Perceptron and Stacked Denoising Auto-encoder (MLP-SAE). The model is trained using a stacked denoising auto-encoder for feature selection and a multilayer perceptron framework for backpropagation. We further improve the model by introducing dropout to prevent overfitting and improve performance. To demonstrate the usage of this model, we apply MLP-SAE to a real genomic datasets with genotypes and gene expression profiles measured in yeast. Our results show that the MLP-SAE model with dropout outperforms other models including Lasso, Random Forests and the MLP-SAE model without dropout. Using the MLP-SAE model with dropout, we show that gene expression quantifications predicted by the model solely based on genotypes, align well with true gene expression patterns. We provide a deep auto-encoder model for predicting gene expression from SNP genotypes. This study demonstrates that deep learning is appropriate for tackling another genomic problem, i.e., building predictive models to understand genotypes' contribution to gene expression. With the emerging availability of richer genomic data, we anticipate that deep learning models play a bigger role in modeling and interpreting genomics.

The 2 × 2 Standpoints Model of Achievement Goals

PubMed Central

Korn, Rachel M.; Elliot, Andrew J.

2016-01-01

In the present research, we proposed and tested a 2 × 2 standpoints model of achievement goals grounded in the development-demonstration and approach-avoidance distinctions. Three empirical studies are presented. Study 1 provided evidence supporting the structure and psychometric properties of a newly developed measure of the goals of the 2 × 2 standpoints model. Study 2 documented the predictive utility of these goal constructs for intrinsic motivation: development-approach and development-avoidance goals were positive predictors, and demonstration-avoidance goals were a negative predictor of intrinsic motivation. Study 3 documented the predictive utility of these goal constructs for performance attainment: Demonstration-approach goals were a positive predictor and demonstration-avoidance goals were a negative predictor of exam performance. The conceptual and empirical contributions of the present research were discussed within the broader context of existing achievement goal theory and research. PMID:27242641

Eddy damping, backscatter, and subgrid stresses in subgrid modeling of turbulence

NASA Technical Reports Server (NTRS)

Zhou, YE

1991-01-01

The Brief Report demonstrates the relationship of eddy-viscosity models to subgrid stresses. A formula that determines the relative importance of the cross stress and the Reynolds stress for the net eddy-damping and backscatter contributions is derived. The cross-stress term with sharp-cut filtering is identified as an important quantity to model. These concepts could prove useful as a basis for constructing specific models for the Reynolds and cross stresses.

Chemical control of rate and onset temperature of nadimide polymerization

NASA Technical Reports Server (NTRS)

Lauver, R. W.

1985-01-01

The chemistry of norbornenyl capped imide compounds (nadimides) is briefly reviewed with emphasis on the contribution of Diels-Alder reversion in controlling the rate and onset of the thermal polymerization reaction. Control of onset temperature of the cure exotherm by adjusting the concentration of maleimide is demonstrated using selected model compounds. The effects of nitrophenyl compounds as free radical retarders on nadimide reactivity are discussed. A simple copolymerization model is proposed for the overall nadimide cure reaction. An approximate numerical analysis is carried out to demonstrate the ability of the model to simulate the trends observed for both maleimide and nitrophenyl additions.

An empirical model to determine the hadronic resonance contributions \\overline{B}{} ^0 → \\overline{K}{} ^{*0} μ ^+ μ ^- to transitions

NASA Astrophysics Data System (ADS)

Blake, T.; Egede, U.; Owen, P.; Petridis, K. A.; Pomery, G.

2018-06-01

A method for analysing the hadronic resonance contributions in \\overline{B}{} ^0 → \\overline{K}{} ^{*0} μ ^+ μ ^- decays is presented. This method uses an empirical model that relies on measurements of the branching fractions and polarisation amplitudes of final states involving J^{PC}=1^{-} resonances, relative to the short-distance component, across the full dimuon mass spectrum of \\overline{B}{} ^0 → \\overline{K}{} ^{*0} μ ^+ μ ^- transitions. The model is in good agreement with existing calculations of hadronic non-local effects. The effect of this contribution to the angular observables is presented and it is demonstrated how the narrow resonances in the q^2 spectrum provide a dramatic enhancement to CP-violating effects in the short-distance amplitude. Finally, a study of the hadronic resonance effects on lepton universality ratios, R_{K^{(*)}}, in the presence of new physics is presented.

Enhancing the resilience of Idaho's transportation system to natural hazards and climate change.

DOT National Transportation Integrated Search

2015-07-01

This research compiled information on past landslides, including date-referencing and geo-locating events; analyzed and mapped variables : contributing to slide susceptibility; demonstrated the conditions of the future climate models that may increas...

Interpreting space-based trends in carbon monoxide with multiple models

DOE PAGES

Strode, Sarah A.; Worden, Helen M.; Damon, Megan; ...

2016-06-10

Here, we use a series of chemical transport model and chemistry climate model simulations to investigate the observed negative trends in MOPITT CO over several regions of the world, and to examine the consistency of time-dependent emission inventories with observations. We also found that simulations driven by the MACCity inventory, used for the Chemistry Climate Modeling Initiative (CCMI), reproduce the negative trends in the CO column observed by MOPITT for 2000–2010 over the eastern United States and Europe. However, the simulations have positive trends over eastern China, in contrast to the negative trends observed by MOPITT. The model bias inmore » CO, after applying MOPITT averaging kernels, contributes to the model–observation discrepancy in the trend over eastern China. This demonstrates that biases in a model's average concentrations can influence the interpretation of the temporal trend compared to satellite observations. The total ozone column plays a role in determining the simulated tropospheric CO trends. A large positive anomaly in the simulated total ozone column in 2010 leads to a negative anomaly in OH and hence a positive anomaly in CO, contributing to the positive trend in simulated CO. Our results demonstrate that accurately simulating variability in the ozone column is important for simulating and interpreting trends in CO.« less

Interpreting space-based trends in carbon monoxide with multiple models

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

Strode, Sarah A.; Worden, Helen M.; Damon, Megan

Here, we use a series of chemical transport model and chemistry climate model simulations to investigate the observed negative trends in MOPITT CO over several regions of the world, and to examine the consistency of time-dependent emission inventories with observations. We also found that simulations driven by the MACCity inventory, used for the Chemistry Climate Modeling Initiative (CCMI), reproduce the negative trends in the CO column observed by MOPITT for 2000–2010 over the eastern United States and Europe. However, the simulations have positive trends over eastern China, in contrast to the negative trends observed by MOPITT. The model bias inmore » CO, after applying MOPITT averaging kernels, contributes to the model–observation discrepancy in the trend over eastern China. This demonstrates that biases in a model's average concentrations can influence the interpretation of the temporal trend compared to satellite observations. The total ozone column plays a role in determining the simulated tropospheric CO trends. A large positive anomaly in the simulated total ozone column in 2010 leads to a negative anomaly in OH and hence a positive anomaly in CO, contributing to the positive trend in simulated CO. Our results demonstrate that accurately simulating variability in the ozone column is important for simulating and interpreting trends in CO.« less

Social Image Captioning: Exploring Visual Attention and User Attention.

PubMed

Wang, Leiquan; Chu, Xiaoliang; Zhang, Weishan; Wei, Yiwei; Sun, Weichen; Wu, Chunlei

2018-02-22

Image captioning with a natural language has been an emerging trend. However, the social image, associated with a set of user-contributed tags, has been rarely investigated for a similar task. The user-contributed tags, which could reflect the user attention, have been neglected in conventional image captioning. Most existing image captioning models cannot be applied directly to social image captioning. In this work, a dual attention model is proposed for social image captioning by combining the visual attention and user attention simultaneously.Visual attention is used to compress a large mount of salient visual information, while user attention is applied to adjust the description of the social images with user-contributed tags. Experiments conducted on the Microsoft (MS) COCO dataset demonstrate the superiority of the proposed method of dual attention.

Social Image Captioning: Exploring Visual Attention and User Attention

PubMed Central

Chu, Xiaoliang; Zhang, Weishan; Wei, Yiwei; Sun, Weichen; Wu, Chunlei

2018-01-01

Image captioning with a natural language has been an emerging trend. However, the social image, associated with a set of user-contributed tags, has been rarely investigated for a similar task. The user-contributed tags, which could reflect the user attention, have been neglected in conventional image captioning. Most existing image captioning models cannot be applied directly to social image captioning. In this work, a dual attention model is proposed for social image captioning by combining the visual attention and user attention simultaneously.Visual attention is used to compress a large mount of salient visual information, while user attention is applied to adjust the description of the social images with user-contributed tags. Experiments conducted on the Microsoft (MS) COCO dataset demonstrate the superiority of the proposed method of dual attention. PMID:29470409

Attention and normalization circuits in macaque V1.

PubMed

Sanayei, M; Herrero, J L; Distler, C; Thiele, A

2015-04-01

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Quantifying the dilution of the radiocesium contamination in Fukushima coastal river sediment (2011-2015)

NASA Astrophysics Data System (ADS)

Evrard, Olivier; Laceby, J. Patrick; Onda, Yuichi; Wakiyama, Yoshifumi; Jaegler, Hugo; Lefèvre, Irène

2016-10-01

Fallout from the Fukushima Dai-ichi nuclear power plant accident resulted in a 3000-km2 radioactive contamination plume. Here, we model the progressive dilution of the radiocesium contamination in 327 sediment samples from two neighboring catchments with different timing of soil decontamination. Overall, we demonstrate that there has been a ~90% decrease of the contribution of upstream contaminated soils to sediment transiting the coastal plains between 2012 (median - M - contribution of 73%, mean absolute deviation - MAD - of 27%) and 2015 (M 9%, MAD 6%). The occurrence of typhoons and the progress of decontamination in different tributaries of the Niida River resulted in temporary increases in local contamination. However, the much lower contribution of upstream contaminated soils to coastal plain sediment in November 2015 demonstrates that the source of the easily erodible, contaminated material has potentially been removed by decontamination, diluted by subsoils, or eroded and transported to the Pacific Ocean.

Coupled stochastic spatial and non-spatial simulations of ErbB1 signaling pathways demonstrate the importance of spatial organization in signal transduction.

PubMed

Costa, Michelle N; Radhakrishnan, Krishnan; Wilson, Bridget S; Vlachos, Dionisios G; Edwards, Jeremy S

2009-07-23

The ErbB family of receptors activates intracellular signaling pathways that control cellular proliferation, growth, differentiation and apoptosis. Given these central roles, it is not surprising that overexpression of the ErbB receptors is often associated with carcinogenesis. Therefore, extensive laboratory studies have been devoted to understanding the signaling events associated with ErbB activation. Systems biology has contributed significantly to our current understanding of ErbB signaling networks. However, although computational models have grown in complexity over the years, little work has been done to consider the spatial-temporal dynamics of receptor interactions and to evaluate how spatial organization of membrane receptors influences signaling transduction. Herein, we explore the impact of spatial organization of the epidermal growth factor receptor (ErbB1/EGFR) on the initiation of downstream signaling. We describe the development of an algorithm that couples a spatial stochastic model of membrane receptors with a nonspatial stochastic model of the reactions and interactions in the cytosol. This novel algorithm provides a computationally efficient method to evaluate the effects of spatial heterogeneity on the coupling of receptors to cytosolic signaling partners. Mathematical models of signal transduction rarely consider the contributions of spatial organization due to high computational costs. A hybrid stochastic approach simplifies analyses of the spatio-temporal aspects of cell signaling and, as an example, demonstrates that receptor clustering contributes significantly to the efficiency of signal propagation from ligand-engaged growth factor receptors.

STAMP-Based HRA Considering Causality Within a Sociotechnical System: A Case of Minuteman III Missile Accident.

PubMed

Rong, Hao; Tian, Jin

2015-05-01

The study contributes to human reliability analysis (HRA) by proposing a method that focuses more on human error causality within a sociotechnical system, illustrating its rationality and feasibility by using a case of the Minuteman (MM) III missile accident. Due to the complexity and dynamics within a sociotechnical system, previous analyses of accidents involving human and organizational factors clearly demonstrated that the methods using a sequential accident model are inadequate to analyze human error within a sociotechnical system. System-theoretic accident model and processes (STAMP) was used to develop a universal framework of human error causal analysis. To elaborate the causal relationships and demonstrate the dynamics of human error, system dynamics (SD) modeling was conducted based on the framework. A total of 41 contributing factors, categorized into four types of human error, were identified through the STAMP-based analysis. All factors are related to a broad view of sociotechnical systems, and more comprehensive than the causation presented in the accident investigation report issued officially. Recommendations regarding both technical and managerial improvement for a lower risk of the accident are proposed. The interests of an interdisciplinary approach provide complementary support between system safety and human factors. The integrated method based on STAMP and SD model contributes to HRA effectively. The proposed method will be beneficial to HRA, risk assessment, and control of the MM III operating process, as well as other sociotechnical systems. © 2014, Human Factors and Ergonomics Society.

Application and Evaluation of a Snowmelt Runoff Model in the Tamor River Basin, Eastern Himalaya Using a Markov Chain Monte Carlo (MCMC) Data Assimilation Approach

NASA Technical Reports Server (NTRS)

Panday, Prajjwal K.; Williams, Christopher A.; Frey, Karen E.; Brown, Molly E.

2013-01-01

Previous studies have drawn attention to substantial hydrological changes taking place in mountainous watersheds where hydrology is dominated by cryospheric processes. Modelling is an important tool for understanding these changes but is particularly challenging in mountainous terrain owing to scarcity of ground observations and uncertainty of model parameters across space and time. This study utilizes a Markov Chain Monte Carlo data assimilation approach to examine and evaluate the performance of a conceptual, degree-day snowmelt runoff model applied in the Tamor River basin in the eastern Nepalese Himalaya. The snowmelt runoff model is calibrated using daily streamflow from 2002 to 2006 with fairly high accuracy (average Nash-Sutcliffe metric approx. 0.84, annual volume bias <3%). The Markov Chain Monte Carlo approach constrains the parameters to which the model is most sensitive (e.g. lapse rate and recession coefficient) and maximizes model fit and performance. Model simulated streamflow using an interpolated precipitation data set decreases the fractional contribution from rainfall compared with simulations using observed station precipitation. The average snowmelt contribution to total runoff in the Tamor River basin for the 2002-2006 period is estimated to be 29.7+/-2.9% (which includes 4.2+/-0.9% from snowfall that promptly melts), whereas 70.3+/-2.6% is attributed to contributions from rainfall. On average, the elevation zone in the 4000-5500m range contributes the most to basin runoff, averaging 56.9+/-3.6% of all snowmelt input and 28.9+/-1.1% of all rainfall input to runoff. Model simulated streamflow using an interpolated precipitation data set decreases the fractional contribution from rainfall versus snowmelt compared with simulations using observed station precipitation. Model experiments indicate that the hydrograph itself does not constrain estimates of snowmelt versus rainfall contributions to total outflow but that this derives from the degree-day melting model. Lastly, we demonstrate that the data assimilation approach is useful for quantifying and reducing uncertainty related to model parameters and thus provides uncertainty bounds on snowmelt and rainfall contributions in such mountainous watersheds.

Radiative contribution to thermal conductance in animal furs and other woolly insulators.

PubMed

Simonis, Priscilla; Rattal, Mourad; Oualim, El Mostafa; Mouhse, Azeddine; Vigneron, Jean-Pol

2014-01-27

This paper deals with radiation's contribution to thermal insulation. The mechanism by which a stack of absorbers limits radiative heat transfer is examined in detail both for black-body shields and grey-body shields. It shows that radiation energy transfer rates should be much faster than conduction rates. It demonstrates that, for opaque screens, increased reflectivity will dramatically reduce the rate of heat transfer, improving thermal insulation. This simple model is thought to contribute to the understanding of how animal furs, human clothes, rockwool insulators, thermo-protective containers, and many other passive energy-saving devices operate.

Human-modified temperatures induce species changes: Joint attribution.

PubMed

Root, Terry L; MacMynowski, Dena P; Mastrandrea, Michael D; Schneider, Stephen H

2005-05-24

Average global surface-air temperature is increasing. Contention exists over relative contributions by natural and anthropogenic forcings. Ecological studies attribute plant and animal changes to observed warming. Until now, temperature-species connections have not been statistically attributed directly to anthropogenic climatic change. Using modeled climatic variables and observed species data, which are independent of thermometer records and paleoclimatic proxies, we demonstrate statistically significant "joint attribution," a two-step linkage: human activities contribute significantly to temperature changes and human-changed temperatures are associated with discernible changes in plant and animal traits. Additionally, our analyses provide independent testing of grid-box-scale temperature projections from a general circulation model (HadCM3).

Optimization of Modeled Land-Atmosphere Exchanges of Water and Energy in an Isotopically-Enabled Land Surface Model by Bayesian Parameter Calibration

NASA Astrophysics Data System (ADS)

Wong, T. E.; Noone, D. C.; Kleiber, W.

2014-12-01

The single largest uncertainty in climate model energy balance is the surface latent heating over tropical land. Furthermore, the partitioning of the total latent heat flux into contributions from surface evaporation and plant transpiration is of great importance, but notoriously poorly constrained. Resolving these issues will require better exploiting information which lies at the interface between observations and advanced modeling tools, both of which are imperfect. There are remarkably few observations which can constrain these fluxes, placing strict requirements on developing statistical methods to maximize the use of limited information to best improve models. Previous work has demonstrated the power of incorporating stable water isotopes into land surface models for further constraining ecosystem processes. We present results from a stable water isotopically-enabled land surface model (iCLM4), including model experiments partitioning the latent heat flux into contributions from plant transpiration and surface evaporation. It is shown that the partitioning results are sensitive to the parameterization of kinetic fractionation used. We discuss and demonstrate an approach to calibrating select model parameters to observational data in a Bayesian estimation framework, requiring Markov Chain Monte Carlo sampling of the posterior distribution, which is shown to constrain uncertain parameters as well as inform relevant values for operational use. Finally, we discuss the application of the estimation scheme to iCLM4, including entropy as a measure of information content and specific challenges which arise in calibration models with a large number of parameters.

Bovine lateral saphenous veins exposed to ergopeptine alkaloids do not relax

USDA-ARS?s Scientific Manuscript database

The ergot alkaloid ergovaline has demonstrated a persistent and sustained contractile response in several different vascular models. It was hypothesized that different alkaloids isolated from tall fescue (Lolium arundinaceum) will contribute to this contractile response differently. The objective wa...

Bovine lateral saphenous veins exposed to ergopeptine alkaloids do not relax

USDA-ARS?s Scientific Manuscript database

The ergot alkaloid, ergovaline has demonstrated a persistent binding and sustained contractile response in several vascular models. It was hypothesized that different alkaloids isolated from tall fescue (Lolium arundinaceum) will contribute to this response differently. The objective was to compare ...

Bayesian outcome-based strategy classification.

PubMed

Lee, Michael D

2016-03-01

Hilbig and Moshagen (Psychonomic Bulletin & Review, 21, 1431-1443, 2014) recently developed a method for making inferences about the decision processes people use in multi-attribute forced choice tasks. Their paper makes a number of worthwhile theoretical and methodological contributions. Theoretically, they provide an insightful psychological motivation for a probabilistic extension of the widely-used "weighted additive" (WADD) model, and show how this model, as well as other important models like "take-the-best" (TTB), can and should be expressed in terms of meaningful priors. Methodologically, they develop an inference approach based on the Minimum Description Length (MDL) principles that balances both the goodness-of-fit and complexity of the decision models they consider. This paper aims to preserve these useful contributions, but provide a complementary Bayesian approach with some theoretical and methodological advantages. We develop a simple graphical model, implemented in JAGS, that allows for fully Bayesian inferences about which models people use to make decisions. To demonstrate the Bayesian approach, we apply it to the models and data considered by Hilbig and Moshagen (Psychonomic Bulletin & Review, 21, 1431-1443, 2014), showing how a prior predictive analysis of the models, and posterior inferences about which models people use and the parameter settings at which they use them, can contribute to our understanding of human decision making.

Applying a Multiple Group Causal Indicator Modeling Framework to the Reading Comprehension Skills of Third, Seventh, and Tenth Grade Students

PubMed Central

Tighe, Elizabeth L.; Wagner, Richard K.; Schatschneider, Christopher

2015-01-01

This study demonstrates the utility of applying a causal indicator modeling framework to investigate important predictors of reading comprehension in third, seventh, and tenth grade students. The results indicated that a 4-factor multiple indicator multiple indicator cause (MIMIC) model of reading comprehension provided adequate fit at each grade level. This model included latent predictor constructs of decoding, verbal reasoning, nonverbal reasoning, and working memory and accounted for a large portion of the reading comprehension variance (73% to 87%) across grade levels. Verbal reasoning contributed the most unique variance to reading comprehension at all grade levels. In addition, we fit a multiple group 4-factor MIMIC model to investigate the relative stability (or variability) of the predictor contributions to reading comprehension across development (i.e., grade levels). The results revealed that the contributions of verbal reasoning, nonverbal reasoning, and working memory to reading comprehension were stable across the three grade levels. Decoding was the only predictor that could not be constrained to be equal across grade levels. The contribution of decoding skills to reading comprehension was higher in third grade and then remained relatively stable between seventh and tenth grade. These findings illustrate the feasibility of using MIMIC models to explain individual differences in reading comprehension across the development of reading skills. PMID:25821346

Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium tuberculosis: A Multiscale Computational Biology Approach

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

Sershen, Cheryl L.; Plimpton, Steven J.; May, Elebeoba E.

Mycobacterium tuberculosis associated granuloma formation can be viewed as a structural immune response that can contain and halt the spread of the pathogen. In several mammalian hosts, including non-human primates, Mtb granulomas are often hypoxic, although this has not been observed in wild type murine infection models. While a presumed consequence, the structural contribution of the granuloma to oxygen limitation and the concomitant impact on Mtb metabolic viability and persistence remains to be fully explored. We develop a multiscale computational model to test to what extent in vivo Mtb granulomas become hypoxic, and investigate the effects of hypoxia on hostmore » immune response efficacy and mycobacterial persistence. Our study integrates a physiological model of oxygen dynamics in the extracellular space of alveolar tissue, an agent-based model of cellular immune response, and a systems biology-based model of Mtb metabolic dynamics. Our theoretical studies suggest that the dynamics of granuloma organization mediates oxygen availability and illustrates the immunological contribution of this structural host response to infection outcome. Furthermore, our integrated model demonstrates the link between structural immune response and mechanistic drivers influencing Mtbs adaptation to its changing microenvironment and the qualitative infection outcome scenarios of clearance, containment, dissemination, and a newly observed theoretical outcome of transient containment. We observed hypoxic regions in the containment granuloma similar in size to granulomas found in mammalian in vivo models of Mtb infection. In the case of the containment outcome, our model uniquely demonstrates that immune response mediated hypoxic conditions help foster the shift down of bacteria through two stages of adaptation similar to thein vitro non-replicating persistence (NRP) observed in the Wayne model of Mtb dormancy. Lastly, the adaptation in part contributes to the ability of Mtb to remain dormant for years after initial infection.« less

Oxygen Modulates the Effectiveness of Granuloma Mediated Host Response to Mycobacterium tuberculosis: A Multiscale Computational Biology Approach

DOE PAGES

Sershen, Cheryl L.; Plimpton, Steven J.; May, Elebeoba E.

2016-02-15

Mycobacterium tuberculosis associated granuloma formation can be viewed as a structural immune response that can contain and halt the spread of the pathogen. In several mammalian hosts, including non-human primates, Mtb granulomas are often hypoxic, although this has not been observed in wild type murine infection models. While a presumed consequence, the structural contribution of the granuloma to oxygen limitation and the concomitant impact on Mtb metabolic viability and persistence remains to be fully explored. We develop a multiscale computational model to test to what extent in vivo Mtb granulomas become hypoxic, and investigate the effects of hypoxia on hostmore » immune response efficacy and mycobacterial persistence. Our study integrates a physiological model of oxygen dynamics in the extracellular space of alveolar tissue, an agent-based model of cellular immune response, and a systems biology-based model of Mtb metabolic dynamics. Our theoretical studies suggest that the dynamics of granuloma organization mediates oxygen availability and illustrates the immunological contribution of this structural host response to infection outcome. Furthermore, our integrated model demonstrates the link between structural immune response and mechanistic drivers influencing Mtbs adaptation to its changing microenvironment and the qualitative infection outcome scenarios of clearance, containment, dissemination, and a newly observed theoretical outcome of transient containment. We observed hypoxic regions in the containment granuloma similar in size to granulomas found in mammalian in vivo models of Mtb infection. In the case of the containment outcome, our model uniquely demonstrates that immune response mediated hypoxic conditions help foster the shift down of bacteria through two stages of adaptation similar to thein vitro non-replicating persistence (NRP) observed in the Wayne model of Mtb dormancy. Lastly, the adaptation in part contributes to the ability of Mtb to remain dormant for years after initial infection.« less

Lipophagy Contributes to Testosterone Biosynthesis in Male Rat Leydig Cells.

PubMed

Ma, Yi; Zhou, Yan; Zhu, Yin-Ci; Wang, Si-Qi; Ping, Ping; Chen, Xiang-Feng

2018-02-01

In recent years, autophagy was found to regulate lipid metabolism through a process termed lipophagy. Lipophagy modulates the degradation of cholesteryl esters to free cholesterol (FC), which is the substrate of testosterone biosynthesis. However, the role of lipophagy in testosterone production is unknown. To investigate this, primary rat Leydig cells and varicocele rat models were administered to inhibit or promote autophagy, and testosterone, lipid droplets (LDs), total cholesterol (TC), and FC were evaluated. The results demonstrated that inhibiting autophagy in primary rat Leydig cells reduced testosterone production. Further studies demonstrated that inhibiting autophagy increased the number and size of LDs and the level of TC, but decreased the level of FC. Furthermore, hypoxia promoted autophagy in Leydig cells. We found that short-term hypoxia stimulated testosterone secretion; however, the inhibition of autophagy abolished stimulated testosterone release. Hypoxia decreased the number and size of LDs in Leydig cells, but the changes could be largely rescued by blocking autophagy. In experimental varicocele rat models, the administration of autophagy inhibitors substantially reduced serum testosterone. These data demonstrate that autophagy contributes to testosterone biosynthesis at least partially through degrading intracellular LDs/TC. Our observations might reveal an autophagic regulatory mode regarding testosterone biosynthesis. Copyright © 2018 Endocrine Society.

Mesospheric Non-Migrating Tides Generated With Planetary Waves: II Influence of Gravity Waves

NASA Technical Reports Server (NTRS)

Mayr, H. G.; Mengel, J. G.; Talaat, E. L.; Porter, H. S.; Chan, K. L.

2003-01-01

We demonstrated that, in our model, non-linear interactions between planetary waves (PW) and migrating tides could generate in the upper mesosphere non-migrating tides with amplitudes comparable to those observed. The Numerical Spectral Model (NSM) we employ incorporates Hines Doppler Spread Parameterization for small-scale gravity waves (GW), which affect in numerous ways the dynamics of the mesosphere. The latitudinal (seasonal) reversals in the temperature and zonal circulation, which are largely caused by GWs (Lindzen, 198l), filter the PWs and contribute to the instabilities that generate the PWs. The PWs in turn are amplified by the momentum deposition of upward propagating GWs, as are the migrating tides. The GWs thus affect significantly the migrating tides and PWs, the building blocks of non-migrating tides. In the present paper, we demonstrate that GW filtering also contributes to the non-linear coupling between PWs and tides. Two computer experiments are presented to make this point. In one, we simply turn off the GW source to show the effect. In the second case, we demonstrate the effect by selectively suppressing the momentum source for the m = 0 non-migrating tides.

Citizen observations contributing to flood modelling: opportunities and challenges

NASA Astrophysics Data System (ADS)

Assumpção, Thaine H.; Popescu, Ioana; Jonoski, Andreja; Solomatine, Dimitri P.

2018-02-01

Citizen contributions to science have been successfully implemented in many fields, and water resources is one of them. Through citizens, it is possible to collect data and obtain a more integrated decision-making process. Specifically, data scarcity has always been an issue in flood modelling, which has been addressed in the last decades by remote sensing and is already being discussed in the citizen science context. With this in mind, this article aims to review the literature on the topic and analyse the opportunities and challenges that lie ahead. The literature on monitoring, mapping and modelling, was evaluated according to the flood-related variable citizens contributed to. Pros and cons of the collection/analysis methods were summarised. Then, pertinent publications were mapped into the flood modelling cycle, considering how citizen data properties (spatial and temporal coverage, uncertainty and volume) are related to its integration into modelling. It was clear that the number of studies in the area is rising. There are positive experiences reported in collection and analysis methods, for instance with velocity and land cover, and also when modelling is concerned, for example by using social media mining. However, matching the data properties necessary for each part of the modelling cycle with citizen-generated data is still challenging. Nevertheless, the concept that citizen contributions can be used for simulation and forecasting is proved and further work lies in continuing to develop and improve not only methods for collection and analysis, but certainly for integration into models as well. Finally, in view of recent automated sensors and satellite technologies, it is through studies as the ones analysed in this article that the value of citizen contributions, complementing such technologies, is demonstrated.

Halogen radicals contribute to photooxidation in coastal and estuarine waters

PubMed Central

Parker, Kimberly M.; Mitch, William A.

2016-01-01

Although halogen radicals are recognized to form as products of hydroxyl radical (•OH) scavenging by halides, their contribution to the phototransformation of marine organic compounds has received little attention. We demonstrate that, relative to freshwater conditions, seawater halides can increase photodegradation rates of domoic acid, a marine algal toxin, and dimethyl sulfide, a volatile precursor to cloud condensation nuclei, up to fivefold. Using synthetic seawater solutions, we show that the increased photodegradation is specific to dissolved organic matter (DOM) and halides, rather than other seawater salt constituents (e.g., carbonates) or photoactive species (e.g., iron and nitrate). Experiments in synthetic and natural coastal and estuarine water samples demonstrate that the halide-specific increase in photodegradation could be attributed to photochemically generated halogen radicals rather than other photoproduced reactive intermediates [e.g., excited-state triplet DOM (3DOM*), reactive oxygen species]. Computational kinetic modeling indicates that seawater halogen radical concentrations are two to three orders of magnitude greater than freshwater •OH concentrations and sufficient to account for the observed halide-specific increase in photodegradation. Dark •OH generation by gamma radiolysis demonstrates that halogen radical production via •OH scavenging by halides is insufficient to explain the observed effect. Using sensitizer models for DOM chromophores, we show that halogen radicals are formed predominantly by direct oxidation of Cl− and Br− by 3DOM*, an •OH-independent pathway. Our results indicate that halogen radicals significantly contribute to the phototransformation of algal products in coastal or estuarine surface waters. PMID:27162335

Functional changes in glutamate transporters and astrocyte biophysical properties in a rodent model of focal cortical dysplasia

PubMed Central

Campbell, Susan L.; Hablitz, John J.; Olsen, Michelle L.

2014-01-01

Cortical dysplasia is associated with intractable epilepsy and developmental delay in young children. Recent work with the rat freeze-induced focal cortical dysplasia (FCD) model has demonstrated that hyperexcitability in the dysplastic cortex is due in part to higher levels of extracellular glutamate. Astrocyte glutamate transporters play a pivotal role in cortical maintaining extracellular glutamate concentrations. Here we examined the function of astrocytic glutamate transporters in a FCD model in rats. Neocortical freeze lesions were made in postnatal day (PN) 1 rat pups and whole cell electrophysiological recordings and biochemical studies were performed at PN 21–28. Synaptically evoked glutamate transporter currents in astrocytes showed a near 10-fold reduction in amplitude compared to sham operated controls. Astrocyte glutamate transporter currents from lesioned animals were also significantly reduced when challenged exogenously applied glutamate. Reduced astrocytic glutamate transport clearance contributed to increased NMDA receptor-mediated current decay kinetics in lesioned animals. The electrophysiological profile of astrocytes in the lesion group was also markedly changed compared to sham operated animals. Control astrocytes demonstrate large-amplitude linear leak currents in response to voltage-steps whereas astrocytes in lesioned animals demonstrated significantly smaller voltage-activated inward and outward currents. Significant decreases in astrocyte resting membrane potential and increases in input resistance were observed in lesioned animals. However, Western blotting, immunohistochemistry and quantitative PCR demonstrated no differences in the expression of the astrocytic glutamate transporter GLT-1 in lesioned animals relative to controls. These data suggest that, in the absence of changes in protein or mRNA expression levels, functional changes in astrocytic glutamate transporters contribute to neuronal hyperexcitability in the FCD model. PMID:25565960

Simulating charge transport to understand the spectral response of Swept Charge Devices

NASA Astrophysics Data System (ADS)

Athiray, P. S.; Sreekumar, P.; Narendranath, S.; Gow, J. P. D.

2015-11-01

Context. Swept Charge Devices (SCD) are novel X-ray detectors optimized for improved spectral performance without any demand for active cooling. The Chandrayaan-1 X-ray Spectrometer (C1XS) experiment onboard the Chandrayaan-1 spacecraft used an array of SCDs to map the global surface elemental abundances on the Moon using the X-ray fluorescence (XRF) technique. The successful demonstration of SCDs in C1XS spurred an enhanced version of the spectrometer on Chandrayaan-2 using the next-generation SCD sensors. Aims: The objective of this paper is to demonstrate validation of a physical model developed to simulate X-ray photon interaction and charge transportation in a SCD. The model helps to understand and identify the origin of individual components that collectively contribute to the energy-dependent spectral response of the SCD. Furthermore, the model provides completeness to various calibration tasks, such as generating spectral matrices (RMFs - redistribution matrix files), estimating efficiency, optimizing event selection logic, and maximizing event recovery to improve photon-collection efficiency in SCDs. Methods: Charge generation and transportation in the SCD at different layers related to channel stops, field zones, and field-free zones due to photon interaction were computed using standard drift and diffusion equations. Charge collected in the buried channel due to photon interaction in different volumes of the detector was computed by assuming a Gaussian radial profile of the charge cloud. The collected charge was processed further to simulate both diagonal clocking read-out, which is a novel design exclusive for SCDs, and event selection logic to construct the energy spectrum. Results: We compare simulation results of the SCD CCD54 with measurements obtained during the ground calibration of C1XS and clearly demonstrate that our model reproduces all the major spectral features seen in calibration data. We also describe our understanding of interactions at different layers of SCD that contribute to the observed spectrum. Using simulation results, we identify the origin of different spectral features and quantify their contributions.

Modeling the elastic energy of alloys: Potential pitfalls of continuum treatments.

PubMed

Baskaran, Arvind; Ratsch, Christian; Smereka, Peter

2015-12-01

Some issues that arise when modeling elastic energy for binary alloys are discussed within the context of a Keating model and density-functional calculations. The Keating model is a simplified atomistic formulation based on modeling elastic interactions of a binary alloy with harmonic springs whose equilibrium length is species dependent. It is demonstrated that the continuum limit for the strain field are the usual equations of linear elasticity for alloys and that they correctly capture the coarse-grained behavior of the displacement field. In addition, it is established that Euler-Lagrange equation of the continuum limit of the elastic energy will yield the same strain field equation. This is the same energy functional that is often used to model elastic effects in binary alloys. However, a direct calculation of the elastic energy atomistic model reveals that the continuum expression for the elastic energy is both qualitatively and quantitatively incorrect. This is because it does not take atomistic scale compositional nonuniformity into account. Importantly, this result also shows that finely mixed alloys tend to have more elastic energy than segregated systems, which is the exact opposite of predictions made by some continuum theories. It is also shown that for strained thin films the traditionally used effective misfit for alloys systematically underestimate the strain energy. In some models, this drawback is handled by including an elastic contribution to the enthalpy of mixing, which is characterized in terms of the continuum concentration. The direct calculation of the atomistic model reveals that this approach suffers serious difficulties. It is demonstrated that elastic contribution to the enthalpy of mixing is nonisotropic and scale dependent. It is also shown that such effects are present in density-functional theory calculations for the Si-Ge system. This work demonstrates that it is critical to include the microscopic arrangements in any elastic model to achieve even qualitatively correct behavior.

Grand European and Asian-Pacific multi-model seasonal forecasts: maximization of skill and of potential economical value to end-users

NASA Astrophysics Data System (ADS)

Alessandri, A.; De Felice, M.; Catalano, F.; Lee, J. Y.; Wang, B.; Lee, D. Y.; Yoo, J. H.; Weisheimer, A.

2017-12-01

By initiating a novel cooperation between the European and the Asian-Pacific climate-prediction communities, this work demonstrates the potential of gathering together their Multi-Model Ensembles (MMEs) to obtain useful climate predictions at seasonal time-scale.MMEs are powerful tools in dynamical climate prediction as they account for the overconfidence and the uncertainties related to single-model ensembles and increasing benefit is expected with the increase of the independence of the contributing Seasonal Prediction Systems (SPSs). In this work we combine the two MME SPSs independently developed by the European (ENSEMBLES) and by the Asian-Pacific (APCC/CliPAS) communities by establishing an unprecedented partnerships. To this aim, all the possible MME combinations obtained by putting together the 5 models from ENSEMBLES and the 11 models from APCC/CliPAS have been evaluated. The Grand ENSEMBLES-APCC/CliPAS MME enhances significantly the skill in predicting 2m temperature and precipitation. Our results show that, in general, the better combinations of SPSs are obtained by mixing ENSEMBLES and APCC/CliPAS models and that only a limited number of SPSs is required to obtain the maximum performance. The selection of models that perform better is usually different depending on the region/phenomenon under consideration so that all models are useful in some cases. It is shown that the incremental performance contribution tends to be higher when adding one model from ENSEMBLES to APCC/CliPAS MMEs and vice versa, confirming that the benefit of using MMEs amplifies with the increase of the independence the contributing models.To verify the above results for a real world application, the Grand MME is used to predict energy demand over Italy as provided by TERNA (Italian Transmission System Operator) for the period 1990-2007. The results demonstrate the useful application of MME seasonal predictions for energy demand forecasting over Italy. It is shown a significant enhancement of the potential economic value of forecasting energy demand when using the better combinations from the Grand MME by comparison to the maximum value obtained from the better combinations of each of the two contributing MMEs. Above results are discussed in a Clim Dyn paper (Alessandri et al., 2017; doi:10.1007/s00382-016-3372-4).

Building Strengths through Adventure Education

ERIC Educational Resources Information Center

Loughmiller, Grover C.

2007-01-01

Campbell Loughmiller (1906-1993) is widely recognized as a leader in therapeutic work with troubled youngsters in outdoor settings. Rejecting punitive or institutional models of intervention, Loughmiller set out to demonstrate that every young person has strengths, desires to make positive changes, can grow in responsibility, and contribute to…

EVALUATING MOLECULAR SITES OF ACTION FOR TOLUENE USING AN IN VIVO MODEL.

EPA Science Inventory

In vitro studies have demonstrated that toluene disrupts the function of several ion channels localized in the brain, including the NMDA-glutamate receptor. This has led to the hypothesis that effects on ion channel function may contribute to toluene neurotoxicity, CNS depres...

Effect of the ordered interfacial water layer in protein complex formation: A nonlocal electrostatic approach

NASA Astrophysics Data System (ADS)

Rubinstein, A.; Sabirianov, R. F.; Mei, W. N.; Namavar, F.; Khoynezhad, A.

2010-08-01

Using a nonlocal electrostatic approach that incorporates the short-range structure of the contacting media, we evaluated the electrostatic contribution to the energy of the complex formation of two model proteins. In this study, we have demonstrated that the existence of an ordered interfacial water layer at the protein-solvent interface reduces the charging energy of the proteins in the aqueous solvent, and consequently increases the electrostatic contribution to the protein binding (change in free energy upon the complex formation of two proteins). This is in contrast with the finding of the continuum electrostatic model, which suggests that electrostatic interactions are not strong enough to compensate for the unfavorable desolvation effects.

Effect of the ordered interfacial water layer in protein complex formation: A nonlocal electrostatic approach.

PubMed

Rubinstein, A; Sabirianov, R F; Mei, W N; Namavar, F; Khoynezhad, A

2010-08-01

Using a nonlocal electrostatic approach that incorporates the short-range structure of the contacting media, we evaluated the electrostatic contribution to the energy of the complex formation of two model proteins. In this study, we have demonstrated that the existence of an ordered interfacial water layer at the protein-solvent interface reduces the charging energy of the proteins in the aqueous solvent, and consequently increases the electrostatic contribution to the protein binding (change in free energy upon the complex formation of two proteins). This is in contrast with the finding of the continuum electrostatic model, which suggests that electrostatic interactions are not strong enough to compensate for the unfavorable desolvation effects.

Andreev reflection enhancement in semiconductor-superconductor structures

NASA Astrophysics Data System (ADS)

Bouscher, Shlomi; Winik, Roni; Hayat, Alex

2018-02-01

We develop a theoretical approach for modeling a wide range of semiconductor-superconductor structures with arbitrary potential barriers and a spatially dependent superconducting order parameter. We demonstrate asymmetry in the conductance spectrum as a result of a Schottky barrier shape. We further show that the Andreev reflection process can be significantly enhanced through resonant tunneling with appropriate barrier configuration, which can incorporate the Schottky barrier as a contributing component of the device. Moreover, we show that resonant tunneling can be achieved in superlattice structures as well. These theoretically demonstrated effects along with our modeling approach enable much more efficient Cooper pair injection into semiconductor-superconductor structures, including superconducting optoelectronic devices.

Neutrino-driven Explosion of a 20 Solar-mass Star in Three Dimensions Enabled by Strange-quark Contributions to Neutrino-Nucleon Scattering

NASA Astrophysics Data System (ADS)

Melson, Tobias; Janka, Hans-Thomas; Bollig, Robert; Hanke, Florian; Marek, Andreas; Müller, Bernhard

2015-08-01

Interactions with neutrons and protons play a crucial role for the neutrino opacity of matter in the supernova core. Their current implementation in many simulation codes, however, is rather schematic and ignores not only modifications for the correlated nuclear medium of the nascent neutron star, but also free-space corrections from nucleon recoil, weak magnetism, or strange quarks, which can easily add up to changes of several 10% for neutrino energies in the spectral peak. In the Garching supernova simulations with the Prometheus-Vertex code, such sophistications have been included for a long time except for the strange-quark contributions to the nucleon spin, which affect neutral-current neutrino scattering. We demonstrate on the basis of a 20 {M}⊙ progenitor star that a moderate strangeness-dependent contribution of {g}{{a}}{{s}}=-0.2 to the axial-vector coupling constant {g}{{a}}≈ 1.26 can turn an unsuccessful three-dimensional (3D) model into a successful explosion. Such a modification is in the direction of current experimental results and reduces the neutral-current scattering opacity of neutrons, which dominate in the medium around and above the neutrinosphere. This leads to increased luminosities and mean energies of all neutrino species and strengthens the neutrino-energy deposition in the heating layer. Higher nonradial kinetic energy in the gain layer signals enhanced buoyancy activity that enables the onset of the explosion at ˜300 ms after bounce, in contrast to the model with vanishing strangeness contributions to neutrino-nucleon scattering. Our results demonstrate the close proximity to explosion of the previously published, unsuccessful 3D models of the Garching group.

Contributions of aircraft arrivals and departures to ultrafine particle counts near Los Angeles International Airport.

PubMed

Hsu, Hsiao-Hsien; Adamkiewicz, Gary; Houseman, E Andres; Zarubiak, Darcy; Spengler, John D; Levy, Jonathan I

2013-02-01

While commercial aircraft are known sources of ultrafine particulate matter (UFP), the relationship between airport activity and local real-time UFP concentrations has not been quantified. Understanding these associations will facilitate interpretation of the exposure and health risk implications of UFP related to aviation emissions. We used time-resolved UFP data along with flight activity and meteorological information to determine the contributions of aircraft departures and arrivals to UFP concentrations. Aircraft flight activity and near-field continuous UFP concentrations (≧ 6 nm) were measured at five monitoring sites over a 42-day field campaign at Los Angeles International Airport (LAX). We developed regression models of UFP concentrations as a function of time-lagged landing and take-off operations (LTO) activity, in the form of arrivals or departures weighted by engine-specific estimates of fuel consumption. Our regression models demonstrate a strong association between departures and elevated total UFP concentrations at the end of the departure runway, with diminishing magnitude and time-lagged impacts with distance from the source. LTO activity contributed a median (95th, 99th percentile) UFP concentration of approximately 150,000 particles/cm(3) (2,000,000, 7,100,000) at a monitor at the end of the departure runway, versus 19,000 particles/cm(3) (80,000, 140,000), and 17,000 particles/cm(3) (50,000, 72,000) for monitors 250 m and 500 m further downwind, respectively. We demonstrated significant contributions from aircraft departure activities to UFP concentrations in close proximity to departure runways, with evidence of rapid plume evolution in the near field. Our methods can inform source attribution and interpretation of dispersion modeling outputs. Copyright © 2012 Elsevier B.V. All rights reserved.

Contribution of Large Region Joint Associations to Complex Traits Genetics

PubMed Central

Paré, Guillaume; Asma, Senay; Deng, Wei Q.

2015-01-01

A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

Characteristics and Source Apportionment of Marine Aerosols over East China Sea Using a Source-oriented Chemical Transport Model

NASA Astrophysics Data System (ADS)

Kang, M.; Zhang, H.; Fu, P.

2017-12-01

Marine aerosols exert a strong influence on global climate change and biogeochemical cycling, as oceans cover beyond 70% of the Earth's surface. However, investigations on marine aerosols are relatively limited at present due to the difficulty and inconvenience in sampling marine aerosols as well as their diverse sources. East China Sea (ECS), lying over the broad shelf of the western North Pacific, is adjacent to the Asian mainland, where continental-scale air pollution could impose a heavy load on the marine atmosphere through long-range atmospheric transport. Thus, contributions of major sources to marine aerosols need to be identified for policy makers to develop cost effective control strategies. In this work, a source-oriented version of the Community Multiscale Air Quality (CMAQ) model, which can directly track the contributions from multiple emission sources to marine aerosols, is used to investigate the contributions from power, industry, transportation, residential, biogenic and biomass burning to marine aerosols over the ECS in May and June 2014. The model simulations indicate significant spatial and temporal variations of concentrations as well as the source contributions. This study demonstrates that the Asian continent can greatly affect the marine atmosphere through long-range transport.

The Chrysler-Weldtech Approach to Retraining Displaced Workers. A Model Project to Develop Specialized Welding Skills Required for Modern Auto Assembly Operations. Final Technical Report.

ERIC Educational Resources Information Center

Lyons, Thomas M.; Knight, Glen A.

A model project was conducted to demonstrate how Chrysler, in partnership with the education community and the government, could provide technical training to enable displaced workers to contribute to the "H-Body" car launch, to improve their job skills, and to enhance their future employability. The training was conducted on a pilot…

Interleukin-6 Contributes to Inflammation and Remodeling in a Model of Adenosine Mediated Lung Injury

PubMed Central

Pedroza, Mesias; Schneider, Daniel J.; Karmouty-Quintana, Harry; Coote, Julie; Shaw, Stevan; Corrigan, Rebecca; Molina, Jose G.; Alcorn, Joseph L.; Galas, David; Gelinas, Richard; Blackburn, Michael R.

2011-01-01

Background Chronic lung diseases are the third leading cause of death in the United States due in part to an incomplete understanding of pathways that govern the progressive tissue remodeling that occurs in these disorders. Adenosine is elevated in the lungs of animal models and humans with chronic lung disease where it promotes air-space destruction and fibrosis. Adenosine signaling increases the production of the pro-fibrotic cytokine interleukin-6 (IL-6). Based on these observations, we hypothesized that IL-6 signaling contributes to tissue destruction and remodeling in a model of chronic lung disease where adenosine levels are elevated. Methodology/Principal Findings We tested this hypothesis by neutralizing or genetically removing IL-6 in adenosine deaminase (ADA)-deficient mice that develop adenosine dependent pulmonary inflammation and remodeling. Results demonstrated that both pharmacologic blockade and genetic removal of IL-6 attenuated pulmonary inflammation, remodeling and fibrosis in this model. The pursuit of mechanisms involved revealed adenosine and IL-6 dependent activation of STAT-3 in airway epithelial cells. Conclusions/Significance These findings demonstrate that adenosine enhances IL-6 signaling pathways to promote aspects of chronic lung disease. This suggests that blocking IL-6 signaling during chronic stages of disease may provide benefit in halting remodeling processes such as fibrosis and air-space destruction. PMID:21799929

Multibody model reduction by component mode synthesis and component cost analysis

NASA Technical Reports Server (NTRS)

Spanos, J. T.; Mingori, D. L.

1990-01-01

The classical assumed-modes method is widely used in modeling the dynamics of flexible multibody systems. According to the method, the elastic deformation of each component in the system is expanded in a series of spatial and temporal functions known as modes and modal coordinates, respectively. This paper focuses on the selection of component modes used in the assumed-modes expansion. A two-stage component modal reduction method is proposed combining Component Mode Synthesis (CMS) with Component Cost Analysis (CCA). First, each component model is truncated such that the contribution of the high frequency subsystem to the static response is preserved. Second, a new CMS procedure is employed to assemble the system model and CCA is used to further truncate component modes in accordance with their contribution to a quadratic cost function of the system output. The proposed method is demonstrated with a simple example of a flexible two-body system.

Enhanced vegetation growth peak and its key mechanisms

NASA Astrophysics Data System (ADS)

Huang, K.; Xia, J.; Wang, Y.; Ahlström, A.; Schwalm, C.; Huntzinger, D. N.; Chen, J.; Cook, R. B.; Fang, Y.; Fisher, J. B.; Jacobson, A. R.; Michalak, A.; Schaefer, K. M.; Wei, Y.; Yan, L.; Luo, Y.

2017-12-01

It remains unclear that whether and how the vegetation growth peak has been shifted globally during the past three decades. Here we used two global datasets of gross primary productivity (GPP) and a satellite-derived Normalized Difference Vegetation Index (NDVI) to characterize recent changes in seasonal peak vegetation growth. The attribution of changes in peak growth to their driving factors was examined with several datasets. We demonstrated that the growth peak of global vegetation has been linearly increasing during the past three decades. About 65% of this trend is evenly explained by the expanding croplands (21%), rising atmospheric [CO2] (22%), and intensifying nitrogen deposition (22%). The contribution of expanding croplands to the peak growth trend was substantiated by measurements from eddy-flux towers, sun-induced chlorophyll fluorescence and a global database of plant traits, all of which demonstrated that croplands have a higher photosynthetic capacity than other vegetation types. The contribution of rising atmospheric [CO2] and nitrogen deposition are consistent with the positive response of leaf growth to elevated [CO2] (25%) and nitrogen addition (8%) from 346 manipulated experiments. The positive effect of rising atmospheric [CO2] was also well captured by 15 terrestrial biosphere models. However, most models underestimated the contributions of land-cover change and nitrogen deposition, but overestimated the positive effect of climate change.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

Testing the Standard Model by precision measurement of the weak charges of quarks

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

Ross Young; Roger Carlini; Anthony Thomas

In a global analysis of the latest parity-violating electron scattering measurements on nuclear targets, we demonstrate a significant improvement in the experimental knowledge of the weak neutral-current lepton-quark interactions at low-energy. The precision of this new result, combined with earlier atomic parity-violation measurements, limits the magnitude of possible contributions from physics beyond the Standard Model - setting a model-independent, lower-bound on the scale of new physics at ~1 TeV.

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease.

PubMed

Gorton, Davina; Sikder, Suchandan; Williams, Natasha L; Chilton, Lisa; Rush, Catherine M; Govan, Brenda L; Cunningham, Madeleine W; Ketheesan, Natkunam

2016-12-01

Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage. We also found evidence that both complement and anti-M protein antibodies in serum from rM5-immunized rats have the potential to contribute to inflammation in heart valves by activating cardiac endothelium. More importantly, we have demonstrated by electrocardiography for the first time in the RAV model that elongation of P-R interval follows repetitive boost with rM5. Our observations provide experimental evidence for cardiac alterations following repeated exposure to GAS M protein with immunological and electrophysiological features resembling that seen in humans following recurrent GAS infection.

Multipoint Green's functions in 1 + 1 dimensional integrable quantum field theories

DOE PAGES

Babujian, H. M.; Karowski, M.; Tsvelik, A. M.

2017-02-14

We calculate the multipoint Green functions in 1+1 dimensional integrable quantum field theories. We use the crossing formula for general models and calculate the 3 and 4 point functions taking in to account only the lower nontrivial intermediate states contributions. Then we apply the general results to the examples of the scaling Z 2 Ising model, sinh-Gordon model and Z 3 scaling Potts model. We demonstrate this calculations explicitly. The results can be applied to physical phenomena as for example to the Raman scattering.

Dissemination, resuspension, and filtration of carbon fibers. [aircraft fires

NASA Technical Reports Server (NTRS)

Elber, W.

1980-01-01

Carbon fiber transport was studied using mathematical models established for other pollution problems. It was demonstrated that resuspension is not a major factor contributing to the risk. Filtration and fragmentation tests revealed that fiber fragmentation shifts the fiber spectrum to shorter mean lengths in high velocity air handling systems.

The Future of Pedagogical Action Research in Psychology

ERIC Educational Resources Information Center

Cormack, Sophie; Bourne, Victoria; Deuker, Charmaine; Norton, Lin; O'Siochcru, Cathal; Watling, Rosamond

2014-01-01

Psychology lecturers are well-qualified to carry out action research which would contribute to the theoretical understanding of learning as well as having practical benefits for students. Pedagogical action research demonstrates how knowledge of psychology can be applied to solve practical problems, providing role models of psychological literacy…

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

Kleiner, J.B.; Amiel, D.; Harwood, F.L.

A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous patellar tendon was utilized to study the early events of autograft cellular dynamics. Biochemical, autoradiographic, histological, and vascular injection techniques demonstrated that the native autograft cell population rapidly necroses. This repopulation occurs without a vascular contribution; cells entering the autograft are reliant upon synovial fluid nutrition.

Quantifying the dilution of the radiocesium contamination in Fukushima coastal river sediment (2011–2015)

PubMed Central

Evrard, Olivier; Laceby, J. Patrick; Onda, Yuichi; Wakiyama, Yoshifumi; Jaegler, Hugo; Lefèvre, Irène

2016-01-01

Fallout from the Fukushima Dai-ichi nuclear power plant accident resulted in a 3000-km2 radioactive contamination plume. Here, we model the progressive dilution of the radiocesium contamination in 327 sediment samples from two neighboring catchments with different timing of soil decontamination. Overall, we demonstrate that there has been a ~90% decrease of the contribution of upstream contaminated soils to sediment transiting the coastal plains between 2012 (median – M – contribution of 73%, mean absolute deviation – MAD – of 27%) and 2015 (M 9%, MAD 6%). The occurrence of typhoons and the progress of decontamination in different tributaries of the Niida River resulted in temporary increases in local contamination. However, the much lower contribution of upstream contaminated soils to coastal plain sediment in November 2015 demonstrates that the source of the easily erodible, contaminated material has potentially been removed by decontamination, diluted by subsoils, or eroded and transported to the Pacific Ocean. PMID:27694832

A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

PubMed Central

Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.; White, Kevin P.; Rzhetsky, Andrey

2013-01-01

Summary Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute non-additively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. PMID:24074861

Associations of PM2.5 and black carbon concentrations with traffic, idling, background pollution, and meteorology during school dismissals.

PubMed

Richmond-Bryant, J; Saganich, C; Bukiewicz, L; Kalin, R

2009-05-01

An air quality study was performed outside a cluster of schools in the East Harlem neighborhood of New York City. PM(2.5) and black carbon concentrations were monitored using real-time equipment with a one-minute averaging interval. Monitoring was performed at 1:45-3:30 PM during school days over the period October 31-November 17, 2006. The designated time period was chosen to capture vehicle emissions during end-of-day dismissals from the schools. During the monitoring period, minute-by-minute volume counts of idling and passing school buses, diesel trucks, and automobiles were obtained. These data were transcribed into time series of number of diesel vehicles idling, number of gasoline automobiles idling, number of diesel vehicles passing, and number of automobiles passing along the block adjacent to the school cluster. Multivariate regression models of the log-transform of PM(2.5) and black carbon (BC) concentrations in the East Harlem street canyon were developed using the observation data and data from the New York State Department of Environmental Conservation on meteorology and background PM(2.5). Analysis of variance was used to test the contribution of each covariate to variability in the log-transformed concentrations as a means to judge the relative contribution of each covariate. The models demonstrated that variability in background PM(2.5) contributes 80.9% of the variability in log[PM(2.5)] and 81.5% of the variability in log[BC]. Local traffic sources were demonstrated to contribute 5.8% of the variability in log[BC] and only 0.43% of the variability in log[PM(2.5)]. Diesel idling and passing were both significant contributors to variability in log[BC], while diesel passing was a significant contributor to log[PM(2.5)]. Automobile idling and passing did not contribute significant levels of variability to either concentration. The remainder of variability in each model was explained by temperature, along-canyon wind, and cross-canyon wind, which were all significant in the models.

Revisiting an old concept: the coupled oscillator model for VCD. Part 1: the generalised coupled oscillator mechanism and its intrinsic connection to the strength of VCD signals.

PubMed

Nicu, Valentin Paul

2016-08-03

Motivated by the renewed interest in the coupled oscillator (CO) model for VCD, in this work a generalised coupled oscillator (GCO) expression is derived by introducing the concept of a coupled oscillator origin. Unlike the standard CO expression, the GCO expression is exact within the harmonic approximation. Using two illustrative example molecules, the theoretical concepts introduced here are demonstrated by performing a GCO decomposition of the rotational strengths computed using DFT. This analysis shows that: (1) the contributions to the rotational strengths that are normally neglected in the standard CO model can be comparable to or larger than the CO contribution, and (2) the GCO mechanism introduced here can affect the VCD intensities of all types of modes in symmetric and asymmetric molecules.

Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

PubMed Central

Li, Feng; Wang, Xujun; Niyibizi, Christopher

2010-01-01

Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

Intellectual Performance Under Stress

DTIC Science & Technology

1976-09-01

graduate programs around the country. Taken together these lists constitute a demonstration of the important “ filter down” impact of money spent on...skills research of th 1950’s and ear ly ‘60’s. A major contributing factor to the pursuit of analytic, explanatory models of skilled performance, aside...and in combination with one and with both of the other two tasks. Tracking performance was described by the Crossover Model of McRuer and Krendel (1959

Effect of the ordered interfacial water layer in protein complex formation: a non-local electrostatic approach

NASA Astrophysics Data System (ADS)

Rubinstein, Alexander; Sabirianov, Renat

2011-03-01

Using a non-local electrostatic approach that incorporates the short-range structure of the contacting media, we evaluated the electrostatic contribution to the energy of the complex formation of two model proteins. In this study, we have demonstrated that the existence of an low-dielectric interfacial water layer at the protein-solvent interface reduces the charging energy of the proteins in the aqueous solvent, and consequently increases the electrostatic contribution to the protein binding (change in free energy upon the complex formation of two proteins). This is in contrast with the finding of the continuum electrostatic model, which suggests that electrostatic interactions are not strong enough to compensate for the unfavorable desolvation effects.

The potential energy landscape contribution to the dynamic heat capacity

NASA Astrophysics Data System (ADS)

Brown, Jonathan R.; McCoy, John D.

2011-05-01

The dynamic heat capacity of a simple polymeric, model glassformer was computed using molecular dynamics simulations by sinusoidally driving the temperature and recording the resultant energy. The underlying potential energy landscape of the system was probed by taking a time series of particle positions and quenching them. The resulting dynamic heat capacity demonstrates that the long time relaxation is the direct result of dynamics resulting from the potential energy landscape. Moreover, the equilibrium (low frequency) portion of the potential energy landscape contribution to the heat capacity is found to increase rapidly at low temperatures and at high packing fractions. This increase in the heat capacity is explained by a statistical mechanical model based on the distribution of minima in the potential energy landscape.

A regional-scale ecological risk framework for environmental flow evaluations

NASA Astrophysics Data System (ADS)

O'Brien, Gordon C.; Dickens, Chris; Hines, Eleanor; Wepener, Victor; Stassen, Retha; Quayle, Leo; Fouchy, Kelly; MacKenzie, James; Graham, P. Mark; Landis, Wayne G.

2018-02-01

Environmental flow (E-flow) frameworks advocate holistic, regional-scale, probabilistic E-flow assessments that consider flow and non-flow drivers of change in a socio-ecological context as best practice. Regional-scale ecological risk assessments of multiple stressors to social and ecological endpoints, which address ecosystem dynamism, have been undertaken internationally at different spatial scales using the relative-risk model since the mid-1990s. With the recent incorporation of Bayesian belief networks into the relative-risk model, a robust regional-scale ecological risk assessment approach is available that can contribute to achieving the best practice recommendations of E-flow frameworks. PROBFLO is a holistic E-flow assessment method that incorporates the relative-risk model and Bayesian belief networks (BN-RRM) into a transparent probabilistic modelling tool that addresses uncertainty explicitly. PROBFLO has been developed to evaluate the socio-ecological consequences of historical, current and future water resource use scenarios and generate E-flow requirements on regional spatial scales. The approach has been implemented in two regional-scale case studies in Africa where its flexibility and functionality has been demonstrated. In both case studies the evidence-based outcomes facilitated informed environmental management decision making, with trade-off considerations in the context of social and ecological aspirations. This paper presents the PROBFLO approach as applied to the Senqu River catchment in Lesotho and further developments and application in the Mara River catchment in Kenya and Tanzania. The 10 BN-RRM procedural steps incorporated in PROBFLO are demonstrated with examples from both case studies. PROBFLO can contribute to the adaptive management of water resources and contribute to the allocation of resources for sustainable use of resources and address protection requirements.

Augmenting Microarray Data with Literature-Based Knowledge to Enhance Gene Regulatory Network Inference

PubMed Central

Kilicoglu, Halil; Shin, Dongwook; Rindflesch, Thomas C.

2014-01-01

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology. PMID:24921649

Augmenting microarray data with literature-based knowledge to enhance gene regulatory network inference.

PubMed

Chen, Guocai; Cairelli, Michael J; Kilicoglu, Halil; Shin, Dongwook; Rindflesch, Thomas C

2014-06-01

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology.

A study of nonlinear dynamics of single- and two-phase flow oscillations

NASA Astrophysics Data System (ADS)

Mawasha, Phetolo Ruby

The dynamics of single- and two-phase flows in channels can be contingent on nonlinearities which are not clearly understood. These nonlinearities could be interfacial forces between the flowing fluid and its walls, variations in fluid properties, growth of voids, etc. The understanding of nonlinear dynamics of fluid flow is critical in physical systems which can undergo undesirable system operating scenarios such an oscillatory behavior which may lead to component failure. A nonlinear lumped mathematical model of a surge tank with a constant inlet flow into the tank and an outlet flow through a channel is derived from first principles. The model is used to demonstrate that surge tanks with inlet and outlet flows contribute to oscillatory behavior in laminar, turbulent, single-phase, and two-phase flow systems. Some oscillations are underdamped while others are self-sustaining. The mechanisms that are active in single-phase oscillations with no heating are presented using specific cases of simplified models. Also, it is demonstrated how an external mechanism such as boiling contributes to the oscillations observed in two-phase flow and gives rise to sustained oscillations (or pressure drop oscillations). A description of the pressure drop oscillation mechanism is presented using the steady state pressure drop versus mass flow rate characteristic curve of the heated channel, available steady state pressure drop versus mass flow rate from the surge tank, and the transient pressure drop versus mass flow rate limit cycle. Parametric studies are used to verify the theoretical pressure drop oscillations model using experimental data by Yuncu's (1990). The following contributions are unique: (1) comparisons of nonlinear pressure drop oscillation models with and without the effect of the wall thermal heat capacity and (2) comparisons of linearized pressure drop oscillation models with and without the effect of the wall thermal heat capacity to identify stability boundaries.

Self-Selection, Optimal Income Taxation, and Redistribution

ERIC Educational Resources Information Center

Amegashie, J. Atsu

2009-01-01

The author makes a pedagogical contribution to optimal income taxation. Using a very simple model adapted from George A. Akerlof (1978), he demonstrates a key result in the approach to public economics and welfare economics pioneered by Nobel laureate James Mirrlees. He shows how incomplete information, in addition to the need to preserve…

Origin of long-lived oscillations in 2D-spectra of a quantum vibronic model: Electronic versus vibrational coherence

NASA Astrophysics Data System (ADS)

Plenio, M. B.; Almeida, J.; Huelga, S. F.

2013-12-01

We demonstrate that the coupling of excitonic and vibrational motion in biological complexes can provide mechanisms to explain the long-lived oscillations that have been obtained in nonlinear spectroscopic signals of different photosynthetic pigment protein complexes and we discuss the contributions of excitonic versus purely vibrational components to these oscillatory features. Considering a dimer model coupled to a structured spectral density we exemplify the fundamental aspects of the electron-phonon dynamics, and by analyzing separately the different contributions to the nonlinear signal, we show that for realistic parameter regimes purely electronic coherence is of the same order as purely vibrational coherence in the electronic ground state. Moreover, we demonstrate how the latter relies upon the excitonic interaction to manifest. These results link recently proposed microscopic, non-equilibrium mechanisms to support long lived coherence at ambient temperatures with actual experimental observations of oscillatory behaviour using 2D photon echo techniques to corroborate the fundamental importance of the interplay of electronic and vibrational degrees of freedom in the dynamics of light harvesting aggregates.

An augmented dopamine system function is present prior to puberty in the methylazoxymethanol acetate rodent model of schizophrenia.

PubMed

Chen, Li; Perez, Stephanie M; Lodge, Daniel J

2014-09-01

Schizophrenia is a disease typically associated with an adolescent onset. Although there have been a considerable number of imaging studies investigating the transition to psychosis in prodromal patients, there are relatively few preclinical studies examining potential mechanisms that may contribute to adolescent onset. We have previously demonstrated, in the methylazoxymethanol acetate (MAM) rodent model of schizophrenia, that an enhanced activity within the ventral hippocampus may underlie the dopamine system hyperfunction, suggested to contribute to positive symptoms in patients. Here we demonstrate that the aberrant regulation of dopamine system function, in MAM-treated rats, is present prior to puberty. Furthermore, we now report that while the afferent regulation of ventral tegmental area dopamine neurons (from the hippocampus and pedunculopontine tegmental area) appears intact in preadolescent rats, the behavioral response to alterations in dopamine system function appears to be attenuated in preadolescent rats. Thus, we posit that the pathological alterations underlying psychosis may be present prior to symptom onset and that the "normal" development of the postsynaptic side of the dopamine system may underlie the transition to psychosis. © 2014 Wiley Periodicals, Inc.

Predicting vapor-liquid phase equilibria with augmented ab initio interatomic potentials

NASA Astrophysics Data System (ADS)

Vlasiuk, Maryna; Sadus, Richard J.

2017-06-01

The ability of ab initio interatomic potentials to accurately predict vapor-liquid phase equilibria is investigated. Monte Carlo simulations are reported for the vapor-liquid equilibria of argon and krypton using recently developed accurate ab initio interatomic potentials. Seventeen interatomic potentials are studied, formulated from different combinations of two-body plus three-body terms. The simulation results are compared to either experimental or reference data for conditions ranging from the triple point to the critical point. It is demonstrated that the use of ab initio potentials enables systematic improvements to the accuracy of predictions via the addition of theoretically based terms. The contribution of three-body interactions is accounted for using the Axilrod-Teller-Muto plus other multipole contributions and the effective Marcelli-Wang-Sadus potentials. The results indicate that the predictive ability of recent interatomic potentials, obtained from quantum chemical calculations, is comparable to that of accurate empirical models. It is demonstrated that the Marcelli-Wang-Sadus potential can be used in combination with accurate two-body ab initio models for the computationally inexpensive and accurate estimation of vapor-liquid phase equilibria.

Predicting vapor-liquid phase equilibria with augmented ab initio interatomic potentials.

PubMed

Vlasiuk, Maryna; Sadus, Richard J

2017-06-28

The ability of ab initio interatomic potentials to accurately predict vapor-liquid phase equilibria is investigated. Monte Carlo simulations are reported for the vapor-liquid equilibria of argon and krypton using recently developed accurate ab initio interatomic potentials. Seventeen interatomic potentials are studied, formulated from different combinations of two-body plus three-body terms. The simulation results are compared to either experimental or reference data for conditions ranging from the triple point to the critical point. It is demonstrated that the use of ab initio potentials enables systematic improvements to the accuracy of predictions via the addition of theoretically based terms. The contribution of three-body interactions is accounted for using the Axilrod-Teller-Muto plus other multipole contributions and the effective Marcelli-Wang-Sadus potentials. The results indicate that the predictive ability of recent interatomic potentials, obtained from quantum chemical calculations, is comparable to that of accurate empirical models. It is demonstrated that the Marcelli-Wang-Sadus potential can be used in combination with accurate two-body ab initio models for the computationally inexpensive and accurate estimation of vapor-liquid phase equilibria.

Environmental sub models for a macroeconomic model: agricultural contribution to climate change and acidification in Denmark.

PubMed

Jensen, Trine S; Jensen, Jørgen D; Hasler, Berit; Illerup, Jytte B; Andersen, Frits M

2007-01-01

Integrated modelling of the interaction between environmental pressure and economic development is a useful tool to evaluate environmental consequences of policy initiatives. However, the usefulness of such models is often restricted by the fact that these models only include a limited set of environmental impacts, which are often energy-related emissions. In order to evaluate the development in the overall environmental pressure correctly, these model systems must be extended. In this article an integrated macroeconomic model system of the Danish economy with environmental modules of energy related emissions is extended to include the agricultural contribution to climate change and acidification. Next to the energy sector, the agricultural sector is the most important contributor to these environmental themes and subsequently the extended model complex calculates more than 99% of the contribution to both climate change and acidification. Environmental sub-models are developed for agriculture-related emissions of CH(4), N(2)O and NH(3). Agricultural emission sources related to the production specific activity variables are mapped and emission dependent parameters are identified in order to calculate emission coefficients. The emission coefficients are linked to the economic activity variables of the Danish agricultural production. The model system is demonstrated by projections of agriculture-related emissions in Denmark under two alternative sets of assumptions: a baseline projection of the general economic development and a policy scenario for changes in the husbandry sector within the agricultural sector.

Separating intrinsic from extrinsic fluctuations in dynamic biological systems

PubMed Central

Paulsson, Johan

2011-01-01

From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems. PMID:21730172

Separating intrinsic from extrinsic fluctuations in dynamic biological systems.

PubMed

Hilfinger, Andreas; Paulsson, Johan

2011-07-19

From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems.

Major Source of Error in QSPR Prediction of Intrinsic Thermodynamic Solubility of Drugs: Solid vs Nonsolid State Contributions?

PubMed

Abramov, Yuriy A

2015-06-01

The main purpose of this study is to define the major limiting factor in the accuracy of the quantitative structure-property relationship (QSPR) models of the thermodynamic intrinsic aqueous solubility of the drug-like compounds. For doing this, the thermodynamic intrinsic aqueous solubility property was suggested to be indirectly "measured" from the contributions of solid state, ΔGfus, and nonsolid state, ΔGmix, properties, which are estimated by the corresponding QSPR models. The QSPR models of ΔGfus and ΔGmix properties were built based on a set of drug-like compounds with available accurate measurements of fusion and thermodynamic solubility properties. For consistency ΔGfus and ΔGmix models were developed using similar algorithms and descriptor sets, and validated against the similar test compounds. Analysis of the relative performances of these two QSPR models clearly demonstrates that it is the solid state contribution which is the limiting factor in the accuracy and predictive power of the QSPR models of the thermodynamic intrinsic solubility. The performed analysis outlines a necessity of development of new descriptor sets for an accurate description of the long-range order (periodicity) phenomenon in the crystalline state. The proposed approach to the analysis of limitations and suggestions for improvement of QSPR-type models may be generalized to other applications in the pharmaceutical industry.

Evaluation of consumer satisfaction using the tetra-class model.

PubMed

Clerfeuille, Fabrice; Poubanne, Yannick; Vakrilova, Milena; Petrova, Guenka

2008-09-01

A number of studies have shown the importance of consumers' satisfaction toward pharmacy services. The measurement of patient satisfaction through different elements of services provided is challenging within the context of a dynamic economic environment. Patient satisfaction is the result of long-term established habits and expectations to the pharmacy as an institution. Few studies to date have attempted to discern whether these changes have led to increased patient satisfaction and loyalty, particularly within developing nations. The objective of this study was to evaluate the elements of the services provided in Bulgarian pharmacies and their contribution to consumer satisfaction using a tetra-class model. Three main hypotheses were tested in pharmacies to validate the model in the case of complex services. Additionally, the contribution of the different service elements to the clients' satisfaction was studied. The analysis was based on a survey of customers in central and district pharmacies in Sofia, Bulgaria. The data were analyzed through a correspondence analysis which was applied to the results of the 752 distributed questionnaires. It was observed that different dimensions of the pharmacies contribute uniquely to customer satisfaction, with consumer gender contributing greatly toward satisfaction, with type/location of pharmacy, consumer age, and educational degree also playing a part. The duration of time over which the consumers have been clients at a given pharmacy influences the subsequent service categorization. This research demonstrated that the tetra-class model is suitable for application in the pharmaceutical sector. The model results could be beneficial for both researchers and pharmacy managers.

A modeling approach to direct interspecies electron transfer process in anaerobic transformation of ethanol to methane.

PubMed

Liu, Yiwen; Zhang, Yaobin; Zhao, Zhiqiang; Ngo, Huu Hao; Guo, Wenshan; Zhou, Junliang; Peng, Lai; Ni, Bing-Jie

2017-01-01

Recent studies have shown that direct interspecies electron transfer (DIET) plays an important part in contributing to methane production from anaerobic digestion. However, so far anaerobic digestion models that have been proposed only consider two pathways for methane production, namely, acetoclastic methanogenesis and hydrogenotrophic methanogenesis, via indirect interspecies hydrogen transfer, which lacks an effective way for incorporating DIET into this paradigm. In this work, a new mathematical model is specifically developed to describe DIET process in anaerobic digestion through introducing extracellular electron transfer as a new pathway for methane production, taking anaerobic transformation of ethanol to methane as an example. The developed model was able to successfully predict experimental data on methane dynamics under different experimental conditions, supporting the validity of the developed model. Modeling predictions clearly demonstrated that DIET plays an important role in contributing to overall methane production (up to 33 %) and conductive material (i.e., carbon cloth) addition would significantly promote DIET through increasing ethanol conversion rate and methane production rate. The model developed in this work will potentially enhance our current understanding on syntrophic metabolism via DIET.

Contribution of crop model structure, parameters and climate projections to uncertainty in climate change impact assessments.

PubMed

Tao, Fulu; Rötter, Reimund P; Palosuo, Taru; Gregorio Hernández Díaz-Ambrona, Carlos; Mínguez, M Inés; Semenov, Mikhail A; Kersebaum, Kurt Christian; Nendel, Claas; Specka, Xenia; Hoffmann, Holger; Ewert, Frank; Dambreville, Anaelle; Martre, Pierre; Rodríguez, Lucía; Ruiz-Ramos, Margarita; Gaiser, Thomas; Höhn, Jukka G; Salo, Tapio; Ferrise, Roberto; Bindi, Marco; Cammarano, Davide; Schulman, Alan H

2018-03-01

Climate change impact assessments are plagued with uncertainties from many sources, such as climate projections or the inadequacies in structure and parameters of the impact model. Previous studies tried to account for the uncertainty from one or two of these. Here, we developed a triple-ensemble probabilistic assessment using seven crop models, multiple sets of model parameters and eight contrasting climate projections together to comprehensively account for uncertainties from these three important sources. We demonstrated the approach in assessing climate change impact on barley growth and yield at Jokioinen, Finland in the Boreal climatic zone and Lleida, Spain in the Mediterranean climatic zone, for the 2050s. We further quantified and compared the contribution of crop model structure, crop model parameters and climate projections to the total variance of ensemble output using Analysis of Variance (ANOVA). Based on the triple-ensemble probabilistic assessment, the median of simulated yield change was -4% and +16%, and the probability of decreasing yield was 63% and 31% in the 2050s, at Jokioinen and Lleida, respectively, relative to 1981-2010. The contribution of crop model structure to the total variance of ensemble output was larger than that from downscaled climate projections and model parameters. The relative contribution of crop model parameters and downscaled climate projections to the total variance of ensemble output varied greatly among the seven crop models and between the two sites. The contribution of downscaled climate projections was on average larger than that of crop model parameters. This information on the uncertainty from different sources can be quite useful for model users to decide where to put the most effort when preparing or choosing models or parameters for impact analyses. We concluded that the triple-ensemble probabilistic approach that accounts for the uncertainties from multiple important sources provide more comprehensive information for quantifying uncertainties in climate change impact assessments as compared to the conventional approaches that are deterministic or only account for the uncertainties from one or two of the uncertainty sources. © 2017 John Wiley & Sons Ltd.

Contribution of the Alternative Respiratory Pathway to PSII Photoprotection in C3 and C4 Plants.

PubMed

Zhang, Zi-Shan; Liu, Mei-Jun; Scheibe, Renate; Selinski, Jennifer; Zhang, Li-Tao; Yang, Cheng; Meng, Xiang-Long; Gao, Hui-Yuan

2017-01-09

The mechanism by which the mitochondrial alternative oxidase (AOX) pathway contributes to photosystem II (PSII) photoprotection is in dispute. It was generally thought that the AOX pathway protects photosystems by dissipating excess reducing equivalents exported from chloroplasts through the malate/oxaloacetate (Mal/OAA) shuttle and thus preventing the over-reduction of chloroplasts. In this study, using the aox1a Arabidopsis mutant and nine other C3 and C4 plant species, we revealed an additional action model of the AOX pathway in PSII photoprotection. Although the AOX pathway contributes to PSII photoprotection in C3 leaves treated with high light, this contribution was observed to disappear when photorespiration was suppressed. Disruption or inhibition of the AOX pathway significantly decreased the photorespiration in C3 leaves. Moreover, the AOX pathway did not respond to high light and contributed little to PSII photoprotection in C4 leaves possessing a highly active Mal/OAA shuttle but with little photorespiration. These results demonstrate that the AOX pathway contributes to PSII photoprotection in C3 plants by maintaining photorespiration to detoxify glycolate and via the indirect export of excess reducing equivalents from chloroplasts by the Mal/OAA shuttle. This new action model explains why the AOX pathway does not contribute to PSII photoprotection in C4 plants. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Analyzing the contribution of climate change to long-term variations in sediment nitrogen sources for reservoirs/lakes.

PubMed

Xia, Xinghui; Wu, Qiong; Zhu, Baotong; Zhao, Pujun; Zhang, Shangwei; Yang, Lingyan

2015-08-01

We applied a mixing model based on stable isotopic δ(13)C, δ(15)N, and C:N ratios to estimate the contributions of multiple sources to sediment nitrogen. We also developed a conceptual model describing and analyzing the impacts of climate change on nitrogen enrichment. These two models were conducted in Miyun Reservoir to analyze the contribution of climate change to the variations in sediment nitrogen sources based on two (210)Pb and (137)Cs dated sediment cores. The results showed that during the past 50years, average contributions of soil and fertilizer, submerged macrophytes, N2-fixing phytoplankton, and non-N2-fixing phytoplankton were 40.7%, 40.3%, 11.8%, and 7.2%, respectively. In addition, total nitrogen (TN) contents in sediment showed significant increasing trends from 1960 to 2010, and sediment nitrogen of both submerged macrophytes and phytoplankton sources exhibited significant increasing trends during the past 50years. In contrast, soil and fertilizer sources showed a significant decreasing trend from 1990 to 2010. According to the changing trend of N2-fixing phytoplankton, changes of temperature and sunshine duration accounted for at least 43% of the trend in the sediment nitrogen enrichment over the past 50years. Regression analysis of the climatic factors on nitrogen sources showed that the contributions of precipitation, temperature, and sunshine duration to the variations in sediment nitrogen sources ranged from 18.5% to 60.3%. The study demonstrates that the mixing model provides a robust method for calculating the contribution of multiple nitrogen sources in sediment, and this study also suggests that N2-fixing phytoplankton could be regarded as an important response factor for assessing the impacts of climate change on nitrogen enrichment. Copyright © 2015 Elsevier B.V. All rights reserved.

Corolla Is a Novel Protein That Contributes to the Architecture of the Synaptonemal Complex of Drosophila

PubMed Central

Collins, Kimberly A.; Unruh, Jay R.; Slaughter, Brian D.; Yu, Zulin; Lake, Cathleen M.; Nielsen, Rachel J.; Box, Kimberly S.; Miller, Danny E.; Blumenstiel, Justin P.; Perera, Anoja G.; Malanowski, Kathryn E.; Hawley, R. Scott

2014-01-01

In most organisms the synaptonemal complex (SC) connects paired homologs along their entire length during much of meiotic prophase. To better understand the structure of the SC, we aim to identify its components and to determine how each of these components contributes to SC function. Here, we report the identification of a novel SC component in Drosophila melanogaster female oocytes, which we have named Corolla. Using structured illumination microscopy, we demonstrate that Corolla is a component of the central region of the SC. Consistent with its localization, we show by yeast two-hybrid analysis that Corolla strongly interacts with Cona, a central element protein, demonstrating the first direct interaction between two inner-synaptonemal complex proteins in Drosophila. These observations help provide a more complete model of SC structure and function in Drosophila females. PMID:24913682

Using an Altimeter-Derived Internal Tide Model to Remove Tides from in Situ Data

NASA Technical Reports Server (NTRS)

Zaron, Edward D.; Ray, Richard D.

2017-01-01

Internal waves at tidal frequencies, i.e., the internal tides, are a prominent source of variability in the ocean associated with significant vertical isopycnal displacements and currents. Because the isopycnal displacements are caused by ageostrophic dynamics, they contribute uncertainty to geostrophic transport inferred from vertical profiles in the ocean. Here it is demonstrated that a newly developed model of the main semidiurnal (M2) internal tide derived from satellite altimetry may be used to partially remove the tide from vertical profile data, as measured by the reduction of steric height variance inferred from the profiles. It is further demonstrated that the internal tide model can account for a component of the near-surface velocity as measured by drogued drifters. These comparisons represent a validation of the internal tide model using independent data and highlight its potential use in removing internal tide signals from in situ observations.

Statistical models for causation: what inferential leverage do they provide?

PubMed

Freedman, David A

2006-12-01

Experiments offer more reliable evidence on causation than observational studies, which is not to gainsay the contribution to knowledge from observation. Experiments should be analyzed as experiments, not as observational studies. A simple comparison of rates might be just the right tool, with little value added by "sophisticated" models. This article discusses current models for causation, as applied to experimental and observational data. The intention-to-treat principle and the effect of treatment on the treated will also be discussed. Flaws in per-protocol and treatment-received estimates will be demonstrated.

Measurement and Modeling of Ultrasonic Pitch/catch Grain Noise

NASA Astrophysics Data System (ADS)

Margetan, F. J.; Gray, T. A.; Thompson, R. B.

2008-02-01

Ultrasonic grain noise arises from the scattering of sound waves by microstructural boundaries, and can limit the detection of weakly-reflecting internal defects in metals. In some cases of practical interest, such as focused-transducer inspections of aircraft engine components, so-called "single scattering" or "independent scatterer" models have proven to be reasonably accurate in predicting grain noise characteristics. In pulse/echo inspections it is difficult to experimentally assess the relative contributions of single scattering and multiple scattering, because both can generally contribute to the backscattered noise seen at any given observation time. For pitch/catch inspections, however, it is relatively easy to construct inspection geometries for which single-scattered noise should be insignificant, and hence any observed noise is presumably due to multiple scattering. This concept is demonstrated using pitch/catch shear-wave measurements performed on a well-characterized stainless-steel specimen. The inspection geometry allows us to control the overlap volume of the intersecting radiation fields of the two transducers. As we proceed from maximally overlapping fields to zero overlap, the single-scattering contribution to the observed grain noise is expected to decrease. Measurements are compared to the predictions of a single-scatterer model, and the relative contributions of single and multiple scattering to the observed grain noise are estimated.

A Thermodynamically Consistent Approach to Phase-Separating Viscous Fluids

NASA Astrophysics Data System (ADS)

Anders, Denis; Weinberg, Kerstin

2018-04-01

The de-mixing properties of heterogeneous viscous fluids are determined by an interplay of diffusion, surface tension and a superposed velocity field. In this contribution a variational model of the decomposition, based on the Navier-Stokes equations for incompressible laminar flow and the extended Korteweg-Cahn-Hilliard equations, is formulated. An exemplary numerical simulation using C1-continuous finite elements demonstrates the capability of this model to compute phase decomposition and coarsening of the moving fluid.

Simple analytical model for low-frequency frequency-modulation noise of monolithic tunable lasers.

PubMed

Huynh, Tam N; Ó Dúill, Seán P; Nguyen, Lim; Rusch, Leslie A; Barry, Liam P

2014-02-10

We employ simple analytical models to construct the entire frequency-modulation (FM)-noise spectrum of tunable semiconductor lasers. Many contributions to the laser FM noise can be clearly identified from the FM-noise spectrum, such as standard Weiner FM noise incorporating laser relaxation oscillation, excess FM noise due to thermal fluctuations, and carrier-induced refractive index fluctuations from stochastic carrier generation in the passive tuning sections. The contribution of the latter effect is identified by noting a correlation between part of the FM-noise spectrum with the FM-modulation response of the passive sections. We pay particular attention to the case of widely tunable lasers with three independent tuning sections, mainly the sampled-grating distributed Bragg reflector laser, and compare with that of a distributed feedback laser. The theoretical model is confirmed with experimental measurements, with the calculations of the important phase-error variance demonstrating excellent agreement.

Best (but oft-forgotten) practices: mediation analysis.

PubMed

Fairchild, Amanda J; McDaniel, Heather L

2017-06-01

This contribution in the "Best (but Oft-Forgotten) Practices" series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. © 2017 American Society for Nutrition.

Best (but oft-forgotten) practices: mediation analysis12

PubMed Central

McDaniel, Heather L

2017-01-01

This contribution in the “Best (but Oft-Forgotten) Practices” series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. PMID:28446497

Modeling Electronic-Nuclear Interactions for Excitation Energy Transfer Processes in Light-Harvesting Complexes.

PubMed

Lee, Mi Kyung; Coker, David F

2016-08-18

An accurate approach for computing intermolecular and intrachromophore contributions to spectral densities to describe the electronic-nuclear interactions relevant for modeling excitation energy transfer processes in light harvesting systems is presented. The approach is based on molecular dynamics (MD) calculations of classical correlation functions of long-range contributions to excitation energy fluctuations and a separate harmonic analysis and single-point gradient quantum calculations for electron-intrachromophore vibrational couplings. A simple model is also presented that enables detailed analysis of the shortcomings of standard MD-based excitation energy fluctuation correlation function approaches. The method introduced here avoids these problems, and its reliability is demonstrated in accurate predictions for bacteriochlorophyll molecules in the Fenna-Matthews-Olson pigment-protein complex, where excellent agreement with experimental spectral densities is found. This efficient approach can provide instantaneous spectral densities for treating the influence of fluctuations in environmental dissipation on fast electronic relaxation.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Evolutionary Self-Questioning Games with Local Contribution

NASA Astrophysics Data System (ADS)

Liu, Yong-Kui; Li, Zhi; Chen, Xiao-Jie; Wang, Long

2009-08-01

We investigate the evolutionary Prisoner's Dilemma and the Snowdrift Game on small-world networks in a realistic social context where individuals consider their local contributions to their group and update their strategies by self-questioning. An individual with introspection can determine whether its current strategy is superior by playing a virtual round of the game and its local contribution is defined as the sum of all the payoffs its neighbors collect against it. In our model, the performance of an individual is determined by both its payoff and local contribution through a linear combination. We demonstrate that the present mechanism can produce very robust cooperative behavior in both games. Furthermore, we provide theoretical analysis based on mean-field approximation, and find that the analytical predictions are qualitatively consistent with the simulation results.

A compact model of the reverse gate-leakage current in GaN-based HEMTs

NASA Astrophysics Data System (ADS)

Ma, Xiaoyu; Huang, Junkai; Fang, Jielin; Deng, Wanling

2016-12-01

The gate-leakage behavior in GaN-based high electron mobility transistors (HEMTs) is studied as a function of applied bias and temperature. A model to calculate this current is given, which shows that trap-assisted tunneling, trap-assisted Frenkel-Poole (FP) emission, and direct Fowler-Nordheim (FN) tunneling have their main contributions at different electric field regions. In addition, the proposed model clearly illustrates the effect of traps and their assistance to the gate leakage. We have demonstrated the validity of the model by comparisons between model simulation results and measured experimental data of HEMTs, and a good agreement is obtained.

Attribution of horizontal and vertical contributions to spurious mixing in an Arbitrary Lagrangian-Eulerian ocean model

NASA Astrophysics Data System (ADS)

Gibson, Angus H.; Hogg, Andrew McC.; Kiss, Andrew E.; Shakespeare, Callum J.; Adcroft, Alistair

2017-11-01

We examine the separate contributions to spurious mixing from horizontal and vertical processes in an ALE ocean model, MOM6, using reference potential energy (RPE). The RPE is a global diagnostic which changes only due to mixing between density classes. We extend this diagnostic to a sub-timestep timescale in order to individually separate contributions to spurious mixing through horizontal (tracer advection) and vertical (regridding/remapping) processes within the model. We both evaluate the overall spurious mixing in MOM6 against previously published output from other models (MOM5, MITGCM and MPAS-O), and investigate impacts on the components of spurious mixing in MOM6 across a suite of test cases: a lock exchange, internal wave propagation, and a baroclinically-unstable eddying channel. The split RPE diagnostic demonstrates that the spurious mixing in a lock exchange test case is dominated by horizontal tracer advection, due to the spatial variability in the velocity field. In contrast, the vertical component of spurious mixing dominates in an internal waves test case. MOM6 performs well in this test case owing to its quasi-Lagrangian implementation of ALE. Finally, the effects of model resolution are examined in a baroclinic eddies test case. In particular, the vertical component of spurious mixing dominates as horizontal resolution increases, an important consideration as global models evolve towards higher horizontal resolutions.

Hydrodynamic modelling of the microbial water quality in a drinking water source as input for risk reduction management

NASA Astrophysics Data System (ADS)

Sokolova, Ekaterina; Pettersson, Thomas J. R.; Bergstedt, Olof; Hermansson, Malte

2013-08-01

To mitigate the faecal contamination of drinking water sources and, consequently, to prevent waterborne disease outbreaks, an estimation of the contribution from different sources to the total faecal contamination at the raw water intake of a drinking water treatment plant is needed. The aim of this article was to estimate how much different sources contributed to the faecal contamination at the water intake in a drinking water source, Lake Rådasjön in Sweden. For this purpose, the fate and transport of faecal indicator Escherichia coli within Lake Rådasjön were simulated by a three-dimensional hydrodynamic model. The calibrated hydrodynamic model described the measured data on vertical temperature distribution in the lake well (the Pearson correlation coefficient was 0.99). The data on the E. coli load from the identified contamination sources were gathered and the fate and transport of E. coli released from these sources within the lake were simulated using the developed hydrodynamic model, taking the decay of the E. coli into account. The obtained modelling results were compared to the observed E. coli concentrations at the water intake. The results illustrated that the sources that contributed the most to the faecal contamination at the water intake in Lake Rådasjön were the discharges from the on-site sewers and the main inflow to the lake - the river Mölndalsån. Based on the modelling results recommendations for water producers were formulated. The study demonstrated that this modelling approach is a useful tool for estimating the contribution from different sources to the faecal contamination at the water intake of a drinking water treatment plant and provided decision-support information for the reduction of risks posed to the drinking water source.

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

Wang, Taiping; Yang, Zhaoqing

Increased eutrophication and degraded water quality in estuarine and coastal waters have been a worldwide environmental concern. While it is commonly accepted that anthropogenic impact plays a major role in many emerging water quality issues, natural conditions such as restricted water circulations controlled by geometry may also substantially contribute to unfavorable water quality in certain ecosystems. To elucidate the contributions from different factors, a hydrodynamic-water quality model that integrates both physical transport and pollutant loadings is particularly warranted. A preliminary modeling study using the Environmental Fluid Dynamic Code (EFDC) is conducted to investigate hydrodynamic circulation and low dissolved oxygen (DO)more » in Hood Canal, a representative fjord in the U.S. Pacific Northwest. Because the water quality modeling work is still ongoing, this paper focuses on the progress in hydrodynamic modeling component. The hydrodynamic model has been set up using the publicly available forcing data and was calibrated against field observations or NOAA predictions for tidal elevation, current, salinity and temperature. The calibrated model was also used to estimate physical transport timescales such as residence time in the estuary. The preliminary model results demonstrate that the EFDC Hood Canal model is capable of capturing the general circulation patterns in Hood Canal, including weak tidal current and strong vertical stratification. The long residence time (i.e., on the order of 100 days for the entire estuary) also indicates that restricted water circulation could contribute to low DO in the estuary and also makes the system especially susceptible to anthropogenic disturbance, such as excess nutrient input.« less

Modeling error in experimental assays using the bootstrap principle: Understanding discrepancies between assays using different dispensing technologies

PubMed Central

Hanson, Sonya M.; Ekins, Sean; Chodera, John D.

2015-01-01

All experimental assay data contains error, but the magnitude, type, and primary origin of this error is often not obvious. Here, we describe a simple set of assay modeling techniques based on the bootstrap principle that allow sources of error and bias to be simulated and propagated into assay results. We demonstrate how deceptively simple operations—such as the creation of a dilution series with a robotic liquid handler—can significantly amplify imprecision and even contribute substantially to bias. To illustrate these techniques, we review an example of how the choice of dispensing technology can impact assay measurements, and show how large contributions to discrepancies between assays can be easily understood and potentially corrected for. These simple modeling techniques—illustrated with an accompanying IPython notebook—can allow modelers to understand the expected error and bias in experimental datasets, and even help experimentalists design assays to more effectively reach accuracy and imprecision goals. PMID:26678597

The contribution of general cognitive abilities and number abilities to different aspects of mathematics in children.

PubMed

Träff, Ulf

2013-10-01

This study examined the relative contributions of general cognitive abilities and number abilities to word problem solving, calculation, and arithmetic fact retrieval in a sample of 134 children aged 10 to 13 years. The following tasks were administered: listening span, visual matrix span, verbal fluency, color naming, Raven's Progressive Matrices, enumeration, number line estimation, and digit comparison. Hierarchical multiple regressions demonstrated that number abilities provided an independent contribution to fact retrieval and word problem solving. General cognitive abilities contributed to problem solving and calculation. All three number tasks accounted for a similar amount of variance in fact retrieval, whereas only the number line estimation task contributed unique variance in word problem solving. Verbal fluency and Raven's matrices accounted for an equal amount of variance in problem solving and calculation. The current findings demonstrate, in accordance with Fuchs and colleagues' developmental model of mathematical learning (Developmental Psychology, 2010, Vol. 46, pp. 1731-1746), that both number abilities and general cognitive abilities underlie 10- to 13-year-olds' proficiency in problem solving, whereas only number abilities underlie arithmetic fact retrieval. Thus, the amount and type of cognitive contribution to arithmetic proficiency varies between the different aspects of arithmetic. Furthermore, how closely linked a specific aspect of arithmetic is to the whole number representation systems is not the only factor determining the amount and type of cognitive contribution in 10- to 13-year-olds. In addition, the mathematical complexity of the task appears to influence the amount and type of cognitive support. Copyright © 2013 Elsevier Inc. All rights reserved.

Using Confirmatory Factor Analysis to Understand Executive Control in Preschool Children: Sources of Variation in Emergent Mathematic Achievement

ERIC Educational Resources Information Center

Bull, Rebecca; Espy, Kimberly Andrews; Wiebe, Sandra A.; Sheffield, Tiffany D.; Nelson, Jennifer Mize

2011-01-01

Latent variable modeling methods have demonstrated utility for understanding the structure of executive control (EC) across development. These methods are utilized to better characterize the relation between EC and mathematics achievement in the preschool period, and to understand contributing sources of individual variation. Using the sample and…

Narrative Autoethnography and the Promotion of Spiritual Well-Being in Teacher Research and Practice

ERIC Educational Resources Information Center

Long, Louise

2008-01-01

This article demonstrates through an example the usefulness of autoethnography as a mechanism for teachers acquiring clarity about their spiritual experiences, which has the potential to contribute to facilitating pupils' spiritual growth. I begin by examining the role of the spiritual dimension in the promotion of a holistic model of education.…

Anticipated Work-Family Conflict: Effects of Gender, Self-Efficacy, and Family Background

ERIC Educational Resources Information Center

Cinamon, Rachel Gali

2006-01-01

Anticipated levels of 2 types of work-family conflict (WFC) were studied among 358 students from 2 universities. The study examined the contribution of gender, parental models of child care and housework, and self-efficacy to the variance in anticipated WFC. Findings demonstrated that the bidirectionality of the relations between work and family…

Higgs decays to Z Z and Z γ in the standard model effective field theory: An NLO analysis

NASA Astrophysics Data System (ADS)

Dawson, S.; Giardino, P. P.

2018-05-01

We calculate the complete one-loop electroweak corrections to the inclusive H →Z Z and H →Z γ decays in the dimension-6 extension of the Standard Model Effective Field Theory (SMEFT). The corrections to H →Z Z are computed for on-shell Z bosons and are a precursor to the physical H →Z f f ¯ calculation. We present compact numerical formulas for our results and demonstrate that the logarithmic contributions that result from the renormalization group evolution of the SMEFT coefficients are larger than the finite next-to-leading-order contributions to the decay widths. As a byproduct of our calculation, we obtain the first complete result for the finite corrections to Gμ in the SMEFT.

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets

PubMed Central

Satterfield, Benjamin A.; Cross, Robert W.; Fenton, Karla A.; Borisevich, Viktoriya; Agans, Krystle N.; Deer, Daniel J.; Graber, Jessica; Basler, Christopher F.; Mire, Chad E.

2016-01-01

ABSTRACT Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. IMPORTANCE Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological impairment, such as that seen in human survivors. This new ferret NiV C and W knockout model may allow, for the first time, the examination of interventions to prevent or mitigate the neurological damage and sequelae experienced by human survivors. PMID:27147733

Nipah Virus C and W Proteins Contribute to Respiratory Disease in Ferrets.

PubMed

Satterfield, Benjamin A; Cross, Robert W; Fenton, Karla A; Borisevich, Viktoriya; Agans, Krystle N; Deer, Daniel J; Graber, Jessica; Basler, Christopher F; Geisbert, Thomas W; Mire, Chad E

2016-07-15

Nipah virus (NiV) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. The ferret model has emerged as the preferred small-animal model with which to study NiV disease, but much is still unknown about the viral determinants of NiV pathogenesis, including the contribution of the C protein in ferrets. Additionally, studies have yet to examine the synergistic effects of the various P gene products on pathogenesis in animal models. Using recombinant NiVs (rNiVs), we examine the sole contribution of the NiV C protein and the combined contributions of the C and W proteins in the ferret model of NiV pathogenesis. We show that an rNiV void of C expression resulted in 100% mortality, though with limited respiratory disease, like our previously reported rNiV void of W expression; this finding is in stark contrast to the attenuated phenotype observed in previous hamster studies utilizing rNiVs void of C expression. We also observed that an rNiV void of both C and W expression resulted in limited respiratory disease; however, there was severe neurological disease leading to 60% mortality, and the surviving ferrets demonstrated sequelae similar to those for human survivors of NiV encephalitis. Nipah virus (NiV) is a human pathogen capable of causing lethal respiratory and neurological disease. Many human survivors have long-lasting neurological impairment. Using a ferret model, this study demonstrated the roles of the NiV C and W proteins in pathogenesis, where lack of either the C or the W protein independently decreased the severity of clinical respiratory disease but did not decrease lethality. Abolishing both C and W expression, however, dramatically decreased the severity of respiratory disease and the level of destruction of splenic germinal centers. These ferrets still suffered severe neurological disease: 60% succumbed to disease, and the survivors experienced long-term neurological impairment, such as that seen in human survivors. This new ferret NiV C and W knockout model may allow, for the first time, the examination of interventions to prevent or mitigate the neurological damage and sequelae experienced by human survivors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

An Improved Model of Cryogenic Propellant Stratification in a Rotating, Reduced Gravity Environment

NASA Technical Reports Server (NTRS)

Oliveira, Justin; Kirk, Daniel R.; Schallhorn, Paul A.; Piquero, Jorge L.; Campbell, Mike; Chase, Sukhdeep

2007-01-01

This paper builds on a series of analytical literature models used to predict thermal stratification within rocket propellant tanks. The primary contribution to the literature is to add the effect of tank rotation and to demonstrate the influence of rotation on stratification times and temperatures. This work also looks levels of thermal stratification for generic propellant tanks (cylindrical shapes) over a parametric range of upper-stage coast times, heating levels, rotation rates, and gravity levels.

Testing the standard model by precision measurement of the weak charges of quarks.

PubMed

Young, R D; Carlini, R D; Thomas, A W; Roche, J

2007-09-21

In a global analysis of the latest parity-violating electron scattering measurements on nuclear targets, we demonstrate a significant improvement in the experimental knowledge of the weak neutral-current lepton-quark interactions at low energy. The precision of this new result, combined with earlier atomic parity-violation measurements, places tight constraints on the size of possible contributions from physics beyond the standard model. Consequently, this result improves the lower-bound on the scale of relevant new physics to approximately 1 TeV.

Demonstrating the improvement of predictive maturity of a computational model

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

Hemez, Francois M; Unal, Cetin; Atamturktur, Huriye S

2010-01-01

We demonstrate an improvement of predictive capability brought to a non-linear material model using a combination of test data, sensitivity analysis, uncertainty quantification, and calibration. A model that captures increasingly complicated phenomena, such as plasticity, temperature and strain rate effects, is analyzed. Predictive maturity is defined, here, as the accuracy of the model to predict multiple Hopkinson bar experiments. A statistical discrepancy quantifies the systematic disagreement (bias) between measurements and predictions. Our hypothesis is that improving the predictive capability of a model should translate into better agreement between measurements and predictions. This agreement, in turn, should lead to a smallermore » discrepancy. We have recently proposed to use discrepancy and coverage, that is, the extent to which the physical experiments used for calibration populate the regime of applicability of the model, as basis to define a Predictive Maturity Index (PMI). It was shown that predictive maturity could be improved when additional physical tests are made available to increase coverage of the regime of applicability. This contribution illustrates how the PMI changes as 'better' physics are implemented in the model. The application is the non-linear Preston-Tonks-Wallace (PTW) strength model applied to Beryllium metal. We demonstrate that our framework tracks the evolution of maturity of the PTW model. Robustness of the PMI with respect to the selection of coefficients needed in its definition is also studied.« less

Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte

PubMed Central

Dasgupta, Sabyasachi; Auth, Thorsten; Gov, Nir S.; Satchwell, Timothy J.; Hanssen, Eric; Zuccala, Elizabeth S.; Riglar, David T.; Toye, Ashley M.; Betz, Timo; Baum, Jake; Gompper, Gerhard

2014-01-01

The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells. PMID:24988340

Increasing anthropogenic nitrogen inputs and riverine DIN exports from the Changjiang River basin under changing human pressures

NASA Astrophysics Data System (ADS)

Yan, Weijin; Mayorga, Emilio; Li, Xinyan; Seitzinger, Sybil P.; Bouwman, A. F.

2010-12-01

In this paper, we estimate the inputs of nitrogen (N) and exports of dissolved inorganic nitrogen (DIN) from the Changjiang River to the estuary for the period 1970-2003, by using the global NEWS-DIN model. Modeled DIN yields range from 260 kg N km-2 yr-1 in 1970 to 895 kg N km-2 yr-1 in 2003, with an increasing trend. The study demonstrated a varied contribution of different N inputs to river DIN yields during the period 1970-2003. Chemical fertilizer and manure together contributed about half of the river DIN yields, while atmospheric N deposition contributed an average of 21% of DIN yields in the period 1970-2003. Biological N fixation contributed 40% of DIN yields in 1970, but substantially decreased to 13% in 2003. Point sewage N input also showed a decreasing trend in contribution to DIN yields, with an average of 8% over the whole period. We also discuss possible future trajectories of DIN export based on the Global NEWS implementation of the Millennium Ecosystem Assessment scenarios. Our result indicates that anthropogenically enhanced N inputs dominate and will continue to dominate river DIN yields under changing human pressures in the basin. Therefore, nitrogen pollution is and will continue to be a great challenge to China.

Contribution of the GOCE gradiometer components to regional gravity solutions

NASA Astrophysics Data System (ADS)

Naeimi, Majid; Bouman, Johannes

2017-05-01

The contribution of the GOCE gravity gradients to regional gravity field solutions is investigated in this study. We employ radial basis functions to recover the gravity field on regional scales over Amazon and Himalayas as our test regions. In the first step, four individual solutions based on the more accurate gravity gradient components Txx, Tyy, Tzz and Txz are derived. The Tzz component gives better solution than the other single-component solutions despite the less accuracy of Tzz compared to Txx and Tyy. Furthermore, we determine five more solutions based on several selected combinations of the gravity gradient components including a combined solution using the four gradient components. The Tzz and Tyy components are shown to be the main contributors in all combined solutions whereas the Txz adds the least value to the regional gravity solutions. We also investigate the contribution of the regularization term. We show that the contribution of the regularization significantly decreases as more gravity gradients are included. For the solution using all gravity gradients, regularization term contributes to about 5 per cent of the total solution. Finally, we demonstrate that in our test areas, regional gravity modelling based on GOCE data provide more reliable gravity signal in medium wavelengths as compared to pre-GOCE global gravity field models such as the EGM2008.

Differential methylation is associated with non-syndromic cleft lip and palate and contributes to penetrance effects.

PubMed

Alvizi, Lucas; Ke, Xiayi; Brito, Luciano Abreu; Seselgyte, Rimante; Moore, Gudrun E; Stanier, Philip; Passos-Bueno, Maria Rita

2017-05-26

Non-syndromic cleft lip and/or palate (NSCLP) is a common congenital malformation with a multifactorial model of inheritance. Although several at-risk alleles have been identified, they do not completely explain the high heritability. We postulate that epigenetic factors as DNA methylation might contribute to this missing heritability. Using a Methylome-wide association study in a Brazilian cohort (67 NSCLP, 59 controls), we found 578 methylation variable positions (MVPs) that were significantly associated with NSCLP. MVPs were enriched in regulatory and active regions of the genome and in pathways already implicated in craniofacial development. In an independent UK cohort (171 NSCLP, 177 controls), we replicated 4 out of 11 tested MVPs. We demonstrated a significant positive correlation between blood and lip tissue DNA methylation, indicating blood as a suitable tissue for NSCLP methylation studies. Next, we quantified CDH1 promoter methylation levels in CDH1 mutation-positive families, including penetrants, non-penetrants or non-carriers for NSCLP. We found methylation levels to be significantly higher in the penetrant individuals. Taken together, our results demonstrated the association of methylation at specific genomic locations as contributing factors to both non-familial and familial NSCLP and altered DNA methylation may be a second hit contributing to penetrance.

Estimate of main local sources to ambient ultrafine particle number concentrations in an urban area

NASA Astrophysics Data System (ADS)

Rahman, Md Mahmudur; Mazaheri, Mandana; Clifford, Sam; Morawska, Lidia

2017-09-01

Quantifying and apportioning the contribution of a range of sources to ultrafine particles (UFPs, D < 100 nm) is a challenge due to the complex nature of the urban environments. Although vehicular emissions have long been considered one of the major sources of ultrafine particles in urban areas, the contribution of other major urban sources is not yet fully understood. This paper aims to determine and quantify the contribution of local ground traffic, nucleated particle (NP) formation and distant non-traffic (e.g. airport, oil refineries, and seaport) sources to the total ambient particle number concentration (PNC) in a busy, inner-city area in Brisbane, Australia using Bayesian statistical modelling and other exploratory tools. The Bayesian model was trained on the PNC data on days where NP formations were known to have not occurred, hourly traffic counts, solar radiation data, and smooth daily trend. The model was applied to apportion and quantify the contribution of NP formations and local traffic and non-traffic sources to UFPs. The data analysis incorporated long-term measured time-series of total PNC (D ≥ 6 nm), particle number size distributions (PSD, D = 8 to 400 nm), PM2.5, PM10, NOx, CO, meteorological parameters and traffic counts at a stationary monitoring site. The developed Bayesian model showed reliable predictive performances in quantifying the contribution of NP formation events to UFPs (up to 4 × 104 particles cm- 3), with a significant day to day variability. The model identified potential NP formation and no-formations days based on PNC data and quantified the sources contribution to UFPs. Exploratory statistical analyses show that total mean PNC during the middle of the day was up to 32% higher than during peak morning and evening traffic periods, which were associated with NP formation events. The majority of UFPs measured during the peak traffic and NP formation periods were between 30-100 nm and smaller than 30 nm, respectively. To date, this is the first application of Bayesian model to apportion different sources contribution to UFPs, and therefore the importance of this study is not only in its modelling outcomes but in demonstrating the applicability and advantages of this statistical approach to air pollution studies.

Boon or bane: 401(k) loans and employee contributions.

PubMed

Wenger, Jeffrey B; Weller, Christian E

2014-09-01

Economic and behavioral theories arrive at different conclusions about the effect of being allowed to borrow from one's defined-contribution (DC) retirement plan on people's contributions to DC plans. Traditional life-cycle models unambiguously suggest that the borrowing option makes people better off than not being able to borrow. Households consequently contribute more to their DC plans than they would absent the borrowing option. Previous research finds that the ability to borrow from a DC plan increases contemporaneous contributions, consistent with traditional models. Behavioral finance, in contrast, suggests that some workers may operate with nonlinear time discounting. They plan on saving more in the future but change their mind and save less than initially planned as time passes. These workers may enjoy higher lifetime utility if they have no loan option because DC plans serve as commitment devices for retirement saving. The money cannot be used prior to retirement. Absent this commitment device, contributions may be lower for some households than would be the case without a DC loan option. We study DC plan contributions for households with heterogeneous preferences about discounting. We separate households into those that demonstrate inconsistent (or paradoxical) borrowing behavior, which may reflect nonlinear time discounting, and those with more consistent borrowing behavior. We find that a DC loan option raises current savings, but does so more for households with consistent borrowing behavior than for those with inconsistent borrowing behavior. © The Author(s) 2013.

Thermocapillary flow contribution to dropwise condensation heat transfer

NASA Astrophysics Data System (ADS)

Phadnis, Akshay; Rykaczewski, Konrad

2017-11-01

With recent developments of durable hydrophobic materials potentially enabling industrial applications of dropwise condensation, accurate modeling of heat transfer during this phase change process is becoming increasingly important. Classical steady state models of dropwise condensation are based on the integration of heat transfer through individual droplets over the entire drop size distribution. These models consider only the conduction heat transfer inside the droplets. However, simple scaling arguments suggest that thermocapillary flows might exist in such droplets. In this work, we used Finite Element heat transfer model to quantify the effect of Marangoni flow on dropwise condensation heat transfer of liquids with a wide range of surface tensions ranging from water to pentane. We confirmed that the Marangoni flow is present for a wide range of droplet sizes, but only has quantifiable effects on heat transfer in drops larger than 10 µm. By integrating the single drop heat transfer simulation results with drop size distribution for the cases considered, we demonstrated that Marangoni flow contributes a 10-30% increase in the overall heat transfer coefficient over conduction only model.

On the proportional abundance of species: Integrating population genetics and community ecology.

PubMed

Marquet, Pablo A; Espinoza, Guillermo; Abades, Sebastian R; Ganz, Angela; Rebolledo, Rolando

2017-12-01

The frequency of genes in interconnected populations and of species in interconnected communities are affected by similar processes, such as birth, death and immigration. The equilibrium distribution of gene frequencies in structured populations is known since the 1930s, under Wright's metapopulation model known as the island model. The equivalent distribution for the species frequency (i.e. the species proportional abundance distribution (SPAD)), at the metacommunity level, however, is unknown. In this contribution, we develop a stochastic model to analytically account for this distribution (SPAD). We show that the same as for genes SPAD follows a beta distribution, which provides a good description of empirical data and applies across a continuum of scales. This stochastic model, based upon a diffusion approximation, provides an alternative to neutral models for the species abundance distribution (SAD), which focus on number of individuals instead of proportions, and demonstrate that the relative frequency of genes in local populations and of species within communities follow the same probability law. We hope our contribution will help stimulate the mathematical and conceptual integration of theories in genetics and ecology.

Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis.

PubMed

Kurhekar, Manish; Deshpande, Umesh

2016-01-01

Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website.

Individual choice in spending accounts. Can we rely on employees to choose well?

PubMed

Schweitzer, M; Hershey, J C; Asch, D A

1996-06-01

Flexible spending accounts (FSA) represent a current health care financing tool that may become an important component of incremental health care reform. Because FSAs require employees to make financial contributions based on anticipated health care needs, contribution decisions are likely to be subject to many of the errors made in other insurance decisions. The authors analyzed the benefits selections, benefits forms completion, and FSA contribution levels of approximately 9,500 employees of the University of Pennsylvania from 1987 to 1992. Default and repeat choice trends characterize the completion of benefits forms and the reselection of health insurance options by employees. Despite the economic benefits of contributing to an FSA, only 14% of employees contributed in any one year and 73% never made a contribution. Multivariate models of these contributions fail to demonstrate the importance of what ought to be relevant influences in contribution decisions (for example, age, income, family status, or underlying health insurance). Whereas most FSA decisions are characterized by default contributions of $0, employees who contribute in one year are most likely to contribute exactly the same amount the next year, even when other circumstances change. The pervasiveness of these patterns raises concerns that health care reform plans that rely on financial incentives at the consumer level--for example, proposed medical saving accounts--will be inefficient.

Interaction of factor H-binding protein of Streptococcus suis with globotriaosylceramide promotes the development of meningitis

PubMed Central

Kong, Decong; Chen, Zhe; Wang, Junping; Lv, Qingyu; Jiang, Hua; Zheng, Yuling; Xu, Maokai; Zhou, Xuyu; Hao, Huaijie; Jiang, Yongqiang

2017-01-01

ABSTRACT Streptococcus suis is an important emerging zoonotic agent that causes acute bacterial meningitis in humans with high mortality and morbidity. Our previous work showed that factor H-binding protein (Fhb) contributed to virulence of S. suis, but the role of Fhb in the development of S. suis meningitis remained unclear. In this study, we demonstrated for the first time that Fhb contributed to the traversal of S. suis across the human blood–brain barrier by allelic-exchange mutagenesis, complementation and specific antibody blocking studies. We also showed that globotriaosylceramide (Gb3), the receptor of Fhb, was involved in this process and affected S. suis infection-induced activation of myosin light chain 2 through Rho/ROCK signaling in hCMEC/D3 cells. Using a murine model of S. suis meningitis, we further demonstrated that Gb3-deficiency prevented the mice from developing severe brain inflammation or injury. Our results demonstrate that the Fhb-Gb3 interaction plays an important role in the development of S. suis meningitis and might be a potential therapeutic target against S. suis infection. PMID:28402705

An open source Bayesian Monte Carlo isotope mixing model with applications in Earth surface processes

NASA Astrophysics Data System (ADS)

Arendt, Carli A.; Aciego, Sarah M.; Hetland, Eric A.

2015-05-01

The implementation of isotopic tracers as constraints on source contributions has become increasingly relevant to understanding Earth surface processes. Interpretation of these isotopic tracers has become more accessible with the development of Bayesian Monte Carlo (BMC) mixing models, which allow uncertainty in mixing end-members and provide methodology for systems with multicomponent mixing. This study presents an open source multiple isotope BMC mixing model that is applicable to Earth surface environments with sources exhibiting distinct end-member isotopic signatures. Our model is first applied to new δ18O and δD measurements from the Athabasca Glacier, which showed expected seasonal melt evolution trends and vigorously assessed the statistical relevance of the resulting fraction estimations. To highlight the broad applicability of our model to a variety of Earth surface environments and relevant isotopic systems, we expand our model to two additional case studies: deriving melt sources from δ18O, δD, and 222Rn measurements of Greenland Ice Sheet bulk water samples and assessing nutrient sources from ɛNd and 87Sr/86Sr measurements of Hawaiian soil cores. The model produces results for the Greenland Ice Sheet and Hawaiian soil data sets that are consistent with the originally published fractional contribution estimates. The advantage of this method is that it quantifies the error induced by variability in the end-member compositions, unrealized by the models previously applied to the above case studies. Results from all three case studies demonstrate the broad applicability of this statistical BMC isotopic mixing model for estimating source contribution fractions in a variety of Earth surface systems.

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.

Controlled Ecological Life Support System (CELSS) modeling

NASA Technical Reports Server (NTRS)

Drysdale, Alan; Thomas, Mark; Fresa, Mark; Wheeler, Ray

1992-01-01

Attention is given to CELSS, a critical technology for the Space Exploration Initiative. OCAM (object-oriented CELSS analysis and modeling) models carbon, hydrogen, and oxygen recycling. Multiple crops and plant types can be simulated. Resource recovery options from inedible biomass include leaching, enzyme treatment, aerobic digestion, and mushroom and fish growth. The benefit of using many small crops overlapping in time, instead of a single large crop, is demonstrated. Unanticipated results include startup transients which reduce the benefit of multiple small crops. The relative contributions of mass, energy, and manpower to system cost are analyzed in order to determine appropriate research directions.

Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

PubMed

Langdahl, Bente; Ferrari, Serge; Dempster, David W

2016-12-01

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.

A Memory-Process Model of Symbolic Assimilation

DTIC Science & Technology

1974-04-01

Systems: Final Report of a Study Group, published for Artificial Intellegence by North-Holland/Amorican...contribution of the methods is answered by evaluating the same program in the context of the field of artificial intelligence. The remainder of the...been widely demonstrated on a diversity of tasks in tha history of artificial intelligence. See [r.71], chapter 2. Given a particular task to be

Mutual Calculations in Creating Accounting Models: A Demonstration of the Power of Matrix Mathematics in Accounting Education

ERIC Educational Resources Information Center

Vysotskaya, Anna; Kolvakh, Oleg; Stoner, Greg

2016-01-01

The aim of this paper is to describe the innovative teaching approach used in the Southern Federal University, Russia, to teach accounting via a form of matrix mathematics. It thereby contributes to disseminating the technique of teaching to solve accounting cases using mutual calculations to a worldwide audience. The approach taken in this course…

Contribution of Sediment Compaction/Loading to the Ganges-Bangladesh Delta Subsidence

NASA Astrophysics Data System (ADS)

Karpytchev, Mikhail; Krien, Yann; Ballu, Valerie; Becker, Melanie; Calmant, Stephane; Spada, Giorgio; Guo, Junyi; Khan, Zahirul; Shum, Ck

2016-04-01

A pronounced spatial variability characterizes the subsidence/uplift rates in the Ganges-Bangladesh delta estimated from both sediment cores and modern geodetic techniques. The large variability of the subsidence rates suggests an interplay of different natural and anthropogenic processes including tectonics, sediment loading and sediment compaction, groundwater extaction among many others drivers of the delta vertical land movements.In this study, we focus on estimating the subsidence rates due to the sediments transported by the Ganges-Brahmaputra since the last 18 000 years. The delta subsidence induced by the sediment loading and the resulting sea level changes are modelled by the TABOO and SELEN software (Spada, 2003; Stocchi and Spada, 2007) in the framework of a gravitationally self-consistent Earth model. The loading history was obtained from available sediment cores and from the isopach map of Goodbread and Kuehl (2000). The results demonstrate that the delta loading enhanced by the Holocene sedimention can be responsable for a regular subsidence across the Ganges-Brahmaputra delta with an amplitude of 1-5 mm/yr along the Bengal coast. These estimates demonstrate that the contribution of the Holocene as well as modern sediment loading should be taken into account in climate change mitigation politicy for Bangladesh.

CD4+ cell-derived interleukin-17 in a model of dysregulated, Borrelia-induced arthritis.

PubMed

Hansen, Emily S; Johnson, Megan E; Schell, Ronald F; Nardelli, Dean T

2016-10-01

Lyme borreliosis, which is caused in the United States by the spirochete Borrelia burgdorferi, may manifest as different arrays of signs, symptoms and severities between infected individuals. Recent studies have indicated that particularly severe forms of Lyme borreliosis in humans are associated with an increased Th17 response. Here, we hypothesized that a murine model combining the dysregulated immune response of an environment lacking interleukin-10 (IL-10) with a robust T-cell-driven inflammatory response would reflect arthritis associated with the production of IL-17 by CD4+ cells. We demonstrate that IL-10 regulates the production of IL-17 by Borrelia-primed CD4+ cells early after interaction with Lyme spirochetes in vitro and that infection of Borrelia-primed mice with B. burgdorferi leads to significant production of IL-17 that contributes to the development of severe arthritis. These results extend our previous findings by demonstrating that a dysregulated adaptive immune response to Lyme spirochetes can contribute to severe, Th17-associated arthritis. These findings may lead to therapeutic measures for individuals with particularly severe symptoms of Lyme borreliosis. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Two decades of numerical modelling to understand long term fluvial archives: Advances and future perspectives

NASA Astrophysics Data System (ADS)

Veldkamp, A.; Baartman, J. E. M.; Coulthard, T. J.; Maddy, D.; Schoorl, J. M.; Storms, J. E. A.; Temme, A. J. A. M.; van Balen, R.; van De Wiel, M. J.; van Gorp, W.; Viveen, W.; Westaway, R.; Whittaker, A. C.

2017-06-01

The development and application of numerical models to investigate fluvial sedimentary archives has increased during the last decades resulting in a sustained growth in the number of scientific publications with keywords, 'fluvial models', 'fluvial process models' and 'fluvial numerical models'. In this context we compile and review the current contributions of numerical modelling to the understanding of fluvial archives. In particular, recent advances, current limitations, previous unexpected results and future perspectives are all discussed. Numerical modelling efforts have demonstrated that fluvial systems can display non-linear behaviour with often unexpected dynamics causing significant delay, amplification, attenuation or blurring of externally controlled signals in their simulated record. Numerical simulations have also demonstrated that fluvial records can be generated by intrinsic dynamics without any change in external controls. Many other model applications demonstrate that fluvial archives, specifically of large fluvial systems, can be convincingly simulated as a function of the interplay of (palaeo) landscape properties and extrinsic climate, base level and crustal controls. All discussed models can, after some calibration, produce believable matches with real world systems suggesting that equifinality - where a given end state can be reached through many different pathways starting from different initial conditions and physical assumptions - plays an important role in fluvial records and their modelling. The overall future challenge lies in the development of new methodologies for a more independent validation of system dynamics and research strategies that allow the separation of intrinsic and extrinsic record signals using combined fieldwork and modelling.

AtlA Mediates Extracellular DNA Release, Which Contributes to Streptococcus mutans Biofilm Formation in an Experimental Rat Model of Infective Endocarditis

PubMed Central

Hsu, Ron-Bin; Shun, Chia-Tung; Hsu, Chih-Chieh

2017-01-01

ABSTRACT Host factors, such as platelets, have been shown to enhance biofilm formation by oral commensal streptococci, inducing infective endocarditis (IE), but how bacterial components contribute to biofilm formation in vivo is still not clear. We demonstrated previously that an isogenic mutant strain of Streptococcus mutans deficient in autolysin AtlA (ΔatlA) showed a reduced ability to cause vegetation in a rat model of bacterial endocarditis. However, the role of AtlA in bacterial biofilm formation is unclear. In this study, confocal laser scanning microscopy analysis showed that extracellular DNA (eDNA) was embedded in S. mutans GS5 floes during biofilm formation on damaged heart valves, but an ΔatlA strain could not form bacterial aggregates. Semiquantification of eDNA by PCR with bacterial 16S rRNA primers demonstrated that the ΔatlA mutant strain produced dramatically less eDNA than the wild type. Similar results were observed with in vitro biofilm models. The addition of polyanethol sulfonate, a chemical lysis inhibitor, revealed that eDNA release mediated by bacterial cell lysis is required for biofilm initiation and maturation in the wild-type strain. Supplementation of cultures with calcium ions reduced wild-type growth but increased eDNA release and biofilm mass. The effect of calcium ions on biofilm formation was abolished in ΔatlA cultures and by the addition of polyanethol sulfonate. The VicK sensor, but not CiaH, was found to be required for the induction of eDNA release or the stimulation of biofilm formation by calcium ions. These data suggest that calcium ion-regulated AtlA maturation mediates the release of eDNA by S. mutans, which contributes to biofilm formation in infective endocarditis. PMID:28674029

Research on teacher education programs: logic model approach.

PubMed

Newton, Xiaoxia A; Poon, Rebecca C; Nunes, Nicole L; Stone, Elisa M

2013-02-01

Teacher education programs in the United States face increasing pressure to demonstrate their effectiveness through pupils' learning gains in classrooms where program graduates teach. The link between teacher candidates' learning in teacher education programs and pupils' learning in K-12 classrooms implicit in the policy discourse suggests a one-to-one correspondence. However, the logical steps leading from what teacher candidates have learned in their programs to what they are doing in classrooms that may contribute to their pupils' learning are anything but straightforward. In this paper, we argue that the logic model approach from scholarship on evaluation can enhance research on teacher education by making explicit the logical links between program processes and intended outcomes. We demonstrate the usefulness of the logic model approach through our own work on designing a longitudinal study that focuses on examining the process and impact of an undergraduate mathematics and science teacher education program. Copyright © 2012 Elsevier Ltd. All rights reserved.

5 CFR 890.1306 - Government premium contributions.

Code of Federal Regulations, 2010 CFR

2010-01-01

....1306 Section 890.1306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Health Benefits Program Demonstration Project § 890.1306 Government premium contributions. The Secretary... family members. The government contribution toward demonstration project premium rates will be determined...

Estimating the contribution of a service delivery organisation to the national modern contraceptive prevalence rate: Marie Stopes International's Impact 2 model

PubMed Central

2013-01-01

Background Individual family planning service delivery organisations currently rely on service provision data and couple-years of protection as health impact measures. Due to the substitution effect and the continuation of users of long-term methods, these metrics cannot estimate an organisation's contribution to the national modern contraceptive prevalence rate (CPR), the standard metric for measuring family planning programme impacts. Increasing CPR is essential for addressing the unmet need for family planning, a recognized global health priority. Current health impact estimation models cannot isolate the impact of an organisation in these efforts. Marie Stopes International designed the Impact 2 model to measure an organisation's contribution to increases in national CPR, as well as resulting health and demographic impacts. This paper aims to describe the methodology for modelling increasing national-level CPR as well as to discuss its benefits and limitations. Methods Impact 2 converts service provision data into estimates of the number of family planning users, accounting for continuation among users of long-term methods and addressing the challenges of converting commodity distribution data of short-term methods into user numbers. These estimates, combined with the client profile and data on the organisation's previous year's CPR contribution, enable Impact 2 to estimate which clients maintain an organisation's baseline contribution, which ones fulfil population growth offsets, and ultimately, which ones increase CPR. Results Illustrative results from Marie Stopes Madagascar show how Impact 2 can be used to estimate an organisation's contribution to national changes in the CPR. Conclusions Impact 2 is a useful tool for service delivery organisations to move beyond cruder output measures to a better understanding of their role in meeting the global unmet need for family planning. By considering health impact from the perspective of an individual organisation, Impact 2 addresses gaps not met by other models for family planning service outcomes. Further, the model helps organisations improve service delivery by demonstrating that increases in the national CPR are not simply about expanding user numbers; rather, the type of user (e.g. adopters, provider changers) must be considered. Impact 2 can be downloaded at http://www.mariestopes.org/impact-2. PMID:23902699

Constitutive β-catenin Activation Induces Male-Specific Tumorigenesis in the Bladder Urothelium

PubMed Central

Lin, Congxing; Yin, Yan; Stemler, Kristina; Humphrey, Peter; Kibel, Adam S.; Mysorekar, Indira U.; Ma, Liang

2013-01-01

The incidence for bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is about three times higher in men than in women. Although this gender difference has been primarily attributed to differential exposures, it is likely that underlying biological causes contribute to the gender inequality. In this study, we report a transgenic mouse bladder tumor model upon induction of constitutively activated β-catenin signaling in the adult urothelium. We showed that the histopathology of the tumors observed in our model closely resembled that of the human low grade urothelial carcinoma. Additionally, we provided evidence supporting the KRT5-positive;KRT7-negative basal cells as the putative cells-of-origin for β-catenin-induced luminal tumor. Intriguingly, the tumorigenesis in this model demonstrated a marked difference between opposite sexes; forty percent of males developed macroscopically detectable luminal tumors in twelve weeks, whereas only three percent of females developed tumors. We investigated the mechanisms underlying this sexual dimorphism in pathogenesis and demonstrated that nuclear translocation of the androgen receptor (AR) in the urothelial cells is a critical mechanism contributing to tumor development in male mice. Finally, we performed global gene profiling experiments and defined the molecular signature for the β-catenin-induced tumorigenesis in males. Altogether, we have established a model for investigating sexual dimorphism in UC development, and implicated synergy between β-catenin signaling and androgen/AR signaling in carcinogenesis of the basal urothelial cells. PMID:23928991

Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

DOE PAGES

Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

2016-01-19

A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Kohler theory to predict themore » effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid–liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. Furthermore, the model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.« less

A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?

PubMed Central

Zhao, Xiao-Nan; Lokanga, Rachel; Allette, Kimaada; Gazy, Inbal; Wu, Di; Usdin, Karen

2016-01-01

The fragile X-related disorders result from expansion of a CGG/CCG microsatellite in the 5’ UTR of the FMR1 gene. We have previously demonstrated that the MSH2/MSH3 complex, MutSβ, that is important for mismatch repair, is essential for almost all expansions in a mouse model of these disorders. Here we show that the MSH2/MSH6 complex, MutSα also contributes to the production of both germ line and somatic expansions as evidenced by the reduction in the number of expansions observed in Msh6-/- mice. This effect is not mediated via an indirect effect of the loss of MSH6 on the level of MSH3. However, since MutSβ is required for 98% of germ line expansions and almost all somatic ones, MutSα is apparently not able to efficiently substitute for MutSβ in the expansion process. Using purified human proteins we demonstrate that MutSα, like MutSβ, binds to substrates with loop-outs of the repeats and increases the thermal stability of the structures that they form. We also show that MutSα facilitates binding of MutSβ to these loop-outs. These data suggest possible models for the contribution of MutSα to repeat expansion. In addition, we show that unlike MutSβ, MutSα may also act to protect against repeat contractions in the Fmr1 gene. PMID:27427765

Modelling compression sensing in ionic polymer metal composites

NASA Astrophysics Data System (ADS)

Volpini, Valentina; Bardella, Lorenzo; Rodella, Andrea; Cha, Youngsu; Porfiri, Maurizio

2017-03-01

Ionic polymer metal composites (IPMCs) consist of an ionomeric membrane, including mobile counterions, sandwiched between two thin noble metal electrodes. IPMCs find application as sensors and actuators, where an imposed mechanical loading generates a voltage across the electrodes, and, vice versa, an imposed electric field causes deformation. Here, we present a predictive modelling approach to elucidate the dynamic sensing response of IPMCs subject to a time-varying through-the-thickness compression (‘compression sensing’). The model relies on the continuum theory recently developed by Porfiri and co-workers, which couples finite deformations to the modified Poisson-Nernst-Planck (PNP) system governing the IPMC electrochemistry. For the ‘compression sensing’ problem we establish a perturbative closed-form solution along with a finite element (FE) solution. The systematic comparison between these two solutions is a central contribution of this study, offering insight on accuracy and mathematical complexity. The method of matched asymptotic expansions is employed to find the analytical solution. To this end, we uncouple the force balance from the modified PNP system and separately linearise the PNP equations in the ionomer bulk and in the boundary layers at the ionomer-electrode interfaces. Comparison with FE results for the fully coupled nonlinear system demonstrates the accuracy of the analytical solution to describe IPMC sensing for moderate deformation levels. We finally demonstrate the potential of the modelling scheme to accurately reproduce experimental results from the literature. The proposed model is expected to aid in the design of IPMC sensors, contribute to an improved understanding of IPMC electrochemomechanical response, and offer insight into the role of nonlinear phenomena across mechanics and electrochemistry.

Measurement and modeling of CO2 mass transfer in brine at reservoir conditions

NASA Astrophysics Data System (ADS)

Shi, Z.; Wen, B.; Hesse, M. A.; Tsotsis, T. T.; Jessen, K.

2018-03-01

In this work, we combine measurements and modeling to investigate the application of pressure-decay experiments towards delineation and interpretation of CO2 solubility, uptake and mass transfer in water/brine systems at elevated pressures of relevance to CO2 storage operations in saline aquifers. Accurate measurements and modeling of mass transfer in this context are crucial to an improved understanding of the longer-term fate of CO2 that is injected into the subsurface for storage purposes. Pressure-decay experiments are presented for CO2/water and CO2/brine systems with and without the presence of unconsolidated porous media. We demonstrate, via high-resolution numerical calculations in 2-D, that natural convection will complicate the interpretation of the experimental observations if the particle size is not sufficiently small. In such settings, we demonstrate that simple 1-D interpretations can result in an overestimation of the uptake (diffusivity) by two orders of magnitude. Furthermore, we demonstrate that high-resolution numerical calculations agree well with the experimental observations for settings where natural convection contributes substantially to the overall mass transfer process.

One-electron versus electron-electron interaction contributions to the spin-spin coupling mechanism in nuclear magnetic resonance spectroscopy: Analysis of basic electronic effects

NASA Astrophysics Data System (ADS)

Gräfenstein, Jürgen; Cremer, Dieter

2004-12-01

For the first time, the nuclear magnetic resonance (NMR) spin-spin coupling mechanism is decomposed into one-electron and electron-electron interaction contributions to demonstrate that spin-information transport between different orbitals is not exclusively an electron-exchange phenomenon. This is done using coupled perturbed density-functional theory in conjunction with the recently developed J-OC-PSP [=J-OC-OC-PSP: Decomposition of J into orbital contributions using orbital currents and partial spin polarization)] method. One-orbital contributions comprise Ramsey response and self-exchange effects and the two-orbital contributions describe first-order delocalization and steric exchange. The two-orbital effects can be characterized as external orbital, echo, and spin transport contributions. A relationship of these electronic effects to zeroth-order orbital theory is demonstrated and their sign and magnitude predicted using simple models and graphical representations of first order orbitals. In the case of methane the two NMR spin-spin coupling constants result from totally different Fermi contact coupling mechanisms. 1J(C,H) is the result of the Ramsey response and the self-exchange of the bond orbital diminished by external first-order delocalization external one-orbital effects whereas 2J(H,H) spin-spin coupling is almost exclusively mitigated by a two-orbital steric exchange effect. From this analysis, a series of prediction can be made how geometrical deformations, electron lone pairs, and substituent effects lead to a change in the values of 1J(C,H) and 2J(H,H), respectively, for hydrocarbons.

Source Attribution of Near-surface Ozone in the Western US: Improved Estimates by TF HTAP2 Multi-model Experiment and Multi-scale Chemical Data Assimilation

NASA Astrophysics Data System (ADS)

Huang, M.; Bowman, K. W.; Carmichael, G. R.; Lee, M.; Park, R.; Henze, D. K.; Chai, T.; Flemming, J.; Lin, M.; Weinheimer, A. J.; Wisthaler, A.; Jaffe, D. A.

2014-12-01

Near-surface ozone in the western US can be sensitive to transported background pollutants from the free troposphere over the eastern Pacific, as well as various local emissions sources. Accurately estimating ozone source contributions in this region has strong policy-relevant significance as the air quality standards tend to go down. Here we improve modeled contributions from local and non-local sources to western US ozone base on the HTAP2 (Task Force on Hemispheric Transport of Air Pollution) multi-model experiment, along with multi-scale chemical data assimilation. We simulate western US air quality using the STEM regional model on a 12 km horizontal resolution grid, during the NASA ARCTAS field campaign period in June 2008. STEM simulations use time-varying boundary conditions downscaled from global GEOS-Chem model simulations. Standard GEOS-Chem simulation overall underpredicted ozone at 1-5 km in the eastern Pacific, resulting in underestimated contributions from the transported background pollutants to surface ozone inland. These negative biases can be reduced by using the output from several global models that support the HTAP2 experiment, which all ran with the HTAP2 harmonized emission inventory and also calculated the contributions from east Asian anthropogenic emissions. We demonstrate that the biases in GEOS-Chem boundary conditions can be more efficiently reduced via assimilating satellite ozone profiles from the Tropospheric Emission Spectrometer (TES) instrument using the three dimensional variational (3D-Var) approach. Base upon these TES-constrained GEOS-Chem boundary conditions, we then update regional nitrogen dioxide and isoprene emissions in STEM through the four dimensional variational (4D-Var) assimilation of the Ozone Monitoring Instrument (OMI) nitrogen dioxide columns and the NASA DC-8 aircraft isoprene measurements. The 4D-Var assimilation spatially redistributed the emissions of nitrogen oxides and isoprene from various US sources, and in the meantime updated the modeled ozone and its US source contributions. Compared with available independent measurements (e.g., ozone observed on the DC-8 aircraft, and at EPA and Mt. Bachelor monitoring stations) during this period, modeled ozone fields after the multi-scale assimilation show overall improvement.

Innate immunity and chronic rhinosinusitis: What we have learned from animal models.

PubMed

London, Nyall R; Lane, Andrew P

2016-06-01

Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial disease characterized by dysregulated inflammation. Abnormalities in innate immune function including sinonasal epithelial cell barrier function, mucociliary clearance, response to pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs), and the contribution of innate immune cells will be highlighted in this review. PubMed literature review. A review of the literature was conducted to determine what we have learned from animal models in relation to innate immunity and chronic rhinosinusitis. Dysregulation of innate immune mechanisms including sinonasal barrier function, mucociliary clearance, PAMPs, and innate immune cells such as eosinophils, mast cells, and innate lymphoid cells may contribute to CRS pathogenesis. Sinonasal inflammation has been studied using mouse, rat, rabbit, pig, and sheep explant or in vivo models. Study using these models has allowed for analysis of experimental therapeutics and furthered our understanding of the aforementioned aspects of the innate immune mechanism as it relates to sinonasal inflammation. These include augmenting mucociliary clearance through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and study of drug toxicity on ciliary beat frequency. Knockout models of Toll-like receptors (TLR) have demonstrated the critical role these PRRs play in allergic inflammation as loss of TLR2 and TLR4 leads to decreased lower airway inflammation. Mast cell deficient mice are less susceptible to ovalbumin-induced sinonasal inflammation. Animal models have shed light as to the potential contribution of dysregulated innate immunity in chronic sinonasal inflammation.

Glaciers and small ice caps in the macro-scale hydrological cycle - an assessment of present conditions and future changes

NASA Astrophysics Data System (ADS)

Lammers, Richard; Hock, Regine; Prusevich, Alexander; Bliss, Andrew; Radic, Valentina; Glidden, Stanley; Grogan, Danielle; Frolking, Steve

2014-05-01

Glacier and small ice cap melt water contributions to the global hydrologic cycle are an important component of human water supply and for sea level rise. This melt water is used in many arid and semi-arid parts of the world for direct human consumption as well as indirect consumption by irrigation for crops, serving as frozen reservoirs of water that supplement runoff during warm and dry periods of summer when it is needed the most. Additionally, this melt water reaching the oceans represents a direct input to sea level rise and therefore accurate estimates of this contribution have profound economic and geopolitical implications. It has been demonstrated that, on the scale of glacierized river catchments, land surface hydrological models can successfully simulate glacier contribution to streamflow. However, at global scales, the implementation of glacier melt in hydrological models has been rudimentary or non-existent. In this study, a global glacier mass balance model is coupled with the University of New Hampshire Water Balance/Transport Model (WBM) to assess recent and projected future glacier contributions to the hydrological cycle over the global land surface (excluding the ice sheets of Greenland and Antarctica). For instance, results of WBM simulations indicate that seasonal glacier melt water in many arid climate watersheds comprises 40 % or more of their discharge. Implicitly coupled glacier and WBM models compute monthly glacier mass changes and resulting runoff at the glacier terminus for each individual glacier from the globally complete Randolph Glacier Inventory including over 200 000 glaciers. The time series of glacier runoff is aggregated over each hydrological modeling unit and delivered to the hydrological model for routing downstream and mixing with non-glacial contribution of runoff to each drainage basin outlet. WBM tracks and uses glacial and non-glacial components of the in-stream water for filling reservoirs, transfers of water between drainage basins (inter-basin hydrological transfers), and irrigation along the global system of rivers with net discharge to the ocean. Climate scenarios from global climate models prepared for IPCC AR5 are used to explore an expected range of possible future glacier outflow variability to estimate the impacts on human use of these valuable waters and their poorly understood net contribution to sea level change.

Measurement of psychological disorders using cognitive diagnosis models.

PubMed

Templin, Jonathan L; Henson, Robert A

2006-09-01

Cognitive diagnosis models are constrained (multiple classification) latent class models that characterize the relationship of questionnaire responses to a set of dichotomous latent variables. Having emanated from educational measurement, several aspects of such models seem well suited to use in psychological assessment and diagnosis. This article presents the development of a new cognitive diagnosis model for use in psychological assessment--the DINO (deterministic input; noisy "or" gate) model--which, as an illustrative example, is applied to evaluate and diagnose pathological gamblers. As part of this example, a demonstration of the estimates obtained by cognitive diagnosis models is provided. Such estimates include the probability an individual meets each of a set of dichotomous Diagnostic and Statistical Manual of Mental Disorders (text revision [DSM-IV-TR]; American Psychiatric Association, 2000) criteria, resulting in an estimate of the probability an individual meets the DSM-IV-TR definition for being a pathological gambler. Furthermore, a demonstration of how the hypothesized underlying factors contributing to pathological gambling can be measured with the DINO model is presented, through use of a covariance structure model for the tetrachoric correlation matrix of the dichotomous latent variables representing DSM-IV-TR criteria. Copyright 2006 APA

Sociality influences cultural complexity.

PubMed

Muthukrishna, Michael; Shulman, Ben W; Vasilescu, Vlad; Henrich, Joseph

2014-01-07

Archaeological and ethnohistorical evidence suggests a link between a population's size and structure, and the diversity or sophistication of its toolkits or technologies. Addressing these patterns, several evolutionary models predict that both the size and social interconnectedness of populations can contribute to the complexity of its cultural repertoire. Some models also predict that a sudden loss of sociality or of population will result in subsequent losses of useful skills/technologies. Here, we test these predictions with two experiments that permit learners to access either one or five models (teachers). Experiment 1 demonstrates that naive participants who could observe five models, integrate this information and generate increasingly effective skills (using an image editing tool) over 10 laboratory generations, whereas those with access to only one model show no improvement. Experiment 2, which began with a generation of trained experts, shows how learners with access to only one model lose skills (in knot-tying) more rapidly than those with access to five models. In the final generation of both experiments, all participants with access to five models demonstrate superior skills to those with access to only one model. These results support theoretical predictions linking sociality to cumulative cultural evolution.

Sociality influences cultural complexity

PubMed Central

Muthukrishna, Michael; Shulman, Ben W.; Vasilescu, Vlad; Henrich, Joseph

2014-01-01

Archaeological and ethnohistorical evidence suggests a link between a population's size and structure, and the diversity or sophistication of its toolkits or technologies. Addressing these patterns, several evolutionary models predict that both the size and social interconnectedness of populations can contribute to the complexity of its cultural repertoire. Some models also predict that a sudden loss of sociality or of population will result in subsequent losses of useful skills/technologies. Here, we test these predictions with two experiments that permit learners to access either one or five models (teachers). Experiment 1 demonstrates that naive participants who could observe five models, integrate this information and generate increasingly effective skills (using an image editing tool) over 10 laboratory generations, whereas those with access to only one model show no improvement. Experiment 2, which began with a generation of trained experts, shows how learners with access to only one model lose skills (in knot-tying) more rapidly than those with access to five models. In the final generation of both experiments, all participants with access to five models demonstrate superior skills to those with access to only one model. These results support theoretical predictions linking sociality to cumulative cultural evolution. PMID:24225461

Fracture Mechanics Method for Word Embedding Generation of Neural Probabilistic Linguistic Model.

PubMed

Bi, Size; Liang, Xiao; Huang, Ting-Lei

2016-01-01

Word embedding, a lexical vector representation generated via the neural linguistic model (NLM), is empirically demonstrated to be appropriate for improvement of the performance of traditional language model. However, the supreme dimensionality that is inherent in NLM contributes to the problems of hyperparameters and long-time training in modeling. Here, we propose a force-directed method to improve such problems for simplifying the generation of word embedding. In this framework, each word is assumed as a point in the real world; thus it can approximately simulate the physical movement following certain mechanics. To simulate the variation of meaning in phrases, we use the fracture mechanics to do the formation and breakdown of meaning combined by a 2-gram word group. With the experiments on the natural linguistic tasks of part-of-speech tagging, named entity recognition and semantic role labeling, the result demonstrated that the 2-dimensional word embedding can rival the word embeddings generated by classic NLMs, in terms of accuracy, recall, and text visualization.

In-silico experiments of zebrafish behaviour: modeling swimming in three dimensions

NASA Astrophysics Data System (ADS)

Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

2017-01-01

Zebrafish is fast becoming a species of choice in biomedical research for the investigation of functional and dysfunctional processes coupled with their genetic and pharmacological modulation. As with mammals, experimentation with zebrafish constitutes a complicated ethical issue that calls for the exploration of alternative testing methods to reduce the number of subjects, refine experimental designs, and replace live animals. Inspired by the demonstrated advantages of computational studies in other life science domains, we establish an authentic data-driven modelling framework to simulate zebrafish swimming in three dimensions. The model encapsulates burst-and-coast swimming style, speed modulation, and wall interaction, laying the foundations for in-silico experiments of zebrafish behaviour. Through computational studies, we demonstrate the ability of the model to replicate common ethological observables such as speed and spatial preference, and anticipate experimental observations on the correlation between tank dimensions on zebrafish behaviour. Reaching to other experimental paradigms, our framework is expected to contribute to a reduction in animal use and suffering.

Using machine learning for sequence-level automated MRI protocol selection in neuroradiology.

PubMed

Brown, Andrew D; Marotta, Thomas R

2018-05-01

Incorrect imaging protocol selection can lead to important clinical findings being missed, contributing to both wasted health care resources and patient harm. We present a machine learning method for analyzing the unstructured text of clinical indications and patient demographics from magnetic resonance imaging (MRI) orders to automatically protocol MRI procedures at the sequence level. We compared 3 machine learning models - support vector machine, gradient boosting machine, and random forest - to a baseline model that predicted the most common protocol for all observations in our test set. The gradient boosting machine model significantly outperformed the baseline and demonstrated the best performance of the 3 models in terms of accuracy (95%), precision (86%), recall (80%), and Hamming loss (0.0487). This demonstrates the feasibility of automating sequence selection by applying machine learning to MRI orders. Automated sequence selection has important safety, quality, and financial implications and may facilitate improvements in the quality and safety of medical imaging service delivery.

In-silico experiments of zebrafish behaviour: modeling swimming in three dimensions

PubMed Central

Mwaffo, Violet; Butail, Sachit; Porfiri, Maurizio

2017-01-01

Zebrafish is fast becoming a species of choice in biomedical research for the investigation of functional and dysfunctional processes coupled with their genetic and pharmacological modulation. As with mammals, experimentation with zebrafish constitutes a complicated ethical issue that calls for the exploration of alternative testing methods to reduce the number of subjects, refine experimental designs, and replace live animals. Inspired by the demonstrated advantages of computational studies in other life science domains, we establish an authentic data-driven modelling framework to simulate zebrafish swimming in three dimensions. The model encapsulates burst-and-coast swimming style, speed modulation, and wall interaction, laying the foundations for in-silico experiments of zebrafish behaviour. Through computational studies, we demonstrate the ability of the model to replicate common ethological observables such as speed and spatial preference, and anticipate experimental observations on the correlation between tank dimensions on zebrafish behaviour. Reaching to other experimental paradigms, our framework is expected to contribute to a reduction in animal use and suffering. PMID:28071731

Coupled electromechanical response of composite beams with embedded piezoelectric sensors and actuators

NASA Technical Reports Server (NTRS)

Saravanos, D. A.; Heyliger, P. R.

1994-01-01

Unified mechanics are developed with the capability to model both sensory and active composite laminates with embedded piezoelectric layers. A discrete-layer formulation enables analysis of both global and local electromechanical response. The mechanics include the contributions from elastic, piezoelectric, and dielectric components. The incorporation of electric potential into the state variables permits representation of general electromechanical boundary conditions. Approximate finite element solutions for the static and free-vibration analysis of beams are presented. Applications on composite beams demonstrate the capability to represent either sensory or active structures and to model the complicated stress-strain fields, the interactions between passive/active layers, interfacial phenomena between sensors and composite plies, and critical damage modes in the material. The capability to predict the dynamic characteristics under various electrical boundary conditions is also demonstrated.

Observation of Solar Wind Charge Exchange Emission from Exospheric Material in and Outside Earth's Magnetosheath

NASA Technical Reports Server (NTRS)

Snowden, S. L.; Collier, M. R.; Cravens, T.; Kuntz, K. D.; Lepri, S. T.; Robertson, I.; Tomas, L.

2008-01-01

A long XMM-Newton exposure is used to observe solar wind charge exchange (SWCX) emission from exospheric material in and outside Earth s magnetosheath. The light curve of the O VII (0.5-0.62 keV) band is compared with a model for the expected emission, and while the emission is faint and the light curve has considerable scatter, the correlation is significant to better than 99.9%. This result demonstrates the validity of the geocoronal SWCX emission model for predicting a contribution to astrophysical observations to a scale factor of order unity (1.36). The results also demonstrate the potential utility of using X-ray observations to study global phenomena of the magnetosheath which currently are only investigated using in situ measurements.

Attributing uncertainty in streamflow simulations due to variable inputs via the Quantile Flow Deviation metric

NASA Astrophysics Data System (ADS)

Shoaib, Syed Abu; Marshall, Lucy; Sharma, Ashish

2018-06-01

Every model to characterise a real world process is affected by uncertainty. Selecting a suitable model is a vital aspect of engineering planning and design. Observation or input errors make the prediction of modelled responses more uncertain. By way of a recently developed attribution metric, this study is aimed at developing a method for analysing variability in model inputs together with model structure variability to quantify their relative contributions in typical hydrological modelling applications. The Quantile Flow Deviation (QFD) metric is used to assess these alternate sources of uncertainty. The Australian Water Availability Project (AWAP) precipitation data for four different Australian catchments is used to analyse the impact of spatial rainfall variability on simulated streamflow variability via the QFD. The QFD metric attributes the variability in flow ensembles to uncertainty associated with the selection of a model structure and input time series. For the case study catchments, the relative contribution of input uncertainty due to rainfall is higher than that due to potential evapotranspiration, and overall input uncertainty is significant compared to model structure and parameter uncertainty. Overall, this study investigates the propagation of input uncertainty in a daily streamflow modelling scenario and demonstrates how input errors manifest across different streamflow magnitudes.

Animal Models of Resistance Exercise and their Application to Neuroscience Research

PubMed Central

Strickland, Justin C.; Smith, Mark A.

2016-01-01

Background Numerous studies have demonstrated that participation in regular resistance exercise (e.g., strength training) is associated with improvements in mental health, memory, and cognition. However, less is known about the neurobiological mechanisms mediating these effects. The goal of this mini-review is to describe and evaluate the available animal models of resistance exercise that may prove useful for examining CNS activity. New Method Various models have been developed to examine resistance exercise in laboratory animals. Comparison with Existing Methods Resistance exercise models vary in how the resistance manipulation is applied, either through direct stimulation of the muscle (e.g., in situ models) or through behavior maintained by operant contingencies (e.g., whole organism models). Each model presents distinct advantages and disadvantages for examining central nervous system (CNS) activity, and consideration of these attributes is essential for the future investigation of underlying neurobiological substrates. Results Potential neurobiological mechanisms mediating the effects of resistance exercise on pain, anxiety, memory, and drug use have been efficiently and effectively investigated using resistance exercise models that minimize stress and maximize the relative contribution of resistance over aerobic factors. Conclusions Whole organism resistance exercise models that (1) limit the use of potentially stressful stimuli and (2) minimize the contribution of aerobic factors will be critical for examining resistance exercise and CNS function. PMID:27498037

Synergy of Earth Observation and In-Situ Monitoring Data for Flood Hazard Early Warning System

NASA Astrophysics Data System (ADS)

Brodsky, Lukas; Kodesova, Radka; Spazierova, Katerina

2010-12-01

In this study, we demonstrate synergy of EO and in-situ monitoring data for early warning flood hazard system in the Czech Republic developed within ESA PECS project FLOREO. The development of the demonstration system is oriented to support existing monitoring activities, especially snow melt and surface water runoff contributing to flooding events. The system consists of two main parts accordingly, the first is snow cover and snow melt monitoring driven mainly by EO data and the other is surface water runoff modeling and monitoring driven by synergy of in-situ and EO data.

Closed-loop conductance scanning tunneling spectroscopy: demonstrating the equivalence to the open-loop alternative.

PubMed

Hellenthal, Chris; Sotthewes, Kai; Siekman, Martin H; Kooij, E Stefan; Zandvliet, Harold J W

2015-01-01

We demonstrate the validity of using closed-loop z(V) conductance scanning tunneling spectroscopy (STS) measurements for the determination of the effective tunneling barrier by comparing them to more conventional open-loop I(z) measurements. Through the development of a numerical model, the individual contributions to the effective tunneling barrier present in these experiments, such as the work function and the presence of an image charge, are determined quantitatively. This opens up the possibility of determining tunneling barriers of both vacuum and molecular systems in an alternative and more detailed manner.

Individualized Prediction of Reading Comprehension Ability Using Gray Matter Volume.

PubMed

Cui, Zaixu; Su, Mengmeng; Li, Liangjie; Shu, Hua; Gong, Gaolang

2018-05-01

Reading comprehension is a crucial reading skill for learning and putatively contains 2 key components: reading decoding and linguistic comprehension. Current understanding of the neural mechanism underlying these reading comprehension components is lacking, and whether and how neuroanatomical features can be used to predict these 2 skills remain largely unexplored. In the present study, we analyzed a large sample from the Human Connectome Project (HCP) dataset and successfully built multivariate predictive models for these 2 skills using whole-brain gray matter volume features. The results showed that these models effectively captured individual differences in these 2 skills and were able to significantly predict these components of reading comprehension for unseen individuals. The strict cross-validation using the HCP cohort and another independent cohort of children demonstrated the model generalizability. The identified gray matter regions contributing to the skill prediction consisted of a wide range of regions covering the putative reading, cerebellum, and subcortical systems. Interestingly, there were gender differences in the predictive models, with the female-specific model overestimating the males' abilities. Moreover, the identified contributing gray matter regions for the female-specific and male-specific models exhibited considerable differences, supporting a gender-dependent neuroanatomical substrate for reading comprehension.

Using Computer Simulations for Promoting Model-based Reasoning. Epistemological and Educational Dimensions

NASA Astrophysics Data System (ADS)

Develaki, Maria

2017-11-01

Scientific reasoning is particularly pertinent to science education since it is closely related to the content and methodologies of science and contributes to scientific literacy. Much of the research in science education investigates the appropriate framework and teaching methods and tools needed to promote students' ability to reason and evaluate in a scientific way. This paper aims (a) to contribute to an extended understanding of the nature and pedagogical importance of model-based reasoning and (b) to exemplify how using computer simulations can support students' model-based reasoning. We provide first a background for both scientific reasoning and computer simulations, based on the relevant philosophical views and the related educational discussion. This background suggests that the model-based framework provides an epistemologically valid and pedagogically appropriate basis for teaching scientific reasoning and for helping students develop sounder reasoning and decision-taking abilities and explains how using computer simulations can foster these abilities. We then provide some examples illustrating the use of computer simulations to support model-based reasoning and evaluation activities in the classroom. The examples reflect the procedure and criteria for evaluating models in science and demonstrate the educational advantages of their application in classroom reasoning activities.

Structure and osmotic pressure of ionic microgel dispersions

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

Hedrick, Mary M.; Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108-6050; Chung, Jun Kyung

We investigate structural and thermodynamic properties of aqueous dispersions of ionic microgels—soft colloidal gel particles that exhibit unusual phase behavior. Starting from a coarse-grained model of microgel macroions as charged spheres that are permeable to microions, we perform simulations and theoretical calculations using two complementary implementations of Poisson-Boltzmann (PB) theory. Within a one-component model, based on a linear-screening approximation for effective electrostatic pair interactions, we perform molecular dynamics simulations to compute macroion-macroion radial distribution functions, static structure factors, and macroion contributions to the osmotic pressure. For the same model, using a variational approximation for the free energy, we compute bothmore » macroion and microion contributions to the osmotic pressure. Within a spherical cell model, which neglects macroion correlations, we solve the nonlinear PB equation to compute microion distributions and osmotic pressures. By comparing the one-component and cell model implementations of PB theory, we demonstrate that the linear-screening approximation is valid for moderately charged microgels. By further comparing cell model predictions with simulation data for osmotic pressure, we chart the cell model’s limits in predicting osmotic pressures of salty dispersions.« less

Closed-Loop Lifecycle Management of Service and Product in the Internet of Things: Semantic Framework for Knowledge Integration.

PubMed

Yoo, Min-Jung; Grozel, Clément; Kiritsis, Dimitris

2016-07-08

This paper describes our conceptual framework of closed-loop lifecycle information sharing for product-service in the Internet of Things (IoT). The framework is based on the ontology model of product-service and a type of IoT message standard, Open Messaging Interface (O-MI) and Open Data Format (O-DF), which ensures data communication. (1) BACKGROUND: Based on an existing product lifecycle management (PLM) methodology, we enhanced the ontology model for the purpose of integrating efficiently the product-service ontology model that was newly developed; (2) METHODS: The IoT message transfer layer is vertically integrated into a semantic knowledge framework inside which a Semantic Info-Node Agent (SINA) uses the message format as a common protocol of product-service lifecycle data transfer; (3) RESULTS: The product-service ontology model facilitates information retrieval and knowledge extraction during the product lifecycle, while making more information available for the sake of service business creation. The vertical integration of IoT message transfer, encompassing all semantic layers, helps achieve a more flexible and modular approach to knowledge sharing in an IoT environment; (4) Contribution: A semantic data annotation applied to IoT can contribute to enhancing collected data types, which entails a richer knowledge extraction. The ontology-based PLM model enables as well the horizontal integration of heterogeneous PLM data while breaking traditional vertical information silos; (5) CONCLUSION: The framework was applied to a fictive case study with an electric car service for the purpose of demonstration. For the purpose of demonstrating the feasibility of the approach, the semantic model is implemented in Sesame APIs, which play the role of an Internet-connected Resource Description Framework (RDF) database.

Closed-Loop Lifecycle Management of Service and Product in the Internet of Things: Semantic Framework for Knowledge Integration

PubMed Central

Yoo, Min-Jung; Grozel, Clément; Kiritsis, Dimitris

2016-01-01

This paper describes our conceptual framework of closed-loop lifecycle information sharing for product-service in the Internet of Things (IoT). The framework is based on the ontology model of product-service and a type of IoT message standard, Open Messaging Interface (O-MI) and Open Data Format (O-DF), which ensures data communication. (1) Background: Based on an existing product lifecycle management (PLM) methodology, we enhanced the ontology model for the purpose of integrating efficiently the product-service ontology model that was newly developed; (2) Methods: The IoT message transfer layer is vertically integrated into a semantic knowledge framework inside which a Semantic Info-Node Agent (SINA) uses the message format as a common protocol of product-service lifecycle data transfer; (3) Results: The product-service ontology model facilitates information retrieval and knowledge extraction during the product lifecycle, while making more information available for the sake of service business creation. The vertical integration of IoT message transfer, encompassing all semantic layers, helps achieve a more flexible and modular approach to knowledge sharing in an IoT environment; (4) Contribution: A semantic data annotation applied to IoT can contribute to enhancing collected data types, which entails a richer knowledge extraction. The ontology-based PLM model enables as well the horizontal integration of heterogeneous PLM data while breaking traditional vertical information silos; (5) Conclusion: The framework was applied to a fictive case study with an electric car service for the purpose of demonstration. For the purpose of demonstrating the feasibility of the approach, the semantic model is implemented in Sesame APIs, which play the role of an Internet-connected Resource Description Framework (RDF) database. PMID:27399717

Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing

PubMed Central

Liang, Hua; Deng, Liufu; Chmura, Steven; Burnette, Byron; Liadis, Nicole; Darga, Thomas; Beckett, Michael A.; Lingen, Mark W.; Witt, MaryEllyn; Weichselbaum, Ralph R.; Fu, Yang-Xin

2013-01-01

Local failures following radiation therapy are multifactorial and the contributions of the tumor and the host are complex. Current models of tumor equilibrium suggest that a balance exists between cell birth and cell death due to insufficient angiogenesis, immune effects, or intrinsic cellular factors. We investigated whether host immune responses contribute to radiation induced tumor equilibrium in animal models. We report an essential role for immune cells and their cytokines in suppressing tumor cell regrowth in two experimental animal model systems. Depletion of T cells or neutralization of interferon-gamma reversed radiation-induced equilibrium leading to tumor regrowth. We also demonstrate that PD-L1 blockade augments T cell responses leading to rejection of tumors in radiation induced equilibrium. We identify an active interplay between tumor cells and immune cells that occurs in radiation-induced tumor equilibrium and suggest a potential role for disruption of the PD-L1/PD-1 axis in increasing local tumor control. PMID:23630355

Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein.

PubMed

Tyson, Trevor; Senchuk, Megan; Cooper, Jason F; George, Sonia; Van Raamsdonk, Jeremy M; Brundin, Patrik

2017-08-08

Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson's disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.

State of the Science: Apathy As a Model for Investigating Behavioral and Psychological Symptoms in Dementia.

PubMed

Massimo, Lauren; Kales, Helen C; Kolanowski, Ann

2018-04-01

Apathy is one of the most common and pervasive of the behavioral and psychological symptoms of dementia (BPSDs). Apathy has profound consequences for morbidity, mortality, and caregiver burden. Treatment of apathy has been hindered because of poor understanding of the mechanisms underlying this heterogeneous syndrome. Research has demonstrated that apathy is associated with disruption of the frontal-striatal system in individuals with neurodegenerative disease. As with other BPSDs, these neural mechanisms alone do not completely account for the syndrome; individual, caregiver, and environmental factors also contribute to apathy. In this article, we modify a current conceptual model of the factors contributing to BPSDs to examine determinants of apathy. This integrative model provides a more complete and theoretically informed understanding of apathy, allowing for greater insight into potential targets for research, intervention, and care. We end by proposing an agenda for moving the science of BPSDs in general, and apathy in particular, forward. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Structural analysis of muscles elevating the hyolaryngeal complex.

PubMed

Pearson, William G; Langmore, Susan E; Yu, Louis B; Zumwalt, Ann C

2012-12-01

A critical event of pharyngeal swallowing is the elevation of the hyolaryngeal complex to open the upper esophageal sphincter. Current swallowing theory assigns this function to the submental and thyrohyoid muscles. However, the attachments of the long pharyngeal muscles indicate that they could contribute to this function, yet their role is uninvestigated in humans. In addition, there is evidence the posterior digastric and stylohyoid contribute to hyoid elevation. A cadaver model was used to document the structural properties of muscles. These properties were used to model muscle groups as force vectors and analyze their potential for hyolaryngeal elevation. Vector magnitude was determined using physiological cross-sectional areas (PCSAs) of muscles calculated from structural properties of muscle taken from 12 hemisected cadaver specimens. Vector direction (lines of action) was calculated from the three-dimensional coordinates of muscle attachment sites. Unit force vectors in the superior direction of submental, suprahyoid (which includes the submental muscles), long pharyngeal, and thyrohyoid muscles were derived and compared by an analysis of variance (ANOVA) to document each muscle's potential contribution to hyolaryngeal elevation. An ANOVA with Tukey HSD post hoc analysis of unit force vectors showed no statistically significant difference between the submental (0.92 ± 0.24 cm(2)) and long pharyngeal (0.73 ± 0.20 cm(2)) muscles. Both demonstrated greater potential to elevate the hyolaryngeal complex than the thyrohyoid (0.49 ± 0.18 cm(2)), with P < 0.01 and P < 0.05, respectively. The suprahyoid muscles (1.52 ± 0.35 cm(2)) demonstrated the greatest potential to elevate the hyolaryngeal complex: greater than both the long pharyngeal muscles (P < 0.01) and the thyrohyoid (P < 0.01). The submental and thyrohyoid muscles by convention are thought to elevate the hyolaryngeal complex. This study demonstrates that structurally the long pharyngeal muscles have similar potential to contribute to this critical function, with the suprahyoid muscles having the greatest potential. If verified by functional data, these findings would amend current swallowing theory.

A simple semi-empirical technique for apportioning the impact of roadways on air quality in an urban neighbourhood

NASA Astrophysics Data System (ADS)

Elangasinghe, M. A.; Dirks, K. N.; Singhal, N.; Costello, S. B.; Longley, I.; Salmond, J. A.

2014-02-01

Air pollution from the transport sector has a marked effect on human health, so isolating the pollutant contribution from a roadway is important in understanding its impact on the local neighbourhood. This paper proposes a novel technique based on a semi-empirical air pollution model to quantify the impact from a roadway on the air quality of a local neighbourhood using ambient records of a single air pollution monitor. We demonstrate the proposed technique using a case study, in which we quantify the contribution from a major highway with respect to the local background concentration in Auckland, New Zealand. Comparing the diurnal variation of the model-separated background contribution with real measurements from a site upwind of the highway shows that the model estimates are reliable. Amongst all of the pollutants considered, the best estimations of the background were achieved for nitrogen oxides. Although the multi-pronged approach worked well for predominantly vehicle-related pollutants, it could not be used effectively to isolate emissions of PM10 due to the complex and less predictable influence of natural sources (such as marine aerosols). The proposed approach is useful in situations where ambient records from an upwind background station are not available (as required by other techniques) and is potentially transferable to situations such as intersections and arterial roads. Applying this technique to longer time series could help to understand the changes in pollutant concentrations from the road and background sources for different emission scenarios, for different years or seasons. Modelling results also show the potential of such a hybrid semi-empirical models to contribute to our understanding of the physical parameters determining air quality and to validate emissions inventory data.

Modeling of Thermal Phase Noise in a Solid Core Photonic Crystal Fiber-Optic Gyroscope.

PubMed

Song, Ningfang; Ma, Kun; Jin, Jing; Teng, Fei; Cai, Wei

2017-10-26

A theoretical model of the thermal phase noise in a square-wave modulated solid core photonic crystal fiber-optic gyroscope has been established, and then verified by measurements. The results demonstrate a good agreement between theory and experiment. The contribution of the thermal phase noise to the random walk coefficient of the gyroscope is derived. A fiber coil with 2.8 km length is used in the experimental solid core photonic crystal fiber-optic gyroscope, showing a random walk coefficient of 9.25 × 10 -5 deg/√h.

The Contributions of Primary and Secondary Memory to Working Memory Capacity: An Individual Differences Analysis of Immediate Free Recall

ERIC Educational Resources Information Center

Unsworth, Nash; Spillers, Gregory J.; Brewer, Gene A.

2010-01-01

The present study tested the dual-component model of working memory capacity (WMC) by examining estimates of primary memory and secondary memory from an immediate free recall task. Participants completed multiple measures of WMC and general intellectual ability as well as multiple trials of an immediate free recall task. It was demonstrated that…

Unusual specific heat of almost dry L-cysteine and L-cystine amino acids.

PubMed

Ishikawa, M S; Lima, T A; Ferreira, F F; Martinho, H S

2015-03-01

A detailed quantitative analysis of the specific heat in the 0.5- to 200-K temperature range for almost dry L-cysteine and its dimer, L-cystine, amino acids is presented. We report the occurrence of a sharp first-order transition at ∼76 K for L-cysteine associated with the thiol group ordering which was successfully modeled with the two-dimensional Ising model. We demonstrated that quantum rotors, two-level systems (TLS), Einstein oscillators, and acoustic phonons (the Debye model) are essential ingredients to correctly describe the overall experimental data. Our analysis pointed out the absence of the TLS contribution to the low temperature specific heat of L-cysteine. This result was similar to that found in other noncrystalline amorphous materials, e.g., amorphous silicon, low density amorphous water, and ultrastable glasses. L-cystine presented an unusual nonlinear acoustic dispersion relation ω(q)=vq0.95 and a Maxwell-Boltzmann-type distribution of tunneling barriers. The presence of Einstein oscillators with ΘE∼70 K was common in both systems and adequately modeled the boson peak contributions.

High Concentration Protein Ultrafiltration: a Comparative Fouling Assessment

NASA Astrophysics Data System (ADS)

Lim, Y. P.; Mohammad, A. W.

2018-05-01

In this paper, the predominant fouling mechanism via pH manipulation in gelatin ultrafiltration (UF) at constant operating pressure was studied. Two 30 kDa molecular weight cut off (MWCO) UF membranes with different hydrophilic/hydrophobic properties were tested at solution pH near gelatin isoelectric point (IEP), pH below and above gelatin’s IEP. The resistance-in-series model was used to determine quantitatively the contribution of each filtration resistance occurred during gelatin UF. The governing fouling mechanisms were investigated using classical blocking laws. The results demonstrated that concentration polarization remain as dominant fouling resistance in gelatin UF, but exceptional case was observed at pH away from gelatin’s IEP, showing that combined reversible and irreversible fouling resistances contributed around 57% and 37%, respectively to the overall fouling resistances. Under all experimental condition tested, permeate flux decline was accurately predicted by all the models studied. Fouling profile was fitted well with “Standard Blocking”, “Intermediate Blocking” and “Cake Filtration” model for regenerated cellulose acetate (RCA) membrane and “Cake Filtration” model for polyethersulphone (PES) membrane.

Development and validation of open-source software for DNA mixture interpretation based on a quantitative continuous model

PubMed Central

Manabe, Sho; Morimoto, Chie; Hamano, Yuya; Fujimoto, Shuntaro

2017-01-01

In criminal investigations, forensic scientists need to evaluate DNA mixtures. The estimation of the number of contributors and evaluation of the contribution of a person of interest (POI) from these samples are challenging. In this study, we developed a new open-source software “Kongoh” for interpreting DNA mixture based on a quantitative continuous model. The model uses quantitative information of peak heights in the DNA profile and considers the effect of artifacts and allelic drop-out. By using this software, the likelihoods of 1–4 persons’ contributions are calculated, and the most optimal number of contributors is automatically determined; this differs from other open-source software. Therefore, we can eliminate the need to manually determine the number of contributors before the analysis. Kongoh also considers allele- or locus-specific effects of biological parameters based on the experimental data. We then validated Kongoh by calculating the likelihood ratio (LR) of a POI’s contribution in true contributors and non-contributors by using 2–4 person mixtures analyzed through a 15 short tandem repeat typing system. Most LR values obtained from Kongoh during true-contributor testing strongly supported the POI’s contribution even for small amounts or degraded DNA samples. Kongoh correctly rejected a false hypothesis in the non-contributor testing, generated reproducible LR values, and demonstrated higher accuracy of the estimated number of contributors than another software based on the quantitative continuous model. Therefore, Kongoh is useful in accurately interpreting DNA evidence like mixtures and small amounts or degraded DNA samples. PMID:29149210

Development and validation of open-source software for DNA mixture interpretation based on a quantitative continuous model.

PubMed

Manabe, Sho; Morimoto, Chie; Hamano, Yuya; Fujimoto, Shuntaro; Tamaki, Keiji

2017-01-01

In criminal investigations, forensic scientists need to evaluate DNA mixtures. The estimation of the number of contributors and evaluation of the contribution of a person of interest (POI) from these samples are challenging. In this study, we developed a new open-source software "Kongoh" for interpreting DNA mixture based on a quantitative continuous model. The model uses quantitative information of peak heights in the DNA profile and considers the effect of artifacts and allelic drop-out. By using this software, the likelihoods of 1-4 persons' contributions are calculated, and the most optimal number of contributors is automatically determined; this differs from other open-source software. Therefore, we can eliminate the need to manually determine the number of contributors before the analysis. Kongoh also considers allele- or locus-specific effects of biological parameters based on the experimental data. We then validated Kongoh by calculating the likelihood ratio (LR) of a POI's contribution in true contributors and non-contributors by using 2-4 person mixtures analyzed through a 15 short tandem repeat typing system. Most LR values obtained from Kongoh during true-contributor testing strongly supported the POI's contribution even for small amounts or degraded DNA samples. Kongoh correctly rejected a false hypothesis in the non-contributor testing, generated reproducible LR values, and demonstrated higher accuracy of the estimated number of contributors than another software based on the quantitative continuous model. Therefore, Kongoh is useful in accurately interpreting DNA evidence like mixtures and small amounts or degraded DNA samples.

Color discrimination with broadband photoreceptors.

PubMed

Schnaitmann, Christopher; Garbers, Christian; Wachtler, Thomas; Tanimoto, Hiromu

2013-12-02

Color vision is commonly assumed to rely on photoreceptors tuned to narrow spectral ranges. In the ommatidium of Drosophila, the four types of so-called inner photoreceptors express different narrow-band opsins. In contrast, the outer photoreceptors have a broadband spectral sensitivity and were thought to exclusively mediate achromatic vision. Using computational models and behavioral experiments, we demonstrate that the broadband outer photoreceptors contribute to color vision in Drosophila. The model of opponent processing that includes the opsin of the outer photoreceptors scored the best fit to wavelength discrimination data. To experimentally uncover the contribution of individual photoreceptor types, we restored phototransduction of targeted photoreceptor combinations in a blind mutant. Dichromatic flies with only broadband photoreceptors and one additional receptor type can discriminate different colors, indicating the existence of a specific output comparison of the outer and inner photoreceptors. Furthermore, blocking interneurons postsynaptic to the outer photoreceptors specifically impaired color but not intensity discrimination. Our findings show that receptors with a complex and broad spectral sensitivity can contribute to color vision and reveal that chromatic and achromatic circuits in the fly share common photoreceptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic modulation of the iris transillumination defect: a systems genetics analysis using the expanded family of BXD glaucoma strains

PubMed Central

Swaminathan, Shankar; Lu, Hong; Williams, Robert W; Lu, Lu; Jablonski, Monica M

2013-01-01

We investigated the contributions of Tyrp1 and Gpnmb to the iris transillumination defect (TID) in five age cohorts of BXD mice. Using systems genetics, we also evaluated the role of other known pigmentation genes (PGs). Mapping studies indicate that Tyrp1 contributes to the phenotype at all ages, yet the TID maps to Gpnmb only in the oldest cohort. Composite interval mapping reveals secondary loci viz. Oca2, Myo5a, Prkcz, and Zbtb20 that modulate the phenotype in the age groups up to 10–13 months. The contributions of Tyrp1 and Gpnmb were highly significant in all age cohorts. Moreover, in young mice, all six gene candidates had substantial interactions in our model. Our model accounted for 71–88% of the explained variance of the TID phenotype across the age bins. These results demonstrate that along with Tyrp1 and Gpnmb, Oca2, Myo5a, Prkcz, and Zbtb20 modulate the TID in an age-dependent manner. PMID:23582180

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2007-08-01

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

Assessing the contribution of different factors in RegCM4.3 regional climate model projections using the Factor Separation method over the Med-CORDEX domain

NASA Astrophysics Data System (ADS)

Zsolt Torma, Csaba; Giorgi, Filippo

2014-05-01

A set of regional climate model (RCM) simulations applying dynamical downscaling of global climate model (GCM) simulations over the Mediterranean domain specified by the international initiative Coordinated Regional Downscaling Experiment (CORDEX) were completed with the Regional Climate Model RegCM, version RegCM4.3. Two GCMs were selected from the Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble to provide the driving fields for the RegCM: HadGEM2-ES (HadGEM) and MPI-ESM-MR (MPI). The simulations consist of an ensemble including multiple physics configurations and different "Reference Concentration Pathways" (RCP4.5 and RCP8.5). In total 15 simulations were carried out with 7 model physics configurations with varying convection and land surface schemes. The horizontal grid spacing of the RCM simulations is 50 km and the simulated period in all cases is 1970-2100 (1970-2099 in case of HadGEM driven simulations). This ensemble includes a combination of experiments in which different model components are changed individually and in combination, and thus lends itself optimally to the application of the Factor Separation (FS) method. This study applies the FS method to investigate the contributions of different factors, along with their synergy, on a set of regional climate model (RCM) projections for the Mediterranean region. The FS method is applied to 6 projections for the period 1970-2100 performed with the regional model RegCM4.3 over the Med-CORDEX domain. Two different sets of factors are intercompared, namely the driving global climate model (HadGEM and MPI) boundary conditions against two model physics settings (convection scheme and irrigation). We find that both the GCM driving conditions and the model physics provide important contributions, depending on the variable analyzed (surface air temperature and precipitation), season (winter vs. summer) and time horizon into the future, while the synergy term mostly tends to counterbalance the contributions of the individual factors. We demonstrate the usefulness of the FS method to assess different sources of uncertainty in RCM-based regional climate projections.

Implementation and evaluation of PM2.5 source contribution ...

EPA Pesticide Factsheets

Source culpability assessments are useful for developing effective emissions control programs. The Integrated Source Apportionment Method (ISAM) has been implemented in the Community Multiscale Air Quality (CMAQ) model to track contributions from source groups and regions to ambient levels and deposited amounts of primary and secondary inorganic PM2.5. Confidence in this approach is established by comparing ISAM source contribution estimates to emissions zero-out simulations recognizing that these approaches are not always expected to provide the same answer. The comparisons are expected to be most similar for more linear processes such as those involving primary emissions of PM2.5 and most different for non-linear systems like ammonium nitrate formation. Primarily emitted PM2.5 (e.g. elemental carbon), sulfur dioxide, ammonia, and nitrogen oxide contribution estimates compare well to zero-out estimates for ambient concentration and deposition. PM2.5 sulfate ion relationships are strong, but nonlinearity is evident and shown to be related to aqueous phase oxidation reactions in the host model. ISAM and zero-out contribution estimates are less strongly related for PM2.5 ammonium nitrate, resulting from instances of non-linear chemistry and negative responses (increases in PM2.5 due to decreases in emissions). ISAM is demonstrated in the context of an annual simulation tracking well characterized emissions source sectors and boundary conditions shows source contri

Bayesian Fundamentalism or Enlightenment? On the explanatory status and theoretical contributions of Bayesian models of cognition.

PubMed

Jones, Matt; Love, Bradley C

2011-08-01

The prominence of Bayesian modeling of cognition has increased recently largely because of mathematical advances in specifying and deriving predictions from complex probabilistic models. Much of this research aims to demonstrate that cognitive behavior can be explained from rational principles alone, without recourse to psychological or neurological processes and representations. We note commonalities between this rational approach and other movements in psychology - namely, Behaviorism and evolutionary psychology - that set aside mechanistic explanations or make use of optimality assumptions. Through these comparisons, we identify a number of challenges that limit the rational program's potential contribution to psychological theory. Specifically, rational Bayesian models are significantly unconstrained, both because they are uninformed by a wide range of process-level data and because their assumptions about the environment are generally not grounded in empirical measurement. The psychological implications of most Bayesian models are also unclear. Bayesian inference itself is conceptually trivial, but strong assumptions are often embedded in the hypothesis sets and the approximation algorithms used to derive model predictions, without a clear delineation between psychological commitments and implementational details. Comparing multiple Bayesian models of the same task is rare, as is the realization that many Bayesian models recapitulate existing (mechanistic level) theories. Despite the expressive power of current Bayesian models, we argue they must be developed in conjunction with mechanistic considerations to offer substantive explanations of cognition. We lay out several means for such an integration, which take into account the representations on which Bayesian inference operates, as well as the algorithms and heuristics that carry it out. We argue this unification will better facilitate lasting contributions to psychological theory, avoiding the pitfalls that have plagued previous theoretical movements.

Phenotypic outcomes in Mouse and Human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms.

PubMed

Haldipur, Parthiv; Dang, Derek; Aldinger, Kimberly A; Janson, Olivia K; Guimiot, Fabien; Adle-Biasette, Homa; Dobyns, William B; Siebert, Joseph R; Russo, Rosa; Millen, Kathleen J

2017-01-16

FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation. Previously, we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule which echoes the posterior vermis DW 'tail sign' observed in human imaging studies. Lineage tracing experiments in Foxc1 mutant mouse cerebella indicate that aberrant migration of granule cell progenitors destined to form the posterior-most lobule causes this unique phenotype. Analyses of rare human del chr 6p25 fetal cerebella demonstrate extensive phenotypic overlap with our Foxc1 mutant mouse models, validating our DWM models and demonstrating that many key mechanisms controlling cerebellar development are likely conserved between mouse and human.

Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery.

PubMed

Mei, Feng; Lehmann-Horn, Klaus; Shen, Yun-An A; Rankin, Kelsey A; Stebbins, Karin J; Lorrain, Daniel S; Pekarek, Kara; A Sagan, Sharon; Xiao, Lan; Teuscher, Cory; von Büdingen, H-Christian; Wess, Jürgen; Lawrence, J Josh; Green, Ari J; Fancy, Stephen Pj; Zamvil, Scott S; Chan, Jonah R

2016-09-27

Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination.

The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.

PubMed

Laifenfeld, Daphna; Gilchrist, Annalyn; Drubin, David; Jorge, Milena; Eddy, Sean F; Frushour, Brian P; Ladd, Bill; Obert, Leslie A; Gosink, Mark M; Cook, Jon C; Criswell, Kay; Somps, Christopher J; Koza-Taylor, Petra; Elliston, Keith O; Lawton, Michael P

2010-01-01

To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE-induced hemangiosarcoma in mice.

The Role of Hypoxia in 2-Butoxyethanol–Induced Hemangiosarcoma

PubMed Central

Laifenfeld, Daphna; Gilchrist, Annalyn; Drubin, David; Jorge, Milena; Eddy, Sean F.; Frushour, Brian P.; Ladd, Bill; Obert, Leslie A.; Gosink, Mark M.; Cook, Jon C.; Criswell, Kay; Somps, Christopher J.; Koza-Taylor, Petra; Elliston, Keith O.; Lawton, Michael P.

2010-01-01

To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE–induced hemangiosarcoma in mice. PMID:19812364

Discrete-time model reduction in limited frequency ranges

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Juang, Jer-Nan; Longman, Richard W.

1991-01-01

A mathematical formulation for model reduction of discrete time systems such that the reduced order model represents the system in a particular frequency range is discussed. The algorithm transforms the full order system into balanced coordinates using frequency weighted discrete controllability and observability grammians. In this form a criterion is derived to guide truncation of states based on their contribution to the frequency range of interest. Minimization of the criterion is accomplished without need for numerical optimization. Balancing requires the computation of discrete frequency weighted grammians. Close form solutions for the computation of frequency weighted grammians are developed. Numerical examples are discussed to demonstrate the algorithm.

A Transgenic Drosophila melanogaster Model To Study Human T-Lymphotropic Virus Oncoprotein Tax-1-Driven Transformation In Vivo

PubMed Central

Shirinian, Margret; Kambris, Zakaria; Hamadeh, Lama; Grabbe, Caroline; Journo, Chloé; Mahieux, Renaud

2015-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma is an aggressive malignancy. HTLV-2 is genetically related to HTLV-1 but does not cause any malignant disease. HTLV-1 Tax transactivator (Tax-1) contributes to leukemogenesis via NF-κB. We describe transgenic Drosophila models expressing Tax in the compound eye and plasmatocytes. We demonstrate that Tax-1 but not Tax-2 induces ommatidial perturbation and increased plasmatocyte proliferation and that the eye phenotype is dependent on Kenny (IKKγ/NEMO), thus validating this new in vivo model. PMID:25995252

Aura Satellite Mission: Oxford/RAL Spring School in Quantitative Earth Observation

NASA Technical Reports Server (NTRS)

Douglass, Anne

2005-01-01

The four instruments on Aura are providing new and exciting measurements of stratospheric and tropospheric ozone, species that contribute to ozone production and loss, and long-lived gases such as nitrous oxide and methane that provide information about atmospheric transport. These discussions of atmospheric chemistry will start with the basic principles of ozone production and loss. Aura data will be used where possible to illustrate the pertinent atmospheric processes. Three-dimensional model simulations will be used both to illustrate present capabilities in constituent modeling and to demonstrate how observations are used to evaluate and improve models and our ability to predict future ozone evolution.

Advanced Stochastic Collocation Methods for Polynomial Chaos in RAVEN

NASA Astrophysics Data System (ADS)

Talbot, Paul W.

As experiment complexity in fields such as nuclear engineering continually increases, so does the demand for robust computational methods to simulate them. In many simulations, input design parameters and intrinsic experiment properties are sources of uncertainty. Often small perturbations in uncertain parameters have significant impact on the experiment outcome. For instance, in nuclear fuel performance, small changes in fuel thermal conductivity can greatly affect maximum stress on the surrounding cladding. The difficulty quantifying input uncertainty impact in such systems has grown with the complexity of numerical models. Traditionally, uncertainty quantification has been approached using random sampling methods like Monte Carlo. For some models, the input parametric space and corresponding response output space is sufficiently explored with few low-cost calculations. For other models, it is computationally costly to obtain good understanding of the output space. To combat the expense of random sampling, this research explores the possibilities of using advanced methods in Stochastic Collocation for generalized Polynomial Chaos (SCgPC) as an alternative to traditional uncertainty quantification techniques such as Monte Carlo (MC) and Latin Hypercube Sampling (LHS) methods for applications in nuclear engineering. We consider traditional SCgPC construction strategies as well as truncated polynomial spaces using Total Degree and Hyperbolic Cross constructions. We also consider applying anisotropy (unequal treatment of different dimensions) to the polynomial space, and offer methods whereby optimal levels of anisotropy can be approximated. We contribute development to existing adaptive polynomial construction strategies. Finally, we consider High-Dimensional Model Reduction (HDMR) expansions, using SCgPC representations for the subspace terms, and contribute new adaptive methods to construct them. We apply these methods on a series of models of increasing complexity. We use analytic models of various levels of complexity, then demonstrate performance on two engineering-scale problems: a single-physics nuclear reactor neutronics problem, and a multiphysics fuel cell problem coupling fuels performance and neutronics. Lastly, we demonstrate sensitivity analysis for a time-dependent fuels performance problem. We demonstrate the application of all the algorithms in RAVEN, a production-level uncertainty quantification framework.

Alfentanil and placebo analgesia: no sex differences detected in models of experimental pain.

PubMed

Olofsen, Erik; Romberg, Raymonda; Bijl, Hans; Mooren, René; Engbers, Frank; Kest, Benjamin; Dahan, Albert

2005-07-01

To assess whether patient sex contributes to the interindividual variability in alfentanil analgesic sensitivity, the authors compared male and female subjects for pain sensitivity after alfentanil using a pharmacokinetic-pharmacodynamic modeling approach. Healthy volunteers received a 30-min alfentanil or placebo infusion on two occasions. Analgesia was measured during the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation (eight men and eight women) of increasing intensity or using visual analog scale scores during treatment with noxious thermal heat (five men and five women). Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic models were applied to the analgesia and sedation data using NONMEM. For electrical pain, the placebo and alfentanil models were combined post hoc. Alfentanil and placebo analgesic responses did not differ between sexes. The placebo effect was successfully incorporated into the alfentanil pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency of alfentanil. However, the placebo effect did not contribute to the analgesic response variability. The pharmacokinetic-pharmacodynamic analysis of the electrical and heat pain data yielded similar values for the potency parameter, but the blood-effect site equilibration half-life was significantly longer for electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min). In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.

An algorithm to detect and communicate the differences in computational models describing biological systems.

PubMed

Scharm, Martin; Wolkenhauer, Olaf; Waltemath, Dagmar

2016-02-15

Repositories support the reuse of models and ensure transparency about results in publications linked to those models. With thousands of models available in repositories, such as the BioModels database or the Physiome Model Repository, a framework to track the differences between models and their versions is essential to compare and combine models. Difference detection not only allows users to study the history of models but also helps in the detection of errors and inconsistencies. Existing repositories lack algorithms to track a model's development over time. Focusing on SBML and CellML, we present an algorithm to accurately detect and describe differences between coexisting versions of a model with respect to (i) the models' encoding, (ii) the structure of biological networks and (iii) mathematical expressions. This algorithm is implemented in a comprehensive and open source library called BiVeS. BiVeS helps to identify and characterize changes in computational models and thereby contributes to the documentation of a model's history. Our work facilitates the reuse and extension of existing models and supports collaborative modelling. Finally, it contributes to better reproducibility of modelling results and to the challenge of model provenance. The workflow described in this article is implemented in BiVeS. BiVeS is freely available as source code and binary from sems.uni-rostock.de. The web interface BudHat demonstrates the capabilities of BiVeS at budhat.sems.uni-rostock.de. © The Author 2015. Published by Oxford University Press.

Source contributions to United States ozone and particulate matter over five decades from 1970 to 2020

NASA Astrophysics Data System (ADS)

Nopmongcol, Uarporn; Alvarez, Yesica; Jung, Jaegun; Grant, John; Kumar, Naresh; Yarwood, Greg

2017-10-01

Evaluating long-term air quality trends can demonstrate effectiveness of control strategies and guide future air quality management planning. Observations have shown that ozone (O3) and fine particulate matter (PM2.5) in the US have declined since as early as 1980 in some areas. But observation trends alone cannot separate effects of changes in local and global emissions to US air quality which are important to air quality planners. This study uses a regional model (CAMx) nested within a global model (GEOS-Chem) to characterize regional changes in O3 and PM2.5 due to the intercontinental transport and local/regional emissions representing six modeling years within five decades (1970-2020). We use the CAMx Source Apportionment Technology (OSAT/PSAT) to estimate contributions from 6 source sectors in 7 source regions plus 6 other groups for a total of 48 tagged contributions. On-road mobile sources consistently make the largest U.S. anthropogenic emissions contribution to O3 in all cities examined even though they decline substantially from 1970 to 2005 and also from 2005 to 2020. Off-road mobile source contributions increase from 1970 to 2005 and then decrease after 2005 in all of the cities. The boundary conditions, mostly from intercontinental transport, contribute more than 20 ppb to high maximum daily 8-h average (MDA8) O3 for all six years. We found that lowering NOx emissions raises O3 formation efficiency (OFE) across all emission categories which will limit potential O3 benefits of local NOx strategies in the near future. PM2.5 benefited from adoption of control devices between 1970 and 1980 and has continued to decline through 2005 and expected to decline further by 2020. Area sources such as residential, commercial and fugitive dust emissions stand out as making large contributions to PM2.5 that are not declining. Inter-regional transport is less important in 2020 than 1990 for both pollutants.

Modeling shockwaves and impact phenomena with Eulerian peridynamics

DOE PAGES

Silling, Stewart A.; Parks, Michael L.; Kamm, James R.; ...

2017-05-09

Most previous development of the peridynamic theory has assumed a Lagrangian formulation, in which the material model refers to an undeformed reference configuration. Here, an Eulerian form of material modeling is developed, in which bond forces depend only on the positions of material points in the deformed configuration. The formulation is consistent with the thermodynamic form of the peridynamic model and is derivable from a suitable expression for the free energy of a material. We show that the resulting formulation of peridynamic material models can be used to simulate strong shock waves and fluid response in which very large deformationsmore » make the Lagrangian form unsuitable. The Eulerian capability is demonstrated in numerical simulations of ejecta from a wavy free surface on a metal subjected to strong shock wave loading. The Eulerian and Lagrangian contributions to bond force can be combined in a single material model, allowing strength and fracture under tensile or shear loading to be modeled consistently with high compressive stresses. Furthermore, we demonstrate this capability in numerical simulation of bird strike against an aircraft, in which both tensile fracture and high pressure response are important.« less

Modeling shockwaves and impact phenomena with Eulerian peridynamics

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

Silling, Stewart A.; Parks, Michael L.; Kamm, James R.

Most previous development of the peridynamic theory has assumed a Lagrangian formulation, in which the material model refers to an undeformed reference configuration. Here, an Eulerian form of material modeling is developed, in which bond forces depend only on the positions of material points in the deformed configuration. The formulation is consistent with the thermodynamic form of the peridynamic model and is derivable from a suitable expression for the free energy of a material. We show that the resulting formulation of peridynamic material models can be used to simulate strong shock waves and fluid response in which very large deformationsmore » make the Lagrangian form unsuitable. The Eulerian capability is demonstrated in numerical simulations of ejecta from a wavy free surface on a metal subjected to strong shock wave loading. The Eulerian and Lagrangian contributions to bond force can be combined in a single material model, allowing strength and fracture under tensile or shear loading to be modeled consistently with high compressive stresses. Furthermore, we demonstrate this capability in numerical simulation of bird strike against an aircraft, in which both tensile fracture and high pressure response are important.« less

Distinguishing dark matter from unresolved point sources in the Inner Galaxy with photon statistics

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

Lee, Samuel K.; Lisanti, Mariangela; Safdi, Benjamin R., E-mail: samuelkl@princeton.edu, E-mail: mlisanti@princeton.edu, E-mail: bsafdi@princeton.edu

2015-05-01

Data from the Fermi Large Area Telescope suggests that there is an extended excess of GeV gamma-ray photons in the Inner Galaxy. Identifying potential astrophysical sources that contribute to this excess is an important step in verifying whether the signal originates from annihilating dark matter. In this paper, we focus on the potential contribution of unresolved point sources, such as millisecond pulsars (MSPs). We propose that the statistics of the photons—in particular, the flux probability density function (PDF) of the photon counts below the point-source detection threshold—can potentially distinguish between the dark-matter and point-source interpretations. We calculate the flux PDFmore » via the method of generating functions for these two models of the excess. Working in the framework of Bayesian model comparison, we then demonstrate that the flux PDF can potentially provide evidence for an unresolved MSP-like point-source population.« less

Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

PubMed Central

Smeets, Bart; Kuppe, Christoph; Sicking, Eva-Maria; Fuss, Astrid; Jirak, Peggy; van Kuppevelt, Toin H.; Endlich, Karlhans; Wetzels, Jack F.M.; Gröne, Hermann-Josef; Floege, Jürgen

2011-01-01

The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis. PMID:21719782

Density functional tight-binding and infrequent metadynamics can capture entropic effects in intramolecular hydrogen transfer reactions

NASA Astrophysics Data System (ADS)

Oliveira, Luiz F. L.; Fu, Christopher D.; Pfaendtner, Jim

2018-04-01

Infrequent metadynamics uses biased simulations to estimate the unbiased kinetics of a system, facilitating the calculation of rates and barriers. Here the method is applied to study intramolecular hydrogen transfer reactions involving peroxy radicals, a class of reactions that is challenging to model due to the entropic contributions of the formation of ring structures in the transition state. Using the self-consistent charge density-functional based tight-binding (DFTB) method, we applied infrequent metadynamics to the study of four intramolecular H-transfer reactions, demonstrating that the method can qualitatively reproduce these high entropic contributions, as observed in experiments and those predicted by transition state theory modeled by higher levels of theory. We also show that infrequent metadynamics and DFTB are successful in describing the relationship between transition state ring size and kinetic coefficients (e.g., activation energies and the pre-exponential factors).

Thin-slice vision: inference of confidence measure from perceptual video quality

NASA Astrophysics Data System (ADS)

Hameed, Abdul; Balas, Benjamin; Dai, Rui

2016-11-01

There has been considerable research on thin-slice judgments, but no study has demonstrated the predictive validity of confidence measures when assessors watch videos acquired from communication systems, in which the perceptual quality of videos could be degraded by limited bandwidth and unreliable network conditions. This paper studies the relationship between high-level thin-slice judgments of human behavior and factors that contribute to perceptual video quality. Based on a large number of subjective test results, it has been found that the confidence of a single individual present in all the videos, called speaker's confidence (SC), could be predicted by a list of features that contribute to perceptual video quality. Two prediction models, one based on artificial neural network and the other based on a decision tree, were built to predict SC. Experimental results have shown that both prediction models can result in high correlation measures.

Frequency Regulation and Oscillation Damping Contributions of Variable-Speed Wind Generators in the U.S. Eastern Interconnection (EI)

DOE PAGES

Liu, Yong; Gracia, Jose R,; King, Jr, Thomas J.; ...

2014-05-16

The U.S. Eastern Interconnection (EI) is one of the largest electric power grids in the world and is expected to have difficulties in dealing with frequency regulation and oscillation damping issues caused by the increasing wind power. On the other side, variable-speed wind generators can actively engage in frequency regulation or oscillation damping with supplementary control loops. This paper creates a 5% wind power penetration simulation scenario based on the 16 000-bus EI system dynamic model and developed the user-defined wind electrical control model in PSS (R) E that incorporates additional frequency regulation and oscillation damping control loops. We evaluatedmore » the potential contributions of variable-speed wind generations to the EI system frequency regulation and oscillation damping, and simulation results demonstrate that current and future penetrations of wind power are promising in the EI system frequency regulation and oscillation damping.« less

Coherent structures in turbulence and Prandtl's mixing length theory (27th Ludwig Prandtl Memorial Lecture)

NASA Astrophysics Data System (ADS)

Landahl, M. T.

1984-08-01

The fundamental ideas behind Prandtl's famous mixing length theory are discussed in the light of newer findings from experimental and theoretical research on coherent turbulence structures in the region near solid walls. A simple theoretical model for 'flat' structures is used to examine the fundamental assumptions behind Prandtl's theory. The model is validated by comparisons with conditionally sampled velocity data obtained in recent channel flow experiments. Particular attention is given to the role of pressure fluctuations on the evolution of flat eddies. The validity of Prandtl's assumption that an element of fluid retains its streamwise momentum as it is moved around by turbulence is confirmed for flat eddies. It is demonstrated that spanwise pressure gradients give rise to a contribution to the vertical displacement of a fluid element which is proportional to the distance from the wall. This contribution is particularly important for eddies that are highly elongated in the streamwise direction.

Learning-related skills and academic achievement in academically at-risk first graders

PubMed Central

Cerda, Carissa A.; Im, Myung Hee; Hughes, Jan N.

2015-01-01

Using an academically at-risk, ethnically diverse sample of 744 first-grade children, this study tested a multi-method (i.e., child performance measures, teacher ratings, and peer ratings) measurement model of learning-related skills (i.e., effortful control [EC], behavioral self-regulation [BSR], and social competence [SC]), and their shared and unique contributions to children's reading and math achievement, above the effect of demographic variables. The hypothesized correlated factor measurement model demonstrated relatively good fit, with BSR and SC correlated highly with one another and moderately with EC. When entered in separate regression equations, EC and BSR each predicted children's reading and math achievement; SC only predicted reading achievement. When considered simultaneously, neither EC, BSR, nor SC contributed independently to reading achievement; however, EC had a direct effect on math achievement and an indirect effect on reading achievement via both BSR and SC. Implications for research and early intervention efforts are discussed. PMID:25908886

Geometric saliency to characterize radar exploitation performance

NASA Astrophysics Data System (ADS)

Nolan, Adam; Keserich, Brad; Lingg, Andrew; Goley, Steve

2014-06-01

Based on the fundamental scattering mechanisms of facetized computer-aided design (CAD) models, we are able to define expected contributions (EC) to the radar signature. The net result of this analysis is the prediction of the salient aspects and contributing vehicle morphology based on the aspect. Although this approach does not provide the fidelity of an asymptotic electromagnetic (EM) simulation, it does provide very fast estimates of the unique scattering that can be consumed by a signature exploitation algorithm. The speed of this approach is particularly relevant when considering the high dimensionality of target configuration variability due to articulating parts which are computationally burdensome to predict. The key scattering phenomena considered in this work are the specular response from a single bounce interaction with surfaces and dihedral response formed between the ground plane and vehicle. Results of this analysis are demonstrated for a set of civilian target models.

Unscreening Modified Gravity in the Matter Power Spectrum.

PubMed

Lombriser, Lucas; Simpson, Fergus; Mead, Alexander

2015-06-26

Viable modifications of gravity that may produce cosmic acceleration need to be screened in high-density regions such as the Solar System, where general relativity is well tested. Screening mechanisms also prevent strong anomalies in the large-scale structure and limit the constraints that can be inferred on these gravity models from cosmology. We find that by suppressing the contribution of the screened high-density regions in the matter power spectrum, allowing a greater contribution of unscreened low densities, modified gravity models can be more readily discriminated from the concordance cosmology. Moreover, by variation of density thresholds, degeneracies with other effects may be dealt with more adequately. Specializing to chameleon gravity as a worked example for screening in modified gravity, employing N-body simulations of f(R) models and the halo model of chameleon theories, we demonstrate the effectiveness of this method. We find that a percent-level measurement of the clipped power at k<0.3h/Mpc can yield constraints on chameleon models that are more stringent than what is inferred from Solar System tests or distance indicators in unscreened dwarf galaxies. Finally, we verify that our method is also applicable to the Vainshtein mechanism.

Landslides! Engaging students in natural hazards and STEM principles through the exploration of landslide analog models

NASA Astrophysics Data System (ADS)

Gochis, E. E.; Lechner, H. N.; Brill, K. A.; Lerner, G.; Ramos, E.

2014-12-01

Graduate students at Michigan Technological University developed the "Landslides!" activity to engage middle & high school students participating in summer engineering programs in a hands-on exploration of geologic engineering and STEM (Science, Technology, Engineering and Math) principles. The inquiry-based lesson plan is aligned to Next Generation Science Standards and is appropriate for 6th-12th grade classrooms. During the activity students focus on the factors contributing to landslide development and engineering practices used to mitigate hazards of slope stability hazards. Students begin by comparing different soil types and by developing predictions of how sediment type may contribute to differences in slope stability. Working in groups, students then build tabletop hill-slope models from the various materials in order to engage in evidence-based reasoning and test their predictions by adding groundwater until each group's modeled slope fails. Lastly students elaborate on their understanding of landslides by designing 'engineering solutions' to mitigate the hazards observed in each model. Post-evaluations from students demonstrate that they enjoyed the hands-on nature of the activity and the application of engineering principles to mitigate a modeled natural hazard.

Event-based rainfall-runoff modelling of the Kelantan River Basin

NASA Astrophysics Data System (ADS)

Basarudin, Z.; Adnan, N. A.; Latif, A. R. A.; Tahir, W.; Syafiqah, N.

2014-02-01

Flood is one of the most common natural disasters in Malaysia. According to hydrologists there are many causes that contribute to flood events. The two most dominant factors are the meteorology factor (i.e climate change) and change in land use. These two factors contributed to floods in recent decade especially in the monsoonal catchment such as Malaysia. This paper intends to quantify the influence of rainfall during extreme rainfall events on the hydrological model in the Kelantan River catchment. Therefore, two dynamic inputs were used in the study: rainfall and river discharge. The extreme flood events in 2008 and 2004 were compared based on rainfall data for both years. The events were modeled via a semi-distributed HEC-HMS hydrological model. Land use change was not incorporated in the study because the study only tries to quantify rainfall changes during these two events to simulate the discharge and runoff value. Therefore, the land use data representing the year 2004 were used as inputs in the 2008 runoff model. The study managed to demonstrate that rainfall change has a significant impact to determine the peak discharge and runoff depth for the study area.

Contribution of cosmic ray particles to radiation environment at high mountain altitude: Comparison of Monte Carlo simulations with experimental data.

PubMed

Mishev, A L

2016-03-01

A numerical model for assessment of the effective dose due to secondary cosmic ray particles of galactic origin at high mountain altitude of about 3000 m above the sea level is presented. The model is based on a newly numerically computed effective dose yield function considering realistic propagation of cosmic rays in the Earth magnetosphere and atmosphere. The yield function is computed using a full Monte Carlo simulation of the atmospheric cascade induced by primary protons and α- particles and subsequent conversion of secondary particle fluence (neutrons, protons, gammas, electrons, positrons, muons and charged pions) to effective dose. A lookup table of the newly computed effective dose yield function is provided. The model is compared with several measurements. The comparison of model simulations with measured spectral energy distributions of secondary cosmic ray neutrons at high mountain altitude shows good consistency. Results from measurements of radiation environment at high mountain station--Basic Environmental Observatory Moussala (42.11 N, 23.35 E, 2925 m a.s.l.) are also shown, specifically the contribution of secondary cosmic ray neutrons. A good agreement with the model is demonstrated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Temperate marine protected area provides recruitment subsidies to local fisheries.

PubMed

Le Port, A; Montgomery, J C; Smith, A N H; Croucher, A E; McLeod, I M; Lavery, S D

2017-10-25

The utility of marine protected areas (MPAs) as a means of protecting exploited species and conserving biodiversity within MPA boundaries is supported by strong empirical evidence. However, the potential contribution of MPAs to fished populations beyond their boundaries is still highly controversial; empirical measures are scarce and modelling studies have produced a range of predictions, including both positive and negative effects. Using a combination of genetic parentage and relatedness analysis, we measured larval subsidies to local fisheries replenishment for Australasian snapper ( Chrysophrys auratus : Sparidae) from a small (5.2 km 2 ), well-established, temperate, coastal MPA in northern New Zealand. Adult snapper within the MPA contributed an estimated 10.6% (95% CI: 5.5-18.1%) of newly settled juveniles to surrounding areas (approx. 400 km 2 ), with no decreasing trend in contributions up to 40 km away. Biophysical modelling of larval dispersal matched experimental data, showing larvae produced inside the MPA dispersed over a comparable distance. These results demonstrate that temperate MPAs have the potential to provide recruitment subsidies at magnitudes and spatial scales relevant to fisheries management. The validated biophysical model provides a cost-efficient opportunity to generalize these findings to other locations and climate conditions, and potentially informs the design of MPA networks for enhancing fisheries management. © 2017 The Author(s).

Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

PubMed

Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory

2015-10-01

Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.

Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

PubMed

Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

2015-02-24

Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

Intra-tubular hydrodynamic forces influence tubulo-interstitial fibrosis in the kidney

PubMed Central

Rohatgi, Rajeev; Flores, Daniel

2010-01-01

Purpose of review Renal epithelial cells respond to mechanical stimuli with immediate transduction events (e.g., activation of ion channels), intermediate biological responses (e.g., changes in gene expression), and long term cellular adaptation (e.g., protein expression). Progressive renal disease is characterized by disturbed glomerular hydrodynamics that contributes to glomerulosclerosis, but, how intra-tubular biomechanical forces contribute to tubulo-interstital inflammation and fibrosis is poorly understood. Recent findings In vivo and in vitro models of obstructive uropathy demonstrate that tubular stretch induces robust expression of transforming growth factor β-1 (TGFβ-1), activation of tubular apoptosis, and induction of NF-κB signaling which contribute to the inflammatory and fibrotic milieu. Non-obstructive structural kidney diseases associated with nephron loss follow a course characterized by compensatory increases of single nephron glomerular filtration rate and tubular flow rate. Resulting increases in tubular fluid shear stress (FSS) reduce tissue-plasminogen activator and urokinase enzymatic activity which diminishes breakdown of extracellular matrix. In models of high dietary Na intake, which increase tubular flow, urinary TGFβ-1 concentrations and renal mitogen activated protein kinase activity are increased. Summary In conclusion, intra-tubular biomechanical forces, stretch and FSS, generate changes in intracellular signaling and gene expression that contribute to the pathobiology of obstructive, and non-obstructive kidney disease. PMID:19851105

Children's perceptions of the classroom environment and social and academic performance: a longitudinal analysis of the contribution of the Responsive Classroom approach.

PubMed

Brock, Laura L; Nishida, Tracy K; Chiong, Cynthia; Grimm, Kevin J; Rimm-Kaufman, Sara E

2008-04-01

This study examines the contribution of the Responsive Classroom (RC) Approach, a set of teaching practices that integrate social and academic learning, to children's perceptions of their classroom, and children's academic and social performance over time. Three questions emerge: (a) What is the concurrent and cumulative relation between children's perceptions of the classroom and social and academic outcomes over time? (b) What is the contribution of teacher's use of RC practices to children's perceptions and social and academic outcomes? (c) Do children's perceptions of the classroom mediate the relation between RC teacher practices and child outcomes? Cross-lagged autoregressive structural equation models were used to analyze teacher and child-report questionnaire data, along with standardized test scores collected over 3 years from a sample of 520 children in grades 3-5. Results indicate a significant positive relation between RC teacher practices and child perceptions and outcomes over time. Further, children's perceptions partially mediated the relation between RC teacher practices and social competence. However, the models did not demonstrate that child perceptions mediated the relation between RC practices and achievement outcomes. Results are explained in terms of the contribution of teacher practices to children's perceptions and student performance.

What can we learn from the self-attraction and loading fingerprints about pre-GRACE mass-loss acceleration from Greenland and Antarctica?

NASA Astrophysics Data System (ADS)

Davis, J. L.; Vinogradova, N. T.

2017-12-01

Tide-gauge records from the North Atlantic reveal significant acceleration in sea level starting in the late 20th century. We have analyzed the tide-gauge data using a model in which the accelerations are assumed to be zero prior to 1990. The estimated accelerations range from -1 to +3 m cy-2 and exhibit a systematic spatial variability. Davis and Vinogradova [2017] demonstrated that to model this variability in sea-level acceleration requires contributions from several distinct physical processes: accelerated mass loss from the Greenland and Antarctic Ice Sheets and acceleration associated with ocean circulation and heat uptake. Atmospheric pressure also contributes to the observed changes in sea level, at a much smaller amplitude. Because we are focusing on sea-level accelerations (i.e., sea-level rate changes), the contribution from Glacial Isostatic Adjustment (GIA) is negligible. Modeling of observed sea-level acceleration is achieved using external constraints for the important physical processes. Using GRACE results, we can calculate the sea-level "fingerprints" for Greenland and Antarctica associated with mass loading and gravitational perturbations. For the North Atlantic, Greenland induces a significant spatial variation in sea-level change—dominated by the solid-Earth response to the mass loss—whereas Antarctica contributes a spatially constant acceleration. The observations prefer a scaling of the solid-Earth/gravitational response, and we present the implications of this result for ice-mass changes prior to the onset of GRACE observations (2002-3).

Simulation of the Groundwater-Flow System in Pierce, Polk, and St. Croix Counties, Wisconsin

USGS Publications Warehouse

Juckem, Paul F.

2009-01-01

Groundwater is the sole source of residential water supply in Pierce, Polk, and St. Croix Counties, Wisconsin. A regional three-dimensional groundwater-flow model and three associated demonstration inset models were developed to simulate the groundwater-flow systems in the three-county area. The models were developed by the U.S. Geological Survey in cooperation with the three county governments. The objectives of the regional model of Pierce, Polk, and St. Croix Counties were to improve understanding of the groundwaterflow system and to develop a tool suitable for evaluating the effects of potential water-management programs. The regional groundwater-flow model described in this report simulates the major hydrogeologic features of the modeled area, including bedrock and surficial aquifers, groundwater/surface-water interactions, and groundwater withdrawals from high-capacity wells. Results from the regional model indicate that about 82 percent of groundwater in the three counties is from recharge within the counties; 15 percent is from surface-water sources, consisting primarily of recirculated groundwater seepage in areas with abrupt surface-water-level changes, such as near waterfalls, dams, and the downgradient side of reservoirs and lakes; and 4 percent is from inflow across the county boundaries. Groundwater flow out of the counties is to streams (85 percent), outflow across county boundaries (14 percent), and pumping wells (1 percent). These results demonstrate that the primary source of groundwater withdrawn by pumping wells is water that recharges within the counties and would otherwise discharge to local streams and lakes. Under current conditions, the St. Croix and Mississippi Rivers are groundwater discharge locations (gaining reaches) and appear to function as 'fully penetrating' hydraulic boundaries such that groundwater does not cross between Wisconsin and Minnesota beneath them. Being hydraulic boundaries, however, they can change in response to water withdrawals. Tributary rivers act as 'partially penetrating' hydraulic boundaries such that groundwater can flow underneath them through the deep sandstone aquifers. The model also demonstrates the effects of development on groundwater in the study area. Water-level declines since predevelopment (no withdrawal wells) are most pronounced where pumping is greatest and flow between layered aquifers is impeded by confining units or faults. The maximum simulated water-level decline is about 40 feet in the deep Mount Simon aquifer below the city of Hudson, Wisconsin. Three inset models were extracted from the regional model to demonstrate the process and additional capabilities of the U.S. Geological Survey MODFLOW code. Although the inset models were designed to provide information about the groundwater-flow system, results from the inset models are presented for demonstration purposes only and are not sufficiently detailed or calibrated to be used for decisionmaking purposes without refinement. Simulation of groundwater/lake-water interaction around Twin Lakes near Roberts, in St. Croix County, Wisconsin, showed that groundwater represents approximately 5 to 20 percent of the overall lake-water budget. Groundwater-contributing areas to streams in western Pierce County are generally similar in size to the surface-water-contributing areas but do not necessarily correspond to the same land area. Transient streamflow simulations of Osceola Creek in Polk County demonstrate how stream base flow can be influenced not only by seasonal precipitation and recharge variability but also by systematic changes to the system, such as groundwater withdrawal from wells.

A two-layer composite model of the vocal fold lamina propria for fundamental frequency regulation.

PubMed

Zhang, Kai; Siegmund, Thomas; Chan, Roger W

2007-08-01

The mechanical properties of the vocal fold lamina propria, including the vocal fold cover and the vocal ligament, play an important role in regulating the fundamental frequency of human phonation. This study examines the equilibrium hyperelastic tensile deformation behavior of cover and ligament specimens isolated from excised human larynges. Ogden's hyperelastic model is used to characterize the tensile stress-stretch behaviors at equilibrium. Several statistically significant differences in the mechanical response differentiating cover and ligament, as well as gender are found. Fundamental frequencies are predicted from a string model and a beam model, both accounting for the cover and the ligament. The beam model predicts nonzero F(0) for the unstretched state of the vocal fold. It is demonstrated that bending stiffness significantly contributes to the predicted F(0), with the ligament contributing to a higher F(0), especially in females. Despite the availability of only a small data set, the model predicts an age dependence of F(0) in males in agreement with experimental findings. Accounting for two mechanisms of fundamental frequency regulation--vocal fold posturing (stretching) and extended clamping--brings predicted F(0) close to the lower bound of the human phonatory range. Advantages and limitations of the current model are discussed.

Diagnostic Air Quality Model Evaluation of Source-Specific ...

EPA Pesticide Factsheets

Ambient measurements of 78 source-specific tracers of primary and secondary carbonaceous fine particulate matter collected at four midwestern United States locations over a full year (March 2004–February 2005) provided an unprecedented opportunity to diagnostically evaluate the results of a numerical air quality model. Previous analyses of these measurements demonstrated excellent mass closure for the variety of contributing sources. In this study, a carbon-apportionment version of the Community Multiscale Air Quality (CMAQ) model was used to track primary organic and elemental carbon emissions from 15 independent sources such as mobile sources and biomass burning in addition to four precursor-specific classes of secondary organic aerosol (SOA) originating from isoprene, terpenes, aromatics, and sesquiterpenes. Conversion of the source-resolved model output into organic tracer concentrations yielded a total of 2416 data pairs for comparison with observations. While emission source contributions to the total model bias varied by season and measurement location, the largest absolute bias of −0.55 μgC/m3 was attributed to insufficient isoprene SOA in the summertime CMAQ simulation. Biomass combustion was responsible for the second largest summertime model bias (−0.46 μgC/m3 on average). Several instances of compensating errors were also evident; model underpredictions in some sectors were masked by overpredictions in others. The National Exposure Research L

Diagnostic air quality model evaluation of source-specific primary and secondary fine particulate carbon.

PubMed

Napelenok, Sergey L; Simon, Heather; Bhave, Prakash V; Pye, Havala O T; Pouliot, George A; Sheesley, Rebecca J; Schauer, James J

2014-01-01

Ambient measurements of 78 source-specific tracers of primary and secondary carbonaceous fine particulate matter collected at four midwestern United States locations over a full year (March 2004-February 2005) provided an unprecedented opportunity to diagnostically evaluate the results of a numerical air quality model. Previous analyses of these measurements demonstrated excellent mass closure for the variety of contributing sources. In this study, a carbon-apportionment version of the Community Multiscale Air Quality (CMAQ) model was used to track primary organic and elemental carbon emissions from 15 independent sources such as mobile sources and biomass burning in addition to four precursor-specific classes of secondary organic aerosol (SOA) originating from isoprene, terpenes, aromatics, and sesquiterpenes. Conversion of the source-resolved model output into organic tracer concentrations yielded a total of 2416 data pairs for comparison with observations. While emission source contributions to the total model bias varied by season and measurement location, the largest absolute bias of -0.55 μgC/m(3) was attributed to insufficient isoprene SOA in the summertime CMAQ simulation. Biomass combustion was responsible for the second largest summertime model bias (-0.46 μgC/m(3) on average). Several instances of compensating errors were also evident; model underpredictions in some sectors were masked by overpredictions in others.

Demonstration of reduced-order urban scale building energy models

DOE PAGES

Heidarinejad, Mohammad; Mattise, Nicholas; Dahlhausen, Matthew; ...

2017-09-08

The aim of this study is to demonstrate a developed framework to rapidly create urban scale reduced-order building energy models using a systematic summary of the simplifications required for the representation of building exterior and thermal zones. These urban scale reduced-order models rely on the contribution of influential variables to the internal, external, and system thermal loads. OpenStudio Application Programming Interface (API) serves as a tool to automate the process of model creation and demonstrate the developed framework. The results of this study show that the accuracy of the developed reduced-order building energy models varies only up to 10% withmore » the selection of different thermal zones. In addition, to assess complexity of the developed reduced-order building energy models, this study develops a novel framework to quantify complexity of the building energy models. Consequently, this study empowers the building energy modelers to quantify their building energy model systematically in order to report the model complexity alongside the building energy model accuracy. An exhaustive analysis on four university campuses suggests that the urban neighborhood buildings lend themselves to simplified typical shapes. Specifically, building energy modelers can utilize the developed typical shapes to represent more than 80% of the U.S. buildings documented in the CBECS database. One main benefits of this developed framework is the opportunity for different models including airflow and solar radiation models to share the same exterior representation, allowing a unifying exchange data. Altogether, the results of this study have implications for a large-scale modeling of buildings in support of urban energy consumption analyses or assessment of a large number of alternative solutions in support of retrofit decision-making in the building industry.« less

Demonstration of reduced-order urban scale building energy models

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

Heidarinejad, Mohammad; Mattise, Nicholas; Dahlhausen, Matthew

The aim of this study is to demonstrate a developed framework to rapidly create urban scale reduced-order building energy models using a systematic summary of the simplifications required for the representation of building exterior and thermal zones. These urban scale reduced-order models rely on the contribution of influential variables to the internal, external, and system thermal loads. OpenStudio Application Programming Interface (API) serves as a tool to automate the process of model creation and demonstrate the developed framework. The results of this study show that the accuracy of the developed reduced-order building energy models varies only up to 10% withmore » the selection of different thermal zones. In addition, to assess complexity of the developed reduced-order building energy models, this study develops a novel framework to quantify complexity of the building energy models. Consequently, this study empowers the building energy modelers to quantify their building energy model systematically in order to report the model complexity alongside the building energy model accuracy. An exhaustive analysis on four university campuses suggests that the urban neighborhood buildings lend themselves to simplified typical shapes. Specifically, building energy modelers can utilize the developed typical shapes to represent more than 80% of the U.S. buildings documented in the CBECS database. One main benefits of this developed framework is the opportunity for different models including airflow and solar radiation models to share the same exterior representation, allowing a unifying exchange data. Altogether, the results of this study have implications for a large-scale modeling of buildings in support of urban energy consumption analyses or assessment of a large number of alternative solutions in support of retrofit decision-making in the building industry.« less

Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors

NASA Astrophysics Data System (ADS)

Ramakrishnan, N.; Tourdot, Richard W.; Eckmann, David M.; Ayyaswamy, Portonovo S.; Muzykantov, Vladimir R.; Radhakrishnan, Ravi

2016-06-01

In order to achieve selective targeting of affinity-ligand coated nanoparticles to the target tissue, it is essential to understand the key mechanisms that govern their capture by the target cell. Next-generation pharmacokinetic (PK) models that systematically account for proteomic and mechanical factors can accelerate the design, validation and translation of targeted nanocarriers (NCs) in the clinic. Towards this objective, we have developed a computational model to delineate the roles played by target protein expression and mechanical factors of the target cell membrane in determining the avidity of functionalized NCs to live cells. Model results show quantitative agreement with in vivo experiments when specific and non-specific contributions to NC binding are taken into account. The specific contributions are accounted for through extensive simulations of multivalent receptor-ligand interactions, membrane mechanics and entropic factors such as membrane undulations and receptor translation. The computed NC avidity is strongly dependent on ligand density, receptor expression, bending mechanics of the target cell membrane, as well as entropic factors associated with the membrane and the receptor motion. Our computational model can predict the in vivo targeting levels of the intracellular adhesion molecule-1 (ICAM1)-coated NCs targeted to the lung, heart, kidney, liver and spleen of mouse, when the contributions due to endothelial capture are accounted for. The effect of other cells (such as monocytes, etc.) do not improve the model predictions at steady state. We demonstrate the predictive utility of our model by predicting partitioning coefficients of functionalized NCs in mice and human tissues and report the statistical accuracy of our model predictions under different scenarios.

Marginal analysis in assessing factors contributing time to physician in the Emergency Department using operations data.

PubMed

Pathan, Sameer A; Bhutta, Zain A; Moinudheen, Jibin; Jenkins, Dominic; Silva, Ashwin D; Sharma, Yogdutt; Saleh, Warda A; Khudabakhsh, Zeenat; Irfan, Furqan B; Thomas, Stephen H

2016-01-01

Background: Standard Emergency Department (ED) operations goals include minimization of the time interval (tMD) between patients' initial ED presentation and initial physician evaluation. This study assessed factors known (or suspected) to influence tMD with a two-step goal. The first step was generation of a multivariate model identifying parameters associated with prolongation of tMD at a single study center. The second step was the use of a study center-specific multivariate tMD model as a basis for predictive marginal probability analysis; the marginal model allowed for prediction of the degree of ED operations benefit that would be affected with specific ED operations improvements. Methods: The study was conducted using one month (May 2015) of data obtained from an ED administrative database (EDAD) in an urban academic tertiary ED with an annual census of approximately 500,000; during the study month, the ED saw 39,593 cases. The EDAD data were used to generate a multivariate linear regression model assessing the various demographic and operational covariates' effects on the dependent variable tMD. Predictive marginal probability analysis was used to calculate the relative contributions of key covariates as well as demonstrate the likely tMD impact on modifying those covariates with operational improvements. Analyses were conducted with Stata 14MP, with significance defined at p  < 0.05 and confidence intervals (CIs) reported at the 95% level. Results: In an acceptable linear regression model that accounted for just over half of the overall variance in tMD (adjusted r 2 0.51), important contributors to tMD included shift census ( p  = 0.008), shift time of day ( p  = 0.002), and physician coverage n ( p  = 0.004). These strong associations remained even after adjusting for each other and other covariates. Marginal predictive probability analysis was used to predict the overall tMD impact (improvement from 50 to 43 minutes, p  < 0.001) of consistent staffing with 22 physicians. Conclusions: The analysis identified expected variables contributing to tMD with regression demonstrating significance and effect magnitude of alterations in covariates including patient census, shift time of day, and number of physicians. Marginal analysis provided operationally useful demonstration of the need to adjust physician coverage numbers, prompting changes at the study ED. The methods used in this analysis may prove useful in other EDs wishing to analyze operations information with the goal of predicting which interventions may have the most benefit.

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information

PubMed Central

Horejs, Christine-Maria; St-Pierre, Jean-Philippe; Ojala, Juha R. M.; Steele, Joseph A. M.; da Silva, Patricia Barros; Rynne-Vidal, Angela; Maynard, Stephanie A.; Hansel, Catherine S.; Rodríguez-Fernández, Clara; Mazo, Manuel M.; You, Amanda Y. F.; Wang, Alex J.; von Erlach, Thomas; Tryggvason, Karl; López-Cabrera, Manuel; Stevens, Molly M.

2017-01-01

Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets. PMID:28593951

Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes

PubMed Central

Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

2016-01-01

Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment. PMID:27272504

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information

NASA Astrophysics Data System (ADS)

Horejs, Christine-Maria; St-Pierre, Jean-Philippe; Ojala, Juha R. M.; Steele, Joseph A. M.; da Silva, Patricia Barros; Rynne-Vidal, Angela; Maynard, Stephanie A.; Hansel, Catherine S.; Rodríguez-Fernández, Clara; Mazo, Manuel M.; You, Amanda Y. F.; Wang, Alex J.; von Erlach, Thomas; Tryggvason, Karl; López-Cabrera, Manuel; Stevens, Molly M.

2017-06-01

Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets.

Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes.

PubMed

Chen, Qing; He, Guiliang; Zhang, Wenyao; Xu, Tong; Qi, Hongliang; Li, Jing; Zhang, Yong; Gao, Ming-Qing

2016-06-07

Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and β-casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-α and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment.

The Spore Coat Protein CotE Facilitates Host Colonization by Clostridium difficile

PubMed Central

Hong, Huynh A; Ferreira, William T; Hosseini, Siamand; Anwar, Saba; Hitri, Krisztina; Wilkinson, Anthony J; Vahjen, Wilfried; Zentek, Jürgen; Soloviev, Mikhail; Cutting, Simon M

2017-01-01

Abstract Clostridium difficile infection (CDI) is an important hospital-acquired infection resulting from the germination of spores in the intestine as a consequence of antibiotic-mediated dysbiosis of the gut microbiota. Key to this is CotE, a protein displayed on the spore surface and carrying 2 functional elements, an N-terminal peroxiredoxin and a C-terminal chitinase domain. Using isogenic mutants, we show in vitro and ex vivo that CotE enables binding of spores to mucus by direct interaction with mucin and contributes to its degradation. In animal models of CDI, we show that when CotE is absent, both colonization and virulence were markedly reduced. We demonstrate here that the attachment of spores to the intestine is essential in the development of CDI. Spores are usually regarded as biochemically dormant, but our findings demonstrate that rather than being simply agents of transmission and dissemination, spores directly contribute to the establishment and promotion of disease. PMID:28968845

Uncoupling apical constriction from tissue invagination

PubMed Central

Chung, SeYeon; Kim, Sangjoon; Andrew, Deborah J

2017-01-01

Apical constriction is a widely utilized cell shape change linked to folding, bending and invagination of polarized epithelia. It remains unclear how apical constriction is regulated spatiotemporally during tissue invagination and how this cellular process contributes to tube formation in different developmental contexts. Using Drosophila salivary gland (SG) invagination as a model, we show that regulation of folded gastrulation expression by the Fork head transcription factor is required for apicomedial accumulation of Rho kinase and non-muscle myosin II, which coordinate apical constriction. We demonstrate that neither loss of spatially coordinated apical constriction nor its complete blockage prevent internalization and tube formation, although such manipulations affect the geometry of invagination. When apical constriction is disrupted, compressing force generated by a tissue-level myosin cable contributes to SG invagination. We demonstrate that fully elongated polarized SGs can form outside the embryo, suggesting that tube formation and elongation are intrinsic properties of the SG. DOI: http://dx.doi.org/10.7554/eLife.22235.001 PMID:28263180

The scope and control of attention as separate aspects of working memory.

PubMed

Shipstead, Zach; Redick, Thomas S; Hicks, Kenny L; Engle, Randall W

2012-01-01

The present study examines two varieties of working memory (WM) capacity task: visual arrays (i.e., a measure of the amount of information that can be maintained in working memory) and complex span (i.e., a task that taps WM-related attentional control). Using previously collected data sets we employ confirmatory factor analysis to demonstrate that visual arrays and complex span tasks load on separate, but correlated, factors. A subsequent series of structural equation models and regression analyses demonstrate that these factors contribute both common and unique variance to the prediction of general fluid intelligence (Gf). However, while visual arrays does contribute uniquely to higher cognition, its overall correlation to Gf is largely mediated by variance associated with the complex span factor. Thus we argue that visual arrays performance is not strictly driven by a limited-capacity storage system (e.g., the focus of attention; Cowan, 2001), but may also rely on control processes such as selective attention and controlled memory search.

Gene expression analysis uncovers novel Hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells

PubMed Central

Zhou, Xiaobo; Qiu, Weiliang; Sathirapongsasuti, J. Fah.; Cho, Michael H.; Mancini, John D.; Lao, Taotao; Thibault, Derek M.; Litonjua, Gus; Bakke, Per S.; Gulsvik, Amund; Lomas, David A.; Beaty, Terri H.; Hersh, Craig P.; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A.; Rennard, Stephen I.; Perrella, Mark A.; Choi, Augustine M.K.; Quackenbush, John; Silverman, Edwin K.

2013-01-01

Hedgehog Interacting Protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis. PMID:23459001

Linear Parameter Varying Identification of Dynamic Joint Stiffness during Time-Varying Voluntary Contractions

PubMed Central

Golkar, Mahsa A.; Sobhani Tehrani, Ehsan; Kearney, Robert E.

2017-01-01

Dynamic joint stiffness is a dynamic, nonlinear relationship between the position of a joint and the torque acting about it, which can be used to describe the biomechanics of the joint and associated limb(s). This paper models and quantifies changes in ankle dynamic stiffness and its individual elements, intrinsic and reflex stiffness, in healthy human subjects during isometric, time-varying (TV) contractions of the ankle plantarflexor muscles. A subspace, linear parameter varying, parallel-cascade (LPV-PC) algorithm was used to identify the model from measured input position perturbations and output torque data using voluntary torque as the LPV scheduling variable (SV). Monte-Carlo simulations demonstrated that the algorithm is accurate, precise, and robust to colored measurement noise. The algorithm was then used to examine stiffness changes associated with TV isometric contractions. The SV was estimated from the Soleus EMG using a Hammerstein model of EMG-torque dynamics identified from unperturbed trials. The LPV-PC algorithm identified (i) a non-parametric LPV impulse response function (LPV IRF) for intrinsic stiffness and (ii) a LPV-Hammerstein model for reflex stiffness consisting of a LPV static nonlinearity followed by a time-invariant state-space model of reflex dynamics. The results demonstrated that: (a) intrinsic stiffness, in particular ankle elasticity, increased significantly and monotonically with activation level; (b) the gain of the reflex pathway increased from rest to around 10–20% of subject's MVC and then declined; and (c) the reflex dynamics were second order. These findings suggest that in healthy human ankle, reflex stiffness contributes most at low muscle contraction levels, whereas, intrinsic contributions monotonically increase with activation level. PMID:28579954

Investigating the role of biofilms in trihalomethane formation in water distribution systems with a multicomponent model.

PubMed

Abokifa, Ahmed A; Yang, Y Jeffrey; Lo, Cynthia S; Biswas, Pratim

2016-11-01

Biofilms are ubiquitous in the pipes of drinking water distribution systems (DWDSs), and recent experimental studies revealed that the chlorination of the microbial carbon associated with the biofilm contributes to the total disinfection by-products (DBPs) formation with distinct mechanisms from those formed from precursors derived from natural organic matter (NOM). A multiple species reactive-transport model was developed to explain the role of biofilms in DBPs formation by accounting for the simultaneous transport and interactions of disinfectants, organic compounds, and biomass. Using parameter values from experimental studies in the literature, the model equations were solved to predict chlorine decay and microbial regrowth dynamics in an actual DWDS, and trihalomethanes (THMs) formation in a pilot-scale distribution system simulator. The model's capability of reproducing the measured concentrations of free chlorine, suspended biomass, and THMs under different hydrodynamic and temperature conditions was demonstrated. The contribution of bacteria-derived precursors to the total THMs production was found to have a significant dependence on the system's hydraulics, seasonal variables, and the quality of the treated drinking water. Under system conditions that promoted fast bacterial re-growth, the transformation of non-microbial into microbial carbon DBP precursors by the biofilms showed a noticeable effect on the kinetics of THMs formation, especially when a high initial chlorine dose was applied. These conditions included elevated water temperature and high concentrations of nutrients in the influent water. The fraction of THMs formed from microbial sources was found to reach a peak of 12% of the total produced THMs under the investigated scenarios. The results demonstrated the importance of integrating bacterial regrowth dynamics in predictive DBPs formation models. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Condensation on Peri-implant Bone Density and Remodeling

PubMed Central

Wang, L.; Wu, Y.; Perez, K.C.; Hyman, S.; Brunski, J.B.; Tulu, U.; Bao, C.; Salmon, B.; Helms, J.A.

2017-01-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability. PMID:28048963

Effects of Condensation on Peri-implant Bone Density and Remodeling.

PubMed

Wang, L; Wu, Y; Perez, K C; Hyman, S; Brunski, J B; Tulu, U; Bao, C; Salmon, B; Helms, J A

2017-04-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability.

Fibrin activates GPVI in human and mouse platelets

PubMed Central

Alshehri, Osama M.; Montague, Samantha; Watson, Stephanie K.; Frampton, Jon; Bender, Markus; Watson, Steve P.

2015-01-01

The glycoprotein VI (GPVI)-Fc receptor γ (FcRγ) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRγ chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the αIIbβ3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRγ chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability. PMID:26282541

3D reconstructions of quail-chick chimeras provide a new fate map of the avian scapula.

PubMed

Shearman, Rebecca M; Tulenko, Frank J; Burke, Ann C

2011-07-01

Limbed vertebrates have functionally integrated postcranial axial and appendicular systems derived from two distinct populations of embryonic mesoderm. The axial skeletal elements arise from the paraxial somites, the appendicular skeleton and sternum arise from the somatic lateral plate mesoderm, and all of the muscles for both systems arise from the somites. Recent studies in amniotes demonstrate that the scapula has a mixed mesodermal origin. Here we determine the relative contribution of somitic and lateral plate mesoderm to the avian scapula from quail-chick chimeras. We generate 3D reconstructions of the grafted tissue in the host revealing a very different distribution of somitic cells in the scapula than previously reported. This novel 3D visualization of the cryptic border between somitic and lateral plate populations reveals the dynamics of musculoskeletal morphogenesis and demonstrates the importance of 3D visualization of chimera data. Reconstructions of chimeras make clear three significant contrasts with existing models of scapular development. First, the majority of the avian scapula is lateral plate derived and the somitic contribution to the scapular blade is significantly smaller than in previous models. Second, the segmentation of the somitic component of the blade is partially lost; and third, there are striking differences in growth rates between different tissues derived from the same somites that contribute to the structures of the cervical thoracic transition, including the scapula. These data call for the reassessment of theories on the development, homology, and evolution of the vertebrate scapula. Copyright © 2011 Elsevier Inc. All rights reserved.

Strategic preparedness for recovery from catastrophic risks to communities and infrastructure systems of systems.

PubMed

Haimes, Yacov Y

2012-11-01

Natural and human-induced disasters affect organizations in myriad ways because of the inherent interconnectedness and interdependencies among human, cyber, and physical infrastructures, but more importantly, because organizations depend on the effectiveness of people and on the leadership they provide to the organizations they serve and represent. These human-organizational-cyber-physical infrastructure entities are termed systems of systems. Given the multiple perspectives that characterize them, they cannot be modeled effectively with a single model. The focus of this article is: (i) the centrality of the states of a system in modeling; (ii) the efficacious role of shared states in modeling systems of systems, in identification, and in the meta-modeling of systems of systems; and (iii) the contributions of the above to strategic preparedness, response to, and recovery from catastrophic risk to such systems. Strategic preparedness connotes a decision-making process and its associated actions. These must be: implemented in advance of a natural or human-induced disaster, aimed at reducing consequences (e.g., recovery time, community suffering, and cost), and/or controlling their likelihood to a level considered acceptable (through the decisionmakers' implicit and explicit acceptance of various risks and tradeoffs). The inoperability input-output model (IIM), which is grounded on Leontief's input/output model, has enabled the modeling of interdependent subsystems. Two separate modeling structures are introduced. These are: phantom system models (PSM), where shared states constitute the essence of modeling coupled systems; and the IIM, where interdependencies among sectors of the economy are manifested by the Leontief matrix of technological coefficients. This article demonstrates the potential contributions of these two models to each other, and thus to more informative modeling of systems of systems schema. The contributions of shared states to this modeling and to systems identification are presented with case studies. © 2012 Society for Risk Analysis.

Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis.

PubMed

Kramann, Rafael; Machado, Flavia; Wu, Haojia; Kusaba, Tetsuro; Hoeft, Konrad; Schneider, Rebekka K; Humphreys, Benjamin D

2018-05-03

Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney fibrosis, we demonstrate that a small fraction of genetically labeled renal myofibroblasts derive from the circulation. Single-cell RNA sequencing confirms this finding but indicates that these cells are circulating monocytes, express few extracellular matrix or other myofibroblast genes, and express many proinflammatory cytokines. We conclude that this small circulating myofibroblast progenitor population contributes to renal fibrosis by paracrine rather than direct mechanisms.

Downregulation of Oligodendrocyte Transcripts is Associated with Impaired Prefrontal Cortex Function in Rats

PubMed Central

Gregg, Justin R.; Herring, Nicole R.; Naydenov, Alipi V.; Hanlin, Ryan P.; Konradi, Christine

2009-01-01

Abnormalities of brain white matter and oligodendroglia are among the most consistent findings in schizophrenia (Sz) research. Various gene expression microarray studies of postmortem Sz brains showed a downregulation of myelin transcripts, while imaging and microscopy studies demonstrated decreases in prefrontal cortical (PFC) white matter volume and oligodendroglia density. Currently, the extent to which reduced oligodendrocyte markers contribute to pathophysiological domains of Sz is unknown. We exposed adolescent rats to cuprizone (CPZ), a copper chelator known to cause demyelination in mice, and examined expression of oligodendrocyte mRNA transcripts and PFC-mediated behavior. Rats on the CPZ diet showed decreased expression of mRNA transcripts encoding oligodendroglial proteins within the medial PFC, but not in the hippocampus or the striatum. These rats also displayed a specific deficit in the ability to shift between perceptual dimensions in the attentional set-shifting task, a PFC-mediated behavioral paradigm modeled after the Wisconsin Card Sorting Test (WCST). The inability to shift strategies corresponds to the deficits exhibited by Sz patients in the WCST. The results demonstrate that a reduction in oligodendrocyte markers is associated with impaired PFC-mediated behaviors. Thus, CPZ exposure of rats can serve as a model to examine the contribution of oligodendrocyte perturbation to cognitive deficits observed in Sz. PMID:19570651

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

PubMed Central

Alhabbab, R.; Blair, P.; Elgueta, R.; Stolarczyk, E.; Marks, E.; Becker, P. D.; Ratnasothy, K.; Smyth, L.; Safinia, N.; Sharif-Paghaleh, E.; O’Connell, S.; Noelle, R. J.; Lord, G. M.; Howard, J. K.; Spencer, J.; Lechler, R. I.; Lombardi, G.

2015-01-01

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility “conventional” (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora. PMID:26109230

The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model.

PubMed

Lin, Hui-Ching; Gean, Po-Wu; Wang, Chao-Chuan; Chan, Yun-Han; Chen, Po See

2013-01-01

The amygdala is an important structure contributing to socio-emotional behavior. However, the role of the amygdala in autism remains inconclusive. In this study, we used the 28-35 days valproate (VPA)-induced rat model of autism to observe the autistic phenotypes and evaluate their synaptic characteristics in the lateral nucleus (LA) of the amygdala. The VPA-treated offspring demonstrated less social interaction, increased anxiety, enhanced fear learning and impaired fear memory extinction. Slice preparation and electrophysiological recordings of the amygdala showed significantly enhanced long-term potentiation (LTP) while stimulating the thalamic-amygdala pathway of the LA. In addition, the pair pulse facilitation (PPF) at 30- and 60-ms intervals decreased significantly. Whole-cell recordings of the LA pyramidal neurons showed an increased miniature excitatory postsynaptic current (EPSC) frequency and amplitude. The relative contributions of the AMPA receptor and NMDA receptor to the EPSCs did not differ significantly between groups. These results suggested that the enhancement of the presynaptic efficiency of excitatory synaptic transmission might be associated with hyperexcitibility and enhanced LTP in LA pyramidal neurons. Disruption of the synaptic excitatory/inhibitory (E/I) balance in the LA of VPA-treated rats might play certain roles in the development of behaviors in the rat that may be relevant to autism. Further experiments to demonstrate the direct link are warranted.

Measuring progress from nationally determined contributions to mid-century strategies

NASA Astrophysics Data System (ADS)

Iyer, Gokul; Ledna, Catherine; Clarke, Leon; Edmonds, James; McJeon, Haewon; Kyle, Page; Williams, James H.

2017-12-01

The Paris Agreement requires countries to articulate near-term emissions reduction strategies through to 2025 or 2030 by communicating nationally determined contributions (NDCs), as well as encouraging the formulation of long-term low-emission development strategies (Article 4.19)1. In response, many countries have either submitted or are preparing mid-century strategies2. Most NDCs set high-level near-term goals—such as limits on emissions or emissions intensity3—which do not provide information about the extent to which they lay the foundations of technology, infrastructure and institutions for deeper reductions in the future, which is a key question for decision makers. Here, using a state-level model of the US embedded within a global integrated assessment model4,5, we demonstrate that although the US NDC lies on a straight-line emissions pathway towards its mid-century strategy, the resulting energy system transitions involve nonlinear transformations. The rates of capacity additions and capital investments in electricity generation beyond 2025 are more than three times the rates during the next decade. Our results demonstrate the need for global stocktaking exercises to evaluate the NDCs using metrics broader than emissions to better illuminate their effectiveness in addressing the Paris Agreement's long-term goals6,7.

Investigating Sources of Ozone over California Using AJAX Airborne Measurements and Models: Assessing the Contribution from Long Range Transport

NASA Technical Reports Server (NTRS)

Ryoo, Ju-Mee; Johnson, Matthew S.; Iraci, Laura T.; Yates, Emma L.; Gore, Warren

2017-01-01

High ozone (O3) concentrations at low altitudes (1.5e4 km) were detected from airborne Alpha Jet Atmospheric eXperiment (AJAX) measurements on 30 May 2012 off the coast of California (CA). We investigate the causes of those elevated O3 concentrations using airborne measurements and various models. GEOS-Chem simulation shows that the contribution from local sources is likely small. A back trajectory model was used to determine the air mass origins and how much they contributed to the O3 over CA. Low-level potential vorticity (PV) from Modern Era Retrospective analysis for Research and Applications 2 (MERRA-2) reanalysis data appears to be a result of the diabatic heating and mixing of airs in the lower altitudes, rather than be a result of direct transport from stratospheric intrusion. The Q diagnostic, which is a measure of the mixing of the air masses, indicates that there is sufficient mixing along the trajectory to indicate that O3 from the different origins is mixed and transported to the western U.S.The back-trajectory model simulation demonstrates the air masses of interest came mostly from the mid troposphere (MT, 76), but the contribution of the lower troposphere (LT, 19) is also significant compared to those from the upper troposphere/lower stratosphere (UTLS, 5). Air coming from the LT appears to be mostly originating over Asia. The possible surface impact of the high O3 transported aloft on the surface O3 concentration through vertical and horizontal transport within a few days is substantiated by the influence maps determined from the Weather Research and Forecasting Stochastic Time Inverted Lagrangian Transport (WRF-STILT) model and the observed increases in surface ozone mixing ratios. Contrasting this complex case with a stratospheric-dominant event emphasizes the contribution of each source to the high O3 concentration in the lower altitudes over CA. Integrated analyses using models, reanalysis, and diagnostic tools, allows high ozone values detected by in-situ measurements to be attributed to multiple source processes.

Evaluation of Geometrically Nonlinear Reduced Order Models with Nonlinear Normal Modes

DOE PAGES

Kuether, Robert J.; Deaner, Brandon J.; Hollkamp, Joseph J.; ...

2015-09-15

Several reduced-order modeling strategies have been developed to create low-order models of geometrically nonlinear structures from detailed finite element models, allowing one to compute the dynamic response of the structure at a dramatically reduced cost. But, the parameters of these reduced-order models are estimated by applying a series of static loads to the finite element model, and the quality of the reduced-order model can be highly sensitive to the amplitudes of the static load cases used and to the type/number of modes used in the basis. Our paper proposes to combine reduced-order modeling and numerical continuation to estimate the nonlinearmore » normal modes of geometrically nonlinear finite element models. Not only does this make it possible to compute the nonlinear normal modes far more quickly than existing approaches, but the nonlinear normal modes are also shown to be an excellent metric by which the quality of the reduced-order model can be assessed. Hence, the second contribution of this work is to demonstrate how nonlinear normal modes can be used as a metric by which nonlinear reduced-order models can be compared. Moreover, various reduced-order models with hardening nonlinearities are compared for two different structures to demonstrate these concepts: a clamped–clamped beam model, and a more complicated finite element model of an exhaust panel cover.« less

The Dopamine Prediction Error: Contributions to Associative Models of Reward Learning

PubMed Central

Nasser, Helen M.; Calu, Donna J.; Schoenbaum, Geoffrey; Sharpe, Melissa J.

2017-01-01

Phasic activity of midbrain dopamine neurons is currently thought to encapsulate the prediction-error signal described in Sutton and Barto’s (1981) model-free reinforcement learning algorithm. This phasic signal is thought to contain information about the quantitative value of reward, which transfers to the reward-predictive cue after learning. This is argued to endow the reward-predictive cue with the value inherent in the reward, motivating behavior toward cues signaling the presence of reward. Yet theoretical and empirical research has implicated prediction-error signaling in learning that extends far beyond a transfer of quantitative value to a reward-predictive cue. Here, we review the research which demonstrates the complexity of how dopaminergic prediction errors facilitate learning. After briefly discussing the literature demonstrating that phasic dopaminergic signals can act in the manner described by Sutton and Barto (1981), we consider how these signals may also influence attentional processing across multiple attentional systems in distinct brain circuits. Then, we discuss how prediction errors encode and promote the development of context-specific associations between cues and rewards. Finally, we consider recent evidence that shows dopaminergic activity contains information about causal relationships between cues and rewards that reflect information garnered from rich associative models of the world that can be adapted in the absence of direct experience. In discussing this research we hope to support the expansion of how dopaminergic prediction errors are thought to contribute to the learning process beyond the traditional concept of transferring quantitative value. PMID:28275359

Modeling of lead air pollution. [Baton Rouge, Louisiana

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

Monteith, C.S.; Henry, J.M.

1982-05-01

A study was performed to determine whether vehicular emissions should be included with industrial emissions when demonstrating attainment of the ambient air quality standard for lead. The impact on ambient lead concentrations of the phaseout of leaded gasoline and improved automobile fuel economy was examined by modeling vehicular emissions for 1972 and 1978. Results show that while automobiles in the Baton Rouge area were a significant source of lead in 1972, the phaseout of leaded gasoline and the increase in fuel economy have resulted in a lower contribution (0.20 ..mu..g/m/sup 3/) by automobiles to the ambient lead concentration in 1978.more » The areas having the greatest potential for exceeding the ambient air quality standard can be identified using CDM (EPA's Climatological Dispersion Model). This information can be used to determine the optimal location for an ambient air monitor to demonstrate compliance with the ambient air quality standard. 9 references, 4 figures, 5 tables. (JMT)« less

LPV Modeling of a Flexible Wing Aircraft Using Modal Alignment and Adaptive Gridding Methods

NASA Technical Reports Server (NTRS)

Al-Jiboory, Ali Khudhair; Zhu, Guoming; Swei, Sean Shan-Min; Su, Weihua; Nguyen, Nhan T.

2017-01-01

One of the earliest approaches in gain-scheduling control is the gridding based approach, in which a set of local linear time-invariant models are obtained at various gridded points corresponding to the varying parameters within the flight envelop. In order to ensure smooth and effective Linear Parameter-Varying control, aligning all the flexible modes within each local model and maintaining small number of representative local models over the gridded parameter space are crucial. In addition, since the flexible structural models tend to have large dimensions, a tractable model reduction process is necessary. In this paper, the notion of s-shifted H2- and H Infinity-norm are introduced and used as a metric to measure the model mismatch. A new modal alignment algorithm is developed which utilizes the defined metric for aligning all the local models over the entire gridded parameter space. Furthermore, an Adaptive Grid Step Size Determination algorithm is developed to minimize the number of local models required to represent the gridded parameter space. For model reduction, we propose to utilize the concept of Composite Modal Cost Analysis, through which the collective contribution of each flexible mode is computed and ranked. Therefore, a reduced-order model is constructed by retaining only those modes with significant contribution. The NASA Generic Transport Model operating at various flight speeds is studied for verification purpose, and the analysis and simulation results demonstrate the effectiveness of the proposed modeling approach.

Characterizing local traffic contributions to particulate air pollution in street canyons using mobile monitoring techniques

NASA Astrophysics Data System (ADS)

Zwack, Leonard M.; Paciorek, Christopher J.; Spengler, John D.; Levy, Jonathan I.

2011-05-01

Traffic within urban street canyons can contribute significantly to ambient concentrations of particulate air pollution. In these settings, it is challenging to separate within-canyon source contributions from urban and regional background concentrations given the highly variable and complex emissions and dispersion characteristics. In this study, we used continuous mobile monitoring of traffic-related particulate air pollutants to assess the contribution to concentrations, above background, of traffic in the street canyons of midtown Manhattan. Concentrations of both ultrafine particles (UFP) and fine particles (PM 2.5) were measured at street level using portable instruments. Statistical modeling techniques accounting for autocorrelation were used to investigate the presence of spatial heterogeneity of pollutant concentrations as well as to quantify the contribution of within-canyon traffic sources. Measurements were also made within Central Park, to examine the impact of offsets from major roadways in this urban environment. On average, an approximate 11% increase in concentrations of UFP and 8% increase in concentrations of PM 2.5 over urban background was estimated during high-traffic periods in street canyons as opposed to low traffic periods. Estimates were 8% and 5%, respectively, after accounting for temporal autocorrelation. Within Central Park, concentrations were 40% higher than background (5% after accounting for temporal autocorrelation) within the first 100 m from the nearest roadway for UFP, with a smaller but statistically significant increase for PM 2.5. Our findings demonstrate the viability of a mobile monitoring protocol coupled with spatiotemporal modeling techniques in characterizing local source contributions in a setting with street canyons.

Nonlinear sigma model in the loop expansion

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

Appelquist, T.; Bernard, C.

1981-01-15

The nonlinear sigma model in four dimensions is discussed in the context of the loop expansion. Since the model is perturbatively nonrenormalizable, divergences not of the form of the Lagrangian are of course expected; what is perhaps surprising is that there are divergences which appear not to be invariant under the original nonlinear symmetry. We demonstrate, however, that these apparently noninvariant terms do not contribute to on-mass-shell quantities and may be eliminated order by order by a field redefinition involving space-time derivatives. The linear sigma model is then examined in detail; it is shown how the nonlinear model, including themore » apparently noninvariant terms, emerges as the limit of the linear model as the sigma mass goes to infinity. Finally, we compare our approach with other treatments of the ''noninvariant'' terms in the nonlinear model.« less

Helplessness and loss as mediators between pain and depressive symptoms in fibromyalgia.

PubMed

Palomino, Rand A; Nicassio, Perry M; Greenberg, Melanie A; Medina, Ernesto P

2007-05-01

This study evaluated the contribution of condition-specific helplessness and loss to depression in fibromyalgia (FM). Two models were tested. The first model examined whether loss, measured by the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) Interference Scale, would mediate the relationship between disability and depression. The second model determined whether condition-specific helplessness and loss would mediate the relationship between pain and depression with disability controlled. Eighty patients with confirmed diagnoses of FM were recruited throughout Southern California from general medical clinics, newspaper advertisements, and rheumatology practices. The study design was cross-sectional, using self-report, observational, and interview measures. A composite measure of depression was adopted, consisting of the Center for Epidemiological Studies-Depression Scale and the Hamilton Rating Scale for Depression. Hierarchical multiple regression analyses were conducted using a path analytic framework to examine each model. In Model 1, loss fully mediated the relationship between disability and depression. In Model 2, condition-specific helplessness mediated the relationship between pain and depression, but the contribution of loss was not significant. The findings confirm the importance of helplessness and demonstrate that the cognitive meaning of having FM plays a more central role in predicting depressive symptomatology than illness-related stressors, such as pain or disability.

Does body fat percentage predict post-exercise heart rate response in non-obese children and adolescents?

PubMed

Jezdimirovic, Tatjana; Stajer, Valdemar; Semeredi, Sasa; Calleja-Gonzalez, Julio; Ostojic, Sergej M

2017-05-24

A correlation between adiposity and post-exercise autonomic regulation has been established in overweight and obese children. However, little information exists about this link in non-obese youth. The main purpose of this cross-sectional study was to describe the relationship between body fat percentage (BFP) and heart rate recovery after exercise [post-exercise heart rate (PEHR)], a marker of autonomic regulation, in normal-weight children and adolescents. We evaluated the body composition of 183 children and adolescents (age 15.0±2.3 years; 132 boys and 51 girls) who performed a maximal graded exercise test on a treadmill, with the heart rate monitored during and immediately after exercise. A strong positive trend was observed in the association between BFP and PEHR (r=0.14; p=0.06). Hierarchical multiple regression revealed that our model explained 18.3% of the variance in PEHR (p=0.00), yet BFP accounted for only 0.9% of the variability in PEHR (p=0.16). The evaluation of the contribution of each independent variable revealed that only two variables made a unique statistically significant contribution to our model (p<0.01), with age contributing 38.7% to our model (p=0.00) while gender accounted for an additional 25.5% (p=0.01). Neither BFP (14.4%; p=0.16) nor cardiorespiratory endurance (5.0%, p=0.60) made a significant unique contribution to the model. Body fatness seems to poorly predict PEHR in our sample of non-obese children and adolescents, while non-modifiable variables (age and gender) were demonstrated as strong predictors of heart rate recovery. The low amount of body fat reported in non-obese young participants was perhaps too small to cause disturbances in autonomic nervous system regulation.

Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease.

PubMed

Fernández-Nogales, Marta; Hernández, Félix; Miguez, Andrés; Alberch, Jordi; Ginés, Silvia; Pérez-Navarro, Esther; Lucas, José J

2015-09-01

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by brain atrophy particularly in striatum leading to personality changes, chorea and dementia. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase in the crossroad of many signaling pathways that is highly pleiotropic as it phosphorylates more than hundred substrates including structural, metabolic, and signaling proteins. Increased GSK-3 activity is believed to contribute to the pathogenesis of neurodegenerative diseases like Alzheimer's disease and GSK-3 inhibitors have been postulated as therapeutic agents for neurodegeneration. Regarding HD, GSK-3 inhibitors have shown beneficial effects in cell and invertebrate animal models but no evident efficacy in mouse models. Intriguingly, those studies were performed without interrogating GSK-3 level and activity in HD brain. Here we aim to explore the level and also the enzymatic activity of GSK-3 in the striatum and other less affected brain regions of HD patients and of the R6/1 mouse model to then elucidate the possible contribution of its alteration to HD pathogenesis by genetic manipulation in mice. We report a dramatic decrease in GSK-3 levels and activity in striatum and cortex of HD patients with similar results in the mouse model. Correction of the GSK-3 deficit in HD mice, by combining with transgenic mice with conditional GSK-3 expression, resulted in amelioration of their brain atrophy and behavioral motor and learning deficits. Thus, our results demonstrate that decreased brain GSK-3 contributes to HD neurological phenotype and open new therapeutic opportunities based on increasing GSK-3 activity or attenuating the harmful consequences of its decrease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene

PubMed Central

Kim, David; Andersen, Melvin E.; Chao, Yi-Chun E.; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2007-01-01

Background Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 × 10−5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 × 10−3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers’ exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). Conclusions PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. PMID:17589597

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

PubMed

Kim, David; Andersen, Melvin E; Chao, Yi-Chun E; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2007-06-01

Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

PubMed Central

Gien, Jason; Roe, Gates; Isenberg, Nicole; Kailey, Jenai; Abman, Steven H.

2013-01-01

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment (P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment (P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment (P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model. PMID:23605003

Forecasting of global solar radiation using anfis and armax techniques

NASA Astrophysics Data System (ADS)

Muhammad, Auwal; Gaya, M. S.; Aliyu, Rakiya; Aliyu Abdulkadir, Rabi'u.; Dauda Umar, Ibrahim; Aminu Yusuf, Lukuman; Umar Ali, Mudassir; Khairi, M. T. M.

2018-01-01

Procurement of measuring device, maintenance cost coupled with calibration of the instrument contributed to the difficulty in forecasting of global solar radiation in underdeveloped countries. Most of the available regressional and mathematical models do not capture well the behavior of the global solar radiation. This paper presents the comparison of Adaptive Neuro Fuzzy Inference System (ANFIS) and Autoregressive Moving Average with eXogenous term (ARMAX) in forecasting global solar radiation. Full-Scale (experimental) data of Nigerian metrological agency, Sultan Abubakar III international airport Sokoto was used to validate the models. The simulation results demonstrated that the ANFIS model having achieved MAPE of 5.34% outperformed the ARMAX model. The ANFIS could be a valuable tool for forecasting the global solar radiation.

Towards an interactive electromechanical model of the heart

PubMed Central

Talbot, Hugo; Marchesseau, Stéphanie; Duriez, Christian; Sermesant, Maxime; Cotin, Stéphane; Delingette, Hervé

2013-01-01

In this work, we develop an interactive framework for rehearsal of and training in cardiac catheter ablation, and for planning cardiac resynchronization therapy. To this end, an interactive and real-time electrophysiology model of the heart is developed to fit patient-specific data. The proposed interactive framework relies on two main contributions. First, an efficient implementation of cardiac electrophysiology is proposed, using the latest graphics processing unit computing techniques. Second, a mechanical simulation is then coupled to the electrophysiological signals to produce realistic motion of the heart. We demonstrate that pathological mechanical and electrophysiological behaviour can be simulated. PMID:24427533

Polarization of photons in matter–antimatter annihilation

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

Moskaliuk, S.S.

2015-03-10

In this work we demonstrate the possibility of generation of linear polarization of the electromagnetic field (EMF) due to the quantum effects in matter-antimatter annihilation process for anisotropic space of the I type according to Bianchi. We study the dynamics of this process to estimate the degree of polarisation of the EMF in the external gravitational field of the anisotropic Bianchi I model. It has been established that the quantum effects in matter-antimatter annihilation process in the external gravitational field of the anisotropic Bianchi I model provide contribution to the degree of polarisation of the EMF in quadrupole harmonics.

Modeling of Thermal Phase Noise in a Solid Core Photonic Crystal Fiber-Optic Gyroscope

PubMed Central

Song, Ningfang; Ma, Kun; Jin, Jing; Teng, Fei; Cai, Wei

2017-01-01

A theoretical model of the thermal phase noise in a square-wave modulated solid core photonic crystal fiber-optic gyroscope has been established, and then verified by measurements. The results demonstrate a good agreement between theory and experiment. The contribution of the thermal phase noise to the random walk coefficient of the gyroscope is derived. A fiber coil with 2.8 km length is used in the experimental solid core photonic crystal fiber-optic gyroscope, showing a random walk coefficient of 9.25 × 10−5 deg/h. PMID:29072605

Numerical simulation of the interaction of transport, diffusion and chemical reactions in an urban plume

NASA Technical Reports Server (NTRS)

Vogel, Bernhard; Vogel, Heike; Fiedler, Franz

1994-01-01

A model system is presented that takes into account the main physical and chemical processes on the regional scale here in an area of 100x100 sq km. The horizontal gridsize used is 2x2 sq km. For a case study, it is demonstrated how the model system can be used to separate the contributions of the processes advection, turbulent diffusion, and chemical reactions to the diurnal cycle of ozone. In this way, typical features which are visible in observations and are reproduced by the numerical simulations can be interpreted.

The time has come for new models in febrile neutropenia: a practical demonstration of the inadequacy of the MASCC score.

PubMed

Carmona-Bayonas, A; Jiménez-Fonseca, P; Virizuela Echaburu, J; Sánchez Cánovas, M; Ayala de la Peña, F

2017-09-01

Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.

Establishment and outcomes of a model primary care pharmacy service system.

PubMed

Carmichael, Jannet M; Alvarez, Autumn; Chaput, Ryan; DiMaggio, Jennifer; Magallon, Heather; Mambourg, Scott

2004-03-01

The establishment and outcomes of a model primary care pharmacy service system are described. A primary care pharmacy practice model was established at a government health care facility in March 1996. The original objective was to establish a primary pharmacy practice model that would demonstrate improved patient outcomes and maximize the pharmacist's contributions to drug therapy. Since its inception, many improvements have been realized and supported by advanced computer and automated systems, expanded disease state management practices, and unique practitioner and administrative support. Many outcomes studies have been performed on the pharmacist-initiated and -managed clinics, leading to improved patient care and conveying the quality-conscious and cost-effective role pharmacists can play as independent practitioners in this environment. These activities demonstrate cutting-edge leadership in health-system pharmacy. Redesign has been used to improve consistent access to a medication expert and has significantly improved the quality of patient care while easing physicians' workload without increasing health care costs. A system using pharmacists as independent practitioners to promote primary care has achieved high-quality and cost-effective patient care.

Investigating the Direct Meltwater Effect in Terrestrial Oxygen-Isotope Paleoclimate Records Using an Isotope-Enabled Earth System Model

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

Zhu, Jiang; Liu, Zhengyu; Brady, Esther C.

Variations in terrestrial oxygen-isotope reconstructions from ice cores and speleothems have been primarily attributed to climatic changes of surface air temperature, precipitation amount, or atmospheric circulation. In this work, we demonstrate with the fully coupled isotope-enabled Community Earth System Model an additional process contributing to the oxygen-isotope variations during glacial meltwater events. This process, termed “the direct meltwater effect,” involves propagating large amounts of isotopically depleted meltwater throughout the hydrological cycle and is independent of climatic changes. We find that the direct meltwater effect can make up 15–35% of the δ 18O signals in precipitation over Greenland and eastern Brazilmore » for large freshwater forcings (0.25–0.50 sverdrup (10 6 m 3/s)). Model simulations further demonstrate that the direct meltwater effect increases with the magnitude and duration of the freshwater forcing and is sensitive to both the location and shape of the meltwater. These new modeling results have important implications for past climate interpretations of δ 18O.« less

Investigating the Direct Meltwater Effect in Terrestrial Oxygen-Isotope Paleoclimate Records Using an Isotope-Enabled Earth System Model

DOE PAGES

Zhu, Jiang; Liu, Zhengyu; Brady, Esther C.; ...

2017-12-28

Variations in terrestrial oxygen-isotope reconstructions from ice cores and speleothems have been primarily attributed to climatic changes of surface air temperature, precipitation amount, or atmospheric circulation. In this work, we demonstrate with the fully coupled isotope-enabled Community Earth System Model an additional process contributing to the oxygen-isotope variations during glacial meltwater events. This process, termed “the direct meltwater effect,” involves propagating large amounts of isotopically depleted meltwater throughout the hydrological cycle and is independent of climatic changes. We find that the direct meltwater effect can make up 15–35% of the δ 18O signals in precipitation over Greenland and eastern Brazilmore » for large freshwater forcings (0.25–0.50 sverdrup (10 6 m 3/s)). Model simulations further demonstrate that the direct meltwater effect increases with the magnitude and duration of the freshwater forcing and is sensitive to both the location and shape of the meltwater. These new modeling results have important implications for past climate interpretations of δ 18O.« less

Forecasting volatility with neural regression: a contribution to model adequacy.

PubMed

Refenes, A N; Holt, W T

2001-01-01

Neural nets' usefulness for forecasting is limited by problems of overfitting and the lack of rigorous procedures for model identification, selection and adequacy testing. This paper describes a methodology for neural model misspecification testing. We introduce a generalization of the Durbin-Watson statistic for neural regression and discuss the general issues of misspecification testing using residual analysis. We derive a generalized influence matrix for neural estimators which enables us to evaluate the distribution of the statistic. We deploy Monte Carlo simulation to compare the power of the test for neural and linear regressors. While residual testing is not a sufficient condition for model adequacy, it is nevertheless a necessary condition to demonstrate that the model is a good approximation to the data generating process, particularly as neural-network estimation procedures are susceptible to partial convergence. The work is also an important step toward developing rigorous procedures for neural model identification, selection and adequacy testing which have started to appear in the literature. We demonstrate its applicability in the nontrivial problem of forecasting implied volatility innovations using high-frequency stock index options. Each step of the model building process is validated using statistical tests to verify variable significance and model adequacy with the results confirming the presence of nonlinear relationships in implied volatility innovations.

Development and Application of a Category System to Describe Pre-Service Science Teachers' Activities in the Process of Scientific Modelling

NASA Astrophysics Data System (ADS)

Krell, Moritz; Walzer, Christine; Hergert, Susann; Krüger, Dirk

2017-09-01

As part of their professional competencies, science teachers need an elaborate meta-modelling knowledge as well as modelling skills in order to guide and monitor modelling practices of their students. However, qualitative studies about (pre-service) science teachers' modelling practices are rare. This study provides a category system which is suitable to analyse and to describe pre-service science teachers' modelling activities and to infer modelling strategies. The category system was developed based on theoretical considerations and was inductively refined within the methodological frame of qualitative content analysis. For the inductive refinement, modelling practices of pre-service teachers (n = 4) have been video-taped and analysed. In this study, one case was selected to demonstrate the application of the category system to infer modelling strategies. The contribution of this study for science education research and science teacher education is discussed.

A tool for efficient, model-independent management optimization under uncertainty

USGS Publications Warehouse

White, Jeremy; Fienen, Michael N.; Barlow, Paul M.; Welter, Dave E.

2018-01-01

To fill a need for risk-based environmental management optimization, we have developed PESTPP-OPT, a model-independent tool for resource management optimization under uncertainty. PESTPP-OPT solves a sequential linear programming (SLP) problem and also implements (optional) efficient, “on-the-fly” (without user intervention) first-order, second-moment (FOSM) uncertainty techniques to estimate model-derived constraint uncertainty. Combined with a user-specified risk value, the constraint uncertainty estimates are used to form chance-constraints for the SLP solution process, so that any optimal solution includes contributions from model input and observation uncertainty. In this way, a “single answer” that includes uncertainty is yielded from the modeling analysis. PESTPP-OPT uses the familiar PEST/PEST++ model interface protocols, which makes it widely applicable to many modeling analyses. The use of PESTPP-OPT is demonstrated with a synthetic, integrated surface-water/groundwater model. The function and implications of chance constraints for this synthetic model are discussed.

A compressibility based model for predicting the tensile strength of directly compressed pharmaceutical powder mixtures.

PubMed

Reynolds, Gavin K; Campbell, Jacqueline I; Roberts, Ron J

2017-10-05

A new model to predict the compressibility and compactability of mixtures of pharmaceutical powders has been developed. The key aspect of the model is consideration of the volumetric occupancy of each powder under an applied compaction pressure and the respective contribution it then makes to the mixture properties. The compressibility and compactability of three pharmaceutical powders: microcrystalline cellulose, mannitol and anhydrous dicalcium phosphate have been characterised. Binary and ternary mixtures of these excipients have been tested and used to demonstrate the predictive capability of the model. Furthermore, the model is shown to be uniquely able to capture a broad range of mixture behaviours, including neutral, negative and positive deviations, illustrating its utility for formulation design. Copyright © 2017 Elsevier B.V. All rights reserved.

Autotrophic nitrogen removal process in a potable water treatment biofilter that simultaneously removes Mn and NH4(+)-N.

PubMed

Cai, Yan'an; Li, Dong; Liang, Yuhai; Zeng, Huiping; Zhang, Jie

2014-11-01

Ammonia (NH4(+)-N) removal pathways were investigated in a potable water treatment biofilter that simultaneously removes manganese (Mn) and NH4(+)-N. The results indicated a significant loss of nitrogen in the biofilter. Both the completely autotrophic nitrogen removal over nitrite (CANON) process and nitrification were more likely to contribute to NH4(+)-N removal. Moreover, the model calculation results demonstrated that the CANON process contributed significantly to the removal of NH4(+)-N. For influent NH4(+)-N levels of 1.030 and 1.749mg/L, the CANON process contribution was about 48.5% and 46.6%, respectively. The most important finding was that anaerobic ammonia oxidation (ANAMMOX) bacteria were detectable in the biofilter. It is interesting that the CANON process was effective even for such low NH4(+)-N concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterization of Puma-Dependent and Puma-Independent Neuronal Cell Death Pathways following Prolonged Proteasomal Inhibition▿

PubMed Central

Tuffy, Liam P.; Concannon, Caoimhín G.; D'Orsi, Beatrice; King, Matthew A.; Woods, Ina; Huber, Heinrich J.; Ward, Manus W.; Prehn, Jochen H. M.

2010-01-01

Proteasomal stress and the accumulation of polyubiquitinated proteins are key features of numerous neurodegenerative disorders. Previously we demonstrated that stabilization of p53 and activation of its target gene, puma (p53-upregulated mediator of apoptosis), mediated proteasome inhibitor-induced apoptosis in cancer cells. Here we demonstrated that Puma also contributed to proteasome inhibitor-induced apoptosis in mouse neocortical neurons. Although protection afforded by puma gene deletion was incomplete, we found little evidence indicating contributions from other proapoptotic BH3-only proteins. Attenuation of bax expression did not further reduce Puma-independent apoptosis, suggesting that pathways other than the mitochondrial apoptosis pathway were activated. Real-time imaging experiments in wild-type and puma-deficient neurons using a fluorescence resonance energy transfer (FRET)-based caspase sensor confirmed the involvement of a second cell death pathway characterized by caspase activation prior to mitochondrial permeabilization and, more prominently, a third, caspase-independent and Puma-independent pathway characterized by rapid cell shrinkage and nuclear condensation. This pathway involved lysosomal permeabilization in the absence of autophagy activation and was sensitive to cathepsin but not autophagy inhibition. Our data demonstrate that proteasomal stress activates distinct cell death pathways in neurons, leading to both caspase-dependent and caspase-independent apoptosis, and demonstrate independent roles for Puma and lysosomal permeabilization in this model. PMID:20921277

Hydrological variability in the Fraser River Basin during the 20th century: A sensitivity study with the VIC model

NASA Astrophysics Data System (ADS)

Kang, D.; Gao, H.; Dery, S. J.

2012-12-01

The Variable Infiltration Capacity (VIC) model, a macroscale surface hydrology model, was applied to the Fraser River Basin (FRB) of British Columbia, Canada. Previous modeling studies have demonstrated that the FRB is a snow-dominated system but with climate change may evolve to a pluvial regime. The ultimate goal of this model application is to evaluate the changing contribution of snowmelt to streamflow in the FRB both spatially and temporally. To this end, the National Centers for Environmental Prediction (NCEP) reanalysis data combined with meteorological observations over 1953 to 2006 are used to drive the model at a resolution of 0.25°. Model simulations are first validated with daily discharge observations from the Water Survey of Canada (WSC). In addition, the snow water equivalent (SWE) results from VIC are compared with snow pillow observations from the B.C. Ministry of Environment. Then peak SWE values simulated each winter are compared with the annual runoff data to quantify the changing contribution of snowmelt to the hydrology of the FRB. With perturbed model forcings such as precipitation and air temperature, how streamflow and surface energy-mass balance are changed is evaluated. Finally, interactions between the land surface and ambient atmosphere are evaluated by analyzing VIC results such as evaporation, soil moisture, snowmelt and sensible-latent heat flux with corresponding meteorological forcings, i.e. precipitation and air temperature.

The mechanics of the primary cilium: an intricate structure with complex function.

PubMed

Hoey, David A; Downs, Matthew E; Jacobs, Christopher R

2012-01-03

The primary cilium is a non-motile singular cellular structure that extends from the surface of nearly every cell in the body. The cilium has been shown to play numerous roles in maintaining tissue homeostasis, through regulating signaling pathways and sensing both biophysical and biochemical changes in the extracellular environment. The structural performance of the cilium is paramount to its function as defective cilia have been linked to numerous pathologies. In particular, the cilium has demonstrated a mechanosensory role in tissues such as the kidney, liver, endothelium and bone, where cilium deflection under mechanical loading triggers a cellular response. Understanding of how cilium structure and subsequent mechanical behavior contributes to the roles that cilium plays in regulating cellular behavior is a compelling question, yet is a relatively untouched research area. Recent advances in biophysical measurements have demonstrated the cilium to be a structurally intricate organelle containing an array of load bearing proteins. Furthermore advances in modeling of this organelle have revealed the importance of these proteins at regulating the cilium's mechanosensitivity. Remarkably, the cilium is capable of adapting its mechanical state, altering its length and possibly it's bending resistance, to regulate its mechanosensitivity demonstrating the importance of cilium mechanics in cellular responses. In this review, we introduce the cilium as a mechanosensor; discuss the advances in the mechanical modeling of cilia; explore the structural features of the cilium, which contribute to its mechanics and finish with possible mechanisms in which alteration in structure may affect ciliary mechanics, consequently affecting ciliary based mechanosensing. Copyright © 2011 Elsevier Ltd. All rights reserved.

Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error.

PubMed

Paylakhi, Seyyedhassan; Labelle-Dumais, Cassandre; Tolman, Nicholas G; Sellarole, Michael A; Seymens, Yusef; Saunders, Joseph; Lakosha, Hesham; deVries, Wilhelmine N; Orr, Andrew C; Topilko, Piotr; John, Simon Wm; Nair, K Saidas

2018-03-01

A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions.

Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error

PubMed Central

Tolman, Nicholas G; Sellarole, Michael A.; Saunders, Joseph; Lakosha, Hesham; Topilko, Piotr; John, Simon WM.

2018-01-01

A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions. PMID:29529029

Modeling driver stop/run behavior at the onset of a yellow indication considering driver run tendency and roadway surface conditions.

PubMed

Elhenawy, Mohammed; Jahangiri, Arash; Rakha, Hesham A; El-Shawarby, Ihab

2015-10-01

The ability to model driver stop/run behavior at signalized intersections considering the roadway surface condition is critical in the design of advanced driver assistance systems. Such systems can reduce intersection crashes and fatalities by predicting driver stop/run behavior. The research presented in this paper uses data collected from two controlled field experiments on the Smart Road at the Virginia Tech Transportation Institute (VTTI) to model driver stop/run behavior at the onset of a yellow indication for different roadway surface conditions. The paper offers two contributions. First, it introduces a new predictor related to driver aggressiveness and demonstrates that this measure enhances the modeling of driver stop/run behavior. Second, it applies well-known artificial intelligence techniques including: adaptive boosting (AdaBoost), random forest, and support vector machine (SVM) algorithms as well as traditional logistic regression techniques on the data in order to develop a model that can be used by traffic signal controllers to predict driver stop/run decisions in a connected vehicle environment. The research demonstrates that by adding the proposed driver aggressiveness predictor to the model, there is a statistically significant increase in the model accuracy. Moreover the false alarm rate is significantly reduced but this reduction is not statistically significant. The study demonstrates that, for the subject data, the SVM machine learning algorithm performs the best in terms of optimum classification accuracy and false positive rates. However, the SVM model produces the best performance in terms of the classification accuracy only. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigating Causality Between Interacting Brain Areas with Multivariate Autoregressive Models of MEG Sensor Data

PubMed Central

Michalareas, George; Schoffelen, Jan-Mathijs; Paterson, Gavin; Gross, Joachim

2013-01-01

Abstract In this work, we investigate the feasibility to estimating causal interactions between brain regions based on multivariate autoregressive models (MAR models) fitted to magnetoencephalographic (MEG) sensor measurements. We first demonstrate the theoretical feasibility of estimating source level causal interactions after projection of the sensor-level model coefficients onto the locations of the neural sources. Next, we show with simulated MEG data that causality, as measured by partial directed coherence (PDC), can be correctly reconstructed if the locations of the interacting brain areas are known. We further demonstrate, if a very large number of brain voxels is considered as potential activation sources, that PDC as a measure to reconstruct causal interactions is less accurate. In such case the MAR model coefficients alone contain meaningful causality information. The proposed method overcomes the problems of model nonrobustness and large computation times encountered during causality analysis by existing methods. These methods first project MEG sensor time-series onto a large number of brain locations after which the MAR model is built on this large number of source-level time-series. Instead, through this work, we demonstrate that by building the MAR model on the sensor-level and then projecting only the MAR coefficients in source space, the true casual pathways are recovered even when a very large number of locations are considered as sources. The main contribution of this work is that by this methodology entire brain causality maps can be efficiently derived without any a priori selection of regions of interest. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc. PMID:22328419

Break modeling for RELAP5 analyses of ISP-27 Bethsy

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

Petelin, S.; Gortnar, O.; Mavko, B.

This paper presents pre- and posttest analyses of International Standard Problem (ISP) 27 on the Bethsy facility and separate RELAP5 break model tests considering the measured boundary condition at break inlet. This contribution also demonstrates modifications which have assured the significant improvement of model response in posttest simulations. Calculations were performed using the RELAP5/MOD2/36.05 and RELAP5/MOD3.5M5 codes on the MicroVAX, SUN, and CONVEX computers. Bethsy is an integral test facility that simulates a typical 900-MW (electric) Framatome pressurized water reactor. The ISP-27 scenario involves a 2-in. cold-leg break without HPSI and with delayed operator procedures for secondary system depressurization.

Instantons and entanglement entropy

NASA Astrophysics Data System (ADS)

Bhattacharyya, Arpan; Hung, Ling-Yan; Melby-Thompson, Charles M.

2017-10-01

We would like to put the area law — believed to be obeyed by entanglement entropies in the ground state of a local field theory — to scrutiny in the presence of nonperturbative effects. We study instanton corrections to entanglement entropy in various models whose instanton contributions are well understood, including U(1) gauge theory in 2+1 dimensions and false vacuum decay in ϕ 4 theory, and we demonstrate that the area law is indeed obeyed in these models. We also perform numerical computations for toy wavefunctions mimicking the theta vacuum of the (1+1)-dimensional Schwinger model. Our results indicate that such superpositions exhibit no more violation of the area law than the logarithmic behavior of a single Fermi surface.

A Transgenic Drosophila melanogaster Model To Study Human T-Lymphotropic Virus Oncoprotein Tax-1-Driven Transformation In Vivo.

PubMed

Shirinian, Margret; Kambris, Zakaria; Hamadeh, Lama; Grabbe, Caroline; Journo, Chloé; Mahieux, Renaud; Bazarbachi, Ali

2015-08-01

Human T-cell lymphotropic virus type 1 (HTLV-1)-induced adult T-cell leukemia/lymphoma is an aggressive malignancy. HTLV-2 is genetically related to HTLV-1 but does not cause any malignant disease. HTLV-1 Tax transactivator (Tax-1) contributes to leukemogenesis via NF-κB. We describe transgenic Drosophila models expressing Tax in the compound eye and plasmatocytes. We demonstrate that Tax-1 but not Tax-2 induces ommatidial perturbation and increased plasmatocyte proliferation and that the eye phenotype is dependent on Kenny (IKKγ/NEMO), thus validating this new in vivo model. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Connecting Cancer to Its Causes Requires Incorporation of Effects on Tissue Microenvironments.

PubMed

DeGregori, James

2017-11-15

In a recent article in Science , Tomasetti and colleagues present an expanded model for cancer risk, which they claim demonstrates the relative contribution of mutations caused by replication errors, environment, and heredity. The foundation of this model is the theory that the overwhelming driver of cancer risk is mutations. This perspective will present experimental evidence and evolutionary theory to challenge the basis of this underlying theory. An argument will be presented that the mutation-centric model of cancer suggests unrealistic solutions to cancer and distracts the research community from more promising approaches that consider tissue context. Cancer Res; 77(22); 6065-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Peplau's Theory of Interpersonal Relations: An Alternate Factor Structure for Patient Experience Data?

PubMed

Hagerty, Thomas A; Samuels, William; Norcini-Pala, Andrea; Gigliotti, Eileen

2017-04-01

A confirmatory factor analysis of data from the responses of 12,436 patients to 16 items on the Consumer Assessment of Healthcare Providers and Systems-Hospital survey was used to test a latent factor structure based on Peplau's middle-range theory of interpersonal relations. A two-factor model based on Peplau's theory fit these data well, whereas a three-factor model also based on Peplau's theory fit them excellently and provided a suitable alternate factor structure for the data. Though neither the two- nor three-factor model fit as well as the original factor structure, these results support using Peplau's theory to demonstrate nursing's extensive contribution to the experiences of hospitalized patients.

Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus

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

Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam

Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the studymore » of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses.« less

The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus

PubMed Central

Bullock, Daniel; Barbas, Helen

2016-01-01

In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective ‘framing’ effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders. PMID:26828203

Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents

PubMed Central

Williams, Vonetta M.; Kokoza, Anatolii; Bashkirova, Svetlana; Duerksen-Hughes, Penelope

2014-01-01

Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. PMID:25478571

Influence of ovarian muscle contraction and oocyte growth on egg chamber elongation in Drosophila.

PubMed

Andersen, Darcy; Horne-Badovinac, Sally

2016-04-15

Organs are formed from multiple cell types that make distinct contributions to their shape. The Drosophila egg chamber provides a tractable model to dissect such contributions during morphogenesis. Egg chambers consist of 16 germ cells (GCs) surrounded by a somatic epithelium. Initially spherical, these structures elongate as they mature. This morphogenesis is thought to occur through a 'molecular corset' mechanism, whereby structural elements within the epithelium become circumferentially organized perpendicular to the elongation axis and resist the expansive growth of the GCs to promote elongation. Whether this epithelial organization provides the hypothesized constraining force has been difficult to discern, however, and a role for GC growth has not been demonstrated. Here, we provide evidence for this mechanism by altering the contractile activity of the tubular muscle sheath that surrounds developing egg chambers. Muscle hypo-contraction indirectly reduces GC growth and shortens the egg, which demonstrates the necessity of GC growth for elongation. Conversely, muscle hyper-contraction enhances the elongation program. Although this is an abnormal function for this muscle, this observation suggests that a corset-like force from the egg chamber's exterior could promote its lengthening. These findings highlight how physical contributions from several cell types are integrated to shape an organ. © 2016. Published by The Company of Biologists Ltd.

Influence of ovarian muscle contraction and oocyte growth on egg chamber elongation in Drosophila

PubMed Central

Andersen, Darcy; Horne-Badovinac, Sally

2016-01-01

Organs are formed from multiple cell types that make distinct contributions to their shape. The Drosophila egg chamber provides a tractable model to dissect such contributions during morphogenesis. Egg chambers consist of 16 germ cells (GCs) surrounded by a somatic epithelium. Initially spherical, these structures elongate as they mature. This morphogenesis is thought to occur through a ‘molecular corset’ mechanism, whereby structural elements within the epithelium become circumferentially organized perpendicular to the elongation axis and resist the expansive growth of the GCs to promote elongation. Whether this epithelial organization provides the hypothesized constraining force has been difficult to discern, however, and a role for GC growth has not been demonstrated. Here, we provide evidence for this mechanism by altering the contractile activity of the tubular muscle sheath that surrounds developing egg chambers. Muscle hypo-contraction indirectly reduces GC growth and shortens the egg, which demonstrates the necessity of GC growth for elongation. Conversely, muscle hyper-contraction enhances the elongation program. Although this is an abnormal function for this muscle, this observation suggests that a corset-like force from the egg chamber's exterior could promote its lengthening. These findings highlight how physical contributions from several cell types are integrated to shape an organ. PMID:26952985

Assembly of the Caenorhabditis elegans gut microbiota from diverse soil microbial environments

PubMed Central

Berg, Maureen; Stenuit, Ben; Ho, Joshua; Wang, Andrew; Parke, Caitlin; Knight, Matthew; Alvarez-Cohen, Lisa; Shapira, Michael

2016-01-01

It is now well accepted that the gut microbiota contributes to our health. However, what determines the microbiota composition is still unclear. Whereas it might be expected that the intestinal niche would be dominant in shaping the microbiota, studies in vertebrates have repeatedly demonstrated dominant effects of external factors such as host diet and environmental microbial diversity. Hypothesizing that genetic variation may interfere with discerning contributions of host factors, we turned to Caenorhabditis elegans as a new model, offering the ability to work with genetically homogenous populations. Deep sequencing of 16S rDNA was used to characterize the (previously unknown) worm gut microbiota as assembled from diverse produce-enriched soil environments under laboratory conditions. Comparisons of worm microbiotas with those in their soil environment revealed that worm microbiotas resembled each other even when assembled from different microbial environments, and enabled defining a shared core gut microbiota. Community analyses indicated that species assortment in the worm gut was non-random and that assembly rules differed from those in their soil habitat, pointing at the importance of competitive interactions between gut-residing taxa. The data presented fills a gap in C. elegans biology. Furthermore, our results demonstrate a dominant contribution of the host niche in shaping the gut microbiota. PMID:26800234

Motion tracking and electromyography-assisted identification of mirror hand contributions to functional near-infrared spectroscopy images acquired during a finger-tapping task performed by children with cerebral palsy.

PubMed

Hervey, Nathan; Khan, Bilal; Shagman, Laura; Tian, Fenghua; Delgado, Mauricio R; Tulchin-Francis, Kirsten; Shierk, Angela; Roberts, Heather; Smith, Linsley; Reid, Dahlia; Clegg, Nancy J; Liu, Hanli; MacFarlane, Duncan; Alexandrakis, George

2014-10-01

Recent studies have demonstrated functional near-infrared spectroscopy (fNIRS) to be a viable and sensitive method for imaging sensorimotor cortex activity in children with cerebral palsy (CP). However, during unilateral finger tapping, children with CP often exhibit unintended motions in the nontapping hand, known as mirror motions, which confuse the interpretation of resulting fNIRS images. This work presents a method for separating some of the mirror motion contributions to fNIRS images and demonstrates its application to fNIRS data from four children with CP performing a finger-tapping task with mirror motions. Finger motion and arm muscle activity were measured simultaneously with fNIRS signals using motion tracking and electromyography (EMG), respectively. Subsequently, subject-specific regressors were created from the motion capture or EMG data and independent component analysis was combined with a general linear model to create an fNIRS image representing activation due to the tapping hand and one image representing activation due to the mirror hand. The proposed method can provide information on how mirror motions contribute to fNIRS images, and in some cases, it helps remove mirror motion contamination from the tapping hand activation images.

Motion tracking and electromyography-assisted identification of mirror hand contributions to functional near-infrared spectroscopy images acquired during a finger-tapping task performed by children with cerebral palsy

PubMed Central

Hervey, Nathan; Khan, Bilal; Shagman, Laura; Tian, Fenghua; Delgado, Mauricio R.; Tulchin-Francis, Kirsten; Shierk, Angela; Roberts, Heather; Smith, Linsley; Reid, Dahlia; Clegg, Nancy J.; Liu, Hanli; MacFarlane, Duncan; Alexandrakis, George

2014-01-01

Abstract. Recent studies have demonstrated functional near-infrared spectroscopy (fNIRS) to be a viable and sensitive method for imaging sensorimotor cortex activity in children with cerebral palsy (CP). However, during unilateral finger tapping, children with CP often exhibit unintended motions in the nontapping hand, known as mirror motions, which confuse the interpretation of resulting fNIRS images. This work presents a method for separating some of the mirror motion contributions to fNIRS images and demonstrates its application to fNIRS data from four children with CP performing a finger-tapping task with mirror motions. Finger motion and arm muscle activity were measured simultaneously with fNIRS signals using motion tracking and electromyography (EMG), respectively. Subsequently, subject-specific regressors were created from the motion capture or EMG data and independent component analysis was combined with a general linear model to create an fNIRS image representing activation due to the tapping hand and one image representing activation due to the mirror hand. The proposed method can provide information on how mirror motions contribute to fNIRS images, and in some cases, it helps remove mirror motion contamination from the tapping hand activation images. PMID:26157980

Do Clustering Monoclonal Antibody Solutions Really Have a Concentration Dependence of Viscosity?

PubMed Central

Pathak, Jai A.; Sologuren, Rumi R.; Narwal, Rojaramani

2013-01-01

Protein solution rheology data in the biophysics literature have incompletely identified factors that govern hydrodynamics. Whereas spontaneous protein adsorption at the air/water (A/W) interface increases the apparent viscosity of surfactant-free globular protein solutions, it is demonstrated here that irreversible clusters also increase system viscosity in the zero shear limit. Solution rheology measured with double gap geometry in a stress-controlled rheometer on a surfactant-free Immunoglobulin solution demonstrated that both irreversible clusters and the A/W interface increased the apparent low shear rate viscosity. Interfacial shear rheology data showed that the A/W interface yields, i.e., shows solid-like behavior. The A/W interface contribution was smaller, yet nonnegligible, in double gap compared to cone-plate geometry. Apparent nonmonotonic composition dependence of viscosity at low shear rates due to irreversible (nonequilibrium) clusters was resolved by filtration to recover a monotonically increasing viscosity-concentration curve, as expected. Although smaller equilibrium clusters also existed, their size and effective volume fraction were unaffected by filtration, rendering their contribution to viscosity invariant. Surfactant-free antibody systems containing clusters have complex hydrodynamic response, reflecting distinct bulk and interface-adsorbed protein as well as irreversible cluster contributions. Literature models for solution viscosity lack the appropriate physics to describe the bulk shear viscosity of unstable surfactant-free antibody solutions. PMID:23442970

Merton C. Flom, OD, PhD--a paradigm of optometric leadership.

PubMed

Polse, Kenneth A

2007-11-01

Dr. Merton Flom serves as the quintessential model for demonstrating what it takes to be an outstanding scientist, clinician, and educator. Professor Flom's career as a clinician, vision scientist, and visionary in optometry is well known to most faculty in optometric institutions, but many in the profession may not be aware of his enormous contributions. This profile captures Dr. Flom's professional and personal views about optometry, vision research, and education.

Contributions of psychology to the understanding and treatment of people with chronic pain: why it matters to ALL psychologists.

PubMed

Jensen, Mark P; Turk, Dennis C

2014-01-01

Chronic pain is a prevalent problem with significant costs to individuals, significant others, and society. In this article, which introduces the American Psychologist special issue on chronic pain, we provide an overview of the seminal contributions made by psychologists to our current understanding of this important problem. We also describe the primary treatments that have been developed based on psychological principles and models of pain, many of which have demonstrated efficacy for reducing pain and its impact on psychological and physical functioning. The article ends with an enumeration of directions for future research and clinical practice. We believe that the chronicle of psychology's role in improving our understanding and treatment of pain provides a model for how psychologists can have a significant influence on many fields, and that the models and approaches developed for understanding and treating pain may be of use to psychologists working in other areas. Thus, we think that chronic pain is an important area of study that offers insights about translational research for ALL psychologists. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Vasotocinergic control of agonistic behavior told by Neotropical fishes.

PubMed

Silva, Ana C; Pandolfi, Matías

2018-04-24

The hypothalamic neuropeptides of the vasopressin-oxytocin family (and their homologs for non-mammalian species) are key modulators of the Social Brain Network, acting via specific receptors reported in all the nuclei of this network. Different conclusive examples have proven the context-dependency actions of hypothalamic nonapeptides on social behavior in several vertebrate taxa. Teleost fishes provide endless possibilities of experimental model systems to explore the underlying mechanisms of nonapeptide actions on social behavior given that they are the most diverse group of vertebrates. Although it has been difficult to identify commonalities of nonapeptide actions across species, indisputable evidence in many teleost species have demonstrated a clear role of vasotocin in the modulation of aggressive and sexual behaviors. Though Neotropical South American fish contribute an important percentage of teleost diversity, most native species remain unexplored as model systems for the study of the neuroendocrine bases of social behavior. In this review, we will revise recent data on the two model systems of Neotropical fish, South American cichlids and weakly electric fish that have contributed to this issue. Copyright © 2018 Elsevier Inc. All rights reserved.

Contributions of cultural services to the ecosystem services agenda

PubMed Central

Daniel, Terry C.; Muhar, Andreas; Arnberger, Arne; Aznar, Olivier; Boyd, James W.; Chan, Kai M. A.; Costanza, Robert; Elmqvist, Thomas; Flint, Courtney G.; Gobster, Paul H.; Grêt-Regamey, Adrienne; Lave, Rebecca; Muhar, Susanne; Penker, Marianne; Ribe, Robert G.; Schauppenlehner, Thomas; Sikor, Thomas; Soloviy, Ihor; Spierenburg, Marja; Taczanowska, Karolina; Tam, Jordan; von der Dunk, Andreas

2012-01-01

Cultural ecosystem services (ES) are consistently recognized but not yet adequately defined or integrated within the ES framework. A substantial body of models, methods, and data relevant to cultural services has been developed within the social and behavioral sciences before and outside of the ES approach. A selective review of work in landscape aesthetics, cultural heritage, outdoor recreation, and spiritual significance demonstrates opportunities for operationally defining cultural services in terms of socioecological models, consistent with the larger set of ES. Such models explicitly link ecological structures and functions with cultural values and benefits, facilitating communication between scientists and stakeholders and enabling economic, multicriterion, deliberative evaluation and other methods that can clarify tradeoffs and synergies involving cultural ES. Based on this approach, a common representation is offered that frames cultural services, along with all ES, by the relative contribution of relevant ecological structures and functions and by applicable social evaluation approaches. This perspective provides a foundation for merging ecological and social science epistemologies to define and integrate cultural services better within the broader ES framework. PMID:22615401

Proteins feel more than they see: fine-tuning of binding affinity by properties of the non-interacting surface.

PubMed

Kastritis, Panagiotis L; Rodrigues, João P G L M; Folkers, Gert E; Boelens, Rolf; Bonvin, Alexandre M J J

2014-07-15

Protein-protein complexes orchestrate most cellular processes such as transcription, signal transduction and apoptosis. The factors governing their affinity remain elusive however, especially when it comes to describing dissociation rates (koff). Here we demonstrate that, next to direct contributions from the interface, the non-interacting surface (NIS) also plays an important role in binding affinity, especially polar and charged residues. Their percentage on the NIS is conserved over orthologous complexes indicating an evolutionary selection pressure. Their effect on binding affinity can be explained by long-range electrostatic contributions and surface-solvent interactions that are known to determine the local frustration of the protein complex surface. Including these in a simple model significantly improves the affinity prediction of protein complexes from structural models. The impact of mutations outside the interacting surface on binding affinity is supported by experimental alanine scanning mutagenesis data. These results enable the development of more sophisticated and integrated biophysical models of binding affinity and open new directions in experimental control and modulation of biomolecular interactions. Copyright © 2014. Published by Elsevier Ltd.

Human scalp permeability to the chemical warfare agent VX.

PubMed

Rolland, P; Bolzinger, M-A; Cruz, C; Briançon, S; Josse, D

2011-12-01

The use of chemical warfare agents such as VX in terrorism act might lead to contamination of the civilian population. Human scalp decontamination may require appropriate products and procedures. Due to ethical reasons, skin decontamination studies usually involve in vitro skin models, but human scalp skin samples are uncommon and expensive. The purpose of this study was to characterize the in vitro permeability to VX of human scalp, and to compare it with (a) human abdominal skin, and (b) pig skin from two different anatomic sites: ear and skull roof, in order to design a relevant model. Based on the VX skin permeation kinetics and distribution, we demonstrated that (a) human scalp was significantly more permeable to VX than abdominal skin and (b) pig-ear skin was the most relevant model to predict the in vitro human scalp permeability. Our results indicated that the follicular pathway significantly contributed to the skin absorption of VX through human scalp. In addition, the hair follicles and the stratum corneum significantly contributed to the formation of a skin reservoir for VX. Copyright © 2011 Elsevier Ltd. All rights reserved.

On the origin of the water vapor continuum absorption within rotational and fundamental vibrational bands

NASA Astrophysics Data System (ADS)

Serov, E. A.; Odintsova, T. A.; Tretyakov, M. Yu.; Semenov, V. E.

2017-05-01

Analysis of the continuum absorption in water vapor at room temperature within the purely rotational and fundamental ro-vibrational bands shows that a significant part (up to a half) of the observed absorption cannot be explained within the framework of the existing concepts of the continuum. Neither of the two most prominent mechanisms of continuum originating, namely, the far wings of monomer lines and the dimers, cannot reproduce the currently available experimental data adequately. We propose a new approach to developing a physically based model of the continuum. It is demonstrated that water dimers and wings of monomer lines may contribute equally to the continuum within the bands, and their contribution should be taken into account in the continuum model. We propose a physical mechanism giving missing justification for the super-Lorentzian behavior of the intermediate line wing. The qualitative validation of the proposed approach is given on the basis of a simple empirical model. The obtained results are directly indicative of the necessity to reconsider the existing line wing theory and can guide this consideration.

A twin study of specific bulimia nervosa symptoms.

PubMed

Mazzeo, S E; Mitchell, K S; Bulik, C M; Aggen, S H; Kendler, K S; Neale, M C

2010-07-01

Twin studies have suggested that additive genetic factors significantly contribute to liability to bulimia nervosa (BN). However, the diagnostic criteria for BN remain controversial. In this study, an item-factor model was used to examine the BN diagnostic criteria and the genetic and environmental contributions to BN in a population-based twin sample. The validity of the equal environment assumption (EEA) for BN was also tested. Participants were 1024 female twins (MZ n=614, DZ n=410) from the population-based Mid-Atlantic Twin Registry. BN was assessed using symptom-level (self-report) items consistent with DSM-IV and ICD-10 diagnostic criteria. Items assessing BN were included in an item-factor model. The EEA was measured by items assessing similarity of childhood and adolescent environment, which have demonstrated construct validity. Scores on the EEA factor were used to specify the degree to which twins shared environmental experiences in this model. The EEA was not violated for BN. Modeling results indicated that the majority of the variance in BN was due to additive genetic factors. There was substantial variability in additive genetic and environmental contributions to specific BN symptoms. Most notably, vomiting was very strongly influenced by additive genetic factors, while other symptoms were much less heritable, including the influence of weight on self-evaluation. These results highlight the importance of assessing eating disorders at the symptom level. Refinement of eating disorder phenotypes could ultimately lead to improvements in treatment and targeted prevention, by clarifying sources of variation for specific components of symptomatology.

A dynamic auditory-cognitive system supports speech-in-noise perception in older adults

PubMed Central

Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

2013-01-01

Understanding speech in noise is one of the most complex activities encountered in everyday life, relying on peripheral hearing, central auditory processing, and cognition. These abilities decline with age, and so older adults are often frustrated by a reduced ability to communicate effectively in noisy environments. Many studies have examined these factors independently; in the last decade, however, the idea of the auditory-cognitive system has emerged, recognizing the need to consider the processing of complex sounds in the context of dynamic neural circuits. Here, we use structural equation modeling to evaluate interacting contributions of peripheral hearing, central processing, cognitive ability, and life experiences to understanding speech in noise. We recruited 120 older adults (ages 55 to 79) and evaluated their peripheral hearing status, cognitive skills, and central processing. We also collected demographic measures of life experiences, such as physical activity, intellectual engagement, and musical training. In our model, central processing and cognitive function predicted a significant proportion of variance in the ability to understand speech in noise. To a lesser extent, life experience predicted hearing-in-noise ability through modulation of brainstem function. Peripheral hearing levels did not significantly contribute to the model. Previous musical experience modulated the relative contributions of cognitive ability and lifestyle factors to hearing in noise. Our models demonstrate the complex interactions required to hear in noise and the importance of targeting cognitive function, lifestyle, and central auditory processing in the management of individuals who are having difficulty hearing in noise. PMID:23541911

Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves

PubMed Central

Mao, Haojie; Unnikrishnan, Ginu; Rakesh, Vineet; Reifman, Jaques

2015-01-01

Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36–45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups. PMID:26458125

Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model

NASA Astrophysics Data System (ADS)

Li, Yungui; Li, Qingqing; Chen, Baoliang

2016-03-01

The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants.

Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model.

PubMed

Li, Yungui; Li, Qingqing; Chen, Baoliang

2016-03-24

The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants.

Recognition errors suggest fast familiarity and slow recollection in rhesus monkeys

PubMed Central

Basile, Benjamin M.; Hampton, Robert R.

2013-01-01

One influential model of recognition posits two underlying memory processes: recollection, which is detailed but relatively slow, and familiarity, which is quick but lacks detail. Most of the evidence for this dual-process model in nonhumans has come from analyses of receiver operating characteristic (ROC) curves in rats, but whether ROC analyses can demonstrate dual processes has been repeatedly challenged. Here, we present independent converging evidence for the dual-process model from analyses of recognition errors made by rhesus monkeys. Recognition choices were made in three different ways depending on processing duration. Short-latency errors were disproportionately false alarms to familiar lures, suggesting control by familiarity. Medium-latency responses were less likely to be false alarms and were more accurate, suggesting onset of a recollective process that could correctly reject familiar lures. Long-latency responses were guesses. A response deadline increased false alarms, suggesting that limiting processing time weakened the contribution of recollection and strengthened the contribution of familiarity. Together, these findings suggest fast familiarity and slow recollection in monkeys, that monkeys use a “recollect to reject” strategy to countermand false familiarity, and that primate recognition performance is well-characterized by a dual-process model consisting of recollection and familiarity. PMID:23864646

Practical limits for reverse engineering of dynamical systems: a statistical analysis of sensitivity and parameter inferability in systems biology models.

PubMed

Erguler, Kamil; Stumpf, Michael P H

2011-05-01

The size and complexity of cellular systems make building predictive models an extremely difficult task. In principle dynamical time-course data can be used to elucidate the structure of the underlying molecular mechanisms, but a central and recurring problem is that many and very different models can be fitted to experimental data, especially when the latter are limited and subject to noise. Even given a model, estimating its parameters remains challenging in real-world systems. Here we present a comprehensive analysis of 180 systems biology models, which allows us to classify the parameters with respect to their contribution to the overall dynamical behaviour of the different systems. Our results reveal candidate elements of control in biochemical pathways that differentially contribute to dynamics. We introduce sensitivity profiles that concisely characterize parameter sensitivity and demonstrate how this can be connected to variability in data. Systematically linking data and model sloppiness allows us to extract features of dynamical systems that determine how well parameters can be estimated from time-course measurements, and associates the extent of data required for parameter inference with the model structure, and also with the global dynamical state of the system. The comprehensive analysis of so many systems biology models reaffirms the inability to estimate precisely most model or kinetic parameters as a generic feature of dynamical systems, and provides safe guidelines for performing better inferences and model predictions in the context of reverse engineering of mathematical models for biological systems.

AtlA Mediates Extracellular DNA Release, Which Contributes to Streptococcus mutans Biofilm Formation in an Experimental Rat Model of Infective Endocarditis.

PubMed

Jung, Chiau-Jing; Hsu, Ron-Bin; Shun, Chia-Tung; Hsu, Chih-Chieh; Chia, Jean-San

2017-09-01

Host factors, such as platelets, have been shown to enhance biofilm formation by oral commensal streptococci, inducing infective endocarditis (IE), but how bacterial components contribute to biofilm formation in vivo is still not clear. We demonstrated previously that an isogenic mutant strain of Streptococcus mutans deficient in autolysin AtlA (Δ atlA ) showed a reduced ability to cause vegetation in a rat model of bacterial endocarditis. However, the role of AtlA in bacterial biofilm formation is unclear. In this study, confocal laser scanning microscopy analysis showed that extracellular DNA (eDNA) was embedded in S. mutans GS5 floes during biofilm formation on damaged heart valves, but an Δ atlA strain could not form bacterial aggregates. Semiquantification of eDNA by PCR with bacterial 16S rRNA primers demonstrated that the Δ atlA mutant strain produced dramatically less eDNA than the wild type. Similar results were observed with in vitro biofilm models. The addition of polyanethol sulfonate, a chemical lysis inhibitor, revealed that eDNA release mediated by bacterial cell lysis is required for biofilm initiation and maturation in the wild-type strain. Supplementation of cultures with calcium ions reduced wild-type growth but increased eDNA release and biofilm mass. The effect of calcium ions on biofilm formation was abolished in Δ atlA cultures and by the addition of polyanethol sulfonate. The VicK sensor, but not CiaH, was found to be required for the induction of eDNA release or the stimulation of biofilm formation by calcium ions. These data suggest that calcium ion-regulated AtlA maturation mediates the release of eDNA by S. mutans , which contributes to biofilm formation in infective endocarditis. Copyright © 2017 American Society for Microbiology.

Modeling dry and wet deposition of sulfate, nitrate, and ammonium ions in Jiuzhaigou National Nature Reserve, China using a source-oriented CMAQ model: Part II. Emission sector and source region contributions.

PubMed

Qiao, Xue; Tang, Ya; Kota, Sri Harsha; Li, Jingyi; Wu, Li; Hu, Jianlin; Zhang, Hongliang; Ying, Qi

2015-11-01

A source-oriented Community Multiscale Air Quality (CMAQ) model driven by the meteorological fields generated by the Weather Research and Forecasting (WRF) model was used to study the dry and wet deposition of nitrate (NO3(-)), sulfate (SO4(2-)), and ammonium (NH4(+)) ions in the Jiuzhaigou National Nature Reserve (JNNR), China from June to August 2010 and to identify the contributions of different emission sectors and source regions that were responsible for the deposition fluxes. Contributions from power plants, industry, transportation, domestic, biogenic, windblown dust, open burning, fertilizer, and manure management sources to deposition fluxes in JNNR watershed and four EANET sites are determined. In JNNR, 96%, 82%, and 87% of the SO4(2-), NO3(-) and NH4(+) deposition fluxes are in the form of wet deposition of the corresponding aerosol species. Industry and power plants are the two major sources of SO4(2-) deposition flux, accounting for 86% of the total wet deposition of SO4(2-), and industry has a higher contribution (56%) than that of power plants (30%). Power plants and industry are also the top sources that are responsible for NO3(-) wet deposition, and contributions from power plants (30%) are generally higher than those from industries (21%). The major sources of NH4(+) wet deposition flux in JNNR are fertilizer (48%) and manure management (39%). Source-region apportionment confirms that SO2 and NOx emissions from local and two nearest counties do not have a significant impact on predicted wet deposition fluxes in JNNR, with contributions less than 10%. While local NH3 emissions account for a higher fraction of the NH4(+) deposition, approximately 70% of NH4(+) wet deposition in JNNR originated from other source regions. This study demonstrates that S and N deposition in JNNR is mostly from long-range transport rather than from local emissions, and to protect JNNR, regional emission reduction controls are needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Being a male nurse in Portugal during Salazar's dictatorship (1940-70).

PubMed

da Silva, Helena

2013-06-01

In several western countries, nursing was clearly seen as an occupation for women. With the creation of the first nursing schools, the gendering of the profession was accelerated. Male nurses' contribution to the development of the profession was limited in comparison with women's. However, the situation was slightly different in Portugal. This article aims at demonstrating a specific example of the gendering of the nursing profession, by simply copying the western model--considered the most developed--without questioning the consequences or even whether it was adapted to the country that had a different nursing tradition. Because the consequences of this gendering are still felt nowadays, this article opens a reflection on how complex it is to follow a foreign nursing model and on the issues associated with such a copy. Qualitative and quantitative analysis of several historical documents and interviews with several retired nurses contributed to an understanding of how men became nurses and how they worked in Portugal, despite gender discrimination, between 1940 and 1970. With different nursing training and job opportunities, Portuguese male nurses still managed to contribute, even beyond that of female nurses, to the improvement of the nursing profession. © 2012 John Wiley & Sons Ltd.

Observation of Solar Wind Charge Exchange Emission From Exospheric Material in and Outside Earth's Magnetosheath 2008 September 25

NASA Technical Reports Server (NTRS)

Snowden, S. L.; Collier, M. R.; Cravens, T.; Kuntz, K. D.; Lepri, S. T.; Robertson, I.; Tomas, L.

2009-01-01

A long XMM-Newton exposure is used to observe solar wind charge exchange (SWCX) emission from exospheric material in and outside Earth's magnetosheath. The light curve of the O vii (0.5-0.62 keV) band is compared with a model for the expected emission, and while the emission is faint and the light curve has considerable scatter, the correlation is significant to better than 99.9%. This result demonstrates the validity of the geocoronal SWCX emission model for predicting a contribution to astrophysical observations to a scale factor of order unity (1.5). In addition, an average value of the SWCX O vii emission from the magnetosheath over the observation of 2.6 +/- 0.5 LU is derived. The results also demonstrate the potential utility of using X-ray observations to study global phenomena of the magnetosheath which currently are only investigated using in situ measurements.

A COMMUNITY MENTAL HEALTH PROFESSIONAL DEVELOPMENT MODEL FOR THE EXPANSION OF REFLECTIVE PRACTICE AND SUPERVISION: EVALUATION OF A PILOT TRAINING SERIES FOR INFANT MENTAL HEALTH PROFESSIONALS.

PubMed

Shea, Sarah E; Goldberg, Sheryl; Weatherston, Deborah J

2016-11-01

The Michigan Association for Infant Mental Health identified a need for reflective supervision training for infant mental health (IMH) specialists providing home-based services to highly vulnerable infants and their families. Findings indicate that this pilot of an IMH community mental health professional development model was successful, as measured by the participants' increased capacity to apply reflective practice and supervisory knowledge and skills. Furthermore, IMH clinicians demonstrated an increase in the frequency of their use of reflective practice skills, and their supervisors demonstrated an increase in their sense of self-efficacy regarding reflective supervisory tasks. Finally, the evaluation included a successful pilot of new measures designed to measure reflective practice, contributing to the growing body of research in the area of reflective supervision. © 2016 Michigan Association for Infant Mental Health.

Calibration and Finite Element Implementation of an Energy-Based Material Model for Shape Memory Alloys

NASA Astrophysics Data System (ADS)

Junker, Philipp; Hackl, Klaus

2016-09-01

Numerical simulations are a powerful tool to analyze the complex thermo-mechanically coupled material behavior of shape memory alloys during product engineering. The benefit of the simulations strongly depends on the quality of the underlying material model. In this contribution, we discuss a variational approach which is based solely on energetic considerations and demonstrate that unique calibration of such a model is sufficient to predict the material behavior at varying ambient temperature. In the beginning, we recall the necessary equations of the material model and explain the fundamental idea. Afterwards, we focus on the numerical implementation and provide all information that is needed for programing. Then, we show two different ways to calibrate the model and discuss the results. Furthermore, we show how this model is used during real-life industrial product engineering.

Prediction of episodic acidification in North-eastern USA: An empirical/mechanistic approach

USGS Publications Warehouse

Davies, T.D.; Tranter, M.; Wigington, P.J.; Eshleman, K.N.; Peters, N.E.; Van Sickle, J.; DeWalle, David R.; Murdoch, Peter S.

1999-01-01

Observations from the US Environmental Protection Agency's Episodic Response Project (ERP) in the North-eastern United States are used to develop an empirical/mechanistic scheme for prediction of the minimum values of acid neutralizing capacity (ANC) during episodes. An acidification episode is defined as a hydrological event during which ANC decreases. The pre-episode ANC is used to index the antecedent condition, and the stream flow increase reflects how much the relative contributions of sources of waters change during the episode. As much as 92% of the total variation in the minimum ANC in individual catchments can be explained (with levels of explanation >70% for nine of the 13 streams) by a multiple linear regression model that includes pre-episode ANC and change in discharge as independent variable. The predictive scheme is demonstrated to be regionally robust, with the regional variance explained ranging from 77 to 83%. The scheme is not successful for each ERP stream, and reasons are suggested for the individual failures. The potential for applying the predictive scheme to other watersheds is demonstrated by testing the model with data from the Panola Mountain Research Watershed in the South-eastern United States, where the variance explained by the model was 74%. The model can also be utilized to assess 'chemically new' and 'chemically old' water sources during acidification episodes.Observations from the US Environmental Protection Agency's Episodic Response Project (ERP) in the Northeastern United States are used to develop an empirical/mechanistic scheme for prediction of the minimum values of acid neutralizing capacity (ANC) during episodes. An acidification episode is defined as a hydrological event during which ANC decreases. The pre-episode ANC is used to index the antecedent condition, and the stream flow increase reflects how much the relative contributions of sources of waters change during the episode. As much as 92% of the total variation in the minimum ANC in individual catchments can be explained (with levels of explanation >70% for nine of the 13 streams) by a multiple linear regression model that includes pre-episode ANC and change in discharge as independent variables. The predictive scheme is demonstrated to be regionally robust, with the regional variance explained ranging from 77 to 83%. The scheme is not successful for each ERP stream, and reasons are suggested for the individual failures. The potential for applying the predictive scheme to other watersheds is demonstrated by testing the model with data from the Panola Mountain Research Watershed in the South-eastern United States, where the variance explained by the model was 74%. The model can also be utilized to assess `chemically new' and `chemically old' water sources during acidification episodes.

Lessons learned: Optimization of a murine small bowel resection model

PubMed Central

Taylor, Janice A.; Martin, Colin A.; Nair, Rajalakshmi; Guo, Jun; Erwin, Christopher R.; Warner, Brad W.

2008-01-01

Background/Purpose Central to the use of murine models of disease is the ability to derive reproducible data. The purpose of this study was to determine factors contributing to variability in our murine model of small bowel resection (SBR). Methods Male C57Bl/6 mice were randomized to sham or 50% SBR. The effect of housing type (pathogen-free versus standard housing), nutrition (reconstituted powder versus tube feeding formulation), and correlates of intestinal morphology with gene expression changes were investigated Multiple linear regression modeling or one-way ANOVA was used for data analysis. Results Pathogen-free mice had significantly shorter ileal villi at baseline and demonstrated greater villus growth after SBR compared to mice housed in standard rooms. Food type did not affect adaptation. Gene expression changes were more consistent and significant in isolated crypt cells that demonstrated adaptive growth when compared with crypts that did not deepen after SBR. Conclusion Maintenance of mice in pathogen-free conditions and restricting gene expression analysis to individual animals exhibiting morphologic adaptation enhances sensitivity and specificity of data derived from this model. These refinements will minimize experimental variability and lead to improved understanding of the complex process of intestinal adaptation. PMID:18558176

Operational modelling: the mechanisms influencing TB diagnostic yield in an Xpert® MTB/RIF-based algorithm.

PubMed

Dunbar, R; Naidoo, P; Beyers, N; Langley, I

2017-04-01

Cape Town, South Africa. To compare the diagnostic yield for smear/culture and Xpert® MTB/RIF algorithms and to investigate the mechanisms influencing tuberculosis (TB) yield. We developed and validated an operational model of the TB diagnostic process, first with the smear/culture algorithm and then with the Xpert algorithm. We modelled scenarios by varying TB prevalence, adherence to diagnostic algorithms and human immunodeficiency virus (HIV) status. This enabled direct comparisons of diagnostic yield in the two algorithms to be made. Routine data showed that diagnostic yield had decreased over the period of the Xpert algorithm roll-out compared to the yield when the smear/culture algorithm was in place. However, modelling yield under identical conditions indicated a 13.3% increase in diagnostic yield from the Xpert algorithm compared to smear/culture. The model demonstrated that the extensive use of culture in the smear/culture algorithm and the decline in TB prevalence are the main factors contributing to not finding an increase in diagnostic yield in the routine data. We demonstrate the benefits of an operational model to determine the effect of scale-up of a new diagnostic algorithm, and recommend that policy makers use operational modelling to make appropriate decisions before new diagnostic algorithms are scaled up.

Modeling of episodic particulate matter events using a 3-D air quality model with fine grid: Applications to a pair of cities in the US/Mexico border

NASA Astrophysics Data System (ADS)

Choi, Yu-Jin; Hyde, Peter; Fernando, H. J. S.

High (episodic) particulate matter (PM) events over the sister cities of Douglas (AZ) and Agua Prieta (Sonora), located in the US-Mexico border, were simulated using the 3D Eulerian air quality model, MODELS-3/CMAQ. The best available input information was used for the simulations, with pollution inventory specified on a fine grid. In spite of inherent uncertainties associated with the emission inventory as well as the chemistry and meteorology of the air quality simulation tool, model evaluations showed acceptable PM predictions, while demonstrating the need for including the interaction between meteorology and emissions in an interactive mode in the model, a capability currently unavailable in MODELS-3/CMAQ when dealing with PM. Sensitivity studies on boundary influence indicate an insignificant regional (advection) contribution of PM to the study area. The contribution of secondary particles to the occurrence of high PM events was trivial. High PM episodes in the study area, therefore, are purely local events that largely depend on local meteorological conditions. The major PM emission sources were identified as vehicular activities on unpaved/paved roads and wind-blown dust. The results will be of immediate utility in devising PM mitigation strategies for the study area, which is one of the US EPA-designated non-attainment areas with respect to PM.

Computational modeling of muscular thin films for cardiac repair

NASA Astrophysics Data System (ADS)

Böl, Markus; Reese, Stefanie; Parker, Kevin Kit; Kuhl, Ellen

2009-03-01

Motivated by recent success in growing biohybrid material from engineered tissues on synthetic polymer films, we derive a computational simulation tool for muscular thin films in cardiac repair. In this model, the polydimethylsiloxane base layer is simulated in terms of microscopically motivated tetrahedral elements. Their behavior is characterized through a volumetric contribution and a chain contribution that explicitly accounts for the polymeric microstructure of networks of long chain molecules. Neonatal rat ventricular cardiomyocytes cultured on these polymeric films are modeled with actively contracting truss elements located on top of the sheet. The force stretch response of these trusses is motivated by the cardiomyocyte force generated during active contraction as suggested by the filament sliding theory. In contrast to existing phenomenological models, all material parameters of this novel model have a clear biophyisical interpretation. The predictive features of the model will be demonstrated through the simulation of muscular thin films. First, the set of parameters will be fitted for one particular experiment documented in the literature. This parameter set is then used to validate the model for various different experiments. Last, we give an outlook of how the proposed simulation tool could be used to virtually predict the response of multi-layered muscular thin films. These three-dimensional constructs show a tremendous regenerative potential in repair of damaged cardiac tissue. The ability to understand, tune and optimize their structural response is thus of great interest in cardiovascular tissue engineering.

Hybrid photovoltaic-thermoelectric system for concentrated solar energy conversion: Experimental realization and modeling

NASA Astrophysics Data System (ADS)

Beeri, Ofer; Rotem, Oded; Hazan, Eden; Katz, Eugene A.; Braun, Avi; Gelbstein, Yaniv

2015-09-01

An experimental demonstration of the combined photovoltaic (PV) and thermoelectric conversion of concentrated sunlight (with concentration factor, X, up to ˜300) into electricity is presented. The hybrid system is based on a multi-junction PV cell and a thermoelectric generator (TEG). The latter increases the electric power of the system and dissipates some of the excessive heat. For X ≤ 200, the system's maximal efficiency, ˜32%, was mostly due to the contribution from the PV cell. With increasing X and system temperature, the PV cell's efficiency decreased while that of the TEG increased. Accordingly, the direct electrical contribution of the TEG started to dominate in the total system power, reaching ˜20% at X ≈ 290. Using a simple steady state finite element modeling, the cooling effect of the TEG on the hybrid system's efficiency was proved to be even more significant than its direct electrical contribution for high solar concentrations. As a result, the total efficiency contribution of the TEG reached ˜40% at X ≈ 200. This suggests a new system optimization concept that takes into account the PV cell's temperature dependence and the trade-off between the direct electrical generation and cooling capabilities of the TEG. It is shown that the hybrid system has a real potential to exceed 50% total efficiency by using more advanced PV cells and TE materials.

Lessons Learned from Numerical Simulations of the F-16XL Aircraft at Flight Conditions

NASA Technical Reports Server (NTRS)

Rizzi, Arthur; Jirasek, Adam; Lamar, John; Crippa, Simone; Badcock, Kenneth; Boelens, Oklo

2009-01-01

Nine groups participating in the Cranked Arrow Wing Aerodynamics Project International (CAWAPI) project have contributed steady and unsteady viscous simulations of a full-scale, semi-span model of the F-16XL aircraft. Three different categories of flight Reynolds/Mach number combinations were computed and compared with flight-test measurements for the purpose of code validation and improved understanding of the flight physics. Steady-state simulations are done with several turbulence models of different complexity with no topology information required and which overcome Boussinesq-assumption problems in vortical flows. Detached-eddy simulation (DES) and its successor delayed detached-eddy simulation (DDES) have been used to compute the time accurate flow development. Common structured and unstructured grids as well as individually-adapted unstructured grids were used. Although discrepancies are observed in the comparisons, overall reasonable agreement is demonstrated for surface pressure distribution, local skin friction and boundary velocity profiles at subsonic speeds. The physical modeling, steady or unsteady, and the grid resolution both contribute to the discrepancies observed in the comparisons with flight data, but at this time it cannot be determined how much each part contributes to the whole. Overall it can be said that the technology readiness of CFD-simulation technology for the study of vehicle performance has matured since 2001 such that it can be used today with a reasonable level of confidence for complex configurations.

Phenotypic outcomes in Mouse and Human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms

PubMed Central

Haldipur, Parthiv; Dang, Derek; Aldinger, Kimberly A; Janson, Olivia K; Guimiot, Fabien; Adle-Biasette, Homa; Dobyns, William B; Siebert, Joseph R; Russo, Rosa; Millen, Kathleen J

2017-01-01

FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation. Previously, we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule which echoes the posterior vermis DW 'tail sign' observed in human imaging studies. Lineage tracing experiments in Foxc1 mutant mouse cerebella indicate that aberrant migration of granule cell progenitors destined to form the posterior-most lobule causes this unique phenotype. Analyses of rare human del chr 6p25 fetal cerebella demonstrate extensive phenotypic overlap with our Foxc1 mutant mouse models, validating our DWM models and demonstrating that many key mechanisms controlling cerebellar development are likely conserved between mouse and human. DOI: http://dx.doi.org/10.7554/eLife.20898.001 PMID:28092268

Accounting for optical errors in microtensiometry.

PubMed

Hinton, Zachary R; Alvarez, Nicolas J

2018-09-15

Drop shape analysis (DSA) techniques measure interfacial tension subject to error in image analysis and the optical system. While considerable efforts have been made to minimize image analysis errors, very little work has treated optical errors. There are two main sources of error when considering the optical system: the angle of misalignment and the choice of focal plane. Due to the convoluted nature of these sources, small angles of misalignment can lead to large errors in measured curvature. We demonstrate using microtensiometry the contributions of these sources to measured errors in radius, and, more importantly, deconvolute the effects of misalignment and focal plane. Our findings are expected to have broad implications on all optical techniques measuring interfacial curvature. A geometric model is developed to analytically determine the contributions of misalignment angle and choice of focal plane on measurement error for spherical cap interfaces. This work utilizes a microtensiometer to validate the geometric model and to quantify the effect of both sources of error. For the case of a microtensiometer, an empirical calibration is demonstrated that corrects for optical errors and drastically simplifies implementation. The combination of geometric modeling and experimental results reveal a convoluted relationship between the true and measured interfacial radius as a function of the misalignment angle and choice of focal plane. The validated geometric model produces a full operating window that is strongly dependent on the capillary radius and spherical cap height. In all cases, the contribution of optical errors is minimized when the height of the spherical cap is equivalent to the capillary radius, i.e. a hemispherical interface. The understanding of these errors allow for correct measure of interfacial curvature and interfacial tension regardless of experimental setup. For the case of microtensiometry, this greatly decreases the time for experimental setup and increases experiential accuracy. In a broad sense, this work outlines the importance of optical errors in all DSA techniques. More specifically, these results have important implications for all microscale and microfluidic measurements of interface curvature. Copyright © 2018 Elsevier Inc. All rights reserved.

Methamphetamine induces autophagy and apoptosis in a mesencephalic dopaminergic neuronal culture model: role of cathepsin-D in methamphetamine-induced apoptotic cell death.

PubMed

Kanthasamy, Arthi; Anantharam, V; Ali, Syed F; Kanthasamy, A G

2006-08-01

Autophagy is a phylogenetically conserved process that plays a critical role in the degradation of oxidatively damaged proteins and organelle turnover. The role of oxidative stress and apoptosis in methamphetamine (METH)-induced neurotoxicity is well known; however, the potential contribution of autophagy to METH-induced oxidative damage in dopaminergic neuronal systems remains unclear. The goals of the present article were twofold: (a) to develop an in vitro dopaminergic cell culture model to study cellular and molecular mechanisms underlying METH-induced autophagy and apoptosis, and (b) to determine whether lysosomal protease cathepsin-D activation, resulting from the loss of lysosomal membrane integrity, contributes to METH-induced apoptosis. To accomplish these goals, we characterized morphological and biochemical changes in an immortalized mesencephalic dopaminergic neuronal cell line (N27 cells) following treatment with METH. Exposure of METH (2 mM) to N27 cells resulted in the appearance of cytoplasmic vacuolar structures reminiscent of autophagic vacuoles within 3 h. In order to ascertain the identity of the vacuolar structures that are formed following METH exposure, immunohistochemical staining for markers of autophagy were performed. LAMP 2, a classical marker of autophagolysosomes, revealed an extensive punctuate pattern of distribution on the vacuolar membrane surface, with exclusive localization in the cytoplasm. Additionally, using DNA fragmentation analysis we showed a dose-dependent increase in fragmented DNA in METH treated N27 cells. Since METH-induced autophagy preceded DNA fragmentation, we tested whether dysfunction of the autophagolysosomal system contributes to nuclear damage. Immunofluorescence studies with cathepsin-d demonstrated a granular pattern of staining in untreated cells, whereas an increased cathepsin- D immunoreactivity with a globular pattern of staining was observed in METH-treated cells. Nevertheless, blockade of cathepsin-D activation by pepstatin-A, cathepsin-D inhibitor, failed to alter METH-induced DNA fragmentation. Collectively, these results demonstrate that N27 dopaminergic neuronal cell model may serve as an excellent in vitro model to study the mechanisms of METH-induced autophagy and apoptosis. Furthermore, it is less likely that cathepsin-D may serve as a trigger for the induction of apoptosis subsequent to exposure of N27 dopaminergic neuronal cells to METH.

Contribution of Urease to Colonization by Shiga Toxin-Producing Escherichia coli

PubMed Central

Steyert, Susan R.

2012-01-01

Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen with a low infectious dose that colonizes the colon in humans and can cause severe clinical manifestations such as hemolytic-uremic syndrome. The urease enzyme, encoded in the STEC chromosome, has been demonstrated to act as a virulence factor in other bacterial pathogens. The NH3 produced as urease hydrolyzes urea can aid in buffering bacteria in acidic environments as well as provide an easily assimilated source of nitrogen that bacteria can use to gain a metabolic advantage over intact microflora. Here, we explore the role of urease in STEC pathogenicity. The STEC urease enzyme exhibited maximum activity near neutral pH and during the stationary-growth phase. Experiments altering growth conditions performed with three phylogenetically distinct urease-positive strains demonstrated that the STEC ure gene cluster is inducible by neither urea nor pH but does respond to nitrogen availability. Quantitative reverse transcription-PCR (qRT-PCR) data indicate that nitrogen inhibits the transcriptional response. The deletion of the ure gene locus was constructed in STEC strain 88-0643, and the ure mutant was used with the wild-type strain in competition experiments in mouse models to examine the contribution of urease. The wild-type strain was twice as likely to survive passage through the acidic stomach and demonstrated an enhanced ability to colonize the intestinal tract compared to the ure mutant strain. These in vivo experiments reveal that, although the benefit STEC gains from urease expression is modest and not absolutely required for colonization, urease can contribute to the pathogenicity of STEC. PMID:22665380

Using operational active remote sensing devices to detect Saharan dust advections and evaluate their contribution to the PM10 levels: The EU LIFE+ "DIAPASON" project

NASA Astrophysics Data System (ADS)

Gobbi, Gian Paolo; Wille, Holger; Sozzi, Roberto; Barnaba, Francesca; Costabile, Francesca; Angelini, Federico; Frey, Steffen; Bolignano, Andrea; Morelli, Matteo

2013-04-01

The contribution of Saharan-dust advections to both daily and annual PM average mass concentrations can be significant all over Southern Europe. The Directive 2008/50/EC allows subtraction of PM10 exceedances caused by natural contributions from the statistic used to determine air-quality levels in Europe. To this purpose, the Commission Staff Working Paper 6771/11 (EC, 2011) provides specific Guidelines on methods to quantify and subtract the contribution of these sources in the framework of the Air Quality Directive. For Saharan dust, the EC methodology is largely based on a thorough analysis performed over the Iberian Peninsula (Escudero et al, 2007), although revision of the current methodology is in progress. In line with the EC Guidelines, the DIAPASON project ("Desert-dust Impact on Air quality through model-Predictions and Advanced Sensors ObservatioNs"), funded under the EC LIFE+ program, has been formulated to provide a robust, user-oriented, and demonstrated method to assess the presence of desert dust and evaluate its contribution to PM10 levels at the monitoring sites. To this end, in addition to satellite-based data and model forecasts already included in the EC Guidelines, DIAPASON will take advantage, in both the Project implementation and demonstration phase, of innovative and affordable technologies (partly prototyped within the project itself), namely operational Polarization Lidar-Ceilometers (PLC) capable of detecting and profiling dust clouds from the ground up to 10 km altitude. The PLC prototypes have been already finalized during the initial phase of the Project. Three of them will be networked in relevant air quality monitoring stations located in the Rome metropolitan area (Italy) during the DIAPASON observational phase (one-year long field campaign) starting in March 2013. The Rome region was chosen as the DIAPASON pilot scale area since highly impacted by urban pollution and frequently affected by Saharan dust transport events. In fact, a preliminary assessment of the role of Saharan dust in this area, based on a four-year dataset (2001-2004) has shown average increases of PM10 levels of the order of 11.9 µg/m3 when Saharan dust presence is either predicted by models or observed by a depolarization lidar. Conversely, PM10 increases computed relying only on the Lidar detections (i.e., presence of dust layers actually observed) were of the order of 15.6 µg/m3. Both analyses indicate the annual average contribution of dust advections to the city PM10 mass concentrations to be of the order of 2.3 µg/m3 (Gobbi et al., 2013). These results confirm Saharan advections in the central Mediterranean as important modulators of PM10 loads and exceedances. After the demonstrative pilot scale study, the DIAPASON results will be spatially generalised to a wider area. The final DIAPASON methodology to detect/quantify the Saharan dust contribution to PM10 will be tailored for a national scale application, and easily transferable to other air-quality and meteorological agencies in Europe. In this work, preliminary results from the combined analysis of Saharan dust model predictions, PM10 data and lidar records performed within DIAPASON will be shown, with particular focus on the added-value provided by continuous polarization lidar data in integrating the present EC Methodology. - EC, Commission Staff Working Paper 6771/11 establishing guidelines for demonstration and subtraction of exceedances attributable to natural sources under the Directive 2008/50/EC on ambient air quality and cleaner air for Europe, European Commission, 2011. - Escudero, M., Querol, X., Pey, J., Alastuey, A., Pérez, N., Ferreira, F., Alonso, S., Rodríguez, S. and Cuevas, E., A methodology for the quantification of the net African dust load in air quality monitoring networks, Atmos. Envir., 41, 5516-5524, 2007. - Gobbi,G. P., F. Angelini, F. Barnaba, F. Costabile, J. M. Baldasano, S. Basart, R. Sozzi and A. Bolignano, Changes in Particulate Matter Physical Properties During Saharan Advections over Rome (Italy): A Four-Year Study, 2001-2004, Atmos. Chem. Phys., Discus., 2013.

The effect of soot modeling on thermal radiation in buoyant turbulent diffusion flames

NASA Astrophysics Data System (ADS)

Snegirev, A.; Kokovina, E.; Tsoy, A.; Harris, J.; Wu, T.

2016-09-01

Radiative impact of buoyant turbulent diffusion flames is the driving force in fire development. Radiation emission and re-absorption is controlled by gaseous combustion products, mainly CO2 and H2O, and by soot. Relative contribution of gas and soot radiation depends on the fuel sooting propensity and on soot distribution in the flame. Soot modeling approaches incorporated in big commercial codes were developed and calibrated for momentum-dominated jet flames, and these approaches must be re-evaluated when applied to the buoyant flames occurring in fires. The purpose of this work is to evaluate the effect of the soot models available in ANSYS FLUENT on the predictions of the radiative fluxes produced by the buoyant turbulent diffusion flames with considerably different soot yields. By means of large eddy simulations, we assess capability of the Moss-Brooks soot formation model combined with two soot oxidation submodels to predict methane- and heptane-fuelled fires, for which radiative flux measurements are available in the literature. We demonstrate that the soot oxidation models could be equally important as soot formation ones to predict the soot yield in the overfire region. Contribution of soot in the radiation emission by the flame is also examined, and predicted radiative fluxes are compared to published experimental data.

Does active ageing contribute to life satisfaction for older people? Testing a new model of active ageing.

PubMed

Marsillas, Sara; De Donder, Liesbeth; Kardol, Tinie; van Regenmortel, Sofie; Dury, Sarah; Brosens, Dorien; Smetcoren, An-Sofie; Braña, Teresa; Varela, Jesús

2017-09-01

Several debates have emerged across the literature about the conceptualisation of active ageing. The aim of this study is to develop a model of the construct that is focused on the individual, including different elements of people's lives that have the potential to be modified by intervention programs. Moreover, the paper examines the contributions of active ageing to life satisfaction, as well as the possible predictive role of coping styles on active ageing. For this purpose, a representative sample of 404 Galician (Spain) community-dwelling older adults (aged ≥60 years) were interviewed using a structured survey. The results demonstrate that the proposed model composed of two broad categories is valid. The model comprises status variables (related to physical, psychological, and social health) as well as different types of activities, called processual variables. This model is tested using partial least squares (PLS) regression. The findings show that active ageing is a fourth-order, formative construct. In addition, PLS analyses indicate that active ageing has a moderate and positive path on life satisfaction and that coping styles may predict active ageing. The discussion highlights the potential of active ageing as a relevant concept for people's lives, drawing out policy implications and suggestions for further research.

3D Air Quality and the Clean Air Interstate Rule: Lagrangian Sampling of CMAQ Model Results to Aid Regional Accountability Metrics

NASA Technical Reports Server (NTRS)

Fairlie, T. D.; Szykman, Jim; Pierce, Robert B.; Gilliland, A. B.; Engel-Cox, Jill; Weber, Stephanie; Kittaka, Chieko; Al-Saadi, Jassim A.; Scheffe, Rich; Dimmick, Fred;

Non-tumor cell IDO1 predominantly contributes to enzyme activity and response to CTLA-4/PD-L1 inhibition in mouse glioblastoma.

PubMed

Zhai, Lijie; Ladomersky, Erik; Dostal, Carlos R; Lauing, Kristen L; Swoap, Kathleen; Billingham, Leah K; Gritsina, Galina; Wu, Meijing; McCusker, Robert H; Binder, David C; Wainwright, Derek A

2017-05-01

Glioblastoma (GBM) is the most common malignant brain tumor in adults with a median survival of 14.6months. A contributing factor to GBM aggressiveness is the intratumoral expression of the potently immunosuppressive enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). The enzymatic activity of IDO1 is associated with the conversion of tryptophan into downstream kynurenine (Kyn), which has previously been hypothesized to contribute toward the suppression of tumor immunity. Utilizing the syngeneic, immunocompetent, intracranial GL261 cell GBM model, we previously demonstrated that tumor cell, but not non-tumor cell IDO1, suppresses T cell-mediated brain tumor regression in mice. Paradoxically, we also showed that the survival advantage mediated by immune checkpoint blockade is abrogated by non-tumor cell IDO1 deficiency. Here, we have built on our past observations and confirm the maladaptive role of tumor cell IDO1 in a novel mouse GBM model. We also demonstrate that, non-tumor cells, rather than mouse GBM cells, are the dominant contributor to IDO1-mediated enzyme activity. Finally, we show the novel associations between maximally-effective immune-checkpoint blockade-mediated survival, non-tumor cell IDO1 and intra-GBM Kyn levels. These data suggest for the first time that, GBM cell-mediated immunosuppression is IDO1 enzyme independent, while the survival benefits of immune checkpoint blockade require non-tumor cell IDO1 enzyme activity. Given that current clinical inhibitors vary in their mechanism of action, in terms of targeting IDO1 enzyme activity versus enzyme-independent effects, this work suggests that choosing an appropriate IDO1 pharmacologic will maximize the effectiveness of future immune checkpoint blockade approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

“I Can Only Work So Hard Before I Burn Out.” A Time Sensitive Conceptual Integration of Ideological Psychological Contract Breach, Work Effort, and Burnout

PubMed Central

Jones, Samantha K.; Griep, Yannick

2018-01-01

Employees often draw meaning from personal experiences and contributions in their work, particularly when engaging in organizational activities that align with their personal identity or values. However, recent empirical findings have demonstrated how meaningful work can also have a negative effect on employee’s well-being as employees feel so invested in their work, they push themselves beyond their limits resulting in strain and susceptibility to burnout. We develop a framework to understand this “double edged” role of meaningful work by drawing from ideological psychological contracts (iPCs), which are characterized by employees and their employer who are working to contribute to a shared ideology or set of values. Limited iPC research has demonstrated employees may actually work harder in response to an iPC breach. In light of these counterintuitive findings, we propose the following conceptual model to theoretically connect our understanding of iPCs, perceptions of breach, increases in work effort, and the potential “dark side” of repeated occurrences of iPC breach. We argue that time plays a central role in the unfolding process of employees’ reactions to iPC breach over time. Further, we propose how perceptions of iPC breach relate to strain and, eventually, burnout. This model contributes to our understanding of the role of time in iPC development and maintenance, expands our exploration of ideology in the PC literature, and provides a framework to understanding why certain occupations are more susceptible to instances of strain and burnout. This framework has the potential to guide future employment interventions in ideology-infused organizations to help mitigate negative employee outcomes. PMID:29479334

"I Can Only Work So Hard Before I Burn Out." A Time Sensitive Conceptual Integration of Ideological Psychological Contract Breach, Work Effort, and Burnout.

PubMed

Jones, Samantha K; Griep, Yannick

2018-01-01

Employees often draw meaning from personal experiences and contributions in their work, particularly when engaging in organizational activities that align with their personal identity or values. However, recent empirical findings have demonstrated how meaningful work can also have a negative effect on employee's well-being as employees feel so invested in their work, they push themselves beyond their limits resulting in strain and susceptibility to burnout. We develop a framework to understand this "double edged" role of meaningful work by drawing from ideological psychological contracts (iPCs), which are characterized by employees and their employer who are working to contribute to a shared ideology or set of values. Limited iPC research has demonstrated employees may actually work harder in response to an iPC breach. In light of these counterintuitive findings, we propose the following conceptual model to theoretically connect our understanding of iPCs, perceptions of breach, increases in work effort, and the potential "dark side" of repeated occurrences of iPC breach. We argue that time plays a central role in the unfolding process of employees' reactions to iPC breach over time. Further, we propose how perceptions of iPC breach relate to strain and, eventually, burnout. This model contributes to our understanding of the role of time in iPC development and maintenance, expands our exploration of ideology in the PC literature, and provides a framework to understanding why certain occupations are more susceptible to instances of strain and burnout. This framework has the potential to guide future employment interventions in ideology-infused organizations to help mitigate negative employee outcomes.

Emotional processing during experiential treatment of depression.

PubMed

Pos, Alberta E; Greenberg, Leslie S; Goldman, Rhonda N; Korman, Lorne M

2003-12-01

This study explored the importance of early and late emotional processing to change in depressive and general symptomology, self-esteem, and interpersonal problems for 34 clients who received 16-20 sessions of experiential treatment for depression. The independent contribution to outcome of the early working alliance was also explored. Early and late emotional processing predicted reductions in reported symptoms and gains in self-esteem. More important, emotional-processing skill significantly improved during treatment. Hierarchical regression models demonstrated that late emotional processing both mediated the relationship between clients' early emotional processing capacity and outcome and was the sole emotional-processing variable that independently predicted improvement. After controlling for emotional processing, the working alliance added an independent contribution to explaining improvement in reported symptomology only. (c) 2003 APA

Polarization and Resummation in Slepton Production at Hadron Colliders

NASA Astrophysics Data System (ADS)

Klasen, M.

2006-10-01

In R-parity conserving supersymmetric (SUSY) models, sleptons are produced in pairs at hadron colliders through neutral and charged electroweak currents. We demonstrate that the polarization of the initial hadron beams allows for a direct extraction of the slepton mixing angle and thus for a determination of the underlying SUSY-breaking mechanism. We also perform a first precision calculation of the transverse-momentum ( q T) spectrum of the slepton pairs by resumming soft multiple-gluon emission at next-to-leading logarithmic order. The results show a relevant contribution of resummation both in the small and intermediate q T-regions, which strongly influences the extraction of the missing transverse-momentum signal and the subsequent slepton mass-determination, and little dependence on unphysical scales and non-perturbative contributions.

Role of Kv 4.3 in vibration-induced muscle pain in the rat

PubMed Central

Conner, Lindsay; Alvarez, Pedro; Bogen, Oliver; Levine, Jon D.

2015-01-01

We hypothesized that changes in the expression of Kv4.3 contribute to the mechanical hyperalgesia induced by vibration injury, a rodent model for hand-arm vibration syndrome in humans. Here we show that the exposure of the gastrocnemius muscle to vibration injury induces muscle hyperalgesia that is accompanied by a significant down-regulation of Kv4.3 in affected sensory nerve fibers in dorsal root ganglia (DRG). We additionally demonstrate that the intrathecal administration of antisense oligonucleotides for Kv4.3 mRNA itself induces muscle hyperalgesia in the rat. Our results suggest that attenuation in the expression of Kv4.3 may contribute to neuropathic pain in people affected by hand-arm vibration syndrome. PMID:26721612

Charles Darwin and psychology at the bicentennial and sesquicentennial: an introduction.

PubMed

Dewsbury, Donald A

2009-01-01

This article provides an introduction to the special issue on Darwin and psychology at the bicentennial of his birth and the sesquicentennial of his publication of On the Origin of Species. His core contributions, as viewed today, were his theory of natural selection, his naturalistic philosophy, and his mass of evidence for evolutionary change. A brief summary of Darwin's life is also presented. Among Darwin's contributions to psychology were his demonstration of the continuity of species, a model for the study of instinct, a book on the expression of the emotions, and a baby biography. Previous celebrations of Darwin and the changing perceptions of his work since its publication are described. Darwin's theory remains an important part of psychology. 2009 APA, all rights reserved

Critical period inhibition of NKCC1 rectifies synapse plasticity in the somatosensory cortex and restores adult tactile response maps in fragile X mice.

PubMed

He, Qionger; Arroyo, Erica D; Smukowski, Samuel N; Xu, Jian; Piochon, Claire; Savas, Jeffrey N; Portera-Cailliau, Carlos; Contractor, Anis

2018-04-27

Sensory perturbations in visual, auditory and tactile perception are core problems in fragile X syndrome (FXS). In the Fmr1 knockout mouse model of FXS, the maturation of synapses and circuits during critical period (CP) development in the somatosensory cortex is delayed, but it is unclear how this contributes to altered tactile sensory processing in the mature CNS. Here we demonstrate that inhibiting the juvenile chloride co-transporter NKCC1, which contributes to altered chloride homeostasis in developing cortical neurons of FXS mice, rectifies the chloride imbalance in layer IV somatosensory cortex neurons and corrects the development of thalamocortical excitatory synapses during the CP. Comparison of protein abundances demonstrated that NKCC1 inhibition during early development caused a broad remodeling of the proteome in the barrel cortex. In addition, the abnormally large size of whisker-evoked cortical maps in adult Fmr1 knockout mice was corrected by rectifying the chloride imbalance during the early CP. These data demonstrate that correcting the disrupted driving force through GABA A receptors during the CP in cortical neurons restores their synaptic development, has an unexpectedly large effect on differentially expressed proteins, and produces a long-lasting correction of somatosensory circuit function in FXS mice.

Testing and selection of cosmological models with (1+z){sup 6} corrections

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

Szydlowski, Marek; Marc Kac Complex Systems Research Centre, Jagiellonian University, ul. Reymonta 4, 30-059 Cracow; Godlowski, Wlodzimierz

2008-02-15

In the paper we check whether the contribution of (-)(1+z){sup 6} type in the Friedmann equation can be tested. We consider some astronomical tests to constrain the density parameters in such models. We describe different interpretations of such an additional term: geometric effects of loop quantum cosmology, effects of braneworld cosmological models, nonstandard cosmological models in metric-affine gravity, and models with spinning fluid. Kinematical (or geometrical) tests based on null geodesics are insufficient to separate individual matter components when they behave like perfect fluid and scale in the same way. Still, it is possible to measure their overall effect. Wemore » use recent measurements of the coordinate distances from the Fanaroff-Riley type IIb radio galaxy data, supernovae type Ia data, baryon oscillation peak and cosmic microwave background radiation observations to obtain stronger bounds for the contribution of the type considered. We demonstrate that, while {rho}{sup 2} corrections are very small, they can be tested by astronomical observations--at least in principle. Bayesian criteria of model selection (the Bayesian factor, AIC, and BIC) are used to check if additional parameters are detectable in the present epoch. As it turns out, the {lambda}CDM model is favored over the bouncing model driven by loop quantum effects. Or, in other words, the bounds obtained from cosmography are very weak, and from the point of view of the present data this model is indistinguishable from the {lambda}CDM one.« less

Modeling plant interspecific interactions from experiments with perennial crop mixtures to predict optimal combinations.

PubMed

Halty, Virginia; Valdés, Matías; Tejera, Mauricio; Picasso, Valentín; Fort, Hugo

2017-12-01

The contribution of plant species richness to productivity and ecosystem functioning is a longstanding issue in ecology, with relevant implications for both conservation and agriculture. Both experiments and quantitative modeling are fundamental to the design of sustainable agroecosystems and the optimization of crop production. We modeled communities of perennial crop mixtures by using a generalized Lotka-Volterra model, i.e., a model such that the interspecific interactions are more general than purely competitive. We estimated model parameters -carrying capacities and interaction coefficients- from, respectively, the observed biomass of monocultures and bicultures measured in a large diversity experiment of seven perennial forage species in Iowa, United States. The sign and absolute value of the interaction coefficients showed that the biological interactions between species pairs included amensalism, competition, and parasitism (asymmetric positive-negative interaction), with various degrees of intensity. We tested the model fit by simulating the combinations of more than two species and comparing them with the polycultures experimental data. Overall, theoretical predictions are in good agreement with the experiments. Using this model, we also simulated species combinations that were not sown. From all possible mixtures (sown and not sown) we identified which are the most productive species combinations. Our results demonstrate that a combination of experiments and modeling can contribute to the design of sustainable agricultural systems in general and to the optimization of crop production in particular. © 2017 by the Ecological Society of America.

Modeling sediment transport after ditch network maintenance of a forested peatland

NASA Astrophysics Data System (ADS)

Haahti, K.; Marttila, H.; Warsta, L.; Kokkonen, T.; Finér, L.; Koivusalo, H.

2016-11-01

Elevated suspended sediment (SS) loads released from peatlands after drainage operations and the resulting negative effect on the ecological status of the receiving water bodies have been widely recognized. Understanding the processes controlling erosion and sediment transport within the ditch network forms a prerequisite for adequate sediment control. While numerous experimental studies have been reported in this field, model based assessments are rare. This study presents a modeling approach to investigate sediment transport in a peatland ditch network. The transport model describes bed erosion, rain-induced bank erosion, floc deposition, and consolidation of the bed. Coupled to a distributed hydrological model, sediment transport was simulated in a 5.2 ha forestry-drained peatland catchment for 2 years after ditch cleaning. Comparing simulation results to measured SS concentrations suggested that the loose peat material, produced during excavation, contributed markedly to elevated SS concentrations immediately after ditch cleaning. Both snowmelt and summer rainstorms contributed critically to annual loads. Springtime peat erosion during snowmelt was driven by ditch flow whereas during summer rainfalls, bank erosion by raindrop impact was identified as an important process. Relating modeling results to observed spatial topographic changes in the ditch network was challenging and the results were difficult to verify. Nevertheless, the model has potential to identify risk areas for erosion. The results demonstrate that modeling is effective in separating the importance of different processes and complements pure experimental approaches. Modeling results can aid planning and designing efficient sediment control measures and guide the focus of experimental studies.

Application of separable parameter space techniques to multi-tracer PET compartment modeling.

PubMed

Zhang, Jeff L; Michael Morey, A; Kadrmas, Dan J

2016-02-07

Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg-Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models.

Application of separable parameter space techniques to multi-tracer PET compartment modeling

NASA Astrophysics Data System (ADS)

Zhang, Jeff L.; Morey, A. Michael; Kadrmas, Dan J.

2016-02-01

Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg-Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models.

Modelling rainfall erosion resulting from climate change

NASA Astrophysics Data System (ADS)

Kinnell, Peter

2016-04-01

It is well known that soil erosion leads to agricultural productivity decline and contributes to water quality decline. The current widely used models for determining soil erosion for management purposes in agriculture focus on long term (~20 years) average annual soil loss and are not well suited to determining variations that occur over short timespans and as a result of climate change. Soil loss resulting from rainfall erosion is directly dependent on the product of runoff and sediment concentration both of which are likely to be influenced by climate change. This presentation demonstrates the capacity of models like the USLE, USLE-M and WEPP to predict variations in runoff and erosion associated with rainfall events eroding bare fallow plots in the USA with a view to modelling rainfall erosion in areas subject to climate change.

Towards greater realism in inclusive fitness models: the case of worker reproduction in insect societies

PubMed Central

Wenseleers, Tom; Helanterä, Heikki; Alves, Denise A.; Dueñez-Guzmán, Edgar; Pamilo, Pekka

2013-01-01

The conflicts over sex allocation and male production in insect societies have long served as an important test bed for Hamilton's theory of inclusive fitness, but have for the most part been considered separately. Here, we develop new coevolutionary models to examine the interaction between these two conflicts and demonstrate that sex ratio and colony productivity costs of worker reproduction can lead to vastly different outcomes even in species that show no variation in their relatedness structure. Empirical data on worker-produced males in eight species of Melipona bees support the predictions from a model that takes into account the demographic details of colony growth and reproduction. Overall, these models contribute significantly to explaining behavioural variation that previous theories could not account for. PMID:24132088

Dynamics of stochastic SEIS epidemic model with varying population size

NASA Astrophysics Data System (ADS)

Liu, Jiamin; Wei, Fengying

2016-12-01

We introduce the stochasticity into a deterministic model which has state variables susceptible-exposed-infected with varying population size in this paper. The infected individuals could return into susceptible compartment after recovering. We show that the stochastic model possesses a unique global solution under building up a suitable Lyapunov function and using generalized Itô's formula. The densities of the exposed and infected tend to extinction when some conditions are being valid. Moreover, the conditions of persistence to a global solution are derived when the parameters are subject to some simple criteria. The stochastic model admits a stationary distribution around the endemic equilibrium, which means that the disease will prevail. To check the validity of the main results, numerical simulations are demonstrated as end of this contribution.

Spin-electron acoustic soliton and exchange interaction in separate spin evolution quantum plasmas

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

Andreev, Pavel A., E-mail: andreevpa@physics.msu.ru

Separate spin evolution quantum hydrodynamics is generalized to include the Coulomb exchange interaction, which is considered as interaction between the spin-down electrons being in quantum states occupied by one electron. The generalized model is applied to study the non-linear spin-electron acoustic waves. Existence of the spin-electron acoustic soliton is demonstrated. Contributions of concentration, spin polarization, and exchange interaction to the properties of the spin electron acoustic soliton are studied.

Electrochemical impedance spectroscopy of supercapacitors: A novel analysis approach using evolutionary programming

NASA Astrophysics Data System (ADS)

Oz, Alon; Hershkovitz, Shany; Tsur, Yoed

2014-11-01

In this contribution we present a novel approach to analyze impedance spectroscopy measurements of supercapacitors. Transforming the impedance data into frequency-dependent capacitance allows us to use Impedance Spectroscopy Genetic Programming (ISGP) in order to find the distribution function of relaxation times (DFRT) of the processes taking place in the tested device. Synthetic data was generated in order to demonstrate this technique and a model for supercapacitor ageing process has been obtained.

On the importance of excited state dynamic response electron correlation in polarizable embedding methods.

PubMed

Eriksen, Janus J; Sauer, Stephan P A; Mikkelsen, Kurt V; Jensen, Hans J Aa; Kongsted, Jacob

2012-09-30

We investigate the effect of including a dynamic reaction field at the lowest possible ab inito wave function level of theory, namely the Hartree-Fock (HF) self-consistent field level within the polarizable embedding (PE) formalism. We formulate HF based PE within the linear response theory picture leading to the PE-random-phase approximation (PE-RPA) and bridge the expressions to a second-order polarization propagator approximation (SOPPA) frame such that dynamic reaction field contributions are included at the RPA level in addition to the static response described at the SOPPA level but with HF induced dipole moments. We conduct calculations on para-nitro-aniline and para-nitro-phenolate using said model in addition to dynamic PE-RPA and PE-CAM-B3LYP. We compare the results to recently published PE-CCSD data and demonstrate how the cost effective SOPPA-based model successfully recovers a great portion of the inherent PE-RPA error when the observable is the solvatochromic shift. We furthermore demonstrate that whenever the change in density resulting from the ground state-excited state electronic transition in the solute is not associated with a significant change in the electric field, dynamic response contributions formulated at the HF level of theory manage to capture the majority of the system response originating from derivative densities. Copyright © 2012 Wiley Periodicals, Inc.

Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

PubMed Central

Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

2016-01-01

Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

Homo sapiens exhibit a distinct pattern of CNV genes regulation: an important role of miRNAs and SNPs in expression plasticity.

PubMed

Dweep, Harsh; Kubikova, Nada; Gretz, Norbert; Voskarides, Konstantinos; Felekkis, Kyriacos

2015-07-16

Gene expression regulation is a complex and highly organized process involving a variety of genomic factors. It is widely accepted that differences in gene expression can contribute to the phenotypic variability between species, and that their interpretation can aid in the understanding of the physiologic variability. CNVs and miRNAs are two major players in the regulation of expression plasticity and may be responsible for the unique phenotypic characteristics observed in different lineages. We have previously demonstrated that a close interaction between these two genomic elements may have contributed to the regulation of gene expression during evolution. This work presents the molecular interactions between CNV and non CNV genes with miRNAs and other genomic elements in eight different species. A comprehensive analysis of these interactions indicates a unique nature of human CNV genes regulation as compared to other species. By using genes with short 3' UTR that abolish the "canonical" miRNA-dependent regulation, as a model, we demonstrate a distinct and tight regulation of human genes that might explain some of the unique features of human physiology. In addition, comparison of gene expression regulation between species indicated that there is a significant difference between humans and mice possibly questioning the effectiveness of the latest as experimental models of human diseases.

Residual attention guidance in blindsight monkeys watching complex natural scenes.

PubMed

Yoshida, Masatoshi; Itti, Laurent; Berg, David J; Ikeda, Takuro; Kato, Rikako; Takaura, Kana; White, Brian J; Munoz, Douglas P; Isa, Tadashi

2012-08-07

Patients with damage to primary visual cortex (V1) demonstrate residual performance on laboratory visual tasks despite denial of conscious seeing (blindsight) [1]. After a period of recovery, which suggests a role for plasticity [2], visual sensitivity higher than chance is observed in humans and monkeys for simple luminance-defined stimuli, grating stimuli, moving gratings, and other stimuli [3-7]. Some residual cognitive processes including bottom-up attention and spatial memory have also been demonstrated [8-10]. To date, little is known about blindsight with natural stimuli and spontaneous visual behavior. In particular, is orienting attention toward salient stimuli during free viewing still possible? We used a computational saliency map model to analyze spontaneous eye movements of monkeys with blindsight from unilateral ablation of V1. Despite general deficits in gaze allocation, monkeys were significantly attracted to salient stimuli. The contribution of orientation features to salience was nearly abolished, whereas contributions of motion, intensity, and color features were preserved. Control experiments employing laboratory stimuli confirmed the free-viewing finding that lesioned monkeys retained color sensitivity. Our results show that attention guidance over complex natural scenes is preserved in the absence of V1, thereby directly challenging theories and models that crucially depend on V1 to compute the low-level visual features that guide attention. Copyright © 2012 Elsevier Ltd. All rights reserved.

Homo sapiens exhibit a distinct pattern of CNV genes regulation: an important role of miRNAs and SNPs in expression plasticity

PubMed Central

Dweep, Harsh; Kubikova, Nada; Gretz, Norbert; Voskarides, Konstantinos; Felekkis, Kyriacos

2015-01-01

Gene expression regulation is a complex and highly organized process involving a variety of genomic factors. It is widely accepted that differences in gene expression can contribute to the phenotypic variability between species, and that their interpretation can aid in the understanding of the physiologic variability. CNVs and miRNAs are two major players in the regulation of expression plasticity and may be responsible for the unique phenotypic characteristics observed in different lineages. We have previously demonstrated that a close interaction between these two genomic elements may have contributed to the regulation of gene expression during evolution. This work presents the molecular interactions between CNV and non CNV genes with miRNAs and other genomic elements in eight different species. A comprehensive analysis of these interactions indicates a unique nature of human CNV genes regulation as compared to other species. By using genes with short 3′ UTR that abolish the “canonical” miRNA-dependent regulation, as a model, we demonstrate a distinct and tight regulation of human genes that might explain some of the unique features of human physiology. In addition, comparison of gene expression regulation between species indicated that there is a significant difference between humans and mice possibly questioning the effectiveness of the latest as experimental models of human diseases. PMID:26178010

Group B Streptococcus β-hemolysin/Cytolysin Breaches Maternal-Fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

PubMed Central

Randis, Tara M.; Gelber, Shari E.; Hooven, Thomas A.; Abellar, Rosanna G.; Akabas, Leor H.; Lewis, Emma L.; Walker, Lindsay B.; Byland, Leah M.; Nizet, Victor; Ratner, Adam J.

2014-01-01

Background. Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. Methods. We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection. Results. Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. Conclusions. Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis. PMID:24474814

Inhibition of Lysosome Membrane Recycling Causes Accumulation of Gangliosides that Contribute to Neurodegeneration.

PubMed

Boutry, Maxime; Branchu, Julien; Lustremant, Céline; Pujol, Claire; Pernelle, Julie; Matusiak, Raphaël; Seyer, Alexandre; Poirel, Marion; Chu-Van, Emeline; Pierga, Alexandre; Dobrenis, Kostantin; Puech, Jean-Philippe; Caillaud, Catherine; Durr, Alexandra; Brice, Alexis; Colsch, Benoit; Mochel, Fanny; El Hachimi, Khalid Hamid; Stevanin, Giovanni; Darios, Frédéric

2018-06-26

Lysosome membrane recycling occurs at the end of the autophagic pathway and requires proteins that are mostly encoded by genes mutated in neurodegenerative diseases. However, its implication in neuronal death is still unclear. Here, we show that spatacsin, which is required for lysosome recycling and whose loss of function leads to hereditary spastic paraplegia 11 (SPG11), promotes clearance of gangliosides from lysosomes in mouse and human SPG11 models. We demonstrate that spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes. Gangliosides contributed to the accumulation of autophagy markers in lysosomes and to neuronal death. In contrast, decreasing ganglioside synthesis prevented neurodegeneration and improved motor phenotype in a SPG11 zebrafish model. Our work reveals how inhibition of lysosome membrane recycling leads to the deleterious accumulation of gangliosides, linking lysosome recycling to neurodegeneration. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Notch-Dependent Pituitary SOX2+ Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

PubMed Central

Zhu, Xiaoyan; Tollkuhn, Jessica; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary Although SOX2+ stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2+ stem cells and hypoplastic gland. Furthermore, we show that the SOX2+ stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2+ stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion. PMID:26651607

Anomalous Behavior of Electronic Heat Capacity of Strongly Correlated Iron Monosilicide

NASA Astrophysics Data System (ADS)

Povzner, A. A.; Volkov, A. G.; Nogovitsyna, T. A.

2018-04-01

The paper deals with the electronic heat capacity of iron monosilicide FeSi subjected to semiconductor-metal thermal transition during which the formation of its spintronic properties is observed. The proposed model which considers pd-hybridization of strongly correlated d-electrons with non-correlated p-electrons, demonstrates a connection of their contribution to heat capacity in the insulator phase with paramagnon effects and fluctuations of occupation numbers for p- and d-states. In a slitless state, the temperature curve of heat capacity is characterized by a maximum appeared due to normalization of the electron density of states using fluctuating exchange fields. At higher temperatures, a linear growth in heat capacity occurs due to paramagnon effects. The correlation between the model parameters and the first-principles calculation provides the electron contribution to heat capacity, which is obtained from the experimental results on phonon heat capacity. Anharmonicity of phonons is connected merely with the thermal expansion of the crystal lattice.

Childhood emotional maltreatment as a robust predictor of suicidal ideation: A multi-wave, prospective investigation

PubMed Central

Miller, Adam Bryant; Jenness, Jessica L.; Oppenheimer, Caroline W.; Barrocas Gottleib, Andrea L.; Young, Jami F.; Hankin, Benjamin L.

2016-01-01

Despite literature suggesting a relationship between child maltreatment and suicidal ideation, few studies have examined the prospective course of this relationship. The current study examined this relationship in a sample of 682 community youth who were followed over the course of 3 years. Repeated measures of suicidal ideation, emotional maltreatment, and depressive symptom severity were examined in multi-wave path analysis models. Overall, results suggest that emotional maltreatment over time contributes uniquely to the prospective prediction of suicidal ideation, even when controlling for age, previous suicidal ideation, biological sex, and depression symptom severity. Unlike previous studies that have only measured emotional maltreatment at one-time point, the current study demonstrates that emotional maltreatment contributes unique risk to suicidal ideation prospectively among youth. Results speak to the importance of examining emotional maltreatment and suicidal ideation within prospective models of risk and suggest that emotional maltreatment is a robust predictor of suicidal ideation, over and above history of suicidal ideation and depression. PMID:27032784

Formal Models of the Network Co-occurrence Underlying Mental Operations.

PubMed

Bzdok, Danilo; Varoquaux, Gaël; Grisel, Olivier; Eickenberg, Michael; Poupon, Cyril; Thirion, Bertrand

2016-06-01

Systems neuroscience has identified a set of canonical large-scale networks in humans. These have predominantly been characterized by resting-state analyses of the task-unconstrained, mind-wandering brain. Their explicit relationship to defined task performance is largely unknown and remains challenging. The present work contributes a multivariate statistical learning approach that can extract the major brain networks and quantify their configuration during various psychological tasks. The method is validated in two extensive datasets (n = 500 and n = 81) by model-based generation of synthetic activity maps from recombination of shared network topographies. To study a use case, we formally revisited the poorly understood difference between neural activity underlying idling versus goal-directed behavior. We demonstrate that task-specific neural activity patterns can be explained by plausible combinations of resting-state networks. The possibility of decomposing a mental task into the relative contributions of major brain networks, the "network co-occurrence architecture" of a given task, opens an alternative access to the neural substrates of human cognition.

Addressing NCDs through research and capacity building in LMICs: lessons learned from tobacco control.

PubMed

Sturke, Rachel; Vorkoper, Susan; Duncan, Kalina; Levintova, Marya; Parascondola, Mark

2016-01-01

Confronting the global non-communicable diseases (NCDs) crisis requires a critical mass of scientists who are well versed in regional health problems and understand the cultural, social, economic, and political contexts that influence the effectiveness of interventions. Investments in global NCD research must be accompanied by contributions to local research capacity. The National Institutes of Health (NIH) and the Fogarty International Center have a long-standing commitment to supporting research capacity building and addressing the growing burden of NCDs in low- and middle-income countries. One program in particular, the NIH International Tobacco and Health Research and Capacity Building Program (TOBAC program), offers an important model for conducting research and building research capacity simultaneously. This article describes the lessons learned from this unique funding model and demonstrates how a relatively modest investment can make important contributions to scientific evidence and capacity building that could inform ongoing and future efforts to tackle the global burden of NCDs.

Addressing NCDs through research and capacity building in LMICs: lessons learned from tobacco control

PubMed Central

Sturke, Rachel; Vorkoper, Susan; Duncan, Kalina; Levintova, Marya; Parascondola, Mark

2016-01-01

Confronting the global non-communicable diseases (NCDs) crisis requires a critical mass of scientists who are well versed in regional health problems and understand the cultural, social, economic, and political contexts that influence the effectiveness of interventions. Investments in global NCD research must be accompanied by contributions to local research capacity. The National Institutes of Health (NIH) and the Fogarty International Center have a long-standing commitment to supporting research capacity building and addressing the growing burden of NCDs in low- and middle-income countries. One program in particular, the NIH International Tobacco and Health Research and Capacity Building Program (TOBAC program), offers an important model for conducting research and building research capacity simultaneously. This article describes the lessons learned from this unique funding model and demonstrates how a relatively modest investment can make important contributions to scientific evidence and capacity building that could inform ongoing and future efforts to tackle the global burden of NCDs. PMID:27545455

Formal Models of the Network Co-occurrence Underlying Mental Operations

PubMed Central

Bzdok, Danilo; Varoquaux, Gaël; Grisel, Olivier; Eickenberg, Michael; Poupon, Cyril; Thirion, Bertrand

2016-01-01

Systems neuroscience has identified a set of canonical large-scale networks in humans. These have predominantly been characterized by resting-state analyses of the task-unconstrained, mind-wandering brain. Their explicit relationship to defined task performance is largely unknown and remains challenging. The present work contributes a multivariate statistical learning approach that can extract the major brain networks and quantify their configuration during various psychological tasks. The method is validated in two extensive datasets (n = 500 and n = 81) by model-based generation of synthetic activity maps from recombination of shared network topographies. To study a use case, we formally revisited the poorly understood difference between neural activity underlying idling versus goal-directed behavior. We demonstrate that task-specific neural activity patterns can be explained by plausible combinations of resting-state networks. The possibility of decomposing a mental task into the relative contributions of major brain networks, the "network co-occurrence architecture" of a given task, opens an alternative access to the neural substrates of human cognition. PMID:27310288

Negative capacitance in (FeCoZr)-(PZT) nanocomposite films

NASA Astrophysics Data System (ADS)

Kołtunowicz, T. N.; Fedotova, J. A.; Zhukowski, P.; Saad, A.; Fedotov, A.; Kasiuk, J. V.; Larkin, A. V.

2013-03-01

In this work, attention was focused on the inductive contribution to the real part of admittance G(T, f) in (Fe0.45Co0.45Zr0.10)x(PZT)(1-x) nanocomposite films deposited in a mixed argon-oxygen atmosphere. The observed G(x, f, T) dependences for the films on the dielectric side of the insulator-metal transition demonstrated the negative capacitance (NC) effect that was maximal for the nanocomposites with 0.40 < x < 0.60, where the metallic FeCoZr nanoparticles were totally oxidized. The NC effect was explained by a specially developed model for the ac hopping conductance of the electrons between the fully oxidized nanoparticles embedded in the PZT matrix. In accordance with the model, under the determined conditions the observed structure of nanocomposites led to an increase in the hopping electron mean lifetime on nanoparticles and hence to the possibility of positive angles of the phase shifts θ and a proper NC (inductive-like contribution) effect.

Life history consequences of mammal sibling rivalry.

PubMed

Stockley, P; Parker, G A

2002-10-01

Mammal life history traits relating to growth and reproduction are extremely diverse. Sibling rivalry may contribute to selection pressures influencing this diversity, because individuals that are relatively large at birth typically have an advantage in competition for milk. However, selection for increased growth rate is likely to be constrained by kin selection and physiological costs. Here, we present and test a model examining the ESS (evolutionarily stable strategy) balance between these constraints and advantages associated with increased prenatal growth in mammal sibling rivalry. Predictions of the model are supported by results of comparative analyses for the Carnivora and Insectivora, which demonstrate an increase in prenatal growth rate with increasing intensity of postnatal scramble competition, and a decrease in postnatal growth rate relative to size at birth. Because increased prenatal growth rates are predicted to select for reduced gestation length under certain conditions, our study also indicates that sibling rivalry may contribute to selection pressures influencing variation in altriciality and precociality among mammals.

Matrix quantum mechanics on S1 /Z2

NASA Astrophysics Data System (ADS)

Betzios, P.; Gürsoy, U.; Papadoulaki, O.

2018-03-01

We study Matrix Quantum Mechanics on the Euclidean time orbifold S1 /Z2. Upon Wick rotation to Lorentzian time and taking the double-scaling limit this theory provides a toy model for a big-bang/big crunch universe in two dimensional non-critical string theory where the orbifold fixed points become cosmological singularities. We derive the MQM partition function both in the canonical and grand canonical ensemble in two different formulations and demonstrate agreement between them. We pinpoint the contribution of twisted states in both of these formulations either in terms of bi-local operators acting at the end-points of time or branch-cuts on the complex plane. We calculate, in the matrix model, the contribution of the twisted states to the torus level partition function explicitly and show that it precisely matches the world-sheet result, providing a non-trivial test of the proposed duality. Finally we discuss some interesting features of the partition function and the possibility of realising it as a τ-function of an integrable hierarchy.

The Ergonomic Program Implementation Continuum (EPIC): integration of health and safety--a process evaluation in the healthcare sector.

PubMed

Baumann, Andrea; Holness, D Linn; Norman, Patrica; Idriss-Wheeler, Dina; Boucher, Patricia

2012-07-01

This article presents a health and safety intervention model and the use of process evaluation to assess a participatory ergonomic intervention. The effectiveness of the Ergonomic Program Implementation Continuum (EPIC) was assessed at six healthcare pilot sites in Ontario, Canada. The model provided a framework to demonstrate evaluation findings. Participants reported that EPIC was thorough and identified improvements related to its use. Participants believed the program contributed to advancing an organizational culture of safety (COS). Main barriers to program uptake included resistance to change and need for adequate funding and resources. The dedication of organizational leaders and consultant coaches was identified as essential to the program's success. In terms of impact on industry, findings contribute to the evidence-based knowledge of health and safety interventions and support use of the framework for creating a robust infrastructure to advance organizational COS and link staff safety and wellness with patient safety in healthcare. Copyright © 2012 National Safety Council and Elsevier Ltd. All rights reserved.

Compact modeling of total ionizing dose and aging effects in MOS technologies

DOE PAGES

Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

2015-06-18

This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimentalmore » I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.« less

The Impact of Psychological Science on Policing in the United States: Procedural Justice, Legitimacy, and Effective Law Enforcement.

PubMed

Tyler, Tom R; Goff, Phillip Atiba; MacCoun, Robert J

2015-12-01

The May 2015 release of the report of the President's Task Force on 21st Century Policing highlighted a fundamental change in the issues dominating discussions about policing in America. That change has moved discussions away from a focus on what is legal or effective in crime control and toward a concern for how the actions of the police influence public trust and confidence in the police. This shift in discourse has been motivated by two factors-first, the recognition by public officials that increases in the professionalism of the police and dramatic declines in the rate of crime have not led to increases in police legitimacy, and second, greater awareness of the limits of the dominant coercive model of policing and of the benefits of an alternative and more consensual model based on public trust and confidence in the police and legal system. Psychological research has played an important role in legitimating this change in the way policymakers think about policing by demonstrating that perceived legitimacy shapes a set of law-related behaviors as well as or better than concerns about the risk of punishment. Those behaviors include compliance with the law and cooperation with legal authorities. These findings demonstrate that legal authorities gain by a focus on legitimacy. Psychological research has further contributed by articulating and demonstrating empirical support for a central role of procedural justice in shaping legitimacy, providing legal authorities with a clear road map of strategies for creating and maintaining public trust. Given evidence of the benefits of legitimacy and a set of guidelines concerning its antecedents, policymakers have increasingly focused on the question of public trust when considering issues in policing. The acceptance of a legitimacy-based consensual model of police authority building on theories and research studies originating within psychology illustrates how psychology can contribute to the development of evidence-based policies in the field of criminal law. © The Author(s) 2015.

Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome

PubMed Central

Nomura, Toshihiro; Zhu, Yiwen; Remmers, Christine L.; Xu, Jian; Nicholson, Daniel A.

2017-01-01

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS. SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS. PMID:29038238

Demonstrating the value of community-based ('citizen science') observations for catchment modelling and characterisation

NASA Astrophysics Data System (ADS)

Starkey, Eleanor; Parkin, Geoff; Birkinshaw, Stephen; Large, Andy; Quinn, Paul; Gibson, Ceri

2017-05-01

Despite there being well-established meteorological and hydrometric monitoring networks in the UK, many smaller catchments remain ungauged. This leaves a challenge for characterisation, modelling, forecasting and management activities. Here we demonstrate the value of community-based ('citizen science') observations for modelling and understanding catchment response as a contribution to catchment science. The scheme implemented within the 42 km2 Haltwhistle Burn catchment, a tributary of the River Tyne in northeast England, has harvested and used quantitative and qualitative observations from the public in a novel way to effectively capture spatial and temporal river response. Community-based rainfall, river level and flood observations have been successfully collected and quality-checked, and used to build and run a physically-based, spatially-distributed catchment model, SHETRAN. Model performance using different combinations of observations is tested against traditionally-derived hydrographs. Our results show how the local network of community-based observations alongside traditional sources of hydro-information supports characterisation of catchment response more accurately than using traditional observations alone over both spatial and temporal scales. We demonstrate that these community-derived datasets are most valuable during local flash flood events, particularly towards peak discharge. This information is often missed or poorly represented by ground-based gauges, or significantly underestimated by rainfall radar, as this study clearly demonstrates. While community-based observations are less valuable during prolonged and widespread floods, or over longer hydrological periods of interest, they can still ground-truth existing traditional sources of catchment data to increase confidence during characterisation and management activities. Involvement of the public in data collection activities also encourages wider community engagement, and provides important information for catchment management.

Functional Redundancy of MyD88-dependent Signaling Pathways in a Murine Model of Histidyl-tRNA Synthetase-induced Myositis

PubMed Central

Fernandez, Irina; Harlow, Lisa; Zang, Yunjuan; Liu-Bryan, Ru; Ridgway, William M.; Clemens, Paula R.; Ascherman, Dana P.

2013-01-01

We have previously shown that intramuscular administration of bacterially expressed murine histidyl-tRNA synthetase (HRS) triggers florid muscle inflammation (relative to appropriate control proteins) in various congenic strains of mice. Because severe disease develops even in the absence of adaptive immune responses to HRS, we sought to identify innate immune signaling components contributing to our model of HRS-induced myositis. In vitro stimulation assays demonstrated HRS-mediated activation of HEK293 cells transfected with either TLR2 or TLR4, revealing an excitatory capacity exceeding that of other bacterially expressed fusion proteins. Corresponding to this apparent functional redundancy of TLR signaling pathways, HRS immunization of B6.TLR2−/− and B6.TLR4−/− single knockout mice yielded significant lymphocytic infiltration of muscle tissue comparable to that produced in C57BL/6 WT mice. In contrast, concomitant elimination of TLR2 and TLR4 signaling in B6.TLR2−/−.TLR4−/− double knockout mice markedly reduced the severity of HRS-induced muscle inflammation. Complementary subfragment analysis demonstrated that amino acids 60–90 of HRS were absolutely required for in vitro as well as in vivo signaling via these MyD88-dependent TLR pathways—effects mediated, in part, through preferential binding of exogenous ligands capable of activating specific TLRs. Collectively, these experiments indicate that multiple MyD88-dependent signaling cascades contribute to this model of HRS-induced myositis, underscoring the antigenic versatility of HRS and confirming the importance of innate immunity in this system. PMID:23842751

Monochloramine Cometabolism by Mixed-Culture Nitrifiers ...

EPA Pesticide Factsheets

The current research investigated monochloramine cometabolism by nitrifying mixed cultures grown under drinking water relevant conditions and harvested from sand-packed reactors before conducting suspended growth batch kinetic experiments. Three batch reactors were used in each experiment: (1) a positive control to estimate ammonia kinetic parameters, (2) a negative control to account for abiotic reactions, and (3) a cometabolism reactor to estimate cometabolism kinetic constants. Kinetic parameters were estimated in AQUASIM with a simultaneous fit to all experimental data. Cometabolism kinetics were best described by a first order model. Monochloramine cometabolism kinetics were similar to those of ammonia metabolism, and monochloramine cometabolism was a significant loss mechanism (30% of the observed monochloramine loss). These results demonstrated that monochloramine cometabolism occurred in mixed cultures similar to those found in drinking water distribution systems; thus, cometabolism may be a significant contribution to monochloramine loss during nitrification episodes in drinking water distribution systems. The results demonstrated that monochloramine cometabolism occurred in mixed cultures similar to those found in drinking water distribution systems; thus, cometabolism may be a significant contribution to monochloramine loss during nitrification episodes in drinking water distribution systems.

Protease Activated Receptor-2 Contributes to Heart Failure

PubMed Central

Antoniak, Silvio; Sparkenbaugh, Erica M.; Tencati, Michael; Rojas, Mauricio; Mackman, Nigel; Pawlinski, Rafal

2013-01-01

Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. PMID:24312345

Source Apportionment and Risk Assessment of Emerging Contaminants: An Approach of Pharmaco-Signature in Water Systems

PubMed Central

Jiang, Jheng Jie; Lee, Chon Lin; Fang, Meng Der; Boyd, Kenneth G.; Gibb, Stuart W.

2015-01-01

This paper presents a methodology based on multivariate data analysis for characterizing potential source contributions of emerging contaminants (ECs) detected in 26 river water samples across multi-scape regions during dry and wet seasons. Based on this methodology, we unveil an approach toward potential source contributions of ECs, a concept we refer to as the “Pharmaco-signature.” Exploratory analysis of data points has been carried out by unsupervised pattern recognition (hierarchical cluster analysis, HCA) and receptor model (principal component analysis-multiple linear regression, PCA-MLR) in an attempt to demonstrate significant source contributions of ECs in different land-use zone. Robust cluster solutions grouped the database according to different EC profiles. PCA-MLR identified that 58.9% of the mean summed ECs were contributed by domestic impact, 9.7% by antibiotics application, and 31.4% by drug abuse. Diclofenac, ibuprofen, codeine, ampicillin, tetracycline, and erythromycin-H2O have significant pollution risk quotients (RQ>1), indicating potentially high risk to aquatic organisms in Taiwan. PMID:25874375

The role of electron heat flux in guide-field magnetic reconnection

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

Hesse, Michael; Kuznetsova, Masha; Birn, Joachim

2004-12-01

A combination of analytical theory and particle-in-cell simulations are employed in order to investigate the electron dynamics near and at the site of guide field magnetic reconnection. A detailed analysis of the contributions to the reconnection electric field shows that both bulk inertia and pressure-based quasiviscous processes are important for the electrons. Analytic scaling demonstrates that conventional approximations for the electron pressure tensor behavior in the dissipation region fail, and that heat flux contributions need to be accounted for. Based on the evolution equation of the heat flux three tensor, which is derived in this paper, an approximate form ofmore » the relevant heat flux contributions to the pressure tensor is developed, which reproduces the numerical modeling result reasonably well. Based on this approximation, it is possible to develop a scaling of the electron current layer in the central dissipation region. It is shown that the pressure tensor contributions become important at the scale length defined by the electron Larmor radius in the guide magnetic field.« less

The role of short-time intensity and envelope power for speech intelligibility and psychoacoustic masking.

PubMed

Biberger, Thomas; Ewert, Stephan D

2017-08-01

The generalized power spectrum model [GPSM; Biberger and Ewert (2016). J. Acoust. Soc. Am. 140, 1023-1038], combining the "classical" concept of the power-spectrum model (PSM) and the envelope power spectrum-model (EPSM), was demonstrated to account for several psychoacoustic and speech intelligibility (SI) experiments. The PSM path of the model uses long-time power signal-to-noise ratios (SNRs), while the EPSM path uses short-time envelope power SNRs. A systematic comparison of existing SI models for several spectro-temporal manipulations of speech maskers and gender combinations of target and masker speakers [Schubotz et al. (2016). J. Acoust. Soc. Am. 140, 524-540] showed the importance of short-time power features. Conversely, Jørgensen et al. [(2013). J. Acoust. Soc. Am. 134, 436-446] demonstrated a higher predictive power of short-time envelope power SNRs than power SNRs using reverberation and spectral subtraction. Here the GPSM was extended to utilize short-time power SNRs and was shown to account for all psychoacoustic and SI data of the three mentioned studies. The best processing strategy was to exclusively use either power or envelope-power SNRs, depending on the experimental task. By analyzing both domains, the suggested model might provide a useful tool for clarifying the contribution of amplitude modulation masking and energetic masking.

Astroparticle physics with solar neutrinos

PubMed Central

NAKAHATA, Masayuki

2011-01-01

Solar neutrino experiments observed fluxes smaller than the expectations from the standard solar model. This discrepancy is known as the “solar neutrino problem”. Flux measurements by Super-Kamiokande and SNO have demonstrated that the solar neutrino problem is due to neutrino oscillations. Combining the results of all solar neutrino experiments, parameters for solar neutrino oscillations are obtained. Correcting for the effect of neutrino oscillations, the observed neutrino fluxes are consistent with the prediction from the standard solar model. In this article, results of solar neutrino experiments are reviewed with detailed descriptions of what Kamiokande and Super-Kamiokande have contributed to the history of astroparticle physics with solar neutrino measurements. PMID:21558758

Dissociation of doubly charged clusters of lithium acetate: Asymmetric fission and breakdown of the liquid drop model: Dissociation of doubly charged clusters of lithium acetate

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

Shukla, Anil

2016-06-08

Unimolecular and collision-induced dissociation of doubly charged lithium acetate clusters, (CH3COOLi)nLi22+, demonstrated that Coulomb fission via charge separation is the dominant dissociation process with no contribution from the neutral evaporation processes for all such ions from the critical limit to larger cluster ions, although latter process have normally been observed in all earlier studies. These results are clearly in disagreement with the Rayleigh’s liquid drop model that has been used successfully to predict the critical size and explain the fragmentation behavior of multiply charged clusters.

Advances in Collaborative Filtering

NASA Astrophysics Data System (ADS)

Koren, Yehuda; Bell, Robert

The collaborative filtering (CF) approach to recommenders has recently enjoyed much interest and progress. The fact that it played a central role within the recently completed Netflix competition has contributed to its popularity. This chapter surveys the recent progress in the field. Matrix factorization techniques, which became a first choice for implementing CF, are described together with recent innovations. We also describe several extensions that bring competitive accuracy into neighborhood methods, which used to dominate the field. The chapter demonstrates how to utilize temporal models and implicit feedback to extend models accuracy. In passing, we include detailed descriptions of some the central methods developed for tackling the challenge of the Netflix Prize competition.

Self-sustained peristaltic waves: Explicit asymptotic solutions

NASA Astrophysics Data System (ADS)

Dudchenko, O. A.; Guria, G. Th.

2012-02-01

A simple nonlinear model for the coupled problem of fluid flow and contractile wall deformation is proposed to describe peristalsis. In the context of the model the ability of a transporting system to perform autonomous peristaltic pumping is interpreted as the ability to propagate sustained waves of wall deformation. Piecewise-linear approximations of nonlinear functions are used to analytically demonstrate the existence of traveling-wave solutions. Explicit formulas are derived which relate the speed of self-sustained peristaltic waves to the rheological properties of the transporting vessel and the transported fluid. The results may contribute to the development of diagnostic and therapeutic procedures for cases of peristaltic motility disorders.

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

Bartolo, Nicola; Guzzetti, Maria Chiara; Liguori, Michele

We investigate the potential for the LISA space-based interferometer to detect the stochastic gravitational wave background produced from different mechanisms during inflation. Focusing on well-motivated scenarios, we study the resulting contributions from particle production during inflation, inflationary spectator fields with varying speed of sound, effective field theories of inflation with specific patterns of symmetry breaking and models leading to the formation of primordial black holes. The projected sensitivities of LISA are used in a model-independent way for various detector designs and configurations. We demonstrate that LISA is able to probe these well-motivated inflationary scenarios beyond the irreducible vacuum tensor modesmore » expected from any inflationary background.« less

How Animal Models Inform Child and Adolescent Psychiatry

PubMed Central

Stevens, Hanna E.; Vaccarino, Flora M.

2015-01-01

Objective Every available approach should be utilized to advance the field of child and adolescent psychiatry. Biological systems are important for the behavioral problems of children. Close examination of non-human animals and the biology and behavior they share with humans is an approach that must be used to advance the clinical work of child psychiatry. Method We review here how model systems are used to contribute to significant insights into childhood psychiatric disorders. Model systems have not only demonstrated causality of risk factors for psychiatric pathophysiology but have also allowed child psychiatrists to think in different ways about risks for psychiatric disorders and multiple levels that might be the basis of recovery and prevention. Results We present examples of how animal systems are utilized to benefit child psychiatry, including through environmental, genetic, and acute biological manipulations. Animal model work has been essential in our current thinking about childhood disorders, including the importance of dose and timing of risk factors, specific features of risk factors that are significant, neurochemistry involved in brain functioning, molecular components of brain development, and the importance of cellular processes previously neglected in psychiatric theories. Conclusion Animal models have clear advantages and disadvantages that must both be considered for these systems to be useful. Coupled with increasingly sophisticated methods for investigating human behavior and biology, animal model systems will continue to make essential contributions to our field. PMID:25901771

Resonance-enhanced electron-impact excitation of Cu-like gold

NASA Astrophysics Data System (ADS)

Xia, L.; Zhang, C. Y.; Si, R.; Guo, X. L.; Chen, Z. B.; Yan, J.; Li, S.; Chen, C. Y.; Wang, K.

2017-09-01

Employing the independent-process and isolated-resonance approximations using distorted-waves (IPIRDW), we have performed a series of calculations of the resonance-enhanced electron-impact excitations (EIE) among 27 singly excited levels from the n ≤ 6 configurations of Cu-like gold (Au, Z = 79). Resonance excitation (RE) contributions from both the n = 4 → 4 - 7 and n = 3 → 4 core excitations have been considered. Our results demonstrate that RE contributions are significant and enhance the effective collision strengths (ϒ) of certain excitations by up to an order of magnitude at low temperature (106.1 K), and are still important at relatively high temperature (107.5 K). Results from test calculations of the resonance-enhanced EIE processes among 16 levels from the n ≤ 5 configurations using both the Dirac R-matrix (DRM) and IPIRDW approaches agree very well with each other. This means that the close-coupling effects are not important for this ion, and thus warrants the reliability of present resonance-enhanced EIE data among the 27 levels. The results from the collisional-radiative model (CRM) show that, at 3000 eV, near where Cu-like Au is most abundant, RE contributions have important effects (up to 25%) on the density diagnostic line intensity ratios, which are sensitive near 1020 cm-3. The present work is the first EIE research including RE contributions for Cu-like Au. Our EIE data are more accurate than previous results due to our consideration of RE contributions, and the data should be helpful for modeling and diagnosing a variety of plasmas.

About the coupling of turbulence closure models with averaged Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Vandromme, D.; Ha Minh, H.

1986-01-01

The MacCormack implicit predictor-corrector model (1981) for numerical solution of the coupled Navier-Stokes equations for turbulent flows is extended to nonconservative multiequation turbulence models, as well as the inclusion of second-order Reynolds stress turbulence closure. A scalar effective pressure turbulent contribution to the pressure field is defined to approximate the effects of the Reynolds stress in strongly sheared flows. The Jacobian matrices of the transport equations are diagonalized to reduce the required computer memory and run time. Techniques are defined for including turbulence in the diagonalization. Application of the method is demonstrated with solutions generated for transonic nozzle flow and for the interaction between a supersonic flat plate boundary layer and a 12 deg compression-expansion ramp.

Modeling of Transient Nectar Flow in Hummingbird Tongues

NASA Astrophysics Data System (ADS)

Rico-Guevara, Alejandro; Fan, Tai-Hsi; Rubega, Margaret

2015-11-01

We demonstrate that hummingbirds do not pick up floral nectar via capillary action. The long believed capillary rise models were mistaken and unable to predict the dynamic nectar intake process. Instead, hummingbird's tongue acts as an elastic micropump. Nectar is drawn into the tongue grooves during elastic expansion after the grooves are squeezed flat by the beak. The new model is compared with experimental data from high-speed videos of 18 species and tens of individuals of wild hummingbirds. Self-similarity and transitions of short-to-long time behaviours have been resolved for the nectar flow driven by expansive filling. The transient dynamics is characterized by the relative contributions of negative excess pressure and the apparent area modulus of the tongue grooves.

Science with the space-based interferometer eLISA. II: gravitational waves from cosmological phase transitions

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

Caprini, Chiara, E-mail: chiara.caprini@cea.fr; Hindmarsh, Mark; Huber, Stephan

We investigate the potential for the eLISA space-based interferometer to detect the stochastic gravitational wave background produced by strong first-order cosmological phase transitions. We discuss the resulting contributions from bubble collisions, magnetohydrodynamic turbulence, and sound waves to the stochastic background, and estimate the total corresponding signal predicted in gravitational waves. The projected sensitivity of eLISA to cosmological phase transitions is computed in a model-independent way for various detector designs and configurations. By applying these results to several specific models, we demonstrate that eLISA is able to probe many well-motivated scenarios beyond the Standard Model of particle physics predicting strong first-ordermore » cosmological phase transitions in the early Universe.« less

Toward a computational and experimental model of a poly-epoxy surface

NASA Astrophysics Data System (ADS)

Duguet, Thomas; Bessaguet, Camille; Aufray, Maëlenn; Esvan, Jérôme; Charvillat, Cédric; Vahlas, Constantin; Lacaze-Dufaure, Corinne

2015-01-01

A model poly-epoxy surface formed by the reaction of DGEBA and EDA is studied by the combination of experiments and DFT calculations. A special synthesis protocol is presented leading to the formation of a surface that is smooth (Sa < 1 nm), chemically homogeneous, and that presents a low-defect density (0.21 μm-2), as shown by AFM characterizations. Then, XPS is used for the determination of the elemental and functional groups' surface composition. DFT allows the identification and assignment of individual bonds contributions to the experimental 1s core-level peaks. Overall, we demonstrate that such a model sample is perfectly suitable for a use as a template for the study of poly-epoxy surface functionalization.

Unfolding an electronic integrate-and-fire circuit.

PubMed

Carrillo, Humberto; Hoppensteadt, Frank

2010-01-01

Many physical and biological phenomena involve accumulation and discharge processes that can occur on significantly different time scales. Models of these processes have contributed to understand excitability self-sustained oscillations and synchronization in arrays of oscillators. Integrate-and-fire (I+F) models are popular minimal fill-and-flush mathematical models. They are used in neuroscience to study spiking and phase locking in single neuron membranes, large scale neural networks, and in a variety of applications in physics and electrical engineering. We show here how the classical first-order I+F model fits into the theory of nonlinear oscillators of van der Pol type by demonstrating that a particular second-order oscillator having small parameters converges in a singular perturbation limit to the I+F model. In this sense, our study provides a novel unfolding of such models and it identifies a constructible electronic circuit that is closely related to I+F.

Intelligent multiagent coordination based on reinforcement hierarchical neuro-fuzzy models.

PubMed

Mendoza, Leonardo Forero; Vellasco, Marley; Figueiredo, Karla

2014-12-01

This paper presents the research and development of two hybrid neuro-fuzzy models for the hierarchical coordination of multiple intelligent agents. The main objective of the models is to have multiple agents interact intelligently with each other in complex systems. We developed two new models of coordination for intelligent multiagent systems, which integrates the Reinforcement Learning Hierarchical Neuro-Fuzzy model with two proposed coordination mechanisms: the MultiAgent Reinforcement Learning Hierarchical Neuro-Fuzzy with a market-driven coordination mechanism (MA-RL-HNFP-MD) and the MultiAgent Reinforcement Learning Hierarchical Neuro-Fuzzy with graph coordination (MA-RL-HNFP-CG). In order to evaluate the proposed models and verify the contribution of the proposed coordination mechanisms, two multiagent benchmark applications were developed: the pursuit game and the robot soccer simulation. The results obtained demonstrated that the proposed coordination mechanisms greatly improve the performance of the multiagent system when compared with other strategies.

Singlet model interference effects with high scale UV physics

DOE PAGES

Dawson, S.; Lewis, I. M.

2017-01-06

One of the simplest extensions of the Standard Model (SM) is the addition of a scalar gauge singlet, S . If S is not forbidden by a symmetry from mixing with the Standard Model Higgs boson, the mixing will generate non-SM rates for Higgs production and decays. Generally, there could also be unknown high energy physics that generates additional effective low energy interactions. We show that interference effects between the scalar resonance of the singlet model and the effective field theory (EFT) operators can have significant effects in the Higgs sector. Here, we examine a non- Z 2 symmetricmore » scalar singlet model and demonstrate that a fit to the 125 GeV Higgs boson couplings and to limits on high mass resonances, S , exhibit an interesting structure and possible large cancellations of effects between the resonance contribution and the new EFT interactions, that invalidate conclusions based on the renormalizable singlet model alone.« less

Development of a recursion RNG-based turbulence model

NASA Technical Reports Server (NTRS)

Zhou, YE; Vahala, George; Thangam, S.

1993-01-01

Reynolds stress closure models based on the recursion renormalization group theory are developed for the prediction of turbulent separated flows. The proposed model uses a finite wavenumber truncation scheme to account for the spectral distribution of energy. In particular, the model incorporates effects of both local and nonlocal interactions. The nonlocal interactions are shown to yield a contribution identical to that from the epsilon-renormalization group (RNG), while the local interactions introduce higher order dispersive effects. A formal analysis of the model is presented and its ability to accurately predict separated flows is analyzed from a combined theoretical and computational stand point. Turbulent flow past a backward facing step is chosen as a test case and the results obtained based on detailed computations demonstrate that the proposed recursion -RNG model with finite cut-off wavenumber can yield very good predictions for the backstep problem.

Analytical modeling for heat transfer in sheared flows of nanofluids.

PubMed

Ferrari, Claudio; Kaoui, Badr; L'vov, Victor S; Procaccia, Itamar; Rudenko, Oleksii; ten Thije Boonkkamp, J H M; Toschi, Federico

2012-07-01

We developed a model for the enhancement of the heat flux by spherical and elongated nanoparticles in sheared laminar flows of nanofluids. Besides the heat flux carried by the nanoparticles, the model accounts for the contribution of their rotation to the heat flux inside and outside the particles. The rotation of the nanoparticles has a twofold effect: it induces a fluid advection around the particle and it strongly influences the statistical distribution of particle orientations. These dynamical effects, which were not included in existing thermal models, are responsible for changing the thermal properties of flowing fluids as compared to quiescent fluids. The proposed model is strongly supported by extensive numerical simulations, demonstrating a potential increase of the heat flux far beyond the Maxwell-Garnett limit for the spherical nanoparticles. The road ahead, which should lead toward robust predictive models of heat flux enhancement, is discussed.

Perceptual control models of pursuit manual tracking demonstrate individual specificity and parameter consistency.

PubMed

Parker, Maximilian G; Tyson, Sarah F; Weightman, Andrew P; Abbott, Bruce; Emsley, Richard; Mansell, Warren

2017-11-01

Computational models that simulate individuals' movements in pursuit-tracking tasks have been used to elucidate mechanisms of human motor control. Whilst there is evidence that individuals demonstrate idiosyncratic control-tracking strategies, it remains unclear whether models can be sensitive to these idiosyncrasies. Perceptual control theory (PCT) provides a unique model architecture with an internally set reference value parameter, and can be optimized to fit an individual's tracking behavior. The current study investigated whether PCT models could show temporal stability and individual specificity over time. Twenty adults completed three blocks of 15 1-min, pursuit-tracking trials. Two blocks (training and post-training) were completed in one session and the third was completed after 1 week (follow-up). The target moved in a one-dimensional, pseudorandom pattern. PCT models were optimized to the training data using a least-mean-squares algorithm, and validated with data from post-training and follow-up. We found significant inter-individual variability (partial η 2 : .464-.697) and intra-individual consistency (Cronbach's α: .880-.976) in parameter estimates. Polynomial regression revealed that all model parameters, including the reference value parameter, contribute to simulation accuracy. Participants' tracking performances were significantly more accurately simulated by models developed from their own tracking data than by models developed from other participants' data. We conclude that PCT models can be optimized to simulate the performance of an individual and that the test-retest reliability of individual models is a necessary criterion for evaluating computational models of human performance.

Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

PubMed

Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

2015-04-01

The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

miR126-5p Downregulation Facilitates Axon Degeneration and NMJ Disruption via a Non-Cell-Autonomous Mechanism in ALS.

PubMed

Maimon, Roy; Ionescu, Ariel; Bonnie, Avichai; Sweetat, Sahar; Wald-Altman, Shane; Inbar, Shani; Gradus, Tal; Trotti, Davide; Weil, Miguel; Behar, Oded; Perlson, Eran

2018-06-13

Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in amyotrophic lateral sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR126-5p in presymptomatic ALS male mice models, and an increase in its targets: axon destabilizing Type 3 Semaphorins and their coreceptor Neuropilins. Using compartmentalized in vitro cocultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 blocking antibody. Finally, overexpressing miR126-5p is sufficient to transiently rescue axon degeneration and NMJ disruption both in vitro and in vivo Thus, we demonstrate a novel mechanism underlying ALS pathology, in which alterations in miR126-5p facilitate a non-cell-autonomous mechanism of motor neuron degeneration in ALS. SIGNIFICANCE STATEMENT Despite some progress, currently no effective treatment is available for amyotrophic lateral sclerosis (ALS). We suggest a novel regulatory role for miR126-5p in ALS and demonstrate, for the first time, a mechanism by which alterations in miR126-5p contribute to axon degeneration and NMJ disruption observed in ALS. We show that miR126-5p is altered in ALS models and that it can modulate Sema3 and NRP protein expression. Furthermore, NRP1 elevations in motor neurons and muscle secretion of Sema3A contribute to axon degeneration and NMJ disruption in ALS. Finally, overexpressing miR126-5p is sufficient to transiently rescue NMJ disruption and axon degeneration both in vitro and in vivo . Copyright © 2018 Maimon et al.

Accuracy Assessment of the Precise Point Positioning for Different Troposphere Models

NASA Astrophysics Data System (ADS)

Oguz Selbesoglu, Mahmut; Gurturk, Mert; Soycan, Metin

2016-04-01

This study investigates the accuracy and repeatability of PPP technique at different latitudes by using different troposphere delay models. Nine IGS stations were selected between 00-800 latitudes at northern hemisphere and southern hemisphere. Coordinates were obtained for 7 days at 1 hour intervals in summer and winter. At first, the coordinates were estimated by using Niell troposphere delay model with and without including north and east gradients in order to investigate the contribution of troposphere delay gradients to the positioning . Secondly, Saastamoinen model was used to eliminate troposphere path delays by using standart atmosphere parameters were extrapolated for all station levels. Finally, coordinates were estimated by using RTCA-MOPS empirical troposphere delay model. Results demonstrate that Niell troposphere delay model with horizontal gradients has better mean values of rms errors 0.09 % and 65 % than the Niell troposphere model without horizontal gradients and RTCA-MOPS model, respectively. Saastamoinen model mean values of rms errors were obtained approximately 4 times bigger than the Niell troposphere delay model with horizontal gradients.

The relative contributions of disease and insects in the decline of a long-lived tree: a stochastic demographic model of whitebark pine (Pinus albicaulis)

USGS Publications Warehouse

Jules, Erik S; Jackson, Jenell I.; van Mantgem, Phillip J.; Beck, Jennifer S.; Murray, Michael P.; Sahara, E. April

2016-01-01

Pathogens and insect pests have become increasingly important drivers of tree mortality in forested ecosystems. Unfortunately, understanding the relative contributions of multiple mortality agents to the population decline of trees is difficult, because it requires frequent measures of tree survival, growth, and recruitment, as well as the incidence of mortality agents. We present a population model of whitebark pine (Pinus albicaulis), a high-elevation tree undergoing rapid decline in western North America. The loss of whitebark pine is thought to be primarily due to an invasive pathogen (white pine blister rust; Cronartium ribicola) and a native insect (mountain pine beetle; Dendroctonus ponderosae). We utilized seven plots in Crater Lake National Park (Oregon, USA) where 1220 trees were surveyed for health and the presence of blister rust and beetle activity annually from 2003–2014, except 2008. We constructed size-based projection matrices for nine years and calculated the deterministic growth rate (λ) using an average matrix and the stochastic growth rate (λs) by simulation for whitebark pine in our study population. We then assessed the roles of blister rust and beetles by calculating λ and λsusing matrices in which we removed trees with blister rust and, separately, trees with beetles. We also conducted life-table response experiments (LTRE) to determine which demographic changes contributed most to differences in λ between ambient conditions and the two other scenarios. The model suggests that whitebark pine in our plots are currently declining 1.1% per year (λ = 0.9888, λs = 0.9899). Removing blister rust from the models resulted in almost no increase in growth (λ = 0.9916, λs = 0.9930), while removing beetles resulted in a larger increase in growth (λ = 1.0028, λs = 1.0045). The LTRE demonstrated that reductions in stasis of the three largest size classes due to beetles contributed most to the smaller λ in the ambient condition. Our work demonstrates a method for assessing the relative effects of different mortality agents on declining tree populations, and it shows that the effects of insects and pathogens can be markedly different from one another. In our study, beetle activity significantly reduced tree population growth while a pathogen had minimal effect, thus management actions to stabilize our study population will likely need to include reducing beetle activity.

Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling.

PubMed

Qosa, Hisham; Abuasal, Bilal S; Romero, Ignacio A; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N; Kaddoumi, Amal

2014-04-01

Alzheimer's disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected (125)I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of (125)I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of (125)I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in (125)I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes Aβ clearance across BBB. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differences in amyloid-β clearance across mouse and human blood-brain barrier models: Kinetic analysis and mechanistic modeling

PubMed Central

Qosa, Hisham; Abuasal, Bilal S.; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N.; Kaddoumi, Amal

2014-01-01

Alzheimer’s disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes Aβ clearance across BBB. PMID:24467845

Relative contributions of microbial and infrastructure heat at a crude oil-contaminated site

NASA Astrophysics Data System (ADS)

Warren, Ean; Bekins, Barbara A.

2018-04-01

Biodegradation of contaminants can increase the temperature in the subsurface due to heat generated from exothermic reactions, making temperature observations a potentially low-cost approach for determining microbial activity. For this technique to gain more widespread acceptance, it is necessary to better understand all the factors affecting the measured temperatures. Biodegradation has been occurring at a crude oil-contaminated site near Bemidji, Minnesota for 39 years, creating a quasi-steady-state plume of contaminants and degradation products. A model of subsurface heat generation and transport helps elucidate the contribution of microbial and infrastructure heating to observed temperature increases at this site. We created a steady-state, two-dimensional, heat transport model using previous-published parameter values for physical, chemical and biodegradation properties. Simulated temperature distributions closely match the observed average annual temperatures measured in the contaminated area at the site within less than 0.2 °C in the unsaturated zone and 0.4 °C in the saturated zone. The model results confirm that the observed subsurface heat from microbial activity is due primarily to methane oxidation in the unsaturated zone resulting in a 3.6 °C increase in average annual temperature. Another important source of subsurface heat is from the active, crude-oil pipelines crossing the site. The pipelines impact temperatures for a distance of 200 m and contribute half the heat. Model results show that not accounting for the heat from the pipelines leads to overestimating the degradation rates by a factor of 1.7, demonstrating the importance of identifying and quantifying all heat sources. The model results also highlighted a zone where previously unknown microbial activity is occurring at the site.

The current contribution of molecular factors to risk estimation in neuroblastoma patients.

PubMed

Berthold, F; Sahin, K; Hero, B; Christiansen, H; Gehring, M; Harms, D; Horz, S; Lampert, F; Schwab, M; Terpe, J

1997-10-01

The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

Relative contributions of microbial and infrastructure heat at a crude oil-contaminated site.

PubMed

Warren, Ean; Bekins, Barbara A

2018-04-01

Biodegradation of contaminants can increase the temperature in the subsurface due to heat generated from exothermic reactions, making temperature observations a potentially low-cost approach for determining microbial activity. For this technique to gain more widespread acceptance, it is necessary to better understand all the factors affecting the measured temperatures. Biodegradation has been occurring at a crude oil-contaminated site near Bemidji, Minnesota for 39 years, creating a quasi-steady-state plume of contaminants and degradation products. A model of subsurface heat generation and transport helps elucidate the contribution of microbial and infrastructure heating to observed temperature increases at this site. We created a steady-state, two-dimensional, heat transport model using previous-published parameter values for physical, chemical and biodegradation properties. Simulated temperature distributions closely match the observed average annual temperatures measured in the contaminated area at the site within less than 0.2 °C in the unsaturated zone and 0.4 °C in the saturated zone. The model results confirm that the observed subsurface heat from microbial activity is due primarily to methane oxidation in the unsaturated zone resulting in a 3.6 °C increase in average annual temperature. Another important source of subsurface heat is from the active, crude-oil pipelines crossing the site. The pipelines impact temperatures for a distance of 200 m and contribute half the heat. Model results show that not accounting for the heat from the pipelines leads to overestimating the degradation rates by a factor of 1.7, demonstrating the importance of identifying and quantifying all heat sources. The model results also highlighted a zone where previously unknown microbial activity is occurring at the site. Published by Elsevier B.V.

An information-theoretic approach to the modeling and analysis of whole-genome bisulfite sequencing data.

PubMed

Jenkinson, Garrett; Abante, Jordi; Feinberg, Andrew P; Goutsias, John

2018-03-07

DNA methylation is a stable form of epigenetic memory used by cells to control gene expression. Whole genome bisulfite sequencing (WGBS) has emerged as a gold-standard experimental technique for studying DNA methylation by producing high resolution genome-wide methylation profiles. Statistical modeling and analysis is employed to computationally extract and quantify information from these profiles in an effort to identify regions of the genome that demonstrate crucial or aberrant epigenetic behavior. However, the performance of most currently available methods for methylation analysis is hampered by their inability to directly account for statistical dependencies between neighboring methylation sites, thus ignoring significant information available in WGBS reads. We present a powerful information-theoretic approach for genome-wide modeling and analysis of WGBS data based on the 1D Ising model of statistical physics. This approach takes into account correlations in methylation by utilizing a joint probability model that encapsulates all information available in WGBS methylation reads and produces accurate results even when applied on single WGBS samples with low coverage. Using the Shannon entropy, our approach provides a rigorous quantification of methylation stochasticity in individual WGBS samples genome-wide. Furthermore, it utilizes the Jensen-Shannon distance to evaluate differences in methylation distributions between a test and a reference sample. Differential performance assessment using simulated and real human lung normal/cancer data demonstrate a clear superiority of our approach over DSS, a recently proposed method for WGBS data analysis. Critically, these results demonstrate that marginal methods become statistically invalid when correlations are present in the data. This contribution demonstrates clear benefits and the necessity of modeling joint probability distributions of methylation using the 1D Ising model of statistical physics and of quantifying methylation stochasticity using concepts from information theory. By employing this methodology, substantial improvement of DNA methylation analysis can be achieved by effectively taking into account the massive amount of statistical information available in WGBS data, which is largely ignored by existing methods.

The Propulsion Model of Creative Contributions Applied to the Arts and Letters.

ERIC Educational Resources Information Center

Sternberg, Robert J.; Kaufman, James C.; Pretz, Jean E.

2001-01-01

This article applies a propulsion model of creative contributions to the arts and letters. It opens with a general discussion of creative contributions and reviews existing models before describing the propulsion model and suggesting eight types of contributions that follow from this model. Examples illustrate use of the model in understanding…

Dynamic Stall of Finite Span Blades and its Control

NASA Astrophysics Data System (ADS)

Taylor, Keith; Leong, Chia; Amitay, Michael

2013-11-01

An experimental investigational study into a dynamically pitching s809 airfoil at a Reynolds number of 220,000 was conducted. Particle Image Velocimetry was employed to visualize and quantify the flow field around the airfoil. This investigation compares a 2-D configuration with 3-D configuration (i.e., a finite span blade). The difference in the flow field between these two configurations is explored, as the vibrations present in the 3-D configuration (due to the dynamic stall) may contribute to a different apparent flow field than classical results would suggest. In addition, a comparison between lift and drag coefficients, measured on the 2-D and 3-D configurations, is explored, demonstrating how time varying lift and drag forces oscillate at characteristic frequencies associated with the primary vibrational modes of the model. In addition, flow control is applied through the actuation of an array of synthetic jets located near the leading edge of the model, in order to effect changes in the flow field around the model, demonstrating how dynamic stall can be delayed or eliminated during dynamic conditions.

Influence of mom and dad: quantitative genetic models for maternal effects and genomic imprinting.

PubMed

Santure, Anna W; Spencer, Hamish G

2006-08-01

The expression of an imprinted gene is dependent on the sex of the parent it was inherited from, and as a result reciprocal heterozygotes may display different phenotypes. In contrast, maternal genetic terms arise when the phenotype of an offspring is influenced by the phenotype of its mother beyond the direct inheritance of alleles. Both maternal effects and imprinting may contribute to resemblance between offspring of the same mother. We demonstrate that two standard quantitative genetic models for deriving breeding values, population variances and covariances between relatives, are not equivalent when maternal genetic effects and imprinting are acting. Maternal and imprinting effects introduce both sex-dependent and generation-dependent effects that result in differences in the way additive and dominance effects are defined for the two approaches. We use a simple example to demonstrate that both imprinting and maternal genetic effects add extra terms to covariances between relatives and that model misspecification may over- or underestimate true covariances or lead to extremely variable parameter estimation. Thus, an understanding of various forms of parental effects is essential in correctly estimating quantitative genetic variance components.

Predicting microRNA-disease associations using label propagation based on linear neighborhood similarity.

PubMed

Li, Guanghui; Luo, Jiawei; Xiao, Qiu; Liang, Cheng; Ding, Pingjian

2018-05-12

Interactions between microRNAs (miRNAs) and diseases can yield important information for uncovering novel prognostic markers. Since experimental determination of disease-miRNA associations is time-consuming and costly, attention has been given to designing efficient and robust computational techniques for identifying undiscovered interactions. In this study, we present a label propagation model with linear neighborhood similarity, called LPLNS, to predict unobserved miRNA-disease associations. Additionally, a preprocessing step is performed to derive new interaction likelihood profiles that will contribute to the prediction since new miRNAs and diseases lack known associations. Our results demonstrate that the LPLNS model based on the known disease-miRNA associations could achieve impressive performance with an AUC of 0.9034. Furthermore, we observed that the LPLNS model based on new interaction likelihood profiles could improve the performance to an AUC of 0.9127. This was better than other comparable methods. In addition, case studies also demonstrated our method's outstanding performance for inferring undiscovered interactions between miRNAs and diseases, especially for novel diseases. Copyright © 2018. Published by Elsevier Inc.

Motion-adapted catheter navigation with real-time instantiation and improved visualisation

PubMed Central

Kwok, Ka-Wai; Wang, Lichao; Riga, Celia; Bicknell, Colin; Cheshire, Nicholas; Yang, Guang-Zhong

2014-01-01

The improvements to catheter manipulation by the use of robot-assisted catheter navigation for endovascular procedures include increased precision, stability of motion and operator comfort. However, navigation through the vasculature under fluoroscopic guidance is still challenging, mostly due to physiological motion and when tortuous vessels are involved. In this paper, we propose a motion-adaptive catheter navigation scheme based on shape modelling to compensate for these dynamic effects, permitting predictive and dynamic navigations. This allows for timed manipulations synchronised with the vascular motion. The technical contribution of the paper includes the following two aspects. Firstly, a dynamic shape modelling and real-time instantiation scheme based on sparse data obtained intra-operatively is proposed for improved visualisation of the 3D vasculature during endovascular intervention. Secondly, a reconstructed frontal view from the catheter tip using the derived dynamic model is used as an interventional aid to user guidance. To demonstrate the practical value of the proposed framework, a simulated aortic branch cannulation procedure is used with detailed user validation to demonstrate the improvement in navigation quality and efficiency. PMID:24744817

On the Direct Correlation between Gamma-Rays and PeV Neutrinos from Blazars

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

Gao, Shan; Pohl, Martin; Winter, Walter, E-mail: shan.gao@desy.de

We study the frequently used assumption in multi-messenger astrophysics that the gamma-ray and neutrino fluxes are directly connected because they are assumed to be produced by the same photohadronic production chain. An interesting candidate source for this test is the flat-spectrum radio quasar PKS B1424-418, which recently called attention to a potential correlation between an IceCube PeV neutrino event and its burst phase. We simulate both the multi-waveband photon and the neutrino emission from this source using a self-consistent radiation model. We demonstrate that a simple hadronic model cannot adequately describe the spectral energy distribution for this source, but amore » lepto-hadronic model with a subdominant hadronic component can reproduce the multi-waveband photon spectrum observed during various activity phases of the blazar. As a conclusion, up to about 0.3 neutrino events may coincide with the burst, which implies that the leptonic contribution dominates in the relevant energy band. We also demonstrate that the time-wise correlation between the neutrino event and burst phase is weak.« less

Unique Identification of Lee-Wick Gauge Bosons at Linear Colliders

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

Rizzo, Thomas G.

2007-12-14

Grinstein, O'Connell and Wise have recently presented an extension of the Standard Model (SM), based on the ideas of Lee and Wick (LW), which demonstrates an interesting way to remove the quadratically divergent contributions to the Higgs mass induced by radiative corrections. This model predicts the existence of negative-norm copies of the usual SM fields at the TeV scale with ghost-like propagators and negative decay widths, but with otherwise SM-like couplings. In earlier work, it was demonstrated that the LW states in the gauge boson sector of these models, though easy to observe, cannot be uniquely identified as such atmore » the LHC. In this paper, we address the issue of whether or not this problem can be resolved at an e{sup +}e{sup -} collider with a suitable center of mass energy range. We find that measurements of the cross section and the left-right polarization asymmetry associated with Bhabha scattering can lead to a unique identification of the neutral electroweak gauge bosons of the Lee-Wick type.« less

Modeling the environmental growth of Pseudogymnoascus destructans and its impact on the white-nose syndrome epidemic.

PubMed

Reynolds, Hannah T; Ingersoll, Tom; Barton, Hazel A

2015-04-01

White-nose syndrome (WNS) has had a devastating effect on North American bat populations. The causal agent of WNS is the fungal pathogen, Pseudogymnoascus destructans (Pd), which has been shown to persist in caves after the eradication of host populations. As nonpathogenic Pseudogymnoascus spp. display saprophytic growth and are among the most commonly isolated fungi from caves, we examined whether Pd could grow in cave sediments and the contribution such growth could have to WNS disease progression. We inoculated a range of diverse cave sediments and demonstrated the growth of Pd in all sediments tested. These data indicate that environmental growth of Pd could lead to the accumulation of spores above the estimated infection threshold for WNS, allowing environment-to-bat infection. The obtained growth parameters were then used in a susceptible-infected-susceptible mathematic model to determine the possible contribution of environmental Pd growth to WNS disease progression in a colony of little brown bats (Myotis lucifugus). This model suggests that the environmental growth of Pd would increase WNS infection rates, particularly in colonies experiencing longer hibernation periods or in hibernacula with high levels of organic detritus. The model also suggests that once introduced, environmental Pd growth would allow the persistence of this pathogen within infected hibernacula for decades, greatly compromising the success of bat reintroduction strategies. Together these data suggest that Pd is not reliant on its host for survival and is capable of environmental growth and amplification that could contribute to the rapid progression and long-term persistence of WNS in the hibernacula of threatened North American bats.

A dynamic auditory-cognitive system supports speech-in-noise perception in older adults.

PubMed

Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

2013-06-01

Understanding speech in noise is one of the most complex activities encountered in everyday life, relying on peripheral hearing, central auditory processing, and cognition. These abilities decline with age, and so older adults are often frustrated by a reduced ability to communicate effectively in noisy environments. Many studies have examined these factors independently; in the last decade, however, the idea of an auditory-cognitive system has emerged, recognizing the need to consider the processing of complex sounds in the context of dynamic neural circuits. Here, we used structural equation modeling to evaluate the interacting contributions of peripheral hearing, central processing, cognitive ability, and life experiences to understanding speech in noise. We recruited 120 older adults (ages 55-79) and evaluated their peripheral hearing status, cognitive skills, and central processing. We also collected demographic measures of life experiences, such as physical activity, intellectual engagement, and musical training. In our model, central processing and cognitive function predicted a significant proportion of variance in the ability to understand speech in noise. To a lesser extent, life experience predicted hearing-in-noise ability through modulation of brainstem function. Peripheral hearing levels did not significantly contribute to the model. Previous musical experience modulated the relative contributions of cognitive ability and lifestyle factors to hearing in noise. Our models demonstrate the complex interactions required to hear in noise and the importance of targeting cognitive function, lifestyle, and central auditory processing in the management of individuals who are having difficulty hearing in noise. Copyright © 2013 Elsevier B.V. All rights reserved.

Thrombopoietin treatment of one graft in a double cord blood transplant provides early platelet recovery while contributing to long-term engraftment in NSG mice.

PubMed

van der Garde, Mark; van Hensbergen, Yvette; Brand, Anneke; Slot, Manon C; de Graaf-Dijkstra, Alice; Mulder, Arend; Watt, Suzanne M; Zwaginga, Jaap Jan

2015-01-01

Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short- and long-term platelet reconstitution, can self-renew, and can give rise to myeloid- and lymphoid-biased HSCs. In previous studies, we have shown that transplantation of human CB CD34(+) cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immune-deficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34(+) cells have a competitive advantage or disadvantage over untreated human CB CD34(+) cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34(+) cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34(+) cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo.

Theory-based practice in a major medical centre.

PubMed

Alligood, Martha Raile

2011-11-01

This project was designed to improve care quality and nursing staff satisfaction. Nursing theory structures thought and action as demonstrated by evidence of improvement in complex health-care settings. Nursing administrators selected Modelling and Role-Modelling (MRM) for the theory-based practice goal in their strategic plan. An action research approach structured implementation of MRM in a 1-year consultation project in 2001-2002. Quality of health care improved according to national quality assessment ratings, as well as patient satisfaction and nurse satisfaction. Modelling and Role-Modelling demonstrated capacity to structure nursing thought and action in patient care in a major medical centre. Uniformity of patient care language was valued by nurses as well as by allied health providers who wished to learn the holistic MRM style of practice. The processes of MRM and action research contributed to project success. A positive health-care change project was carried out in a large medical centre with action research. Introducing MRM theory-based practice was a beneficial decision by nursing administration that improved care and nurse satisfaction. Attention to nursing practice stimulated career development among the nurses to pursue bachelors, masters, and doctoral degrees. © 2011 Blackwell Publishing Ltd.

Osteopontin in Systemic Sclerosis and its Role in Dermal Fibrosis

PubMed Central

Wu, Minghua; Schneider, Daniel J.; Mayes, Maureen D; Assassi, Shervin; Arnett, Frank C.; Tan, Filemon K.; Blackburn, Michael R.; Agarwal, Sandeep K.

2012-01-01

Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic properties. Previous reports demonstrate a role for OPN in wound healing and pulmonary fibrosis. Herein, we determined if OPN levels are increased in a large cohort of systemic sclerosis (SSc) patients and if OPN contributes dermal fibrosis. Plasma OPN levels were increased in SSc patients, including patients with limited and diffuse disease, compared to healthy controls. Immunohistology demonstrated OPN on fibroblast-like and inflammatory cells in SSc skin and lesional skin from mice in the bleomycin-induced dermal fibrosis model. OPN deficient (OPN−/−) mice developed less dermal fibrosis compared to wild-type mice in the bleomycin-induced dermal fibrosis model. Additional in vivo studies demonstrated that lesional skin from OPN−/− mice had fewer Mac-3+ cells, fewer myofibroblasts, decreased TGF-beta (TGFβ) and genes in the TGFβ pathway and decreased numbers of cells expressing phosphorylated SMAD2 (pSMAD) and ERK. In vitro, OPN−/− dermal fibroblasts had decreased migratory capacity but similar phosphorylation of SMAD2 by TGFβ. Finally, TGFβ production by OPN deficient macrophages was reduced compared to wild type. These data demonstrate an important role for OPN in the development of dermal fibrosis and suggest that OPN may be a novel therapeutic target in SSc. PMID:22402440

The large area crop inventory experiment: An experiment to demonstrate how space-age technology can contribute to solving critical problems here on earth

NASA Technical Reports Server (NTRS)

1977-01-01

The large area crop inventory experiment is being developed to predict crop production through satellite photographs. This experiment demonstrates how space age technology can contribute to solving practical problems of agriculture management.

Fatigue Failure of Space Shuttle Main Engine Turbine Blades

NASA Technical Reports Server (NTRS)

Swanson, Gregrory R.; Arakere, Nagaraj K.

2000-01-01

Experimental validation of finite element modeling of single crystal turbine blades is presented. Experimental results from uniaxial high cycle fatigue (HCF) test specimens and full scale Space Shuttle Main Engine test firings with the High Pressure Fuel Turbopump Alternate Turbopump (HPFTP/AT) provide the data used for the validation. The conclusions show the significant contribution of the crystal orientation within the blade on the resulting life of the component, that the analysis can predict this variation, and that experimental testing demonstrates it.

Optimal estimates of free energies from multistate nonequilibrium work data.

PubMed

Maragakis, Paul; Spichty, Martin; Karplus, Martin

2006-03-17

We derive the optimal estimates of the free energies of an arbitrary number of thermodynamic states from nonequilibrium work measurements; the work data are collected from forward and reverse switching processes and obey a fluctuation theorem. The maximum likelihood formulation properly reweights all pathways contributing to a free energy difference and is directly applicable to simulations and experiments. We demonstrate dramatic gains in efficiency by combining the analysis with parallel tempering simulations for alchemical mutations of model amino acids.

Aerodynamic repellency of impacting liquids

NASA Astrophysics Data System (ADS)

Gauthier, Anaïs; Bouillant, Ambre; Clanet, Christophe; Quéré, David

2018-05-01

Impacting liquids can be reflected by moving solid plates, provided the surface is fast enough. We describe and model here the threshold speed of bouncing, in particular as a function of the impact velocity of the incoming liquid. We also demonstrate that the aerodynamic force responsible for the nonwetting behavior induces an oblique rebound, which contributes to the liquid removal. In summary, this situation repels viscous, low surface tension drops of any size, all kinds of cases where repellency is impossible to achieve by other means.

Sex as a Biological Variable: Who, What, When, Why, and How.

PubMed

Bale, Tracy L; Epperson, C Neill

2017-01-01

The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience.

A New Paradigm for Diagnosing Contributions to Model Aerosol Forcing Error

NASA Astrophysics Data System (ADS)

Jones, A. L.; Feldman, D. R.; Freidenreich, S.; Paynter, D.; Ramaswamy, V.; Collins, W. D.; Pincus, R.

2017-12-01

A new paradigm in benchmark absorption-scattering radiative transfer is presented that enables both the globally averaged and spatially resolved testing of climate model radiation parameterizations in order to uncover persistent sources of biases in the aerosol instantaneous radiative effect (IRE). A proof of concept is demonstrated with the Geophysical Fluid Dynamics Laboratory AM4 and Community Earth System Model 1.2.2 climate models. Instead of prescribing atmospheric conditions and aerosols, as in prior intercomparisons, native snapshots of the atmospheric state and aerosol optical properties from the participating models are used as inputs to an accurate radiation solver to uncover model-relevant biases. These diagnostic results show that the models' aerosol IRE bias is of the same magnitude as the persistent range cited ( 1 W/m2) and also varies spatially and with intrinsic aerosol optical properties. The findings underscore the significance of native model error analysis and its dispositive ability to diagnose global biases, confirming its fundamental value for the Radiative Forcing Model Intercomparison Project.

Forecast of severe fever with thrombocytopenia syndrome incidence with meteorological factors.

PubMed

Sun, Ji-Min; Lu, Liang; Liu, Ke-Ke; Yang, Jun; Wu, Hai-Xia; Liu, Qi-Yong

2018-06-01

Severe fever with thrombocytopenia syndrome (SFTS) is emerging and some studies reported that SFTS incidence was associated with meteorological factors, while no report on SFTS forecast models was reported up to date. In this study, we constructed and compared three forecast models using autoregressive integrated moving average (ARIMA) model, negative binomial regression model (NBM), and quasi-Poisson generalized additive model (GAM). The dataset from 2011 to 2015 were used for model construction and the dataset in 2016 were used for external validity assessment. All the three models fitted the SFTS cases reasonably well during the training process and forecast process, while the NBM model forecasted better than other two models. Moreover, we demonstrated that temperature and relative humidity played key roles in explaining the temporal dynamics of SFTS occurrence. Our study contributes to better understanding of SFTS dynamics and provides predictive tools for the control and prevention of SFTS. Copyright © 2018 Elsevier B.V. All rights reserved.

Monte-Carlo-based uncertainty propagation with hierarchical models—a case study in dynamic torque

NASA Astrophysics Data System (ADS)

Klaus, Leonard; Eichstädt, Sascha

2018-04-01

For a dynamic calibration, a torque transducer is described by a mechanical model, and the corresponding model parameters are to be identified from measurement data. A measuring device for the primary calibration of dynamic torque, and a corresponding model-based calibration approach, have recently been developed at PTB. The complete mechanical model of the calibration set-up is very complex, and involves several calibration steps—making a straightforward implementation of a Monte Carlo uncertainty evaluation tedious. With this in mind, we here propose to separate the complete model into sub-models, with each sub-model being treated with individual experiments and analysis. The uncertainty evaluation for the overall model then has to combine the information from the sub-models in line with Supplement 2 of the Guide to the Expression of Uncertainty in Measurement. In this contribution, we demonstrate how to carry this out using the Monte Carlo method. The uncertainty evaluation involves various input quantities of different origin and the solution of a numerical optimisation problem.

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines

PubMed Central

Lopez, Cecilia M.; Yu, Peter Y.; Zhang, Xiaoli; Yilmaz, Ayse Selen; London, Cheryl A.

2018-01-01

Background Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. Methodology and principal findings RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. Conclusions These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA. PMID:29293555

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

PubMed

Lopez, Cecilia M; Yu, Peter Y; Zhang, Xiaoli; Yilmaz, Ayse Selen; London, Cheryl A; Fenger, Joelle M

2018-01-01

Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

Designing sustainable and economically attractive brownfield revitalization options using an integrated assessment model.

PubMed

Schädler, S; Morio, M; Bartke, S; Rohr-Zänker, R; Finkel, M

2011-03-01

We describe the development of an integrated assessment model which evaluates redevelopment options of large contaminated brownfields and we present the application of the model in a case study. Aiming to support efficient and sustainable revitalization and communication between stakeholders, the presented assessment model integrates three pinnacles of brownfield revitalization: (i) subsurface remediation and site preparation costs, (ii) market-oriented economic appraisal, and (iii) the expected contribution of planned future land use to sustainable community and regional development. For the assessment, focus is set on the early stage of the brownfield redevelopment process, which is characterized by limited data availability and by flexibility in land use planning and development scope. At this stage, revealing the consequences of adjustments and alterations in planning options can foster efficiency in communication between the involved parties and thereby facilitates the brownfield revitalization process. Results from the case-study application indicate that the integrated assessment provides help in the identification of land use options beneficial in both a sustainable and an economical sense. For the study site it is shown on one hand that brownfield redevelopment is not automatically in line with sustainable regional development, and on the other hand it is demonstrated that additional contributions to sustainability are not intrinsically tied to increased costs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Adolescent Depression: Stress and Reward Dysfunction

PubMed Central

Auerbach, Randy P.; Admon, Roee; Pizzagalli, Diego A.

2014-01-01

Adolescence is a peak period for the onset of depression, and it is also a time marked by substantial stress as well as neural development within the brain reward circuitry. In the current review, we provide a selective overview of current animal and human research investigating the relationship among reward processes, stress, and depression. Three separate, but related, etiological models examine the differential roles that stress may play with regard to reward dysfunction and adolescent depression. First, the reward mediation model suggests that acute and chronic stress contribute to reward deficits, which in turn, potentiate depressive symptoms and/or increase the risk for depression. Second, in line with the stress generation perspective, it is plausible that premorbid reward-related dysfunction generates stress, in particular interpersonal stress, which then leads to the manifestation of depressive symptoms. Last, consistent with a diathesis-stress model, the interaction between stress and premorbid reward dysfunction may contribute to the onset of depression. Given the equifinal nature of depression, these models could shed important light on different etiological pathways during adolescence, particularly as they may relate to understanding the heterogeneity of depression. To highlight the translational potential of these insights, a hypothetical case study is provided as means of demonstrating the importance of targeting reward dysfunction in both assessment and treatment of adolescent depression. PMID:24704785

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

DOE PAGES

McCluskey, Kevin; Baker, Scott E.

2017-02-17

As model organisms filamentous fungi have been important since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycetemore » filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Likewise, shared data has contributed to the success of model systems. Furthermore, the scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.« less

Diverse data supports the transition of filamentous fungal model organisms into the post-genomics era

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

McCluskey, Kevin; Baker, Scott E.

As model organisms filamentous fungi have been important since the beginning of modern biological inquiry and have benefitted from open data since the earliest genetic maps were shared. From early origins in simple Mendelian genetics of mating types, parasexual genetics of colony colour, and the foundational demonstration of the segregation of a nutritional requirement, the contribution of research systems utilising filamentous fungi has spanned the biochemical genetics era, through the molecular genetics era, and now are at the very foundation of diverse omics approaches to research and development. Fungal model organisms have come from most major taxonomic groups although Ascomycetemore » filamentous fungi have seen the most major sustained effort. In addition to the published material about filamentous fungi, shared molecular tools have found application in every area of fungal biology. Likewise, shared data has contributed to the success of model systems. Furthermore, the scale of data supporting research with filamentous fungi has grown by 10 to 12 orders of magnitude. From genetic to molecular maps, expression databases, and finally genome resources, the open and collaborative nature of the research communities has assured that the rising tide of data has lifted all of the research systems together.« less

Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model

PubMed Central

Li, Yungui; Li, Qingqing; Chen, Baoliang

2016-01-01

The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants. PMID:27009902

Making the MagIC (Magnetics Information Consortium) Web Application Accessible to New Users and Useful to Experts

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.

2017-12-01

Challenges are faced by both new and experienced users interested in contributing their data to community repositories, in data discovery, or engaged in potentially transformative science. The Magnetics Information Consortium (https://earthref.org/MagIC) has recently simplified its data model and developed a new containerized web application to reduce the friction in contributing, exploring, and combining valuable and complex datasets for the paleo-, geo-, and rock magnetic scientific community. The new data model more closely reflects the hierarchical workflow in paleomagnetic experiments to enable adequate annotation of scientific results and ensure reproducibility. The new open-source (https://github.com/earthref/MagIC) application includes an upload tool that is integrated with the data model to provide early data validation feedback and ease the friction of contributing and updating datasets. The search interface provides a powerful full text search of contributions indexed by ElasticSearch and a wide array of filters, including specific geographic and geological timescale filtering, to support both novice users exploring the database and experts interested in compiling new datasets with specific criteria across thousands of studies and millions of measurements. The datasets are not large, but they are complex, with many results from evolving experimental and analytical approaches. These data are also extremely valuable due to the cost in collecting or creating physical samples and the, often, destructive nature of the experiments. MagIC is heavily invested in encouraging young scientists as well as established labs to cultivate workflows that facilitate contributing their data in a consistent format. This eLightning presentation includes a live demonstration of the MagIC web application, developed as a configurable container hosting an isomorphic Meteor JavaScript application, MongoDB database, and ElasticSearch search engine. Visitors can explore the MagIC Database through maps and image or plot galleries or search and filter the raw measurements and their derived hierarchy of analytical interpretations.

Mapping Emissions that Contribute to Air Pollution Using Adjoint Sensitivity Analysis

NASA Astrophysics Data System (ADS)

Bastien, L. A. J.; Mcdonald, B. C.; Brown, N. J.; Harley, R.

2014-12-01

The adjoint of the Community Multiscale Air Quality model (CMAQ) is used to map emissions that contribute to air pollution at receptors of interest. Adjoint tools provide an efficient way to calculate the sensitivity of a model response to a large number of model inputs, a task that would require thousands of simulations using a more traditional forward sensitivity approach. Initial applications of this technique, demonstrated here, are to benzene and directly-emitted diesel particulate matter, for which atmospheric reactions are neglected. Emissions of these pollutants are strongly influenced by light-duty gasoline vehicles and heavy-duty diesel trucks, respectively. We study air quality responses in three receptor areas where populations have been identified as especially susceptible to, and adversely affected by air pollution. Population-weighted air basin-wide responses for each pollutant are also evaluated for the entire San Francisco Bay area. High-resolution (1 km horizontal grid) emission inventories have been developed for on-road motor vehicle emission sources, based on observed traffic count data. Emission estimates represent diurnal, day of week, and seasonal variations of on-road vehicle activity, with separate descriptions for gasoline and diesel sources. Emissions that contribute to air pollution at each receptor have been mapped in space and time using the adjoint method. Effects on air quality of both relative (multiplicative) and absolute (additive) perturbations to underlying emission inventories are analyzed. The contributions of local versus upwind sources to air quality in each receptor area are quantified, and weekday/weekend and seasonal variations in the influence of emissions from upwind areas are investigated. The contribution of local sources to the total air pollution burden within the receptor areas increases from about 40% in the summer to about 50% in the winter due to increased atmospheric stagnation. The effectiveness of control strategies based on region-wide exposure metrics is compared with strategies that focus on improving air quality at specific receptors.

Introduction to the Special Issue on Neuropsychology Practices in Integrated Care Teams.

PubMed

Festa, Joanne R

2018-05-01

This special issue on neuropsychology practices in integrated healthcare teams demonstrates how neuropsychologists have transformed their practices in an evolving healthcare landscape. These contributions are an overview of the many ways in which neuropsychologists function in integrated care teams. The experiences of integrated neuropsychologists serve as a model for those seeking new practice opportunities by providing highly practical, clinically relevant information. Included in this volume are articles on education and reimbursement issues, information about clinical practices that address diagnostic issues, prognostics and clinical management, as well as surgical treatment planning and outcome prediction. Authors highlight the value of their services, their contribution to improving team and patient communication, as well as the biopsychosocial understanding of the patient. Several unexpected challenges are detailed among the pearls and pitfalls of these practices.

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

PubMed Central

Torossian, Frédéric; Guerton, Bernadette; Anginot, Adrienne; Alexander, Kylie A.; Desterke, Christophe; Soave, Sabrina; Tseng, Hsu-Wen; Arouche, Nassim; Boutin, Laetitia; Kulina, Irina; Salga, Marjorie; Jose, Beulah; Pettit, Allison R.; Clay, Denis; Vlachos, Erica; Genet, Guillaume; Debaud, Charlotte; Denormandie, Philippe; Genet, François; Sims, Natalie A.; Banzet, Sébastien; Levesque, Jean-Pierre; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2017-01-01

Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury–induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad. PMID:29093266

Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferin.

PubMed

Rivera, Dagmar García; Balmaseda, Ivones Hernández; León, Alina Alvarez; Hernández, Belkis Cancio; Montiel, Lucía Márquez; Garrido, Gabino Garrido; Cuzzocrea, Salvatore; Hernández, René Delgado

2006-03-01

Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract.

Demonstration of successful malaria forecasts for Botswana using an operational seasonal climate model

NASA Astrophysics Data System (ADS)

MacLeod, Dave A.; Jones, Anne; Di Giuseppe, Francesca; Caminade, Cyril; Morse, Andrew P.

2015-04-01

The severity and timing of seasonal malaria epidemics is strongly linked with temperature and rainfall. Advance warning of meteorological conditions from seasonal climate models can therefore potentially anticipate unusually strong epidemic events, building resilience and adapting to possible changes in the frequency of such events. Here we present validation of a process-based, dynamic malaria model driven by hindcasts from a state-of-the-art seasonal climate model from the European Centre for Medium-Range Weather Forecasts. We validate the climate and malaria models against observed meteorological and incidence data for Botswana over the period 1982-2006 the longest record of observed incidence data which has been used to validate a modeling system of this kind. We consider the impact of climate model biases, the relationship between climate and epidemiological predictability and the potential for skillful malaria forecasts. Forecast skill is demonstrated for upper tercile malaria incidence for the Botswana malaria season (January-May), using forecasts issued at the start of November; the forecast system anticipates six out of the seven upper tercile malaria seasons in the observational period. The length of the validation time series gives confidence in the conclusion that it is possible to make reliable forecasts of seasonal malaria risk, forming a key part of a health early warning system for Botswana and contributing to efforts to adapt to climate change.

DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias

PubMed Central

Casorelli, Ida; Bossa, Cecilia; Bignami, Margherita

2012-01-01

Most antitumour therapies damage tumour cell DNA either directly or indirectly. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum, ataxia-telangiectasia and Fanconi anemia. Notably, DNA damage responses, and particularly DNA repair, influence the outcome of therapy. Because DNA repair normally excises lethal DNA lesions, it is intuitive that efficient repair will contribute to intrinsic drug resistance. Unexpectedly, a paradoxical relationship between DNA mismatch repair and drug sensitivity has been revealed by model studies in cell lines. This suggests that connections between DNA repair mechanism efficiency and tumour therapy might be more complex. Here, we review the evidence for the contribution of carcinogenic properties of several drugs as well as of alterations in specific mechanisms involved in drug-induced DNA damage response and repair in the pathogenesis of therapy-related cancers. PMID:23066388

Mitochondrial protein hyperacetylation in the failing heart

PubMed Central

Horton, Julie L.; Martin, Ola J.; Lai, Ling; Richards, Alicia L.; Vega, Rick B.; Leone, Teresa C.; Pagliarini, David J.; Muoio, Deborah M.; Bedi, Kenneth C.; Coon, Joshua J.

2016-01-01

Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II–driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure. PMID:26998524

Mitochondrial protein hyperacetylation in the failing heart.

PubMed

Horton, Julie L; Martin, Ola J; Lai, Ling; Riley, Nicholas M; Richards, Alicia L; Vega, Rick B; Leone, Teresa C; Pagliarini, David J; Muoio, Deborah M; Bedi, Kenneth C; Margulies, Kenneth B; Coon, Joshua J; Kelly, Daniel P

2016-02-01

Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II-driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure.

Predictors of adherence with self-care guidelines among persons with type 2 diabetes: results from a logistic regression tree analysis.

PubMed

Yamashita, Takashi; Kart, Cary S; Noe, Douglas A

2012-12-01

Type 2 diabetes is known to contribute to health disparities in the U.S. and failure to adhere to recommended self-care behaviors is a contributing factor. Intervention programs face difficulties as a result of patient diversity and limited resources. With data from the 2005 Behavioral Risk Factor Surveillance System, this study employs a logistic regression tree algorithm to identify characteristics of sub-populations with type 2 diabetes according to their reported frequency of adherence to four recommended diabetes self-care behaviors including blood glucose monitoring, foot examination, eye examination and HbA1c testing. Using Andersen's health behavior model, need factors appear to dominate the definition of which sub-groups were at greatest risk for low as well as high adherence. Findings demonstrate the utility of easily interpreted tree diagrams to design specific culturally appropriate intervention programs targeting sub-populations of diabetes patients who need to improve their self-care behaviors. Limitations and contributions of the study are discussed.

Global warming hiatus contributed to the increased occurrence of intense tropical cyclones in the coastal regions along East Asia.

PubMed

Zhao, Jiuwei; Zhan, Ruifen; Wang, Yuqing

2018-04-16

The recent global warming hiatus (GWH) was characterized by a La Niña-like cooling in the tropical Eastern Pacific accompanied with the Indian Ocean and the tropical Atlantic Ocean warming. Here we show that the recent GWH contributed significantly to the increased occurrence of intense tropical cyclones in the coastal regions along East Asia since 1998. The GWH associated sea surface temperature anomalies triggered a pair of anomalous cyclonic and anticyclonic circulations and equatorial easterly anomalies over the Northwest Pacific, which favored TC genesis and intensification over the western Northwest Pacific but suppressed TC genesis and intensification over the southeastern Northwest Pacific due to increased vertical wind shear and anticyclonic circulation anomalies. Results from atmospheric general circulation model experiments demonstrate that the Pacific La Niña-like cooling dominated the Indian Ocean and the tropical Atlantic Ocean warming in contributing to the observed GWH-related anomalous atmospheric circulation over the Northwest Pacific.

Serotonin, atherosclerosis, and collateral vessel spasm

NASA Technical Reports Server (NTRS)

Hollenberg, N.

1988-01-01

Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.

A tank-to-wheel analysis tool for energy and emissions studies in road vehicles.

PubMed

Silva, C M; Gonçalves, G A; Farias, T L; Mendes-Lopes, J M C

2006-08-15

Currently, oil based fuels are the primary energy source of road transport. The growing need for oil independence and CO(2) mitigation has lead to the increasing importance of alternative fuel usage. CO(2) is produced not only as the fuel is used in the vehicle (tank-to-wheel contribution), but also upstream, from the fuel extraction to the refueling station (well-to-tank contribution), and the life cycle of the fuel production (well-to-wheel contribution) must be considered in order to analyse the global impact of the fuel utilization. A road vehicle tank-to-wheel analysis tool that may be integrated with well-to-tank models was developed in the present study. The integration in a demonstration case study allowed to perform a life cycle assessment concerning the utilization of diesel and natural gas fuels in a specific network line of a bus transit company operating in the city of Porto, Portugal.

Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

PubMed Central

McGill, Jodi L.; Rusk, Rachel A.; Guerra-Maupome, Mariana; Briggs, Robert E.; Sacco, Randy E.

2016-01-01

Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and γδ T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing γδ T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and γδ T cells in the pathogenesis of BRDC. PMID:26942409

Murine models of osteosarcoma: A piece of the translational puzzle.

PubMed

Walia, Mannu K; Castillo-Tandazo, Wilson; Mutsaers, Anthony J; Martin, Thomas John; Walkley, Carl R

2018-06-01

Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. While our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targets, in addition to testing the role of additional mutations in vivo. Most recently these models have begun to be used for discovery based approaches and screens, which hold significant promise in furthering our understanding of the genetic and therapeutic sensitivities of OS. In this review, we discuss the mouse models of OS that have been reported in the last 3-5 years and newly identified pathways from these studies. Finally, we discuss the preclinical utilization of the mouse models of OS for identifying and validating actionable targets to improve patient outcome. © 2017 Wiley Periodicals, Inc.

The Junior Faculty Laboratory: An Innovative Model of Peer Mentoring

PubMed Central

Johnson, Kimberly S.; Hastings, S. Nicole; Purser, Jama L; Whitson, Heather E

2013-01-01

Mentoring in academic medicine has been shown to contribute to the success of junior faculty, resulting in increased productivity, career satisfaction, and opportunities for networking. Although traditional dyadic mentoring, involving one senior faculty member and one junior protégé, is the dominant model for mentoring in the academic environment, there is increasing recognition that the sharing of knowledge, skills, and experiences among peers may also contribute to the career development of junior faculty. The authors describe the structure, activities, and outcomes of the Junior Faculty Laboratory (JFL), a self-organized, flexible, and dynamic peer mentoring model within the Duke University Center for the Study of Aging and Human Development. As an innovative mentoring model, JFL is entirely peer-driven and its activities are determined by the real-time needs of members. In contrast to some other peer mentoring models, JFL lacks senior faculty input or a structured curriculum, members are multidisciplinary, meeting times are project-driven rather than preset, and participation in collaborative projects is optional based on the interests and needs of group members. Additionally, JFL was not formed as a substitute for, but as a complement to the dyadic mentoring relationships enjoyed by its members. The model, now in its fifth year, has demonstrated success and sustainability. The authors present the JFL as an innovative, mentoring model that can be reproduced by other junior faculty seeking to foster collegial relationships with peers while simultaneously enhancing their career development. PMID:22030756

The Junior Faculty Laboratory: an innovative model of peer mentoring.

PubMed

Johnson, Kimberly S; Hastings, S Nicole; Purser, Jama L; Whitson, Heather E

2011-12-01

Mentoring in academic medicine has been shown to contribute to the success of junior faculty, resulting in increased productivity, career satisfaction, and opportunities for networking. Although traditional dyadic mentoring, involving one senior faculty member and one junior protégé, is the dominant model for mentoring in the academic environment, there is increasing recognition that the sharing of knowledge, skills, and experiences among peers may also contribute to the career development of junior faculty. The authors describe the structure, activities, and outcomes of the Junior Faculty Laboratory (JFL), a self-organized, flexible, and dynamic peer-mentoring model within the Duke University Center for the Study of Aging and Human Development. As an innovative mentoring model, JFL is entirely peer driven, and its activities are determined by the real-time needs of members. In contrast to some other peer-mentoring models, JFL lacks senior faculty input or a structured curriculum, members are multidisciplinary, meeting times are project driven rather than preset, and participation in collaborative projects is optional based on the interests and needs of group members. Additionally, JFL was not formed as a substitute for, but as a complement to, the dyadic mentoring relationships enjoyed by its members. The model, now in its fifth year, has demonstrated success and sustainability. The authors present the JFL as an innovative, mentoring model that can be reproduced by other junior faculty seeking to foster collegial relationships with peers while simultaneously enhancing their career development.

A hybrid modeling with data assimilation to evaluate human exposure level

NASA Astrophysics Data System (ADS)

Koo, Y. S.; Cheong, H. K.; Choi, D.; Kim, A. L.; Yun, H. Y.

2015-12-01

Exposure models are designed to better represent human contact with PM (Particulate Matter) and other air pollutants such as CO, SO2, O3, and NO2. The exposure concentrations of the air pollutants to human are determined by global and regional long range transport of global and regional scales from Europe and China as well as local emissions from urban and road vehicle sources. To assess the exposure level in detail, the multiple scale influence from background to local sources should be considered. A hybrid air quality modeling methodology combing a grid-based chemical transport model with a local plume dispersion model was used to provide spatially and temporally resolved air quality concentration for human exposure levels in Korea. In the hybrid modeling approach, concentrations from a grid-based chemical transport model and a local plume dispersion model are added to provide contributions from photochemical interactions, long-range (regional) transport and local-scale dispersion. The CAMx (Comprehensive Air quality Model with Extensions was used for the background concentrations from anthropogenic and natural emissions in East Asia including Korea while the road dispersion by vehicle emission was calculated by CALPUFF model. The total exposure level of the pollutants was finally assessed by summing the background and road contributions. In the hybrid modeling, the data assimilation method based on the optimal interpolation was applied to overcome the discrepancies between the model predicted concentrations and observations. The air quality data from the air quality monitoring stations in Korea. The spatial resolution of the hybrid model was 50m for the Seoul Metropolitan Ares. This example clearly demonstrates that the exposure level could be estimated to the fine scale for the exposure assessment by using the hybrid modeling approach with data assimilation.

Applications of information theory, genetic algorithms, and neural models to predict oil flow

NASA Astrophysics Data System (ADS)

Ludwig, Oswaldo; Nunes, Urbano; Araújo, Rui; Schnitman, Leizer; Lepikson, Herman Augusto

2009-07-01

This work introduces a new information-theoretic methodology for choosing variables and their time lags in a prediction setting, particularly when neural networks are used in non-linear modeling. The first contribution of this work is the Cross Entropy Function (XEF) proposed to select input variables and their lags in order to compose the input vector of black-box prediction models. The proposed XEF method is more appropriate than the usually applied Cross Correlation Function (XCF) when the relationship among the input and output signals comes from a non-linear dynamic system. The second contribution is a method that minimizes the Joint Conditional Entropy (JCE) between the input and output variables by means of a Genetic Algorithm (GA). The aim is to take into account the dependence among the input variables when selecting the most appropriate set of inputs for a prediction problem. In short, theses methods can be used to assist the selection of input training data that have the necessary information to predict the target data. The proposed methods are applied to a petroleum engineering problem; predicting oil production. Experimental results obtained with a real-world dataset are presented demonstrating the feasibility and effectiveness of the method.

A Tale of Two Trails: Exploring Different Paths to Success

PubMed Central

Walker, Jennifer G.; Evenson, Kelly R.; Davis, William J.; Bors, Philip; Rodríguez, Daniel A.

2016-01-01

Background This comparative case study investigates 2 successful community trail initiatives, using the Active Living By Design (ALBD) Community Action Model as an analytical framework. The model includes 5 strategies: preparation, promotion, programs, policy, and physical projects. Methods Key stakeholders at 2 sites participated in in-depth interviews (N = 14). Data were analyzed for content using Atlas Ti and grouped according to the 5 strategies. Results Preparation Securing trail resources was challenging, but shared responsibilities facilitated trail development. Promotions The initiatives demonstrated minimal physical activity encouragement strategies. Programs Community stakeholders did not coordinate programmatic opportunities for routine physical activity. Policy Trails’ inclusion in regional greenway master plans contributed to trail funding and development. Policies that were formally institutionalized and enforced led to more consistent trail construction and safer conditions for users. Physical Projects Consistent standards for way finding signage and design safety features enhanced trail usability and safety. Conclusions Communities with different levels of government support contributed unique lessons to inform best practices of trail initiatives. This study revealed a disparity between trail development and use-encouragement strategies, which may limit trails’ impact on physical activity. The ALBD Community Action Model provided a viable framework to structure cross-disciplinary community trail initiatives. PMID:21597125

Modeling triple-negative breast cancer heterogeneity: effects of stromal macrophages, fibroblasts and tumor vasculature.

PubMed

Norton, Kerri-Ann; Jin, Kideok; Popel, Aleksander S

2018-05-08

A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates. Copyright © 2018. Published by Elsevier Ltd.

Validation of oxygen extraction fraction measurement by qBOLD technique.

PubMed

He, Xiang; Zhu, Mingming; Yablonskiy, Dmitriy A

2008-10-01

Measurement of brain tissue oxygen extraction fraction (OEF) in both baseline and functionally activated states can provide important information on brain functioning in health and disease. The recently proposed quantitative BOLD (qBOLD) technique is MRI-based and provides a regional in vivo OEF measurement (He and Yablonskiy, MRM 2007, 57:115-126). It is based on a previously developed analytical BOLD model and incorporates prior knowledge about the brain tissue composition including the contributions from grey matter, white matter, cerebrospinal fluid, interstitial fluid and intravascular blood. The qBOLD model also allows for the separation of contributions to the BOLD signal from OEF and the deoxyhemoglobin containing blood volume (DBV). The objective of this study is to validate OEF measurements provided by the qBOLD approach. To this end we use a rat model and compare qBOLD OEF measurements against direct measurements of the blood oxygenation level obtained from venous blood drawn directly from the superior sagittal sinus. The cerebral venous oxygenation level of the rat was manipulated by utilizing different anestheisa methods. The study demonstrates a very good agreement between qBOLD approach and direct measurements. (c) 2008 Wiley-Liss, Inc.

Phase-field model with plastic flow for grain growth in nanocrystalline material

NASA Astrophysics Data System (ADS)

Steinbach, Ingo; Song, Xiaoyan; Hartmaier, Alexander

2010-01-01

A phase-field model is presented which considers the accumulation of structural defects in grain boundaries by an isotropic eigenstrain associated with the grain boundaries. It is demonstrated that the elastic energy caused by dilatation of the grain boundary with respect to the bulk crystal contributes largely to the grain boundary energy. The sign of this contribution can be both positive and negative dependent on the local stress state in the grain boundary. Self-diffusion of atoms is taken into account to relax the stress caused by the dilatation of the grain boundary. Application of the model to discontinuous grain growth in pure nanocrystalline cobalt material is presented. Linear grain growth is found in the nanocrystalline state, which is explained by the interpretation of grain boundary motion as a diffusive process defining an upper limit of the grain boundary velocity independent of the grain boundary curvature but dependent on temperature. The transition to regular grain growth at a critical temperature, as observed experimentally, is explained by the drop of theoretical grain boundary velocity due to its mean curvature during coarsening of the nanograin structure below the maximum velocity.

Why Medical Informatics (still) Needs Cognitive and Social Sciences.

PubMed

Declerck, G; Aimé, X

2013-01-01

To summarize current excellent medical informatics research in the field of human factors and organizational issues. Using PubMed, a total of 3,024 papers were selected from 17 journals. The papers were evaluated on the basis of their title, keywords, and abstract, using several exclusion and inclusion criteria. 15 preselected papers were carefully evaluated by six referees using a standard evaluation grid. Six best papers were selected exemplifying the central role cognitive and social sciences can play in medical informatics research. Among other contributions, those studies: (i) make use of the distributed cognition paradigm to model and understand clinical care situations; (ii) take into account organizational issues to analyse the impact of HIT on information exchange and coordination processes; (iii) illustrate how models and empirical data from cognitive psychology can be used in medical informatics; and (iv) highlight the need of qualitative studies to analyze the unexpected side effects of HIT on cognitive and work processes. The selected papers demonstrate that paradigms, methodologies, models, and results from cognitive and social sciences can help to bridge the gap between HIT and end users, and contribute to limit adoption failures that are reported regularly.

5 CFR 890.1306 - Government premium contributions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Government premium contributions. 890... Health Benefits Program Demonstration Project § 890.1306 Government premium contributions. The Secretary of Defense is responsible for the government contribution for enrolled eligible beneficiaries and...

5 CFR 890.1306 - Government premium contributions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Government premium contributions. 890... Health Benefits Program Demonstration Project § 890.1306 Government premium contributions. The Secretary of Defense is responsible for the government contribution for enrolled eligible beneficiaries and...

Fear-avoidance beliefs and temporal summation of evoked thermal pain influence self-report of disability in patients with chronic low back pain.

PubMed

George, Steven Z; Wittmer, Virgil T; Fillingim, Roger B; Robinson, Michael E

2006-03-01

Quantitative sensory testing has demonstrated a promising link between experimentally determined pain sensitivity and clinical pain. However, previous studies of quantitative sensory testing have not routinely considered the important influence of psychological factors on clinical pain. This study investigated whether measures of thermal pain sensitivity (temporal summation, first pulse response, and tolerance) contributed to clinical pain reports for patients with chronic low back pain, after controlling for depression or fear-avoidance beliefs about work. Consecutive patients (n=27) with chronic low back pain were recruited from an interdisciplinary pain rehabilitation program in Jacksonville, FL. Patients completed validated self-report questionnaires for depression, fear-avoidance beliefs, clinical pain intensity, and clinical pain related disability. Patients also underwent quantitative sensory testing from previously described protocols to determine thermal pain sensitivity (temporal summation, first pulse response, and tolerance). Hierarchical regression models investigated the contribution of depression and thermal pain sensitivity to clinical pain intensity, and fear-avoidance beliefs and thermal pain sensitivity to clinical pain related disability. None of the measures of thermal pain sensitivity contributed to clinical pain intensity after controlling for depression. Temporal summation of evoked thermal pain significantly contributed to clinical pain disability after controlling for fear-avoidance beliefs about work. Measures of thermal pain sensitivity did not contribute to pain intensity, after controlling for depression. Fear-avoidance beliefs about work and temporal summation of evoked thermal pain significantly influenced pain related disability. These factors should be considered as potential outcome predictors for patients with work-related low back pain. This study supported the neuromatrix theory of pain for patients with CLBP, as cognitive-evaluative factor contributed to pain perception, and cognitive-evaluative and sensory-discriminative factors uniquely contributed to an action program in response to chronic pain. Future research will determine if a predictive model consisting of fear-avoidance beliefs and temporal summation of evoked thermal pain has predictive validity for determining clinical outcome in rehabilitation or vocational settings.

Differential Contribution of Bilateral Supplementary Motor Area to the Effective Connectivity Networks Induced by Task Conditions Using Dynamic Causal Modeling

PubMed Central

Tao, Zhongping; Zhang, Mu

2014-01-01

Abstract Functional imaging studies have indicated hemispheric asymmetry of activation in bilateral supplementary motor area (SMA) during unimanual motor tasks. However, the hemispherically special roles of bilateral SMAs on primary motor cortex (M1) in the effective connectivity networks (ECN) during lateralized tasks remain unclear. Aiming to study the differential contribution of bilateral SMAs during the motor execution and motor imagery tasks, and the hemispherically asymmetric patterns of ECN among regions involved, the present study used dynamic causal modeling to analyze the functional magnetic resonance imaging data of the unimanual motor execution/imagery tasks in 12 right-handed subjects. Our results demonstrated that distributions of network parameters underlying motor execution and motor imagery were significantly different. The variation was mainly induced by task condition modulations of intrinsic coupling. Particularly, regardless of the performing hand, the task input modulations of intrinsic coupling from the contralateral SMA to contralateral M1 were positive during motor execution, while varied to be negative during motor imagery. The results suggested that the inhibitive modulation suppressed the overt movement during motor imagery. In addition, the left SMA also helped accomplishing left hand tasks through task input modulation of left SMA→right SMA connection, implying that hemispheric recruitment occurred when performing nondominant hand tasks. The results specified differential and altered contributions of bilateral SMAs to the ECN during unimanual motor execution and motor imagery, and highlighted the contributions induced by the task input of motor execution/imagery. PMID:24606178

50 years of computer simulation of the human thermoregulatory system.

PubMed

Hensley, Daniel W; Mark, Andrew E; Abella, Jayvee R; Netscher, George M; Wissler, Eugene H; Diller, Kenneth R

2013-02-01

This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.

Figure-Ground Segmentation Using Factor Graphs

PubMed Central

Shen, Huiying; Coughlan, James; Ivanchenko, Volodymyr

2009-01-01

Foreground-background segmentation has recently been applied [26,12] to the detection and segmentation of specific objects or structures of interest from the background as an efficient alternative to techniques such as deformable templates [27]. We introduce a graphical model (i.e. Markov random field)-based formulation of structure-specific figure-ground segmentation based on simple geometric features extracted from an image, such as local configurations of linear features, that are characteristic of the desired figure structure. Our formulation is novel in that it is based on factor graphs, which are graphical models that encode interactions among arbitrary numbers of random variables. The ability of factor graphs to express interactions higher than pairwise order (the highest order encountered in most graphical models used in computer vision) is useful for modeling a variety of pattern recognition problems. In particular, we show how this property makes factor graphs a natural framework for performing grouping and segmentation, and demonstrate that the factor graph framework emerges naturally from a simple maximum entropy model of figure-ground segmentation. We cast our approach in a learning framework, in which the contributions of multiple grouping cues are learned from training data, and apply our framework to the problem of finding printed text in natural scenes. Experimental results are described, including a performance analysis that demonstrates the feasibility of the approach. PMID:20160994

Statistical label fusion with hierarchical performance models

PubMed Central

Asman, Andrew J.; Dagley, Alexander S.; Landman, Bennett A.

2014-01-01

Label fusion is a critical step in many image segmentation frameworks (e.g., multi-atlas segmentation) as it provides a mechanism for generalizing a collection of labeled examples into a single estimate of the underlying segmentation. In the multi-label case, typical label fusion algorithms treat all labels equally – fully neglecting the known, yet complex, anatomical relationships exhibited in the data. To address this problem, we propose a generalized statistical fusion framework using hierarchical models of rater performance. Building on the seminal work in statistical fusion, we reformulate the traditional rater performance model from a multi-tiered hierarchical perspective. This new approach provides a natural framework for leveraging known anatomical relationships and accurately modeling the types of errors that raters (or atlases) make within a hierarchically consistent formulation. Herein, we describe several contributions. First, we derive a theoretical advancement to the statistical fusion framework that enables the simultaneous estimation of multiple (hierarchical) performance models within the statistical fusion context. Second, we demonstrate that the proposed hierarchical formulation is highly amenable to the state-of-the-art advancements that have been made to the statistical fusion framework. Lastly, in an empirical whole-brain segmentation task we demonstrate substantial qualitative and significant quantitative improvement in overall segmentation accuracy. PMID:24817809

Why the elderly could bankrupt Canada and how demographic imperatives will force the redesign of acute care service delivery.

PubMed

Sinha, Samir K

2011-01-01

Canada's aging population poses a significant challenge for the existing healthcare system. While individuals 65 and older accounted for 13.7% of the population in 2005, they accounted for 60% of all acute care service spending. This paper further illustrates how the heterogeneity of the older population and its impact on patterns of healthcare use demonstrate the failings of our current care systems. Our outdated acute care models frequently disadvantage the system's highest users, who are often characterized by factors such as poly-morbidity, functional impairment and social frailty. Understanding how implementing innovative models that challenge deeply ingrained ways of providing care has proven to be a significant challenge, this paper highlights one hospital's mission to transform current traditional paradigms of care by developing and implementing an elder-friendly hospital integrated service delivery model. This hospital aims to demonstrate wide-ranging benefits of this model that can contribute toward optimizing the outcomes of hospitalization for older adults and the system as a whole. The establishment of a national agency that could support the development of a national aging strategy to promote best practice dissemination and implementation could also ensure that the significant health, social and economic benefits that better care models can realize could be more easily achieved.

Methamphetamine Administration Modifies Leukocyte Proliferation and Cytokine Production in Murine Tissues

PubMed Central

Peerzada, Habibullah; Ghandi, Jay A.; Guimaraes, Allan J.; Nosanchuk, Joshua D.; Martinez, Luis R.

2013-01-01

Methamphetamine (METH) is a potent and highly addictive central nervous system (CNS) stimulant. Additionally, METH adversely impacts immunological responses, which might contribute to the higher rate and more rapid progression of certain infections in drug abusers. However no studies have shown the impact of METH on inflammation within specific organs, cellular participation and cytokine production. Using a murine model of METH administration, we demonstrated that METH modifies, with variable degrees, leukocyte recruitment and alters cellular mediators in the lungs, liver, spleen and kidneys of mice. Our findings demonstrate the pleotropic effects of METH on the immune response within diverse tissues. These alterations have profound implications on tissue homeostasis and the capacity of the host to respond to diverse insults, including invading pathogens. PMID:23518444

Seasonal variability of atmospheric tides in the mesosphere and lower thermosphere: meteor radar data and simulations

NASA Astrophysics Data System (ADS)

Pokhotelov, Dimitry; Becker, Erich; Stober, Gunter; Chau, Jorge L.

2018-06-01

Thermal tides play an important role in the global atmospheric dynamics and provide a key mechanism for the forcing of thermosphere-ionosphere dynamics from below. A method for extracting tidal contributions, based on the adaptive filtering, is applied to analyse multi-year observations of mesospheric winds from ground-based meteor radars located in northern Germany and Norway. The observed seasonal variability of tides is compared to simulations with the Kühlungsborn Mechanistic Circulation Model (KMCM). It is demonstrated that the model provides reasonable representation of the tidal amplitudes, though substantial differences from observations are also noticed. The limitations of applying a conventionally coarse-resolution model in combination with parametrisation of gravity waves are discussed. The work is aimed towards the development of an ionospheric model driven by the dynamics of the KMCM.

Modeling pure culture heterotrophic production of polyhydroxybutyrate (PHB).

PubMed

Mozumder, Md Salatul Islam; Goormachtigh, Laurens; Garcia-Gonzalez, Linsey; De Wever, Heleen; Volcke, Eveline I P

2014-03-01

In this contribution a mechanistic model describing the production of polyhydroxybutyrate (PHB) through pure-culture fermentation was developed, calibrated and validated for two different substrates, namely glucose and waste glycerol. In both cases, non-growth-associated PHB production was triggered by applying nitrogen limitation. The occurrence of some growth-associated PHB production besides non-growth-associated PHB production was demonstrated, although it is inhibited in the presence of nitrogen. Other phenomena observed experimentally and described by the model included biomass growth on PHB and non-linear product inhibition of PHB production. The accumulated impurities from the waste substrate negatively affected the obtained maximum PHB content. Overall, the developed mathematical model provided an accurate prediction of the dynamic behavior of heterotrophic biomass growth and PHB production in a two-phase pure culture system. Copyright © 2013 Elsevier Ltd. All rights reserved.

The NASA/Industry Design Analysis Methods for Vibrations (DAMVIBS) Program - A government overview. [of rotorcraft technology development using finite element method

NASA Technical Reports Server (NTRS)

Kvaternik, Raymond G.

1992-01-01

An overview is presented of government contributions to the program called Design Analysis Methods for Vibrations (DAMV) which attempted to develop finite-element-based analyses of rotorcraft vibrations. NASA initiated the program with a finite-element modeling program for the CH-47D tandem-rotor helicopter. The DAMV program emphasized four areas including: airframe finite-element modeling, difficult components studies, coupled rotor-airframe vibrations, and airframe structural optimization. Key accomplishments of the program include industrywide standards for modeling metal and composite airframes, improved industrial designs for vibrations, and the identification of critical structural contributors to airframe vibratory responses. The program also demonstrated the value of incorporating secondary modeling details to improving correlation, and the findings provide the basis for an improved finite-element-based dynamics design-analysis capability.

Model-Driven Safety Analysis of Closed-Loop Medical Systems

PubMed Central

Pajic, Miroslav; Mangharam, Rahul; Sokolsky, Oleg; Arney, David; Goldman, Julian; Lee, Insup

2013-01-01

In modern hospitals, patients are treated using a wide array of medical devices that are increasingly interacting with each other over the network, thus offering a perfect example of a cyber-physical system. We study the safety of a medical device system for the physiologic closed-loop control of drug infusion. The main contribution of the paper is the verification approach for the safety properties of closed-loop medical device systems. We demonstrate, using a case study, that the approach can be applied to a system of clinical importance. Our method combines simulation-based analysis of a detailed model of the system that contains continuous patient dynamics with model checking of a more abstract timed automata model. We show that the relationship between the two models preserves the crucial aspect of the timing behavior that ensures the conservativeness of the safety analysis. We also describe system design that can provide open-loop safety under network failure. PMID:24177176

Model-Driven Safety Analysis of Closed-Loop Medical Systems.

PubMed

Pajic, Miroslav; Mangharam, Rahul; Sokolsky, Oleg; Arney, David; Goldman, Julian; Lee, Insup

2012-10-26

In modern hospitals, patients are treated using a wide array of medical devices that are increasingly interacting with each other over the network, thus offering a perfect example of a cyber-physical system. We study the safety of a medical device system for the physiologic closed-loop control of drug infusion. The main contribution of the paper is the verification approach for the safety properties of closed-loop medical device systems. We demonstrate, using a case study, that the approach can be applied to a system of clinical importance. Our method combines simulation-based analysis of a detailed model of the system that contains continuous patient dynamics with model checking of a more abstract timed automata model. We show that the relationship between the two models preserves the crucial aspect of the timing behavior that ensures the conservativeness of the safety analysis. We also describe system design that can provide open-loop safety under network failure.

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

Dawson, S.; Lewis, I. M.

One of the simplest extensions of the Standard Model (SM) is the addition of a scalar gauge singlet, S . If S is not forbidden by a symmetry from mixing with the Standard Model Higgs boson, the mixing will generate non-SM rates for Higgs production and decays. Generally, there could also be unknown high energy physics that generates additional effective low energy interactions. We show that interference effects between the scalar resonance of the singlet model and the effective field theory (EFT) operators can have significant effects in the Higgs sector. Here, we examine a non- Z 2 symmetricmore » scalar singlet model and demonstrate that a fit to the 125 GeV Higgs boson couplings and to limits on high mass resonances, S , exhibit an interesting structure and possible large cancellations of effects between the resonance contribution and the new EFT interactions, that invalidate conclusions based on the renormalizable singlet model alone.« less

Snaps, Selfies, and Shares: How Three Popular Social Media Platforms Contribute to the Sociocultural Model of Disordered Eating Among Young Women.

PubMed

Saunders, Jessica F; Eaton, Asia A

2018-06-01

The current study aimed to integrate and test the sociocultural model of disordered eating with theories explaining the impact of mass media on the development of disordered eating for users of three popular social networking platforms. Young women social networking site (SNS) users (age 18-24) who had never received an eating disorder diagnosis (N = 637) completed questions capturing their SNS gratifications and usage, body surveillance, social comparisons, body dissatisfaction, and eating pathology. Measures were administered in one online session. Model relationships were similar across users of all three SNS platforms: Facebook, Instagram, and Snapchat. Users of all platforms demonstrated a significant positive relationship between upward comparisons and disordered eating outcomes, and between body surveillance and disordered eating outcomes, although differences between models did emerge. Empirical findings support extending the sociocultural model of disordered eating to include SNS uses and gratifications.

A numerical study of tropospheric ozone in the springtime in East Asia

NASA Astrophysics Data System (ADS)

Zhang, Meigen; Xu, Yongfu; Itsushi, Uno; Hajime, Akimoto

2004-04-01

The Models-3 Community Multi-scale Air Quality modeling system (CMAQ) coupled with the Regional Atmospheric Modeling System (RAMS) is applied to East Asia to study the transport and photochemical transformation of tropospheric ozone in March 1998. The calculated mixing ratios of ozone and carbon monoxide are compared with ground level observations at three remote sites in Japan and it is found that the model reproduces the observed features very well. Examination of several high episodes of ozone and carbon monoxide indicates that these elevated levels are found in association with continental outflow, demonstrating the critical role of the rapid transport of carbon monoxide and other ozone precursors from the continental boundary layer. In comparison with available ozonesonde data, it is found that the model-calculated ozone concentrations are generally in good agreement with the measurements, and the stratospheric contribution to surface ozone mixing ratios is quite limited.

Contribution to the meaning and understanding of anticipatory systems

NASA Astrophysics Data System (ADS)

Kljajić, Miroljub

2001-06-01

The present article discusses the cybernetic method in the modelling and understanding of complex systems from the epistemological, semantic as well as psychological point of view. Biological and organisational systems are the most important among complex systems. According to Rosen [1] anticipatory systems is another name for complex systems because, in a way, they function to anticipate the future state in order to preserve its structure and functioning. This paper demonstrates a strong analogy between Rosen's modified definition of anticipatory systems [2] and decision-making through simulation in organisational systems. The possible meaning of several models modified in the anticipatory mode will also be discussed as for example: a) The modified Verhaulst Model and its anticipatory modification in the case of the description of human behavior, b) The Prey-Predator Model, and c) The Evans Market Model under different conditions of the demand and supply function.

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.

PubMed

Shi, Junxiu; Wang, Yifan; He, Jian; Li, Pingping; Jin, Rong; Wang, Ke; Xu, Xi; Hao, Jie; Zhang, Yan; Liu, Hongju; Chen, Xiaoping; Wu, Hounan; Ge, Qing

2017-08-01

Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. © FASEB.

Extrathermodynamic interpretation of retention equilibria in reversed-phase liquid chromatography using octadecylsilyl-silica gels bonded to C1 and C18 ligands of different densities

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

Miyabe, Kanji; Guiochon, Georges A

2005-09-01

The retention behavior on silica gels bonded to C{sub 18} and C{sub 1} alkyl ligands of different densities was studied in reversed-phase liquid chromatography (RPLC) from the viewpoints of two extrathermodynamic relationships, enthalpy-entropy compensation (EEC) and linear free energy relationship (LFER). First, the four tests proposed by Krug et al. were applied to the values of the retention equilibrium constants (K) normalized by the alkyl ligand density. These tests showed that a real EEC of the retention equilibrium originates from substantial physico-chemical effects. Second, we derived a new model based on the EEC to explain the LFER between the retentionmore » equilibria under different RPLC conditions. The new model indicates how the slope and intercept of the LFER are correlated to the compensation temperatures derived from the EEC analyses and to several parameters characterizing the molecular contributions to the changes in enthalpy and entropy. Finally, we calculated K under various RPLC conditions from only one original experimental K datum by assuming that the contributions of the C{sub 18} and C{sub 1} ligands to K are additive and that their contributions are proportional to the density of each ligand. The estimated K values are in agreement with the corresponding experimental data, demonstrating that our model is useful to explain the variations of K due to changes in the RPLC conditions.« less

keep your models up-to-date: connecting community mapping data to complex urban flood modelling

NASA Astrophysics Data System (ADS)

Winsemius, Hessel; Eilander, Dirk; Ward, Philip; Diaz Loaiza, Andres; Iliffe, Mark; Mawanda, Shaban; Luo, Tianyi; Kimacha, Nyambiri; Chen, Jorik

2017-04-01

The world is urbanizing rapidly. According to the United Nation's World Urbanization Prospect, 50% of the global population already lives in urban areas today. This number is expected to grow to 66% by 2050. The rapid changes in these urban environments go hand in hand with rapid changes in natural hazard risks, in particular in informal unplanned neighbourhoods. In Dar Es Salaam - Tanzania, flood risk dominates and given the rapid changes in the city, continuous updates of detailed street level hazard and risk mapping are needed to adequately support decision making for urban planning, infrastructure design and disaster response. Over the past years, the Ramani Huria and Zuia Mafuriko projects have mapped the most flood prone neighbourhoods, including roads, buildings, drainage and land use and contributed data to the open-source OpenStreetMap database. In this contribution, we will demonstrate how we mobilize these contributed data to establish dynamic flood models for Dar Es Salaam and keep these up-to-date by making a direct link between the data, and model schematization. The tools automatically establish a sound 1D drainage network as well as a high resolution terrain dataset, by fusing the OpenStreetMap data with existing lower resolution terrain data such as the globally available satellite based SRTM 30. It then translates these fully automatically into the inputs required for the D-HYDRO modeling suite. Our tools are built such that community and stakeholder knowledge can be included in the model details through workshops with the tools so that missing essential information about the city's details can be augmented on-the-fly. This process creates a continuous dialogue between members of the community that collect data, and stakeholders requiring data for flood models. Moreover, used taxonomy and data filtering can be configured to conditions in other cities, making the tools generic and scalable. The tools are made available open-source.

Directional sensitivity of the retina: A layered scattering model of outer-segment photoreceptor pigments

PubMed Central

Vohnsen, Brian

2014-01-01

Photoreceptor outer segments have been modeled as stacked arrays of discs or membrane infoldings containing visual pigments with light-induced dipole moments. Waveguiding has been excluded so fields diffract beyond the physical boundaries of each photoreceptor cell. Optical reciprocity is used to argue for identical radiative and light gathering properties of pigments to model vision. Two models have been introduced: one a macroscopic model that assumes a uniform pigment density across each layer and another microscopic model that includes the spatial location of each pigment molecule within each layer. Both models result in highly similar directionality at the pupil plane which proves to be insensitive to the exact details of the outer-segment packing being predominantly determined by the first and last contributing layers as set by the fraction of bleaching. The versatility of the microscopic model is demonstrated with an array of examples that includes the Stiles-Crawford effect, visibility of a focused beam of light and the role of defocus. PMID:24877016

The Impact of Racism on the Sexual and Reproductive Health of African American Women

PubMed Central

Prather, Cynthia; Fuller, Taleria R.; Marshall, Khiya J.; Jeffries, William L.

2016-01-01

African American women are disproportionately affected by multiple sexual and reproductive health conditions compared with women of other races/ethnicities. Research suggests that social determinants of health, including poverty, unemployment, and limited education, contribute to health disparities. However, racism is a probable underlying determinant of these social conditions. This article uses a socioecological model to describe racism and its impact on African American women’s sexual and reproductive health. Although similar models have been used for specific infectious and chronic diseases, they have not described how the historical underpinnings of racism affect current sexual and reproductive health outcomes among African American women. We propose a socioecological model that demonstrates how social determinants grounded in racism affect individual behaviors and interpersonal relationships, which may contribute to sexual and reproductive health outcomes. This model provides a perspective to understand how these unique contextual experiences are intertwined with the daily lived experiences of African American women and how they are potentially linked to poor sexual and reproductive health outcomes. The model also presents an opportunity to increase dialog and research among public health practitioners and encourages them to consider the role of these contextual experiences and supportive data when developing prevention interventions. Considerations address the provision of opportunities to promote health equity by reducing the effects of racism and improving African American women’s sexual and reproductive health. PMID:27227533

Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models

PubMed Central

Lakner, Pirmin H.; Monaghan, Michael G.; Möller, Yvonne; Olayioye, Monilola A.; Schenke-Layland, Katja

2017-01-01

Fluorescence lifetime imaging microscopy (FLIM) can measure and discriminate endogenous fluorophores present in biological samples. This study seeks to identify FLIM as a suitable method to non-invasively detect a shift in cellular metabolic activity towards glycolysis or oxidative phosphorylation in 3D Caco-2 models of colorectal carcinoma. These models were treated with potassium cyanide or hydrogen peroxide as controls, and epidermal growth factor (EGF) as a physiologically-relevant influencer of cell metabolic behaviour. Autofluorescence, attributed to nicotinamide adenine dinucleotide (NADH), was induced by two-photon laser excitation and its lifetime decay was analysed using a standard multi-exponential decay approach and also a novel custom-written code for phasor-based analysis. While both methods enabled detection of a statistically significant shift of metabolic activity towards glycolysis using potassium cyanide, and oxidative phosphorylation using hydrogen peroxide, employing the phasor approach required fewer initial assumptions to quantify the lifetimes of contributing fluorophores. 3D Caco-2 models treated with EGF had increased glucose consumption, production of lactate, and presence of ATP. FLIM analyses of these cultures revealed a significant shift in the contribution of protein-bound NADH towards free NADH, indicating increased glycolysis-mediated metabolic activity. This data demonstrate that FLIM is suitable to interpret metabolic changes in 3D in vitro models. PMID:28211922

Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models.

PubMed

Lakner, Pirmin H; Monaghan, Michael G; Möller, Yvonne; Olayioye, Monilola A; Schenke-Layland, Katja

2017-02-13

Fluorescence lifetime imaging microscopy (FLIM) can measure and discriminate endogenous fluorophores present in biological samples. This study seeks to identify FLIM as a suitable method to non-invasively detect a shift in cellular metabolic activity towards glycolysis or oxidative phosphorylation in 3D Caco-2 models of colorectal carcinoma. These models were treated with potassium cyanide or hydrogen peroxide as controls, and epidermal growth factor (EGF) as a physiologically-relevant influencer of cell metabolic behaviour. Autofluorescence, attributed to nicotinamide adenine dinucleotide (NADH), was induced by two-photon laser excitation and its lifetime decay was analysed using a standard multi-exponential decay approach and also a novel custom-written code for phasor-based analysis. While both methods enabled detection of a statistically significant shift of metabolic activity towards glycolysis using potassium cyanide, and oxidative phosphorylation using hydrogen peroxide, employing the phasor approach required fewer initial assumptions to quantify the lifetimes of contributing fluorophores. 3D Caco-2 models treated with EGF had increased glucose consumption, production of lactate, and presence of ATP. FLIM analyses of these cultures revealed a significant shift in the contribution of protein-bound NADH towards free NADH, indicating increased glycolysis-mediated metabolic activity. This data demonstrate that FLIM is suitable to interpret metabolic changes in 3D in vitro models.

Coupled Modeling of Rhizosphere and Reactive Transport Processes

NASA Astrophysics Data System (ADS)

Roque-Malo, S.; Kumar, P.

2017-12-01

The rhizosphere, as a bio-diverse plant root-soil interface, hosts many hydrologic and biochemical processes, including nutrient cycling, hydraulic redistribution, and soil carbon dynamics among others. The biogeochemical function of root networks, including the facilitation of nutrient cycling through absorption and rhizodeposition, interaction with micro-organisms and fungi, contribution to biomass, etc., plays an important role in myriad Critical Zone processes. Despite this knowledge, the role of the rhizosphere on watershed-scale ecohydrologic functions in the Critical Zone has not been fully characterized, and specifically, the extensive capabilities of reactive transport models (RTMs) have not been applied to these hydrobiogeochemical dynamics. This study uniquely links rhizospheric processes with reactive transport modeling to couple soil biogeochemistry, biological processes, hydrologic flow, hydraulic redistribution, and vegetation dynamics. Key factors in the novel modeling approach are: (i) bi-directional effects of root-soil interaction, such as simultaneous root exudation and nutrient absorption; (ii) multi-state biomass fractions in soil (i.e. living, dormant, and dead biological and root materials); (iii) expression of three-dimensional fluxes to represent both vertical and lateral interconnected flows and processes; and (iv) the potential to include the influence of non-stationary external forcing and climatic factors. We anticipate that the resulting model will demonstrate the extensive effects of plant root dynamics on ecohydrologic functions at the watershed scale and will ultimately contribute to a better characterization of efflux from both agricultural and natural systems.

SDF-1 promotes endochondral bone repair during fracture healing at the traumatic brain injury condition.

PubMed

Liu, Xiaoqi; Zhou, Changlong; Li, Yanjing; Ji, Ye; Xu, Gongping; Wang, Xintao; Yan, Jinglong

2013-01-01

The objective of this study was to investigate the role of stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, on bone healing and whether SDF-1 contributes to accelerating bone repair in traumatic brain injury (TBI)/fracture model. Real-time polymerase chain reaction and immunohistochemical analysis were used to detect the expression of SDF-1 during the repair of femoral bone in TBI/fracture model. The TBI/fracture model was treated with anti-SDF-1 neutralizing antibody or AMD3100, an antagonist for CXCR4, and evaluated by histomorphometry. In vitro and in vivo migration assays were used to evaluate the functional effect of SDF-1 on primary mesenchymal stem cells. The expression of SDF1 and CXCR4 messenger RNA was increased during the bone healing in TBI/fracture model but was less increased in fracture only model. High expression of SDF-1 protein was observed in the surrounding tissue of the damaged bone. Treated with anti-SDF-1 antibody or AMD3100 could inhibit new bone formation. SDF-1 increased mesenchymal stem cell chemotaxis in vitro in a dose-dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF-1 participate in endochondral bone repair. The SDF-1/CXCR4 axis plays a crucial role in the accelerating fracture healing under the condition of TBI and contributes to endochondral bone repair.

The Impact of Racism on the Sexual and Reproductive Health of African American Women.

PubMed

Prather, Cynthia; Fuller, Taleria R; Marshall, Khiya J; Jeffries, William L

2016-07-01

African American women are disproportionately affected by multiple sexual and reproductive health conditions compared with women of other races/ethnicities. Research suggests that social determinants of health, including poverty, unemployment, and limited education, contribute to health disparities. However, racism is a probable underlying determinant of these social conditions. This article uses a socioecological model to describe racism and its impact on African American women's sexual and reproductive health. Although similar models have been used for specific infectious and chronic diseases, they have not described how the historical underpinnings of racism affect current sexual and reproductive health outcomes among African American women. We propose a socioecological model that demonstrates how social determinants grounded in racism affect individual behaviors and interpersonal relationships, which may contribute to sexual and reproductive health outcomes. This model provides a perspective to understand how these unique contextual experiences are intertwined with the daily lived experiences of African American women and how they are potentially linked to poor sexual and reproductive health outcomes. The model also presents an opportunity to increase dialog and research among public health practitioners and encourages them to consider the role of these contextual experiences and supportive data when developing prevention interventions. Considerations address the provision of opportunities to promote health equity by reducing the effects of racism and improving African American women's sexual and reproductive health.