Anaesthetic modulation of nicotinic ion channel kinetics in bovine chromaffin cells.

PubMed Central

Charlesworth, P; Richards, C D

1995-01-01

1. We have investigated the action of the anaesthetics methoxyflurane, methohexitone and etomidate on the nicotinic acetylcholine receptor channel of bovine adrenal chromaffin cells using the whole cell patch clamp technique. 2. Spectral analysis of macroscopic currents evoked by 25 microM carbachol revealed that each of the agents tested reduced the lifetime of the channel open state in a dose-dependent manner. The whole cell current was inhibited in a concentration-dependent fashion by each agent. 3. Channel gating parameters were calculated from single channel studies and the results used to test models explaining the modulation of nicotinic acetylcholine receptor channels by anaesthetics. 4. Each of the agents studied reduced the mean channel open time in a concentration-dependent manner. Anaesthetic concentrations reducing mean open time by 50% were: 370 microM methoxyflurane, 30 microM methohexitone or 23 microM etomidate. 5. Methohexitone and etomidate produced an increase in the number of brief closures within bursts, while no such increase was observed with methoxyflurane. Despite these inter-burst gaps, mean burst length was reduced by each of the agents tested. 6. It is concluded that a simple sequential blocking model fails to account for the action of these anaesthetics. An extended model, in which blocked channels can close, may be applicable. PMID:7773553

A microphysical parameterization of aqSOA and sulfate formation in clouds

NASA Astrophysics Data System (ADS)

McVay, Renee; Ervens, Barbara

2017-07-01

Sulfate and secondary organic aerosol (cloud aqSOA) can be chemically formed in cloud water. Model implementation of these processes represents a computational burden due to the large number of microphysical and chemical parameters. Chemical mechanisms have been condensed by reducing the number of chemical parameters. Here an alternative is presented to reduce the number of microphysical parameters (number of cloud droplet size classes). In-cloud mass formation is surface and volume dependent due to surface-limited oxidant uptake and/or size-dependent pH. Box and parcel model simulations show that using the effective cloud droplet diameter (proportional to total volume-to-surface ratio) reproduces sulfate and aqSOA formation rates within ≤30% as compared to full droplet distributions; other single diameters lead to much greater deviations. This single-class approach reduces computing time significantly and can be included in models when total liquid water content and effective diameter are available.

Computation of Alfvèn eigenmode stability and saturation through a reduced fast ion transport model in the TRANSP tokamak transport code

NASA Astrophysics Data System (ADS)

Podestà, M.; Gorelenkova, M.; Gorelenkov, N. N.; White, R. B.

2017-09-01

Alfvénic instabilities (AEs) are well known as a potential cause of enhanced fast ion transport in fusion devices. Given a specific plasma scenario, quantitative predictions of (i) expected unstable AE spectrum and (ii) resulting fast ion transport are required to prevent or mitigate the AE-induced degradation in fusion performance. Reduced models are becoming an attractive tool to analyze existing scenarios as well as for scenario prediction in time-dependent simulations. In this work, a neutral beam heated NSTX discharge is used as reference to illustrate the potential of a reduced fast ion transport model, known as kick model, that has been recently implemented for interpretive and predictive analysis within the framework of the time-dependent tokamak transport code TRANSP. Predictive capabilities for AE stability and saturation amplitude are first assessed, based on given thermal plasma profiles only. Predictions are then compared to experimental results, and the interpretive capabilities of the model further discussed. Overall, the reduced model captures the main properties of the instabilities and associated effects on the fast ion population. Additional information from the actual experiment enables further tuning of the model’s parameters to achieve a close match with measurements.

Electrode effects in dielectric spectroscopy of colloidal suspensions

NASA Astrophysics Data System (ADS)

Cirkel, P. A.; van der Ploeg, J. P. M.; Koper, G. J. M.

1997-02-01

We present a simple model to account for electrode polarization in colloidal suspensions. Apart from correctly predicting the ω {-3}/{2} dependence for the dielectric permittivity at low frequencies ω, the model provides an explicit dependence of the effect on electrode spacing. The predictions are tested for the sodium bis(2-ethylhexyl) sulfosuccinate (AOT) water-in-oil microemulsion with iso-octane as continuous phase. In particular, the dependence of electrode polarization effects on electrode spacing has been measured and is found to be in accordance with the model prediction. Methods to reduce or account for electrode polarization are briefly discussed.

Thermal Analysis of a TREAT Fuel Assembly

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

Papadias, Dionissios; Wright, Arthur E.

2014-07-09

The objective of this study was to explore options as to reduce peak cladding temperatures despite an increase in peak fuel temperatures. A 3D thermal-hydraulic model for a single TREAT fuel assembly was benchmarked to reproduce results obtained with previous thermal models developed for a TREAT HEU fuel assembly. In exercising this model, and variants thereof depending on the scope of analysis, various options were explored to reduce the peak cladding temperatures.

A new method for calculating time-dependent atomic level populations

NASA Technical Reports Server (NTRS)

Kastner, S. O.

1981-01-01

A method is described for reducing the number of levels to be dealt with in calculating time-dependent populations of atoms or ions in plasmas. The procedure effectively extends the collisional-radiative model to consecutive stages of ionization, treating ground and metastable levels explicitly and excited levels implicitly. Direct comparisons of full and simulated systems are carried out for five-level models.

Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

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

Kirman, Christopher R., E-mail: ckirman@summittoxi

To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs.more » Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (< 0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. - Highlights: • SIDMS allows for measurement of Cr(VI) reduction rate in gastric fluid ex vivo • Human gastric fluid has three reducing pools • Cr(VI) in drinking water at < 0.7 mg/L is rapidly reduced in human gastric fluid • Reduction rate is concentration- and pH-dependent • A refined PK model is used to characterize inter-individual variability in Cr(VI) gastric reduction capacity.« less

CFCI3 (CFC-11): UV Absorption Spectrum Temperature Dependence Measurements and the Impact on Atmospheric Lifetime and Uncertainty

NASA Technical Reports Server (NTRS)

Mcgillen, Max R.; Fleming, Eric L.; Jackman, Charles H.; Burkholder, James B.

2014-01-01

CFCl3 (CFC-11) is both an atmospheric ozone-depleting and potent greenhouse gas that is removed primarily via stratospheric UV photolysis. Uncertainty in the temperature dependence of its UV absorption spectrum is a significant contributing factor to the overall uncertainty in its global lifetime and, thus, model calculations of stratospheric ozone recovery and climate change. In this work, the CFC-11 UV absorption spectrum was measured over a range of wavelength (184.95 - 230 nm) and temperature (216 - 296 K). We report a spectrum temperature dependence that is less than currently recommended for use in atmospheric models. The impact on its atmospheric lifetime was quantified using a 2-D model and the spectrum parameterization developed in this work. The obtained global annually averaged lifetime was 58.1 +- 0.7 years (2 sigma uncertainty due solely to the spectrum uncertainty). The lifetime is slightly reduced and the uncertainty significantly reduced from that obtained using current spectrum recommendations

On absence of steady state in the Bouchaud-Mézard network model

NASA Astrophysics Data System (ADS)

Liu, Zhiyuan; Serota, R. A.

2018-02-01

In the limit of infinite number of nodes (agents), the Itô-reduced Bouchaud-Mézard network model of economic exchange has a time-independent mean and a steady-state inverse gamma distribution. We show that for a finite number of nodes the mean is actually distributed as a time-dependent lognormal and inverse gamma is quasi-stationary, with the time-dependent scale parameter.

A parametric model order reduction technique for poroelastic finite element models.

PubMed

Lappano, Ettore; Polanz, Markus; Desmet, Wim; Mundo, Domenico

2017-10-01

This research presents a parametric model order reduction approach for vibro-acoustic problems in the frequency domain of systems containing poroelastic materials (PEM). The method is applied to the Finite Element (FE) discretization of the weak u-p integral formulation based on the Biot-Allard theory and makes use of reduced basis (RB) methods typically employed for parametric problems. The parametric reduction is obtained rewriting the Biot-Allard FE equations for poroelastic materials using an affine representation of the frequency (therefore allowing for RB methods) and projecting the frequency-dependent PEM system on a global reduced order basis generated with the proper orthogonal decomposition instead of standard modal approaches. This has proven to be better suited to describe the nonlinear frequency dependence and the strong coupling introduced by damping. The methodology presented is tested on two three-dimensional systems: in the first experiment, the surface impedance of a PEM layer sample is calculated and compared with results of the literature; in the second, the reduced order model of a multilayer system coupled to an air cavity is assessed and the results are compared to those of the reference FE model.

Reduced-Order Modeling for Flutter/LCO Using Recurrent Artificial Neural Network

NASA Technical Reports Server (NTRS)

Yao, Weigang; Liou, Meng-Sing

2012-01-01

The present study demonstrates the efficacy of a recurrent artificial neural network to provide a high fidelity time-dependent nonlinear reduced-order model (ROM) for flutter/limit-cycle oscillation (LCO) modeling. An artificial neural network is a relatively straightforward nonlinear method for modeling an input-output relationship from a set of known data, for which we use the radial basis function (RBF) with its parameters determined through a training process. The resulting RBF neural network, however, is only static and is not yet adequate for an application to problems of dynamic nature. The recurrent neural network method [1] is applied to construct a reduced order model resulting from a series of high-fidelity time-dependent data of aero-elastic simulations. Once the RBF neural network ROM is constructed properly, an accurate approximate solution can be obtained at a fraction of the cost of a full-order computation. The method derived during the study has been validated for predicting nonlinear aerodynamic forces in transonic flow and is capable of accurate flutter/LCO simulations. The obtained results indicate that the present recurrent RBF neural network is accurate and efficient for nonlinear aero-elastic system analysis

Blockade of Endocannabinoid Hydrolytic Enzymes Attenuates Precipitated Opioid Withdrawal Symptoms in MiceS⃞

PubMed Central

Ramesh, Divya; Ross, Gracious R.; Schlosburg, Joel E.; Owens, Robert A.; Abdullah, Rehab A.; Kinsey, Steven G.; Long, Jonathan Z.; Nomura, Daniel K.; Sim-Selley, Laura J.; Cravatt, Benjamin F.; Akbarali, Hamid I.

2011-01-01

Δ9-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB1 receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB1 receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate that endocannabinoid catabolic enzymes are promising targets to treat opioid dependence. PMID:21719468

Finding a planet's heartbeat: surprising results from patient Mars

NASA Astrophysics Data System (ADS)

Stamenkovic, Vlada; Ward, Lewis; Fischer, Woodward; Russell, Michael J.

2016-10-01

We explore, from a 3D time-dependent perspective, the evolution of oxidizing and reducing planetary niches and how they form a planetary-scale redox network - from a planet's deep interior to its atmosphere. Such redox networks are similar to the circulatory system of animals, but instead of pressure gradients redox gradients drive the flow of electrons and create hotspots for nutrients and metabolic activity.Using time-dependent geodynamic and atmospheric models, we compute for Mars the time-dependent 3D distribution of 1) hydrogen- and methane-rich reducing subsurface environments, driven by serpentinization and radiolysis of water, and 2) oxygen-rich oases as a product of atmosphere-brine interactions governed by climate and surface chemistry.This is only a first step towards our greater goal to globally model the evolution of local redox environments through time for rocky planets. However, already now our preliminary results show where on Mars oxidizing and reducing oases might have existed and might still exist today. This opens the window to search for extinct and extant life on Mars from a probabilistic global 3D perspective.

A continuum state variable theory to model the size-dependent surface energy of nanostructures.

PubMed

Jamshidian, Mostafa; Thamburaja, Prakash; Rabczuk, Timon

2015-10-14

We propose a continuum-based state variable theory to quantify the excess surface free energy density throughout a nanostructure. The size-dependent effect exhibited by nanoplates and spherical nanoparticles i.e. the reduction of surface energy with reducing nanostructure size is well-captured by our continuum state variable theory. Our constitutive theory is also able to predict the reducing energetic difference between the surface and interior (bulk) portions of a nanostructure with decreasing nanostructure size.

Quantum dynamics of a two-atom-qubit system

NASA Astrophysics Data System (ADS)

Van Hieu, Nguyen; Bich Ha, Nguyen; Linh, Le Thi Ha

2009-09-01

A physical model of the quantum information exchange between two qubits is studied theoretically. The qubits are two identical two-level atoms, the physical mechanism of the quantum information exchange is the mutual dependence of the reduced density matrices of two qubits generated by their couplings with a multimode radiation field. The Lehmberg-Agarwal master equation is exactly solved. The explicit form of the mutual dependence of two reduced density matrices is established. The application to study the entanglement of two qubits is discussed.

A stabilized MFE reduced-order extrapolation model based on POD for the 2D unsteady conduction-convection problem.

PubMed

Xia, Hong; Luo, Zhendong

2017-01-01

In this study, we devote ourselves to establishing a stabilized mixed finite element (MFE) reduced-order extrapolation (SMFEROE) model holding seldom unknowns for the two-dimensional (2D) unsteady conduction-convection problem via the proper orthogonal decomposition (POD) technique, analyzing the existence and uniqueness and the stability as well as the convergence of the SMFEROE solutions and validating the correctness and dependability of the SMFEROE model by means of numerical simulations.

Cohesive zone model for direct silicon wafer bonding

NASA Astrophysics Data System (ADS)

Kubair, D. V.; Spearing, S. M.

2007-05-01

Direct silicon wafer bonding and decohesion are simulated using a spectral scheme in conjunction with a rate-dependent cohesive model. The cohesive model is derived assuming the presence of a thin continuum liquid layer at the interface. Cohesive tractions due to the presence of a liquid meniscus always tend to reduce the separation distance between the wafers, thereby opposing debonding, while assisting the bonding process. In the absence of the rate-dependence effects the energy needed to bond a pair of wafers is equal to that needed to separate them. When rate-dependence is considered in the cohesive law, the experimentally observed asymmetry in the energetics can be explained. The derived cohesive model has the potential to form a bridge between experiments and a multiscale-modelling approach to understand the mechanics of wafer bonding.

Reducing US Oil Dependence Using Simulation

NASA Technical Reports Server (NTRS)

Ayoub, Fadi; Arnaout, Georges M.

2011-01-01

People across the world are addicted to oil; as a result, the instability of oil prices and the shortage of oil reserves have influenced human behaviors and global businesses. Today, the United States makes up only 5% of the global population but consumes 25% of the. world total energy. Most of this energy is generated from fossil fuels in the form of electricity. The contribution of this paper is to examine the possibilities of replacing fossil fuel with renewable energies to generate electricity as well as to examine other methods to reduce oil and gas consumption. We propose a system dynamics model in an attempt to predict the future US dependence on fossil fuels by using renewable energy resources such as, nuclear, wind, solar, and hydro powers. Based on the findings of our model, the study expects to provide insights towards promising solutions of the oil dependency problem.

Mechanisms controlling the dependence of surface warming on cumulative carbon emissions over the next century in a suite of Earth system models

NASA Astrophysics Data System (ADS)

Williams, Richard; Roussenov, Vassil; Goodwin, Philip; Resplandy, Laure; Bopp, Laurent

2017-04-01

Insight into how to avoid dangerous climate may be obtained from Earth system model projections, which reveal a near-linear dependence of global-mean surface warming on cumulative carbon emissions. This dependence of surface warming on carbon emissions is interpreted in terms of a product of three terms: the dependence of surface warming on radiative forcing, the fractional radiative forcing contribution from atmospheric CO2 and the dependence of radiative forcing from atmospheric CO2 on cumulative carbon emissions. Mechanistically each of these dependences varies, respectively, with ocean heat uptake, the CO2 and non-CO2 radiative forcing, and the ocean and terrestrial uptake of carbon. An ensemble of 9 Earth System models forced by up to 4 Representative Concentration Pathways are diagnosed. In all cases, the dependence of surface warming on carbon emissions evolves primarily due to competing effects of heat and carbon uptake over the upper ocean: there is a reduced effect of radiative forcing from CO2 due to ocean carbon uptake, which is partly compensated by enhanced surface warming due to a reduced effect of ocean heat uptake. There is a wide spread in the dependence of surface warming on carbon emissions, undermining the ability to identify the maximum permitted carbon emission to avoid dangerous climate. Our framework reveals how uncertainty in the future warming trend is high over the next few decades due to relatively high uncertainties in ocean heat uptake, non-CO2 radiative forcing and the undersaturation of carbon in the ocean.

Approaches to highly parameterized inversion: A guide to using PEST for model-parameter and predictive-uncertainty analysis

USGS Publications Warehouse

Doherty, John E.; Hunt, Randall J.; Tonkin, Matthew J.

2010-01-01

Analysis of the uncertainty associated with parameters used by a numerical model, and with predictions that depend on those parameters, is fundamental to the use of modeling in support of decisionmaking. Unfortunately, predictive uncertainty analysis with regard to models can be very computationally demanding, due in part to complex constraints on parameters that arise from expert knowledge of system properties on the one hand (knowledge constraints) and from the necessity for the model parameters to assume values that allow the model to reproduce historical system behavior on the other hand (calibration constraints). Enforcement of knowledge and calibration constraints on parameters used by a model does not eliminate the uncertainty in those parameters. In fact, in many cases, enforcement of calibration constraints simply reduces the uncertainties associated with a number of broad-scale combinations of model parameters that collectively describe spatially averaged system properties. The uncertainties associated with other combinations of parameters, especially those that pertain to small-scale parameter heterogeneity, may not be reduced through the calibration process. To the extent that a prediction depends on system-property detail, its postcalibration variability may be reduced very little, if at all, by applying calibration constraints; knowledge constraints remain the only limits on the variability of predictions that depend on such detail. Regrettably, in many common modeling applications, these constraints are weak. Though the PEST software suite was initially developed as a tool for model calibration, recent developments have focused on the evaluation of model-parameter and predictive uncertainty. As a complement to functionality that it provides for highly parameterized inversion (calibration) by means of formal mathematical regularization techniques, the PEST suite provides utilities for linear and nonlinear error-variance and uncertainty analysis in these highly parameterized modeling contexts. Availability of these utilities is particularly important because, in many cases, a significant proportion of the uncertainty associated with model parameters-and the predictions that depend on them-arises from differences between the complex properties of the real world and the simplified representation of those properties that is expressed by the calibrated model. This report is intended to guide intermediate to advanced modelers in the use of capabilities available with the PEST suite of programs for evaluating model predictive error and uncertainty. A brief theoretical background is presented on sources of parameter and predictive uncertainty and on the means for evaluating this uncertainty. Applications of PEST tools are then discussed for overdetermined and underdetermined problems, both linear and nonlinear. PEST tools for calculating contributions to model predictive uncertainty, as well as optimization of data acquisition for reducing parameter and predictive uncertainty, are presented. The appendixes list the relevant PEST variables, files, and utilities required for the analyses described in the document.

The Acute and Chronic Effects of the Novel Anticonvulsant Lacosamide in an Experimental Model of Status Epilepticus

PubMed Central

Wasterlain, Claude G.; Stöhr, Thomas; Matagne, Alain

2011-01-01

The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE. Rats were treated with lacosamide (3, 10, 30 or 50 mg/kg) either 10 minutes (early treatment) or 40 minutes (late treatment) after the initiation of perforant path stimulation. Early lacosamide treatment significantly and dose-dependently reduced acute SE seizure activity; late treatment showed only a non-significant trend towards reduced seizure activity. Early lacosamide treatment also dose-dependently reduced the number of spontaneous recurrent seizures following a 6-week waiting period, with 70% reduction at the highest dose tested (50 mg/kg); there was also a significant reduction in the number of spikes and the cumulative time spent in seizures. Late treatment with high-dose lacosamide (30–50 mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P <0.05), but did not significantly reduce seizure severity or frequency in rats that developed spontaneous recurrent seizures.. The results presented here suggest that lacosamide deserves investigation for the clinical treatment of SE. Potential for disease modification in this rat model of self-sustaining SE will require further studies. PMID:21277168

Spatial dependence of extreme rainfall

NASA Astrophysics Data System (ADS)

Radi, Noor Fadhilah Ahmad; Zakaria, Roslinazairimah; Satari, Siti Zanariah; Azman, Muhammad Az-zuhri

2017-05-01

This study aims to model the spatial extreme daily rainfall process using the max-stable model. The max-stable model is used to capture the dependence structure of spatial properties of extreme rainfall. Three models from max-stable are considered namely Smith, Schlather and Brown-Resnick models. The methods are applied on 12 selected rainfall stations in Kelantan, Malaysia. Most of the extreme rainfall data occur during wet season from October to December of 1971 to 2012. This period is chosen to assure the available data is enough to satisfy the assumption of stationarity. The dependence parameters including the range and smoothness, are estimated using composite likelihood approach. Then, the bootstrap approach is applied to generate synthetic extreme rainfall data for all models using the estimated dependence parameters. The goodness of fit between the observed extreme rainfall and the synthetic data is assessed using the composite likelihood information criterion (CLIC). Results show that Schlather model is the best followed by Brown-Resnick and Smith models based on the smallest CLIC's value. Thus, the max-stable model is suitable to be used to model extreme rainfall in Kelantan. The study on spatial dependence in extreme rainfall modelling is important to reduce the uncertainties of the point estimates for the tail index. If the spatial dependency is estimated individually, the uncertainties will be large. Furthermore, in the case of joint return level is of interest, taking into accounts the spatial dependence properties will improve the estimation process.

[Policies to reduce health inequalities].

PubMed

Borrell, Carme; Artazcoz, Lucía

2008-01-01

This paper reviews policies to reduce social inequalities in health and presents some examples. Previously it presents the model on social determinants of health inequalities. The model described on the determinants of health inequalities is used by the Commission on Social Determinants of Health of the World Health Organisation that contains three main elements: the socio-economic and political context, socioeconomic status and intermediary factors. It describes 10 principles to keep in mind to launch interventions aimed at reducing inequalities in health and describes various policies depending on different "entry points" considered in the conceptual model. Finally we present two examples: The Public Health Policy of Sweden and the programme "Barrio Adentro" in Venezuela.

The Cost Effectiveness of Nalmefene for Reduction of Alcohol Consumption in Alcohol-Dependent Patients with High or Very High Drinking-Risk Levels from a UK Societal Perspective.

PubMed

Brodtkorb, Thor-Henrik; Bell, Melissa; Irving, Adam H; Laramée, Philippe

2016-02-01

To evaluate costs and health outcomes of nalmefene plus psychosocial support, compared with psychosocial intervention alone, for reducing alcohol consumption in alcohol-dependent patients, specifically focusing on societal costs related to productivity losses and crime. A Markov model was constructed to model costs and health outcomes of the treatments over 5 years. Analyses were conducted for nalmefene's licensed population: adults with both alcohol dependence and high or very high drinking-risk levels (DRLs) who do not require immediate detoxification and who have high or very high DRLs after initial assessment. The main outcome measure was cost per quality-adjusted life-year (QALY) gained as assessed from a UK societal perspective. Alcohol-attributable productivity loss, crime and health events occurring at different levels of alcohol consumption were taken from published risk-relation studies. Health-related and societal costs were drawn from public data and the literature. Data on the treatment effect, as well as baseline characteristics of the modelled population and utilities, came from three pivotal phase 3 trials of nalmefene. Nalmefene plus psychosocial support was dominant compared with psychosocial intervention alone, resulting in QALYs gained and reduced societal costs. Sensitivity analyses showed that this conclusion was robust. Nalmefene plus psychosocial support led to per-patient reduced costs of £3324 and £2483, due to reduced productivity losses and crime events, respectively. Nalmefene is cost effective from a UK societal perspective, resulting in greater QALY gains and lower costs compared with psychosocial support alone. Nalmefene demonstrates considerable public benefits by reducing alcohol-attributable productivity losses and crime events in adults with both alcohol dependence and high or very high DRLs who do not require immediate detoxification and who have high or very high DRLs after initial assessment.

A Model for Pharmacological Research-Treatment of Cocaine Dependence

PubMed Central

Montoya, Ivan D.; Hess, Judith M.; Preston, Kenzie L.; Gorelick, David A.

2008-01-01

Major problems for research on pharmacological treatments for cocaine dependence are lack of comparability of results from different treatment research programs and poor validity and/or reliability of results. Double-blind, placebo-controlled, random assignment, experimental designs, using standard intake and assessment procedures help to reduce these problems. Cessation or reduction of drug use and/or craving, retention in treatment, and medical and psychosocial improvement are some of the outcome variables collected in treatment research programs. A model to be followed across different outpatient clinical trials for pharmacological treatment of cocaine dependence is presented here. This model represents an effort to standardize data collection to make results more valid and comparable. PMID:8749725

Metric versus observable operator representation, higher spin models

NASA Astrophysics Data System (ADS)

Fring, Andreas; Frith, Thomas

2018-02-01

We elaborate further on the metric representation that is obtained by transferring the time-dependence from a Hermitian Hamiltonian to the metric operator in a related non-Hermitian system. We provide further insight into the procedure on how to employ the time-dependent Dyson relation and the quasi-Hermiticity relation to solve time-dependent Hermitian Hamiltonian systems. By solving both equations separately we argue here that it is in general easier to solve the former. We solve the mutually related time-dependent Schrödinger equation for a Hermitian and non-Hermitian spin 1/2, 1 and 3/2 model with time-independent and time-dependent metric, respectively. In all models the overdetermined coupled system of equations for the Dyson map can be decoupled algebraic manipulations and reduces to simple linear differential equations and an equation that can be converted into the non-linear Ermakov-Pinney equation.

Towards a universal master curve in magnetorheology

NASA Astrophysics Data System (ADS)

Ruiz-López, José Antonio; Hidalgo-Alvarez, Roque; de Vicente, Juan

2017-05-01

We demonstrate that inverse ferrofluids behave as model magnetorheological fluids. A universal master curve is proposed, using a reduced Mason number, under the frame of a structural viscosity model where the magnetic field strength dependence is solely contained in the Mason number and the particle concentration is solely contained in the critical Mason number (i.e. the yield stress). A linear dependence of the critical Mason number with the particle concentration is observed that is in good agreement with a mean (average) magnetization approximation, particle level dynamic simulations and micromechanical models available in the literature.

Parametric Study of a YAV-8B Harrier in Ground Effect Using Time-Dependent Navier-Stokes Computations

NASA Technical Reports Server (NTRS)

Shishir, Pandya; Chaderjian, Neal; Ahmad, Jsaim; Kwak, Dochan (Technical Monitor)

2001-01-01

Flow simulations using the time-dependent Navier-Stokes equations remain a challenge for several reasons. Principal among them are the difficulty to accurately model complex flows, and the time needed to perform the computations. A parametric study of such complex problems is not considered practical due to the large cost associated with computing many time-dependent solutions. The computation time for each solution must be reduced in order to make a parametric study possible. With successful reduction of computation time, the issue of accuracy, and appropriateness of turbulence models will become more tractable.

Capturing tensile size-dependency in polymer nanofiber elasticity.

PubMed

Yuan, Bo; Wang, Jun; Han, Ray P S

2015-02-01

As the name implies, tensile size-dependency refers to the size-dependent response under uniaxial tension. It defers markedly from bending size-dependency in terms of onset and magnitude of the size-dependent response; the former begins earlier but rises to a smaller value than the latter. Experimentally, tensile size-dependent behavior is much harder to capture than its bending counterpart. This is also true in the computational effort; bending size-dependency models are more prevalent and well-developed. Indeed, many have questioned the existence of tensile size-dependency. However, recent experiments seem to support the existence of this phenomenon. Current strain gradient elasticity theories can accurately predict bending size-dependency but are unable to track tensile size-dependency. To rectify this deficiency a higher-order strain gradient elasticity model is constructed by including the second gradient of the strain into the deformation energy. Tensile experiments involving 10 wt% polycaprolactone nanofibers are performed to calibrate and verify our model. The results reveal that for the selected nanofibers, their size-dependency begins when their diameters reduce to 600 nm and below. Further, their characteristic length-scale parameter is found to be 1095.8 nm. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source.

PubMed

White, Shane A; Landry, Guillaume; Fonseca, Gabriel Paiva; Holt, Randy; Rusch, Thomas; Beaulieu, Luc; Verhaegen, Frank; Reniers, Brigitte

2014-06-01

The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans. A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (Dw,m) and dose to medium (Dm,m), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D90 to PTV was reduced by between ~4% and ~40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%-15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources.

Marine ice sheet model performance depends on basal sliding physics and sub-shelf melting

NASA Astrophysics Data System (ADS)

Gladstone, Rupert Michael; Warner, Roland Charles; Galton-Fenzi, Benjamin Keith; Gagliardini, Olivier; Zwinger, Thomas; Greve, Ralf

2017-01-01

Computer models are necessary for understanding and predicting marine ice sheet behaviour. However, there is uncertainty over implementation of physical processes at the ice base, both for grounded and floating glacial ice. Here we implement several sliding relations in a marine ice sheet flow-line model accounting for all stress components and demonstrate that model resolution requirements are strongly dependent on both the choice of basal sliding relation and the spatial distribution of ice shelf basal melting.Sliding relations that reduce the magnitude of the step change in basal drag from grounded ice to floating ice (where basal drag is set to zero) show reduced dependence on resolution compared to a commonly used relation, in which basal drag is purely a power law function of basal ice velocity. Sliding relations in which basal drag goes smoothly to zero as the grounding line is approached from inland (due to a physically motivated incorporation of effective pressure at the bed) provide further reduction in resolution dependence.A similar issue is found with the imposition of basal melt under the floating part of the ice shelf: melt parameterisations that reduce the abruptness of change in basal melting from grounded ice (where basal melt is set to zero) to floating ice provide improved convergence with resolution compared to parameterisations in which high melt occurs adjacent to the grounding line.Thus physical processes, such as sub-glacial outflow (which could cause high melt near the grounding line), impact on capability to simulate marine ice sheets. If there exists an abrupt change across the grounding line in either basal drag or basal melting, then high resolution will be required to solve the problem. However, the plausible combination of a physical dependency of basal drag on effective pressure, and the possibility of low ice shelf basal melt rates next to the grounding line, may mean that some marine ice sheet systems can be reliably simulated at a coarser resolution than currently thought necessary.

Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

PubMed

Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2017-10-01

Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

Hidden Markov model for dependent mark loss and survival estimation

USGS Publications Warehouse

Laake, Jeffrey L.; Johnson, Devin S.; Diefenbach, Duane R.; Ternent, Mark A.

2014-01-01

Mark-recapture estimators assume no loss of marks to provide unbiased estimates of population parameters. We describe a hidden Markov model (HMM) framework that integrates a mark loss model with a Cormack–Jolly–Seber model for survival estimation. Mark loss can be estimated with single-marked animals as long as a sub-sample of animals has a permanent mark. Double-marking provides an estimate of mark loss assuming independence but dependence can be modeled with a permanently marked sub-sample. We use a log-linear approach to include covariates for mark loss and dependence which is more flexible than existing published methods for integrated models. The HMM approach is demonstrated with a dataset of black bears (Ursus americanus) with two ear tags and a subset of which were permanently marked with tattoos. The data were analyzed with and without the tattoo. Dropping the tattoos resulted in estimates of survival that were reduced by 0.005–0.035 due to tag loss dependence that could not be modeled. We also analyzed the data with and without the tattoo using a single tag. By not using.

Voltage-dependent K+ channels improve the energy efficiency of signalling in blowfly photoreceptors

PubMed Central

2017-01-01

Voltage-dependent conductances in many spiking neurons are tuned to reduce action potential energy consumption, so improving the energy efficiency of spike coding. However, the contribution of voltage-dependent conductances to the energy efficiency of analogue coding, by graded potentials in dendrites and non-spiking neurons, remains unclear. We investigate the contribution of voltage-dependent conductances to the energy efficiency of analogue coding by modelling blowfly R1-6 photoreceptor membrane. Two voltage-dependent delayed rectifier K+ conductances (DRs) shape the membrane's voltage response and contribute to light adaptation. They make two types of energy saving. By reducing membrane resistance upon depolarization they convert the cheap, low bandwidth membrane needed in dim light to the expensive high bandwidth membrane needed in bright light. This investment of energy in bandwidth according to functional requirements can halve daily energy consumption. Second, DRs produce negative feedback that reduces membrane impedance and increases bandwidth. This negative feedback allows an active membrane with DRs to consume at least 30% less energy than a passive membrane with the same capacitance and bandwidth. Voltage-dependent conductances in other non-spiking neurons, and in dendrites, might be organized to make similar savings. PMID:28381642

Voltage-dependent K+ channels improve the energy efficiency of signalling in blowfly photoreceptors.

PubMed

Heras, Francisco J H; Anderson, John; Laughlin, Simon B; Niven, Jeremy E

2017-04-01

Voltage-dependent conductances in many spiking neurons are tuned to reduce action potential energy consumption, so improving the energy efficiency of spike coding. However, the contribution of voltage-dependent conductances to the energy efficiency of analogue coding, by graded potentials in dendrites and non-spiking neurons, remains unclear. We investigate the contribution of voltage-dependent conductances to the energy efficiency of analogue coding by modelling blowfly R1-6 photoreceptor membrane. Two voltage-dependent delayed rectifier K + conductances (DRs) shape the membrane's voltage response and contribute to light adaptation. They make two types of energy saving. By reducing membrane resistance upon depolarization they convert the cheap, low bandwidth membrane needed in dim light to the expensive high bandwidth membrane needed in bright light. This investment of energy in bandwidth according to functional requirements can halve daily energy consumption. Second, DRs produce negative feedback that reduces membrane impedance and increases bandwidth. This negative feedback allows an active membrane with DRs to consume at least 30% less energy than a passive membrane with the same capacitance and bandwidth. Voltage-dependent conductances in other non-spiking neurons, and in dendrites, might be organized to make similar savings. © 2017 The Author(s).

A dynamic analysis of the motion of a low-wing general aviation aircraft about its calculated equilibrium flat spin mode

NASA Technical Reports Server (NTRS)

Tischler, M. B.; Barlow, J. B.

1980-01-01

The properties of the flat spin mode of a general aviation configuration have been studied through analysis of rotary balance data, numerical simulation, and analytical study of the equilibrium state. The equilibrium state is predicted well from rotary balance data. The variations of yawing moment and pitching moment as functions of sideslip have been shown to be of great importance in obtaining accurate modeling. These dependencies are not presently available with sufficient accuracy from previous tests or theories. The stability of the flat spin mode has been examined extensively using numerical linearization, classical perturbation methods, and reduced order modeling. The stability exhibited by the time histories and the eigenvalue analyses is shown to be strongly dependent on certain static cross derivatives and more so on the dynamic derivatives. Explicit stability criteria are obtained from the reduced order models.

The effect of intrinsic muscular nonlinearities on the energetics of locomotion in a computational model of an anguilliform swimmer.

PubMed

Hamlet, Christina; Fauci, Lisa J; Tytell, Eric D

2015-11-21

Animals move through their environments using muscles to produce force. When an animal׳s nervous system activates a muscle, the muscle produces different amounts of force depending on its length, its shortening velocity, and its time history of force production. These muscle forces interact with forces from passive tissue properties and forces from the external environment. Using an integrative computational model that couples an elastic, actuated model of an anguilliform, lamprey-like swimmer with a surrounding Navier-Stokes fluid, we study the effects of this coupling between the muscle force and the body motion. Swimmers with different forms of this coupling can achieve similar motions, but use different amounts of energy. The velocity dependence is the most important property of the ones we considered for reducing energy costs and helping us to stabilize oscillations. These effects are strongly influenced by how rapidly the muscle deactivates; if force decays too slowly, muscles on opposite sides of the body end up fighting each other, increasing energy cost. Work-dependent deactivation, an effect that causes a muscle to deactivate more rapidly if it has recently produced mechanical work, works together with the velocity dependence to reduce the energy cost of swimming. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimating inelastic heavy-particle - hydrogen collision data. II. Simplified model for ionic collisions and application to barium-hydrogen ionic collisions

NASA Astrophysics Data System (ADS)

Belyaev, Andrey K.; Yakovleva, Svetlana A.

2017-12-01

Aims: A simplified model is derived for estimating rate coefficients for inelastic processes in low-energy collisions of heavy particles with hydrogen, in particular, the rate coefficients with high and moderate values. Such processes are important for non-local thermodynamic equilibrium modeling of cool stellar atmospheres. Methods: The derived method is based on the asymptotic approach for electronic structure calculations and the Landau-Zener model for nonadiabatic transition probability determination. Results: It is found that the rate coefficients are expressed via statistical probabilities and reduced rate coefficients. It is shown that the reduced rate coefficients for neutralization and ion-pair formation processes depend on single electronic bound energies of an atomic particle, while the reduced rate coefficients for excitation and de-excitation processes depend on two electronic bound energies. The reduced rate coefficients are calculated and tabulated as functions of electronic bound energies. The derived model is applied to barium-hydrogen ionic collisions. For the first time, rate coefficients are evaluated for inelastic processes in Ba+ + H and Ba2+ + H- collisions for all transitions between the states from the ground and up to and including the ionic state. Tables with calculated data are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/608/A33

Estimating inelastic heavy-particle-hydrogen collision data. I. Simplified model and application to potassium-hydrogen collisions

NASA Astrophysics Data System (ADS)

Belyaev, Andrey K.; Yakovleva, Svetlana A.

2017-10-01

Aims: We derive a simplified model for estimating atomic data on inelastic processes in low-energy collisions of heavy-particles with hydrogen, in particular for the inelastic processes with high and moderate rate coefficients. It is known that these processes are important for non-LTE modeling of cool stellar atmospheres. Methods: Rate coefficients are evaluated using a derived method, which is a simplified version of a recently proposed approach based on the asymptotic method for electronic structure calculations and the Landau-Zener model for nonadiabatic transition probability determination. Results: The rate coefficients are found to be expressed via statistical probabilities and reduced rate coefficients. It turns out that the reduced rate coefficients for mutual neutralization and ion-pair formation processes depend on single electronic bound energies of an atom, while the reduced rate coefficients for excitation and de-excitation processes depend on two electronic bound energies. The reduced rate coefficients are calculated and tabulated as functions of electronic bound energies. The derived model is applied to potassium-hydrogen collisions. For the first time, rate coefficients are evaluated for inelastic processes in K+H and K++H- collisions for all transitions from ground states up to and including ionic states. Tables with calculated data are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/606/A147

Accelerated solution of discrete ordinates approximation to the Boltzmann transport equation via model reduction

DOE PAGES

Tencer, John; Carlberg, Kevin; Larsen, Marvin; ...

2017-06-17

Radiation heat transfer is an important phenomenon in many physical systems of practical interest. When participating media is important, the radiative transfer equation (RTE) must be solved for the radiative intensity as a function of location, time, direction, and wavelength. In many heat-transfer applications, a quasi-steady assumption is valid, thereby removing time dependence. The dependence on wavelength is often treated through a weighted sum of gray gases (WSGG) approach. The discrete ordinates method (DOM) is one of the most common methods for approximating the angular (i.e., directional) dependence. The DOM exactly solves for the radiative intensity for a finite numbermore » of discrete ordinate directions and computes approximations to integrals over the angular space using a quadrature rule; the chosen ordinate directions correspond to the nodes of this quadrature rule. This paper applies a projection-based model-reduction approach to make high-order quadrature computationally feasible for the DOM for purely absorbing applications. First, the proposed approach constructs a reduced basis from (high-fidelity) solutions of the radiative intensity computed at a relatively small number of ordinate directions. Then, the method computes inexpensive approximations of the radiative intensity at the (remaining) quadrature points of a high-order quadrature using a reduced-order model constructed from the reduced basis. Finally, this results in a much more accurate solution than might have been achieved using only the ordinate directions used to compute the reduced basis. One- and three-dimensional test problems highlight the efficiency of the proposed method.« less

Accelerated solution of discrete ordinates approximation to the Boltzmann transport equation via model reduction

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

Tencer, John; Carlberg, Kevin; Larsen, Marvin

Radiation heat transfer is an important phenomenon in many physical systems of practical interest. When participating media is important, the radiative transfer equation (RTE) must be solved for the radiative intensity as a function of location, time, direction, and wavelength. In many heat-transfer applications, a quasi-steady assumption is valid, thereby removing time dependence. The dependence on wavelength is often treated through a weighted sum of gray gases (WSGG) approach. The discrete ordinates method (DOM) is one of the most common methods for approximating the angular (i.e., directional) dependence. The DOM exactly solves for the radiative intensity for a finite numbermore » of discrete ordinate directions and computes approximations to integrals over the angular space using a quadrature rule; the chosen ordinate directions correspond to the nodes of this quadrature rule. This paper applies a projection-based model-reduction approach to make high-order quadrature computationally feasible for the DOM for purely absorbing applications. First, the proposed approach constructs a reduced basis from (high-fidelity) solutions of the radiative intensity computed at a relatively small number of ordinate directions. Then, the method computes inexpensive approximations of the radiative intensity at the (remaining) quadrature points of a high-order quadrature using a reduced-order model constructed from the reduced basis. Finally, this results in a much more accurate solution than might have been achieved using only the ordinate directions used to compute the reduced basis. One- and three-dimensional test problems highlight the efficiency of the proposed method.« less

1D-3D hybrid modeling-from multi-compartment models to full resolution models in space and time.

PubMed

Grein, Stephan; Stepniewski, Martin; Reiter, Sebastian; Knodel, Markus M; Queisser, Gillian

2014-01-01

Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator-which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D-simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics.

Enhanced Polyubiquitination of Shank3 and NMDA receptor in a mouse model of Autism

PubMed Central

Bangash, M Ali; Park, Joo Min; Melnikova, Tatiana; Wang, Dehua; Jeon, Soo Kyeong; Lee, Deidre; Syeda, Sbaa; Kim, Juno; Kouser, Mehreen; Schwartz, Joshua; Cui, Yiyuan; Zhao, Xia; Speed, Haley E.; Kee, Sara E.; Tu, Jian Cheng; Hu, Jia-Hua; Petralia, Ronald S.; Linden, David J.; Powell, Craig M.; Savonenko, Alena; Xiao, Bo; Worley, Paul F.

2011-01-01

Summary We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C-terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the WT gene product and results in >90 % reduction of Shank3 at synapses. This “gain of function” phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of post-synaptic density proteins, spine morphology and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. PMID:21565394

Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.

PubMed

Bangash, M Ali; Park, Joo Min; Melnikova, Tatiana; Wang, Dehua; Jeon, Soo Kyeong; Lee, Deidre; Syeda, Sbaa; Kim, Juno; Kouser, Mehreen; Schwartz, Joshua; Cui, Yiyuan; Zhao, Xia; Speed, Haley E; Kee, Sara E; Tu, Jian Cheng; Hu, Jia-Hua; Petralia, Ronald S; Linden, David J; Powell, Craig M; Savonenko, Alena; Xiao, Bo; Worley, Paul F

2011-05-27

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. Copyright © 2011 Elsevier Inc. All rights reserved.

Determining Reduced Order Models for Optimal Stochastic Reduced Order Models

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

Bonney, Matthew S.; Brake, Matthew R.W.

2015-08-01

The use of parameterized reduced order models(PROMs) within the stochastic reduced order model (SROM) framework is a logical progression for both methods. In this report, five different parameterized reduced order models are selected and critiqued against the other models along with truth model for the example of the Brake-Reuss beam. The models are: a Taylor series using finite difference, a proper orthogonal decomposition of the the output, a Craig-Bampton representation of the model, a method that uses Hyper-Dual numbers to determine the sensitivities, and a Meta-Model method that uses the Hyper-Dual results and constructs a polynomial curve to better representmore » the output data. The methods are compared against a parameter sweep and a distribution propagation where the first four statistical moments are used as a comparison. Each method produces very accurate results with the Craig-Bampton reduction having the least accurate results. The models are also compared based on time requirements for the evaluation of each model where the Meta- Model requires the least amount of time for computation by a significant amount. Each of the five models provided accurate results in a reasonable time frame. The determination of which model to use is dependent on the availability of the high-fidelity model and how many evaluations can be performed. Analysis of the output distribution is examined by using a large Monte-Carlo simulation along with a reduced simulation using Latin Hypercube and the stochastic reduced order model sampling technique. Both techniques produced accurate results. The stochastic reduced order modeling technique produced less error when compared to an exhaustive sampling for the majority of methods.« less

Model's sparse representation based on reduced mixed GMsFE basis methods

NASA Astrophysics Data System (ADS)

Jiang, Lijian; Li, Qiuqi

2017-06-01

In this paper, we propose a model's sparse representation based on reduced mixed generalized multiscale finite element (GMsFE) basis methods for elliptic PDEs with random inputs. A typical application for the elliptic PDEs is the flow in heterogeneous random porous media. Mixed generalized multiscale finite element method (GMsFEM) is one of the accurate and efficient approaches to solve the flow problem in a coarse grid and obtain the velocity with local mass conservation. When the inputs of the PDEs are parameterized by the random variables, the GMsFE basis functions usually depend on the random parameters. This leads to a large number degree of freedoms for the mixed GMsFEM and substantially impacts on the computation efficiency. In order to overcome the difficulty, we develop reduced mixed GMsFE basis methods such that the multiscale basis functions are independent of the random parameters and span a low-dimensional space. To this end, a greedy algorithm is used to find a set of optimal samples from a training set scattered in the parameter space. Reduced mixed GMsFE basis functions are constructed based on the optimal samples using two optimal sampling strategies: basis-oriented cross-validation and proper orthogonal decomposition. Although the dimension of the space spanned by the reduced mixed GMsFE basis functions is much smaller than the dimension of the original full order model, the online computation still depends on the number of coarse degree of freedoms. To significantly improve the online computation, we integrate the reduced mixed GMsFE basis methods with sparse tensor approximation and obtain a sparse representation for the model's outputs. The sparse representation is very efficient for evaluating the model's outputs for many instances of parameters. To illustrate the efficacy of the proposed methods, we present a few numerical examples for elliptic PDEs with multiscale and random inputs. In particular, a two-phase flow model in random porous media is simulated by the proposed sparse representation method.

Model's sparse representation based on reduced mixed GMsFE basis methods

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

Jiang, Lijian, E-mail: ljjiang@hnu.edu.cn; Li, Qiuqi, E-mail: qiuqili@hnu.edu.cn

2017-06-01

In this paper, we propose a model's sparse representation based on reduced mixed generalized multiscale finite element (GMsFE) basis methods for elliptic PDEs with random inputs. A typical application for the elliptic PDEs is the flow in heterogeneous random porous media. Mixed generalized multiscale finite element method (GMsFEM) is one of the accurate and efficient approaches to solve the flow problem in a coarse grid and obtain the velocity with local mass conservation. When the inputs of the PDEs are parameterized by the random variables, the GMsFE basis functions usually depend on the random parameters. This leads to a largemore » number degree of freedoms for the mixed GMsFEM and substantially impacts on the computation efficiency. In order to overcome the difficulty, we develop reduced mixed GMsFE basis methods such that the multiscale basis functions are independent of the random parameters and span a low-dimensional space. To this end, a greedy algorithm is used to find a set of optimal samples from a training set scattered in the parameter space. Reduced mixed GMsFE basis functions are constructed based on the optimal samples using two optimal sampling strategies: basis-oriented cross-validation and proper orthogonal decomposition. Although the dimension of the space spanned by the reduced mixed GMsFE basis functions is much smaller than the dimension of the original full order model, the online computation still depends on the number of coarse degree of freedoms. To significantly improve the online computation, we integrate the reduced mixed GMsFE basis methods with sparse tensor approximation and obtain a sparse representation for the model's outputs. The sparse representation is very efficient for evaluating the model's outputs for many instances of parameters. To illustrate the efficacy of the proposed methods, we present a few numerical examples for elliptic PDEs with multiscale and random inputs. In particular, a two-phase flow model in random porous media is simulated by the proposed sparse representation method.« less

Continuous piecewise-linear, reduced-order electrochemical model for lithium-ion batteries in real-time applications

NASA Astrophysics Data System (ADS)

Farag, Mohammed; Fleckenstein, Matthias; Habibi, Saeid

2017-02-01

Model-order reduction and minimization of the CPU run-time while maintaining the model accuracy are critical requirements for real-time implementation of lithium-ion electrochemical battery models. In this paper, an isothermal, continuous, piecewise-linear, electrode-average model is developed by using an optimal knot placement technique. The proposed model reduces the univariate nonlinear function of the electrode's open circuit potential dependence on the state of charge to continuous piecewise regions. The parameterization experiments were chosen to provide a trade-off between extensive experimental characterization techniques and purely identifying all parameters using optimization techniques. The model is then parameterized in each continuous, piecewise-linear, region. Applying the proposed technique cuts down the CPU run-time by around 20%, compared to the reduced-order, electrode-average model. Finally, the model validation against real-time driving profiles (FTP-72, WLTP) demonstrates the ability of the model to predict the cell voltage accurately with less than 2% error.

Geometry-dependent atomic multipole models for the water molecule.

PubMed

Loboda, O; Millot, C

2017-10-28

Models of atomic electric multipoles for the water molecule have been optimized in order to reproduce the electric potential around the molecule computed by ab initio calculations at the coupled cluster level of theory with up to noniterative triple excitations in an augmented triple-zeta quality basis set. Different models of increasing complexity, from atomic charges up to models containing atomic charges, dipoles, and quadrupoles, have been obtained. The geometry dependence of these atomic multipole models has been investigated by changing bond lengths and HOH angle to generate 125 molecular structures (reduced to 75 symmetry-unique ones). For several models, the atomic multipole components have been fitted as a function of the geometry by a Taylor series of fourth order in monomer coordinate displacements.

Geometry-dependent atomic multipole models for the water molecule

NASA Astrophysics Data System (ADS)

Loboda, O.; Millot, C.

2017-10-01

Models of atomic electric multipoles for the water molecule have been optimized in order to reproduce the electric potential around the molecule computed by ab initio calculations at the coupled cluster level of theory with up to noniterative triple excitations in an augmented triple-zeta quality basis set. Different models of increasing complexity, from atomic charges up to models containing atomic charges, dipoles, and quadrupoles, have been obtained. The geometry dependence of these atomic multipole models has been investigated by changing bond lengths and HOH angle to generate 125 molecular structures (reduced to 75 symmetry-unique ones). For several models, the atomic multipole components have been fitted as a function of the geometry by a Taylor series of fourth order in monomer coordinate displacements.

1D-3D hybrid modeling—from multi-compartment models to full resolution models in space and time

PubMed Central

Grein, Stephan; Stepniewski, Martin; Reiter, Sebastian; Knodel, Markus M.; Queisser, Gillian

2014-01-01

Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator—which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D-simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics. PMID:25120463

Amplitude and Phase Characteristics of Signals at the Output of Spatially Separated Antennas for Paths with Scattering

NASA Astrophysics Data System (ADS)

Anikin, A. S.

2018-06-01

Conditional statistical characteristics of the phase difference are considered depending on the ratio of instantaneous output signal amplitudes of spatially separated weakly directional antennas for the normal field model for paths with radio-wave scattering. The dependences obtained are related to the physical processes on the radio-wave propagation path. The normal model parameters are established at which the statistical characteristics of the phase difference depend on the ratio of the instantaneous amplitudes and hence can be used to measure the phase difference. Using Shannon's formula, the amount of information on the phase difference of signals contained in the ratio of their amplitudes is calculated depending on the parameters of the normal field model. Approaches are suggested to reduce the shift of phase difference measured for paths with radio-wave scattering. A comparison with results of computer simulation by the Monte Carlo method is performed.

Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology

PubMed Central

Tesseur, Ina; Zou, Kun; Esposito, Luke; Bard, Frederique; Berber, Elisabeth; Can, Judith Van; Lin, Amy H.; Crews, Leslie; Tremblay, Patrick; Mathews, Paul; Mucke, Lennart; Masliah, Eliezer; Wyss-Coray, Tony

2006-01-01

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and cerebral accumulation of the β-amyloid peptide (Aβ), but it is unknown what makes neurons susceptible to degeneration. We report that the TGF-β type II receptor (TβRII) is mainly expressed by neurons, and that TβRII levels are reduced in human AD brain and correlate with pathological hallmarks of the disease. Reducing neuronal TGF-β signaling in mice resulted in age-dependent neurodegeneration and promoted Aβ accumulation and dendritic loss in a mouse model of AD. In cultured cells, reduced TGF-β signaling caused neuronal degeneration and resulted in increased levels of secreted Aβ and β-secretase–cleaved soluble amyloid precursor protein. These results show that reduced neuronal TGF-β signaling increases age-dependent neurodegeneration and AD-like disease in vivo. Increasing neuronal TGF-β signaling may thus reduce neurodegeneration and be beneficial in AD. PMID:17080199

Dependence of stratocumulus-topped boundary-layer entrainment on cloud-water sedimentation: Impact on global aerosol indirect effect in GISS ModelE3 single column model and global simulations

NASA Astrophysics Data System (ADS)

Ackerman, A. S.; Kelley, M.; Cheng, Y.; Fridlind, A. M.; Del Genio, A. D.; Bauer, S.

2017-12-01

Reduction in cloud-water sedimentation induced by increasing droplet concentrations has been shown in large-eddy simulations (LES) and direct numerical simulation (DNS) to enhance boundary-layer entrainment, thereby reducing cloud liquid water path and offsetting the Twomey effect when the overlying air is sufficiently dry, which is typical. Among recent upgrades to ModelE3, the latest version of the NASA Goddard Institute for Space Studies (GISS) general circulation model (GCM), are a two-moment stratiform cloud microphysics treatment with prognostic precipitation and a moist turbulence scheme that includes an option in its entrainment closure of a simple parameterization for the effect of cloud-water sedimentation. Single column model (SCM) simulations are compared to LES results for a stratocumulus case study and show that invoking the sedimentation-entrainment parameterization option indeed reduces the dependence of cloud liquid water path on increasing aerosol concentrations. Impacts of variations of the SCM configuration and the sedimentation-entrainment parameterization will be explored. Its impact on global aerosol indirect forcing in the framework of idealized atmospheric GCM simulations will also be assessed.

Chronic Wasting Disease: Transmission Mechanisms and the Possibility of Harvest Management

PubMed Central

Potapov, Alex; Merrill, Evelyn; Pybus, Margo; Lewis, Mark A.

2016-01-01

We develop a model of CWD management by nonselective deer harvest, currently the most feasible approach available for managing CWD in wild populations. We use the model to explore the effects of 6 common harvest strategies on disease prevalence and to identify potential optimal harvest policies for reducing disease prevalence without population collapse. The model includes 4 deer categories (juveniles, adult females, younger adult males, older adult males) that may be harvested at different rates, a food-based carrying capacity, which influences juvenile survival but not adult reproduction or survival, and seasonal force of infection terms for each deer category under differing frequency-dependent transmission dynamics resulting from environmental and direct contact mechanisms. Numerical experiments show that the interval of transmission coefficients β where the disease can be controlled is generally narrow and efficiency of a harvest policy to reduce disease prevalence depends crucially on the details of the disease transmission mechanism, in particular on the intensity of disease transmission to juveniles and the potential differences in the behavior of older and younger males that influence contact rates. Optimal harvest policy to minimize disease prevalence for each of the assumed transmission mechanisms is shown to depend on harvest intensity. Across mechanisms, a harvest that focuses on antlered deer, without distinguishing between age classes reduces disease prevalence most consistently, whereas distinguishing between young and older antlered deer produces higher uncertainty in the harvest effects on disease prevalence. Our results show that, despite uncertainties, a modelling approach can determine classes of harvest strategy that are most likely to be effective in combatting CWD. PMID:26963921

Neuromodulation impact on nonlinear firing behavior of a reduced model motoneuron with the active dendrite

PubMed Central

Kim, Hojeong; Heckman, C. J.

2014-01-01

Neuromodulatory inputs from brainstem systems modulate the normal function of spinal motoneurons by altering the activation properties of persistent inward currents (PICs) in their dendrites. However, the effect of the PIC on firing outputs also depends on its location in the dendritic tree. To investigate the interaction between PIC neuromodulation and PIC location dependence, we used a two-compartment model that was biologically realistic in that it retains directional and frequency-dependent electrical coupling between the soma and the dendrites, as seen in multi-compartment models based on full anatomical reconstructions of motoneurons. Our two-compartment approach allowed us to systematically vary the coupling parameters between the soma and the dendrite to accurately reproduce the effect of location of the dendritic PIC on the generation of nonlinear (hysteretic) motoneuron firing patterns. Our results show that as a single parameter value for PIC activation was either increased or decreased by 20% from its default value, the solution space of the coupling parameter values for nonlinear firing outputs was drastically reduced by approximately 80%. As a result, the model tended to fire only in a linear mode at the majority of dendritic PIC sites. The same results were obtained when all parameters for the PIC activation simultaneously changed only by approximately ±10%. Our results suggest the democratization effect of neuromodulation: the neuromodulation by the brainstem systems may play a role in switching the motoneurons with PICs at different dendritic locations to a similar mode of firing by reducing the effect of the dendritic location of PICs on the firing behavior. PMID:25309410

Population viability analysis for endangered Roanoke logperch

USGS Publications Warehouse

Roberts, James H.; Angermeier, Paul; Anderson, Gregory B.

2016-01-01

A common strategy for recovering endangered species is ensuring that populations exceed the minimum viable population size (MVP), a demographic benchmark that theoretically ensures low long-term extinction risk. One method of establishing MVP is population viability analysis, a modeling technique that simulates population trajectories and forecasts extinction risk based on a series of biological, environmental, and management assumptions. Such models also help identify key uncertainties that have a large influence on extinction risk. We used stochastic count-based simulation models to explore extinction risk, MVP, and the possible benefits of alternative management strategies in populations of Roanoke logperch Percina rex, an endangered stream fish. Estimates of extinction risk were sensitive to the assumed population growth rate and model type, carrying capacity, and catastrophe regime (frequency and severity of anthropogenic fish kills), whereas demographic augmentation did little to reduce extinction risk. Under density-dependent growth, the estimated MVP for Roanoke logperch ranged from 200 to 4200 individuals, depending on the assumed severity of catastrophes. Thus, depending on the MVP threshold, anywhere from two to all five of the logperch populations we assessed were projected to be viable. Despite this uncertainty, these results help identify populations with the greatest relative extinction risk, as well as management strategies that might reduce this risk the most, such as increasing carrying capacity and reducing fish kills. Better estimates of population growth parameters and catastrophe regimes would facilitate the refinement of MVP and extinction-risk estimates, and they should be a high priority for future research on Roanoke logperch and other imperiled stream-fish species.

Modeling the resilience of critical infrastructure: the role of network dependencies.

PubMed

Guidotti, Roberto; Chmielewski, Hana; Unnikrishnan, Vipin; Gardoni, Paolo; McAllister, Therese; van de Lindt, John

2016-01-01

Water and wastewater network, electric power network, transportation network, communication network, and information technology network are among the critical infrastructure in our communities; their disruption during and after hazard events greatly affects communities' well-being, economic security, social welfare, and public health. In addition, a disruption in one network may cause disruption to other networks and lead to their reduced functionality. This paper presents a unified theoretical methodology for the modeling of dependent/interdependent infrastructure networks and incorporates it in a six-step probabilistic procedure to assess their resilience. Both the methodology and the procedure are general, can be applied to any infrastructure network and hazard, and can model different types of dependencies between networks. As an illustration, the paper models the direct effects of seismic events on the functionality of a potable water distribution network and the cascading effects of the damage of the electric power network (EPN) on the potable water distribution network (WN). The results quantify the loss of functionality and delay in the recovery process due to dependency of the WN on the EPN. The results show the importance of capturing the dependency between networks in modeling the resilience of critical infrastructure.

Modeling the resilience of critical infrastructure: the role of network dependencies

PubMed Central

Guidotti, Roberto; Chmielewski, Hana; Unnikrishnan, Vipin; Gardoni, Paolo; McAllister, Therese; van de Lindt, John

2017-01-01

Water and wastewater network, electric power network, transportation network, communication network, and information technology network are among the critical infrastructure in our communities; their disruption during and after hazard events greatly affects communities’ well-being, economic security, social welfare, and public health. In addition, a disruption in one network may cause disruption to other networks and lead to their reduced functionality. This paper presents a unified theoretical methodology for the modeling of dependent/interdependent infrastructure networks and incorporates it in a six-step probabilistic procedure to assess their resilience. Both the methodology and the procedure are general, can be applied to any infrastructure network and hazard, and can model different types of dependencies between networks. As an illustration, the paper models the direct effects of seismic events on the functionality of a potable water distribution network and the cascading effects of the damage of the electric power network (EPN) on the potable water distribution network (WN). The results quantify the loss of functionality and delay in the recovery process due to dependency of the WN on the EPN. The results show the importance of capturing the dependency between networks in modeling the resilience of critical infrastructure. PMID:28825037

On Defect Cluster Aggregation and Non-Reducibilty in Tin-Doped Indium Oxide

NASA Astrophysics Data System (ADS)

Warschkow, Oliver; Ellis, Donald E.; Gonzalez, Gabriela; Mason, Thomas O.

2003-03-01

The conductivity of tin-doped indium oxide (ITO), a transparent conductor, is critically dependent on the amount of tin-doping and oxygen partial pressure during preparation and annealing. Frank and Kostlin (Appl. Phys. A 27 (1982) 197-206) rationalized the carrier concentration dependence by postulating the formation of two types of neutral defect clusters at medium tin-doping levels: "Reducible" and "non-reducible" defect clusters; so named to indicate their ability to create carriers under reduction. According to Frank and Kostlin, both are composed of a single oxygen interstitial and two tin atoms substituting for indium, positioned in non-nearest and nearest coordination, respectively. This present work, seeking to distinguish reducible and non-reducible clusters by use of an atomistic model, finds only a weak correlation of oxygen interstitial binding energies with the relative positioning of dopants. Instead, the number of tin-dopants in the vicinity of the interstitial has a much larger effect on how strongly it is bound, a simple consequence of Coulomb interactions. We postulate that oxygen interstitials become non-reducible when clustered with three or more Sn_In. This occurs at higher doping levels as reducible clusters aggregate and share tin atoms. A simple probabilistic model, estimating the average number of clusters so aggregated, provides a qualitatively correct description of the carrier density in reduced ITO as a function of Sn doping level.

A variable turbulent Prandtl and Schmidt number model study for scramjet applications

NASA Astrophysics Data System (ADS)

Keistler, Patrick

A turbulence model that allows for the calculation of the variable turbulent Prandtl (Prt) and Schmidt (Sct) numbers as part of the solution is presented. The model also accounts for the interactions between turbulence and chemistry by modeling the corresponding terms. Four equations are added to the baseline k-zeta turbulence model: two equations for enthalpy variance and its dissipation rate to calculate the turbulent diffusivity, and two equations for the concentrations variance and its dissipation rate to calculate the turbulent diffusion coefficient. The underlying turbulence model already accounts for compressibility effects. The variable Prt /Sct turbulence model is validated and tuned by simulating a wide variety of experiments. Included in the experiments are two-dimensional, axisymmetric, and three-dimensional mixing and combustion cases. The combustion cases involved either hydrogen and air, or hydrogen, ethylene, and air. Two chemical kinetic models are employed for each of these situations. For the hydrogen and air cases, a seven species/seven reaction model where the reaction rates are temperature dependent and a nine species/nineteen reaction model where the reaction rates are dependent on both pressure and temperature are used. For the cases involving ethylene, a 15 species/44 reaction reduced model that is both pressure and temperature dependent is used, along with a 22 species/18 global reaction reduced model that makes use of the quasi-steady-state approximation. In general, fair to good agreement is indicated for all simulated experiments. The turbulence/chemistry interaction terms are found to have a significant impact on flame location for the two-dimensional combustion case, with excellent experimental agreement when the terms are included. In most cases, the hydrogen chemical mechanisms behave nearly identically, but for one case, the pressure dependent model would not auto-ignite at the same conditions as the experiment and the other chemical model. The model was artificially ignited in that case. For the cases involving ethylene combustion, the chemical model has a profound impact on the flame size, shape, and ignition location. However, without quantitative experimental data, it is difficult to determine which one is more suitable for this particular application.

Comprehensive Analyses of Ventricular Myocyte Models Identify Targets Exhibiting Favorable Rate Dependence

PubMed Central

Bugana, Marco; Severi, Stefano; Sobie, Eric A.

2014-01-01

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs. PMID:24675446

Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

PubMed

Cummins, Megan A; Dalal, Pavan J; Bugana, Marco; Severi, Stefano; Sobie, Eric A

2014-03-01

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs.

Multi-objective and Perishable Fuzzy Inventory Models Having Weibull Life-time With Time Dependent Demand, Demand Dependent Production and Time Varying Holding Cost: A Possibility/Necessity Approach

NASA Astrophysics Data System (ADS)

Pathak, Savita; Mondal, Seema Sarkar

2010-10-01

A multi-objective inventory model of deteriorating item has been developed with Weibull rate of decay, time dependent demand, demand dependent production, time varying holding cost allowing shortages in fuzzy environments for non- integrated and integrated businesses. Here objective is to maximize the profit from different deteriorating items with space constraint. The impreciseness of inventory parameters and goals for non-integrated business has been expressed by linear membership functions. The compromised solutions are obtained by different fuzzy optimization methods. To incorporate the relative importance of the objectives, the different cardinal weights crisp/fuzzy have been assigned. The models are illustrated with numerical examples and results of models with crisp/fuzzy weights are compared. The result for the model assuming them to be integrated business is obtained by using Generalized Reduced Gradient Method (GRG). The fuzzy integrated model with imprecise inventory cost is formulated to optimize the possibility necessity measure of fuzzy goal of the objective function by using credibility measure of fuzzy event by taking fuzzy expectation. The results of crisp/fuzzy integrated model are illustrated with numerical examples and results are compared.

On the Directional Dependence and Null Space Freedom in Uncertainty Bound Identification

NASA Technical Reports Server (NTRS)

Lim, K. B.; Giesy, D. P.

1997-01-01

In previous work, the determination of uncertainty models via minimum norm model validation is based on a single set of input and output measurement data. Since uncertainty bounds at each frequency is directionally dependent for multivariable systems, this will lead to optimistic uncertainty levels. In addition, the design freedom in the uncertainty model has not been utilized to further reduce uncertainty levels. The above issues are addressed by formulating a min- max problem. An analytical solution to the min-max problem is given to within a generalized eigenvalue problem, thus avoiding a direct numerical approach. This result will lead to less conservative and more realistic uncertainty models for use in robust control.

Dimensional Reduction for the General Markov Model on Phylogenetic Trees.

PubMed

Sumner, Jeremy G

2017-03-01

We present a method of dimensional reduction for the general Markov model of sequence evolution on a phylogenetic tree. We show that taking certain linear combinations of the associated random variables (site pattern counts) reduces the dimensionality of the model from exponential in the number of extant taxa, to quadratic in the number of taxa, while retaining the ability to statistically identify phylogenetic divergence events. A key feature is the identification of an invariant subspace which depends only bilinearly on the model parameters, in contrast to the usual multi-linear dependence in the full space. We discuss potential applications including the computation of split (edge) weights on phylogenetic trees from observed sequence data.

Role of the Charge-Transfer State in Reduced Langevin Recombination in Organic Solar Cells: A Theoretical Study

PubMed Central

2015-01-01

Reduced Langevin recombination has been observed in organic solar cells (OSCs) for many years, but its origin is still unclear. A recent work by Burke et al. (Adv. Energy Mater.2015, 5, 1500123-1) was inspired by this reduced Langevin recombination, and they proposed an equilibrium model of charge-transfer (CT) states that correlates the open-circuit voltage of OSCs with experimentally available device parameters. In this work, we extend Burke et al.’s CT model further and for the first time directly correlate the reduced Langevin recombination with the energetic and dynamic behavior of the CT state. Recombination through CT states leads in a straightforward manner to a decrease in the Langevin reduction factor with increasing temperature, without explicit consideration of the temperature dependence of the mobility. To verify the correlation between the CT states and reduced Langevin recombination, we incorporated this CT model and the reduced Langevin model into drift-diffusion simulations of a bilayer OSC. The simulations not only successfully reproduced realistic current–voltage (J–V) characteristics of the bilayer OSC, but also demonstrate that the two models consistently lead to same value of the apparent Langevin reduction factor. PMID:26640611

Effective size of density-dependent two-sex populations: the effect of mating systems.

PubMed

Myhre, A M; Engen, S; SAEther, B-E

2017-08-01

Density dependence in vital rates is a key feature affecting temporal fluctuations of natural populations. This has important implications for the rate of random genetic drift. Mating systems also greatly affect effective population sizes, but knowledge of how mating system and density regulation interact to affect random genetic drift is poor. Using theoretical models and simulations, we compare N e in short-lived, density-dependent animal populations with different mating systems. We study the impact of a fluctuating, density-dependent sex ratio and consider both a stable and a fluctuating environment. We find a negative relationship between annual N e /N and adult population size N due to density dependence, suggesting that loss of genetic variation is reduced at small densities. The magnitude of this decrease was affected by mating system and life history. A male-biased, density-dependent sex ratio reduces the rate of genetic drift compared to an equal, density-independent sex ratio, but a stochastic change towards male bias reduces the N e /N ratio. Environmental stochasticity amplifies temporal fluctuations in population size and is thus vital to consider in estimation of effective population sizes over longer time periods. Our results on the reduced loss of genetic variation at small densities, particularly in polygamous populations, indicate that density regulation may facilitate adaptive evolution at small population sizes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Rosuvastatin protects against angiotensin II-induced renal injury in a dose-dependent fashion.

PubMed

Park, Joon-Keun; Mervaala, Eero Ma; Muller, Dominik N; Menne, Jan; Fiebeler, Anette; Luft, Friedrich C; Haller, Hermann

2009-03-01

We showed earlier that statin treatment ameliorates target-organ injury in a transgenic model of angiotensin (Ang) II-induced hypertension. We now test the hypothesis that rosuvastatin (1, 10, and 50 mg/kg/day) influences leukocyte adhesion and infiltration, prevents induction of inducible nitric oxide synthase (iNOS), and ameliorates target-organ damage in a dose-dependent fashion. We treated rats harboring the human renin and human angiotensinogen genes (dTGR) from week 4 to 8 (n = 20 per group). Untreated dTGR developed severe hypertension, cardiac hypertrophy, and renal damage, with a 100-fold increased albuminuria and focal cortical necrosis. Mortality of untreated dTGR at age 8 weeks was 59%. Rosuvastatin treatment decreased mortality dose-dependently. Blood pressure was not affected. Albuminuria was reduced dose-dependently. Interstitial adhesion molecule (ICAM)-1 expression was markedly reduced by rosuvastatin, as were neutrophil and monocyte infiltration. Immunohistochemistry showed an increased endothelial and medial iNOS expression in small vessels, infiltrating cells, afferent arterioles, and glomeruli of dTGR. Immunoreactivity was stronger in cortex than medulla. Rosuvastatin markedly reduced the iNOS expression in both cortex and medulla. Finally, matrix protein (type IV collagen, fibronectin) expression was also dose- dependently reduced by rosuvastatin. Our findings indicate that rosuvastatin dose- dependently ameliorates angiotensin II-induced-organ damage and almost completely prevents inflammation at the highest dose. The data implicate 3-hydroxy-3-methylglutaryl coenzyme A function in signaling events leading to target-organ damage.

Dependence of Attenuation of Common Mode Radiation from Indoor Power Line Communication System on Structure of Reinforced Concrete Wall

NASA Astrophysics Data System (ADS)

Wu, Ifong; Ishigami, Shinobu; Gotoh, Kaoru; Matsumoto, Yasushi

The attenuation effect of the walls of a building on the electromagnetic (EM) field generated by an indoor power line communication (PLC) system is numerically investigated using the finite integration (FI) method. In particular, we focus on the frequency range 2-6MHz, for which the attenuation effect has not yet been sufficiently analyzed. We model a single, finite-sized wall instead of an entire house, to focus on the dependence of the EM field on the wall structure and also reduce the computational resources required. The EM field strength is evaluated at many points on a view plane 10m from the wall model, and the results are statistically processed to determine the attenuation effect of the wall. We show that the leakage of an EM field at 2-6MHz is suppressed by about 30dB by a reinforced concrete wall. We also show that the main contributor to the attenuation effect is the rebar in the wall. We then investigate the relation between the attenuation effect of a single-wall model and that of a house model. The results show that the attenuation effect of a house model is almost the same as that of a 15-m-wall model. We conclude that the use of a single-wall model instead of a house model is effective in determining the attenuation of the EM leakage. This simple structure reduces analytic space, time, and memory in the evaluation of the dependence on the wall structure of the EM leakage from indoor PLC systems.

Effect of aerodynamic detuning on supersonic rotor discrete frequency noise generation

NASA Technical Reports Server (NTRS)

Hoyniak, D.; Fleeter, Sanford

1988-01-01

A mathematical model was developed to predict the effect of alternate blade circumferential aerodynamic detuning on the discrete frequency noise generation of a supersonic rotor. Aerodynamic detuning was shown to have a small beneficial effect on the noise generation for reduced frequencies less than 3. For reduced frequencies greater than 3, however, the aerodynamic detuning either increased or decreased the noise generated, depending on the value of the reduced frequency.

Abnormal Thiamine-Dependent Processes in Alzheimer’s Disease. Lessons from Diabetes

PubMed Central

Gibson, Gary E.; Hirsch, Joseph A.; Cirio, Rosanna T.; Jordan, Barry D.; Fonzetti, Pasquale; Elder, Jessica

2013-01-01

Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. PMID:22982063

Software dependability in the Tandem GUARDIAN system

NASA Technical Reports Server (NTRS)

Lee, Inhwan; Iyer, Ravishankar K.

1995-01-01

Based on extensive field failure data for Tandem's GUARDIAN operating system this paper discusses evaluation of the dependability of operational software. Software faults considered are major defects that result in processor failures and invoke backup processes to take over. The paper categorizes the underlying causes of software failures and evaluates the effectiveness of the process pair technique in tolerating software faults. A model to describe the impact of software faults on the reliability of an overall system is proposed. The model is used to evaluate the significance of key factors that determine software dependability and to identify areas for improvement. An analysis of the data shows that about 77% of processor failures that are initially considered due to software are confirmed as software problems. The analysis shows that the use of process pairs to provide checkpointing and restart (originally intended for tolerating hardware faults) allows the system to tolerate about 75% of reported software faults that result in processor failures. The loose coupling between processors, which results in the backup execution (the processor state and the sequence of events) being different from the original execution, is a major reason for the measured software fault tolerance. Over two-thirds (72%) of measured software failures are recurrences of previously reported faults. Modeling, based on the data, shows that, in addition to reducing the number of software faults, software dependability can be enhanced by reducing the recurrence rate.

The Interplay of School Readiness and Teacher Readiness for Educational Technology Integration: A Structural Equation Model

ERIC Educational Resources Information Center

Petko, Dominik; Prasse, Doreen; Cantieni, Andrea

2018-01-01

Decades of research have shown that technological change in schools depends on multiple interrelated factors. Structural equation models explaining the interplay of factors often suffer from high complexity and low coherence. To reduce complexity, a more robust structural equation model was built with data from a survey of 349 Swiss primary school…

A New Method for Setting Calculation Sequence of Directional Relay Protection in Multi-Loop Networks

NASA Astrophysics Data System (ADS)

Haijun, Xiong; Qi, Zhang

2016-08-01

Workload of relay protection setting calculation in multi-loop networks may be reduced effectively by optimization setting calculation sequences. A new method of setting calculation sequences of directional distance relay protection in multi-loop networks based on minimum broken nodes cost vector (MBNCV) was proposed to solve the problem experienced in current methods. Existing methods based on minimum breakpoint set (MBPS) lead to more break edges when untying the loops in dependent relationships of relays leading to possibly more iterative calculation workloads in setting calculations. A model driven approach based on behavior trees (BT) was presented to improve adaptability of similar problems. After extending the BT model by adding real-time system characters, timed BT was derived and the dependency relationship in multi-loop networks was then modeled. The model was translated into communication sequence process (CSP) models and an optimization setting calculation sequence in multi-loop networks was finally calculated by tools. A 5-nodes multi-loop network was applied as an example to demonstrate effectiveness of the modeling and calculation method. Several examples were then calculated with results indicating the method effectively reduces the number of forced broken edges for protection setting calculation in multi-loop networks.

Finite metapopulation models with density-dependent migration and stochastic local dynamics

PubMed Central

Saether, B.-E.; Engen, S.; Lande, R.

1999-01-01

The effects of small density-dependent migration on the dynamics of a metapopulation are studied in a model with stochastic local dynamics. We use a diffusion approximation to study how changes in the migration rate and habitat occupancy affect the rates of local colonization and extinction. If the emigration rate increases or if the immigration rate decreases with local population size, a positive expected rate of change in habitat occupancy is found for a greater range of habitat occupancies than when the migration is density-independent. In contrast, the reverse patterns of density dependence in respective emigration and immigration reduce the range of habitat occupancies where the metapopulation will be viable. This occurs because density-dependent migration strongly influences both the establishment and rescue effects in the local dynamics of metapopulations.

Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-11-01

We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Reduced-Order Model for Efficient Simulation of Synthetic Jet Actuators

NASA Technical Reports Server (NTRS)

Yamaleev, Nail K.; Carpenter, Mark H.

2003-01-01

A new reduced-order model of multidimensional synthetic jet actuators that combines the accuracy and conservation properties of full numerical simulation methods with the efficiency of simplified zero-order models is proposed. The multidimensional actuator is simulated by solving the time-dependent compressible quasi-1-D Euler equations, while the diaphragm is modeled as a moving boundary. The governing equations are approximated with a fourth-order finite difference scheme on a moving mesh such that one of the mesh boundaries coincides with the diaphragm. The reduced-order model of the actuator has several advantages. In contrast to the 3-D models, this approach provides conservation of mass, momentum, and energy. Furthermore, the new method is computationally much more efficient than the multidimensional Navier-Stokes simulation of the actuator cavity flow, while providing practically the same accuracy in the exterior flowfield. The most distinctive feature of the present model is its ability to predict the resonance characteristics of synthetic jet actuators; this is not practical when using the 3-D models because of the computational cost involved. Numerical results demonstrating the accuracy of the new reduced-order model and its limitations are presented.

The Effect of the Psychiatric Nursing Approach Based on the Tidal Model on Coping and Self-esteem in People with Alcohol Dependency: A Randomized Trial.

PubMed

Savaşan, Ayşegül; Çam, Olcay

2017-06-01

People with alcohol dependency have lower self-esteem than controls and when their alcohol use increases, their self-esteem decreases. Coping skills in alcohol related issues are predicted to reduce vulnerability to relapse. It is important to adapt care to individual needs so as to prevent a return to the cycle of alcohol use. The Tidal Model focuses on providing support and services to people who need to live a constructive life. The aim of the randomized study was to determine the effect of the psychiatric nursing approach based on the Tidal Model on coping and self-esteem in people with alcohol dependency. The study was semi-experimental in design with a control group, and was conducted on 36 individuals (18 experimental, 18 control). An experimental and a control group were formed by assigning persons to each group using the stratified randomization technique in the order in which they were admitted to hospital. The Coping Inventory (COPE) and the Coopersmith Self-Esteem Inventory (CSEI) were used as measurement instruments. The measurement instruments were applied before the application and three months after the application. In addition to routine treatment and follow-up, the psychiatric nursing approach based on the Tidal Model was applied to the experimental group in the One-to-One Sessions. The psychiatric nursing approach based on the Tidal Model is an approach which is effective in increasing the scores of people with alcohol dependency in positive reinterpretation and growth, active coping, restraint, emotional social support and planning and reducing their scores in behavioral disengagement. It was seen that self-esteem rose, but the difference from the control group did not reach significance. The psychiatric nursing approach based on the Tidal Model has an effect on people with alcohol dependency in maintaining their abstinence. The results of the study may provide practices on a theoretical basis for improving coping behaviors and self-esteem and facilitating the recovery process of alcohol dependents with implications for mental health nursing. Copyright © 2017 Elsevier Inc. All rights reserved.

Isoprene and monoterpene emissions in south-east Australia: comparison of a multi-layer canopy model with MEGAN and with atmospheric observations

NASA Astrophysics Data System (ADS)

Emmerson, Kathryn M.; Cope, Martin E.; Galbally, Ian E.; Lee, Sunhee; Nelson, Peter F.

2018-05-01

One of the key challenges in atmospheric chemistry is to reduce the uncertainty of biogenic volatile organic compound (BVOC) emission estimates from vegetation to the atmosphere. In Australia, eucalypt trees are a primary source of biogenic emissions, but their contribution to Australian air sheds is poorly quantified. The Model of Emissions of Gases and Aerosols from Nature (MEGAN) has performed poorly against Australian isoprene and monoterpene observations. Finding reasons for the MEGAN discrepancies and strengthening our understanding of biogenic emissions in this region is our focus. We compare MEGAN to the locally produced Australian Biogenic Canopy and Grass Emissions Model (ABCGEM), to identify the uncertainties associated with the emission estimates and the data requirements necessary to improve isoprene and monoterpene emissions estimates for the application of MEGAN in Australia. Previously unpublished, ABCGEM is applied as an online biogenic emissions inventory to model BVOCs in the air shed overlaying Sydney, Australia. The two models use the same meteorological inputs and chemical mechanism, but independent inputs of leaf area index (LAI), plant functional type (PFT) and emission factors. We find that LAI, a proxy for leaf biomass, has a small role in spatial, temporal and inter-model biogenic emission variability, particularly in urban areas for ABCGEM. After removing LAI as the source of the differences, we found large differences in the emission activity function for monoterpenes. In MEGAN monoterpenes are partially light dependent, reducing their dependence on temperature. In ABCGEM monoterpenes are not light dependent, meaning they continue to be emitted at high rates during hot summer days, and at night. When the light dependence of monoterpenes is switched off in MEGAN, night-time emissions increase by 90-100 % improving the comparison with observations, suggesting the possibility that monoterpenes emitted from Australian vegetation may not be as light dependent as vegetation globally. Targeted measurements of emissions from in situ Australian vegetation, particularly of the light dependence issue are critical to improving MEGAN for one of the world's major biogenic emitting regions.

CP violation in multibody B decays from QCD factorization

NASA Astrophysics Data System (ADS)

Klein, Rebecca; Mannel, Thomas; Virto, Javier; Vos, K. Keri

2017-10-01

We test a data-driven approach based on QCD factorization for charmless three-body B-decays by confronting it to measurements of CP violation in B - → π - π + π -. While some of the needed non-perturbative objects can be directly extracted from data, some others can, so far, only be modelled. Although this approach is currently model dependent, we comment on the perspectives to reduce this model dependence. While our model naturally accommodates the gross features of the Dalitz distribution, it cannot quantitatively explain the details seen in the current experimental data on local CP asymmetries. We comment on possible refinements of our simple model and conclude by briefly discussing a possible extension of the model to large invariant masses, where large local CP asymmetries have been measured.

Metabolomic studies identify changes in transmethylation and polyamine metabolism in a brain-specific mouse model of tuberous sclerosis complex.

PubMed

McKenna, James; Kapfhamer, David; Kinchen, Jason M; Wasek, Brandi; Dunworth, Matthew; Murray-Stewart, Tracy; Bottiglieri, Teodoro; Casero, Robert A; Gambello, Michael J

2018-06-15

Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental disorder and the quintessential disorder of mechanistic Target of Rapamycin Complex 1 (mTORC1) dysregulation. Loss of either causative gene, TSC1 or TSC2, leads to constitutive mTORC1 kinase activation and a pathologically anabolic state of macromolecular biosynthesis. Little is known about the organ-specific metabolic reprogramming that occurs in TSC-affected organs. Using a mouse model of TSC in which Tsc2 is disrupted in radial glial precursors and their neuronal and glial descendants, we performed an unbiased metabolomic analysis of hippocampi to identify Tsc2-dependent metabolic changes. Significant metabolic reprogramming was found in well-established pathways associated with mTORC1 activation, including redox homeostasis, glutamine/tricarboxylic acid cycle, pentose and nucleotide metabolism. Changes in two novel pathways were identified: transmethylation and polyamine metabolism. Changes in transmethylation included reduced methionine, cystathionine, S-adenosylmethionine (SAM-the major methyl donor), reduced SAM/S-adenosylhomocysteine ratio (cellular methylation potential), and elevated betaine, an alternative methyl donor. These changes were associated with alterations in SAM-dependent methylation pathways and expression of the enzymes methionine adenosyltransferase 2A and cystathionine beta synthase. We also found increased levels of the polyamine putrescine due to increased activity of ornithine decarboxylase, the rate-determining enzyme in polyamine synthesis. Treatment of Tsc2+/- mice with the ornithine decarboxylase inhibitor α-difluoromethylornithine, to reduce putrescine synthesis dose-dependently reduced hippocampal astrogliosis. These data establish roles for SAM-dependent methylation reactions and polyamine metabolism in TSC neuropathology. Importantly, both pathways are amenable to nutritional or pharmacologic therapy.

Impacts of correcting the inter-variable correlation of climate model outputs on hydrological modeling

NASA Astrophysics Data System (ADS)

Chen, Jie; Li, Chao; Brissette, François P.; Chen, Hua; Wang, Mingna; Essou, Gilles R. C.

2018-05-01

Bias correction is usually implemented prior to using climate model outputs for impact studies. However, bias correction methods that are commonly used treat climate variables independently and often ignore inter-variable dependencies. The effects of ignoring such dependencies on impact studies need to be investigated. This study aims to assess the impacts of correcting the inter-variable correlation of climate model outputs on hydrological modeling. To this end, a joint bias correction (JBC) method which corrects the joint distribution of two variables as a whole is compared with an independent bias correction (IBC) method; this is considered in terms of correcting simulations of precipitation and temperature from 26 climate models for hydrological modeling over 12 watersheds located in various climate regimes. The results show that the simulated precipitation and temperature are considerably biased not only in the individual distributions, but also in their correlations, which in turn result in biased hydrological simulations. In addition to reducing the biases of the individual characteristics of precipitation and temperature, the JBC method can also reduce the bias in precipitation-temperature (P-T) correlations. In terms of hydrological modeling, the JBC method performs significantly better than the IBC method for 11 out of the 12 watersheds over the calibration period. For the validation period, the advantages of the JBC method are greatly reduced as the performance becomes dependent on the watershed, GCM and hydrological metric considered. For arid/tropical and snowfall-rainfall-mixed watersheds, JBC performs better than IBC. For snowfall- or rainfall-dominated watersheds, however, the two methods behave similarly, with IBC performing somewhat better than JBC. Overall, the results emphasize the advantages of correcting the P-T correlation when using climate model-simulated precipitation and temperature to assess the impact of climate change on watershed hydrology. However, a thorough validation and a comparison with other methods are recommended before using the JBC method, since it may perform worse than the IBC method for some cases due to bias nonstationarity of climate model outputs.

Assessing the utility of frequency dependent nudging for reducing biases in biogeochemical models

NASA Astrophysics Data System (ADS)

Lagman, Karl B.; Fennel, Katja; Thompson, Keith R.; Bianucci, Laura

2014-09-01

Bias errors, resulting from inaccurate boundary and forcing conditions, incorrect model parameterization, etc. are a common problem in environmental models including biogeochemical ocean models. While it is important to correct bias errors wherever possible, it is unlikely that any environmental model will ever be entirely free of such errors. Hence, methods for bias reduction are necessary. A widely used technique for online bias reduction is nudging, where simulated fields are continuously forced toward observations or a climatology. Nudging is robust and easy to implement, but suppresses high-frequency variability and introduces artificial phase shifts. As a solution to this problem Thompson et al. (2006) introduced frequency dependent nudging where nudging occurs only in prescribed frequency bands, typically centered on the mean and the annual cycle. They showed this method to be effective for eddy resolving ocean circulation models. Here we add a stability term to the previous form of frequency dependent nudging which makes the method more robust for non-linear biological models. Then we assess the utility of frequency dependent nudging for biological models by first applying the method to a simple predator-prey model and then to a 1D ocean biogeochemical model. In both cases we only nudge in two frequency bands centered on the mean and the annual cycle, and then assess how well the variability in higher frequency bands is recovered. We evaluate the effectiveness of frequency dependent nudging in comparison to conventional nudging and find significant improvements with the former.

Analysis of Wind Tunnel Lateral Oscillatory Data of the F-16XL Aircraft

NASA Technical Reports Server (NTRS)

Klein, Vladislav; Murphy, Patrick C.; Szyba, Nathan M.

2004-01-01

Static and dynamic wind tunnel tests were performed on an 18% scale model of the F-16XL aircraft. These tests were performed over a wide range of angles of attack and sideslip with oscillation amplitudes from 5 deg. to 30 deg. and reduced frequencies from 0.073 to 0.269. Harmonic analysis was used to estimate Fourier coefficients and in-phase and out-of-phase components. For frequency dependent data from rolling oscillations, a two-step regression method was used to obtain unsteady models (indicial functions), and derivatives due to sideslip angle, roll rate and yaw rate from in-phase and out-of-phase components. Frequency dependence was found for angles of attack between 20 deg. and 50 deg. Reduced values of coefficient of determination and increased values of fit error were found for angles of attack between 35 deg. and 45 deg. An attempt to estimate model parameters from yaw oscillations failed, probably due to the low number of test cases at different frequencies.

Anomalous temperature dependence of layer spacing of de Vries liquid crystals: Compensation model

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

Merkel, K.; Kocot, A.; Vij, J. K., E-mail: jvij@tcd.ie

Smectic liquid crystals that exhibit temperature independent layer thickness offer technological advantages for their use in displays and photonic devices. The dependence of the layer spacing in SmA and SmC phases of de Vries liquid crystals is found to exhibit distinct features. On entering the SmC phase, the layer thickness initially decreases below SmA to SmC (T{sub A–C}) transition temperature but increases anomalously with reducing temperature despite the molecular tilt increasing. This anomalous observation is being explained quantitatively. Results of IR spectroscopy show that layer shrinkage is caused by tilt of the mesogen's rigid core, whereas the expansion is causedmore » by the chains getting more ordered with reducing temperature. This mutual compensation arising from molecular fragments contributing to the layer thickness differs from the previous models. The orientational order parameter of the rigid core of the mesogen provides direct evidence for de Vries cone model in the SmA phase for the two compounds investigated.« less

Evaluation of Smoking Prevention Television Messages Based on the Elaboration Likelihood Model

ERIC Educational Resources Information Center

Flynn, Brian S.; Worden, John K.; Bunn, Janice Yanushka; Connolly, Scott W.; Dorwaldt, Anne L.

2011-01-01

Progress in reducing youth smoking may depend on developing improved methods to communicate with higher risk youth. This study explored the potential of smoking prevention messages based on the Elaboration Likelihood Model (ELM) to address these needs. Structured evaluations of 12 smoking prevention messages based on three strategies derived from…

Cardiac transient outward potassium current: a pulse chemistry model of frequency-dependent properties.

PubMed

Liu, L; Krinsky, V I; Grant, A O; Starmer, C F

1996-01-01

Recent voltage-clamp studies of isolated myocytes have demonstrated widespread occurrence of a transient outward current (I(to)) carried by potassium ions. In the canine ventricle, this current is well developed in epicardial cells but not in endocardial cells. The resultant spatial dispersion of refractoriness is potentially proarrhythmic and may be amplified by channel blockade. The inactivation and recovery time constants of this channel are in excess of several hundred milliseconds, and consequently channel availability is frequency dependent at physiological stimulation rates. When the time constants associated with transitions between different channel conformations are rapid relative to drug binding kinetics, the interactions between drugs and an ion channel can be approximated by a sequence of first-order reactions, in which binding occurs in pulses in response to pulse train stimulation (pulse chemistry). When channel conformation transition time constants do not meet this constraint, analytical characterizations of the drug-channel interaction must then be modified to reflect the channel time-dependent properties. Here we report that the rate and steady-state amount of frequency-dependent inactivation of I(to) are consistent with a generalization of the channel blockade model: channel availability is reduced in a pulsatile exponential pattern as the stimulation frequency is increased, and the rate of reduction is a linear function of the pulse train depolarizing and recovery intervals. I(to) was reduced in the presence of quinidine. After accounting for the use-dependent availability of I(to) channels, we found little evidence of an additional use-dependent component of block after exposure to quinidine, suggesting that quinidine reacts with both open and closed I(to) channels as though the binding site is continuously accessible. The model provides a useful tool for assessing drug-channel interactions when the reaction cannot be continuously monitored.

Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence

PubMed Central

Gomez, Juan L.; Cunningham, Christopher L.; Finn, Deborah A.; Young, Emily A.; Helpenstell, Lily K.; Schuette, Lindsey M.; Fidler, Tara L.; Kosten, Therese A.; Ryabinin, Andrey E.

2015-01-01

An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increased alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects to ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies. PMID:26051399

The role of 3D visualisation as an analytical tool preparatory to numerical modelling [rapid communication

NASA Astrophysics Data System (ADS)

Robins, N. S.; Rutter, H. K.; Dumpleton, S.; Peach, D. W.

2005-01-01

Groundwater investigation has long depended on the process of developing a conceptual flow model as a precursor to developing a mathematical model, which in turn may lead in complex aquifers to the development of a numerical approximation model. The assumptions made in the development of the conceptual model depend heavily on the geological framework defining the aquifer, and if the conceptual model is inappropriate then subsequent modelling will also be incorrect. Paradoxically, the development of a robust conceptual model remains difficult, not least because this 3D paradigm is usually reduced to 2D plans and sections. 3D visualisation software is now available to facilitate the development of the conceptual model, to make the model more robust and defensible and to assist in demonstrating the hydraulics of the aquifer system. Case studies are presented to demonstrate the role and cost-effectiveness of the visualisation process.

Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

PubMed

Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

2015-01-15

Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (P<0.05). Also, the swimmer morphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (P<0.05), higher levels of sucrose preference (P<0.001) than sedentary rats. Voluntary consumption of oral morphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (P<0.01). We conclude that regular swimming exercise reduces the severity of morphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamic Data-Driven Reduced-Order Models of Macroscale Quantities for the Prediction of Equilibrium System State for Multiphase Porous Medium Systems

NASA Astrophysics Data System (ADS)

Talbot, C.; McClure, J. E.; Armstrong, R. T.; Mostaghimi, P.; Hu, Y.; Miller, C. T.

2017-12-01

Microscale simulation of multiphase flow in realistic, highly-resolved porous medium systems of a sufficient size to support macroscale evaluation is computationally demanding. Such approaches can, however, reveal the dynamic, steady, and equilibrium states of a system. We evaluate methods to utilize dynamic data to reduce the cost associated with modeling a steady or equilibrium state. We construct data-driven models using extensions to dynamic mode decomposition (DMD) and its connections to Koopman Operator Theory. DMD and its variants comprise a class of equation-free methods for dimensionality reduction of time-dependent nonlinear dynamical systems. DMD furnishes an explicit reduced representation of system states in terms of spatiotemporally varying modes with time-dependent oscillation frequencies and amplitudes. We use DMD to predict the steady and equilibrium macroscale state of a realistic two-fluid porous medium system imaged using micro-computed tomography (µCT) and simulated using the lattice Boltzmann method (LBM). We apply Koopman DMD to direct numerical simulation data resulting from simulations of multiphase fluid flow through a 1440x1440x4320 section of a full 1600x1600x5280 realization of imaged sandstone. We determine a representative set of system observables via dimensionality reduction techniques including linear and kernel principal component analysis. We demonstrate how this subset of macroscale quantities furnishes a representation of the time-evolution of the system in terms of dynamic modes, and discuss the selection of a subset of DMD modes yielding the optimal reduced model, as well as the time-dependence of the error in the predicted equilibrium value of each macroscale quantity. Finally, we describe how the above procedure, modified to incorporate methods from compressed sensing and random projection techniques, may be used in an online fashion to facilitate adaptive time-stepping and parsimonious storage of system states over time.

A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices

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

Schlosser, Paul M., E-mail: schlosser.paul@epa.gov; Sasso, Alan F.

Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function ofmore » Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.« less

Use of machine learning methods to reduce predictive error of groundwater models.

PubMed

Xu, Tianfang; Valocchi, Albert J; Choi, Jaesik; Amir, Eyal

2014-01-01

Quantitative analyses of groundwater flow and transport typically rely on a physically-based model, which is inherently subject to error. Errors in model structure, parameter and data lead to both random and systematic error even in the output of a calibrated model. We develop complementary data-driven models (DDMs) to reduce the predictive error of physically-based groundwater models. Two machine learning techniques, the instance-based weighting and support vector regression, are used to build the DDMs. This approach is illustrated using two real-world case studies of the Republican River Compact Administration model and the Spokane Valley-Rathdrum Prairie model. The two groundwater models have different hydrogeologic settings, parameterization, and calibration methods. In the first case study, cluster analysis is introduced for data preprocessing to make the DDMs more robust and computationally efficient. The DDMs reduce the root-mean-square error (RMSE) of the temporal, spatial, and spatiotemporal prediction of piezometric head of the groundwater model by 82%, 60%, and 48%, respectively. In the second case study, the DDMs reduce the RMSE of the temporal prediction of piezometric head of the groundwater model by 77%. It is further demonstrated that the effectiveness of the DDMs depends on the existence and extent of the structure in the error of the physically-based model. © 2013, National GroundWater Association.

Modeled Microgravity Disrupts Collagen I/Integrin Signaling During Osteoblastic Differentiation of Human Mesenchymal Stem Cells

NASA Technical Reports Server (NTRS)

Meyers, Valerie E.; Zayzafoon, Majd; Gonda, Steven R.; Gathings, William E.; McDonald, Jay M.

2004-01-01

Spaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following seven days culture in modeled microgravity. One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen-integrin interactions and reduced integrin signaling. Integrins are heterodimeric transmembrane receptors that bind extracellular matrix proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of modeled microgravity on integrin expression and function in hMSC. We demonstrate that seven days of culture in modeled microgravity leads to reduced expression of the extracellular matrix protein, type I collagen (Col I). Conversely, modeled microgravity consistently increases Col I-specific alpha2 and beta1 integrin protein expression. Despite this increase in integrin sub-unit expression, autophosphorylation of adhesion-dependent kinases, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), is significantly reduced. Activation of Akt is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras-MAPK pathway is evidenced by a reduction in Ras and ERK activation. Taken together, our findings indicate that modeled microgravity decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis.

Model for Ultrafast Carrier Scattering in Semiconductors

DTIC Science & Technology

2012-11-14

energy transfer between semi-classical carrier drift-diffusion under an electric field and quantum kinetics of interband /intersubband transitions...from an electron during each phonon-emission event. The net rate of phonon emission is determined by the Boltzmann scattering equation which depends ...energy-drift term under a strong dc field was demonstrated to reduce the field- dependent drift velocity and mobility. The Doppler shift in the energy

Structural design optimization with survivability dependent constraints application: Primary wing box of a multi-role fighter

NASA Technical Reports Server (NTRS)

Dolvin, Douglas J.

1992-01-01

The superior survivability of a multirole fighter is dependent upon balanced integration of technologies for reduced vulnerability and susceptability. The objective is to develop a methodology for structural design optimization with survivability dependent constraints. The design criteria for optimization will be survivability in a tactical laser environment. The following analyses are studied to establish a dependent design relationship between structural weight and survivability: (1) develop a physically linked global design model of survivability variables; and (2) apply conventional constraints to quantify survivability dependent design. It was not possible to develop an exact approach which would include all aspects of survivability dependent design, therefore guidelines are offered for solving similar problems.

Specific heat capacity of molten salt-based alumina nanofluid.

PubMed

Lu, Ming-Chang; Huang, Chien-Hsun

2013-06-21

There is no consensus on the effect of nanoparticle (NP) addition on the specific heat capacity (SHC) of fluids. In addition, the predictions from the existing model have a large discrepancy from the measured SHCs in nanofluids. We show that the SHC of the molten salt-based alumina nanofluid decreases with reducing particle size and increasing particle concentration. The NP size-dependent SHC is resulted from an augmentation of the nanolayer effect as particle size reduces. A model considering the nanolayer effect which supports the experimental results was proposed.

Specific heat capacity of molten salt-based alumina nanofluid

PubMed Central

2013-01-01

There is no consensus on the effect of nanoparticle (NP) addition on the specific heat capacity (SHC) of fluids. In addition, the predictions from the existing model have a large discrepancy from the measured SHCs in nanofluids. We show that the SHC of the molten salt-based alumina nanofluid decreases with reducing particle size and increasing particle concentration. The NP size-dependent SHC is resulted from an augmentation of the nanolayer effect as particle size reduces. A model considering the nanolayer effect which supports the experimental results was proposed. PMID:23800321

Comparison of detailed and reduced kinetics mechanisms of silane oxidation in the basis of detonation wave structure problem

NASA Astrophysics Data System (ADS)

Fedorov, A. V.; Tropin, D. A.; Fomin, P. A.

2018-03-01

The paper deals with the problem of the structure of detonation waves in the silane-air mixture within the framework of mathematical model of a nonequilibrium gas dynamics. Detailed kinetic scheme of silane oxidation as well as the newly developed reduced kinetic model of detonation combustion of silane are used. On its basis the detonation wave (DW) structure in stoichiometric silane - air mixture and dependences of Chapman-Jouguet parameters of mixture on stoichiometric ratio between the fuel (silane) and an oxidizer (air) were obtained.

Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics

NASA Astrophysics Data System (ADS)

Greulich, Philip; Doležal, Jakub; Scott, Matthew; Evans, Martin R.; Allen, Rosalind J.

2017-12-01

Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance—yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic. Our results depend strongly on whether the antibiotic shows reversible transport and/or low-affinity ribosome binding (‘low-affinity antibiotic’) or, in contrast, irreversible transport and/or high affinity ribosome binding (‘high-affinity antibiotic’). For low-affinity antibiotics, our model predicts that growth inhibition depends on the duration of the antibiotic pulse, and can show a transient period of very fast growth following removal of the antibiotic. For high-affinity antibiotics, growth inhibition depends on peak dosage rather than dose duration, and the model predicts a pronounced post-antibiotic effect, due to hysteresis, in which growth can be suppressed for long times after the antibiotic dose has ended. These predictions are experimentally testable and may be of clinical significance.

Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics

PubMed Central

Greulich, Philip; Doležal, Jakub; Scott, Matthew; Evans, Martin R; Allen, Rosalind J

2017-01-01

Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance—yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic. Our results depend strongly on whether the antibiotic shows reversible transport and/or low-affinity ribosome binding (‘low-affinity antibiotic’) or, in contrast, irreversible transport and/or high affinity ribosome binding (‘high-affinity antibiotic’). For low-affinity antibiotics, our model predicts that growth inhibition depends on the duration of the antibiotic pulse, and can show a transient period of very fast growth following removal of the antibiotic. For high-affinity antibiotics, growth inhibition depends on peak dosage rather than dose duration, and the model predicts a pronounced post-antibiotic effect, due to hysteresis, in which growth can be suppressed for long times after the antibiotic dose has ended. These predictions are experimentally testable and may be of clinical significance. PMID:28714461

On the Estimation of Disease Prevalence by Latent Class Models for Screening Studies Using Two Screening Tests with Categorical Disease Status Verified in Test Positives Only

PubMed Central

Chu, Haitao; Zhou, Yijie; Cole, Stephen R.; Ibrahim, Joseph G.

2010-01-01

Summary To evaluate the probabilities of a disease state, ideally all subjects in a study should be diagnosed by a definitive diagnostic or gold standard test. However, since definitive diagnostic tests are often invasive and expensive, it is generally unethical to apply them to subjects whose screening tests are negative. In this article, we consider latent class models for screening studies with two imperfect binary diagnostic tests and a definitive categorical disease status measured only for those with at least one positive screening test. Specifically, we discuss a conditional independent and three homogeneous conditional dependent latent class models and assess the impact of misspecification of the dependence structure on the estimation of disease category probabilities using frequentist and Bayesian approaches. Interestingly, the three homogeneous dependent models can provide identical goodness-of-fit but substantively different estimates for a given study. However, the parametric form of the assumed dependence structure itself is not “testable” from the data, and thus the dependence structure modeling considered here can only be viewed as a sensitivity analysis concerning a more complicated non-identifiable model potentially involving heterogeneous dependence structure. Furthermore, we discuss Bayesian model averaging together with its limitations as an alternative way to partially address this particularly challenging problem. The methods are applied to two cancer screening studies, and simulations are conducted to evaluate the performance of these methods. In summary, further research is needed to reduce the impact of model misspecification on the estimation of disease prevalence in such settings. PMID:20191614

A reliable facility location design model with site-dependent disruption in the imperfect information context

PubMed Central

Yun, Lifen; Wang, Xifu; Fan, Hongqiang; Li, Xiaopeng

2017-01-01

This paper proposes a reliable facility location design model under imperfect information with site-dependent disruptions; i.e., each facility is subject to a unique disruption probability that varies across the space. In the imperfect information contexts, customers adopt a realistic “trial-and-error” strategy to visit facilities; i.e., they visit a number of pre-assigned facilities sequentially until they arrive at the first operational facility or give up looking for the service. This proposed model aims to balance initial facility investment and expected long-term operational cost by finding the optimal facility locations. A nonlinear integer programming model is proposed to describe this problem. We apply a linearization technique to reduce the difficulty of solving the proposed model. A number of problem instances are studied to illustrate the performance of the proposed model. The results indicate that our proposed model can reveal a number of interesting insights into the facility location design with site-dependent disruptions, including the benefit of backup facilities and system robustness against variation of the loss-of-service penalty. PMID:28486564

The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells

PubMed Central

Shao, Li-Rong; Halvorsrud, Ragnhild; Borg-Graham, Lyle; Storm, Johan F

1999-01-01

The role of large-conductance Ca2+-dependent K+ channels (BK-channels; also known as maxi-K- or slo-channels) in spike broadening during repetitive firing was studied in CA1 pyramidal cells, using sharp electrode intracellular recordings in rat hippocampal slices, and computer modelling. Trains of action potentials elicited by depolarizing current pulses showed a progressive, frequency-dependent spike broadening, reflecting a reduced rate of repolarization. During a 50 ms long 5 spike train, the spike duration increased by 63·6 ± 3·4% from the 1st to the 3rd spike. The amplitude of the fast after-hyperpolarization (fAHP) also rapidly declined during each train. Suppression of BK-channel activity with (a) the selective BK-channel blocker iberiotoxin (IbTX, 60 nM), (b) the non-peptidergic BK-channel blocker paxilline (2–10 μM), or (c) calcium-free medium, broadened the 1st spike to a similar degree (≈60%). BK-channel suppression also caused a similar change in spike waveform as observed during repetitive firing, and eliminated (occluded) most of the spike broadening during repetitive firing. Computer simulations using a reduced compartmental model with transient BK-channel current and 10 other active ionic currents, produced an activity-dependent spike broadening that was strongly reduced when the BK-channel inactivation mechanism was removed. These results, which are supported by recent voltage-clamp data, strongly suggest that in CA1 pyramidal cells, fast inactivation of a transient BK-channel current (ICT), substantially contributes to frequency-dependent spike broadening during repetitive firing. PMID:10562340

An improved non-Markovian degradation model with long-term dependency and item-to-item uncertainty

NASA Astrophysics Data System (ADS)

Xi, Xiaopeng; Chen, Maoyin; Zhang, Hanwen; Zhou, Donghua

2018-05-01

It is widely noted in the literature that the degradation should be simplified into a memoryless Markovian process for the purpose of predicting the remaining useful life (RUL). However, there actually exists the long-term dependency in the degradation processes of some industrial systems, including electromechanical equipments, oil tankers, and large blast furnaces. This implies the new degradation state depends not only on the current state, but also on the historical states. Such dynamic systems cannot be accurately described by traditional Markovian models. Here we present an improved non-Markovian degradation model with both the long-term dependency and the item-to-item uncertainty. As a typical non-stationary process with dependent increments, fractional Brownian motion (FBM) is utilized to simulate the fractal diffusion of practical degradations. The uncertainty among multiple items can be represented by a random variable of the drift. Based on this model, the unknown parameters are estimated through the maximum likelihood (ML) algorithm, while a closed-form solution to the RUL distribution is further derived using a weak convergence theorem. The practicability of the proposed model is fully verified by two real-world examples. The results demonstrate that the proposed method can effectively reduce the prediction error.

Anoxic atmospheres on Mars driven by volcanism: Implications for past environments and life

NASA Astrophysics Data System (ADS)

Sholes, Steven F.; Smith, Megan L.; Claire, Mark W.; Zahnle, Kevin J.; Catling, David C.

2017-07-01

Mars today has no active volcanism and its atmosphere is oxidizing, dominated by the photochemistry of CO2 and H2O. Mars experienced widespread volcanism in the past and volcanic emissions should have included reducing gases, such as H2 and CO, as well as sulfur-bearing gases. Using a one-dimensional photochemical model, we consider whether plausible volcanic gas fluxes could have switched the redox-state of the past martian atmosphere to reducing conditions. In our model, the total quantity and proportions of volcanic gases depend on the water content, outgassing pressure, and oxygen fugacity of the source melt. We find that, with reasonable melt parameters, the past martian atmosphere (∼3.5 Gyr to present) could have easily reached reducing and anoxic conditions with modest levels of volcanism, >0.14 km3 yr-1, which are well within the range of estimates from thermal evolution models or photogeological studies. Counter-intuitively we also find that more reducing melts with lower oxygen fugacity require greater amounts of volcanism to switch a paleo-atmosphere from oxidizing to reducing. The reason is that sulfur is more stable in such melts and lower absolute fluxes of sulfur-bearing gases more than compensate for increases in the proportions of H2 and CO. These results imply that ancient Mars should have experienced periods with anoxic and reducing atmospheres even through the mid-Amazonian whenever volcanic outgassing was sustained at sufficient levels. Reducing anoxic conditions are potentially conducive to the synthesis of prebiotic organic compounds, such as amino acids, and are therefore relevant to the possibility of life on Mars. Also, anoxic reducing conditions should have influenced the type of minerals that were formed on the surface or deposited from the atmosphere. We suggest looking for elemental polysulfur (S8) as a signature of past reducing atmospheres. Finally, our models allow us to estimate the amount of volcanically sourced atmospheric sulfate deposited over Mars' history, approximately ∼106-109 Tmol, with a spread depending on assumed outgassing rate history and magmatic source conditions.

Global asymptotic stability of plant-seed bank models.

PubMed

Eager, Eric Alan; Rebarber, Richard; Tenhumberg, Brigitte

2014-07-01

Many plant populations have persistent seed banks, which consist of viable seeds that remain dormant in the soil for many years. Seed banks are important for plant population dynamics because they buffer against environmental perturbations and reduce the probability of extinction. Viability of the seeds in the seed bank can depend on the seed's age, hence it is important to keep track of the age distribution of seeds in the seed bank. In this paper we construct a general density-dependent plant-seed bank model where the seed bank is age-structured. We consider density dependence in both seedling establishment and seed production, since previous work has highlighted that overcrowding can suppress both of these processes. Under certain assumptions on the density dependence, we prove that there is a globally stable equilibrium population vector which is independent of the initial state. We derive an analytical formula for the equilibrium population using methods from feedback control theory. We apply these results to a model for the plant species Cirsium palustre and its seed bank.

Post-seismic and interseismic fault creep I: model description

NASA Astrophysics Data System (ADS)

Hetland, E. A.; Simons, M.; Dunham, E. M.

2010-04-01

We present a model of localized, aseismic fault creep during the full interseismic period, including both transient and steady fault creep, in response to a sequence of imposed coseismic slip events and tectonic loading. We consider the behaviour of models with linear viscous, non-linear viscous, rate-dependent friction, and rate- and state-dependent friction fault rheologies. Both the transient post-seismic creep and the pattern of steady interseismic creep rates surrounding asperities depend on recent coseismic slip and fault rheologies. In these models, post-seismic fault creep is manifest as pulses of elevated creep rates that propagate from the coseismic slip, these pulses feature sharper fronts and are longer lived in models with rate-state friction compared to other models. With small characteristic slip distances in rate-state friction models, interseismic creep is similar to that in models with rate-dependent friction faults, except for the earliest periods of post-seismic creep. Our model can be used to constrain fault rheologies from geodetic observations in cases where the coseismic slip history is relatively well known. When only considering surface deformation over a short period of time, there are strong trade-offs between fault rheology and the details of the imposed coseismic slip. Geodetic observations over longer times following an earthquake will reduce these trade-offs, while simultaneous modelling of interseismic and post-seismic observations provide the strongest constraints on fault rheologies.

ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension.

PubMed

Budas, Grant R; Boehm, Mario; Kojonazarov, Baktybek; Viswanathan, Gayathri; Tian, Xia; Veeroju, Swathi; Novoyatleva, Tatyana; Grimminger, Friedrich; Hinojosa-Kirschenbaum, Ford; Ghofrani, Hossein A; Weissmann, Norbert; Seeger, Werner; Liles, John T; Schermuly, Ralph T

2018-02-01

Progression of pulmonary arterial hypertension (PAH) is associated with pathological remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of MAPKs (mitogen-activated protein kinases), which stimulate apoptosis, inflammation, and fibrosis. We investigated whether pharmacological inhibition of the redox-sensitive apical MAPK, ASK1 (apoptosis signal-regulating kinase 1), can halt the progression of pulmonary vascular and RV remodeling. A selective, orally available ASK1 inhibitor, GS-444217, was administered to two preclinical rat models of PAH (monocrotaline and Sugen/hypoxia), a murine model of RV pressure overload induced by pulmonary artery banding, and cellular models. Oral administration of GS-444217 dose dependently reduced pulmonary arterial pressure and reduced RV hypertrophy in PAH models. The therapeutic efficacy of GS-444217 was associated with reduced ASK1 phosphorylation, reduced muscularization of the pulmonary arteries, and reduced fibrotic gene expression in the RV. Importantly, efficacy was observed when GS-444217 was administered to animals with established disease and also directly reduced cardiac fibrosis and improved cardiac function in a model of isolated RV pressure overload. In cellular models, GS-444217 reduced phosphorylation of p38 and JNK (c-Jun N-terminal kinase) induced by adenoviral overexpression of ASK1 in rat cardiomyocytes and reduced activation/migration of primary mouse cardiac fibroblasts and human pulmonary adventitial fibroblasts derived from patients with PAH. ASK1 inhibition reduced pathological remodeling of the pulmonary vasculature and the right ventricle and halted progression of pulmonary hypertension in rodent models. These preclinical data inform the first description of a causal role of ASK1 in PAH disease pathogenesis.

Interacting epidemics and coinfection on contact networks.

PubMed

Newman, M E J; Ferrario, Carrie R

2013-01-01

The spread of certain diseases can be promoted, in some cases substantially, by prior infection with another disease. One example is that of HIV, whose immunosuppressant effects significantly increase the chances of infection with other pathogens. Such coinfection processes, when combined with nontrivial structure in the contact networks over which diseases spread, can lead to complex patterns of epidemiological behavior. Here we consider a mathematical model of two diseases spreading through a single population, where infection with one disease is dependent on prior infection with the other. We solve exactly for the sizes of the outbreaks of both diseases in the limit of large population size, along with the complete phase diagram of the system. Among other things, we use our model to demonstrate how diseases can be controlled not only by reducing the rate of their spread, but also by reducing the spread of other infections upon which they depend.

Models of resource allocation optimization when solving the control problems in organizational systems

NASA Astrophysics Data System (ADS)

Menshikh, V.; Samorokovskiy, A.; Avsentev, O.

2018-03-01

The mathematical model of optimizing the allocation of resources to reduce the time for management decisions and algorithms to solve the general problem of resource allocation. The optimization problem of choice of resources in organizational systems in order to reduce the total execution time of a job is solved. This problem is a complex three-level combinatorial problem, for the solving of which it is necessary to implement the solution to several specific problems: to estimate the duration of performing each action, depending on the number of performers within the group that performs this action; to estimate the total execution time of all actions depending on the quantitative composition of groups of performers; to find such a distribution of the existing resource of performers in groups to minimize the total execution time of all actions. In addition, algorithms to solve the general problem of resource allocation are proposed.

A model-reduction approach to the micromechanical analysis of polycrystalline materials

NASA Astrophysics Data System (ADS)

Michel, Jean-Claude; Suquet, Pierre

2016-03-01

The present study is devoted to the extension to polycrystals of a model-reduction technique introduced by the authors, called the nonuniform transformation field analysis (NTFA). This new reduced model is obtained in two steps. First the local fields of internal variables are decomposed on a reduced basis of modes as in the NTFA. Second the dissipation potential of the phases is replaced by its tangent second-order (TSO) expansion. The reduced evolution equations of the model can be entirely expressed in terms of quantities which can be pre-computed once for all. Roughly speaking, these pre-computed quantities depend only on the average and fluctuations per phase of the modes and of the associated stress fields. The accuracy of the new NTFA-TSO model is assessed by comparison with full-field simulations on two specific applications, creep of polycrystalline ice and response of polycrystalline copper to a cyclic tension-compression test. The new reduced evolution equations is faster than the full-field computations by two orders of magnitude in the two examples.

Wavelet Filtering to Reduce Conservatism in Aeroservoelastic Robust Stability Margins

NASA Technical Reports Server (NTRS)

Brenner, Marty; Lind, Rick

1998-01-01

Wavelet analysis for filtering and system identification was used to improve the estimation of aeroservoelastic stability margins. The conservatism of the robust stability margins was reduced with parametric and nonparametric time-frequency analysis of flight data in the model validation process. Nonparametric wavelet processing of data was used to reduce the effects of external desirableness and unmodeled dynamics. Parametric estimates of modal stability were also extracted using the wavelet transform. Computation of robust stability margins for stability boundary prediction depends on uncertainty descriptions derived from the data for model validation. F-18 high Alpha Research Vehicle aeroservoelastic flight test data demonstrated improved robust stability prediction by extension of the stability boundary beyond the flight regime.

Evaluating Exercise as a Therapeutic Intervention for Methamphetamine Addiction-Like Behavior1

PubMed Central

Somkuwar, Sucharita S.; Staples, Miranda C.; Fannon, McKenzie J.; Ghofranian, Atoosa; Mandyam, Chitra D.

2015-01-01

Abstract The need for effective treatments for addiction and dependence to the illicit stimulant methamphetamine in primary care settings is increasing, yet no effective medications have been FDA approved to reduce dependence [1]. This is partially attributed to the complex and dynamic neurobiology underlying the various stages of addiction [2]. Therapeutic strategies to treat methamphetamine addiction, particularly the relapse stage of addiction, could revolutionize methamphetamine addiction treatment. In this context, preclinical studies demonstrate that voluntary exercise (sustained physical activity) could be used as an intervention to reduce methamphetamine addiction. Therefore, it appears that methamphetamine disrupts normal functioning in the brain and this disruption is prevented or reduced by engaging in exercise. This review discusses animal models of methamphetamine addiction and sustained physical activity and the interactions between exercise and methamphetamine behaviors. The review highlights how methamphetamine and exercise affect neuronal plasticity and neurotoxicity in the adult mammalian striatum, hippocampus, and prefrontal cortex, and presents the emerging mechanisms of exercise in attenuating intake and in preventing relapse to methamphetamine seeking in preclinical models of methamphetamine addiction. PMID:29765835

Aripiprazole blocks reinstatement of cocaine seeking in an animal model of relapse.

PubMed

Feltenstein, Matthew W; Altar, C Anthony; See, Ronald E

2007-03-01

Aripiprazole (Abilify) is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D2 receptors and low side effects. Based on pharmacologic properties that include a stabilization of mesocorticolimbic DA activity, a pathway implicated in addiction, aripiprazole was tested for its ability to prevent relapse to cocaine seeking in rats. We assessed the dose-dependent effects of aripiprazole on conditioned cue-induced and cocaine-primed reinstatement of drug-seeking behavior following chronic intravenous cocaine self-administration in an animal model of relapse. Aripiprazole potently and dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned-cued reinstatement. Aripiprazole was effective at doses that failed to alter cocaine self-administration, food self-administration, reinstatement of food-seeking behavior, or basal locomotor activity, suggesting selective effects of aripiprazole on motivated drug-seeking behavior. These results in a relapse model show that aripiprazole can block cocaine seeking without affecting other behaviors. The D2 partial agonist properties of aripiprazole likely account for the blockade of reinstatement of cocaine-seeking behavior. Given its established efficacy and tolerability as a treatment for psychosis, aripiprazole may be an excellent therapeutic choice for reducing craving and preventing relapse in people with cocaine dependency.

Molecular dynamics studies of a DNA-binding protein: 2. An evaluation of implicit and explicit solvent models for the molecular dynamics simulation of the Escherichia coli trp repressor.

PubMed Central

Guenot, J.; Kollman, P. A.

1992-01-01

Although aqueous simulations with periodic boundary conditions more accurately describe protein dynamics than in vacuo simulations, these are computationally intensive for most proteins. Trp repressor dynamic simulations with a small water shell surrounding the starting model yield protein trajectories that are markedly improved over gas phase, yet computationally efficient. Explicit water in molecular dynamics simulations maintains surface exposure of protein hydrophilic atoms and burial of hydrophobic atoms by opposing the otherwise asymmetric protein-protein forces. This properly orients protein surface side chains, reduces protein fluctuations, and lowers the overall root mean square deviation from the crystal structure. For simulations with crystallographic waters only, a linear or sigmoidal distance-dependent dielectric yields a much better trajectory than does a constant dielectric model. As more water is added to the starting model, the differences between using distance-dependent and constant dielectric models becomes smaller, although the linear distance-dependent dielectric yields an average structure closer to the crystal structure than does a constant dielectric model. Multiplicative constants greater than one, for the linear distance-dependent dielectric simulations, produced trajectories that are progressively worse in describing trp repressor dynamics. Simulations of bovine pancreatic trypsin were used to ensure that the trp repressor results were not protein dependent and to explore the effect of the nonbonded cutoff on the distance-dependent and constant dielectric simulation models. The nonbonded cutoff markedly affected the constant but not distance-dependent dielectric bovine pancreatic trypsin inhibitor simulations. As with trp repressor, the distance-dependent dielectric model with a shell of water surrounding the protein produced a trajectory in better agreement with the crystal structure than a constant dielectric model, and the physical properties of the trajectory average structure, both with and without a nonbonded cutoff, were comparable. PMID:1304396

Nuclear stopping in central Xe+Sn collisions: Confrontation with experimental data

NASA Astrophysics Data System (ADS)

Rajni, Vermani, Yogesh K.

2018-05-01

The influence of symmetry energy and cross section on nuclear stopping is studied in central 54129Xe+50 120Sn Sn collisions at Fermi energies (Elab≈ 20-100 MeV/nucleon). The analysis is conducted using isospin dependent quantum molecular dynamics (IQMD) transport model. Model calculations are done using reduced isospin dependent nucleon-nucleon cross section (σiso) and isospin independent cross section (σnoiso). Calculations using the two versions of cross section are analyzed with and without symmetry energy (Esym). The results are then compared with the experimental data taken with 4π multidetector INDRA. From this comparison, we conclude that nuclear stopping and related production of light charged particles (LCPs) are strongly influenced by isospin dependence of nucleon-nucleon cross section.

Quantifying and Reducing Uncertainty in Correlated Multi-Area Short-Term Load Forecasting

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

Sun, Yannan; Hou, Zhangshuan; Meng, Da

2016-07-17

In this study, we represent and reduce the uncertainties in short-term electric load forecasting by integrating time series analysis tools including ARIMA modeling, sequential Gaussian simulation, and principal component analysis. The approaches are mainly focusing on maintaining the inter-dependency between multiple geographically related areas. These approaches are applied onto cross-correlated load time series as well as their forecast errors. Multiple short-term prediction realizations are then generated from the reduced uncertainty ranges, which are useful for power system risk analyses.

Assessment of production risks for winter wheat in different German regions under climate change conditions

NASA Astrophysics Data System (ADS)

Kersebaum, K. C.; Gandorfer, M.; Wegehenkel, M.

2012-04-01

The study shows climate change impacts on wheat production in selected regions across Germany. To estimate yield and economic effects the agro-ecosystem model HERMES was used. The model performed runs using 2 different releases of the model WETTREG providing statistically downscaled climate change scenarios for the weather station network of the German Weather Service. Simulations were done using intersected GIS information on soil types and land use identifying the most relevant sites for wheat production. The production risks for wheat yields at the middle of this century were compared to a reference of the present climate. The irrigation demand was determined by the model using an automatic irrigation mode. Production risks with and without irrigation were assessed and the economic feasibility to reduce production risks by irrigation was evaluated. Costs and benefits were compared. Additionally, environmental effects, e.g. groundwater recharge and nitrogen emissions were assessed for irrigated and rain fed systems. Results show that positive and negative effects of climate change occur within most regions depending on the site conditions. Water holding capacity and groundwater distance were the most important factors which determined the vulnerability of sites. Under climate change condition in the middle of the next century we can expect especially at sites with low water holding capacity decreasing average gross margins, higher production risks and a reduced nitrogen use efficiency under rainfed conditions. Irrigation seems to be profitable and risk reducing at those sites, provided that water for irrigation is available. Additionally, the use of irrigation can also increase nitrogen use efficiency which reduced emissions by leaching. Despite the site conditions results depend strongly on the used regional climate scenario and the model approach to consider the effect of elevated CO2 in the atmosphere.

Inverse regression-based uncertainty quantification algorithms for high-dimensional models: Theory and practice

NASA Astrophysics Data System (ADS)

Li, Weixuan; Lin, Guang; Li, Bing

2016-09-01

Many uncertainty quantification (UQ) approaches suffer from the curse of dimensionality, that is, their computational costs become intractable for problems involving a large number of uncertainty parameters. In these situations, the classic Monte Carlo often remains the preferred method of choice because its convergence rate O (n - 1 / 2), where n is the required number of model simulations, does not depend on the dimension of the problem. However, many high-dimensional UQ problems are intrinsically low-dimensional, because the variation of the quantity of interest (QoI) is often caused by only a few latent parameters varying within a low-dimensional subspace, known as the sufficient dimension reduction (SDR) subspace in the statistics literature. Motivated by this observation, we propose two inverse regression-based UQ algorithms (IRUQ) for high-dimensional problems. Both algorithms use inverse regression to convert the original high-dimensional problem to a low-dimensional one, which is then efficiently solved by building a response surface for the reduced model, for example via the polynomial chaos expansion. The first algorithm, which is for the situations where an exact SDR subspace exists, is proved to converge at rate O (n-1), hence much faster than MC. The second algorithm, which doesn't require an exact SDR, employs the reduced model as a control variate to reduce the error of the MC estimate. The accuracy gain could still be significant, depending on how well the reduced model approximates the original high-dimensional one. IRUQ also provides several additional practical advantages: it is non-intrusive; it does not require computing the high-dimensional gradient of the QoI; and it reports an error bar so the user knows how reliable the result is.

Video Super-Resolution via Bidirectional Recurrent Convolutional Networks.

PubMed

Huang, Yan; Wang, Wei; Wang, Liang

2018-04-01

Super resolving a low-resolution video, namely video super-resolution (SR), is usually handled by either single-image SR or multi-frame SR. Single-Image SR deals with each video frame independently, and ignores intrinsic temporal dependency of video frames which actually plays a very important role in video SR. Multi-Frame SR generally extracts motion information, e.g., optical flow, to model the temporal dependency, but often shows high computational cost. Considering that recurrent neural networks (RNNs) can model long-term temporal dependency of video sequences well, we propose a fully convolutional RNN named bidirectional recurrent convolutional network for efficient multi-frame SR. Different from vanilla RNNs, 1) the commonly-used full feedforward and recurrent connections are replaced with weight-sharing convolutional connections. So they can greatly reduce the large number of network parameters and well model the temporal dependency in a finer level, i.e., patch-based rather than frame-based, and 2) connections from input layers at previous timesteps to the current hidden layer are added by 3D feedforward convolutions, which aim to capture discriminate spatio-temporal patterns for short-term fast-varying motions in local adjacent frames. Due to the cheap convolutional operations, our model has a low computational complexity and runs orders of magnitude faster than other multi-frame SR methods. With the powerful temporal dependency modeling, our model can super resolve videos with complex motions and achieve well performance.

Pointwise influence matrices for functional-response regression.

PubMed

Reiss, Philip T; Huang, Lei; Wu, Pei-Shien; Chen, Huaihou; Colcombe, Stan

2017-12-01

We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise influence matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers in an analysis of the development of white matter microstructure in the brain. © 2017, The International Biometric Society.

Turgidity-dependent petiole flexibility enables efficient water use by a tree subjected to water stress.

PubMed

Gonzalez-Rodriguez, David; Cournède, Paul-Henry; de Langre, Emmanuel

2016-06-07

Water stress is a major cause of tree mortality. In response to drought, leaves wilt due to an increase in petiole flexibility. We present an analytical model coupling petiole mechanics, thermal balance, and xylem hydraulics to investigate the role of petiole flexibility in protecting a tree from water stress. Our model suggests that turgidity-dependent petiole flexibility can significantly attenuate the minimal xylem pressure and thus reduce the risk of cavitation. Moreover, we show that petiole flexibility increases water use efficiency by trees under water stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Statistical simulation of the magnetorotational dynamo.

PubMed

Squire, J; Bhattacharjee, A

2015-02-27

Turbulence and dynamo induced by the magnetorotational instability (MRI) are analyzed using quasilinear statistical simulation methods. It is found that homogenous turbulence is unstable to a large-scale dynamo instability, which saturates to an inhomogenous equilibrium with a strong dependence on the magnetic Prandtl number (Pm). Despite its enormously reduced nonlinearity, the dependence of the angular momentum transport on Pm in the quasilinear model is qualitatively similar to that of nonlinear MRI turbulence. This demonstrates the importance of the large-scale dynamo and suggests how dramatically simplified models may be used to gain insight into the astrophysically relevant regimes of very low or high Pm.

High tidal volume ventilation induces NOS2 and impairs cAMP- dependent air space fluid clearance.

PubMed

Frank, James A; Pittet, Jean-Francois; Lee, Hyon; Godzich, Micaela; Matthay, Michael A

2003-05-01

Tidal volume reduction during mechanical ventilation reduces mortality in patients with acute lung injury and the acute respiratory distress syndrome. To determine the mechanisms underlying the protective effect of low tidal volume ventilation, we studied the time course and reversibility of ventilator-induced changes in permeability and distal air space edema fluid clearance in a rat model of ventilator-induced lung injury. Anesthetized rats were ventilated with a high tidal volume (30 ml/kg) or with a high tidal volume followed by ventilation with a low tidal volume of 6 ml/kg. Endothelial and epithelial protein permeability were significantly increased after high tidal volume ventilation but returned to baseline levels when tidal volume was reduced. The basal distal air space fluid clearance (AFC) rate decreased by 43% (P < 0.05) after 1 h of high tidal volume but returned to the preventilation rate 2 h after tidal volume was reduced. Not all of the effects of high tidal volume ventilation were reversible. The cAMP-dependent AFC rate after 1 h of 30 ml/kg ventilation was significantly reduced and was not restored when tidal volume was reduced. High tidal volume ventilation also increased lung inducible nitric oxide synthase (NOS2) expression and air space total nitrite at 3 h. Inhibition of NOS2 activity preserved cAMP-dependent AFC. Because air space edema fluid inactivates surfactant and reduces ventilated lung volume, the reduction of cAMP-dependent AFC by reactive nitrogen species may be an important mechanism of clinical ventilator-associated lung injury.

Differential Potassium Channel Gene Regulation in BXD Mice Reveals Novel Targets for Pharmacogenetic Therapies to Reduce Heavy Alcohol Drinking

PubMed Central

Rinker, Jennifer A.; Fulmer, Diana B.; Trantham-Davidson, Heather; Smith, Maren L.; Williams, Robert W.; Lopez, Marcelo F.; Randall, Patrick K.; Chandler, L. Judson; Miles, Michael F.; Becker, Howard C.; Mulholland, Patrick J.

2016-01-01

Alcohol (ethanol) dependence is a chronic relapsing brain disorder partially influenced by genetics and characterized by an inability to regulate harmful levels of drinking. Emerging evidence has linked genes that encode KV7, KIR, and KCa2 K+ channels with variation in alcohol-related behaviors in rodents and humans. This led us to experimentally test relations between K+ channel genes and escalation of drinking in a chronic intermittent ethanol (CIE) exposure model of dependence in BXD recombinant inbred strains of mice. Transcript levels for K+ channel genes in the prefrontal cortex (PFC) and nucleus accumbens (NAc) covary with voluntary ethanol drinking in a non-dependent cohort. Transcripts that encode KV7 channels covary negatively with drinking in non-dependent BXD strains. Using a pharmacological approach to validate the genetic findings, C57BL/6J mice were allowed intermittent access to ethanol to establish baseline consumption before they were treated with retigabine, an FDA-approved KV7 channel positive modulator. Systemic administration significantly reduced drinking, and consistent with previous evidence, retigabine was more effective at reducing voluntary consumption in high-drinking than low-drinking subjects. We evaluated the specific K+ channel genes that were most sensitive to CIE exposure and identified a gene subset in the NAc and PFC dysregulated in the alcohol-dependent BXD cohort. CIE-induced modulation of nine genes in the NAc and six genes in the PFC covaried well with the changes in drinking induced by ethanol dependence. Here we identified novel candidate genes in the NAc and PFC that are regulated by ethanol dependence and correlate with voluntary drinking in non-dependent and dependent BXD mice. The findings that Kcnq expression correlate with drinking and that retigabine reduces consumption suggest that KV7 channels could be pharmacogenetic targets to treat individuals with alcohol addiction. PMID:27432260

Suppression of acute and anticipatory nausea by peripherally restricted fatty acid amide hydrolase inhibitor in animal models: role of PPARα and CB1 receptors.

PubMed

Rock, Erin M; Moreno-Sanz, Guillermo; Limebeer, Cheryl L; Petrie, Gavin N; Angelini, Roberto; Piomelli, Daniele; Parker, Linda A

2017-11-01

Effective treatments of nausea are limited. In this study we evaluated the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937, to suppress acute and anticipatory nausea in rats and examined the pharmacological mechanism of this effect. We investigated the potential of URB937 (administered i.p.) to reduce the establishment of lithium chloride-induced conditioned gaping (model of acute nausea) and to reduce the expression of contextually-elicited conditioned gaping (model of anticipatory nausea) in rats. The role of CB 1 receptors, CB 2 receptors and PPARα in the anti-nausea effect of URB937 was examined. The potential of URB937 to suppress FAAH activity in tissue collected from the area postrema (AP), prefrontal cortex (PFC), liver and duodenum and to elevate levels of FAAH substrates - anandamide (AEA), N-oleoylethanolamide (OEO) and N-palmitoylethanolamide (PEA) - in the AP was also evaluated. URB937 reduced acute nausea by a PPARα-dependent mechanism and reduced anticipatory nausea by a CB 1 receptor-dependent mechanism. The PPARα agonist, GW7647, similarly attenuated acute nausea. URB937 reduced FAAH activity in the liver and the duodenum but not in the PFC. In addition, URB937 reduced FAAH activity and elevated levels of fatty-acid ethanolamides in the AP, a brain region that is not protected by the blood-brain barrier. The anti-nausea action of URB937 may occur in the AP and may involve PPARα to suppress acute nausea and CB 1 receptors to suppress anticipatory nausea. © 2017 The British Pharmacological Society.

Machine Learning Based Multi-Physical-Model Blending for Enhancing Renewable Energy Forecast -- Improvement via Situation Dependent Error Correction

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

Lu, Siyuan; Hwang, Youngdeok; Khabibrakhmanov, Ildar

With increasing penetration of solar and wind energy to the total energy supply mix, the pressing need for accurate energy forecasting has become well-recognized. Here we report the development of a machine-learning based model blending approach for statistically combining multiple meteorological models for improving the accuracy of solar/wind power forecast. Importantly, we demonstrate that in addition to parameters to be predicted (such as solar irradiance and power), including additional atmospheric state parameters which collectively define weather situations as machine learning input provides further enhanced accuracy for the blended result. Functional analysis of variance shows that the error of individual modelmore » has substantial dependence on the weather situation. The machine-learning approach effectively reduces such situation dependent error thus produces more accurate results compared to conventional multi-model ensemble approaches based on simplistic equally or unequally weighted model averaging. Validation over an extended period of time results show over 30% improvement in solar irradiance/power forecast accuracy compared to forecasts based on the best individual model.« less

Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC

PubMed Central

Amato, Katherine R.; Wang, Shan; Hastings, Andrew K.; Youngblood, Victoria M.; Santapuram, Pranav R.; Chen, Haiying; Cates, Justin M.; Colvin, Daniel C.; Ye, Fei; Brantley-Sieders, Dana M.; Cook, Rebecca S.; Tan, Li; Gray, Nathanael S.; Chen, Jin

2014-01-01

Genome-wide analyses determined previously that the receptor tyrosine kinase (RTK) EPHA2 is commonly overexpressed in non–small cell lung cancers (NSCLCs). EPHA2 overexpression is associated with poor clinical outcomes; therefore, EPHA2 may represent a promising therapeutic target for patients with NSCLC. In support of this hypothesis, here we have shown that targeted disruption of EphA2 in a murine model of aggressive Kras-mutant NSCLC impairs tumor growth. Knockdown of EPHA2 in human NSCLC cell lines reduced cell growth and viability, confirming the epithelial cell autonomous requirements for EPHA2 in NSCLCs. Targeting EPHA2 in NSCLCs decreased S6K1-mediated phosphorylation of cell death agonist BAD and induced apoptosis. Induction of EPHA2 knockdown within established NSCLC tumors in a subcutaneous murine model reduced tumor volume and induced tumor cell death. Furthermore, an ATP-competitive EPHA2 RTK inhibitor, ALW-II-41-27, reduced the number of viable NSCLC cells in a time-dependent and dose-dependent manner in vitro and induced tumor regression in human NSCLC xenografts in vivo. Collectively, these data demonstrate a role for EPHA2 in the maintenance and progression of NSCLCs and provide evidence that ALW-II-41-27 effectively inhibits EPHA2-mediated tumor growth in preclinical models of NSCLC. PMID:24713656

Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

PubMed Central

Bell, Richard L.; Sable, Helen J.K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

2012-01-01

The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence. PMID:22841890

Electrical Advantages of Dendritic Spines

PubMed Central

Gulledge, Allan T.; Carnevale, Nicholas T.; Stuart, Greg J.

2012-01-01

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations. PMID:22532875

Seed-predator satiation and Janzen-Connell effects vary with spatial scales for seed-feeding insects.

PubMed

Xiao, Zhishu; Mi, Xiangcheng; Holyoak, Marcel; Xie, Wenhua; Cao, Ke; Yang, Xifu; Huang, Xiaoqun; Krebs, Charles J

2017-01-01

The Janzen-Connell model predicts that common species suffer high seed predation from specialized natural enemies as a function of distance from parent trees, and consequently as a function of conspecific density, whereas the predator satiation hypothesis predicts that seed attack is reduced due to predator satiation at high seed densities. Pre-dispersal predation by insects was studied while seeds are still on parent trees, which represents a frequently overlooked stage in which seed predation occurs. Reproductive tree density and seed production were investigated from ten Quercus serrata populations located in south-west China, quantifying density-dependent pre-dispersal seed predation over two years by three insect groups. Acorn infestation was nearly twice as high in the low-seed year as that in the high-seed year, with considerable spatio-temporal variation in the direction and magnitude of density-dependent pre-dispersal seed predation evident. Across whole populations of trees, a high density of reproductive trees caused predator satiation and reduced insect attack in the high-seed year. Within individual trees, and consistent with the Janzen-Connell model, overall insect seed predation was positively correlated with seed production in the low-seed year. In addition, there was variation among insect taxa, with positive density-dependent seed predation by Curculio weevils in the high-seed year and moths in the low-seed year, but apparent density independence by Cyllorhynchites weevils in both years. The overall trend of negative density-dependent, pre-dispersal seed predation suggests that predator satiation limited the occurrence of Janzen-Connell effects across Q. serrata populations. Such effects may have large impacts on plant population dynamics and tree diversity, depending on the extent to which they are reduced by counteracting positive density-dependent predation for seeds on individual trees and other factors affecting successful recruitment. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Abscisic acid induces a transient shift in signaling that enhances NF-κB-mediated parasite killing in the midgut of Anopheles stephensi without reducing lifespan or fecundity.

PubMed

Glennon, Elizabeth K K; Torrevillas, Brandi K; Morrissey, Shannon F; Ejercito, Jadrian M; Luckhart, Shirley

2017-07-13

Abscisic acid (ABA) is naturally present in mammalian blood and circulating levels can be increased by oral supplementation. We showed previously that oral ABA supplementation in a mouse model of Plasmodium yoelii 17XNL infection reduced parasitemia and gametocytemia, spleen and liver pathology, and parasite transmission to the mosquito Anopheles stephensi fed on these mice. Treatment of cultured Plasmodium falciparum with ABA at levels detected in our model had no effects on asexual growth or gametocyte formation in vitro. However, ABA treatment of cultured P. falciparum immediately prior to mosquito feeding significantly reduced oocyst development in A. stephensi via ABA-dependent synthesis of nitric oxide (NO) in the mosquito midgut. Here we describe the mechanisms of effects of ABA on mosquito physiology, which are dependent on phosphorylation of TGF-β-activated kinase 1 (TAK1) and associated with changes in homeostatic gene expression and activity of kinases that are central to metabolic regulation in the midgut epithelium. Collectively, the timing of these effects suggests a transient physiological shift that enhances NF-κB-dependent innate immunity without significantly altering mosquito lifespan or fecundity. ABA is a highly conserved regulator of immune and metabolic homeostasis within the malaria vector A. stephensi with potential as a transmission-blocking supplemental treatment.

Modeling the spread and control of foot-and-mouth disease in Pennsylvania following its discovery and options for control

PubMed Central

Tildesley, Michael J.; Smith, Gary; Keeling, Matt J.

2013-01-01

In this paper, we simulate outbreaks of foot-and-mouth disease in the Commonwealth of Pennsylvania, USA – after the introduction of a state-wide movement ban – as they might unfold in the presence of mitigation strategies. We have adapted a model previously used to investigate FMD control policies in the UK to examine the potential for disease spread given an infection seeded in each county in Pennsylvania. The results are highly dependent upon the county of introduction and the spatial scale of transmission. Should the transmission kernel be identical to that for the UK, the epidemic impact is limited to fewer than 20 premises, regardless of the county of introduction. However, for wider kernels where infection can spread further, outbreaks seeded in or near the county with highest density of premises and animals result in large epidemics (>150 premises). Ring culling and vaccination reduce epidemic size, with the optimal radius of the rings being dependent upon the county of introduction. Should the kernel width exceed a given county-dependent threshold, ring culling is unable to control the epidemic. We find that a vaccinate-to-live policy is generally preferred to ring culling (in terms of reducing the overall number of premises culled), indicating that well-targeted control can dramatically reduce the risk of large scale outbreaks of foot-and-mouth disease occurring in Pennsylvania. PMID:22169708

Theoretical Systematics of Future Baryon Acoustic Oscillation Surveys

NASA Astrophysics Data System (ADS)

Ding, Zhejie; Seo, Hee-Jong; Vlah, Zvonimir; Feng, Yu; Schmittfull, Marcel; Beutler, Florian

2018-05-01

Future Baryon Acoustic Oscillation surveys aim at observing galaxy clustering over a wide range of redshift and galaxy populations at great precision, reaching tenths of a percent, in order to detect any deviation of dark energy from the ΛCDM model. We utilize a set of paired quasi-N-body FastPM simulations that were designed to mitigate the sample variance effect on the BAO feature and evaluated the BAO systematics as precisely as ˜0.01%. We report anisotropic BAO scale shifts before and after density field reconstruction in the presence of redshift-space distortions over a wide range of redshift, galaxy/halo biases, and shot noise levels. We test different reconstruction schemes and different smoothing filter scales, and introduce physically-motivated BAO fitting models. For the first time, we derive a Galilean-invariant infrared resummed model for halos in real and redshift space. We test these models from the perspective of robust BAO measurements and non-BAO information such as growth rate and nonlinear bias. We find that pre-reconstruction BAO scale has moderate fitting-model dependence at the level of 0.1% - 0.2% for matter while the dependence is substantially reduced to less than 0.07% for halos. We find that post-reconstruction BAO shifts are generally reduced to below 0.1% in the presence of galaxy/halo bias and show much smaller fitting model dependence. Different reconstruction conventions can potentially make a much larger difference on the line-of-sight BAO scale, upto 0.3%. Meanwhile, the precision (error) of the BAO measurements is quite consistent regardless of the choice of the fitting model or reconstruction convention.

Risk of dependence associated with health, social support, and lifestyle

PubMed Central

Alcañiz, Manuela; Brugulat, Pilar; Guillén, Montserrat; Medina-Bustos, Antonia; Mompart-Penina, Anna; Solé-Auró, Aïda

2015-01-01

OBJECTIVE To analyze the prevalence of individuals at risk of dependence and its associated factors. METHODS The study was based on data from the Catalan Health Survey, Spain conducted in 2010 and 2011. Logistic regression models from a random sample of 3,842 individuals aged ≥ 15 years were used to classify individuals according to the state of their personal autonomy. Predictive models were proposed to identify indicators that helped distinguish dependent individuals from those at risk of dependence. Variables on health status, social support, and lifestyles were considered. RESULTS We found that 18.6% of the population presented a risk of dependence, especially after age 65. Compared with this group, individuals who reported dependence (11.0%) had difficulties performing activities of daily living and had to receive support to perform them. Habits such as smoking, excessive alcohol consumption, and being sedentary were associated with a higher probability of dependence, particularly for women. CONCLUSIONS Difficulties in carrying out activities of daily living precede the onset of dependence. Preserving personal autonomy and function without receiving support appear to be a preventive factor. Adopting an active and healthy lifestyle helps reduce the risk of dependence. PMID:26018786

Risk of dependence associated with health, social support, and lifestyle.

PubMed

Alcañiz, Manuela; Brugulat, Pilar; Guillén, Montserrat; Medina-Bustos, Antonia; Mompart-Penina, Anna; Solé-Auró, Aïda

2015-01-01

OBJECTIVE To analyze the prevalence of individuals at risk of dependence and its associated factors. METHODS The study was based on data from the Catalan Health Survey, Spain conducted in 2010 and 2011. Logistic regression models from a random sample of 3,842 individuals aged ≥ 15 years were used to classify individuals according to the state of their personal autonomy. Predictive models were proposed to identify indicators that helped distinguish dependent individuals from those at risk of dependence. Variables on health status, social support, and lifestyles were considered. RESULTS We found that 18.6% of the population presented a risk of dependence, especially after age 65. Compared with this group, individuals who reported dependence (11.0%) had difficulties performing activities of daily living and had to receive support to perform them. Habits such as smoking, excessive alcohol consumption, and being sedentary were associated with a higher probability of dependence, particularly for women. CONCLUSIONS Difficulties in carrying out activities of daily living precede the onset of dependence. Preserving personal autonomy and function without receiving support appear to be a preventive factor. Adopting an active and healthy lifestyle helps reduce the risk of dependence.

Geometry-dependent distributed polarizability models for the water molecule

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

Loboda, Oleksandr; Ingrosso, Francesca; Ruiz-López, Manuel F.

2016-01-21

Geometry-dependent distributed polarizability models have been constructed by fits to ab initio calculations at the coupled cluster level of theory with up to noniterative triple excitations in an augmented triple-zeta quality basis set for the water molecule in the field of a point charge. The investigated models include (i) charge-flow polarizabilities between chemically bonded atoms, (ii) isotropic or anisotropic dipolar polarizabilities on oxygen atom or on all atoms, and (iii) combinations of models (i) and (ii). For each model, the polarizability parameters have been optimized to reproduce the induction energy of a water molecule polarized by a point charge successivelymore » occupying a grid of points surrounding the molecule. The quality of the models is ascertained by examining their ability to reproduce these induction energies as well as the molecular dipolar and quadrupolar polarizabilities. The geometry dependence of the distributed polarizability models has been explored by changing bond lengths and HOH angle to generate 125 molecular structures (reduced to 75 symmetry-unique ones). For each considered model, the distributed polarizability components have been fitted as a function of the geometry by a Taylor expansion in monomer coordinate displacements up to the sum of powers equal to 4.« less

Predicting Young’s Modulus of Glass/Ceramic Sealant for Solid Oxide Fuel Cell Considering the Combined Effects of Aging, Micro-Voids and Self-Healing

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

Liu, Wenning N.; Sun, Xin; Khaleel, Mohammad A.

We study the temperature dependent Young’s modulus for the glass/ceramic seal material used in Solid Oxide Fuel Cells (SOFCs). With longer heat treatment or aging time during operation, further devitrification may reduce the residual glass content in the seal material while boosting the ceramic crystalline content. In the meantime, micro-voids induced by the cooling process from the high operating temperature to room temperature can potentially degrade the mechanical properties of the glass/ceramic sealant. Upon reheating to the SOFC operating temperature, possible self-healing phenomenon may occur in the glass/ceramic sealant which can potentially restore some of its mechanical properties. A phenomenologicalmore » model is developed to model the temperature dependent Young’s modulus of glass/ceramic seal considering the combined effects of aging, micro-voids, and possible self-healing. An aging-time-dependent crystalline content model is first developed to describe the increase of the crystalline content due to the continuing devitrification under high operating temperature. A continuum damage mechanics (CDM) model is then adapted to model the effects of both cooling induced micro-voids and reheating induced self-healing. This model is applied to model the glass-ceramic G18, a candidate SOFC seal material previously developed at PNNL. Experimentally determined temperature dependent Young’s modulus is used to validate the model predictions« less

Coupling between lower-tropospheric convective mixing and low-level clouds: Physical mechanisms and dependence on convection scheme.

PubMed

Vial, Jessica; Bony, Sandrine; Dufresne, Jean-Louis; Roehrig, Romain

2016-12-01

Several studies have pointed out the dependence of low-cloud feedbacks on the strength of the lower-tropospheric convective mixing. By analyzing a series of single-column model experiments run by a climate model using two different convective parametrizations, this study elucidates the physical mechanisms through which marine boundary-layer clouds depend on this mixing in the present-day climate and under surface warming. An increased lower-tropospheric convective mixing leads to a reduction of low-cloud fraction. However, the rate of decrease strongly depends on how the surface latent heat flux couples to the convective mixing and to boundary-layer cloud radiative effects: (i) on the one hand, the latent heat flux is enhanced by the lower-tropospheric drying induced by the convective mixing, which damps the reduction of the low-cloud fraction, (ii) on the other hand, the latent heat flux is reduced as the lower troposphere stabilizes under the effect of reduced low-cloud radiative cooling, which enhances the reduction of the low-cloud fraction. The relative importance of these two different processes depends on the closure of the convective parameterization. The convective scheme that favors the coupling between latent heat flux and low-cloud radiative cooling exhibits a stronger sensitivity of low-clouds to convective mixing in the present-day climate, and a stronger low-cloud feedback in response to surface warming. In this model, the low-cloud feedback is stronger when the present-day convective mixing is weaker and when present-day clouds are shallower and more radiatively active. The implications of these insights for constraining the strength of low-cloud feedbacks observationally is discussed.

Coupling between lower‐tropospheric convective mixing and low‐level clouds: Physical mechanisms and dependence on convection scheme

PubMed Central

Bony, Sandrine; Dufresne, Jean‐Louis; Roehrig, Romain

2016-01-01

Abstract Several studies have pointed out the dependence of low‐cloud feedbacks on the strength of the lower‐tropospheric convective mixing. By analyzing a series of single‐column model experiments run by a climate model using two different convective parametrizations, this study elucidates the physical mechanisms through which marine boundary‐layer clouds depend on this mixing in the present‐day climate and under surface warming. An increased lower‐tropospheric convective mixing leads to a reduction of low‐cloud fraction. However, the rate of decrease strongly depends on how the surface latent heat flux couples to the convective mixing and to boundary‐layer cloud radiative effects: (i) on the one hand, the latent heat flux is enhanced by the lower‐tropospheric drying induced by the convective mixing, which damps the reduction of the low‐cloud fraction, (ii) on the other hand, the latent heat flux is reduced as the lower troposphere stabilizes under the effect of reduced low‐cloud radiative cooling, which enhances the reduction of the low‐cloud fraction. The relative importance of these two different processes depends on the closure of the convective parameterization. The convective scheme that favors the coupling between latent heat flux and low‐cloud radiative cooling exhibits a stronger sensitivity of low‐clouds to convective mixing in the present‐day climate, and a stronger low‐cloud feedback in response to surface warming. In this model, the low‐cloud feedback is stronger when the present‐day convective mixing is weaker and when present‐day clouds are shallower and more radiatively active. The implications of these insights for constraining the strength of low‐cloud feedbacks observationally is discussed. PMID:28239438

The climate impacts of bioenergy systems depend on market and regulatory policy contexts.

PubMed

Lemoine, Derek M; Plevin, Richard J; Cohn, Avery S; Jones, Andrew D; Brandt, Adam R; Vergara, Sintana E; Kammen, Daniel M

2010-10-01

Biomass can help reduce greenhouse gas (GHG) emissions by displacing petroleum in the transportation sector, by displacing fossil-based electricity, and by sequestering atmospheric carbon. Which use mitigates the most emissions depends on market and regulatory contexts outside the scope of attributional life cycle assessments. We show that bioelectricity's advantage over liquid biofuels depends on the GHG intensity of the electricity displaced. Bioelectricity that displaces coal-fired electricity could reduce GHG emissions, but bioelectricity that displaces wind electricity could increase GHG emissions. The electricity displaced depends upon existing infrastructure and policies affecting the electric grid. These findings demonstrate how model assumptions about whether the vehicle fleet and bioenergy use are fixed or free parameters constrain the policy questions an analysis can inform. Our bioenergy life cycle assessment can inform questions about a bioenergy mandate's optimal allocation between liquid fuels and electricity generation, but questions about the optimal level of bioenergy use require analyses with different assumptions about fixed and free parameters.

Local energetic frustration affects the dependence of green fluorescent protein folding on the chaperonin GroEL.

PubMed

Bandyopadhyay, Boudhayan; Goldenzweig, Adi; Unger, Tamar; Adato, Orit; Fleishman, Sarel J; Unger, Ron; Horovitz, Amnon

2017-12-15

The GroE chaperonin system in Escherichia coli comprises GroEL and GroES and facilitates ATP-dependent protein folding in vivo and in vitro Proteins with very similar sequences and structures can differ in their dependence on GroEL for efficient folding. One potential but unverified source for GroEL dependence is frustration, wherein not all interactions in the native state are optimized energetically, thereby potentiating slow folding and misfolding. Here, we chose enhanced green fluorescent protein as a model system and subjected it to random mutagenesis, followed by screening for variants whose in vivo folding displays increased or decreased GroEL dependence. We confirmed the altered GroEL dependence of these variants with in vitro folding assays. Strikingly, mutations at positions predicted to be highly frustrated were found to correlate with decreased GroEL dependence. Conversely, mutations at positions with low frustration were found to correlate with increased GroEL dependence. Further support for this finding was obtained by showing that folding of an enhanced green fluorescent protein variant designed computationally to have reduced frustration is indeed less GroEL-dependent. Our results indicate that changes in local frustration also affect partitioning in vivo between spontaneous and chaperonin-mediated folding. Hence, the design of minimally frustrated sequences can reduce chaperonin dependence and improve protein expression levels. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Eye lens radiation exposure during ureteroscopy with and without a face protection shield: Investigations on a phantom model].

PubMed

Zöller, G; Figel, M; Denk, J; Schulz, K; Sabo, A

2016-03-01

Eye lens radiation exposure during radiologically-guided endoscopic procedures may result in radiation-induced cataracts; therefore, we investigated the ocular radiation exposure during ureteroscopy on a phantom model. Using an Alderson phantom model and eye lens dosimeters, we measured the ocular radiation exposure depending on the number of X-ray images and on the duration of fluoroscopic imaging. The measurements were done with and without using a face protection shield. We could demonstrate that a significant ocular radiation exposure can occur, depending on the number of X-ray images and on the duration time of fluoroscopy. Eye lens doses up to 0.025 mSv were recorded even using modern digital X-ray systems. Using face protection shields this ocular radiation exposure can be reduced to a minimum. The International Commission on Radiological Protection (ICRP) recommendations of a mean eye lens dosage of 20 mSv/year may be exceeded during repeated ureteroscopy by a high volume surgeon. Using a face protection shield, the eye lens dose during ureteroscopy could be reduced to a minimum in a phantom model. Further investigations will show whether these results can be transferred to real life ureteroscopic procedures.

Model predictions of realgar precipitation by reaction of As(III) with synthetic mackinawite under anoxic conditions

USGS Publications Warehouse

Gallegos, T.J.; Han, Y.-S.; Hayes, K.F.

2008-01-01

This study investigates the removal of As(III) from solution using mackinawite, a nanoparticulate reduced iron sulfide. Mackinawite suspensions (0.1-40 g/L) effectively lower initial concentrations of 1.3 ?? 10 -5 M As(III) from pH 5-10, with maximum removal occurring under acidic conditions. Based on Eh measurements, it was found that the redox state of the system depended on the mackinawite solids concentration and pH. Higher initial mackinawite concentrations and alkaline pH resulted in a more reducing redox condition. Given this, the pH edge data were modeled thermodynamically using pe (-log[e-]) as a fitting parameter and linear pe-pH relationships within the range of measured Eh values as a function of pH and mackinawite concentration. The model predicts removal of As(III) from solution by precipitation of realgar with the formation of secondary oxidation products, greigite or a mixed-valence iron oxide phase, depending on pH. This study demonstrates that mackinawite is an effective sequestration agent for As(III) and highlights the importance of incorporating redox into models describing the As-Fe-S-H2O system. ?? 2008 American Chemical Society.

Bioheat model evaluations of laser effects on tissues: role of water evaporation and diffusion

NASA Astrophysics Data System (ADS)

Nagulapally, Deepthi; Joshi, Ravi P.; Thomas, Robert J.

2011-03-01

A two-dimensional, time-dependent bioheat model is applied to evaluate changes in temperature and water content in tissues subjected to laser irradiation. Our approach takes account of liquid-to-vapor phase changes and a simple diffusive flow of water within the biotissue. An energy balance equation considers blood perfusion, metabolic heat generation, laser absorption, and water evaporation. The model also accounts for the water dependence of tissue properties (both thermal and optical), and variations in blood perfusion rates based on local tissue injury. Our calculations show that water diffusion would reduce the local temperature increases and hot spots in comparison to simple models that ignore the role of water in the overall thermal and mass transport. Also, the reduced suppression of perfusion rates due to tissue heating and damage with water diffusion affect the necrotic depth. Two-dimensional results for the dynamic temperature, water content, and damage distributions will be presented for skin simulations. It is argued that reduction in temperature gradients due to water diffusion would mitigate local refractive index variations, and hence influence the phenomenon of thermal lensing. Finally, simple quantitative evaluations of pressure increases within the tissue due to laser absorption are presented.

Understanding the Day Cent model: Calibration, sensitivity, and identifiability through inverse modeling

USGS Publications Warehouse

Necpálová, Magdalena; Anex, Robert P.; Fienen, Michael N.; Del Grosso, Stephen J.; Castellano, Michael J.; Sawyer, John E.; Iqbal, Javed; Pantoja, Jose L.; Barker, Daniel W.

2015-01-01

The ability of biogeochemical ecosystem models to represent agro-ecosystems depends on their correct integration with field observations. We report simultaneous calibration of 67 DayCent model parameters using multiple observation types through inverse modeling using the PEST parameter estimation software. Parameter estimation reduced the total sum of weighted squared residuals by 56% and improved model fit to crop productivity, soil carbon, volumetric soil water content, soil temperature, N2O, and soil3NO− compared to the default simulation. Inverse modeling substantially reduced predictive model error relative to the default model for all model predictions, except for soil 3NO− and 4NH+. Post-processing analyses provided insights into parameter–observation relationships based on parameter correlations, sensitivity and identifiability. Inverse modeling tools are shown to be a powerful way to systematize and accelerate the process of biogeochemical model interrogation, improving our understanding of model function and the underlying ecosystem biogeochemical processes that they represent.

Expanding Stress Generation Theory: Test of a Transdiagnostic Model

PubMed Central

Conway, Christopher C.; Hammen, Constance; Brennan, Patricia A.

2016-01-01

Originally formulated to understand the recurrence of depressive disorders, the stress generation hypothesis has recently been applied in research on anxiety and externalizing disorders. Results from these investigations, in combination with findings of extensive comorbidity between depression and other mental disorders, suggest the need for an expansion of stress generation models to include the stress generating effects of transdiagnostic pathology as well as those of specific syndromes. Employing latent variable modeling techniques to parse the general and specific elements of commonly co-occurring Axis I syndromes, the current study examined the associations of transdiagnostic internalizing and externalizing dimensions with stressful life events over time. Analyses revealed that, after adjusting for the covariation between the dimensions, internalizing was a significant predictor of interpersonal dependent stress, whereas externalizing was a significant predictor of noninterpersonal dependent stress. Neither latent dimension was associated with the occurrence of independent, or fateful, stressful life events. At the syndrome level, once variance due to the internalizing factor was partialled out, unipolar depression contributed incrementally to the generation of interpersonal dependent stress. In contrast, the presence of panic disorder produced a “stress inhibition” effect, predicting reduced exposure to interpersonal dependent stress. Additionally, dysthymia was associated with an excess of noninterpersonal dependent stress. The latent variable modeling framework used here is discussed in terms of its potential as an integrative model for stress generation research. PMID:22428789

Preserving Lagrangian Structure in Nonlinear Model Reduction with Application to Structural Dynamics

DOE PAGES

Carlberg, Kevin; Tuminaro, Ray; Boggs, Paul

2015-03-11

Our work proposes a model-reduction methodology that preserves Lagrangian structure and achieves computational efficiency in the presence of high-order nonlinearities and arbitrary parameter dependence. As such, the resulting reduced-order model retains key properties such as energy conservation and symplectic time-evolution maps. We focus on parameterized simple mechanical systems subjected to Rayleigh damping and external forces, and consider an application to nonlinear structural dynamics. To preserve structure, the method first approximates the system's “Lagrangian ingredients''---the Riemannian metric, the potential-energy function, the dissipation function, and the external force---and subsequently derives reduced-order equations of motion by applying the (forced) Euler--Lagrange equation with thesemore » quantities. Moreover, from the algebraic perspective, key contributions include two efficient techniques for approximating parameterized reduced matrices while preserving symmetry and positive definiteness: matrix gappy proper orthogonal decomposition and reduced-basis sparsification. Our results for a parameterized truss-structure problem demonstrate the practical importance of preserving Lagrangian structure and illustrate the proposed method's merits: it reduces computation time while maintaining high accuracy and stability, in contrast to existing nonlinear model-reduction techniques that do not preserve structure.« less

Preserving Lagrangian Structure in Nonlinear Model Reduction with Application to Structural Dynamics

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

Carlberg, Kevin; Tuminaro, Ray; Boggs, Paul

Our work proposes a model-reduction methodology that preserves Lagrangian structure and achieves computational efficiency in the presence of high-order nonlinearities and arbitrary parameter dependence. As such, the resulting reduced-order model retains key properties such as energy conservation and symplectic time-evolution maps. We focus on parameterized simple mechanical systems subjected to Rayleigh damping and external forces, and consider an application to nonlinear structural dynamics. To preserve structure, the method first approximates the system's “Lagrangian ingredients''---the Riemannian metric, the potential-energy function, the dissipation function, and the external force---and subsequently derives reduced-order equations of motion by applying the (forced) Euler--Lagrange equation with thesemore » quantities. Moreover, from the algebraic perspective, key contributions include two efficient techniques for approximating parameterized reduced matrices while preserving symmetry and positive definiteness: matrix gappy proper orthogonal decomposition and reduced-basis sparsification. Our results for a parameterized truss-structure problem demonstrate the practical importance of preserving Lagrangian structure and illustrate the proposed method's merits: it reduces computation time while maintaining high accuracy and stability, in contrast to existing nonlinear model-reduction techniques that do not preserve structure.« less

Some consequences of shear on galactic dynamos with helicity fluxes

NASA Astrophysics Data System (ADS)

Zhou, Hongzhe; Blackman, Eric G.

2017-08-01

Galactic dynamo models sustained by supernova (SN) driven turbulence and differential rotation have revealed that the sustenance of large-scale fields requires a flux of small-scale magnetic helicity to be viable. Here we generalize a minimalist analytic version of such galactic dynamos to explore some heretofore unincluded contributions from shear on the total turbulent energy and turbulent correlation time, with the helicity fluxes maintained by either winds, diffusion or magnetic buoyancy. We construct an analytic framework for modelling the turbulent energy and correlation time as a function of SN rate and shear. We compare our prescription with previous approaches that include only rotation. The solutions depend separately on the rotation period and the eddy turnover time and not just on their ratio (the Rossby number). We consider models in which these two time-scales are allowed to be independent and also a case in which they are mutually dependent on radius when a radial-dependent SN rate model is invoked. For the case of a fixed rotation period (or a fixed radius), we show that the influence of shear is dramatic for low Rossby numbers, reducing the correlation time of the turbulence, which, in turn, strongly reduces the saturation value of the dynamo compared to the case when the shear is ignored. We also show that even in the absence of winds or diffusive fluxes, magnetic buoyancy may be able to sustain sufficient helicity fluxes to avoid quenching.

Microwave Backscatter and Attenuation Dependence of Leaf Area Index for Flooded Rice Fields

NASA Technical Reports Server (NTRS)

Durden, Stephen L.; Morrissey, Leslie A.; Livingston, Gerald P.

1995-01-01

Wetlands are important for their role in global climate as a source of methane and other reduced trace gases. As part of an effort to determine whether radar is suitable for wetland vegetation monitoring, we have studied the dependence of microwave backscatter and attenuation on leaf area index (LAI) for flooded rice fields. We find that the radar return from a flooded rice field does show dependence on LAI. In particular, the C-band VV cross section per unit area decreases with increasing LAI. A simple model for scattering from rice fields is derived and fit to the observed HH and VV data. The model fit provides insight into the relation of backscatter to LAI and is also used to calculate the canopy path attenuation as a function of LAI.

Urban water infrastructure optimization to reduce environmental impacts and costs.

PubMed

Lim, Seong-Rin; Suh, Sangwon; Kim, Jung-Hoon; Park, Hung Suck

2010-01-01

Urban water planning and policy have been focusing on environmentally benign and economically viable water management. The objective of this study is to develop a mathematical model to integrate and optimize urban water infrastructures for supply-side planning and policy: freshwater resources and treated wastewater are allocated to various water demand categories in order to reduce contaminants in the influents supplied for drinking water, and to reduce consumption of the water resources imported from the regions beyond a city boundary. A case study is performed to validate the proposed model. An optimal urban water system of a metropolitan city is calculated on the basis of the model and compared to the existing water system. The integration and optimization decrease (i) average concentrations of the influents supplied for drinking water, which can improve human health and hygiene; (ii) total consumption of water resources, as well as electricity, reducing overall environmental impacts; (iii) life cycle cost; and (iv) water resource dependency on other regions, improving regional water security. This model contributes to sustainable urban water planning and policy. 2009 Elsevier Ltd. All rights reserved.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935

Flying mirror model for interaction of a super-intense laser pulse with a thin plasma layer: Transparency and shaping of linearly polarized laser pulses

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

Kulagin, Victor V.; Cherepenin, Vladimir A.; Hur, Min Sup

2007-11-15

A self-consistent one-dimensional (1D) flying mirror model is developed for description of an interaction of an ultra-intense laser pulse with a thin plasma layer (foil). In this model, electrons of the foil can have large longitudinal displacements and relativistic longitudinal momenta. An approximate analytical solution for a transmitted field is derived. Transmittance of the foil shows not only a nonlinear dependence on the amplitude of the incident laser pulse, but also time dependence and shape dependence in the high-transparency regime. The results are compared with particle-in-cell (PIC) simulations and a good agreement is ascertained. Shaping of incident laser pulses usingmore » the flying mirror model is also considered. It can be used either for removing a prepulse or for reducing the length of a short laser pulse. The parameters of the system for effective shaping are specified. Predictions of the flying mirror model for shaping are compared with the 1D PIC simulations, showing good agreement.« less

Atmospheric Moisture Budget and Spatial Resolution Dependence of Precipitation Extremes in Aquaplanet Simulations

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

Yang, Qing; Leung, Lai-Yung R.; Rauscher, Sara

This study investigates the resolution dependency of precipitation extremes in an aqua-planet framework. Strong resolution dependency of precipitation extremes is seen over both tropics and extra-tropics, and the magnitude of this dependency also varies with dynamical cores. Moisture budget analyses based on aqua-planet simulations with the Community Atmosphere Model (CAM) using the Model for Prediction Across Scales (MPAS) and High Order Method Modeling Environment (HOMME) dynamical cores but the same physics parameterizations suggest that during precipitation extremes moisture supply for surface precipitation is mainly derived from advective moisture convergence. The resolution dependency of precipitation extremes mainly originates from advective moisturemore » transport in the vertical direction. At most vertical levels over the tropics and in the lower atmosphere over the subtropics, the vertical eddy transport of mean moisture field dominates the contribution to precipitation extremes and its resolution dependency. Over the subtropics, the source of moisture, its associated energy, and the resolution dependency during extremes are dominated by eddy transport of eddies moisture at the mid- and upper-troposphere. With both MPAS and HOMME dynamical cores, the resolution dependency of the vertical advective moisture convergence is mainly explained by dynamical changes (related to vertical velocity or omega), although the vertical gradients of moisture act like averaging kernels to determine the sensitivity of the overall resolution dependency to the changes in omega at different vertical levels. The natural reduction of variability with coarser resolution, represented by areal data averaging (aggregation) effect, largely explains the resolution dependency in omega. The thermodynamic changes, which likely result from non-linear feedback in response to the large dynamical changes, are small compared to the overall changes in dynamics (omega). However, after excluding the data aggregation effect in omega, thermodynamic changes become relatively significant in offsetting the effect of dynamics leading to reduce differences between the simulated and aggregated results. Compared to MPAS, the simulated stronger vertical motion with HOMME also results in larger resolution dependency. Compared to the simulation at fine resolution, the vertical motion during extremes is insufficiently resolved/parameterized at the coarser resolution even after accounting for the natural reduction in variability with coarser resolution, and this is more distinct in the simulation with HOMME. To reduce uncertainties in simulated precipitation extremes, future development in cloud parameterizations must address their sensitivity to spatial resolution as well as dynamical cores.« less

Challenges in reducing the computational time of QSTS simulations for distribution system analysis.

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

Deboever, Jeremiah; Zhang, Xiaochen; Reno, Matthew J.

The rapid increase in penetration of distributed energy resources on the electric power distribution system has created a need for more comprehensive interconnection modelling and impact analysis. Unlike conventional scenario - based studies , quasi - static time - series (QSTS) simulation s can realistically model time - dependent voltage controllers and the diversity of potential impacts that can occur at different times of year . However, to accurately model a distribution system with all its controllable devices, a yearlong simulation at 1 - second resolution is often required , which could take conventional computers a computational time of 10more » to 120 hours when an actual unbalanced distribution feeder is modeled . This computational burden is a clear l imitation to the adoption of QSTS simulation s in interconnection studies and for determining optimal control solutions for utility operations . Our ongoing research to improve the speed of QSTS simulation has revealed many unique aspects of distribution system modelling and sequential power flow analysis that make fast QSTS a very difficult problem to solve. In this report , the most relevant challenges in reducing the computational time of QSTS simulations are presented: number of power flows to solve, circuit complexity, time dependence between time steps, multiple valid power flow solutions, controllable element interactions, and extensive accurate simulation analysis.« less

Entanglement of a quantum field with a dispersive medium.

PubMed

Klich, Israel

2012-08-10

In this Letter we study the entanglement of a quantum radiation field interacting with a dielectric medium. In particular, we describe the quantum mixed state of a field interacting with a dielectric through plasma and Drude models and show that these generate very different entanglement behavior, as manifested in the entanglement entropy of the field. We also present a formula for a "Casimir" entanglement entropy, i.e., the distance dependence of the field entropy. Finally, we study a toy model of the interaction between two plates. In this model, the field entanglement entropy is divergent; however, as in the Casimir effect, its distance-dependent part is finite, and the field matter entanglement is reduced when the objects are far.

Solvent effects in time-dependent self-consistent field methods. II. Variational formulations and analytical gradients

DOE PAGES

Bjorgaard, J. A.; Velizhanin, K. A.; Tretiak, S.

2015-08-06

This study describes variational energy expressions and analytical excited state energy gradients for time-dependent self-consistent field methods with polarizable solvent effects. Linear response, vertical excitation, and state-specific solventmodels are examined. Enforcing a variational ground stateenergy expression in the state-specific model is found to reduce it to the vertical excitation model. Variational excited state energy expressions are then provided for the linear response and vertical excitation models and analytical gradients are formulated. Using semiempiricalmodel chemistry, the variational expressions are verified by numerical and analytical differentiation with respect to a static external electric field. Lastly, analytical gradients are further tested by performingmore » microcanonical excited state molecular dynamics with p-nitroaniline.« less

State-space modeling to support management of brucellosis in the Yellowstone bison population

USGS Publications Warehouse

Hobbs, N. Thompson; Geremia, Chris; Treanor, John; Wallen, Rick; White, P.J.; Hooten, Mevin B.; Rhyan, Jack C.

2015-01-01

The bison (Bison bison) of the Yellowstone ecosystem, USA, exemplify the difficulty of conserving large mammals that migrate across the boundaries of conservation areas. Bison are infected with brucellosis (Brucella abortus) and their seasonal movements can expose livestock to infection. Yellowstone National Park has embarked on a program of adaptive management of bison, which requires a model that assimilates data to support management decisions. We constructed a Bayesian state-space model to reveal the influence of brucellosis on the Yellowstone bison population. A frequency-dependent model of brucellosis transmission was superior to a density-dependent model in predicting out-of-sample observations of horizontal transmission probability. A mixture model including both transmission mechanisms converged on frequency dependence. Conditional on the frequency-dependent model, brucellosis median transmission rate was 1.87 yr−1. The median of the posterior distribution of the basic reproductive ratio (R0) was 1.75. Seroprevalence of adult females varied around 60% over two decades, but only 9.6 of 100 adult females were infectious. Brucellosis depressed recruitment; estimated population growth rate λ averaged 1.07 for an infected population and 1.11 for a healthy population. We used five-year forecasting to evaluate the ability of different actions to meet management goals relative to no action. Annually removing 200 seropositive female bison increased by 30-fold the probability of reducing seroprevalence below 40% and increased by a factor of 120 the probability of achieving a 50% reduction in transmission probability relative to no action. Annually vaccinating 200 seronegative animals increased the likelihood of a 50% reduction in transmission probability by fivefold over no action. However, including uncertainty in the ability to implement management by representing stochastic variation in the number of accessible bison dramatically reduced the probability of achieving goals using interventions relative to no action. Because the width of the posterior predictive distributions of future population states expands rapidly with increases in the forecast horizon, managers must accept high levels of uncertainty. These findings emphasize the necessity of iterative, adaptive management with relatively short-term commitment to action and frequent reevaluation in response to new data and model forecasts. We believe our approach has broad applications.

Active Brownian agents with concentration-dependent chemotactic sensitivity.

PubMed

Meyer, Marcel; Schimansky-Geier, Lutz; Romanczuk, Pawel

2014-02-01

We study a biologically motivated model of overdamped, autochemotactic Brownian agents with concentration-dependent chemotactic sensitivity. The agents in our model move stochastically and produce a chemical ligand at their current position. The ligand concentration obeys a reaction-diffusion equation and acts as a chemoattractant for the agents, which bias their motion towards higher concentrations of the dynamically altered chemical field. We explore the impact of concentration-dependent response to chemoattractant gradients on large-scale pattern formation, by deriving a coarse-grained macroscopic description of the individual-based model, and compare the conditions for emergence of inhomogeneous solutions for different variants of the chemotactic sensitivity. We focus primarily on the so-called receptor-law sensitivity, which models a nonlinear decrease of chemotactic sensitivity with increasing ligand concentration. Our results reveal qualitative differences between the receptor law, the constant chemotactic response, and the so-called log law, with respect to stability of the homogeneous solution, as well as the emergence of different patterns (labyrinthine structures, clusters, and bubbles) via spinodal decomposition or nucleation. We discuss two limiting cases, where the model can be reduced to the dynamics of single species: (I) the agent density governed by a density-dependent effective diffusion coefficient and (II) the ligand field with an effective bistable, time-dependent reaction rate. In the end, we turn to single clusters of agents, studying domain growth and determining mean characteristics of the stationary inhomogeneous state. Analytical results are confirmed and extended by large-scale GPU simulations of the individual based model.

Modeling the time-varying and level-dependent effects of the medial olivocochlear reflex in auditory nerve responses.

PubMed

Smalt, Christopher J; Heinz, Michael G; Strickland, Elizabeth A

2014-04-01

The medial olivocochlear reflex (MOCR) has been hypothesized to provide benefit for listening in noisy environments. This advantage can be attributed to a feedback mechanism that suppresses auditory nerve (AN) firing in continuous background noise, resulting in increased sensitivity to a tone or speech. MOC neurons synapse on outer hair cells (OHCs), and their activity effectively reduces cochlear gain. The computational model developed in this study implements the time-varying, characteristic frequency (CF) and level-dependent effects of the MOCR within the framework of a well-established model for normal and hearing-impaired AN responses. A second-order linear system was used to model the time-course of the MOCR using physiological data in humans. The stimulus-level-dependent parameters of the efferent pathway were estimated by fitting AN sensitivity derived from responses in decerebrate cats using a tone-in-noise paradigm. The resulting model uses a binaural, time-varying, CF-dependent, level-dependent OHC gain reduction for both ipsilateral and contralateral stimuli that improves detection of a tone in noise, similarly to recorded AN responses. The MOCR may be important for speech recognition in continuous background noise as well as for protection from acoustic trauma. Further study of this model and its efferent feedback loop may improve our understanding of the effects of sensorineural hearing loss in noisy situations, a condition in which hearing aids currently struggle to restore normal speech perception.

Response of water temperature to surface wave effects in the Baltic Sea: simulations with the coupled NEMO-WAM model

NASA Astrophysics Data System (ADS)

Alari, Victor; Staneva, Joanna; Breivik, Øyvind; Bidlot, Jean-Raymond; Mogensen, Kristian; Janssen, Peter

2016-04-01

The effects of wind waves on the Baltic Sea water temperature has been studied by coupling the hydrodynamical model NEMO with the wave model WAM. The wave forcing terms that have been taken into consideration are: Stokes-Coriolis force, seastate dependent energy flux and sea-state dependent momentum flux. The combined role of these processes as well as their individual contributions on simulated temperature is analysed. The results indicate a pronounced effect of waves on surface temperature, on the distribution of vertical temperature and on upwellinǵs. In northern parts of the Baltic Sea a warming of the surface layer occurs in the wave included simulations. This in turn reduces the cold bias between simulated and measured data. The warming is primarily caused by sea-state dependent energy flux. Wave induced cooling is mostly observed in near coastal areas and is mainly due to Stokes-Coriolis forcing. The latter triggers effect of intensifying upwellings near the coasts, depending on the direction of the wind. The effect of sea-state dependent momentum flux is predominantly to warm the surface layer. During the summer the wave induced water temperature changes were up to 1 °C.

Multiscale modeling of a rectifying bipolar nanopore: explicit-water versus implicit-water simulations.

PubMed

Ható, Zoltán; Valiskó, Mónika; Kristóf, Tamás; Gillespie, Dirk; Boda, Dezsö

2017-07-21

In a multiscale modeling approach, we present computer simulation results for a rectifying bipolar nanopore at two modeling levels. In an all-atom model, we use explicit water to simulate ion transport directly with the molecular dynamics technique. In a reduced model, we use implicit water and apply the Local Equilibrium Monte Carlo method together with the Nernst-Planck transport equation. This hybrid method makes the fast calculation of ion transport possible at the price of lost details. We show that the implicit-water model is an appropriate representation of the explicit-water model when we look at the system at the device (i.e., input vs. output) level. The two models produce qualitatively similar behavior of the electrical current for different voltages and model parameters. Looking at the details of concentration and potential profiles, we find profound differences between the two models. These differences, however, do not influence the basic behavior of the model as a device because they do not influence the z-dependence of the concentration profiles which are the main determinants of current. These results then address an old paradox: how do reduced models, whose assumptions should break down in a nanoscale device, predict experimental data? Our simulations show that reduced models can still capture the overall device physics correctly, even though they get some important aspects of the molecular-scale physics quite wrong; reduced models work because they include the physics that is necessary from the point of view of device function. Therefore, reduced models can suffice for general device understanding and device design, but more detailed models might be needed for molecular level understanding.

The role of landscape-dependent disturbance and dispersal in metapopulation persistence.

PubMed

Elkin, Ché M; Possingham, Hugh

2008-10-01

The fundamental processes that influence metapopulation dynamics (extinction and recolonization) will often depend on landscape structure. Disturbances that increase patch extinction rates will frequently be landscape dependent such that they are spatially aggregated and have an increased likelihood of occurring in some areas. Similarly, landscape structure can influence organism movement, producing asymmetric dispersal between patches. Using a stochastic, spatially explicit model, we examine how landscape-dependent correlations between dispersal and disturbance rates influence metapopulation dynamics. Habitat patches that are situated in areas where the likelihood of disturbance is low will experience lower extinction rates and will function as partial refuges. We discovered that the presence of partial refuges increases metapopulation viability and that the value of partial refuges was contingent on whether dispersal was also landscape dependent. Somewhat counterintuitively, metapopulation viability was reduced when individuals had a preponderance to disperse away from refuges and was highest when there was biased dispersal toward refuges. Our work demonstrates that landscape structure needs to be incorporated into metapopulation models when there is either empirical data or ecological rationale for extinction and/or dispersal rates being landscape dependent.

Application of gamma irradiation for inhibition of food allergy

NASA Astrophysics Data System (ADS)

Byun, Myung-Woo; Lee, Ju-Woon; Yook, Hong-Sun; Jo, Cheorun; Kim, Hee-Yun

2002-03-01

This study was carried out to evaluate the application of food irradiation technology as a method for reducing food allergy. Milk β-lactoglobulin, chicken egg albumin, and shrimp tropomyosin were used as model food allergens for experiments on allergenic and molecular properties by gamma irradiation. The amount of intact allergens in an irradiated solution was reduced by gamma irradiation depending upon the dose. These results showed that epitopes on the allergens were structurally altered by radiation treatment and that the irradiation technology can be applied to reduce allergenicity of allergic foods.

Automating Risk Analysis of Software Design Models

PubMed Central

Ruiz, Guifré; Heymann, Elisa; César, Eduardo; Miller, Barton P.

2014-01-01

The growth of the internet and networked systems has exposed software to an increased amount of security threats. One of the responses from software developers to these threats is the introduction of security activities in the software development lifecycle. This paper describes an approach to reduce the need for costly human expertise to perform risk analysis in software, which is common in secure development methodologies, by automating threat modeling. Reducing the dependency on security experts aims at reducing the cost of secure development by allowing non-security-aware developers to apply secure development with little to no additional cost, making secure development more accessible. To automate threat modeling two data structures are introduced, identification trees and mitigation trees, to identify threats in software designs and advise mitigation techniques, while taking into account specification requirements and cost concerns. These are the components of our model for automated threat modeling, AutSEC. We validated AutSEC by implementing it in a tool based on data flow diagrams, from the Microsoft security development methodology, and applying it to VOMS, a grid middleware component, to evaluate our model's performance. PMID:25136688

Automating risk analysis of software design models.

PubMed

Frydman, Maxime; Ruiz, Guifré; Heymann, Elisa; César, Eduardo; Miller, Barton P

2014-01-01

The growth of the internet and networked systems has exposed software to an increased amount of security threats. One of the responses from software developers to these threats is the introduction of security activities in the software development lifecycle. This paper describes an approach to reduce the need for costly human expertise to perform risk analysis in software, which is common in secure development methodologies, by automating threat modeling. Reducing the dependency on security experts aims at reducing the cost of secure development by allowing non-security-aware developers to apply secure development with little to no additional cost, making secure development more accessible. To automate threat modeling two data structures are introduced, identification trees and mitigation trees, to identify threats in software designs and advise mitigation techniques, while taking into account specification requirements and cost concerns. These are the components of our model for automated threat modeling, AutSEC. We validated AutSEC by implementing it in a tool based on data flow diagrams, from the Microsoft security development methodology, and applying it to VOMS, a grid middleware component, to evaluate our model's performance.

Gaussian functional regression for output prediction: Model assimilation and experimental design

NASA Astrophysics Data System (ADS)

Nguyen, N. C.; Peraire, J.

2016-03-01

In this paper, we introduce a Gaussian functional regression (GFR) technique that integrates multi-fidelity models with model reduction to efficiently predict the input-output relationship of a high-fidelity model. The GFR method combines the high-fidelity model with a low-fidelity model to provide an estimate of the output of the high-fidelity model in the form of a posterior distribution that can characterize uncertainty in the prediction. A reduced basis approximation is constructed upon the low-fidelity model and incorporated into the GFR method to yield an inexpensive posterior distribution of the output estimate. As this posterior distribution depends crucially on a set of training inputs at which the high-fidelity models are simulated, we develop a greedy sampling algorithm to select the training inputs. Our approach results in an output prediction model that inherits the fidelity of the high-fidelity model and has the computational complexity of the reduced basis approximation. Numerical results are presented to demonstrate the proposed approach.

Two-phase strategy of controlling motor coordination determined by task performance optimality.

PubMed

Shimansky, Yury P; Rand, Miya K

2013-02-01

A quantitative model of optimal coordination between hand transport and grip aperture has been derived in our previous studies of reach-to-grasp movements without utilizing explicit knowledge of the optimality criterion or motor plant dynamics. The model's utility for experimental data analysis has been demonstrated. Here we show how to generalize this model for a broad class of reaching-type, goal-directed movements. The model allows for measuring the variability of motor coordination and studying its dependence on movement phase. The experimentally found characteristics of that dependence imply that execution noise is low and does not affect motor coordination significantly. From those characteristics it is inferred that the cost of neural computations required for information acquisition and processing is included in the criterion of task performance optimality as a function of precision demand for state estimation and decision making. The precision demand is an additional optimized control variable that regulates the amount of neurocomputational resources activated dynamically. It is shown that an optimal control strategy in this case comprises two different phases. During the initial phase, the cost of neural computations is significantly reduced at the expense of reducing the demand for their precision, which results in speed-accuracy tradeoff violation and significant inter-trial variability of motor coordination. During the final phase, neural computations and thus motor coordination are considerably more precise to reduce the cost of errors in making a contact with the target object. The generality of the optimal coordination model and the two-phase control strategy is illustrated on several diverse examples.

Dependence of Snowmelt Simulations on Scaling of the Forcing Processes (Invited)

NASA Astrophysics Data System (ADS)

Winstral, A. H.; Marks, D. G.; Gurney, R. J.

2009-12-01

The spatial organization and scaling relationships of snow distribution in mountain environs is ultimately dependent on the controlling processes. These processes include interactions between weather, topography, vegetation, snow state, and seasonally-dependent radiation inputs. In large scale snow modeling it is vital to know these dependencies to obtain accurate predictions while reducing computational costs. This study examined the scaling characteristics of the forcing processes and the dependency of distributed snowmelt simulations to their scaling. A base model simulation characterized these processes with 10m resolution over a 14.0 km2 basin with an elevation range of 1474 - 2244 masl. Each of the major processes affecting snow accumulation and melt - precipitation, wind speed, solar radiation, thermal radiation, temperature, and vapor pressure - were independently degraded to 1 km resolution. Seasonal and event-specific results were analyzed. Results indicated that scale effects on melt vary by process and weather conditions. The dependence of melt simulations on the scaling of solar radiation fluxes also had a seasonal component. These process-based scaling characteristics should remain static through time as they are based on physical considerations. As such, these results not only provide guidance for current modeling efforts, but are also well suited to predicting how potential climate changes will affect the heterogeneity of mountain snow distributions.

Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin.

PubMed

Thomas, Evan A; Petrou, Steven

2013-07-01

A common notion of the mechanism by which the antiepileptic drugs (AEDs) carbamazepine and phenytoin act is that they block sodium channels by binding preferentially to the inactivated state, thereby allowing normal neuronal firing while blocking ictal activity. However, these drugs have unpredictable efficacy and, in some cases, may exacerbate seizures. Previous studies have suggested that reducing sodium channel availability in the dentate gyrus (DG) paradoxically increases excitability. We used a biophysically detailed computer model of the DG to test the hypothesis that AEDs increase excitability by disproportionately reducing negative feedback mechanisms. We built a Markov model of sodium channel gating that reproduces responses to voltage clamp experiments in the presence of carbamazepine and phenytoin. We incorporated this validated Markov model into a biophysically realistic computer model of DG neurons and networks. Simulated drug concentrations were similar to those measured in cerebral spinal fluid in medicated patients. Single neuron models were stimulated with current injections, and networks were stimulated with perforant path synaptic input. In the network model, environmental effects were studied by introducing mossy fiber sprouting. As expected, drugs reduced sodium channel availability, which in turn reduced action potential amplitude. This had only a small effect on action potential (AP) firing rate during brief (100 msec) current injections. Paradoxically, long current injections (2,500 msec) increased AP firing rates. This was caused by reduced calcium entry and consequently reduced activation of calcium activated potassium channels. It is important to note that the main determinant of drug effect was resting membrane potential (RMP) and not action potential firing rate. Binding of phenytoin and carbamazepine is slow and, thus drug effects are largely determined by the long term state of the RMP. This paradoxical AP firing increase was dependent on the unusually large calcium-activated potassium conductances expressed by DG granule cells. This predicts that drug efficacy in a given network will depend on the precise makeup of conductances in the network. RMP is expected to vary with the level of activity in the network. We simulated the effects of drugs on single shot stimulus responses in networks with mossy fiber sprouting and varied the RMP in all neurons as a model for network activity. For an RMP of -50 mV, representing an active network, drugs had no effect, or in some cases, increased excitability. Drugs had an increasingly larger inhibitory effect on network responses as RMP decreased. An important prediction is that drugs will be unable to block ictal activity invading an active network. Our key findings are that drug effects depend on both intrinsic properties of the network and its behavioral state. This may explain the paradoxical and unpredictable effects of some AEDs on seizure control in some patients. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Effects of Rivaroxaban on Platelet Activation and Platelet–Coagulation Pathway Interaction

PubMed Central

Heitmeier, Stefan; Laux, Volker

2015-01-01

Introduction: Activation of coagulation and platelets is closely linked, and arterial thrombosis involves coagulation activation as well as platelet activation and aggregation. In these studies, we investigated the possible synergistic effects of rivaroxaban in combination with antiplatelet agents on thrombin generation and platelet aggregation in vitro and on arterial thrombosis and hemostasis in rat models. Materials and Methods: Thrombin generation was measured by the Calibrated Automated Thrombogram method (0.5 pmol/L tissue factor) using human platelet-rich plasma (PRP) spiked with rivaroxaban (15, 30, or 60 ng/mL), ticagrelor (1.0 µg/mL), and acetylsalicylic acid (ASA; 100 µg/mL). Tissue factor-induced platelet aggregation was measured in PRP spiked with rivaroxaban (15 or 30 ng/mL), ticagrelor (1 or 3 µg/mL), or a combination of these. An arteriovenous (AV) shunt model in rats was used to determine the effects of rivaroxaban (0.01, 0.03, or 0.1 mg/kg), clopidogrel (1 mg/kg), ASA (3 mg/kg), and combinations on arterial thrombosis. Results: Rivaroxaban inhibited thrombin generation in a concentration-dependent manner and the effect was enhanced with ticagrelor and ticagrelor plus ASA. Rivaroxaban and ticagrelor also concentration-dependently inhibited tissue factor-induced platelet aggregation, and their combination increased the inhibition synergistically. In the AV shunt model, rivaroxaban dose-dependently reduced thrombus formation. Combining subefficacious or weakly efficacious doses of rivaroxaban with ASA or ASA plus clopidogrel increased the antithrombotic effect. Conclusion: These data indicate that the combination of rivaroxaban with single or dual antiplatelet agents works synergistically to reduce platelet activation, which may in turn lead to the delayed/reduced formation of coagulation complexes and vice versa, thereby enhancing antithrombotic potency. PMID:25848131

Human-machine interactions

DOEpatents

Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM

2009-04-28

Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

Down-regulation of respiration in pear fruit depends on temperature.

PubMed

Ho, Quang Tri; Hertog, Maarten L A T M; Verboven, Pieter; Ambaw, Alemayehu; Rogge, Seppe; Verlinden, Bert E; Nicolaï, Bart M

2018-04-09

The respiration rate of plant tissues decreases when the amount of available O2 is reduced. There is, however, a debate on whether the respiration rate is controlled either by diffusion limitation of oxygen or through regulatory processes at the level of the transcriptome. We used experimental and modelling approaches to demonstrate that both diffusion limitation and metabolic regulation affect the response of respiration of bulky plant organs such as fruit to reduced O2 levels in the surrounding atmosphere. Diffusion limitation greatly affects fruit respiration at high temperature, but at low temperature respiration is reduced through a regulatory process, presumably a response to a signal generated by a plant oxygen sensor. The response of respiration to O2 is time dependent and is highly sensitive, particularly at low O2 levels in the surrounding atmosphere. Down-regulation of the respiration at low temperatures may save internal O2 and relieve hypoxic conditions in the fruit.

The development and evaluation of accident predictive models

NASA Astrophysics Data System (ADS)

Maleck, T. L.

1980-12-01

A mathematical model that will predict the incremental change in the dependent variables (accident types) resulting from changes in the independent variables is developed. The end product is a tool for estimating the expected number and type of accidents for a given highway segment. The data segments (accidents) are separated in exclusive groups via a branching process and variance is further reduced using stepwise multiple regression. The standard error of the estimate is calculated for each model. The dependent variables are the frequency, density, and rate of 18 types of accidents among the independent variables are: district, county, highway geometry, land use, type of zone, speed limit, signal code, type of intersection, number of intersection legs, number of turn lanes, left-turn control, all-red interval, average daily traffic, and outlier code. Models for nonintersectional accidents did not fit nor validate as well as models for intersectional accidents.

Formation of model-free motor memories during motor adaptation depends on perturbation schedule.

PubMed

Orban de Xivry, Jean-Jacques; Lefèvre, Philippe

2015-04-01

Motor adaptation to an external perturbation relies on several mechanisms such as model-based, model-free, strategic, or repetition-dependent learning. Depending on the experimental conditions, each of these mechanisms has more or less weight in the final adaptation state. Here we focused on the conditions that lead to the formation of a model-free motor memory (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787-801, 2011), i.e., a memory that does not depend on an internal model or on the size or direction of the errors experienced during the learning. The formation of such model-free motor memory was hypothesized to depend on the schedule of the perturbation (Orban de Xivry JJ, Ahmadi-Pajouh MA, Harran MD, Salimpour Y, Shadmehr R. J Neurophysiol 109: 124-136, 2013). Here we built on this observation by directly testing the nature of the motor memory after abrupt or gradual introduction of a visuomotor rotation, in an experimental paradigm where the presence of model-free motor memory can be identified (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787-801, 2011). We found that relearning was faster after abrupt than gradual perturbation, which suggests that model-free learning is reduced during gradual adaptation to a visuomotor rotation. In addition, the presence of savings after abrupt introduction of the perturbation but gradual extinction of the motor memory suggests that unexpected errors are necessary to induce a model-free motor memory. Overall, these data support the hypothesis that different perturbation schedules do not lead to a more or less stabilized motor memory but to distinct motor memories with different attributes and neural representations. Copyright © 2015 the American Physiological Society.

Formation of model-free motor memories during motor adaptation depends on perturbation schedule

PubMed Central

Lefèvre, Philippe

2015-01-01

Motor adaptation to an external perturbation relies on several mechanisms such as model-based, model-free, strategic, or repetition-dependent learning. Depending on the experimental conditions, each of these mechanisms has more or less weight in the final adaptation state. Here we focused on the conditions that lead to the formation of a model-free motor memory (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787–801, 2011), i.e., a memory that does not depend on an internal model or on the size or direction of the errors experienced during the learning. The formation of such model-free motor memory was hypothesized to depend on the schedule of the perturbation (Orban de Xivry JJ, Ahmadi-Pajouh MA, Harran MD, Salimpour Y, Shadmehr R. J Neurophysiol 109: 124–136, 2013). Here we built on this observation by directly testing the nature of the motor memory after abrupt or gradual introduction of a visuomotor rotation, in an experimental paradigm where the presence of model-free motor memory can be identified (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787–801, 2011). We found that relearning was faster after abrupt than gradual perturbation, which suggests that model-free learning is reduced during gradual adaptation to a visuomotor rotation. In addition, the presence of savings after abrupt introduction of the perturbation but gradual extinction of the motor memory suggests that unexpected errors are necessary to induce a model-free motor memory. Overall, these data support the hypothesis that different perturbation schedules do not lead to a more or less stabilized motor memory but to distinct motor memories with different attributes and neural representations. PMID:25673736

Inhibition of TYK2 and JAK1 Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis by Inhibiting IL-22 and the IL-23/IL-17 axis

PubMed Central

Works, Melissa G.; Yin, Fangfang; Yin, Catherine C.; Yiu, Ying; Shew, Kenneth; Tran, Thanh-Thuy; Dunlap, Nahoko; Lam, Jennifer; Mitchell, Tim; Reader, John; Stein, Paul L.; D’Andrea, Annalisa

2014-01-01

Psoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making Janus kinase (JAK) inhibition an appealing strategy for the treatment of psoriasis. Here we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and Tyrosine Kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose-dependently (1 nM-10 μM) inhibited JAK1 and/or TYK2 dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild type mice with SAR-20347 significantly reduced IL-12 induced IFN-γ production and IL-22-dependent Serum Amyloid A (SAA) to similar extents, indicating that in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes, and proinflammatory cytokine levels compared to both TYK2 mutant mice and wild type controls. Taken together, these data indicate that targeting both JAK1 and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis. PMID:25156366

Physical activity moderates the association between nicotine dependence and depression among U.S. smokers.

PubMed

Loprinzi, Paul D; Walker, Jerome F; Kane, Christy; Cardinal, Bradley J

2014-01-01

Research demonstrates that nicotine dependence and depression are associated and that physical activity is effective in reducing depression symptoms. However, our understanding of the potential beneficial effects of physical activity on depression in current smokers is more limited. The purpose of this study was to examine whether physical activity moderates the association between nicotine dependence and depression in U.S. smokers. Cross-sectional. National Health and Nutrition Examination Survey 2005-2006. Four hundred forty-one current adult smokers. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess nicotine dependence and depression. Effect modification and statistical interaction models were used. Both models were significant. With regard to the statistical interaction model, and after controlling for age, gender, race/ethnicity, education, comorbidity index, homocysteine, cotinine, total cholesterol, sedentary behavior, and vitamins C, D, and E, objectively measured physical activity moderated the association between nicotine dependence and depression (interaction variable: odds ratio = 3.43; 95% confidence interval: 1.02-11.51; p = .04). In this national sample of current smokers, physical activity moderated the association between nicotine dependence and depression. These results suggest that those individuals with nicotine dependence and who are less physically active are more likely to be depressed than what would be expected on the basis of the individual effects of nicotine and physical inactivity separately.

Consequences of cannibalism and competition for food in a smallmouth bass population: An individual-based modeling study

USGS Publications Warehouse

Dong, Q.; DeAngelis, D.L.

1998-01-01

We used an individual-based modeling approach to study the consequences of cannibalism and competition for food in a freshwater fish population. We simulated the daily foraging, growth, and survival of the age-0 fish and older juvenile individuals of a sample population to reconstruct patterns of density dependence in the age-0 fish during the growth season. Cannibalism occurs as a part of the foraging process. For age-0 fish, older juvenile fish are both potential cannibals and competitors of food. We found that competition and cannibalism produced intraclass and interclass density dependence. Our modeling results suggested the following. (1) With low density of juvenile fish and weak interclass interactions, the age-0 fish recruitment shows a Beverton-Holt type of density dependence. (2) With high density of juvenile fish and strong interclass interactions, the age-0 fish recruitment shows a Ricker type of density dependence, and overcompensation occurs. (3) Interclass competition of food is responsible for much of the overcompensation. (4) Cannibalism intensifies the changes in the recruitment that are brought about by competition. Cannibalism can (a) generally reduce the recruitment, (b) particularly reduce the maximum level of recruitment, (c) cause overcompensation to occur at lower densities, and (d) produce a stronger overcompensation. (5) Growth is also a function of density. Cannibalism generally improves average growth of cannibals. (6) Variation in the lengths of age-0 fish increases with density and with a decreased average growth. These results imply that cannibalism and competition for food could strongly affect recruitment dynamics. Our model also showed that the rate of cannibalism either could be fairly even through the whole season or could vary dramatically. The individual-based modeling approach can help ecologists understand the mechanistic connection between daily behavioral and physiological processes operating at the level of individual organisms and seasonal patterns of population structure and dynamics. ?? Copyright by the American Fisheries Society 1998.

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

Phillips, William Scott

This seminar presentation describes amplitude models and yield estimations that look at the data in order to inform legislation. The following points were brought forth in the summary: global models that will predict three-component amplitudes (R-T-Z) were produced; Q models match regional geology; corrected source spectra can be used for discrimination and yield estimation; three-component data increase coverage and reduce scatter in source spectral estimates; three-component efforts must include distance-dependent effects; a community effort on instrument calibration is needed.

High-speed tracking control of piezoelectric actuators using an ellipse-based hysteresis model.

PubMed

Gu, Guoying; Zhu, Limin

2010-08-01

In this paper, an ellipse-based mathematic model is developed to characterize the rate-dependent hysteresis in piezoelectric actuators. Based on the proposed model, an expanded input space is constructed to describe the multivalued hysteresis function H[u](t) by a multiple input single output (MISO) mapping Gamma:R(2)-->R. Subsequently, the inverse MISO mapping Gamma(-1)(H[u](t),H[u](t);u(t)) is proposed for real-time hysteresis compensation. In controller design, a hybrid control strategy combining a model-based feedforward controller and a proportional integral differential (PID) feedback loop is used for high-accuracy and high-speed tracking control of piezoelectric actuators. The real-time feedforward controller is developed to cancel the rate-dependent hysteresis based on the inverse hysteresis model, while the PID controller is used to compensate for the creep, modeling errors, and parameter uncertainties. Finally, experiments with and without hysteresis compensation are conducted and the experimental results are compared. The experimental results show that the hysteresis compensation in the feedforward path can reduce the hysteresis-caused error by up to 88% and the tracking performance of the hybrid controller is greatly improved in high-speed tracking control applications, e.g., the root-mean-square tracking error is reduced to only 0.34% of the displacement range under the input frequency of 100 Hz.

Consumers limit the abundance and dynamics of a perennial shrub with a seed bank

USGS Publications Warehouse

Kauffman, M.J.; Maron, J.L.

2006-01-01

For nearly 30 years, ecologists have argued that predators of seeds and seedlings seldom have population-level effects on plants with persistent seed banks and density-dependent seedling survival. We parameterized stage-based population models that incorporated density dependence and seed dormancy with data from a 5.5-year experiment that quantified how granivorous mice and herbivorous voles influence bush lupine (Lupinus arboreus) demography. We asked how seed dormancy and density-dependent seedling survival mediate the impacts of these consumers in dune and grassland habitats. In dune habitat, mice reduced analytical ?? (the intrinsic rate of population growth) by 39%, the equilibrium number of above-ground plants by 90%, and the seed bank by 98%; voles had minimal effects. In adjacent grasslands, mice had minimal effects, but seedling herbivory by voles reduced analytical ?? by 15% and reduced both the equilibrium number of aboveground plants and dormant seeds by 63%. A bootstrap analysis demonstrated that these consumer effects were robust to parameter uncertainty. Our results demonstrate that the quantitative strengths of seed dormancy and density-dependent seedling survival-not their mere existence-critically mediate consumer effects. This study suggests that plant population dynamics and distribution may be more strongly influenced by consumers of seeds and seedlings than is currently recognized. ?? 2006 by The University of Chicago.

A Simplified Ab Initio Cosmic-ray Modulation Model with Simulated Time Dependence and Predictive Capability

NASA Astrophysics Data System (ADS)

Moloto, K. D.; Engelbrecht, N. E.; Burger, R. A.

2018-06-01

A simplified ab initio approach is followed to model cosmic-ray proton modulation, using a steady-state three-dimensional stochastic solver of the Parker transport equation that simulates some effects of time dependence. Standard diffusion coefficients based on Quasilinear Theory and Nonlinear Guiding Center Theory are employed. The spatial and temporal dependences of the various turbulence quantities required as inputs for the diffusion, as well as the turbulence-reduced drift coefficients, follow from parametric fits to results from a turbulence transport model as well as from spacecraft observations of these turbulence quantities. Effective values are used for the solar wind speed, magnetic field magnitude, and tilt angle in the modulation model to simulate temporal effects due to changes in the large-scale heliospheric plasma. The unusually high cosmic-ray intensities observed during the 2009 solar minimum follow naturally from the current model for most of the energies considered. This demonstrates that changes in turbulence contribute significantly to the high intensities during that solar minimum. We also discuss and illustrate how this model can be used to predict future cosmic-ray intensities, and comment on the reliability of such predictions.

Reducing uncertainty in species sensitivity distributions with interspecies toxicity estimation models

EPA Science Inventory

Determining harmful levels of contaminants for a wide range of species is limited by available toxicological data. Ecological risk assessments typically depend on empirical data from only a few species that represent a narrow range of the life history spectrum. Extrapolation mo...

The microbial fermentation characteristics depend on both carbohydrate source and heat processing: a model experiment with ileo-cannulated pigs.

PubMed

Nielsen, Tina Skau; Jørgensen, Henry; Knudsen, Knud Erik Bach; Lærke, Helle Nygaard

2017-11-01

The effects of carbohydrate (CHO) source and processing (extrusion cooking) on large intestinal fermentation products were studied in ileo-cannulated pigs as a model for humans. Pigs were fed diets containing barley, pea or a mixture of potato starch:wheat bran (PSWB) either raw or extrusion cooked. Extrusion cooking reduced the amount of starch fermented in the large intestine by 52-96% depending on the CHO source and the total pool of butyrate in the distal small intestine + large intestine by on average 60% across diets. Overall, extrusion cooking caused a shift in the composition of short-chain fatty acids (SCFA) produced towards more acetate and less propionate and butyrate. The CHO source and processing highly affected the fermentation characteristics and extrusion cooking generally reduced large intestinal fermentation and resulted in a less desirable composition of the fermentation products. The latter outcome is non-conducive to a healthy large intestinal environment and its resulting metabolic health.

Cardioprotection induced in a mouse model of neuropathic pain via anterior nucleus of paraventricular thalamus.

PubMed

Cheng, Yi-Fen; Chang, Ya-Ting; Chen, Wei-Hsin; Shih, Hsi-Chien; Chen, Yen-Hui; Shyu, Bai-Chuang; Chen, Chien-Chang

2017-10-10

Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway. Pharmacological inhibition of extracellular signal-regulated kinase activation in the PVA abolishes neuropathic pain-induced cardioprotection, whereas activation of PVA neurons pharmacologically, or optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore, neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve is responsible for this unexpected cardioprotective effect of chronic neuropathic pain in mice.Various forms of preconditioning can prevent ischemic-reperfusion injury after myocardial infarction. Here, the authors show that in mice, the presence of chronic neuropathic pain can have a cardioprotective effect, and that this is dependent on neural activation in the paraventricular thalamus.

First-principles calculations of orientation dependence of Si thermal oxidation based on Si emission model

NASA Astrophysics Data System (ADS)

Nagura, Takuya; Kawachi, Shingo; Chokawa, Kenta; Shirakawa, Hiroki; Araidai, Masaaki; Kageshima, Hiroyuki; Endoh, Tetsuo; Shiraishi, Kenji

2018-04-01

It is expected that the off-state leakage current of MOSFETs can be reduced by employing vertical body channel MOSFETs (V-MOSFETs). However, in fabricating these devices, the structure of the Si pillars sometimes cannot be maintained during oxidation, since Si atoms sometimes disappear from the Si/oxide interface (Si missing). Thus, in this study, we used first-principles calculations based on the density functional theory, and investigated the Si emission behavior at the various interfaces on the basis of the Si emission model including its atomistic structure and dependence on Si crystal orientation. The results show that the order in which Si atoms are more likely to be emitted during thermal oxidation is (111) > (110) > (310) > (100). Moreover, the emission of Si atoms is enhanced as the compressive strain increases. Therefore, the emission of Si atoms occurs more easily in V-MOSFETs than in planar MOSFETs. To reduce Si missing in V-MOSFETs, oxidation processes that induce less strain, such as wet or pyrogenic oxidation, are necessary.

Modeling gravity-dependent plasticity of the angular vestibuloocular reflex with a physiologically based neural network.

PubMed

Xiang, Yongqing; Yakushin, Sergei B; Cohen, Bernard; Raphan, Theodore

2006-12-01

A neural network model was developed to explain the gravity-dependent properties of gain adaptation of the angular vestibuloocular reflex (aVOR). Gain changes are maximal at the head orientation where the gain is adapted and decrease as the head is tilted away from that position and can be described by the sum of gravity-independent and gravity-dependent components. The adaptation process was modeled by modifying the weights and bias values of a three-dimensional physiologically based neural network of canal-otolith-convergent neurons that drive the aVOR. Model parameters were trained using experimental vertical aVOR gain values. The learning rule aimed to reduce the error between eye velocities obtained from experimental gain values and model output in the position of adaptation. Although the model was trained only at specific head positions, the model predicted the experimental data at all head positions in three dimensions. Altering the relative learning rates of the weights and bias improved the model-data fits. Model predictions in three dimensions compared favorably with those of a double-sinusoid function, which is a fit that minimized the mean square error at every head position and served as the standard by which we compared the model predictions. The model supports the hypothesis that gravity-dependent adaptation of the aVOR is realized in three dimensions by a direct otolith input to canal-otolith neurons, whose canal sensitivities are adapted by the visual-vestibular mismatch. The adaptation is tuned by how the weights from otolith input to the canal-otolith-convergent neurons are adapted for a given head orientation.

The Importance of Three Physical Processes in a Minimal Three-Dimensional Tropical Cyclone Model.

NASA Astrophysics Data System (ADS)

Zhu, Hongyan; Smith, Roger K.

2002-06-01

The minimal three-dimensional tropical cyclone model developed by Zhu et al. is used to explore the role of shallow convection, precipitation-cooled downdrafts, and the vertical transport of momentum by deep convection on the dynamics of tropical cyclone intensification. The model is formulated in coordinates and has three vertical levels, one characterizing a shallow boundary layer, and the other two representing the upper and lower troposphere, respectively. It has three options for treating cumulus convection on the subgrid scale and a simple scheme for the explicit release of latent heat on the grid scale.In the model, as in reality, shallow convection transports air with low moist static energy from the lower troposphere to the boundary layer, stabilizing the atmosphere not only to itself, but also to deep convection. Also it moistens and cools the lower troposphere. For realistic parameter values, the stabilization in the vortex core region is the primary effect: it reduces the deep convective mass flux and therefore the rate of heating and drying in the troposphere. This reduced heating, together with the direct cooling of the lower troposphere by shallow convection, diminishes the buoyancy in the vortex core and thereby the vortex intensification rate.The effects of precipitation-cooled downdrafts depend on the closure scheme chosen for deep convection. In the two closures in which the deep cloud mass flux depends on the degree of convective instability, the downdrafts do not change the total mass flux of air that subsides into the boundary layer, but they carry air with a lower moist static energy into this layer than does subsidence outside downdrafts. As a result they decrease the rate of intensification during the early development stage. Nevertheless, by reducing the deep convective mass flux and the drying effect of compensating subsidence, they enable grid scale saturation, and therefore rapid intensification, to occur earlier than in calculations where they are excluded. In the closure in which the deep cloud mass flux depends on the mass convergence in the boundary layer, downdrafts reduce the gestation period and increase the intensification rate.Convective momentum transport as represented in the model weakens both the primary and secondary circulations of the vortex. However, it does not significantly reduce the maximum intensity attained after the period of rapid development. The weakening of the secondary circulation impedes vortex development and significantly prolongs the gestation period.Where possible the results are compared with those found in other studies.

Influence of ecohydrologic feedbacks from simulated crop growth on integrated regional hydrologic simulations under climate scenarios

NASA Astrophysics Data System (ADS)

van Walsum, P. E. V.; Supit, I.

2012-06-01

Hydrologic climate change modelling is hampered by climate-dependent model parameterizations. To reduce this dependency, we extended the regional hydrologic modelling framework SIMGRO to host a two-way coupling between the soil moisture model MetaSWAP and the crop growth simulation model WOFOST, accounting for ecohydrologic feedbacks in terms of radiation fraction that reaches the soil, crop coefficient, interception fraction of rainfall, interception storage capacity, and root zone depth. Except for the last, these feedbacks are dependent on the leaf area index (LAI). The influence of regional groundwater on crop growth is included via a coupling to MODFLOW. Two versions of the MetaSWAP-WOFOST coupling were set up: one with exogenous vegetation parameters, the "static" model, and one with endogenous crop growth simulation, the "dynamic" model. Parameterization of the static and dynamic models ensured that for the current climate the simulated long-term averages of actual evapotranspiration are the same for both models. Simulations were made for two climate scenarios and two crops: grass and potato. In the dynamic model, higher temperatures in a warm year under the current climate resulted in accelerated crop development, and in the case of potato a shorter growing season, thus partly avoiding the late summer heat. The static model has a higher potential transpiration; depending on the available soil moisture, this translates to a higher actual transpiration. This difference between static and dynamic models is enlarged by climate change in combination with higher CO2 concentrations. Including the dynamic crop simulation gives for potato (and other annual arable land crops) systematically higher effects on the predicted recharge change due to climate change. Crop yields from soils with poor water retention capacities strongly depend on capillary rise if moisture supply from other sources is limited. Thus, including a crop simulation model in an integrated hydrologic simulation provides a valuable addition for hydrologic modelling as well as for crop modelling.

Secisbp2 Is Essential for Embryonic Development and Enhances Selenoprotein Expression

PubMed Central

Seeher, Sandra; Atassi, Tarik; Mahdi, Yassin; Carlson, Bradley A.; Braun, Doreen; Wirth, Eva K.; Klein, Marc O.; Reix, Nathalie; Miniard, Angela C.; Schomburg, Lutz; Hatfield, Dolph L.; Driscoll, Donna M.

2014-01-01

Abstract Aims: The selenocysteine insertion sequence (SECIS)-binding protein 2 (Secisbp2) binds to SECIS elements located in the 3′-untranslated region of eukaryotic selenoprotein mRNAs. Selenoproteins contain the rare amino acid selenocysteine (Sec). Mutations in SECISBP2 in humans lead to reduced selenoprotein expression thereby affecting thyroid hormone-dependent growth and differentiation processes. The most severe cases also display myopathy, hearing impairment, male infertility, increased photosensitivity, mental retardation, and ataxia. Mouse models are needed to understand selenoprotein-dependent processes underlying the patients' pleiotropic phenotypes. Results: Unlike tRNA[Ser]Sec-deficient embryos, homozygous Secisbp2-deleted embryos implant, but fail before gastrulation. Heterozygous inactivation of Secisbp2 reduced the amount of selenoprotein expressed, but did not affect the thyroid hormone axis or growth. Conditional deletion of Secisbp2 in hepatocytes significantly decreased selenoprotein expression. Unexpectedly, the loss of Secisbp2 reduced the abundance of many, but not all, selenoprotein mRNAs. Transcript-specific and gender-selective effects on selenoprotein mRNA abundance were greater in Secisbp2-deficient hepatocytes than in tRNA[Ser]Sec-deficient cells. Despite the massive reduction of Dio1 and Sepp1 mRNAs, significantly more corresponding protein was detected in primary hepatocytes lacking Secisbp2 than in cells lacking tRNA[Ser]Sec. Regarding selenoprotein expression, compensatory nuclear factor, erythroid-derived, like 2 (Nrf2)-dependent gene expression, or embryonic development, phenotypes were always milder in Secisbp2-deficient than in tRNA[Ser]Sec-deficient mice. Innovation: We report the first Secisbp2 mutant mouse models. The conditional mutants provide a model for analyzing Secisbp2 function in organs not accessible in patients. Conclusion: In hepatocyte-specific conditional mouse models, Secisbp2 gene inactivation is less detrimental than tRNA[Ser]Sec inactivation. A role of Secisbp2 in stabilizing selenoprotein mRNAs in vivo was uncovered. Antioxid. Redox Signal. 21, 835–849. PMID:24274065

Modeling ecological traps for the control of feral pigs

PubMed Central

Dexter, Nick; McLeod, Steven R

2015-01-01

Ecological traps are habitat sinks that are preferred by dispersing animals but have higher mortality or reduced fecundity compared to source habitats. Theory suggests that if mortality rates are sufficiently high, then ecological traps can result in extinction. An ecological trap may be created when pest animals are controlled in one area, but not in another area of equal habitat quality, and when there is density-dependent immigration from the high-density uncontrolled area to the low-density controlled area. We used a logistic population model to explore how varying the proportion of habitat controlled, control mortality rate, and strength of density-dependent immigration for feral pigs could affect the long-term population abundance and time to extinction. Increasing control mortality, the proportion of habitat controlled and the strength of density-dependent immigration decreased abundance both within and outside the area controlled. At higher levels of these parameters, extinction was achieved for feral pigs. We extended the analysis with a more complex stochastic, interactive model of feral pig dynamics in the Australian rangelands to examine how the same variables as the logistic model affected long-term abundance in the controlled and uncontrolled area and time to extinction. Compared to the logistic model of feral pig dynamics, the stochastic interactive model predicted lower abundances and extinction at lower control mortalities and proportions of habitat controlled. To improve the realism of the stochastic interactive model, we substituted fixed mortality rates with a density-dependent control mortality function, empirically derived from helicopter shooting exercises in Australia. Compared to the stochastic interactive model with fixed mortality rates, the model with the density-dependent control mortality function did not predict as substantial decline in abundance in controlled or uncontrolled areas or extinction for any combination of variables. These models demonstrate that pest eradication is theoretically possible without the pest being controlled throughout its range because of density-dependent immigration into the area controlled. The stronger the density-dependent immigration, the better the overall control in controlled and uncontrolled habitat combined. However, the stronger the density-dependent immigration, the poorer the control in the area controlled. For feral pigs, incorporating environmental stochasticity improves the prospects for eradication, but adding a realistic density-dependent control function eliminates these prospects. PMID:26045954

Modal Substructuring of Geometrically Nonlinear Finite-Element Models

DOE PAGES

Kuether, Robert J.; Allen, Matthew S.; Hollkamp, Joseph J.

2015-12-21

The efficiency of a modal substructuring method depends on the component modes used to reduce each subcomponent model. Methods such as Craig–Bampton have been used extensively to reduce linear finite-element models with thousands or even millions of degrees of freedom down orders of magnitude while maintaining acceptable accuracy. A novel reduction method is proposed here for geometrically nonlinear finite-element models using the fixed-interface and constraint modes of the linearized system to reduce each subcomponent model. The geometric nonlinearity requires an additional cubic and quadratic polynomial function in the modal equations, and the nonlinear stiffness coefficients are determined by applying amore » series of static loads and using the finite-element code to compute the response. The geometrically nonlinear, reduced modal equations for each subcomponent are then coupled by satisfying compatibility and force equilibrium. This modal substructuring approach is an extension of the Craig–Bampton method and is readily applied to geometrically nonlinear models built directly within commercial finite-element packages. The efficiency of this new approach is demonstrated on two example problems: one that couples two geometrically nonlinear beams at a shared rotational degree of freedom, and another that couples an axial spring element to the axial degree of freedom of a geometrically nonlinear beam. The nonlinear normal modes of the assembled models are compared with those of a truth model to assess the accuracy of the novel modal substructuring approach.« less

Modal Substructuring of Geometrically Nonlinear Finite-Element Models

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

Kuether, Robert J.; Allen, Matthew S.; Hollkamp, Joseph J.

The efficiency of a modal substructuring method depends on the component modes used to reduce each subcomponent model. Methods such as Craig–Bampton have been used extensively to reduce linear finite-element models with thousands or even millions of degrees of freedom down orders of magnitude while maintaining acceptable accuracy. A novel reduction method is proposed here for geometrically nonlinear finite-element models using the fixed-interface and constraint modes of the linearized system to reduce each subcomponent model. The geometric nonlinearity requires an additional cubic and quadratic polynomial function in the modal equations, and the nonlinear stiffness coefficients are determined by applying amore » series of static loads and using the finite-element code to compute the response. The geometrically nonlinear, reduced modal equations for each subcomponent are then coupled by satisfying compatibility and force equilibrium. This modal substructuring approach is an extension of the Craig–Bampton method and is readily applied to geometrically nonlinear models built directly within commercial finite-element packages. The efficiency of this new approach is demonstrated on two example problems: one that couples two geometrically nonlinear beams at a shared rotational degree of freedom, and another that couples an axial spring element to the axial degree of freedom of a geometrically nonlinear beam. The nonlinear normal modes of the assembled models are compared with those of a truth model to assess the accuracy of the novel modal substructuring approach.« less

Analytical results for a stochastic model of gene expression with arbitrary partitioning of proteins

NASA Astrophysics Data System (ADS)

Tschirhart, Hugo; Platini, Thierry

2018-05-01

In biophysics, the search for analytical solutions of stochastic models of cellular processes is often a challenging task. In recent work on models of gene expression, it was shown that a mapping based on partitioning of Poisson arrivals (PPA-mapping) can lead to exact solutions for previously unsolved problems. While the approach can be used in general when the model involves Poisson processes corresponding to creation or degradation, current applications of the method and new results derived using it have been limited to date. In this paper, we present the exact solution of a variation of the two-stage model of gene expression (with time dependent transition rates) describing the arbitrary partitioning of proteins. The methodology proposed makes full use of the PPA-mapping by transforming the original problem into a new process describing the evolution of three biological switches. Based on a succession of transformations, the method leads to a hierarchy of reduced models. We give an integral expression of the time dependent generating function as well as explicit results for the mean, variance, and correlation function. Finally, we discuss how results for time dependent parameters can be extended to the three-stage model and used to make inferences about models with parameter fluctuations induced by hidden stochastic variables.

Mathematical Modeling of Dual Layer Shell Type Recuperation System for Biogas Dehumidification

NASA Astrophysics Data System (ADS)

Gendelis, S.; Timuhins, A.; Laizans, A.; Bandeniece, L.

2015-12-01

The main aim of the current paper is to create a mathematical model for dual layer shell type recuperation system, which allows reducing the heat losses from the biomass digester and water amount in the biogas without any additional mechanical or chemical components. The idea of this system is to reduce the temperature of the outflowing gas by creating two-layered counter-flow heat exchanger around the walls of biogas digester, thus increasing a thermal resistance and the gas temperature, resulting in a condensation on a colder surface. Complex mathematical model, including surface condensation, is developed for this type of biogas dehumidifier and the parameter study is carried out for a wide range of parameters. The model is reduced to 1D case to make numerical calculations faster. It is shown that latent heat of condensation is very important for the total heat balance and the condensation rate is highly dependent on insulation between layers and outside temperature. Modelling results allow finding optimal geometrical parameters for the known gas flow and predicting the condensation rate for different system setups and seasons.

Validation of Potential Models for Li2O in Classical Molecular Dynamics Simulation

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

Oda, Takuji; Oya, Yasuhisa; Tanaka, Satoru

2007-08-01

Four Buckingham-type pairwise potential models for Li2O were assessed by molecular static and dynamics simulations. In the static simulation, all models afforded acceptable agreement with experimental values and ab initio calculation results for the crystalline properties. Moreover, the superionic phase transition was realized in the dynamics simulation. However, the Li diffusivity and the lattice expansion were not adequately reproduced at the same time by any model. When using these models in future radiation simulation, these features should be taken into account, in order to reduce the model dependency of the results.

Effectiveness of Gross Model-Based Emotion Regulation Strategies Training on Anger Reduction in Drug-Dependent Individuals and its Sustainability in Follow-up.

PubMed

Massah, Omid; Sohrabi, Faramarz; A'azami, Yousef; Doostian, Younes; Farhoudian, Ali; Daneshmand, Reza

2016-03-01

Emotion plays an important role in adapting to life changes and stressful events. Difficulty regulating emotions is one of the problems drug abusers often face, and teaching these individuals to express and manage their emotions can be effective on improving their difficult circumstances. The present study aimed to determine the effectiveness of the Gross model-based emotion regulation strategies training on anger reduction in drug-dependent individuals. The present study had a quasi-experimental design wherein pretest-posttest evaluations were applied using a control group. The population under study included addicts attending Marivan's methadone maintenance therapy centers in 2012 - 2013. Convenience sampling was used to select 30 substance-dependent individuals undergoing maintenance treatment who were then randomly assigned to the experiment and control groups. The experiment group received its training in eight two-hour sessions. Data were analyzed using analysis of co-variance and paired t-test. There was significant reduction in anger symptoms of drug-dependent individuals after gross model based emotion regulation training (ERT) (P < 0.001). Moreover, the effectiveness of the training on anger was persistent in the follow-up period. Symptoms of anger in drug-dependent individuals of this study were reduced by gross model-based emotion regulation strategies training. Based on the results of this study, we may conclude that the gross model based emotion regulation strategies training can be applied alongside other therapies to treat drug abusers undergoing rehabilitation.

Fractional modeling of viscoelasticity in 3D cerebral arteries and aneurysms

NASA Astrophysics Data System (ADS)

Yu, Yue; Perdikaris, Paris; Karniadakis, George Em

2016-10-01

We develop efficient numerical methods for fractional order PDEs, and employ them to investigate viscoelastic constitutive laws for arterial wall mechanics. Recent simulations using one-dimensional models [1] have indicated that fractional order models may offer a more powerful alternative for modeling the arterial wall response, exhibiting reduced sensitivity to parametric uncertainties compared with the integer-calculus-based models. Here, we study three-dimensional (3D) fractional PDEs that naturally model the continuous relaxation properties of soft tissue, and for the first time employ them to simulate flow structure interactions for patient-specific brain aneurysms. To deal with the high memory requirements and in order to accelerate the numerical evaluation of hereditary integrals, we employ a fast convolution method [2] that reduces the memory cost to O (log ⁡ (N)) and the computational complexity to O (Nlog ⁡ (N)). Furthermore, we combine the fast convolution with high-order backward differentiation to achieve third-order time integration accuracy. We confirm that in 3D viscoelastic simulations, the integer order models strongly depends on the relaxation parameters, while the fractional order models are less sensitive. As an application to long-time simulations in complex geometries, we also apply the method to modeling fluid-structure interaction of a 3D patient-specific compliant cerebral artery with an aneurysm. Taken together, our findings demonstrate that fractional calculus can be employed effectively in modeling complex behavior of materials in realistic 3D time-dependent problems if properly designed efficient algorithms are employed to overcome the extra memory requirements and computational complexity associated with the non-local character of fractional derivatives.

Fractional modeling of viscoelasticity in 3D cerebral arteries and aneurysms

PubMed Central

Perdikaris, Paris; Karniadakis, George Em

2017-01-01

We develop efficient numerical methods for fractional order PDEs, and employ them to investigate viscoelastic constitutive laws for arterial wall mechanics. Recent simulations using one-dimensional models [1] have indicated that fractional order models may offer a more powerful alternative for modeling the arterial wall response, exhibiting reduced sensitivity to parametric uncertainties compared with the integer-calculus-based models. Here, we study three-dimensional (3D) fractional PDEs that naturally model the continuous relaxation properties of soft tissue, and for the first time employ them to simulate flow structure interactions for patient-specific brain aneurysms. To deal with the high memory requirements and in order to accelerate the numerical evaluation of hereditary integrals, we employ a fast convolution method [2] that reduces the memory cost to O(log(N)) and the computational complexity to O(N log(N)). Furthermore, we combine the fast convolution with high-order backward differentiation to achieve third-order time integration accuracy. We confirm that in 3D viscoelastic simulations, the integer order models strongly depends on the relaxation parameters, while the fractional order models are less sensitive. As an application to long-time simulations in complex geometries, we also apply the method to modeling fluid–structure interaction of a 3D patient-specific compliant cerebral artery with an aneurysm. Taken together, our findings demonstrate that fractional calculus can be employed effectively in modeling complex behavior of materials in realistic 3D time-dependent problems if properly designed efficient algorithms are employed to overcome the extra memory requirements and computational complexity associated with the non-local character of fractional derivatives. PMID:29104310

Changing crops in response to climate: virtual Nang Rong, Thailand in an agent based simulation

PubMed Central

Malanson, George P.; Verdery, Ashton M.; Walsh, Stephen J.; Sawangdee, Yothin; Heumann, Benjamin W.; McDaniel, Philip M.; Frizzelle, Brian G.; Williams, Nathalie E.; Yao, Xiaozheng; Entwisle, Barbara; Rindfuss, Ronald R.

2014-01-01

The effects of extended climatic variability on agricultural land use were explored for the type of system found in villages of northeastern Thailand. An agent based model developed for the Nang Rong district was used to simulate land allotted to jasmine rice, heavy rice, cassava, and sugar cane. The land use choices in the model depended on likely economic outcomes, but included elements of bounded rationality in dependence on household demography. The socioeconomic dynamics are endogenous in the system, and climate changes were added as exogenous drivers. Villages changed their agricultural effort in many different ways. Most villages reduced the amount of land under cultivation, primarily with reduction in jasmine rice, but others did not. The variation in responses to climate change indicates potential sensitivity to initial conditions and path dependence for this type of system. The differences between our virtual villages and the real villages of the region indicate effects of bounded rationality and limits on model applications. PMID:25061240

Postseismic viscoelastic deformation and stress. Part 2: Stress theory and computation; dependence of displacement, strain, and stress on fault parameters

NASA Technical Reports Server (NTRS)

Cohen, S. C.

1979-01-01

A viscoelastic model for deformation and stress associated with earthquakes is reported. The model consists of a rectangular dislocation (strike slip fault) in a viscoelastic layer (lithosphere) lying over a viscoelastic half space (asthenosphere). The time dependent surface stresses are analyzed. The model predicts that near the fault a significant fraction of the stress that was reduced during the earthquake is recovered by viscoelastic softening of the lithosphere. By contrast, the strain shows very little change near the fault. The model also predicts that the stress changes associated with asthenospheric flow extend over a broader region than those associated with lithospheric relaxation even though the peak value is less. The dependence of the displacements, stresses on fault parameters studied. Peak values of strain and stress drop increase with increasing fault height and decrease with fault depth. Under many circumstances postseismic strains and stresses show an increase with decreasing depth to the lithosphere-asthenosphere boundary. Values of the strain and stress at distant points from the fault increase with fault area but are relatively insensitive to fault depth.

A Theory of Age-Dependent Mutation and Senescence

PubMed Central

Moorad, Jacob A.; Promislow, Daniel E. L.

2008-01-01

Laboratory experiments show us that the deleterious character of accumulated novel age-specific mutations is reduced and made less variable with increased age. While theories of aging predict that the frequency of deleterious mutations at mutation–selection equilibrium will increase with the mutation's age of effect, they do not account for these age-related changes in the distribution of de novo mutational effects. Furthermore, no model predicts why this dependence of mutational effects upon age exists. Because the nature of mutational distributions plays a critical role in shaping patterns of senescence, we need to develop aging theory that explains and incorporates these effects. Here we propose a model that explains the age dependency of mutational effects by extending Fisher's geometrical model of adaptation to include a temporal dimension. Using a combination of simple analytical arguments and simulations, we show that our model predicts age-specific mutational distributions that are consistent with observations from mutation-accumulation experiments. Simulations show us that these age-specific mutational effects may generate patterns of senescence at mutation–selection equilibrium that are consistent with observed demographic patterns that are otherwise difficult to explain. PMID:18660535

Comparison of algorithms to generate event times conditional on time-dependent covariates.

PubMed

Sylvestre, Marie-Pierre; Abrahamowicz, Michal

2008-06-30

The Cox proportional hazards model with time-dependent covariates (TDC) is now a part of the standard statistical analysis toolbox in medical research. As new methods involving more complex modeling of time-dependent variables are developed, simulations could often be used to systematically assess the performance of these models. Yet, generating event times conditional on TDC requires well-designed and efficient algorithms. We compare two classes of such algorithms: permutational algorithms (PAs) and algorithms based on a binomial model. We also propose a modification of the PA to incorporate a rejection sampler. We performed a simulation study to assess the accuracy, stability, and speed of these algorithms in several scenarios. Both classes of algorithms generated data sets that, once analyzed, provided virtually unbiased estimates with comparable variances. In terms of computational efficiency, the PA with the rejection sampler reduced the time necessary to generate data by more than 50 per cent relative to alternative methods. The PAs also allowed more flexibility in the specification of the marginal distributions of event times and required less calibration.

Analysis of Network and Non-Network Factors on Traveler Choice toward Improving Modeling Accuracy for Better Transportation Decisionmaking

DOT National Transportation Integrated Search

2014-09-01

The need to reduce congestion, enhance safety, and make the U.S. transportation system and cities more sustainable has given rise to various programs, technologies, and policies. The effectiveness of these interventions depends on how users eventuall...

A simple antireflection overcoat for opaque coatings in the submillimeter region

NASA Technical Reports Server (NTRS)

Smith, S. M.

1986-01-01

An antireflection overcoat for opaque baffle coatings in the far infrared (FIR)/submillimeter region was made from a simple Teflon spray-on lubricant. The Teflon overcoat reduced the specular reflectance of four different opaque coatings by nearly a factor of two. Analysis, based on the interference term of a reflecting-layer model, indicates that in the submillimeter region the reduced reflectance depends primarily on the refractive index of the overcoat and very little on its thickness.

Simulation and Optimization of an Astrophotonic Reformatter

NASA Astrophysics Data System (ADS)

Anagnos, Th; Harris, R. J.; Corrigan, M. K.; Reeves, A. P.; Townson, M. J.; MacLachlan, D. G.; Thomson, R. R.; Morris, T. J.; Schwab, C.; Quirrenbach, A.

2018-05-01

Image slicing is a powerful technique in astronomy. It allows the instrument designer to reduce the slit width of the spectrograph, increasing spectral resolving power whilst retaining throughput. Conventionally this is done using bulk optics, such as mirrors and prisms, however more recently astrophotonic components known as PLs and photonic reformatters have also been used. These devices reformat the MM input light from a telescope into SM outputs, which can then be re-arranged to suit the spectrograph. The PD is one such device, designed to reduce the dependence of spectrograph size on telescope aperture and eliminate modal noise. We simulate the PD, by optimising the throughput and geometrical design using Soapy and BeamProp. The simulated device shows a transmission between 8 and 20 %, depending upon the type of AO correction applied, matching the experimental results well. We also investigate our idealised model of the PD and show that the barycentre of the slit varies only slightly with time, meaning that the modal noise contribution is very low when compared to conventional fibre systems. We further optimise our model device for both higher throughput and reduced modal noise. This device improves throughput by 6.4 % and reduces the movement of the slit output by 50%, further improving stability. This shows the importance of properly simulating such devices, including atmospheric effects. Our work complements recent work in the field and is essential for optimising future photonic reformatters.

Modeling of the HiPco process for carbon nanotube production. I. Chemical kinetics

NASA Technical Reports Server (NTRS)

Dateo, Christopher E.; Gokcen, Tahir; Meyyappan, M.

2002-01-01

A chemical kinetic model is developed to help understand and optimize the production of single-walled carbon nanotubes via the high-pressure carbon monoxide (HiPco) process, which employs iron pentacarbonyl as the catalyst precursor and carbon monoxide as the carbon feedstock. The model separates the HiPco process into three steps, precursor decomposition, catalyst growth and evaporation, and carbon nanotube production resulting from the catalyst-enhanced disproportionation of carbon monoxide, known as the Boudouard reaction: 2 CO(g)-->C(s) + CO2(g). The resulting detailed model contains 971 species and 1948 chemical reactions. A second model with a reduced reaction set containing 14 species and 22 chemical reactions is developed on the basis of the detailed model and reproduces the chemistry of the major species. Results showing the parametric dependence of temperature, total pressure, and initial precursor partial pressures are presented, with comparison between the two models. The reduced model is more amenable to coupled reacting flow-field simulations, presented in the following article.

Fractal Tomlinson model for mesoscopic friction: from microscopic velocity-dependent damping to macroscopic Coulomb friction.

PubMed

Filippov, A E; Popov, V L

2007-02-01

A modified Tomlinson equation with fractal potential is studied. The effective potential is numerically generated and its mesoscopic structure is gradually adjusted to different scales by a number of Fourier modes. It is shown that with the change of scale the intensity of velocity-dependent damping in an effective Langevin equation can be gradually substituted by an equivalent constant "dry friction." For smooth macrosopic surfaces the effective equation completely reduces to the well known Coulomb law.

Heuristic Modeling for TRMM Lifetime Predictions

NASA Technical Reports Server (NTRS)

Jordan, P. S.; Sharer, P. J.; DeFazio, R. L.

1996-01-01

Analysis time for computing the expected mission lifetimes of proposed frequently maneuvering, tightly altitude constrained, Earth orbiting spacecraft have been significantly reduced by means of a heuristic modeling method implemented in a commercial-off-the-shelf spreadsheet product (QuattroPro) running on a personal computer (PC). The method uses a look-up table to estimate the maneuver frequency per month as a function of the spacecraft ballistic coefficient and the solar flux index, then computes the associated fuel use by a simple engine model. Maneuver frequency data points are produced by means of a single 1-month run of traditional mission analysis software for each of the 12 to 25 data points required for the table. As the data point computations are required only a mission design start-up and on the occasion of significant mission redesigns, the dependence on time consuming traditional modeling methods is dramatically reduced. Results to date have agreed with traditional methods to within 1 to 1.5 percent. The spreadsheet approach is applicable to a wide variety of Earth orbiting spacecraft with tight altitude constraints. It will be particularly useful to such missions as the Tropical Rainfall Measurement Mission scheduled for launch in 1997, whose mission lifetime calculations are heavily dependent on frequently revised solar flux predictions.

Reduced Coupling of Oxidative Phosphorylation In Vivo Precedes Electron Transport Chain Defects Due to Mild Oxidative Stress in Mice

PubMed Central

Siegel, Michael P.; Kruse, Shane E.; Knowels, Gary; Salmon, Adam; Beyer, Richard; Xie, Hui; Van Remmen, Holly; Smith, Steven R.; Marcinek, David J.

2011-01-01

Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ) treatment of wild type mice) and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1−/−)) models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O) at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax) was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain. PMID:22132085

From solitons to rogue waves in nonlinear left-handed metamaterials.

PubMed

Shen, Yannan; Kevrekidis, P G; Veldes, G P; Frantzeskakis, D J; DiMarzio, D; Lan, X; Radisic, V

2017-03-01

In the present work, we explore soliton and roguelike wave solutions in the transmission line analog of a nonlinear left-handed metamaterial. The nonlinearity is expressed through a voltage-dependent, symmetric capacitance motivated by recently developed ferroelectric barium strontium titanate thin-film capacitor designs. We develop both the corresponding nonlinear dynamical lattice and its reduction via a multiple scales expansion to a nonlinear Schrödinger (NLS) model for the envelope of a given carrier wave. The reduced model can feature either a focusing or a defocusing nonlinearity depending on the frequency (wave number) of the carrier. We then consider the robustness of different types of solitary waves of the reduced model within the original nonlinear left-handed medium. We find that both bright and dark solitons persist in a suitable parametric regime, where the reduction to the NLS model is valid. Additionally, for suitable initial conditions, we observe a rogue wave type of behavior that differs significantly from the classic Peregrine rogue wave evolution, including most notably the breakup of a single Peregrine-like pattern into solutions with multiple wave peaks. Finally, we touch upon the behavior of generalized members of the family of the Peregrine solitons, namely, Akhmediev breathers and Kuznetsov-Ma solitons, and explore how these evolve in the left-handed transmission line.

Effects of C1 Inhibitor on Tissue Damage in a Porcine Model of Controlled Hemorrhage

DTIC Science & Technology

2012-07-01

and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups...damage in a dose-dependent man- ner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis ... acidosis , reduced circulating tumor necrosis factor !, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on

Dynamics of atom-field entanglement for Tavis-Cummings models

NASA Astrophysics Data System (ADS)

Bashkirov, Eugene K.

2018-04-01

An exact solution of the problem of two-atom one- and two-mode Jaynes-Cummings model with intensity- dependent coupling is presented. Asymptotic solutions for system state vectors are obtained in the approximation of large initial coherent fields. The atom-field entanglement is investigated on the basis of the reduced atomic entropy dynamics. The possibility of the system being initially in a pure disentangled state to revive into this state during the evolution process for both models is shown. Conditions and times of disentanglement are derived.

Effects of Extinction Context and Retrieval Cues on Renewal of Alcohol-Cue Reactivity Among Alcohol-Dependent Outpatients

PubMed Central

Stasiewicz, Paul R.; Brandon, Thomas H.; Bradizza, Clara M.

2013-01-01

Pavlovian conditioning models have led to cue-exposure treatments for drug abuse. However, conditioned responding to drug stimuli can return (be renewed) following treatment. Animal research and a previous study of social drinkers indicated that extinction is highly context dependent but that renewal could be reduced by the inclusion of a cue from the extinction context. This study extends this research to a clinical sample. Alcohol-dependent outpatients (N = 143) completed an extinction trial to reduce craving and salivation responses to alcohol cues. They were then randomized to renewal tests in either the same context as extinction, a different context, the different context containing an extinction cue, or the different context with cue plus a manipulation to increase the salience of the cue. Contrary to predictions, the different context did not produce the expected renewal effect. Although the generalization of extinction effects beyond the cue-exposure context is a positive clinical finding, it is inconsistent with basic research findings on the context dependence of extinction. Possible explanations for this inconsistency are discussed. PMID:17563145

Calibration and temperature correction of heat dissipation matric potential sensors

USGS Publications Warehouse

Flint, A.L.; Campbell, G.S.; Ellett, K.M.; Calissendorff, C.

2002-01-01

This paper describes how heat dissipation sensors, used to measure soil water matric potential, were analyzed to develop a normalized calibration equation and a temperature correction method. Inference of soil matric potential depends on a correlation between the variable thermal conductance of the sensor's porous ceramic and matric poten-tial. Although this correlation varies among sensors, we demonstrate a normalizing procedure that produces a single calibration relationship. Using sensors from three sources and different calibration methods, the normalized calibration resulted in a mean absolute error of 23% over a matric potential range of -0.01 to -35 MPa. Because the thermal conductivity of variably saturated porous media is temperature dependent, a temperature correction is required for application of heat dissipation sensors in field soils. A temperature correction procedure is outlined that reduces temperature dependent errors by 10 times, which reduces the matric potential measurement errors by more than 30%. The temperature dependence is well described by a thermal conductivity model that allows for the correction of measurements at any temperature to measurements at the calibration temperature.

Effects of extinction context and retrieval cues on renewal of alcohol-cue reactivity among alcohol-dependent outpatients.

PubMed

Stasiewicz, Paul R; Brandon, Thomas H; Bradizza, Clara M

2007-06-01

Pavlovian conditioning models have led to cue-exposure treatments for drug abuse. However, conditioned responding to drug stimuli can return (be renewed) following treatment. Animal research and a previous study of social drinkers indicated that extinction is highly context dependent but that renewal could be reduced by the inclusion of a cue from the extinction context. This study extends this research to a clinical sample. Alcohol-dependent outpatients (N = 143) completed an extinction trial to reduce craving and salivation responses to alcohol cues. They were then randomized to renewal tests in either the same context as extinction, a different context, the different context containing an extinction cue, or the different context with cue plus a manipulation to increase the salience of the cue. Contrary to predictions, the different context did not produce the expected renewal effect. Although the generalization of extinction effects beyond the cue-exposure context is a positive clinical finding, it is inconsistent with basic research findings on the context dependence of extinction. Possible explanations for this inconsistency are discussed.

A Rationale for System-Dependent Advantages and Disadvantages of Solution Crystal Growth at Low Gravity

NASA Technical Reports Server (NTRS)

Rosenberger, Franz; Vekilov, Peter G.; Lin, Hong; Alexander, J. Iwan D.

1997-01-01

Protein crystallization experiments at reduced gravity have yielded crystals that, depending on the specific material, are either superior or inferior in their structural perfection compared to counterparts grown at normal gravity. A reduction of the crystals' quality due to their growth at low gravity cannot be understood from existing models. Our experimental investigations of the ground-based crystallization of the protein lysozyme have revealed pronounced unsteady growth layer dynamics and associated defect formation under steady external conditions. Through scaling analysis and numerical simulations we show that the observed fluctuations originate from the coupling of bulk transport with non-linear interface kinetics under mixed kinetics-transport control of the growth rate. The amplitude of the fluctuations is smallest when either transport or interfacial kinetics dominate the control of the crystallization process. Thus, depending on the specific system, crystal quality may be improved by either enhancing or suppressing the transport in the solution. These considerations provide, for the first time, a material-dependent rationale for the advantages, as well as the disadvantages, of reduced gravity for (protein) crystallization.

Multiple robustness in factorized likelihood models.

PubMed

Molina, J; Rotnitzky, A; Sued, M; Robins, J M

2017-09-01

We consider inference under a nonparametric or semiparametric model with likelihood that factorizes as the product of two or more variation-independent factors. We are interested in a finite-dimensional parameter that depends on only one of the likelihood factors and whose estimation requires the auxiliary estimation of one or several nuisance functions. We investigate general structures conducive to the construction of so-called multiply robust estimating functions, whose computation requires postulating several dimension-reducing models but which have mean zero at the true parameter value provided one of these models is correct.

Technology Status and Expected Greenhouse Gas Emissions of Battery, Plug-In Hybrid, and Fuel Cell Electric Vehicles

NASA Astrophysics Data System (ADS)

Lipman, Timothy E.

2011-11-01

Electric vehicles (EVs) of various types are experiencing a commercial renaissance but of uncertain ultimate success. Many new electric-drive models are being introduced by different automakers with significant technical improvements from earlier models, particularly with regard to further refinement of drivetrain systems and important improvements in battery and fuel cell systems. The various types of hybrid and all-electric vehicles can offer significant greenhouse gas (GHG) reductions when compared to conventional vehicles on a full fuel-cycle basis. In fact, most EVs used under most condition are expected to significantly reduce lifecycle GHG emissions. This paper reviews the current technology status of EVs and compares various estimates of their potential to reduce GHGs on a fuel cycle basis. In general, various studies show that battery powered EVs reduce GHGs by a widely disparate amount depending on the type of powerplant used and the particular region involved, among other factors. Reductions typical of the United States would be on the order of 20-50%, depending on the relative level of coal versus natural gas and renewables in the powerplant feedstock mix. However, much deeper reductions of over 90% are possible for battery EVs running on renewable or nuclear power sources. Plug-in hybrid vehicles running on gasoline can reduce emissions by 20-60%, and fuel cell EV reduce GHGs by 30-50% when running on natural gas-derived hydrogen and up to 95% or more when the hydrogen is made (and potentially compressed) using renewable feedstocks. These are all in comparison to what is usually assumed to be a more advanced gasoline vehicle "baseline" of comparison, with some incremental improvements by 2020 or 2030. Thus, the emissions from all of these EV types are highly variable depending on the details of how the electric fuel or hydrogen is produced.

Observations of geographically correlated orbit errors for TOPEX/Poseidon using the global positioning system

NASA Technical Reports Server (NTRS)

Christensen, E. J.; Haines, B. J.; Mccoll, K. C.; Nerem, R. S.

1994-01-01

We have compared Global Positioning System (GPS)-based dynamic and reduced-dynamic TOPEX/Poseidon orbits over three 10-day repeat cycles of the ground-track. The results suggest that the prelaunch joint gravity model (JGM-1) introduces geographically correlated errors (GCEs) which have a strong meridional dependence. The global distribution and magnitude of these GCEs are consistent with a prelaunch covariance analysis, with estimated and predicted global rms error statistics of 2.3 and 2.4 cm rms, respectively. Repeating the analysis with the post-launch joint gravity model (JGM-2) suggests that a portion of the meridional dependence observed in JGM-1 still remains, with global rms error of 1.2 cm.

Hybrid method for numerical modelling of LWR coolant chemistry

NASA Astrophysics Data System (ADS)

Swiatla-Wojcik, Dorota

2016-10-01

A comprehensive approach is proposed to model radiation chemistry of the cooling water under exposure to neutron and gamma radiation at 300 °C. It covers diffusion-kinetic processes in radiation tracks and secondary reactions in the bulk coolant. Steady-state concentrations of the radiolytic products have been assessed based on the simulated time dependent concentration profiles. The principal reactions contributing to the formation of H2, O2 and H2O2 were indicated. Simulation was carried out depending on the amount of extra hydrogen dissolved in the coolant to reduce concentration of corrosive agents. High sensitivity to the rate of reaction H+H2O=OH+H2 is shown and discussed.

Temperature dependence of frequency dispersion in III–V metal-oxide-semiconductor C-V and the capture/emission process of border traps

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

Vais, Abhitosh, E-mail: Abhitosh.Vais@imec.be; Martens, Koen; DeMeyer, Kristin

2015-08-03

This paper presents a detailed investigation of the temperature dependence of frequency dispersion observed in capacitance-voltage (C-V) measurements of III-V metal-oxide-semiconductor (MOS) devices. The dispersion in the accumulation region of the capacitance data is found to change from 4%–9% (per decade frequency) to ∼0% when the temperature is reduced from 300 K to 4 K in a wide range of MOS capacitors with different gate dielectrics and III-V substrates. We show that such significant temperature dependence of C-V frequency dispersion cannot be due to the temperature dependence of channel electrostatics, i.e., carrier density and surface potential. We also show that the temperaturemore » dependence of frequency dispersion, and hence, the capture/emission process of border traps can be modeled by a combination of tunneling and a “temperature-activated” process described by a non-radiative multi-phonon model, instead of a widely believed single-step elastic tunneling process.« less

Optimal vibration control of a rotating plate with self-sensing active constrained layer damping

NASA Astrophysics Data System (ADS)

Xie, Zhengchao; Wong, Pak Kin; Lo, Kin Heng

2012-04-01

This paper proposes a finite element model for optimally controlled constrained layer damped (CLD) rotating plate with self-sensing technique and frequency-dependent material property in both the time and frequency domain. Constrained layer damping with viscoelastic material can effectively reduce the vibration in rotating structures. However, most existing research models use complex modulus approach to model viscoelastic material, and an additional iterative approach which is only available in frequency domain has to be used to include the material's frequency dependency. It is meaningful to model the viscoelastic damping layer in rotating part by using the anelastic displacement fields (ADF) in order to include the frequency dependency in both the time and frequency domain. Also, unlike previous ones, this finite element model treats all three layers as having the both shear and extension strains, so all types of damping are taken into account. Thus, in this work, a single layer finite element is adopted to model a three-layer active constrained layer damped rotating plate in which the constraining layer is made of piezoelectric material to work as both the self-sensing sensor and actuator under an linear quadratic regulation (LQR) controller. After being compared with verified data, this newly proposed finite element model is validated and could be used for future research.

Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells: The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species

PubMed Central

Berndt, Nikolaus; Bulik, Sascha; Holzhütter, Hermann-Georg

2012-01-01

Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease. In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model. Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential. By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters. As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production. The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition. Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases. PMID:22719765

Amino Acids Inhibitory Effects and Mechanism on 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b]Pyridine (PhIP) Formation in the Maillard Reaction Model Systems.

PubMed

Linghu, Ziyi; Karim, Faris; Smith, J Scott

2017-12-01

This study was to investigate the inhibitory effects of amino acids (AAs) on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and to evaluate the inhibition mechanism of PhIP in Maillard model systems. Different AAs were individually added into model systems heat-treated at 180 °C/1 h. The PhIP, phenylacetaldehyde (PheAce), and pyrazines derivatives were determined using HPLC and GC-MS. AAs significantly reduced (P < 0.05) PhIP levels in a dose-dependent response, ranking as: Trp = Lys > Pro > Leu > Met > Val > Ile > Thr > Phe > Asp, at the highest molar ratio. The PheAce content was gradually reduced with increasing AAs levels, suggesting that AAs may inhibit PhIP formation through scavenging the available PheAce. A correlation between PhIP inhibition and PheAce-scavenging activity of AAs was observed when PheAce and AAs were heated. The variety and quantity of pyrazines formed are highly depending on the type of AAs. © 2017 Institute of Food Technologists®.

A new DFT approach to model small polarons in oxides with proper account for long-range polarization

NASA Astrophysics Data System (ADS)

Kokott, Sebastian; Levchenko, Sergey V.; Scheffler, Matthias; Theory Department Team

In this work, we address two important challenges in the DFT description of small polarons (excess charges localized within one unit cell): sensitivity to the errors in exchange-correlation (XC) treatment and finite-size effects in supercell calculations. The polaron properties are obtained using a modified neutral potential-energy surface (PES). Using the hybrid HSE functional and considering the whole range 0 <= α <= 1 , we show that the modified PES model significantly reduces the dependence of the polaron level and binding energy in MgO and TiO2 on the XC functional. It does not eliminate the dependence on supercell size. Based on Pekar's model, we derive the proper long-range behavior of the polaron and a finite-size correction that allows to obtain the polaron properties in the dilute limit (tested for supercells containing up to 1,000 atoms). The developed approach reduces drastically the computational time for exploring the polaron PES, and gives a consistent description of polarons for the whole range of α. It allowed us to find a self-trapped hole in MgO that is noticeably more stable than reported previously. partially supported by UniCat (Deutsche Forschungsgemeinschaft).

Evaluating Outdoor Water Use Demand under Changing Climatic and Demographic Conditions: An Agent-based Modeling Approach

NASA Astrophysics Data System (ADS)

Kanta, L.

2016-12-01

Outdoor water use for landscape and irrigation constitutes a significant end use in residential water demand. In periods of water shortages, utilities may reduce garden demands by implementing irrigation system audits, rebate programs, local ordinances, and voluntary or mandatory water use restrictions. Because utilities do not typically record outdoor and indoor water uses separately, the effects of policies for reducing garden demands cannot be readily calculated. The volume of water required to meet garden demands depends on the housing density or lawn size, type of vegetation, climatic conditions, efficiency of garden irrigation systems, and consumer water-use behaviors. Many existing outdoor demand estimation methods are deterministic and do not include consumer responses to conservation campaigns. In addition, mandatory restrictions may have a substantial impact on reducing outdoor demands, but the effectiveness of mandatory restrictions depends on the timing and the frequency of restrictions, in addition to the distribution of housing density and consumer types within a community. This research investigates a garden end-use model by coupling an agent-based modeling approach and a mechanistic-stochastic water demand model to create a methodology for estimating garden demand and evaluating demand reduction policies. The garden demand model is developed for two water utilities, using a diverse data sets, including residential customer billing records, records of outdoor conservation programs, frequency and type of mandatory water use restrictions, lot size distribution, population growth, and climatic data. A set of garden irrigation parameter values, which are based on the efficiency of irrigation systems and irrigation habits of consumers, are determined for a set of conservation ordinances and restrictions. The model parameters are then validated using customer water usage data from the participating water utilities. A sensitivity analysis is conducted for garden irrigation parameters to determine the most significant factors that should be considered by water utilities to reduce outdoor demand. Data from multiple sources and the agent-based modeling methodology are integrated using a holistic approach to assist utilities in efficiently and sustainably managing outdoor demand.

Evaluating Outdoor Water Use Demand under Changing Climatic and Demographic Conditions: An Agent-based Modeling Approach

NASA Astrophysics Data System (ADS)

Kanta, L.; Berglund, E. Z.; Soh, M. H.

2017-12-01

Outdoor water-use for landscape and irrigation constitutes a significant end-use in total residential water demand. In periods of water shortages, utilities may reduce garden demands by implementing irrigation system audits, rebate programs, local ordinances, and voluntary or mandatory water-use restrictions. Because utilities do not typically record outdoor and indoor water-uses separately, the effects of policies for reducing garden demands cannot be readily calculated. The volume of water required to meet garden demands depends on the housing density, lawn size, type of vegetation, climatic conditions, efficiency of garden irrigation systems, and consumer water-use behaviors. Many existing outdoor demand estimation methods are deterministic and do not include consumer responses to conservation campaigns. In addition, mandatory restrictions may have a substantial impact on reducing outdoor demands, but the effectiveness of mandatory restrictions depends on the timing and the frequency of restrictions, in addition to the distribution of housing density and consumer types within a community. This research investigates a garden end-use model by coupling an agent-based modeling approach and a mechanistic-stochastic water demand model to create a methodology for estimating garden demand and evaluating demand reduction policies. The garden demand model is developed for two water utilities, using a diverse data sets, including residential customer billing records, outdoor conservation programs, frequency and type of mandatory water-use restrictions, lot size distribution, population growth, and climatic data. A set of garden irrigation parameter values, which are based on the efficiency of irrigation systems and irrigation habits of consumers, are determined for a set of conservation ordinances and restrictions. The model parameters are then validated using customer water usage data from the participating water utilities. A sensitivity analysis is conducted for garden irrigation parameters to determine the most significant factors that should be considered by water utilities to reduce outdoor demand. Data from multiple sources and the agent-based modeling methodology are integrated using a holistic approach to assist utilities in efficiently and sustainably managing outdoor demand.

Coupled modelling of groundwater flow-heat transport for assessing river-aquifer interactions

NASA Astrophysics Data System (ADS)

Engeler, I.; Hendricks Franssen, H. J.; Müller, R.; Stauffer, F.

2010-05-01

A three-dimensional finite element model for coupled variably saturated groundwater flow and heat transport was developed for the aquifer below the city of Zurich. The piezometric heads in the aquifer are strongly influenced by the river Limmat. In the model region, the river Limmat looses water to the aquifer. The river-aquifer interaction was modelled with the standard linear leakage concept. Coupling was implemented by considering temperature dependence of the hydraulic conductivity and of the leakage coefficient (via water viscosity) and density dependent transport. Calibration was performed for isothermal conditions by inverse modelling using the pilot point method. Independent model testing was carried out with help of the available dense monitoring network for piezometric heads and groundwater temperature. The model was tested by residuals analysis with the help of measurements for both groundwater temperature and head. The comparison of model results and measurements showed high accuracy for temperature except for the Southern part of the model area, where important geological heterogeneity is expected, which could not be reproduced by the model. The comparison of simulated and measured head showed that especially in the vicinity of river Limmat model results were improved by a temperature dependent leakage coefficient. Residuals were reduced up to 30% compared to isothermal leakage coefficients. This holds particularly for regions, where the river stage is considerably above the groundwater level. Furthermore additional analysis confirmed prior findings, that seepage rates during flood events cannot be reproduced with the implemented linear leakage-concept. Infiltration during flood events is larger than expected, which can be potentially attributed to additional infiltration areas. It is concluded that the temperature dependent leakage concept improves the model results for this study area significantly, and that we expect that this is also for other areas the case.

Multiphysics numerical modeling of the continuous flow microwave-assisted transesterification process.

PubMed

Muley, Pranjali D; Boldor, Dorin

2012-01-01

Use of advanced microwave technology for biodiesel production from vegetable oil is a relatively new technology. Microwave dielectric heating increases the process efficiency and reduces reaction time. Microwave heating depends on various factors such as material properties (dielectric and thermo-physical), frequency of operation and system design. Although lab scale results are promising, it is important to study these parameters and optimize the process before scaling up. Numerical modeling approach can be applied for predicting heating and temperature profiles including at larger scale. The process can be studied for optimization without actually performing the experiments, reducing the amount of experimental work required. A basic numerical model of continuous electromagnetic heating of biodiesel precursors was developed. A finite element model was built using COMSOL Multiphysics 4.2 software by coupling the electromagnetic problem with the fluid flow and heat transfer problem. Chemical reaction was not taken into account. Material dielectric properties were obtained experimentally, while the thermal properties were obtained from the literature (all the properties were temperature dependent). The model was tested for the two different power levels 4000 W and 4700 W at a constant flow rate of 840ml/min. The electric field, electromagnetic power density flow and temperature profiles were studied. Resulting temperature profiles were validated by comparing to the temperatures obtained at specific locations from the experiment. The results obtained were in good agreement with the experimental data.

Quantifying and Mitigating the Effect of Preferential Sampling on Phylodynamic Inference

PubMed Central

Karcher, Michael D.; Palacios, Julia A.; Bedford, Trevor; Suchard, Marc A.; Minin, Vladimir N.

2016-01-01

Phylodynamics seeks to estimate effective population size fluctuations from molecular sequences of individuals sampled from a population of interest. One way to accomplish this task formulates an observed sequence data likelihood exploiting a coalescent model for the sampled individuals’ genealogy and then integrating over all possible genealogies via Monte Carlo or, less efficiently, by conditioning on one genealogy estimated from the sequence data. However, when analyzing sequences sampled serially through time, current methods implicitly assume either that sampling times are fixed deterministically by the data collection protocol or that their distribution does not depend on the size of the population. Through simulation, we first show that, when sampling times do probabilistically depend on effective population size, estimation methods may be systematically biased. To correct for this deficiency, we propose a new model that explicitly accounts for preferential sampling by modeling the sampling times as an inhomogeneous Poisson process dependent on effective population size. We demonstrate that in the presence of preferential sampling our new model not only reduces bias, but also improves estimation precision. Finally, we compare the performance of the currently used phylodynamic methods with our proposed model through clinically-relevant, seasonal human influenza examples. PMID:26938243

Estimated effects of temperature on secondary organic aerosol concentrations.

PubMed

Sheehan, P E; Bowman, F M

2001-06-01

The temperature-dependence of secondary organic aerosol (SOA) concentrations is explored using an absorptive-partitioning model under a variety of simplified atmospheric conditions. Experimentally determined partitioning parameters for high yield aromatics are used. Variation of vapor pressures with temperature is assumed to be the main source of temperature effects. Known semivolatile products are used to define a modeling range of vaporization enthalpy of 10-25 kcal/mol-1. The effect of diurnal temperature variations on model predictions for various assumed vaporization enthalpies, precursor emission rates, and primary organic concentrations is explored. Results show that temperature is likely to have a significant influence on SOA partitioning and resulting SOA concentrations. A 10 degrees C decrease in temperature is estimated to increase SOA yields by 20-150%, depending on the assumed vaporization enthalpy. In model simulations, high daytime temperatures tend to reduce SOA concentrations by 16-24%, while cooler nighttime temperatures lead to a 22-34% increase, compared to constant temperature conditions. Results suggest that currently available constant temperature partitioning coefficients do not adequately represent atmospheric SOA partitioning behavior. Air quality models neglecting the temperature dependence of partitioning are expected to underpredict peak SOA concentrations as well as mistime their occurrence.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

PubMed

Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole

2017-07-05

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1-10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. Copyright © 2017 Dickie et al.

Multi-Factor Impact Analysis of Agricultural Production in Bangladesh with Climate Change

NASA Technical Reports Server (NTRS)

Ruane, Alex C.; Major, David C.; Yu, Winston H.; Alam, Mozaharul; Hussain, Sk. Ghulam; Khan, Abu Saleh; Hassan, Ahmadul; Al Hossain, Bhuiya Md. Tamim; Goldberg, Richard; Horton, Radley M.;

Angular dependence models for radiance to flux conversion

NASA Technical Reports Server (NTRS)

Green, Richard N.; Suttles, John T.; Wielicki, Bruce A.

1990-01-01

Angular dependence models (ADM) used for converting the measured radiance to flux at the top of the atmosphere are reviewed, and emphasis is placed on the measure of their effectiveness and the implications of requiring the ADMs to satisfy reciprocity. The overall significance of the ADMs is figured out by analyzing the same satellite data with a single Lambertian model, single mean model, and the 12 Earth Radiation Budget Experiment (ERBE) ADMs. It is shown that the Lambertian ADM is inadequate, while the mean ADM results in nearly unbiased fluxes but creates substantial differences for individual pixel fluxes. The standard ERBE ADM works well except for a 10-pct to 15-pct albedo growth across the scan; a modified ADM based on the standard ERBE ADM but forced to satisfy the principle of reciprocity increases the limb brightening and reduces the albedo growth but does not improve the scanner and nonscanner intercomparison.

Predator Persistence through Variability of Resource Productivity in Tritrophic Systems.

PubMed

Soudijn, Floor H; de Roos, André M

2017-12-01

The trophic structure of species communities depends on the energy transfer between trophic levels. Primary productivity varies strongly through time, challenging the persistence of species at higher trophic levels. Yet resource variability has mostly been studied in systems with only one or two trophic levels. We test the effect of variability in resource productivity in a tritrophic model system including a resource, a size-structured consumer, and a size-specific predator. The model complies with fundamental principles of mass conservation and the body-size dependence of individual-level energetics and predator-prey interactions. Surprisingly, we find that resource variability may promote predator persistence. The positive effect of variability on the predator arises through periods with starvation mortality of juvenile prey, which reduces the intraspecific competition in the prey population. With increasing variability in productivity and starvation mortality in the juvenile prey, the prey availability increases in the size range preferred by the predator. The positive effect of prey mortality on the trophic transfer efficiency depends on the biologically realistic consideration of body size-dependent and food-dependent functions for growth and reproduction in our model. Our findings show that variability may promote the trophic transfer efficiency, indicating that environmental variability may sustain species at higher trophic levels in natural ecosystems.

Reduced order modelling in searches for continuous gravitational waves - I. Barycentring time delays

NASA Astrophysics Data System (ADS)

Pitkin, M.; Doolan, S.; McMenamin, L.; Wette, K.

2018-06-01

The frequencies and phases of emission from extra-solar sources measured by Earth-bound observers are modulated by the motions of the observer with respect to the source, and through relativistic effects. These modulations depend critically on the source's sky-location. Precise knowledge of the modulations are required to coherently track the source's phase over long observations, for example, in pulsar timing, or searches for continuous gravitational waves. The modulations can be modelled as sky-location and time-dependent time delays that convert arrival times at the observer to the inertial frame of the source, which can often be the Solar system barycentre. We study the use of reduced order modelling for speeding up the calculation of this time delay for any sky-location. We find that the time delay model can be decomposed into just four basis vectors, and with these the delay for any sky-location can be reconstructed to sub-nanosecond accuracy. When compared to standard routines for time delay calculation in gravitational wave searches, using the reduced basis can lead to speed-ups of 30 times. We have also studied components of time delays for sources in binary systems. Assuming eccentricities <0.25, we can reconstruct the delays to within 100 s of nanoseconds, with best case speed-ups of a factor of 10, or factors of two when interpolating the basis for different orbital periods or time stamps. In long-duration phase-coherent searches for sources with sky-position uncertainties, or binary parameter uncertainties, these speed-ups could allow enhancements in their scopes without large additional computational burdens.

Resource-dependent growth models for Sierran mixed-conifer saplings

Treesearch

S.W. Bigelow; M.P. North; W.R. Horwath

2009-01-01

Thinning to reduce wildfire hazard is a common management practice in frequent-fire forests of the American west, but it is uncertain whether projects will help regenerate fire-resistant, shade-intolerant pines. We studied naturally established saplings of six conifer species in mixed-conifer forest in northern California, USA to...

Modeling the Effect of Olivocochlear Efferents on the Subcortical Envelope Following Response in Humans

DTIC Science & Technology

2016-11-28

olivocochlear reflex (MOCR), a feedback mechanism that controls gain of the outer hair cells, is thought to provide protection and enhancement for a listener in...effectively reduce the outer hair cell gain, depending on the stimulus frequency, level, and timing. Human Envelope Following Responses (EFRs

Comparative trends in forage nutritional quality across the growing season in thirteen grasses

USDA-ARS?s Scientific Manuscript database

Based on recent climate change models, landscapes are likely going to get drier and hotter; thus reducing the available water to support herbage production in species heavily dependent on water for persistence and production such as perennial ryegrass (Lolium perenne L.), orchardgrass (Dactylis glom...

Evaluation of confidence intervals for a steady-state leaky aquifer model

USGS Publications Warehouse

Christensen, S.; Cooley, R.L.

1999-01-01

The fact that dependent variables of groundwater models are generally nonlinear functions of model parameters is shown to be a potentially significant factor in calculating accurate confidence intervals for both model parameters and functions of the parameters, such as the values of dependent variables calculated by the model. The Lagrangian method of Vecchia and Cooley [Vecchia, A.V. and Cooley, R.L., Water Resources Research, 1987, 23(7), 1237-1250] was used to calculate nonlinear Scheffe-type confidence intervals for the parameters and the simulated heads of a steady-state groundwater flow model covering 450 km2 of a leaky aquifer. The nonlinear confidence intervals are compared to corresponding linear intervals. As suggested by the significant nonlinearity of the regression model, linear confidence intervals are often not accurate. The commonly made assumption that widths of linear confidence intervals always underestimate the actual (nonlinear) widths was not correct. Results show that nonlinear effects can cause the nonlinear intervals to be asymmetric and either larger or smaller than the linear approximations. Prior information on transmissivities helps reduce the size of the confidence intervals, with the most notable effects occurring for the parameters on which there is prior information and for head values in parameter zones for which there is prior information on the parameters.The fact that dependent variables of groundwater models are generally nonlinear functions of model parameters is shown to be a potentially significant factor in calculating accurate confidence intervals for both model parameters and functions of the parameters, such as the values of dependent variables calculated by the model. The Lagrangian method of Vecchia and Cooley was used to calculate nonlinear Scheffe-type confidence intervals for the parameters and the simulated heads of a steady-state groundwater flow model covering 450 km2 of a leaky aquifer. The nonlinear confidence intervals are compared to corresponding linear intervals. As suggested by the significant nonlinearity of the regression model, linear confidence intervals are often not accurate. The commonly made assumption that widths of linear confidence intervals always underestimate the actual (nonlinear) widths was not correct. Results show that nonlinear effects can cause the nonlinear intervals to be asymmetric and either larger or smaller than the linear approximations. Prior information on transmissivities helps reduce the size of the confidence intervals, with the most notable effects occurring for the parameters on which there is prior information and for head values in parameter zones for which there is prior information on the parameters.

Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation.

PubMed

Wan, Xia; Lu, Yungang; Chen, Xueqin; Xiong, Jian; Zhou, Yuanda; Li, Ping; Xia, Bingqing; Li, Min; Zhu, Michael X; Gao, Zhaobing

2014-07-01

Transient receptor potential A1 (TRPA1) is implicated in somatosensory processing and pathological pain sensation. Although not strictly voltage-gated, ionic currents of TRPA1 typically rectify outwardly, indicating channel activation at depolarized membrane potentials. However, some reports also showed TRPA1 inactivation at high positive potentials, implicating voltage-dependent inactivation. Here we report a conserved leucine residue, L906, in the putative pore helix, which strongly impacts the voltage dependency of TRPA1. Mutation of the leucine to cysteine (L906C) converted the channel from outward to inward rectification independent of divalent cations and irrespective to stimulation by allyl isothiocyanate. The mutant, but not the wild-type channel, displayed exclusively voltage-dependent inactivation at positive potentials. The L906C mutation also exhibited reduced sensitivity to inhibition by TRPA1 blockers, HC030031 and ruthenium red. Further mutagenesis of the leucine to all natural amino acids individually revealed that most substitutions at L906 (15/19) resulted in inward rectification, with exceptions of three amino acids that dramatically reduced channel activity and one, methionine, which mimicked the wild-type channel. Our data are plausibly explained by a bimodal gating model involving both voltage-dependent activation and inactivation of TRPA1. We propose that the key pore helix residue, L906, plays an essential role in responding to the voltage-dependent gating.

LVQ and backpropagation neural networks applied to NASA SSME data

NASA Technical Reports Server (NTRS)

Doniere, Timothy F.; Dhawan, Atam P.

1993-01-01

Feedfoward neural networks with backpropagation learning have been used as function approximators for modeling the space shuttle main engine (SSME) sensor signals. The modeling of these sensor signals is aimed at the development of a sensor fault detection system that can be used during ground test firings. The generalization capability of a neural network based function approximator depends on the training vectors which in this application may be derived from a number of SSME ground test-firings. This yields a large number of training vectors. Large training sets can cause the time required to train the network to be very large. Also, the network may not be able to generalize for large training sets. To reduce the size of the training sets, the SSME test-firing data is reduced using the learning vector quantization (LVQ) based technique. Different compression ratios were used to obtain compressed data in training the neural network model. The performance of the neural model trained using reduced sets of training patterns is presented and compared with the performance of the model trained using complete data. The LVQ can also be used as a function approximator. The performance of the LVQ as a function approximator using reduced training sets is presented and compared with the performance of the backpropagation network.

Biorelevant Dissolution Models for a Weak Base To Facilitate Formulation Development and Overcome Reduced Bioavailability Caused by Hypochlordyria or Achlorhydria.

PubMed

Kou, Dawen; Dwaraknath, Sudharsan; Fischer, Yannick; Nguyen, Daniel; Kim, Myeonghui; Yiu, Hiuwing; Patel, Preeti; Ng, Tania; Mao, Chen; Durk, Matthew; Chinn, Leslie; Winter, Helen; Wigman, Larry; Yehl, Peter

2017-10-02

In this study, two dissolution models were developed to achieve in vitro-in vivo relationship for immediate release formulations of Compound-A, a poorly soluble weak base with pH-dependent solubility and low bioavailability in hypochlorhydric and achlorhydric patients. The dissolution models were designed to approximate the hypo-/achlorhydric and normal fasted stomach conditions after a glass of water was ingested with the drug. The dissolution data from the two models were predictive of the relative in vivo bioavailability of various formulations under the same gastric condition, hypo-/achlorhydric or normal. Furthermore, the dissolution data were able to estimate the relative performance under hypo-/achlorhydric and normal fasted conditions for the same formulation. Together, these biorelevant dissolution models facilitated formulation development for Compound-A by identifying the right type and amount of key excipient to enhance bioavailability and mitigate the negative effect of hypo-/achlorhydria due to drug-drug interaction with acid-reducing agents. The dissolution models use readily available USP apparatus 2, and their broader utility can be evaluated on other BCS 2B compounds with reduced bioavailability caused by hypo-/achlorhydria.

SU-F-T-158: Experimental Characterization of Field Size Dependence of Dose and Lateral Beam Profiles of Scanning Proton and Carbon Ion Beams for Empirical Model in Air

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

Li, Y; Hsi, W; Zhao, J

2016-06-15

Purpose: The Gaussian model for the lateral profiles in air is crucial for an accurate treatment planning system. The field size dependence of dose and the lateral beam profiles of scanning proton and carbon ion beams are due mainly to particles undergoing multiple Coulomb scattering in the beam line components and secondary particles produced by nuclear interactions in the target, both of which depend upon the energy and species of the beam. In this work, lateral profile shape parameters were fitted to measurements of field size dependence dose at the center of field size in air. Methods: Previous studies havemore » employed empirical fits to measured profile data to significantly reduce the QA time required for measurements. From this approach to derive the weight and sigma of lateral profiles in air, empirical model formulations were simulated for three selected energies for both proton and carbon beams. Results: The 20%–80% lateral penumbras predicted by the double model for proton and single model for carbon with the error functions agreed with the measurements within 1 mm. The standard deviation between measured and fitted field size dependence of dose for empirical model in air has a maximum accuracy of 0.74% for proton with double Gaussian, and of 0.57% for carbon with single Gaussian. Conclusion: We have demonstrated that the double Gaussian model of lateral beam profiles is significantly better than the single Gaussian model for proton while a single Gaussian model is sufficient for carbon. The empirical equation may be used to double check the separately obtained model that is currently used by the planning system. The empirical model in air for dose of spot scanning proton and carbon ion beams cannot be directly used for irregular shaped patient fields, but can be to provide reference values for clinical use and quality assurance.« less

Status of the \\varvec{Λ (1405)}

NASA Astrophysics Data System (ADS)

Mai, Maxim

2018-07-01

I give an overview of the current status of the lowest s-wave baryon resonance in the strangeness (S=-1) channel, the Λ (1405). Recent results from Lattice QCD calculations and new high-precision data from photoproduction experiments are highlighted in this talk. On the theoretical side various directions have been explored over the last two decades on the basis of coupled-channel chiral unitary models. New photoproduction data can be used to reduce statistical uncertainty of the predictions of such models. As for the systematic uncertainties, a recent comparative analysis of modern approaches exhibits many similarities but also large ambiguities in some of the predicted properties of the antikaon-nucleon scattering amplitudes. Some possible ways to reduce such a model dependence are discussed at the end of this manuscript.

The role of density-dependent individual growth in the persistence of freshwater salmonid populations.

PubMed

Vincenzi, Simone; Crivelli, Alain J; Jesensek, Dusan; De Leo, Giulio A

2008-06-01

Theoretical and empirical models of populations dynamics have paid little attention to the implications of density-dependent individual growth on the persistence and regulation of small freshwater salmonid populations. We have therefore designed a study aimed at testing our hypothesis that density-dependent individual growth is a process that enhances population recovery and reduces extinction risk in salmonid populations in a variable environment subject to disturbance events. This hypothesis was tested in two newly introduced marble trout (Salmo marmoratus) populations living in Slovenian streams (Zakojska and Gorska) subject to severe autumn floods. We developed a discrete-time stochastic individual-based model of population dynamics for each population with demographic parameters and compensatory responses tightly calibrated on data from individually tagged marble trout. The occurrence of severe flood events causing population collapses was explicitly accounted for in the model. We used the model in a population viability analysis setting to estimate the quasi-extinction risk and demographic indexes of the two marble trout populations when individual growth was density-dependent. We ran a set of simulations in which the effect of floods on population abundance was explicitly accounted for and another set of simulations in which flood events were not included in the model. These simulation results were compared with those of scenarios in which individual growth was modelled with density-independent Von Bertalanffy growth curves. Our results show how density-dependent individual growth may confer remarkable resilience to marble trout populations in case of major flood events. The resilience to flood events shown by the simulation results can be explained by the increase in size-dependent fecundity as a consequence of the drop in population size after a severe flood, which allows the population to quickly recover to the pre-event conditions. Our results suggest that density-dependent individual growth plays a potentially powerful role in the persistence of freshwater salmonids living in streams subject to recurrent yet unpredictable flood events.

The effect of zero-point energy differences on the isotope dependence of the formation of ozone: a classical trajectory study.

PubMed

Schinke, Reinhard; Fleurat-Lessard, Paul

2005-03-01

The effect of zero-point energy differences (DeltaZPE) between the possible fragmentation channels of highly excited O(3) complexes on the isotope dependence of the formation of ozone is investigated by means of classical trajectory calculations and a strong-collision model. DeltaZPE is incorporated in the calculations in a phenomenological way by adjusting the potential energy surface in the product channels so that the correct exothermicities and endothermicities are matched. The model contains two parameters, the frequency of stabilizing collisions omega and an energy dependent parameter Delta(damp), which favors the lower energies in the Maxwell-Boltzmann distribution. The stabilization frequency is used to adjust the pressure dependence of the absolute formation rate while Delta(damp) is utilized to control its isotope dependence. The calculations for several isotope combinations of oxygen atoms show a clear dependence of relative formation rates on DeltaZPE. The results are similar to those of Gao and Marcus [J. Chem. Phys. 116, 137 (2002)] obtained within a statistical model. In particular, like in the statistical approach an ad hoc parameter eta approximately 1.14, which effectively reduces the formation rates of the symmetric ABA ozone molecules, has to be introduced in order to obtain good agreement with the measured relative rates of Janssen et al. [Phys. Chem. Chem. Phys. 3, 4718 (2001)]. The temperature dependence of the recombination rate is also addressed.

Machine learning to construct reduced-order models and scaling laws for reactive-transport applications

NASA Astrophysics Data System (ADS)

Mudunuru, M. K.; Karra, S.; Vesselinov, V. V.

2017-12-01

The efficiency of many hydrogeological applications such as reactive-transport and contaminant remediation vastly depends on the macroscopic mixing occurring in the aquifer. In the case of remediation activities, it is fundamental to enhancement and control of the mixing through impact of the structure of flow field which is impacted by groundwater pumping/extraction, heterogeneity, and anisotropy of the flow medium. However, the relative importance of these hydrogeological parameters to understand mixing process is not well studied. This is partially because to understand and quantify mixing, one needs to perform multiple runs of high-fidelity numerical simulations for various subsurface model inputs. Typically, high-fidelity simulations of existing subsurface models take hours to complete on several thousands of processors. As a result, they may not be feasible to study the importance and impact of model inputs on mixing. Hence, there is a pressing need to develop computationally efficient models to accurately predict the desired QoIs for remediation and reactive-transport applications. An attractive way to construct computationally efficient models is through reduced-order modeling using machine learning. These approaches can substantially improve our capabilities to model and predict remediation process. Reduced-Order Models (ROMs) are similar to analytical solutions or lookup tables. However, the method in which ROMs are constructed is different. Here, we present a physics-informed ML framework to construct ROMs based on high-fidelity numerical simulations. First, random forests, F-test, and mutual information are used to evaluate the importance of model inputs. Second, SVMs are used to construct ROMs based on these inputs. These ROMs are then used to understand mixing under perturbed vortex flows. Finally, we construct scaling laws for certain important QoIs such as degree of mixing and product yield. Scaling law parameters dependence on model inputs are evaluated using cluster analysis. We demonstrate application of the developed method for model analyses of reactive-transport and contaminant remediation at the Los Alamos National Laboratory (LANL) chromium contamination sites. The developed method is directly applicable for analyses of alternative site remediation scenarios.

Eradication of melanoma in vitro and in vivo via targeting with a Killer-Red-containing telomerase-dependent adenovirus.

PubMed

Takehara, Kiyoto; Yano, Shuya; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Narii, Nobuhiro; Mizuguchi, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-08-18

Melanoma is a highly recalcitrant cancer and transformative therapy is necessary for the cure of this disease. We recently developed a telomerase-dependent adenovirus containing the fluorescent protein Killer-Red. In the present report, we first determined the efficacy of Killer-Red adenovirus combined with laser irradiation on human melanoma cell lines in vitro. Cell viability of human melanoma cells was reduced in a dose-dependent and irradiation-time-dependent manner. We used an intradermal xenografted melanoma model in nude mice to determine efficacy of the Killer-Red adenovirus. Intratumoral injection of Killer-Red adenovirus, combined with laser irradiation, eradicated the melanoma indicating the potential of a new paradigm of cancer therapy.

In-medium Υ suppression and feed-down in UU and PbPb collisions

NASA Astrophysics Data System (ADS)

Hoelck, J.; Nendzig, F.; Wolschin, G.

2017-02-01

The suppression of Υ mesons in the hot quark-gluon plasma (QGP) versus reduced feed-down is investigated in UU collisions at energies currently available at the BNL Relativistic Heavy Ion Collider and PbPb collisions at energies available at the CERN Large Hadron Collider. Our centrality- and pT-dependent model encompasses screening, collisional damping, and gluodissociation in the QGP. For Υ (1 S ) it is in agreement with data from both STAR and CMS collaborations provided the relativistic Doppler effect and the reduced feed-down from the Υ (n S ) and χb(n P ) states are properly considered. At both energies, most of the Υ (1 S ) suppression is found to be due to reduced feed-down, whereas most of the Υ (2 S ) suppression is caused by hot-medium effects. The importance of the latter increases with energy. The pT dependence is flat due to the relativistic Doppler effect and reduced feed-down. We predict the Υ (1 S ) suppression in PbPb at √{sN N}=5.02 T e V .

Antibody side chain conformations are position-dependent.

PubMed

Leem, Jinwoo; Georges, Guy; Shi, Jiye; Deane, Charlotte M

2018-04-01

Side chain prediction is an integral component of computational antibody design and structure prediction. Current antibody modelling tools use backbone-dependent rotamer libraries with conformations taken from general proteins. Here we present our antibody-specific rotamer library, where rotamers are binned according to their immunogenetics (IMGT) position, rather than their local backbone geometry. We find that for some amino acid types at certain positions, only a restricted number of side chain conformations are ever observed. Using this information, we are able to reduce the breadth of the rotamer sampling space. Based on our rotamer library, we built a side chain predictor, position-dependent antibody rotamer swapper (PEARS). On a blind test set of 95 antibody model structures, PEARS had the highest average χ 1 and χ1+2 accuracy (78.7% and 64.8%) compared to three leading backbone-dependent side chain predictors. Our use of IMGT position, rather than backbone ϕ/ψ, meant that PEARS was more robust to errors in the backbone of the model structure. PEARS also achieved the lowest number of side chain-side chain clashes. PEARS is freely available as a web application at http://opig.stats.ox.ac.uk/webapps/pears. © 2018 Wiley Periodicals, Inc.

Creep and shrinkage effects on integral abutment bridges

NASA Astrophysics Data System (ADS)

Munuswamy, Sivakumar

Integral abutment bridges provide bridge engineers an economical design alternative to traditional bridges with expansion joints owing to the benefits, arising from elimination of expensive joints installation and reduced maintenance cost. The superstructure for integral abutment bridges is cast integrally with abutments. Time-dependent effects of creep, shrinkage of concrete, relaxation of prestressing steel, temperature gradient, restraints provided by abutment foundation and backfill and statical indeterminacy of the structure introduce time-dependent variations in the redundant forces. An analytical model and numerical procedure to predict instantaneous linear behavior and non-linear time dependent long-term behavior of continuous composite superstructure are developed in which the redundant forces in the integral abutment bridges are derived considering the time-dependent effects. The redistributions of moments due to time-dependent effects have been considered in the analysis. The analysis includes nonlinearity due to cracking of the concrete, as well as the time-dependent deformations. American Concrete Institute (ACI) and American Association of State Highway and Transportation Officials (AASHTO) models for creep and shrinkage are considered in modeling the time dependent material behavior. The variations in the material property of the cross-section corresponding to the constituent materials are incorporated and age-adjusted effective modulus method with relaxation procedure is followed to include the creep behavior of concrete. The partial restraint provided by the abutment-pile-soil system is modeled using discrete spring stiffness as translational and rotational degrees of freedom. Numerical simulation of the behavior is carried out on continuous composite integral abutment bridges and the deformations and stresses due to time-dependent effects due to typical sustained loads are computed. The results from the analytical model are compared with the published laboratory experimental and field data. The behavior of the laterally loaded piles supporting the integral abutments is evaluated and presented in terms of the lateral deflection, bending moment, shear force and stress along the pile depth.

Drought assessment in the Duero basin (Central Spain) by means of multivariate extreme value statistics

NASA Astrophysics Data System (ADS)

Kallache, M.

2012-04-01

Droughts cause important losses. On the Iberian Peninsula, for example, non-irrigated agriculture and the tourism sector are affected in regular intervals. The goal of this study is the description of droughts and their dependence in the Duero basin in Central Spain. To do so, daily or monthly precipitation data is used. Here cumulative precipitation deficits below a threshold define meteorological droughts. This drought indicator is similar to the commonly used standard precipitation index. However, here the focus lies on the modeling of severe droughts, which is done by applying multivariate extreme value theory (MEVT) to model extreme drought events. Data from several stations are assessed jointly, thus the uncertainty of the results is reduced. Droughts are a complex phenomenon, their severity, spatial extension and duration has to be taken into account. Our approach captures severity and spatial extension. In general we find a high correlation between deficit volumes and drought duration, thus the duration is not explicitely modeled. We apply a MEVT model with asymmetric logistic dependence function, which is capable to model asymptotic dependence and independence (cf. Ramos and Ledford, 2009). To summarize the information on the dependence in the joint tail of the extreme drought events, we utilise the fragility index (Geluk et al., 2007). Results show that droughts also occur frequently in winter. Moreover, it is very common for one site to suffer dry conditions, whilst neighboring areas experience normal or even humid conditions. Interpolation is thus difficult. Bivariate extremal dependence is present in the data. However, most stations are at least asymptotically independent. The according fragility indices are important information for risk calculations. The emerging spatial patterns for bivariate dependence are mostly influenced by topography. When looking at the dependence between more than two stations, it shows that joint extremes can occur more often than randomly for up to 6 stations, this depends on the distance between the stations.

Variable horizon in a peridynamic medium

DOE PAGES

Silling, Stewart A.; Littlewood, David J.; Seleson, Pablo

2015-12-10

Here, a notion of material homogeneity is proposed for peridynamic bodies with variable horizon but constant bulk properties. A relation is derived that scales the force state according to the position-dependent horizon while keeping the bulk properties unchanged. Using this scaling relation, if the horizon depends on position, artifacts called ghost forces may arise in a body under a homogeneous deformation. These artifacts depend on the second derivative of the horizon and can be reduced by employing a modified equilibrium equation using a new quantity called the partial stress. Bodies with piecewise constant horizon can be modeled without ghost forcesmore » by using a simpler technique called a splice. As a limiting case of zero horizon, both the partial stress and splice techniques can be used to achieve local-nonlocal coupling. Computational examples, including dynamic fracture in a one-dimensional model with local-nonlocal coupling, illustrate the methods.« less

From Spiking Neuron Models to Linear-Nonlinear Models

PubMed Central

Ostojic, Srdjan; Brunel, Nicolas

2011-01-01

Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates. PMID:21283777

From spiking neuron models to linear-nonlinear models.

PubMed

Ostojic, Srdjan; Brunel, Nicolas

2011-01-20

Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.

Using discharge data to reduce structural deficits in a hydrological model with a Bayesian inference approach and the implications for the prediction of critical source areas

NASA Astrophysics Data System (ADS)

Frey, M. P.; Stamm, C.; Schneider, M. K.; Reichert, P.

2011-12-01

A distributed hydrological model was used to simulate the distribution of fast runoff formation as a proxy for critical source areas for herbicide pollution in a small agricultural catchment in Switzerland. We tested to what degree predictions based on prior knowledge without local measurements could be improved upon relying on observed discharge. This learning process consisted of five steps: For the prior prediction (step 1), knowledge of the model parameters was coarse and predictions were fairly uncertain. In the second step, discharge data were used to update the prior parameter distribution. Effects of uncertainty in input data and model structure were accounted for by an autoregressive error model. This step decreased the width of the marginal distributions of parameters describing the lower boundary (percolation rates) but hardly affected soil hydraulic parameters. Residual analysis (step 3) revealed model structure deficits. We modified the model, and in the subsequent Bayesian updating (step 4) the widths of the posterior marginal distributions were reduced for most parameters compared to those of the prior. This incremental procedure led to a strong reduction in the uncertainty of the spatial prediction. Thus, despite only using spatially integrated data (discharge), the spatially distributed effect of the improved model structure can be expected to improve the spatially distributed predictions also. The fifth step consisted of a test with independent spatial data on herbicide losses and revealed ambiguous results. The comparison depended critically on the ratio of event to preevent water that was discharged. This ratio cannot be estimated from hydrological data only. The results demonstrate that the value of local data is strongly dependent on a correct model structure. An iterative procedure of Bayesian updating, model testing, and model modification is suggested.

Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis.

PubMed

Hao, S; Takahata, O; Iwasaki, H

2001-03-01

Clinical and basic science studies suggest that spinal alpha-2-adrenergic receptor agonists and local anesthetics produce analgesia, but interaction between alpha-2-adrenergic receptor agonists and local anesthetics in the persistent pain model has not been examined. In the present study, using isobolographic analysis, we investigated the antinociceptive interaction of intrathecal clonidine and lidocaine in the rat formalin test. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters, and were tested for paw flinch by formalin injection. Biphasic painful behavior was counted. Intrathecal clonidine (3-12 nmol) was administered 15 min before formalin, and intrathecal lidocaine (375-1850 nmol) was administered 5 min before formalin. To examine the interaction of intrathecal clonidine and lidocaine, an isobolographic design was used. Spinal administration of clonidine produced dose-dependent suppression of the biphasic responses in the formalin test. Spinal lidocaine resulted in dose-dependent transient motor dysfunction and the motor dysfunction recovered to normal at 10-15 min after administration. Spinal lidocaine produced dose-dependent suppression of phase-2 activity in the formalin test. Isobolographic analysis showed that the combination of intrathecal clonidine and lidocaine synergistically reduced Phase-2 activity. We conclude that intrathecal clonidine synergistically interacts with lidocaine in reducing the nociceptive response in the formalin test. Preformalin administration of intrathecal clonidine and lidocaine dose-dependently produced antinociception in the formalin test. The combination of clonidine and lidocaine, synergistically produced suppression of nociceptive response in the persistent pain model.

On the impact of reducing global geophysical fluid model deformations in SLR data processing

NASA Astrophysics Data System (ADS)

Weigelt, Matthias; Thaller, Daniela

2016-04-01

Mass redistributions in the atmosphere, oceans and the continental hydrology cause elastic loading deformations of the Earth's crust and thus systematically influence Earth-bound observation systems such as VLBI, GNSS or SLR. Causing non-linear station variations, these loading deformations have a direct impact on the estimated station coordinates and an indirect impact on other parameters of global space-geodetic solutions, e.g. Earth orientation parameters, geocenter coordinates, satellite orbits or troposphere parameters. Generally, the impact can be mitigated by co-parameterisation or by reducing deformations derived from global geophysical fluid models. Here, we focus on the latter approach. A number of data sets modelling the (non-tidal) loading deformations are generated by various groups. They show regionally and locally significant differences and consequently the impact on the space-geodetic solutions heavily depends on the available network geometry. We present and discuss the differences between these models and choose SLR as the speace-geodetic technique of interest in order to discuss the impact of atmospheric, oceanic and hydrological loading on the parameters of space-geodetic solutions when correcting for the global geophysical fluid models at the observation level. Special emphasis is given to a consistent usage of models for geometric and gravimetric corrections during the data processing. We quantify the impact of the different deformation models on the station coordinates and discuss the improvement in the Earth orientation parameters and the geocenter motion. We also show that a significant reduction in the RMS of the station coordinates can be achieved depending on the model of choice.

Selecting a climate model subset to optimise key ensemble properties

NASA Astrophysics Data System (ADS)

Herger, Nadja; Abramowitz, Gab; Knutti, Reto; Angélil, Oliver; Lehmann, Karsten; Sanderson, Benjamin M.

2018-02-01

End users studying impacts and risks caused by human-induced climate change are often presented with large multi-model ensembles of climate projections whose composition and size are arbitrarily determined. An efficient and versatile method that finds a subset which maintains certain key properties from the full ensemble is needed, but very little work has been done in this area. Therefore, users typically make their own somewhat subjective subset choices and commonly use the equally weighted model mean as a best estimate. However, different climate model simulations cannot necessarily be regarded as independent estimates due to the presence of duplicated code and shared development history. Here, we present an efficient and flexible tool that makes better use of the ensemble as a whole by finding a subset with improved mean performance compared to the multi-model mean while at the same time maintaining the spread and addressing the problem of model interdependence. Out-of-sample skill and reliability are demonstrated using model-as-truth experiments. This approach is illustrated with one set of optimisation criteria but we also highlight the flexibility of cost functions, depending on the focus of different users. The technique is useful for a range of applications that, for example, minimise present-day bias to obtain an accurate ensemble mean, reduce dependence in ensemble spread, maximise future spread, ensure good performance of individual models in an ensemble, reduce the ensemble size while maintaining important ensemble characteristics, or optimise several of these at the same time. As in any calibration exercise, the final ensemble is sensitive to the metric, observational product, and pre-processing steps used.

Time-Dependent Cryospheric Longwave Surface Emissivity Feedback in the Community Earth System Model

NASA Astrophysics Data System (ADS)

Kuo, Chaincy; Feldman, Daniel R.; Huang, Xianglei; Flanner, Mark; Yang, Ping; Chen, Xiuhong

2018-01-01

Frozen and unfrozen surfaces exhibit different longwave surface emissivities with different spectral characteristics, and outgoing longwave radiation and cooling rates are reduced for unfrozen scenes relative to frozen ones. Here physically realistic modeling of spectrally resolved surface emissivity throughout the coupled model components of the Community Earth System Model (CESM) is advanced, and implications for model high-latitude biases and feedbacks are evaluated. It is shown that despite a surface emissivity feedback amplitude that is, at most, a few percent of the surface albedo feedback amplitude, the inclusion of realistic, harmonized longwave, spectrally resolved emissivity information in CESM1.2.2 reduces wintertime Arctic surface temperature biases from -7.2 ± 0.9 K to -1.1 ± 1.2 K, relative to observations. The bias reduction is most pronounced in the Arctic Ocean, a region for which Coupled Model Intercomparison Project version 5 (CMIP5) models exhibit the largest mean wintertime cold bias, suggesting that persistent polar temperature biases can be lessened by including this physically based process across model components. The ice emissivity feedback of CESM1.2.2 is evaluated under a warming scenario with a kernel-based approach, and it is found that emissivity radiative kernels exhibit water vapor and cloud cover dependence, thereby varying spatially and decreasing in magnitude over the course of the scenario from secular changes in atmospheric thermodynamics and cloud patterns. Accounting for the temporally varying radiative responses can yield diagnosed feedbacks that differ in sign from those obtained from conventional climatological feedback analysis methods.

FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.

PubMed

Lublin, Alex; Isoda, Fumiko; Patel, Harshil; Yen, Kelvin; Nguyen, Linda; Hajje, Daher; Schwartz, Marc; Mobbs, Charles

2011-01-01

Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.

Temperature-dependent field-effect carrier mobility in organic thin-film transistors with a gate SiO2 dielectric modified by H2O2 treatment

NASA Astrophysics Data System (ADS)

Lin, Yow-Jon; Hung, Cheng-Chun

2018-02-01

The effect of the modification of a gate SiO2 dielectric using an H2O2 solution on the temperature-dependent behavior of carrier transport for pentacene-based organic thin-film transistors (OTFTs) is studied. H2O2 treatment leads to the formation of Si(-OH) x (i.e., the formation of a hydroxylated layer) on the SiO2 surface that serves to reduce the SiO2 capacitance and weaken the pentacene-SiO2 interaction, thus increasing the field-effect carrier mobility ( µ) in OTFTs. The temperature-dependent behavior of carrier transport is dominated by the multiple trapping model. Note that H2O2 treatment leads to a reduction in the activation energy. The increased value of µ is also attributed to the weakening of the interactions of the charge carriers with the SiO2 dielectric that serves to reduce the activation energy.

Effects of Varenicline on Ethanol-Induced Conditioned Place Preference, Locomotor Stimulation, and Sensitization

PubMed Central

Gubner, Noah R.; McKinnon, Carrie S.; Phillips, Tamara J.

2014-01-01

Background Varenicline, a partial nicotinic acetylcholine receptor (nAChR) agonist, is a promising new drug for the treatment of alcohol (ethanol) dependence. Varenicline has been approved by the Food and Drug Administration as a smoking cessation therapeutic and has also been found to reduce ethanol consumption in humans and animal models of alcohol use. The current studies examined the hypotheses that varenicline attenuates the stimulant and sensitizing effects of ethanol, and reduces the motivational effects of ethanol-associated cues. The goal was to determine if these effects of varenicline contribute to its pharmacotherapeutic effects for alcohol dependence. In addition, effects of varenicline on acute stimulation and/or on the acquisition of sensitization would suggest a role for nAChR involvement in these effects of ethanol. Methods Dose-dependent effects of varenicline on the expression of ethanol-induced conditioned place preference (CPP), locomotor activation, and behavioral sensitization were examined. These measures model motivational effects of ethanol-associated cues, euphoric or stimulatory effects of ethanol, and ethanol-induced neuroadaptation. All studies used DBA/2J mice, an inbred strain with high sensitivity to these ethanol-related effects. Results Varenicline did not significantly attenuate the expression of ethanol-induced CPP. Varenicline reduced locomotor activity and had the most pronounced effect in the presence of ethanol, with the largest effect on acute ethanol-induced locomotor stimulation and a trend for varenicline to attenuate the expression of ethanol-induced sensitization. Conclusions Because varenicline did not attenuate the expression of ethanol-induced CPP, it may not be effective at reducing the motivational effects of ethanol-associated cues. This outcome suggests that reductions in the motivational effects of ethanol-associated cues may not be involved in how varenicline reduces ethanol consumption. However, varenicline did have effects on locomotor behavior and significantly attenuated acute ethanol-induced locomotor stimulation. In humans who drink while taking varenicline, it might similarly reduce stimulant responses and have an impact on continued drinking. General sedative effects in such individuals should be carefully considered. PMID:25581658

Climate change threatens polar bear populations: a stochastic demographic analysis.

PubMed

Hunter, Christine M; Caswell, Hal; Runge, Michael C; Regehr, Eric V; Amstrup, Steve C; Stirling, Ian

2010-10-01

The polar bear (Ursus maritimus) depends on sea ice for feeding, breeding, and movement. Significant reductions in Arctic sea ice are forecast to continue because of climate warming. We evaluated the impacts of climate change on polar bears in the southern Beaufort Sea by means of a demographic analysis, combining deterministic, stochastic, environment-dependent matrix population models with forecasts of future sea ice conditions from IPCC general circulation models (GCMs). The matrix population models classified individuals by age and breeding status; mothers and dependent cubs were treated as units. Parameter estimates were obtained from a capture-recapture study conducted from 2001 to 2006. Candidate statistical models allowed vital rates to vary with time and as functions of a sea ice covariate. Model averaging was used to produce the vital rate estimates, and a parametric bootstrap procedure was used to quantify model selection and parameter estimation uncertainty. Deterministic models projected population growth in years with more extensive ice coverage (2001-2003) and population decline in years with less ice coverage (2004-2005). LTRE (life table response experiment) analysis showed that the reduction in lambda in years with low sea ice was due primarily to reduced adult female survival, and secondarily to reduced breeding. A stochastic model with two environmental states, good and poor sea ice conditions, projected a declining stochastic growth rate, log lambdas, as the frequency of poor ice years increased. The observed frequency of poor ice years since 1979 would imply log lambdas approximately - 0.01, which agrees with available (albeit crude) observations of population size. The stochastic model was linked to a set of 10 GCMs compiled by the IPCC; the models were chosen for their ability to reproduce historical observations of sea ice and were forced with "business as usual" (A1B) greenhouse gas emissions. The resulting stochastic population projections showed drastic declines in the polar bear population by the end of the 21st century. These projections were instrumental in the decision to list the polar bear as a threatened species under the U.S. Endangered Species Act.

Climate change threatens polar bear populations: A stochastic demographic analysis

USGS Publications Warehouse

Hunter, C.M.; Caswell, H.; Runge, M.C.; Regehr, E.V.; Amstrup, Steven C.; Stirling, I.

2010-01-01

The polar bear (Ursus maritimus) depends on sea ice for feeding, breeding, and movement. Significant reductions in Arctic sea ice are forecast to continue because of climate warming. We evaluated the impacts of climate change on polar bears in the southern Beaufort Sea by means of a demographic analysis, combining deterministic, stochastic, environment-dependent matrix population models with forecasts of future sea ice conditions from IPCC general circulation models (GCMs). The matrix population models classified individuals by age and breeding status; mothers and dependent cubs were treated as units. Parameter estimates were obtained from a capture-recapture study conducted from 2001 to 2006. Candidate statistical models allowed vital rates to vary with time and as functions of a sea ice covariate. Model averaging was used to produce the vital rate estimates, and a parametric bootstrap procedure was used to quantify model selection and parameter estimation uncertainty. Deterministic models projected population growth in years with more extensive ice coverage (2001-2003) and population decline in years with less ice coverage (2004-2005). LTRE (life table response experiment) analysis showed that the reduction in ?? in years with low sea ice was due primarily to reduced adult female survival, and secondarily to reduced breeding. A stochastic model with two environmental states, good and poor sea ice conditions, projected a declining stochastic growth rate, log ??s, as the frequency of poor ice years increased. The observed frequency of poor ice years since 1979 would imply log ??s ' - 0.01, which agrees with available (albeit crude) observations of population size. The stochastic model was linked to a set of 10 GCMs compiled by the IPCC; the models were chosen for their ability to reproduce historical observations of sea ice and were forced with "business as usual" (A1B) greenhouse gas emissions. The resulting stochastic population projections showed drastic declines in the polar bear population by the end of the 21st century. These projections were instrumental in the decision to list the polar bear as a threatened species under the U.S. Endangered Species Act. ?? 2010 by the Ecological Society of America.

Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models

PubMed Central

Ostler, Joseph E.; Maurya, Santosh K.; Dials, Justin; Roof, Steve R.; Devor, Steven T.; Ziolo, Mark T.

2014-01-01

Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/db mice when compared with lean controls and more severely reduced in the overtly diabetic db/db mice. In contrast to db/db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/db muscle. In addition, prediabetic (6-wk-old) and diabetic (12-wk-old) db/db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/db mice improved glucose tolerance and exercise capacity, reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are animal model-dependent. PMID:24425761

Conflict over condition-dependent sex allocation can lead to mixed sex-determination systems

PubMed Central

Kuijper, Bram; Pen, Ido

2014-01-01

Theory suggests that genetic conflicts drive turnovers between sex-determining mechanisms, yet these studies only apply to cases where sex allocation is independent of environment or condition. Here, we model parent–offspring conflict in the presence of condition-dependent sex allocation, where the environment has sex-specific fitness consequences. Additionally, one sex is assumed to be more costly to produce than the other, which leads offspring to favor a sex ratio less biased toward the cheaper sex in comparison to the sex ratio favored by mothers. The scope for parent–offspring conflict depends on the relative frequency of both environments: when one environment is less common than the other, parent–offspring conflict can be reduced or even entirely absent, despite a biased population sex ratio. The model shows that conflict-driven invasions of condition-independent sex factors (e.g., sex chromosomes) result either in the loss of condition-dependent sex allocation, or, interestingly, lead to stable mixtures of condition-dependent and condition-independent sex factors. The latter outcome corresponds to empirical observations in which sex chromosomes are present in organisms with environment-dependent sex determination. Finally, conflict can also favor errors in environmental perception, potentially resulting in the loss of condition-dependent sex allocation without genetic changes to sex-determining loci. PMID:25180669

Water for electricity in India: A multi-model study of future challenges and linkages to climate change mitigation

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

Srinivasan, Shweta; Kholod, Nazar; Chaturvedi, Vaibhav

This paper provides projections of water withdrawals and consumption for electricity generation in India through 2050. Based on the results from five energy-economic modeling teams, the paper explores the implications of economic growth, power plant cooling policies, and electricity CO2 emissions reductions on water withdrawals and consumption. To isolate modeling differences, the five teams used harmonized assumptions regarding economic and population growth, the distribution of power plants by cooling technologies, and withdrawals and consumption intensities. The results demonstrate the different but potentially complementary implications of cooling technology policies and efforts to reduce CO2 emissions. The application of closed-loop cooling technologiesmore » substantially reduces water withdrawals but increases consumption. The water implications of CO2 emissions reductions, depend critically on the approach to these reductions. Focusing on wind and solar power reduces consumption and withdrawals; a focus on nuclear power increases both; and a focus on hydroelectric power could increase consumptive losses through evaporation.« less

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

Shi, X.P.

Empirical studies on the effectiveness of workplace safety regulations are inconclusive. This study hypothesizes that the asynchronous effects of safety regulations occur because regulations need time to become effective. Safety regulations will work initially by reducing the most serious accidents, and later by improving overall safety performance. The hypothesis is tested by studying a provincial level aggregate panel dataset for China's coal industry using two different models with different sets of dependent variables: a fixed-effects model on mortality rate, which is defined as fatalities per 1,000 employees; and a negative binominal model on the annual number (frequency) of disastrous accidents.more » Safety regulations can reduce the frequency of disastrous accidents, but have not reduced mortality rate, which represents overall safety performance. Policy recommendations are made, including shifting production from small to large mines through industrial consolidation, improving the safety performance of large mines, addressing consequences of decentralization, and facilitating the implementation of regulations through carrying on institutional actions and supporting legislation.« less

Reducing racial disparities in obesity: simulating the effects of improved education and social network influence on diet behavior.

PubMed

Orr, Mark G; Galea, Sandro; Riddle, Matt; Kaplan, George A

2014-08-01

Understanding how to mitigate the present black-white obesity disparity in the United States is a complex issue, stemming from a multitude of intertwined causes. An appropriate but underused approach to guiding policy approaches to this problem is to account for this complexity using simulation modeling. We explored the efficacy of a policy that improved the quality of neighborhood schools in reducing racial disparities in obesity-related behavior and the dependence of this effect on social network influence and norms. We used an empirically grounded agent-based model to generate simulation experiments. We used a 2 × 2 × 2 factorial design that represented the presence or absence of improved neighborhood school quality, the presence or absence of social influence, and the type of social norm (healthy or unhealthy). Analyses focused on time trends in sociodemographic variables and diet quality. First, the quality of schools and social network influence had independent and interactive effects on diet behavior. Second, the black-white disparity in diet behavior was considerably reduced under some conditions, but never completely eliminated. Third, the degree to which the disparity in diet behavior was reduced was a function of the type of social norm that was in place; the reduction was the smallest when the type of social norm was healthy. Improving school quality can reduce, but not eliminate racial disparities in obesity-related behavior, and the degree to which this is true depends partly on social network effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

PubMed Central

Walker, Naomi F.; Clark, Simon O.; Oni, Tolu; Andreu, Nuria; Tezera, Liku; Singh, Shivani; Saraiva, Luísa; Pedersen, Bernadette; Kelly, Dominic L.; Tree, Julia A.; D'Armiento, Jeanine M.; Meintjes, Graeme; Mauri, Francesco A.; Williams, Ann; Wilkinson, Robert J.; Friedland, Jon S.

2012-01-01

Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB. PMID:22345579

Evaluation of Cox's model and logistic regression for matched case-control data with time-dependent covariates: a simulation study.

PubMed

Leffondré, Karen; Abrahamowicz, Michal; Siemiatycki, Jack

2003-12-30

Case-control studies are typically analysed using the conventional logistic model, which does not directly account for changes in the covariate values over time. Yet, many exposures may vary over time. The most natural alternative to handle such exposures would be to use the Cox model with time-dependent covariates. However, its application to case-control data opens the question of how to manipulate the risk sets. Through a simulation study, we investigate how the accuracy of the estimates of Cox's model depends on the operational definition of risk sets and/or on some aspects of the time-varying exposure. We also assess the estimates obtained from conventional logistic regression. The lifetime experience of a hypothetical population is first generated, and a matched case-control study is then simulated from this population. We control the frequency, the age at initiation, and the total duration of exposure, as well as the strengths of their effects. All models considered include a fixed-in-time covariate and one or two time-dependent covariate(s): the indicator of current exposure and/or the exposure duration. Simulation results show that none of the models always performs well. The discrepancies between the odds ratios yielded by logistic regression and the 'true' hazard ratio depend on both the type of the covariate and the strength of its effect. In addition, it seems that logistic regression has difficulty separating the effects of inter-correlated time-dependent covariates. By contrast, each of the two versions of Cox's model systematically induces either a serious under-estimation or a moderate over-estimation bias. The magnitude of the latter bias is proportional to the true effect, suggesting that an improved manipulation of the risk sets may eliminate, or at least reduce, the bias. Copyright 2003 JohnWiley & Sons, Ltd.

The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib

PubMed Central

Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Kirkwood, John; Avogadri-Connors, Francesca; Cutler Jr, Richard E.; Lalani, Alshad S.; Dent, Paul

2018-01-01

ABSTRACT The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins. PMID:29219657

The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.

PubMed

Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Kirkwood, John; Sander, Cindy; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dent, Paul

2018-02-01

The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins.

Effectiveness of Gross Model-Based Emotion Regulation Strategies Training on Anger Reduction in Drug-Dependent Individuals and its Sustainability in Follow-up

PubMed Central

Massah, Omid; Sohrabi, Faramarz; A’azami, Yousef; Doostian, Younes; Farhoudian, Ali; Daneshmand, Reza

2016-01-01

Background Emotion plays an important role in adapting to life changes and stressful events. Difficulty regulating emotions is one of the problems drug abusers often face, and teaching these individuals to express and manage their emotions can be effective on improving their difficult circumstances. Objectives The present study aimed to determine the effectiveness of the Gross model-based emotion regulation strategies training on anger reduction in drug-dependent individuals. Patients and Methods The present study had a quasi-experimental design wherein pretest-posttest evaluations were applied using a control group. The population under study included addicts attending Marivan’s methadone maintenance therapy centers in 2012 - 2013. Convenience sampling was used to select 30 substance-dependent individuals undergoing maintenance treatment who were then randomly assigned to the experiment and control groups. The experiment group received its training in eight two-hour sessions. Data were analyzed using analysis of co-variance and paired t-test. Results There was significant reduction in anger symptoms of drug-dependent individuals after gross model based emotion regulation training (ERT) (P < 0.001). Moreover, the effectiveness of the training on anger was persistent in the follow-up period. Conclusions Symptoms of anger in drug-dependent individuals of this study were reduced by gross model-based emotion regulation strategies training. Based on the results of this study, we may conclude that the gross model based emotion regulation strategies training can be applied alongside other therapies to treat drug abusers undergoing rehabilitation. PMID:27162759

Frequency-dependent local field factors in dielectric liquids by a polarizable force field and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Davari, Nazanin; Haghdani, Shokouh; Åstrand, Per-Olof

2015-12-01

A force field model for calculating local field factors, i.e. the linear response of the local electric field for example at a nucleus in a molecule with respect to an applied electric field, is discussed. It is based on a combined charge-transfer and point-dipole interaction model for the polarizability, and thereby it includes two physically distinct terms for describing electronic polarization: changes in atomic charges arising from transfer of charge between the atoms and atomic induced dipole moments. A time dependence is included both for the atomic charges and the atomic dipole moments and if they are assumed to oscillate with the same frequency as the applied electric field, a model for frequency-dependent properties are obtained. Furthermore, if a life-time of excited states are included, a model for the complex frequency-dependent polariability is obtained including also information about excited states and the absorption spectrum. We thus present a model for the frequency-dependent local field factors through the first molecular excitation energy. It is combined with molecular dynamics simulations of liquids where a large set of configurations are sampled and for which local field factors are calculated. We are normally not interested in the average of the local field factor but rather in configurations where it is as high as possible. In electrical insulation, we would like to avoid high local field factors to reduce the risk for electrical breakdown, whereas for example in surface-enhanced Raman spectroscopy, high local field factors are desired to give dramatically increased intensities.

Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells.

PubMed

Choi, Hyun Ju; Lim, Do Young; Park, Jung Han Yoon

2009-05-29

3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both in vivo and in vitro models. We have previously determined that DIM (0 - 30 micromol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells. HT-29 cells were cultured with various concentrations of DIM (0 - 30 micromol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and in vitro kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted. The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1 and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1. Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.

An a priori solar radiation pressure model for the QZSS Michibiki satellite

NASA Astrophysics Data System (ADS)

Zhao, Qile; Chen, Guo; Guo, Jing; Liu, Jingnan; Liu, Xianglin

2018-02-01

It has been noted that the satellite laser ranging (SLR) residuals of the Quasi-Zenith Satellite System (QZSS) Michibiki satellite orbits show very marked dependence on the elevation angle of the Sun above the orbital plane (i.e., the β angle). It is well recognized that the systematic error is caused by mismodeling of the solar radiation pressure (SRP). Although the error can be reduced by the updated ECOM SRP model, the orbit error is still very large when the satellite switches to orbit-normal (ON) orientation. In this study, an a priori SRP model was established for the QZSS Michibiki satellite to enhance the ECOM model. This model is expressed in ECOM's D, Y, and B axes (DYB) using seven parameters for the yaw-steering (YS) mode, and additional three parameters are used to compensate the remaining modeling deficiencies, particularly the perturbations in the Y axis, based on a redefined DYB for the ON mode. With the proposed a priori model, QZSS Michibiki's precise orbits over 21 months were determined. SLR validation indicated that the systematic β -angle-dependent error was reduced when the satellite was in the YS mode, and better than an 8-cm root mean square (RMS) was achieved. More importantly, the orbit quality was also improved significantly when the satellite was in the ON mode. Relative to ECOM and adjustable box-wing model, the proposed SRP model showed the best performance in the ON mode, and the RMS of the SLR residuals was better than 15 cm, which was a two times improvement over the ECOM without a priori model used, but was still two times worse than the YS mode.

A Long-Term Mathematical Model for Mining Industries

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

Achdou, Yves, E-mail: achdou@ljll.univ-paris-diderot.fr; Giraud, Pierre-Noel; Lasry, Jean-Michel

A parcimonious long term model is proposed for a mining industry. Knowing the dynamics of the global reserve, the strategy of each production unit consists of an optimal control problem with two controls, first the flux invested into prospection and the building of new extraction facilities, second the production rate. In turn, the dynamics of the global reserve depends on the individual strategies of the producers, so the models leads to an equilibrium, which is described by low dimensional systems of partial differential equations. The dimensionality depends on the number of technologies that a mining producer can choose. In somemore » cases, the systems may be reduced to a Hamilton–Jacobi equation which is degenerate at the boundary and whose right hand side may blow up at the boundary. A mathematical analysis is supplied. Then numerical simulations for models with one or two technologies are described. In particular, a numerical calibration of the model in order to fit the historical data is carried out.« less

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner

PubMed Central

Hughes, K. R.; Harnisch, L. C.; Alcon-Giner, C.; Mitra, S.; Wright, C. J.; Ketskemety, J.

2017-01-01

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes. PMID:28123052

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.

PubMed

Hughes, K R; Harnisch, L C; Alcon-Giner, C; Mitra, S; Wright, C J; Ketskemety, J; van Sinderen, D; Watson, A J M; Hall, L J

2017-01-01

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi-a process termed 'cell shedding'. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes. © 2017 The Authors.

Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis

PubMed Central

Park, Sei-Kyoung; Hong, Joo Y.; Arslan, Fatih; Tietsort, Alex; Tank, Elizabeth M. H.; Li, Xingli

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43’s effect on toxicity, cell shape and proteolysis. The strength of these effects was influenced by the presence of the endogenous yeast prion, [PIN+]. Although overexpression of Sis1 altered the TDP-43 aggregation pattern, we did not detect physical association of Sis1 with TDP-43, suggesting the possibility of indirect effects on TDP-43 aggregation. Furthermore, overexpression of the mammalian Sis1 homologue, DNAJB1, relieves TDP-43 mediated toxicity in primary rodent cortical neurons, suggesting that Sis1 and its homologues may have neuroprotective effects in ALS. PMID:28531192

Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways.

PubMed

Martínez, Irene; Zhu, Jiangfeng; Lin, Henry; Bennett, George N; San, Ka-Yiu

2008-11-01

Reactions requiring reducing equivalents, NAD(P)H, are of enormous importance for the synthesis of industrially valuable compounds such as carotenoids, polymers, antibiotics and chiral alcohols among others. The use of whole-cell biocatalysis can reduce process cost by acting as catalyst and cofactor regenerator at the same time; however, product yields might be limited by cofactor availability within the cell. Thus, our study focussed on the genetic manipulation of a whole-cell system by modifying metabolic pathways and enzymes to improve the overall production process. In the present work, we genetically engineered an Escherichia coli strain to increase NADPH availability to improve the productivity of products that require NADPH in its biosynthesis. The approach involved an alteration of the glycolysis step where glyceraldehyde-3-phosphate (GAP) is oxidized to 1,3 bisphophoglycerate (1,3-BPG). This reaction is catalyzed by NAD-dependent endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) encoded by the gapA gene. We constructed a recombinant E. coli strain by replacing the native NAD-dependent gapA gene with a NADP-dependent GAPDH from Clostridium acetobutylicum, encoded by the gene gapC. The beauty of this approach is that the recombinant E. coli strain produces 2 mol of NADPH, instead of NADH, per mole of glucose consumed. Metabolic flux analysis showed that the flux through the pentose phosphate (PP) pathway, one of the main pathways that produce NADPH, was reduced significantly in the recombinant strain when compared to that of the parent strain. The effectiveness of the NADPH enhancing system was tested using the production of lycopene and epsilon-caprolactone as model systems using two different background strains. The recombinant strains, with increased NADPH availability, consistently showed significant higher productivity than the parent strains.

Understanding Zipf's law of word frequencies through sample-space collapse in sentence formation

PubMed Central

Thurner, Stefan; Hanel, Rudolf; Liu, Bo; Corominas-Murtra, Bernat

2015-01-01

The formation of sentences is a highly structured and history-dependent process. The probability of using a specific word in a sentence strongly depends on the ‘history’ of word usage earlier in that sentence. We study a simple history-dependent model of text generation assuming that the sample-space of word usage reduces along sentence formation, on average. We first show that the model explains the approximate Zipf law found in word frequencies as a direct consequence of sample-space reduction. We then empirically quantify the amount of sample-space reduction in the sentences of 10 famous English books, by analysis of corresponding word-transition tables that capture which words can follow any given word in a text. We find a highly nested structure in these transition tables and show that this ‘nestedness’ is tightly related to the power law exponents of the observed word frequency distributions. With the proposed model, it is possible to understand that the nestedness of a text can be the origin of the actual scaling exponent and that deviations from the exact Zipf law can be understood by variations of the degree of nestedness on a book-by-book basis. On a theoretical level, we are able to show that in the case of weak nesting, Zipf's law breaks down in a fast transition. Unlike previous attempts to understand Zipf's law in language the sample-space reducing model is not based on assumptions of multiplicative, preferential or self-organized critical mechanisms behind language formation, but simply uses the empirically quantifiable parameter ‘nestedness’ to understand the statistics of word frequencies. PMID:26063827

Understanding Zipf's law of word frequencies through sample-space collapse in sentence formation.

PubMed

Thurner, Stefan; Hanel, Rudolf; Liu, Bo; Corominas-Murtra, Bernat

2015-07-06

The formation of sentences is a highly structured and history-dependent process. The probability of using a specific word in a sentence strongly depends on the 'history' of word usage earlier in that sentence. We study a simple history-dependent model of text generation assuming that the sample-space of word usage reduces along sentence formation, on average. We first show that the model explains the approximate Zipf law found in word frequencies as a direct consequence of sample-space reduction. We then empirically quantify the amount of sample-space reduction in the sentences of 10 famous English books, by analysis of corresponding word-transition tables that capture which words can follow any given word in a text. We find a highly nested structure in these transition tables and show that this 'nestedness' is tightly related to the power law exponents of the observed word frequency distributions. With the proposed model, it is possible to understand that the nestedness of a text can be the origin of the actual scaling exponent and that deviations from the exact Zipf law can be understood by variations of the degree of nestedness on a book-by-book basis. On a theoretical level, we are able to show that in the case of weak nesting, Zipf's law breaks down in a fast transition. Unlike previous attempts to understand Zipf's law in language the sample-space reducing model is not based on assumptions of multiplicative, preferential or self-organized critical mechanisms behind language formation, but simply uses the empirically quantifiable parameter 'nestedness' to understand the statistics of word frequencies. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

USDA-ARS?s Scientific Manuscript database

Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

Deficiency of the Cyclin-Dependent Kinase Inhibitor, CDKN1B, Results in Overgrowth and Neurodevelopmental Delay

PubMed Central

Grey, William; Izatt, Louise; Sahraoui, Wafa; Ng, Yiu-Ming; Ogilvie, Caroline; Hulse, Anthony; Tse, Eric; Holic, Roman; Yu, Veronica

2013-01-01

Germline mutations in the cyclin-dependent kinase inhibitor, CDKN1B, have been described in patients with multiple endocrine neoplasia (MEN), a cancer predisposition syndrome with adult onset neoplasia and no additional phenotypes. Here, we describe the first human case of CDKN1B deficiency, which recapitulates features of the murine CDKN1B knockout mouse model, including gigantism and neurodevelopmental defects. Decreased mRNA and protein expression of CDKN1B were confirmed in the proband's peripheral blood, which is not seen in MEN syndrome patients. We ascribed the decreased protein level to a maternally derived deletion on chromosome 12p13 encompassing the CDKN1B locus (which reduced mRNA expression) and a de novo allelic variant (c.-73G>A) in the CDKN1B promoter (which reduced protein translation). We propose a recessive model where decreased dosage of CDKN1B during development in humans results in a neuronal phenotype akin to that described in mice, placing CDKN1B as a candidate gene involved in developmental delay. PMID:23505216

Nanophase diagram of binary eutectic Au-Ge nanoalloys for vapor-liquid-solid semiconductor nanowires growth

NASA Astrophysics Data System (ADS)

Lu, Haiming; Meng, Xiangkang

2015-06-01

Although the vapor-liquid-solid growth of semiconductor nanowire is a non-equilibrium process, the equilibrium phase diagram of binary alloy provides important guidance on the growth conditions, such as the temperature and the equilibrium composition of the alloy. Given the small dimensions of the alloy seeds and the nanowires, the known phase diagram of bulk binary alloy cannot be expected to accurately predict the behavior of the nanowire growth. Here, we developed a unified model to describe the size- and dimensionality-dependent equilibrium phase diagram of Au-Ge binary eutectic nanoalloys based on the size-dependent cohesive energy model. It is found that the liquidus curves reduce and shift leftward with decreasing size and dimensionality. Moreover, the effects of size and dimensionality on the eutectic composition are small and negligible when both components in binary eutectic alloys have the same dimensionality. However, when two components have different dimensionality (e.g. Au nanoparticle-Ge nanowire usually used in the semiconductor nanowires growth), the eutectic composition reduces with decreasing size.

Mass-imbalanced Hubbard model in optical lattice with site-dependent interactions

NASA Astrophysics Data System (ADS)

Le, Duc-Anh; Tran, Thi-Thu-Trang; Hoang, Anh-Tuan; Nguyen, Toan-Thang; Tran, Minh-Tien

2018-03-01

We study the half-filled mass-imbalanced Hubbard model with spatially alternating interactions on an optical bipartite lattice by means of the dynamical mean-field theory. The Mott transition is investigated via the spin-dependent density of states and double occupancies. The phase diagrams for the homogeneous phases at zero temperature are constructed numerically. The boundary between metallic and insulating phases at zero temperature is analytically derived within the dynamical mean field theory using the equation of motion approach as the impurity solver. We found that the metallic region is reduced with increasing interaction anisotropy or mass imbalance. Our results are closely relevant to current researches in ultracold fermion experiments and can be verified through experimental observations.

Temperature and velocity conditions of air flow in vertical channel of hinged ventilated facade of a multistory building.

NASA Astrophysics Data System (ADS)

Statsenko, Elena; Ostrovaia, Anastasia; Pigurin, Andrey

2018-03-01

This article considers the influence of the building's tallness and the presence of mounting grooved lines on the parameters of heat transfer in the gap of a hinged ventilated facade. A numerical description of the processes occurring in a heat-gravitational flow is given. The average velocity and temperature of the heat-gravitational flow of a structure with open and sealed rusts are determined with unchanged geometric parameters of the gap. The dependence of the parameters influencing the thermomechanical characteristics of the enclosing structure is derived depending on the internal parameters of the system. Physical modeling of real multistory structures is performed by projecting actual parameters onto a reduced laboratory model (scaling).

Interaction effect in the Kondo energy of the periodic Anderson-Hubbard model

NASA Astrophysics Data System (ADS)

Itai, K.; Fazekas, P.

1996-07-01

We extend the periodic Anderson model by switching on a Hubbard U for the conduction band. The nearly integral valent limit of the Anderson-Hubbard model is studied with the Gutzwiller variational method. The lattice Kondo energy shows U dependence both in the prefactor and the exponent. Switching on U reduces the Kondo scale, which can be understood to result from the blocking of hybridization. At half filling, we find a Brinkman-Rice-type transition from a Kondo insulator to a Mott insulator. Our findings should be relevant for a number of correlated two-band models of recent interest.

Enhanced uranium immobilization and reduction by Geobacter sulfurreducens biofilms.

PubMed

Cologgi, Dena L; Speers, Allison M; Bullard, Blair A; Kelly, Shelly D; Reguera, Gemma

2014-11-01

Biofilms formed by dissimilatory metal reducers are of interest to develop permeable biobarriers for the immobilization of soluble contaminants such as uranium. Here we show that biofilms of the model uranium-reducing bacterium Geobacter sulfurreducens immobilized substantially more U(VI) than planktonic cells and did so for longer periods of time, reductively precipitating it to a mononuclear U(IV) phase involving carbon ligands. The biofilms also tolerated high and otherwise toxic concentrations (up to 5 mM) of uranium, consistent with a respiratory strategy that also protected the cells from uranium toxicity. The enhanced ability of the biofilms to immobilize uranium correlated only partially with the biofilm biomass and thickness and depended greatly on the area of the biofilm exposed to the soluble contaminant. In contrast, uranium reduction depended on the expression of Geobacter conductive pili and, to a lesser extent, on the presence of the c cytochrome OmcZ in the biofilm matrix. The results support a model in which the electroactive biofilm matrix immobilizes and reduces the uranium in the top stratum. This mechanism prevents the permeation and mineralization of uranium in the cell envelope, thereby preserving essential cellular functions and enhancing the catalytic capacity of Geobacter cells to reduce uranium. Hence, the biofilms provide cells with a physically and chemically protected environment for the sustained immobilization and reduction of uranium that is of interest for the development of improved strategies for the in situ bioremediation of environments impacted by uranium contamination. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Enhanced Uranium Immobilization and Reduction by Geobacter sulfurreducens Biofilms

PubMed Central

Cologgi, Dena L.; Speers, Allison M.; Bullard, Blair A.; Kelly, Shelly D.

2014-01-01

Biofilms formed by dissimilatory metal reducers are of interest to develop permeable biobarriers for the immobilization of soluble contaminants such as uranium. Here we show that biofilms of the model uranium-reducing bacterium Geobacter sulfurreducens immobilized substantially more U(VI) than planktonic cells and did so for longer periods of time, reductively precipitating it to a mononuclear U(IV) phase involving carbon ligands. The biofilms also tolerated high and otherwise toxic concentrations (up to 5 mM) of uranium, consistent with a respiratory strategy that also protected the cells from uranium toxicity. The enhanced ability of the biofilms to immobilize uranium correlated only partially with the biofilm biomass and thickness and depended greatly on the area of the biofilm exposed to the soluble contaminant. In contrast, uranium reduction depended on the expression of Geobacter conductive pili and, to a lesser extent, on the presence of the c cytochrome OmcZ in the biofilm matrix. The results support a model in which the electroactive biofilm matrix immobilizes and reduces the uranium in the top stratum. This mechanism prevents the permeation and mineralization of uranium in the cell envelope, thereby preserving essential cellular functions and enhancing the catalytic capacity of Geobacter cells to reduce uranium. Hence, the biofilms provide cells with a physically and chemically protected environment for the sustained immobilization and reduction of uranium that is of interest for the development of improved strategies for the in situ bioremediation of environments impacted by uranium contamination. PMID:25128347

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

Smith, Kandler; Shi, Ying; Santhanagopalan, Shriram

Predictive models of Li-ion battery lifetime must consider a multiplicity of electrochemical, thermal, and mechanical degradation modes experienced by batteries in application environments. To complicate matters, Li-ion batteries can experience different degradation trajectories that depend on storage and cycling history of the application environment. Rates of degradation are controlled by factors such as temperature history, electrochemical operating window, and charge/discharge rate. We present a generalized battery life prognostic model framework for battery systems design and control. The model framework consists of trial functions that are statistically regressed to Li-ion cell life datasets wherein the cells have been aged under differentmore » levels of stress. Degradation mechanisms and rate laws dependent on temperature, storage, and cycling condition are regressed to the data, with multiple model hypotheses evaluated and the best model down-selected based on statistics. The resulting life prognostic model, implemented in state variable form, is extensible to arbitrary real-world scenarios. The model is applicable in real-time control algorithms to maximize battery life and performance. We discuss efforts to reduce lifetime prediction error and accommodate its inevitable impact in controller design.« less

Normal tissue complication probability modelling of tissue fibrosis following breast radiotherapy

NASA Astrophysics Data System (ADS)

Alexander, M. A. R.; Brooks, W. A.; Blake, S. W.

2007-04-01

Cosmetic late effects of radiotherapy such as tissue fibrosis are increasingly regarded as being of importance. It is generally considered that the complication probability of a radiotherapy plan is dependent on the dose uniformity, and can be reduced by using better compensation to remove dose hotspots. This work aimed to model the effects of improved dose homogeneity on complication probability. The Lyman and relative seriality NTCP models were fitted to clinical fibrosis data for the breast collated from the literature. Breast outlines were obtained from a commercially available Rando phantom using the Osiris system. Multislice breast treatment plans were produced using a variety of compensation methods. Dose-volume histograms (DVHs) obtained for each treatment plan were reduced to simple numerical parameters using the equivalent uniform dose and effective volume DVH reduction methods. These parameters were input into the models to obtain complication probability predictions. The fitted model parameters were consistent with a parallel tissue architecture. Conventional clinical plans generally showed reducing complication probabilities with increasing compensation sophistication. Extremely homogenous plans representing idealized IMRT treatments showed increased complication probabilities compared to conventional planning methods, as a result of increased dose to areas receiving sub-prescription doses using conventional techniques.

Reduced rank models for travel time estimation of low order mode pulses.

PubMed

Chandrayadula, Tarun K; Wage, Kathleen E; Worcester, Peter F; Dzieciuch, Matthew A; Mercer, James A; Andrew, Rex K; Howe, Bruce M

2013-10-01

Mode travel time estimation in the presence of internal waves (IWs) is a challenging problem. IWs perturb the sound speed, which results in travel time wander and mode scattering. A standard approach to travel time estimation is to pulse compress the broadband signal, pick the peak of the compressed time series, and average the peak time over multiple receptions to reduce variance. The peak-picking approach implicitly assumes there is a single strong arrival and does not perform well when there are multiple arrivals due to scattering. This article presents a statistical model for the scattered mode arrivals and uses the model to design improved travel time estimators. The model is based on an Empirical Orthogonal Function (EOF) analysis of the mode time series. Range-dependent simulations and data from the Long-range Ocean Acoustic Propagation Experiment (LOAPEX) indicate that the modes are represented by a small number of EOFs. The reduced-rank EOF model is used to construct a travel time estimator based on the Matched Subspace Detector (MSD). Analysis of simulation and experimental data show that the MSDs are more robust to IW scattering than peak picking. The simulation analysis also highlights how IWs affect the mode excitation by the source.

C/EBPβ-LAP*/LAP Expression Is Mediated by RSK/eIF4B-Dependent Signalling and Boosted by Increased Protein Stability in Models of Monocytic Differentiation

PubMed Central

Christmann, Martin; Friesenhagen, Judith; Westphal, Andreas; Pietsch, Daniel; Brand, Korbinian

2015-01-01

The transcription factor C/EBPβ plays a key role in monocytic differentiation and inflammation. Its small isoform LIP is associated with proliferation at early premonocytic developmental stages and regulated via mTOR-dependent signalling. During later stages of (pre)monocytic differentiation there is a considerable increase in the large C/EBPβ isoforms LAP*/LAP which inhibit proliferation thus supporting terminal differentiation. Here, we showed in different models of monocytic differentiation that this dramatic increase in the LAP*/LAP protein and LAP/LIP ratio was accompanied by an only modest/retarded mRNA increase suggesting an important role for (post)translational mechanisms. We found that LAP*/LAP formation was induced via MEK/RSK-dependent cascades, whereas mTOR/S6K1 were not involved. Remarkably, LAP*/LAP expression was dependent on phosphorylated eIF4B, an acceleratory protein of RNA helicase eIF4A. PKR inhibition reduced the expression of eIF4B and C/EBPβ in an eIF2α-independent manner. Furthermore, under our conditions a marked stabilisation of LAP*/LAP protein occurred, accompanied by reduced chymotrypsin-like proteasome/calpain activities and increased calpastatin levels. Our study elucidates new signalling pathways inducing LAP*/LAP expression and indicates new alternative PKR functions in monocytes. The switch from mTOR- to RSK-mediated signalling to orchestrate eIF4B-dependent LAP*/LAP translation, accompanied by increased protein stability but only small mRNA changes, may be a prototypical example for the regulation of protein expression during selected processes of differentiation/proliferation. PMID:26646662

Energy Models for One-Carrier Transport in Semiconductor Devices

NASA Technical Reports Server (NTRS)

Jerome, Joseph W.; Shu, Chi-Wang

1991-01-01

Moment models of carrier transport, derived from the Boltzmann equation, made possible the simulation of certain key effects through such realistic assumptions as energy dependent mobility functions. This type of global dependence permits the observation of velocity overshoot in the vicinity of device junctions, not discerned via classical drift-diffusion models, which are primarily local in nature. It was found that a critical role is played in the hydrodynamic model by the heat conduction term. When ignored, the overshoot is inappropriately damped. When the standard choice of the Wiedemann-Franz law is made for the conductivity, spurious overshoot is observed. Agreement with Monte-Carlo simulation in this regime required empirical modification of this law, or nonstandard choices. Simulations of the hydrodynamic model in one and two dimensions, as well as simulations of a newly developed energy model, the RT model, are presented. The RT model, intermediate between the hydrodynamic and drift-diffusion model, was developed to eliminate the parabolic energy band and Maxwellian distribution assumptions, and to reduce the spurious overshoot with physically consistent assumptions. The algorithms employed for both models are the essentially non-oscillatory shock capturing algorithms. Some mathematical results are presented and contrasted with the highly developed state of the drift-diffusion model.

Effects of distance from models on the fitness of floral mimics.

PubMed

Duffy, K J; Johnson, S D

2017-05-01

Rewardless plants can attract pollinators by mimicking floral traits of rewarding heterospecific plants. This should result in the pollination success of floral mimics being dependent on the relative abundance of their models, as pollinator abundance and conditioning on model signals should be higher in the vicinity of the models. However, the attraction of pollinators to signals of the models may be partially innate, such that spatial isolation of mimics from model species may not strongly affect pollination success of mimics. We tested whether pollination rates and fruit set of the rewardless orchid Disa pulchra were influenced by proximity and abundance of its rewarding model species, Watsonia lepida. Pollination success of the orchid increased with proximity to the model species, while fruit set of the orchid increased with local abundance of the model species. Orchids that were experimentally translocated outside the model population experienced reduced pollinaria removal and increased pollinator-mediated self-pollination. These results confirm predictions that the pollination success of floral mimics should be dependent on the proximity and abundance of model taxa, and thus highlight the importance of ecological facilitation among species involved in mimicry systems. © 2017 German Botanical Society and The Royal Botanical Society of the Netherlands.

Evaluating a multispecies adaptive management framework: Must uncertainty impede effective decision-making?

USGS Publications Warehouse

Smith, David R.; McGowan, Conor P.; Daily, Jonathan P.; Nichols, James D.; Sweka, John A.; Lyons, James E.

2013-01-01

Application of adaptive management to complex natural resource systems requires careful evaluation to ensure that the process leads to improved decision-making. As part of that evaluation, adaptive policies can be compared with alternative nonadaptive management scenarios. Also, the value of reducing structural (ecological) uncertainty to achieving management objectives can be quantified.A multispecies adaptive management framework was recently adopted by the Atlantic States Marine Fisheries Commission for sustainable harvest of Delaware Bay horseshoe crabs Limulus polyphemus, while maintaining adequate stopover habitat for migrating red knots Calidris canutus rufa, the focal shorebird species. The predictive model set encompassed the structural uncertainty in the relationships between horseshoe crab spawning, red knot weight gain and red knot vital rates. Stochastic dynamic programming was used to generate a state-dependent strategy for harvest decisions given that uncertainty. In this paper, we employed a management strategy evaluation approach to evaluate the performance of this adaptive management framework. Active adaptive management was used by including model weights as state variables in the optimization and reducing structural uncertainty by model weight updating.We found that the value of information for reducing structural uncertainty is expected to be low, because the uncertainty does not appear to impede effective management. Harvest policy responded to abundance levels of both species regardless of uncertainty in the specific relationship that generated those abundances. Thus, the expected horseshoe crab harvest and red knot abundance were similar when the population generating model was uncertain or known, and harvest policy was robust to structural uncertainty as specified.Synthesis and applications. The combination of management strategy evaluation with state-dependent strategies from stochastic dynamic programming was an informative approach to evaluate adaptive management performance and value of learning. Although natural resource decisions are characterized by uncertainty, not all uncertainty will cause decisions to be altered substantially, as we found in this case. It is important to incorporate uncertainty into the decision framing and evaluate the effect of reducing that uncertainty on achieving the desired outcomes

Error modeling for surrogates of dynamical systems using machine learning: Machine-learning-based error model for surrogates of dynamical systems

DOE PAGES

Trehan, Sumeet; Carlberg, Kevin T.; Durlofsky, Louis J.

2017-07-14

A machine learning–based framework for modeling the error introduced by surrogate models of parameterized dynamical systems is proposed. The framework entails the use of high-dimensional regression techniques (eg, random forests, and LASSO) to map a large set of inexpensively computed “error indicators” (ie, features) produced by the surrogate model at a given time instance to a prediction of the surrogate-model error in a quantity of interest (QoI). This eliminates the need for the user to hand-select a small number of informative features. The methodology requires a training set of parameter instances at which the time-dependent surrogate-model error is computed bymore » simulating both the high-fidelity and surrogate models. Using these training data, the method first determines regression-model locality (via classification or clustering) and subsequently constructs a “local” regression model to predict the time-instantaneous error within each identified region of feature space. We consider 2 uses for the resulting error model: (1) as a correction to the surrogate-model QoI prediction at each time instance and (2) as a way to statistically model arbitrary functions of the time-dependent surrogate-model error (eg, time-integrated errors). We then apply the proposed framework to model errors in reduced-order models of nonlinear oil-water subsurface flow simulations, with time-varying well-control (bottom-hole pressure) parameters. The reduced-order models used in this work entail application of trajectory piecewise linearization in conjunction with proper orthogonal decomposition. Moreover, when the first use of the method is considered, numerical experiments demonstrate consistent improvement in accuracy in the time-instantaneous QoI prediction relative to the original surrogate model, across a large number of test cases. When the second use is considered, results show that the proposed method provides accurate statistical predictions of the time- and well-averaged errors.« less

Error modeling for surrogates of dynamical systems using machine learning: Machine-learning-based error model for surrogates of dynamical systems

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

Trehan, Sumeet; Carlberg, Kevin T.; Durlofsky, Louis J.

A machine learning–based framework for modeling the error introduced by surrogate models of parameterized dynamical systems is proposed. The framework entails the use of high-dimensional regression techniques (eg, random forests, and LASSO) to map a large set of inexpensively computed “error indicators” (ie, features) produced by the surrogate model at a given time instance to a prediction of the surrogate-model error in a quantity of interest (QoI). This eliminates the need for the user to hand-select a small number of informative features. The methodology requires a training set of parameter instances at which the time-dependent surrogate-model error is computed bymore » simulating both the high-fidelity and surrogate models. Using these training data, the method first determines regression-model locality (via classification or clustering) and subsequently constructs a “local” regression model to predict the time-instantaneous error within each identified region of feature space. We consider 2 uses for the resulting error model: (1) as a correction to the surrogate-model QoI prediction at each time instance and (2) as a way to statistically model arbitrary functions of the time-dependent surrogate-model error (eg, time-integrated errors). We then apply the proposed framework to model errors in reduced-order models of nonlinear oil-water subsurface flow simulations, with time-varying well-control (bottom-hole pressure) parameters. The reduced-order models used in this work entail application of trajectory piecewise linearization in conjunction with proper orthogonal decomposition. Moreover, when the first use of the method is considered, numerical experiments demonstrate consistent improvement in accuracy in the time-instantaneous QoI prediction relative to the original surrogate model, across a large number of test cases. When the second use is considered, results show that the proposed method provides accurate statistical predictions of the time- and well-averaged errors.« less

An interactive ocean surface albedo scheme (OSAv1.0): formulation and evaluation in ARPEGE-Climat (V6.1) and LMDZ (V5A)

NASA Astrophysics Data System (ADS)

Séférian, Roland; Baek, Sunghye; Boucher, Olivier; Dufresne, Jean-Louis; Decharme, Bertrand; Saint-Martin, David; Roehrig, Romain

2018-01-01

Ocean surface represents roughly 70 % of the Earth's surface, playing a large role in the partitioning of the energy flow within the climate system. The ocean surface albedo (OSA) is an important parameter in this partitioning because it governs the amount of energy penetrating into the ocean or reflected towards space. The old OSA schemes in the ARPEGE-Climat and LMDZ models only resolve the latitudinal dependence in an ad hoc way without an accurate representation of the solar zenith angle dependence. Here, we propose a new interactive OSA scheme suited for Earth system models, which enables coupling between Earth system model components like surface ocean waves and marine biogeochemistry. This scheme resolves spectrally the various contributions of the surface for direct and diffuse solar radiation. The implementation of this scheme in two Earth system models leads to substantial improvements in simulated OSA. At the local scale, models using the interactive OSA scheme better replicate the day-to-day distribution of OSA derived from ground-based observations in contrast to old schemes. At global scale, the improved representation of OSA for diffuse radiation reduces model biases by up to 80 % over the tropical oceans, reducing annual-mean model-data error in surface upwelling shortwave radiation by up to 7 W m-2 over this domain. The spatial correlation coefficient between modeled and observed OSA at monthly resolution has been increased from 0.1 to 0.8. Despite its complexity, this interactive OSA scheme is computationally efficient for enabling precise OSA calculation without penalizing the elapsed model time.

Study on Frequency Dependency of ON-Resistance and Pulse-Loss Calculation of MOSFETs for Switch Mode Power Supply

NASA Astrophysics Data System (ADS)

Yamamura, Hideho; Sato, Ryohei; Iwata, Yoshiharu

Global efforts toward energy conservation, increasing data centers, and the increasing use of IT equipments are leading to a demand in reduced power consumption of equipments, and power efficiency improvement of power supply units is becoming a necessity. MOSFETs are widely used for their low ON-resistances. Power efficiency is designed using time-domain circuit simulators, except for transformer copper-loss, which has frequency dependency which is calculated separately using methods based on skin and proximity effects. As semiconductor technology reduces the ON-resistance of MOSFETs, frequency dependency due to the skin effect or proximity effect is anticipated. In this study, ON-resistance of MOSFETs are measured and frequency dependency is confirmed. Power loss against rectangular current pulse is calculated. The calculation method for transformer copper-loss is expanded to MOSFETs. A frequency function for the resistance model is newly developed and parametric calculation is enabled. Acceleration of calculation is enabled by eliminating summation terms. Using this method, it is shown that the frequency dependent component of the measured MOSFETs increases the dissipation from 11% to 32% at a switching frequency of 100kHz. From above, this paper points out the importance of the frequency dependency of MOSFETs' ON-resistance, provides means of calculating its pulse losses, and improves loss calculation accuracy of SMPSs.

Quantifying the history dependency of muscle recovery from a fatiguing intermittent task.

PubMed

Rashedi, Ehsan; Nussbaum, Maury A

2017-01-25

Muscle fatigue and recovery are complex processes influencing muscle force generation capacity. While fatigue reduces this capacity, recovery acts to restore the unfatigued muscle state. Many factors can potentially affect muscle recovery, and among these may be a task dependency of recovery following an exercise. However, little has been reported regarding the history dependency of recovery after fatiguing contractions. We examined the dependency of muscle recovery subsequent to four different histories of fatiguing muscle contractions, imposed using two cycle times (30 and 60s) during low to moderate levels (15% and 25% of maximum voluntary contraction (MVC)) of intermittent static exertions involving index finger abduction. MVC and low-frequency electrical stimulation (LFES) measures (i.e., magnitude, rise and relaxation rates) of muscle capacity were used, all of which indicated a dependency of muscle recovery on the muscle capacity state existing immediately after fatiguing exercise. This dependency did not appear to be modified by either the cycle time or exertion level leading to that state. These results imply that the post-exercise rate of recovery is primarily influenced by the immediate post-exercise muscle contractile status (estimated by MVC and LFES measures). Such results may help improve existing models of muscle recovery, facilitating more accurate predictions of localized muscle fatigue development and thereby helping to enhance muscle performance and reduce the risk of injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bayesian explorations of fault slip evolution over the earthquake cycle

NASA Astrophysics Data System (ADS)

Duputel, Z.; Jolivet, R.; Benoit, A.; Gombert, B.

2017-12-01

The ever-increasing amount of geophysical data continuously opens new perspectives on fundamental aspects of the seismogenic behavior of active faults. In this context, the recent fleet of SAR satellites including Sentinel-1 and COSMO-SkyMED permits the use of InSAR for time-dependent slip modeling with unprecedented resolution in time and space. However, existing time-dependent slip models rely on spatial smoothing regularization schemes, which can produce unrealistically smooth slip distributions. In addition, these models usually do not include uncertainty estimates thereby reducing the utility of such estimates. Here, we develop an entirely new approach to derive probabilistic time-dependent slip models. This Markov-Chain Monte Carlo method involves a series of transitional steps to predict and update posterior Probability Density Functions (PDFs) of slip as a function of time. We assess the viability of our approach using various slow-slip event scenarios. Using a dense set of SAR images, we also use this method to quantify the spatial distribution and temporal evolution of slip along a creeping segment of the North Anatolian Fault. This allows us to track a shallow aseismic slip transient lasting for about a month with a maximum slip of about 2 cm.

EVALUATING RISK-PREDICTION MODELS USING DATA FROM ELECTRONIC HEALTH RECORDS.

PubMed

Wang, L E; Shaw, Pamela A; Mathelier, Hansie M; Kimmel, Stephen E; French, Benjamin

2016-03-01

The availability of data from electronic health records facilitates the development and evaluation of risk-prediction models, but estimation of prediction accuracy could be limited by outcome misclassification, which can arise if events are not captured. We evaluate the robustness of prediction accuracy summaries, obtained from receiver operating characteristic curves and risk-reclassification methods, if events are not captured (i.e., "false negatives"). We derive estimators for sensitivity and specificity if misclassification is independent of marker values. In simulation studies, we quantify the potential for bias in prediction accuracy summaries if misclassification depends on marker values. We compare the accuracy of alternative prognostic models for 30-day all-cause hospital readmission among 4548 patients discharged from the University of Pennsylvania Health System with a primary diagnosis of heart failure. Simulation studies indicate that if misclassification depends on marker values, then the estimated accuracy improvement is also biased, but the direction of the bias depends on the direction of the association between markers and the probability of misclassification. In our application, 29% of the 1143 readmitted patients were readmitted to a hospital elsewhere in Pennsylvania, which reduced prediction accuracy. Outcome misclassification can result in erroneous conclusions regarding the accuracy of risk-prediction models.

Size-dependent geometrically nonlinear free vibration analysis of fractional viscoelastic nanobeams based on the nonlocal elasticity theory

NASA Astrophysics Data System (ADS)

Ansari, R.; Faraji Oskouie, M.; Gholami, R.

2016-01-01

In recent decades, mathematical modeling and engineering applications of fractional-order calculus have been extensively utilized to provide efficient simulation tools in the field of solid mechanics. In this paper, a nonlinear fractional nonlocal Euler-Bernoulli beam model is established using the concept of fractional derivative and nonlocal elasticity theory to investigate the size-dependent geometrically nonlinear free vibration of fractional viscoelastic nanobeams. The non-classical fractional integro-differential Euler-Bernoulli beam model contains the nonlocal parameter, viscoelasticity coefficient and order of the fractional derivative to interpret the size effect, viscoelastic material and fractional behavior in the nanoscale fractional viscoelastic structures, respectively. In the solution procedure, the Galerkin method is employed to reduce the fractional integro-partial differential governing equation to a fractional ordinary differential equation in the time domain. Afterwards, the predictor-corrector method is used to solve the nonlinear fractional time-dependent equation. Finally, the influences of nonlocal parameter, order of fractional derivative and viscoelasticity coefficient on the nonlinear time response of fractional viscoelastic nanobeams are discussed in detail. Moreover, comparisons are made between the time responses of linear and nonlinear models.

Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus.

PubMed

Papanastasiou, Giorgos; Williams, Michelle C; Kershaw, Lucy E; Dweck, Marc R; Alam, Shirjel; Mirsadraee, Saeed; Connell, Martin; Gray, Calum; MacGillivray, Tom; Newby, David E; Semple, Scott Ik

2015-02-17

Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods. Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05. Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling. Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.

Vegetation turnover and nitrogen feedback drive temperate forest carbon sequestration in response to elevated CO[2]. A multi-model structural analysis

NASA Astrophysics Data System (ADS)

Walker, A. P.; Zaehle, S.; Medlyn, B. E.; De Kauwe, M. G.; Asao, S.; Hickler, T.; Lomas, M. R.; Pak, B. C.; Parton, W. J.; Quegan, S.; Ricciuto, D. M.; Wang, Y.; Warlind, D.; Norby, R. J.

2013-12-01

Predicting forest carbon (C) sequestration requires understanding the processes leading to rates of biomass C accrual (net primary productivity; NPP) and loss (turnover). In temperate forest ecosystems, experiments and models have shown that feedback via progressive nitrogen limitation (PNL) is a key driver of NPP responses to elevated CO[2]. In this analysis we show that while still important, PNL may not be as severe a constraint on NPP as indicated by some studies and that the response of turnover to elevated CO[2] could be as important, especially in the near to medium term. Seven terrestrial ecosystem and biosphere models that couple C and N cycles with varying assumptions and complexity were used to simulate responses over 300 years to a step change in CO[2] to 550 ppmv. Simulations were run for the evergreen needleleaf Duke forest and the deciduous broadleaf Oak Ridge forest FACE experiments. Whether or not a model simulated PNL under elevated CO[2] depended on model structure and the timescale of observation. Avoiding PNL depended on mechanisms that reduced ecosystem N losses. The two key assumptions that reduced N losses were whether plant N uptake was based on plant N demand and whether ecosystem N losses (volatisation and leaching) were dependent on the concentration of N in the soil solution. Assumptions on allocation and turnover resulted in very different responses of turnover to elevated CO[2], which had profound implications for C sequestration. For example, at equilibrium CABLE2.0 predicted an increase in vegetation C sequestration despite decreased NPP, while O-CN predicted much less vegetation C sequestration than would be expected from predicted NPP increases alone. Generally elevated CO[2] favoured a shift in C partitioning towards longer lived wood biomass, which increased vegetation turnover and enhanced C sequestration. Enhanced wood partitioning was overlaid by increases or decreases in self-thinning depended on whether self-thinning was simply a function of forest structure, or structure and NPP. Self-thinning assumptions altered equilibrium C sequestration and were extremely important for the immediate transient response and near-term prediction of C sequestration.

The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model

PubMed Central

Laramée, Philippe; Brodtkorb, Thor-Henrik; Rahhali, Nora; Knight, Chris; Barbosa, Carolina; François, Clément; Toumi, Mondher; Daeppen, Jean-Bernard; Rehm, Jürgen

2014-01-01

Objectives To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths. Design Decision modelling using Markov chains compared costs and effects over 5 years. Setting The analysis was from the perspective of the National Health Service (NHS) in England and Wales. Participants The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment. Data sources We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources. Main outcome measures We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided. Results Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20 000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100 000 patients compared to psychosocial support alone over the course of 5 years. Conclusions Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits. Trial registration numbers This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941). PMID:25227627

Experimental investigation of lateral forces induced by flow through model labyrinth glands

NASA Technical Reports Server (NTRS)

Leong, Y. M. M. S.; Brown, R. D.

1984-01-01

The lateral forces induced by flow through model labyrinth glands were investigated. Circumferential pressure distributions, lateral forces and stiffness coefficients data obtained are discussed. The force system is represented as a negative spring and a tangential force orthogonal to eccentricity. The magnitude of these forces are dependent on eccentricity, entry swirl, rotor peripheral velocity and seal size. A pressure equalization chamber at midgland tests should in significantly reduced forces and stiffness coefficients.

Climatic Stress during Stand Development Alters the Sign and Magnitude of Age-Related Growth Responses in a Subtropical Mountain Pine.

PubMed

Ruiz-Benito, Paloma; Madrigal-González, Jaime; Young, Sarah; Mercatoris, Pierre; Cavin, Liam; Huang, Tsurng-Juhn; Chen, Jan-Chang; Jump, Alistair S

2015-01-01

The modification of typical age-related growth by environmental changes is poorly understood, In part because there is a lack of consensus at individual tree level regarding age-dependent growth responses to climate warming as stands develop. To increase our current understanding about how multiple drivers of environmental change can modify growth responses as trees age we used tree ring data of a mountain subtropical pine species along an altitudinal gradient covering more than 2,200 m of altitude. We applied mixed-linear models to determine how absolute and relative age-dependent growth varies depending on stand development; and to quantify the relative importance of tree age and climate on individual tree growth responses. Tree age was the most important factor for tree growth in models parameterised using data from all forest developmental stages. Contrastingly, the relationship found between tree age and growth became non-significant in models parameterised using data corresponding to mature stages. These results suggest that although absolute tree growth can continuously increase along tree size when trees reach maturity age had no effect on growth. Tree growth was strongly reduced under increased annual temperature, leading to more constant age-related growth responses. Furthermore, young trees were the most sensitive to reductions in relative growth rates, but absolute growth was strongly reduced under increased temperature in old trees. Our results help to reconcile previous contrasting findings of age-related growth responses at the individual tree level, suggesting that the sign and magnitude of age-related growth responses vary with stand development. The different responses found to climate for absolute and relative growth rates suggest that young trees are particularly vulnerable under warming climate, but reduced absolute growth in old trees could alter the species' potential as a carbon sink in the future.

A numerical study on piezoelectric energy harvesting by combining transverse galloping and parametric instability phenomena

NASA Astrophysics Data System (ADS)

Franzini, Guilherme Rosa; Santos, Rebeca Caramêz Saraiva; Pesce, Celso Pupo

2017-12-01

This paper aims to numerically investigate the effects of parametric instability on piezoelectric energy harvesting from the transverse galloping of a square prism. A two degrees-of-freedom reduced-order model for this problem is proposed and numerically integrated. A usual quasi-steady galloping model is applied, where the transverse force coefficient is adopted as a cubic polynomial function with respect to the angle of attack. Time-histories of nondimensional prism displacement, electric voltage and power dissipated at both the dashpot and the electrical resistance are obtained as functions of the reduced velocity. Both, oscillation amplitude and electric voltage, increased with the reduced velocity for all parametric excitation conditions tested. For low values of reduced velocity, 2:1 parametric excitation enhances the electric voltage. On the other hand, for higher reduced velocities, a 1:1 parametric excitation (i.e., the same as the natural frequency) enhances both oscillation amplitude and electric voltage. It has been also found that, depending on the parametric excitation frequency, the harvested electrical power can be amplified in 70% when compared to the case under no parametric excitation.

Theoretical predictions of latitude dependencies in the solar wind

NASA Technical Reports Server (NTRS)

Winge, C. R., Jr.; Coleman, P. J., Jr.

1974-01-01

Results are presented which were obtained with the Winge-Coleman model for theoretical predictions of latitudinal dependencies in the solar wind. A first-order expansion is described which allows analysis of first-order latitudinal variations in the coronal boundary conditions and results in a second-order partial differential equation for the perturbation stream function. Latitudinal dependencies are analytically separated out in the form of Legendre polynomials and their derivative, and are reduced to the solution of radial differential equations. This analysis is shown to supply an estimate of how large the coronal variation in latitude must be to produce an 11 km/sec/deg gradient in the radial velocity of the solar wind, assuming steady-state processes.

Measuring the reduced scattering coefficient and γ with SFR spectroscopy: studying the phase function dependence (Conference Presentation)

NASA Astrophysics Data System (ADS)

Post, Anouk L.; Zhang, Xu; Bosschaart, Nienke; Van Leeuwen, Ton G.; Sterenborg, Henricus J. C. M.; Faber, Dirk J.

2016-03-01

Both Optical Coherence Tomography (OCT) and Single Fiber Reflectance Spectroscopy (SFR) are used to determine various optical properties of tissue. We developed a method combining these two techniques to measure the scattering anisotropy (g1) and γ (=1-g2/1-g1), related to the 1st and 2nd order moments of the phase function. The phase function is intimately associated with the cellular organization and ultrastructure of tissue, physical parameters that may change during disease onset and progression. Quantification of these parameters may therefore allow for improved non-invasive, in vivo discrimination between healthy and diseased tissue. With SFR the reduced scattering coefficient and γ can be extracted from the reflectance spectrum (Kanick et al., Biomedical Optics Express 2(6), 2011). With OCT the scattering coefficient can be extracted from the signal as a function of depth (Faber et al., Optics Express 12(19), 2004). Consequently, by combining SFR and OCT measurements at the same wavelengths, the scattering anisotropy (g) can be resolved using µs'= µs*(1-g). We performed measurements on a suspension of silica spheres as a proof of principle. The SFR model for the reflectance as a function of the reduced scattering coefficient and γ is based on semi-empirical modelling. These models feature Monte-Carlo (MC) based model constants. The validity of these constants - and thus the accuracy of the estimated parameters - depends on the phase function employed in the MC simulations. Since the phase function is not known when measuring in tissue, we will investigate the influence of assuming an incorrect phase function on the accuracy of the derived parameters.

Improvements to image quality using hybrid and model-based iterative reconstructions: a phantom study.

PubMed

Aurumskjöld, Marie-Louise; Ydström, Kristina; Tingberg, Anders; Söderberg, Marcus

2017-01-01

The number of computed tomography (CT) examinations is increasing and leading to an increase in total patient exposure. It is therefore important to optimize CT scan imaging conditions in order to reduce the radiation dose. The introduction of iterative reconstruction methods has enabled an improvement in image quality and a reduction in radiation dose. To investigate how image quality depends on reconstruction method and to discuss patient dose reduction resulting from the use of hybrid and model-based iterative reconstruction. An image quality phantom (Catphan® 600) and an anthropomorphic torso phantom were examined on a Philips Brilliance iCT. The image quality was evaluated in terms of CT numbers, noise, noise power spectra (NPS), contrast-to-noise ratio (CNR), low-contrast resolution, and spatial resolution for different scan parameters and dose levels. The images were reconstructed using filtered back projection (FBP) and different settings of hybrid (iDose 4 ) and model-based (IMR) iterative reconstruction methods. iDose 4 decreased the noise by 15-45% compared with FBP depending on the level of iDose 4 . The IMR reduced the noise even further, by 60-75% compared to FBP. The results are independent of dose. The NPS showed changes in the noise distribution for different reconstruction methods. The low-contrast resolution and CNR were improved with iDose 4 , and the improvement was even greater with IMR. There is great potential to reduce noise and thereby improve image quality by using hybrid or, in particular, model-based iterative reconstruction methods, or to lower radiation dose and maintain image quality. © The Foundation Acta Radiologica 2016.

AnimalFinder: A semi-automated system for animal detection in time-lapse camera trap images

USGS Publications Warehouse

Price Tack, Jennifer L.; West, Brian S.; McGowan, Conor P.; Ditchkoff, Stephen S.; Reeves, Stanley J.; Keever, Allison; Grand, James B.

2017-01-01

Although the use of camera traps in wildlife management is well established, technologies to automate image processing have been much slower in development, despite their potential to drastically reduce personnel time and cost required to review photos. We developed AnimalFinder in MATLAB® to identify animal presence in time-lapse camera trap images by comparing individual photos to all images contained within the subset of images (i.e. photos from the same survey and site), with some manual processing required to remove false positives and collect other relevant data (species, sex, etc.). We tested AnimalFinder on a set of camera trap images and compared the presence/absence results with manual-only review with white-tailed deer (Odocoileus virginianus), wild pigs (Sus scrofa), and raccoons (Procyon lotor). We compared abundance estimates, model rankings, and coefficient estimates of detection and abundance for white-tailed deer using N-mixture models. AnimalFinder performance varied depending on a threshold value that affects program sensitivity to frequently occurring pixels in a series of images. Higher threshold values led to fewer false negatives (missed deer images) but increased manual processing time, but even at the highest threshold value, the program reduced the images requiring manual review by ~40% and correctly identified >90% of deer, raccoon, and wild pig images. Estimates of white-tailed deer were similar between AnimalFinder and the manual-only method (~1–2 deer difference, depending on the model), as were model rankings and coefficient estimates. Our results show that the program significantly reduced data processing time and may increase efficiency of camera trapping surveys.

Central Action of Peripherally Applied Botulinum Toxin Type A on Pain and Dural Protein Extravasation in Rat Model of Trigeminal Neuropathy

PubMed Central

Filipović, Boris; Matak, Ivica; Bach-Rojecky, Lidija; Lacković, Zdravko

2012-01-01

Background Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model. Methodology/Principal Findings Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg) into vibrissal pad. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue - plasma protein complexes. Presence of dural extravasation was also examined in orofacial formalin-induced pain. Unilateral IoNC, as well as formalin injection, produced bilateral dural extravasation. Single unilateral BoNT/A injection bilaterally reduced IoNC induced dural extravasation, as well as allodynia (lasting more than 2 weeks). Similarly, BoNT/A reduced formalin-induced pain and dural extravasation. Effects of BoNT/A on pain and dural extravasation in IoNC model were dependent on axonal transport through sensory neurons, as evidenced by colchicine injections (5 mM, 2 µl) into the trigeminal ganglion completely preventing BoNT/A effects. Conclusions/Significance Two different types of pain, IoNC and formalin, are accompanied by dural extravasation. The lasting effect of a unilateral injection of BoNT/A in experimental animals suggests that BoNT/A might have a long-term beneficial effect in craniofacial pain associated with dural neurogenic inflammation. Bilateral effects of BoNT/A and dependence on retrograde axonal transport suggest a central site of its action. PMID:22238656

Dynamic simulation of crime perpetration and reporting to examine community intervention strategies.

PubMed

Yonas, Michael A; Burke, Jessica G; Brown, Shawn T; Borrebach, Jeffrey D; Garland, Richard; Burke, Donald S; Grefenstette, John J

2013-10-01

To develop a conceptual computational agent-based model (ABM) to explore community-wide versus spatially focused crime reporting interventions to reduce community crime perpetrated by youth. Agents within the model represent individual residents and interact on a two-dimensional grid representing an abstract nonempirically grounded community setting. Juvenile agents are assigned initial random probabilities of perpetrating a crime and adults are assigned random probabilities of witnessing and reporting crimes. The agents' behavioral probabilities modify depending on the individual's experience with criminal behavior and punishment, and exposure to community crime interventions. Cost-effectiveness analyses assessed the impact of activating different percentages of adults to increase reporting and reduce community crime activity. Community-wide interventions were compared with spatially focused interventions, in which activated adults were focused in areas of highest crime prevalence. The ABM suggests that both community-wide and spatially focused interventions can be effective in reducing overall offenses, but their relative effectiveness may depend on the intensity and cost of the interventions. Although spatially focused intervention yielded localized reductions in crimes, such interventions were shown to move crime to nearby communities. Community-wide interventions can achieve larger reductions in overall community crime offenses than spatially focused interventions, as long as sufficient resources are available. The ABM demonstrates that community-wide and spatially focused crime strategies produce unique intervention dynamics influencing juvenile crime behaviors through the decisions and actions of community adults. It shows how such models might be used to investigate community-supported crime intervention programs by integrating community input and expertise and provides a simulated setting for assessing dimensions of cost comparison and intervention effect sustainability. ABM illustrates how intervention models might be used to investigate community-supported crime intervention programs.

Deer density and disease prevalence influence transmission of Chronic Wasting Disease in White-tailed Deer

USGS Publications Warehouse

Samuel, Michael D.; Richards, Bryan J.; Storm, Daniel J.; Rolley, Robert E.; Shelton, Paul; Nicholas S. Keuler,; Timothy R. Van Deelen,

2013-01-01

Host-parasite dynamics and strategies for managing infectious diseases of wildlife depend on the functional relationship between disease transmission rates and host density. However, the disease transmission function is rarely known for free-living wildlife, leading to uncertainty regarding the impacts of diseases on host populations and effective control actions. We evaluated the influence of deer density, landscape features, and soil clay content on transmission of chronic wasting disease (CWD) in young (<2-year-old) white-tailed deer (Odocoileus virginianus) in south-central Wisconsin, USA. We evaluated how frequency-dependent, density-dependent, and intermediate transmission models predicted CWD incidence rates in harvested yearling deer. An intermediate transmission model, incorporating both disease prevalence and density of infected deer, performed better than simple density- and frequency-dependent models. Our results indicate a combination of social structure, non-linear relationships between infectious contact and deer density, and distribution of disease among groups are important factors driving CWD infection in young deer. The landscape covariates % deciduous forest cover and forest edge density also were positively associated with infection rates, but soil clay content had no measurable influences on CWD transmission. Lack of strong density-dependent transmission rates indicates that controlling CWD by reducing deer density will be difficult. The consequences of non-linear disease transmission and aggregation of disease on cervid populations deserves further consideration.

Climate: Policy, Modeling, and Federal Priorities (Invited)

NASA Astrophysics Data System (ADS)

Koonin, S.; Department Of Energy Office Of The Under SecretaryScience

2010-12-01

The Administration has set ambitious national goals to reduce our dependence on fossil fuels and reduce anthropogenic greenhouse gas (GHG) emissions. The US and other countries involved in the U.N. Framework Convention on Climate Change continue to work toward a goal of establishing a viable treaty that would encompass limits on emissions and codify actions that nations would take to reduce emissions. These negotiations are informed by the science of climate change and by our understanding of how changes in technology and the economy might affect the overall climate in the future. I will describe the present efforts within the U.S. Department of Energy, and the federal government more generally, to address issues related to climate change. These include state-of-the-art climate modeling and uncertainty assessment, economic and climate scenario planning based on best estimates of different technology trajectories, adaption strategies for climate change, and monitoring and reporting for treaty verification.

Coral reefs reduce tsunami impact in model simulations

NASA Astrophysics Data System (ADS)

Kunkel, Catherine M.; Hallberg, Robert W.; Oppenheimer, Michael

2006-12-01

Significant buffering of the impact of tsunamis by coral reefs is suggested by limited observations and some anecdotal reports, particularly following the 2004 Indian Ocean tsunami. Here we simulate tsunami run-up on idealized topographies in one and two dimensions using a nonlinear shallow water model and show that a sufficiently wide barrier reef within a meter or two of the surface reduces run-up on land on the order of 50%. We studied topographies representative of volcanic islands (islands with no continental shelf) but our conclusions may pertain to other topographies. Effectiveness depends on the amplitude and wavelength of the incident tsunami, as well as the geometry and health of the reef and the offshore distance of the reef. Reducing the threat to reefs from anthropogenic nutrients, sedimentation, fishing practices, channel-building, and global warming would help to protect some islands against tsunamis.

Contraction and stress-dependent growth shape the forebrain of the early chicken embryo.

PubMed

Garcia, Kara E; Okamoto, Ruth J; Bayly, Philip V; Taber, Larry A

2017-01-01

During early vertebrate development, local constrictions, or sulci, form to divide the forebrain into the diencephalon, telencephalon, and optic vesicles. These partitions are maintained and exaggerated as the brain tube inflates, grows, and bends. Combining quantitative experiments on chick embryos with computational modeling, we investigated the biophysical mechanisms that drive these changes in brain shape. Chemical perturbations of contractility indicated that actomyosin contraction plays a major role in the creation of initial constrictions (Hamburger-Hamilton stages HH11-12), and fluorescent staining revealed that F-actin is circumferentially aligned at all constrictions. A finite element model based on these findings shows that the observed shape changes are consistent with circumferential contraction in these regions. To explain why sulci continue to deepen as the forebrain expands (HH12-20), we speculate that growth depends on wall stress. This idea was examined by including stress-dependent growth in a model with cerebrospinal fluid pressure and bending (cephalic flexure). The results given by the model agree with observed morphological changes that occur in the brain tube under normal and reduced eCSF pressure, quantitative measurements of relative sulcal depth versus time, and previously published patterns of cell proliferation. Taken together, our results support a biphasic mechanism for forebrain morphogenesis consisting of differential contractility (early) and stress-dependent growth (late). Copyright © 2016 Elsevier Ltd. All rights reserved.

First-principles X-ray absorption dose calculation for time-dependent mass and optical density.

PubMed

Berejnov, Viatcheslav; Rubinstein, Boris; Melo, Lis G A; Hitchcock, Adam P

2018-05-01

A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

Global growth and stability of agricultural yield decrease with pollinator dependence

PubMed Central

Garibaldi, Lucas A.; Aizen, Marcelo A.; Klein, Alexandra M.; Cunningham, Saul A.; Harder, Lawrence D.

2011-01-01

Human welfare depends on the amount and stability of agricultural production, as determined by crop yield and cultivated area. Yield increases asymptotically with the resources provided by farmers’ inputs and environmentally sensitive ecosystem services. Declining yield growth with increased inputs prompts conversion of more land to cultivation, but at the risk of eroding ecosystem services. To explore the interdependence of agricultural production and its stability on ecosystem services, we present and test a general graphical model, based on Jensen's inequality, of yield–resource relations and consider implications for land conversion. For the case of animal pollination as a resource influencing crop yield, this model predicts that incomplete and variable pollen delivery reduces yield mean and stability (inverse of variability) more for crops with greater dependence on pollinators. Data collected by the Food and Agriculture Organization of the United Nations during 1961–2008 support these predictions. Specifically, crops with greater pollinator dependence had lower mean and stability in relative yield and yield growth, despite global yield increases for most crops. Lower yield growth was compensated by increased land cultivation to enhance production of pollinator-dependent crops. Area stability also decreased with pollinator dependence, as it correlated positively with yield stability among crops. These results reveal that pollen limitation hinders yield growth of pollinator-dependent crops, decreasing temporal stability of global agricultural production, while promoting compensatory land conversion to agriculture. Although we examined crop pollination, our model applies to other ecosystem services for which the benefits to human welfare decelerate as the maximum is approached. PMID:21422295

Bottom-up coarse-grained models that accurately describe the structure, pressure, and compressibility of molecular liquids

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

Dunn, Nicholas J. H.; Noid, W. G., E-mail: wnoid@chem.psu.edu

2015-12-28

The present work investigates the capability of bottom-up coarse-graining (CG) methods for accurately modeling both structural and thermodynamic properties of all-atom (AA) models for molecular liquids. In particular, we consider 1, 2, and 3-site CG models for heptane, as well as 1 and 3-site CG models for toluene. For each model, we employ the multiscale coarse-graining method to determine interaction potentials that optimally approximate the configuration dependence of the many-body potential of mean force (PMF). We employ a previously developed “pressure-matching” variational principle to determine a volume-dependent contribution to the potential, U{sub V}(V), that approximates the volume-dependence of the PMF.more » We demonstrate that the resulting CG models describe AA density fluctuations with qualitative, but not quantitative, accuracy. Accordingly, we develop a self-consistent approach for further optimizing U{sub V}, such that the CG models accurately reproduce the equilibrium density, compressibility, and average pressure of the AA models, although the CG models still significantly underestimate the atomic pressure fluctuations. Additionally, by comparing this array of models that accurately describe the structure and thermodynamic pressure of heptane and toluene at a range of different resolutions, we investigate the impact of bottom-up coarse-graining upon thermodynamic properties. In particular, we demonstrate that U{sub V} accounts for the reduced cohesion in the CG models. Finally, we observe that bottom-up coarse-graining introduces subtle correlations between the resolution, the cohesive energy density, and the “simplicity” of the model.« less

Systematic study of α decay of nuclei around the Z =82 , N =126 shell closures within the cluster-formation model and proximity potential 1977 formalism

NASA Astrophysics Data System (ADS)

Deng, Jun-Gang; Zhao, Jie-Cheng; Chu, Peng-Cheng; Li, Xiao-Hua

2018-04-01

In the present work, we systematically study the α decay preformation factors Pα within the cluster-formation model and α decay half-lives by the proximity potential 1977 formalism for nuclei around Z =82 ,N =126 closed shells. The calculations show that the realistic Pα is linearly dependent on the product of valance protons (holes) and valance neutrons (holes) NpNn . It is consistent with our previous works [Sun et al., Phys. Rev. C 94, 024338 (2016), 10.1103/PhysRevC.94.024338; Deng et al., Phys. Rev. C 96, 024318 (2017), 10.1103/PhysRevC.96.024318], in which Pα are model dependent and extracted from the ratios of calculated α half-lives to experimental data. Combining with our previous works, we confirm that the valance proton-neutron interaction plays a key role in the α preformation for nuclei around Z =82 ,N =126 shell closures whether the Pα is model dependent or microcosmic. In addition, our calculated α decay half-lives by using the proximity potential 1977 formalism taking Pα evaluated by the cluster-formation model can well reproduce the experimental data and significantly reduce the errors.

Kinetics of gravity-driven slug flow in partially wettable capillaries of varying cross section

NASA Astrophysics Data System (ADS)

Nissan, Alon; Wang, Qiuling; Wallach, Rony

2016-11-01

A mathematical model for slug (finite liquid volume) motion in not-fully-wettable capillary tubes with sinusoidally varying cross-sectional areas was developed. The model, based on the Navier-Stokes equation, accounts for the full viscous terms due to nonuniform geometry, the inertial term, the slug's front and rear meniscus hysteresis effect, and dependence of contact angle on flow velocity (dynamic contact angle). The model includes a velocity-dependent film that is left behind the advancing slug, reducing its mass. The model was successfully verified experimentally by recording slug movement in uniform and sinusoidal capillary tubes with a gray-scale high-speed camera. Simulation showed that tube nonuniformity has a substantial effect on slug flow pattern: in a uniform tube it is monotonic and depends mainly on the slug's momentary mass/length; an undulating tube radius results in nonmonotonic flow characteristics. The static nonzero contact angle varies locally in nonuniform tubes owing to the additional effect of wall slope. Moreover, the nonuniform cross-sectional area induces slug acceleration, deceleration, blockage, and metastable-equilibrium locations. Increasing contact angle further amplifies the geometry effect on slug propagation. The developed model provides a modified means of emulating slug flow in differently wettable porous media for intermittent inlet water supply (e.g., raindrops on the soil surface).

Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

PubMed Central

Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

2015-01-01

Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

A video, text, and speech-driven realistic 3-d virtual head for human-machine interface.

PubMed

Yu, Jun; Wang, Zeng-Fu

2015-05-01

A multiple inputs-driven realistic facial animation system based on 3-D virtual head for human-machine interface is proposed. The system can be driven independently by video, text, and speech, thus can interact with humans through diverse interfaces. The combination of parameterized model and muscular model is used to obtain a tradeoff between computational efficiency and high realism of 3-D facial animation. The online appearance model is used to track 3-D facial motion from video in the framework of particle filtering, and multiple measurements, i.e., pixel color value of input image and Gabor wavelet coefficient of illumination ratio image, are infused to reduce the influence of lighting and person dependence for the construction of online appearance model. The tri-phone model is used to reduce the computational consumption of visual co-articulation in speech synchronized viseme synthesis without sacrificing any performance. The objective and subjective experiments show that the system is suitable for human-machine interaction.

Analyzing neuronal networks using discrete-time dynamics

NASA Astrophysics Data System (ADS)

Ahn, Sungwoo; Smith, Brian H.; Borisyuk, Alla; Terman, David

2010-05-01

We develop mathematical techniques for analyzing detailed Hodgkin-Huxley like models for excitatory-inhibitory neuronal networks. Our strategy for studying a given network is to first reduce it to a discrete-time dynamical system. The discrete model is considerably easier to analyze, both mathematically and computationally, and parameters in the discrete model correspond directly to parameters in the original system of differential equations. While these networks arise in many important applications, a primary focus of this paper is to better understand mechanisms that underlie temporally dynamic responses in early processing of olfactory sensory information. The models presented here exhibit several properties that have been described for olfactory codes in an insect’s Antennal Lobe. These include transient patterns of synchronization and decorrelation of sensory inputs. By reducing the model to a discrete system, we are able to systematically study how properties of the dynamics, including the complex structure of the transients and attractors, depend on factors related to connectivity and the intrinsic and synaptic properties of cells within the network.

Uniform California earthquake rupture forecast, version 2 (UCERF 2)

USGS Publications Warehouse

Field, E.H.; Dawson, T.E.; Felzer, K.R.; Frankel, A.D.; Gupta, V.; Jordan, T.H.; Parsons, T.; Petersen, M.D.; Stein, R.S.; Weldon, R.J.; Wills, C.J.

2009-01-01

The 2007 Working Group on California Earthquake Probabilities (WGCEP, 2007) presents the Uniform California Earthquake Rupture Forecast, Version 2 (UCERF 2). This model comprises a time-independent (Poisson-process) earthquake rate model, developed jointly with the National Seismic Hazard Mapping Program and a time-dependent earthquake-probability model, based on recent earthquake rates and stress-renewal statistics conditioned on the date of last event. The models were developed from updated statewide earthquake catalogs and fault deformation databases using a uniform methodology across all regions and implemented in the modular, extensible Open Seismic Hazard Analysis framework. The rate model satisfies integrating measures of deformation across the plate-boundary zone and is consistent with historical seismicity data. An overprediction of earthquake rates found at intermediate magnitudes (6.5 ??? M ???7.0) in previous models has been reduced to within the 95% confidence bounds of the historical earthquake catalog. A logic tree with 480 branches represents the epistemic uncertainties of the full time-dependent model. The mean UCERF 2 time-dependent probability of one or more M ???6.7 earthquakes in the California region during the next 30 yr is 99.7%; this probability decreases to 46% for M ???7.5 and to 4.5% for M ???8.0. These probabilities do not include the Cascadia subduction zone, largely north of California, for which the estimated 30 yr, M ???8.0 time-dependent probability is 10%. The M ???6.7 probabilities on major strike-slip faults are consistent with the WGCEP (2003) study in the San Francisco Bay Area and the WGCEP (1995) study in southern California, except for significantly lower estimates along the San Jacinto and Elsinore faults, owing to provisions for larger multisegment ruptures. Important model limitations are discussed.

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

PubMed Central

WILCOX, CHRISTOPHER S.; PEARLMAN, ADAM

2009-01-01

Nitroxides can undergo one- or two-electron reduction reactions to hydroxylamines or oxammonium cations, respectively, which themselves are interconvertible, thereby providing redox metabolic actions. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) is the most extensively studied nitroxide. It is a cell membrane-permeable amphilite that dismutates superoxide catalytically, facilitates hydrogen peroxide metabolism by catalase-like actions, and limits formation of toxic hydroxyl radicals produced by Fenton reactions. It is broadly effective in detoxifying these reactive oxygen species in cell and animal studies. When administered intravenously to hypertensive rodent models, tempol caused rapid and reversible dose-dependent reductions in blood pressure in 22 of 26 studies. This was accompanied by vasodilation, increased nitric oxide activity, reduced sympathetic nervous system activity at central and peripheral sites, and enhanced potassium channel conductance in blood vessels and neurons. When administered orally or by infusion over days or weeks to hypertensive rodent models, it reduced blood pressure in 59 of 68 studies. This was accompanied by correction of salt sensitivity and endothelial dysfunction and reduced agonist-evoked oxidative stress and contractility of blood vessels, reduced renal vascular resistance, and increased renal tissue oxygen tension. Thus, tempol is broadly effective in reducing blood pressure, whether given by acute intravenous injection or by prolonged administration, in a wide range of rodent models of hypertension. PMID:19112152

Density functional theory of electron transfer beyond the Born-Oppenheimer approximation: Case study of LiF

NASA Astrophysics Data System (ADS)

Li, Chen; Requist, Ryan; Gross, E. K. U.

2018-02-01

We perform model calculations for a stretched LiF molecule, demonstrating that nonadiabatic charge transfer effects can be accurately and seamlessly described within a density functional framework. In alkali halides like LiF, there is an abrupt change in the ground state electronic distribution due to an electron transfer at a critical bond length R = Rc, where an avoided crossing of the lowest adiabatic potential energy surfaces calls the validity of the Born-Oppenheimer approximation into doubt. Modeling the R-dependent electronic structure of LiF within a two-site Hubbard model, we find that nonadiabatic electron-nuclear coupling produces a sizable elongation of the critical Rc by 0.5 bohr. This effect is very accurately captured by a simple and rigorously derived correction, with an M-1 prefactor, to the exchange-correlation potential in density functional theory, M = reduced nuclear mass. Since this nonadiabatic term depends on gradients of the nuclear wave function and conditional electronic density, ∇Rχ(R) and ∇Rn(r, R), it couples the Kohn-Sham equations at neighboring R points. Motivated by an observed localization of nonadiabatic effects in nuclear configuration space, we propose a local conditional density approximation—an approximation that reduces the search for nonadiabatic density functionals to the search for a single function y(n).

A numerical study of magnetohydrodynamic transport of nanofluids over a vertical stretching sheet with exponential temperature-dependent viscosity and buoyancy effects

NASA Astrophysics Data System (ADS)

Akbar, Noreen Sher; Tripathi, Dharmendra; Khan, Zafar Hayat; Bég, O. Anwar

2016-09-01

In this paper, a mathematical study is conducted of steady incompressible flow of a temperature-dependent viscous nanofluid from a vertical stretching sheet under applied external magnetic field and gravitational body force effects. The Reynolds exponential viscosity model is deployed. Electrically-conducting nanofluids are considered which comprise a suspension of uniform dimension nanoparticles suspended in viscous base fluid. The nanofluid sheet is extended with a linear velocity in the axial direction. The Buonjiornio model is utilized which features Brownian motion and thermophoresis effects. The partial differential equations for mass, momentum, energy and species (nano-particle concentration) are formulated with magnetic body force term. Viscous and Joule dissipation effects are neglected. The emerging nonlinear, coupled, boundary value problem is solved numerically using the Runge-Kutta fourth order method along with a shooting technique. Graphical solutions for velocity, temperature, concentration field, skin friction and Nusselt number are presented. Furthermore stream function plots are also included. Validation with Nakamura's finite difference algorithm is included. Increasing nanofluid viscosity is observed to enhance temperatures and concentrations but to reduce velocity magnitudes. Nusselt number is enhanced with both thermal and species Grashof numbers whereas it is reduced with increasing thermophoresis parameter and Schmidt number. The model is applicable in nano-material manufacturing processes involving extruding sheets.

Implications of shale gas development for climate change.

PubMed

Newell, Richard G; Raimi, Daniel

2014-01-01

Advances in technologies for extracting oil and gas from shale formations have dramatically increased U.S. production of natural gas. As production expands domestically and abroad, natural gas prices will be lower than without shale gas. Lower prices have two main effects: increasing overall energy consumption, and encouraging substitution away from sources such as coal, nuclear, renewables, and electricity. We examine the evidence and analyze modeling projections to understand how these two dynamics affect greenhouse gas emissions. Most evidence indicates that natural gas as a substitute for coal in electricity production, gasoline in transport, and electricity in buildings decreases greenhouse gases, although as an electricity substitute this depends on the electricity mix displaced. Modeling suggests that absent substantial policy changes, increased natural gas production slightly increases overall energy use, more substantially encourages fuel-switching, and that the combined effect slightly alters economy wide GHG emissions; whether the net effect is a slight decrease or increase depends on modeling assumptions including upstream methane emissions. Our main conclusions are that natural gas can help reduce GHG emissions, but in the absence of targeted climate policy measures, it will not substantially change the course of global GHG concentrations. Abundant natural gas can, however, help reduce the costs of achieving GHG reduction goals.

Sounding Rocket Microgravity Experiments Elucidating Diffusive and Radiative Transport Effects on Flame Spread over Thermally-Thick Solids

NASA Technical Reports Server (NTRS)

Olson, Sandra L.; Hegde, U.; Bhattacharjee, S.; Deering, J. L.; Tang, L.; Altenkirch, R. A.

2003-01-01

A series of 6-minute microgravity combustion experiments of opposed flow flame spread over thermally-thick PMMA has been conducted to extend data previously reported at high opposed flows to almost two decades lower in flow. The effect of flow velocity on flame spread shows a square root power law dependence rather than the linear dependence predicted by thermal theory. The experiments demonstrate that opposed flow flame spread is viable to very low velocities and more robust than expected from the numerical model, which predicts that at very low velocities (less than 5 centimeters per second), flame spread rates fall off more rapidly as flow is reduced. It is hypothesized that the enhanced flame spread observed in the experiments may be due to three- dimensional hydrodynamic effects, which are not included in the zero-gravity, two-dimensional hydrodynamic model. The effect of external irradiation was found to be more complex that the model predicted over the 0-2 Watts per square centimeter range. In the experiments, the flame compensated for the increased irradiation by stabilizing farther from the surface. A surface energy balance reveals that the imposed flux was at least partially offset by a reduced conductive flux from the increased standoff distance, so that the effect on flame spread was weaker than anticipated.

The coupled response to slope-dependent basal melting

NASA Astrophysics Data System (ADS)

Little, C. M.; Goldberg, D. N.; Sergienko, O. V.; Gnanadesikan, A.

2009-12-01

Ice shelf basal melting is likely to be strongly controlled by basal slope. If ice shelves steepen in response to intensified melting, it suggests instability in the coupled ice-ocean system. The dynamic response of ice shelves governs what stable morphologies are possible, and thus the influence of melting on buttressing and grounding line migration. Simulations performed using a 3-D ocean model indicate that a simple form of slope-dependent melting is robust under more complex oceanographic conditions. Here we utilize this parameterization to investigate the shape and grounding line evolution of ice shelves, using a shallow-shelf approximation-based model that includes lateral drag. The distribution of melting substantially affects the shape and aspect ratio of unbuttressed ice shelves. Slope-dependent melting thins the ice shelf near the grounding line, reducing velocities throughout the shelf. Sharp ice thickness gradients evolve at high melting rates, yet grounding lines remain static. In foredeepened, buttressed ice shelves, changes in grounding line flux allow two additional options: stable or unstable retreat. Under some conditions, slope-dependent melting results in stable configurations even at high melt rates.

Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume fraction in clinical diffusion-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Jerome, N. P.; d'Arcy, J. A.; Feiweier, T.; Koh, D.-M.; Leach, M. O.; Collins, D. J.; Orton, M. R.

2016-12-01

The bi-exponential intravoxel-incoherent-motion (IVIM) model for diffusion-weighted MRI (DWI) fails to account for differential T 2 s in the model compartments, resulting in overestimation of pseudodiffusion fraction f. An extended model, T2-IVIM, allows removal of the confounding echo-time (TE) dependence of f, and provides direct compartment T 2 estimates. Two consented healthy volunteer cohorts (n  =  5, 6) underwent DWI comprising multiple TE/b-value combinations (Protocol 1: TE  =  62-102 ms, b  =  0-250 mm-2s, 30 combinations. Protocol 2: 8 b-values 0-800 mm-2s at TE  =  62 ms, with 3 additional b-values 0-50 mm-2s at TE  =  80, 100 ms scanned twice). Data from liver ROIs were fitted with IVIM at individual TEs, and with the T2-IVIM model using all data. Repeat-measures coefficients of variation were assessed for Protocol 2. Conventional IVIM modelling at individual TEs (Protocol 1) demonstrated apparent f increasing with longer TE: 22.4  ±  7% (TE  =  62 ms) to 30.7  ±  11% (TE  =  102 ms) T2-IVIM model fitting accounted for all data variation. Fitting of Protocol 2 data using T2-IVIM yielded reduced f estimates (IVIM: 27.9  ±  6%, T2-IVIM: 18.3  ±  7%), as well as T 2  =  42.1  ±  7 ms, 77.6  ±  30 ms for true and pseudodiffusion compartments, respectively. A reduced Protocol 2 dataset yielded comparable results in a clinical time frame (11 min). The confounding dependence of IVIM f on TE can be accounted for using additional b/TE images and the extended T2-IVIM model.

Optimal control for a tuberculosis model with undetected cases in Cameroon

NASA Astrophysics Data System (ADS)

Moualeu, D. P.; Weiser, M.; Ehrig, R.; Deuflhard, P.

2015-03-01

This paper considers the optimal control of tuberculosis through education, diagnosis campaign and chemoprophylaxis of latently infected. A mathematical model which includes important components such as undiagnosed infectious, diagnosed infectious, latently infected and lost-sight infectious is formulated. The model combines a frequency dependent and a density dependent force of infection for TB transmission. Through optimal control theory and numerical simulations, a cost-effective balance of two different intervention methods is obtained. Seeking to minimize the amount of money the government spends when tuberculosis remain endemic in the Cameroonian population, Pontryagin's maximum principle is used to characterize the optimal control. The optimality system is derived and solved numerically using the forward-backward sweep method (FBSM). Results provide a framework for designing cost-effective strategies for diseases with multiple intervention methods. It comes out that combining chemoprophylaxis and education, the burden of TB can be reduced by 80% in 10 years.

Loss of the Sexually Dimorphic Neuro-Inflammatory Response in a Transgenic Mouse Model of Huntington's Disease.

PubMed

Renoir, Thibault; Pang, Terence Y; Shikano, Yoshiko; Li, Shanshan; Hannan, Anthony J

2015-01-01

We previously reported sex differences in depression-like behaviours in a mouse model of Huntington's disease (HD). We hypothesized that immune response could also be altered in HD mice in a sex-dependent manner. Here, we assessed the molecular effects of an acute challenge with lipopolysaccharides (LPS) in female versus male R6/1 transgenic HD mice. We found an enhancement of LPS-induced TNF-α gene expression in the hypothalamus of female HD mice. TNF-α serum levels following LPS administration were also higher in female HD mice compared to WT animals. In contrast, male HD mice exhibited reduced LPS-induced TNF-α gene expression compared to WT animals. Our findings suggest that immune response to LPS is altered in HD mice in a sex-dependent manner. These pro-inflammatory abnormalities may contribute to the sexually dimorphic depression-like behaviours displayed by this mouse model of HD.

Tool use and the effect of action on the imagination.

PubMed

Schwartz, D L; Holton, D L

2000-11-01

Three studies examined the claim that hand movements can facilitate imagery for object rotations but that this facilitation depends on people's model of the situation. In Experiment 1, physically turning a block without vision reduced mental rotation times compared with imagining the same rotation without bodily movement. In Experiment 2, pulling a string from a spool facilitated participants' mental rotation of an object sitting on the spool. In Experiment 3, depending on participants' model of the spool, the exact same pulling movement facilitated or interfered with the exact same imagery transformation. Results of Experiments 2 and 3 indicate that the geometric characteristics of an action do not specify the trajectory of an imagery transformation. Instead, they point to people's ability to model the tools that mediate between motor activity and its environmental consequences and to transfer tool knowledge to a new situation.

Restricted maximum likelihood estimation of genetic principal components and smoothed covariance matrices

PubMed Central

Meyer, Karin; Kirkpatrick, Mark

2005-01-01

Principal component analysis is a widely used 'dimension reduction' technique, albeit generally at a phenotypic level. It is shown that we can estimate genetic principal components directly through a simple reparameterisation of the usual linear, mixed model. This is applicable to any analysis fitting multiple, correlated genetic effects, whether effects for individual traits or sets of random regression coefficients to model trajectories. Depending on the magnitude of genetic correlation, a subset of the principal component generally suffices to capture the bulk of genetic variation. Corresponding estimates of genetic covariance matrices are more parsimonious, have reduced rank and are smoothed, with the number of parameters required to model the dispersion structure reduced from k(k + 1)/2 to m(2k - m + 1)/2 for k effects and m principal components. Estimation of these parameters, the largest eigenvalues and pertaining eigenvectors of the genetic covariance matrix, via restricted maximum likelihood using derivatives of the likelihood, is described. It is shown that reduced rank estimation can reduce computational requirements of multivariate analyses substantially. An application to the analysis of eight traits recorded via live ultrasound scanning of beef cattle is given. PMID:15588566

Non-intrusive reduced order modeling of nonlinear problems using neural networks

NASA Astrophysics Data System (ADS)

Hesthaven, J. S.; Ubbiali, S.

2018-06-01

We develop a non-intrusive reduced basis (RB) method for parametrized steady-state partial differential equations (PDEs). The method extracts a reduced basis from a collection of high-fidelity solutions via a proper orthogonal decomposition (POD) and employs artificial neural networks (ANNs), particularly multi-layer perceptrons (MLPs), to accurately approximate the coefficients of the reduced model. The search for the optimal number of neurons and the minimum amount of training samples to avoid overfitting is carried out in the offline phase through an automatic routine, relying upon a joint use of the Latin hypercube sampling (LHS) and the Levenberg-Marquardt (LM) training algorithm. This guarantees a complete offline-online decoupling, leading to an efficient RB method - referred to as POD-NN - suitable also for general nonlinear problems with a non-affine parametric dependence. Numerical studies are presented for the nonlinear Poisson equation and for driven cavity viscous flows, modeled through the steady incompressible Navier-Stokes equations. Both physical and geometrical parametrizations are considered. Several results confirm the accuracy of the POD-NN method and show the substantial speed-up enabled at the online stage as compared to a traditional RB strategy.

Selective tissue factor/factor VIIa Inhibitor, ER-410660, and its prodrug, E5539, have anti-venous and anti-arterial thrombotic effects with a low risk of bleeding.

PubMed

Nagakura, Tadashi; Tabata, Kimiyo; Kira, Kazunobu; Hirota, Shinsuke; Clark, Richard; Matsuura, Fumiyoshi; Hiyoshi, Hironobu

2013-08-01

Many anticoagulant drugs target factors common to both the intrinsic and extrinsic coagulation pathways, which may lead to bleeding complications. Since the tissue factor (TF)/factor VIIa complex is associated with thrombosis onset and specifically activates the extrinsic coagulation pathway, compounds that inhibit this complex may provide therapeutic and/or prophylactic benefits with a decreased risk of bleeding. The in vitro enzyme profile and anticoagulation selectivity of the TF/VIIa complex inhibitor, ER-410660, and its prodrug E5539 were assessed using enzyme inhibitory and plasma clotting assays. In vivo effects of ER-410660 and E5539 were determined using a TF-induced, thrombin generation rhesus monkey model; a stasis-induced, venous thrombosis rat model; a photochemically induced, arterial thrombosis rat model; and a rat tail-cut bleeding model. ER-410660 selectively prolonged prothrombin time, but had a less potent anticoagulant effect on the intrinsic pathway. It also exhibited a dose-dependent inhibitory effect on thrombin generation caused by TF-injection in the rhesus monkey model. ER-410660 also reduced venous thrombus weights in the TF-administered, stasis-induced, venous thrombosis rat model and prolonged the occlusion time induced by arterial thrombus formation after vascular injury. The compound was capable of doubling the total bleeding time in the rat tail-cut model, albeit with a considerably higher dose compared to the effective dose in the venous and arterial thrombosis models. Moreover, E5539, an orally available ER-410660 prodrug, reduced the thrombin-anti-thrombin complex levels, induced by TF-injection, in a dose-dependent manner. Selective TF/VIIa inhibitors have potential as novel anticoagulants with a lower propensity for enhancing bleeding. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bayesian Techniques for Comparing Time-dependent GRMHD Simulations to Variable Event Horizon Telescope Observations

NASA Astrophysics Data System (ADS)

Kim, Junhan; Marrone, Daniel P.; Chan, Chi-Kwan; Medeiros, Lia; Özel, Feryal; Psaltis, Dimitrios

2016-12-01

The Event Horizon Telescope (EHT) is a millimeter-wavelength, very-long-baseline interferometry (VLBI) experiment that is capable of observing black holes with horizon-scale resolution. Early observations have revealed variable horizon-scale emission in the Galactic Center black hole, Sagittarius A* (Sgr A*). Comparing such observations to time-dependent general relativistic magnetohydrodynamic (GRMHD) simulations requires statistical tools that explicitly consider the variability in both the data and the models. We develop here a Bayesian method to compare time-resolved simulation images to variable VLBI data, in order to infer model parameters and perform model comparisons. We use mock EHT data based on GRMHD simulations to explore the robustness of this Bayesian method and contrast it to approaches that do not consider the effects of variability. We find that time-independent models lead to offset values of the inferred parameters with artificially reduced uncertainties. Moreover, neglecting the variability in the data and the models often leads to erroneous model selections. We finally apply our method to the early EHT data on Sgr A*.

BAYESIAN TECHNIQUES FOR COMPARING TIME-DEPENDENT GRMHD SIMULATIONS TO VARIABLE EVENT HORIZON TELESCOPE OBSERVATIONS

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

Kim, Junhan; Marrone, Daniel P.; Chan, Chi-Kwan

2016-12-01

The Event Horizon Telescope (EHT) is a millimeter-wavelength, very-long-baseline interferometry (VLBI) experiment that is capable of observing black holes with horizon-scale resolution. Early observations have revealed variable horizon-scale emission in the Galactic Center black hole, Sagittarius A* (Sgr A*). Comparing such observations to time-dependent general relativistic magnetohydrodynamic (GRMHD) simulations requires statistical tools that explicitly consider the variability in both the data and the models. We develop here a Bayesian method to compare time-resolved simulation images to variable VLBI data, in order to infer model parameters and perform model comparisons. We use mock EHT data based on GRMHD simulations to explore themore » robustness of this Bayesian method and contrast it to approaches that do not consider the effects of variability. We find that time-independent models lead to offset values of the inferred parameters with artificially reduced uncertainties. Moreover, neglecting the variability in the data and the models often leads to erroneous model selections. We finally apply our method to the early EHT data on Sgr A*.« less

Frequency-Dependent Selection: The High Potential for Permanent Genetic Variation in the Diallelic, Pairwise Interaction Model

PubMed Central

Asmussen, M. A.; Basnayake, E.

1990-01-01

A detailed analytic and numerical study is made of the potential for permanent genetic variation in frequency-dependent models based on pairwise interactions among genotypes at a single diallelic locus. The full equilibrium structure and qualitative gene-frequency dynamics are derived analytically for a symmetric model, in which pairwise fitnesses are chiefly determined by the genetic similarity of the individuals involved. This is supplemented by an extensive numerical investigation of the general model, the symmetric model, and nine other special cases. Together the results show that there is a high potential for permanent genetic diversity in the pairwise interaction model, and provide insight into the extent to which various forms of genotypic interactions enhance or reduce this potential. Technically, although two stable polymorphic equilibria are possible, the increased likelihood of maintaining both alleles, and the poor performance of protected polymorphism conditions as a measure of this likelihood, are primarily due to a greater variety and frequency of equilibrium patterns with one stable polymorphic equilibrium, in conjunction with a disproportionately large domain of attraction for stable internal equilibria. PMID:2341034

Exact Scheffé-type confidence intervals for output from groundwater flow models: 2. Combined use of hydrogeologic information and calibration data

USGS Publications Warehouse

Cooley, Richard L.

1993-01-01

Calibration data (observed values corresponding to model-computed values of dependent variables) are incorporated into a general method of computing exact Scheffé-type confidence intervals analogous to the confidence intervals developed in part 1 (Cooley, this issue) for a function of parameters derived from a groundwater flow model. Parameter uncertainty is specified by a distribution of parameters conditioned on the calibration data. This distribution was obtained as a posterior distribution by applying Bayes' theorem to the hydrogeologically derived prior distribution of parameters from part 1 and a distribution of differences between the calibration data and corresponding model-computed dependent variables. Tests show that the new confidence intervals can be much smaller than the intervals of part 1 because the prior parameter variance-covariance structure is altered so that combinations of parameters that give poor model fit to the data are unlikely. The confidence intervals of part 1 and the new confidence intervals can be effectively employed in a sequential method of model construction whereby new information is used to reduce confidence interval widths at each stage.

Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development

PubMed Central

Jäckel, Sven; Saffarzadeh, Mona; Langer, Florian

2017-01-01

Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity, and the coagulation and complement cascades. Here we show in a tissue factor (TF)–dependent model of flow restriction-induced venous thrombosis that complement factors make distinct contributions to platelet activation and fibrin deposition. Complement factor 3 (C3) deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro. Initial fibrin deposition at the vessel wall over 6 hours in this model was dependent on protein disulfide isomerase (PDI) and TF expression by myeloid cells, but did not require neutrophil extracellular trap formation involving peptidyl arginine deiminase 4. In contrast to C3−/− mice, C5-deficient mice had no apparent defect in platelet activation in vitro, and vessel wall platelet deposition and initial hemostasis in vivo. However, fibrin formation, the exposure of negatively charged phosphatidylserine (PS) on adherent leukocytes, and clot burden after 48 hours were significantly reduced in C5−/− mice compared with wild-type controls. These results delineate that C3 plays specific roles in platelet activation independent of formation of the terminal complement complex and provide in vivo evidence for contributions of complement-dependent membrane perturbations to prothrombotic TF activation on myeloid cells. PMID:28223279

In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

PubMed Central

Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

2015-01-01

The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

Classifying geometric variability by dominant eigenmodes of deformation in regressing tumours during active breath-hold lung cancer radiotherapy

NASA Astrophysics Data System (ADS)

Badawi, Ahmed M.; Weiss, Elisabeth; Sleeman, William C., IV; Hugo, Geoffrey D.

2012-01-01

The purpose of this study is to develop and evaluate a lung tumour interfraction geometric variability classification scheme as a means to guide adaptive radiotherapy and improve measurement of treatment response. Principal component analysis (PCA) was used to generate statistical shape models of the gross tumour volume (GTV) for 12 patients with weekly breath hold CT scans. Each eigenmode of the PCA model was classified as ‘trending’ or ‘non-trending’ depending on whether its contribution to the overall GTV variability included a time trend over the treatment course. Trending eigenmodes were used to reconstruct the original semi-automatically delineated GTVs into a reduced model containing only time trends. Reduced models were compared to the original GTVs by analyzing the reconstruction error in the GTV and position. Both retrospective (all weekly images) and prospective (only the first four weekly images) were evaluated. The average volume difference from the original GTV was 4.3% ± 2.4% for the trending model. The positional variability of the GTV over the treatment course, as measured by the standard deviation of the GTV centroid, was 1.9 ± 1.4 mm for the original GTVs, which was reduced to 1.2 ± 0.6 mm for the trending-only model. In 3/13 cases, the dominant eigenmode changed class between the prospective and retrospective models. The trending-only model preserved GTV and shape relative to the original GTVs, while reducing spurious positional variability. The classification scheme appears feasible for separating types of geometric variability by time trend.

Trimming a hazard logic tree with a new model-order-reduction technique

USGS Publications Warehouse

Porter, Keith; Field, Edward; Milner, Kevin R

2017-01-01

The size of the logic tree within the Uniform California Earthquake Rupture Forecast Version 3, Time-Dependent (UCERF3-TD) model can challenge risk analyses of large portfolios. An insurer or catastrophe risk modeler concerned with losses to a California portfolio might have to evaluate a portfolio 57,600 times to estimate risk in light of the hazard possibility space. Which branches of the logic tree matter most, and which can one ignore? We employed two model-order-reduction techniques to simplify the model. We sought a subset of parameters that must vary, and the specific fixed values for the remaining parameters, to produce approximately the same loss distribution as the original model. The techniques are (1) a tornado-diagram approach we employed previously for UCERF2, and (2) an apparently novel probabilistic sensitivity approach that seems better suited to functions of nominal random variables. The new approach produces a reduced-order model with only 60 of the original 57,600 leaves. One can use the results to reduce computational effort in loss analyses by orders of magnitude.

Nonlinear aeroacoustic characterization of Helmholtz resonators with a local-linear neuro-fuzzy network model

NASA Astrophysics Data System (ADS)

Förner, K.; Polifke, W.

2017-10-01

The nonlinear acoustic behavior of Helmholtz resonators is characterized by a data-based reduced-order model, which is obtained by a combination of high-resolution CFD simulation and system identification. It is shown that even in the nonlinear regime, a linear model is capable of describing the reflection behavior at a particular amplitude with quantitative accuracy. This observation motivates to choose a local-linear model structure for this study, which consists of a network of parallel linear submodels. A so-called fuzzy-neuron layer distributes the input signal over the linear submodels, depending on the root mean square of the particle velocity at the resonator surface. The resulting model structure is referred to as an local-linear neuro-fuzzy network. System identification techniques are used to estimate the free parameters of this model from training data. The training data are generated by CFD simulations of the resonator, with persistent acoustic excitation over a wide range of frequencies and sound pressure levels. The estimated nonlinear, reduced-order models show good agreement with CFD and experimental data over a wide range of amplitudes for several test cases.

Galleria mellonella as an in vivo model for assessing the efficacy of antimicrobial agents against Enterobacter cloacae infection.

PubMed

Yang, Hai-Fei; Pan, Ai-Jun; Hu, Li-Fen; Liu, Yan-Yan; Cheng, Jun; Ye, Ying; Li, Jia-Bin

2017-02-01

Enterobacter cloacae is a well-recognized nosocomial pathogen. Use of a rapid, in vivo infection model for E. cloacae that can determine the efficacy of antibiotic therapies could help facilitate screening for new treatments. Nonmammalian model systems of infection, such as Galleria mellonella, have significant logistical and ethical advantages over mammalian models. We utilized G. mellonella larvae to determine the utility of this infection model to study antibacterial efficacy. G. mellonella killing with heat-killed or live clinical isolates (E. cloacae GN1059 and GN0791) was tested. We also investigated the effect of postinoculation incubation temperature on the survival of infected larvae. The protection of administration of antibiotics to infected larvae was investigated. Finally, we determined the G. mellonella hemolymph burden of E. cloacae after administration of different antibiotics. With live bacterial inocula, G. mellonella killing was significantly dependent on the number of E. cloacae cells injected in a dose-dependent manner. Further, we observed that survival was reduced with increasing the postinoculation temperature. Treatment of a lethal E. cloacae infection with antibiotics that had in vitro activity significantly prolonged the survival of larvae compared with treatment with antibiotics to which the bacteria were resistant. The therapeutic benefit arising from administration of antibiotic correlated with a reduced burden of E. cloacae cells in the hemolymph. The G. mellonella infection model has the potential to be used to facilitate the in vivo study of host-pathogen interactions in E. cloacae and the efficacy of antibacterial agents. Copyright © 2014. Published by Elsevier B.V.

[Changes of telemetry electrical activity in the infralimbic cortex of morphine-dependent rats with extinguished drug-seeking behavior].

PubMed

Li, Jing; Pan, Qunwan; Zhu, Zaiman; Li, Min; Bai, Yu; Yu, Ran

2015-05-01

To investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior. SD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system. In rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period. Morphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.

Diffusion in different models of active Brownian motion

NASA Astrophysics Data System (ADS)

Lindner, B.; Nicola, E. M.

2008-04-01

Active Brownian particles (ABP) have served as phenomenological models of self-propelled motion in biology. We study the effective diffusion coefficient of two one-dimensional ABP models (simplified depot model and Rayleigh-Helmholtz model) differing in their nonlinear friction functions. Depending on the choice of the friction function the diffusion coefficient does or does not attain a minimum as a function of noise intensity. We furthermore discuss the case of an additional bias breaking the left-right symmetry of the system. We show that this bias induces a drift and that it generally reduces the diffusion coefficient. For a finite range of values of the bias, both models can exhibit a maximum in the diffusion coefficient vs. noise intensity.

Wharton's Jelly Mesenchymal Stem Cells Protect the Immature Brain in Rats and Modulate Cell Fate.

PubMed

Mueller, Martin; Oppliger, Byron; Joerger-Messerli, Marianne; Reinhart, Ursula; Barnea, Eytan; Paidas, Michael; Kramer, Boris W; Surbek, Daniel V; Schoeberlein, Andreina

2017-02-15

The development of a mammalian brain is a complex and long-lasting process. Not surprisingly, preterm birth is the leading cause of death in newborns and children. Advances in perinatal care reduced mortality, but morbidity still represents a major burden. New therapeutic approaches are thus desperately needed. Given that mesenchymal stem/stromal cells (MSCs) emerged as a promising candidate for cell therapy, we transplanted MSCs derived from the Wharton's Jelly (WJ-MSCs) to reduce the burden of immature brain injury in a murine animal model. WJ-MSCs transplantation resulted in protective activity characterized by reduced myelin loss and astroglial activation. WJ-MSCs improved locomotor behavior as well. To address the underlying mechanisms, we tested the key regulators of responses to DNA-damaging agents, such as cyclic AMP-dependent protein kinase/calcium-dependent protein kinase (PKA/PKC), cyclin-dependent kinase (CDK), ataxia-telangiectasia-mutated/ATM- and Rad3-related (ATM/ATR) substrates, protein kinase B (Akt), and 14-3-3 binding protein partners. We characterized WJ-MSCs using a specific profiler polymerase chain reaction array. We provide evidence that WJ-MSCs target pivotal regulators of the cell fate such as CDK/14-3-3/Akt signaling. We identified leukemia inhibitory factor as a potential candidate of WJ-MSCs' induced modifications as well. We hypothesize that WJ-MSCs may exert adaptive responses depending on the type of injury they are facing, making them prominent candidates for cell therapy in perinatal injuries.

Reduced anterior insula, enlarged amygdala in alcoholism and associated depleted von Economo neurons

PubMed Central

Senatorov, Vladimir V.; Damadzic, Ruslan; Mann, Claire L.; Schwandt, Melanie L.; George, David T.; Hommer, Daniel W.; Heilig, Markus

2015-01-01

The insula, a structure involved in higher order representation of interoceptive states, has recently been implicated in drug craving and social stress. Here, we performed brain magnetic resonance imaging to measure volumes of the insula and amygdala, a structure with reciprocal insular connections, in 26 alcohol-dependent patients and 24 healthy volunteers (aged 22–56 years, nine females in each group). We used an established morphometry method to quantify total and regional insular volumes. Volumetric measurements of the amygdala were obtained using a model-based segmentation/registration tool. In alcohol-dependent patients, anterior insula volumes were bilaterally reduced compared to healthy volunteers (left by 10%, right by 11%, normalized to total brain volumes). Furthermore, alcohol-dependent patients, compared with healthy volunteers, had bilaterally increased amygdala volumes. The left amygdala was increased by 28% and the right by 29%, normalized to total brain volumes. Post-mortem studies of the anterior insula showed that the reduced anterior insular volume may be associated with a population of von Economo neurons, which were 60% diminished in subjects with a history of alcoholism (n = 6) as compared to subjects without a history of alcoholism (n = 6) (aged 32–56 years, all males). The pattern of neuroanatomical change observed in our alcohol-dependent patients might result in a loss of top-down control of amygdala function, potentially contributing to impaired social cognition as well as an inability to control negatively reinforced alcohol seeking and use. PMID:25367022

A comparison of time dependent Cox regression, pooled logistic regression and cross sectional pooling with simulations and an application to the Framingham Heart Study.

PubMed

Ngwa, Julius S; Cabral, Howard J; Cheng, Debbie M; Pencina, Michael J; Gagnon, David R; LaValley, Michael P; Cupples, L Adrienne

2016-11-03

Typical survival studies follow individuals to an event and measure explanatory variables for that event, sometimes repeatedly over the course of follow up. The Cox regression model has been used widely in the analyses of time to diagnosis or death from disease. The associations between the survival outcome and time dependent measures may be biased unless they are modeled appropriately. In this paper we explore the Time Dependent Cox Regression Model (TDCM), which quantifies the effect of repeated measures of covariates in the analysis of time to event data. This model is commonly used in biomedical research but sometimes does not explicitly adjust for the times at which time dependent explanatory variables are measured. This approach can yield different estimates of association compared to a model that adjusts for these times. In order to address the question of how different these estimates are from a statistical perspective, we compare the TDCM to Pooled Logistic Regression (PLR) and Cross Sectional Pooling (CSP), considering models that adjust and do not adjust for time in PLR and CSP. In a series of simulations we found that time adjusted CSP provided identical results to the TDCM while the PLR showed larger parameter estimates compared to the time adjusted CSP and the TDCM in scenarios with high event rates. We also observed upwardly biased estimates in the unadjusted CSP and unadjusted PLR methods. The time adjusted PLR had a positive bias in the time dependent Age effect with reduced bias when the event rate is low. The PLR methods showed a negative bias in the Sex effect, a subject level covariate, when compared to the other methods. The Cox models yielded reliable estimates for the Sex effect in all scenarios considered. We conclude that survival analyses that explicitly account in the statistical model for the times at which time dependent covariates are measured provide more reliable estimates compared to unadjusted analyses. We present results from the Framingham Heart Study in which lipid measurements and myocardial infarction data events were collected over a period of 26 years.

Influence of climate drivers on colonization and extinction dynamics of wetland-dependent species

USGS Publications Warehouse

Ray, Andrew M.; Gould, William R.; Hossack, Blake R.; Sepulveda, Adam; Thoma, David P.; Patla, Debra A.; Daley, Rob; Al-Chokhachy, Robert K.

2016-01-01

Freshwater wetlands are particularly vulnerable to climate change. Specifically, changes in temperature, precipitation, and evapotranspiration (i.e., climate drivers) are likely to alter flooding regimes of wetlands and affect the vital rates, abundance, and distributions of wetland-dependent species. Amphibians may be among the most climate-sensitive wetland-dependent groups, as many species rely on shallow or intermittently flooded wetland habitats for breeding. Here, we integrated multiple years of high-resolution gridded climate and amphibian monitoring data from Grand Teton and Yellowstone National Parks to explicitly model how variations in climate drivers and habitat conditions affect the occurrence and breeding dynamics (i.e., annual extinction and colonization rates) of amphibians. Our results showed that models incorporating climate drivers outperformed models of amphibian breeding dynamics that were exclusively habitat based. Moreover, climate-driven variation in extinction rates, but not colonization rates, disproportionately influenced amphibian occupancy in monitored wetlands. Long-term monitoring from national parks coupled with high-resolution climate data sets will be crucial to describing population dynamics and characterizing the sensitivity of amphibians and other wetland-dependent species to climate change. Further, long-term monitoring of wetlands in national parks will help reduce uncertainty surrounding wetland resources and strengthen opportunities to make informed, science-based decisions that have far-reaching benefits.

Vertical dependence of black carbon, sulphate and biomass burning aerosol radiative forcing

NASA Astrophysics Data System (ADS)

Samset, Bjørn H.; Myhre, Gunnar

2011-12-01

A global radiative transfer model is used to calculate the vertical profile of shortwave radiative forcing from a prescribed amount of aerosols. We study black carbon (BC), sulphate (SO4) and a black and organic carbon mixture typical of biomass burning (BIO), by prescribing aerosol burdens in layers between 1000 hPa and 20 hPa and calculating the resulting direct radiative forcing divided by the burden (NDRF). We find a strong sensitivity in the NDRF for BC with altitude, with a tenfold increase between BC close to the surface and the lower part of the stratosphere. Clouds are a major contributor to this dependence with altitude, but other factors also contribute. We break down and explain the different physical contributors to this strong sensitivity. The results show a modest regional dependence of the altitudinal dependence of BC NDRF between industrial regions, while for regions with properties deviating from the global mean NDRF variability is significant. Variations due to seasons and interannual changes in cloud conditions are found to be small. We explore the effect that large altitudinal variation in NDRF may have on model estimates of BC radiative forcing when vertical aerosol distributions are insufficiently constrained, and discuss possible applications of the present results for reducing inter-model differences.

Building a Habitat Conversion Model for San Francisco Bay Wetlands: A Multi-species Approach for Integrating GIS and Field Data

Treesearch

Diana Stralberg; Nils Warnock; Nadav Nur; Hildie Spautz; Gary W. Page

2005-01-01

More than 80 percent of San Francisco Bay's original tidal wetlands have been altered or displaced, reducing available habitat for a range of tidal marsh-dependent species, including the Federally listed California Clapper Rail (Rallus longirostris obsoletus) and three endemic Song Sparrow (Melospiza melodia) subspecies. In...

Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models

PubMed Central

Bisht, Savita; Karikari, Collins; Garrido-Laguna, Ignacio; Rasheed, Zeshaan; Ottenhof, Niki A; Dadon, Tikva; Alvarez, Hector; Fendrich, Volker; Rajeshkumar, NV; Matsui, William; Brossart, Peter; Hidalgo, Manuel; Bannerji, Rajat

2011-01-01

Pancreatic cancer is one of the most lethal of human malignancies, and potent therapeutic options are lacking. Inhibition of cell cycle progression through pharmacological blockade of cyclin-dependent kinases (CDK) has been suggested as a potential treatment option for human cancers with deregulated cell cycle control. Dinaciclib (SCH727965) is a novel small molecule multi-CDK inhibitor with low nanomolar potency against CDK1, CDK2, CDK5 and CDK9 that has shown favorable toxicity and efficacy in preliminary mouse experiments, and has been well tolerated in Phase I clinical trials. In the current study, the therapeutic efficacy of SCH727965 on human pancreatic cancer cells was tested using in vitro and in vivo model systems. Treatment with SCH727965 significantly reduced in vitro cell growth, motility and colony formation in soft agar of MIAPaCa-2 and Pa20C cells. These phenotypic changes were accompanied by marked reduction of phosphorylation of Retinoblastoma (Rb) and reduced activation of RalA. Single agent therapy with SCH727965 (40 mg/kg i.p. twice weekly) for 4 weeks significantly reduced subcutaneous tumor growth in 10/10 (100%) of tested low-passage human pancreatic cancer xenografts. Treatment of low passage pancreatic cancer xenografts with a combination of SCH727965 and gemcitabine was significantly more effective than either agent alone. Gene Set Enrichment Analysis identified overrepresentation of the Notch and Transforming Growth Factor-β (TGFβ) signaling pathways in the xenografts least responsive to SCH727965 treatment. Treatment with the cyclin-dependent kinase inhibitor SCH727965 alone or in combination is a highly promising novel experimental therapeutic strategy against pancreatic cancer. PMID:21768779

Leaky gate model: intensity-dependent coding of pain and itch in the spinal cord

PubMed Central

Sun, Shuohao; Xu, Qian; Guo, Changxiong; Guan, Yun; Liu, Qin; Dong, Xinzhong

2017-01-01

SUMMARY Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. When activated, these Grp+ neurons generated rarely-seen simultaneous robust pain and itch responses that were intensity-dependent. Accordingly, we propose a “leaky gate” model, in which Grp+ neurons transmit both itch and weak pain signals, however upon strong painful stimuli the recruitment of endogenous opioids works to close this gate, reducing overwhelming pain generated by parallel pathways. Consistent with our model, loss of these Grp+ neurons increased pain responses while itch was decreased. Our new model serves as an example of non-monotonic coding in the spinal cord and better explains observations in human psychophysical studies. PMID:28231466

An economic production model for deteriorating items and time dependent demand with rework and multiple production setups

NASA Astrophysics Data System (ADS)

Uthayakumar, R.; Tharani, S.

2017-12-01

Recently, much emphasis has given to study the control and maintenance of production inventories of the deteriorating items. Rework is one of the main issues in reverse logistic and green supply chain, since it can reduce production cost and the environmental problem. Many researchers have focused on developing rework model, but few of them have developed model for deteriorating items. Due to this fact, we take up productivity and rework with deterioration as the major concern in this paper. In this paper, a production-inventory model with deteriorative items in which one cycle has n production setups and one rework setup (n, 1) policy is considered for deteriorating items with stock-dependent demand in case 1 and exponential demand in case 2. An effective iterative solution procedure is developed to achieve optimal time, so that the total cost of the system is minimized. Numerical and sensitivity analyses are discussed to examine the outcome of the proposed solution procedure presented in this research.

Forecasting Temporal Dynamics of Cutaneous Leishmaniasis in Northeast Brazil

PubMed Central

Lewnard, Joseph A.; Jirmanus, Lara; Júnior, Nivison Nery; Machado, Paulo R.; Glesby, Marshall J.; Ko, Albert I.; Carvalho, Edgar M.; Schriefer, Albert; Weinberger, Daniel M.

2014-01-01

Introduction Cutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions. Methodology/Principal Findings We fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation. Significance These outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets. PMID:25356734

Forecasting temporal dynamics of cutaneous leishmaniasis in Northeast Brazil.

PubMed

Lewnard, Joseph A; Jirmanus, Lara; Júnior, Nivison Nery; Machado, Paulo R; Glesby, Marshall J; Ko, Albert I; Carvalho, Edgar M; Schriefer, Albert; Weinberger, Daniel M

2014-10-01

Cutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions. We fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation. These outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets.

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

N.D. Francis

The objective of this calculation is to develop a time dependent in-drift effective thermal conductivity parameter that will approximate heat conduction, thermal radiation, and natural convection heat transfer using a single mode of heat transfer (heat conduction). In order to reduce the physical and numerical complexity of the heat transfer processes that occur (and must be modeled) as a result of the emplacement of heat generating wastes, a single parameter will be developed that approximates all forms of heat transfer from the waste package surface to the drift wall (or from one surface exchanging heat with another). Subsequently, with thismore » single parameter, one heat transfer mechanism (e.g., conduction heat transfer) can be used in the models. The resulting parameter is to be used as input in the drift-scale process-level models applied in total system performance assessments for the site recommendation (TSPA-SR). The format of this parameter will be a time-dependent table for direct input into the thermal-hydrologic (TH) and the thermal-hydrologic-chemical (THC) models.« less

Efficient prediction of terahertz quantum cascade laser dynamics from steady-state simulations

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

Agnew, G.; Lim, Y. L.; Nikolić, M.

2015-04-20

Terahertz-frequency quantum cascade lasers (THz QCLs) based on bound-to-continuum active regions are difficult to model owing to their large number of quantum states. We present a computationally efficient reduced rate equation (RE) model that reproduces the experimentally observed variation of THz power with respect to drive current and heat-sink temperature. We also present dynamic (time-domain) simulations under a range of drive currents and predict an increase in modulation bandwidth as the current approaches the peak of the light–current curve, as observed experimentally in mid-infrared QCLs. We account for temperature and bias dependence of the carrier lifetimes, gain, and injection efficiency,more » calculated from a full rate equation model. The temperature dependence of the simulated threshold current, emitted power, and cut-off current are thus all reproduced accurately with only one fitting parameter, the interface roughness, in the full REs. We propose that the model could therefore be used for rapid dynamical simulation of QCL designs.« less

The Dependence of Tropical Cyclone Count and Size on Rotation Rate

NASA Astrophysics Data System (ADS)

Chavas, D. R.; Reed, K. A.

2017-12-01

Both theory and idealized equilibrium modeling studies indicate that tropical cyclone size decreases with background rotation rate. In contrast, in real-world observations size tends to increase with latitude. Here we seek to resolve this apparent contradiction via a set of reduced-complexity global aquaplanet simulations with varying planetary rotation rates using the NCAR Community Atmosphere Model 5. The latitudinal distribution of both storm count and size are found to vary markedly with rotation rate, yielding insight into the dynamical constraints on tropical cyclone activity on a rotating planet. Moreover, storm size is found to vary non-monotonically with latitude, indicating that non-equilibrium effects are crucial to the life-cycle evolution of size in nature. Results are then compared to experiments in idealized, time-dependent limited-area modeling simulations using CM1 in axisymmetric and three-dimensional geometry. Taken together, this hierarchy of models is used to quantify the role of equilibrium versus transient controls on storm size and the relevance of each to real storms in nature.

Rimonabant reduces the essential value of food in the genetically obese Zucker rat: an exponential demand analysis.

PubMed

Rasmussen, Erin B; Reilly, William; Buckley, Jessica; Boomhower, Steven R

2012-02-01

Research on free-food intake suggests that cannabinoids are implicated in the regulation of feeding. Few studies, however, have characterized how environmental factors that affect food procurement interact with cannabinoid drugs that reduce food intake. Demand analysis provides a framework to understand how cannabinoid blockers, such as rimonabant, interact with effort in reducing demand for food. The present study examined the effects rimonabant had on demand for sucrose in obese Zucker rats when effort to obtain food varied and characterized the data using the exponential ("essential value") model of demand. Twenty-nine male (15 lean, 14 obese) Zucker rats lever-pressed under eight fixed ratio (FR) schedules of sucrose reinforcement, in which the number of lever-presses to gain access to a single sucrose pellet varied between 1 and 300. After behavior stabilized under each FR schedule, acute doses of rimonabant (1-10mg/kg) were administered prior to some sessions. The number of food reinforcers and responses in each condition was averaged and the exponential and linear demand equations were fit to the data. These demand equations quantify the value of a reinforcer by its sensitivity to price (FR) increases. Under vehicle conditions, obese Zucker rats consumed more sucrose pellets than leans at smaller fixed ratios; however, they were equally sensitive to price increases with both models of demand. Rimonabant dose-dependently reduced reinforcers and responses for lean and obese rats across all FR schedules. Data from the exponential analysis suggest that rimonabant dose-dependently increased elasticity, i.e., reduced the essential value of sucrose, a finding that is consistent with graphical depictions of normalized demand curves. Copyright © 2011 Elsevier Inc. All rights reserved.

The ARPA-E Innovation Model: A Glimpse into the Future of Automotive Battery Technology

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

Gur, Ilan

2014-03-07

The Department of Energy's Advanced Research Projects Agency-Energy (ARPA-E) focuses on funding game-changing R&D aimed at reducing U.S. foreign energy dependence and emissions. ARPA-E has made a strong commitment to support breakthrough energy storage technologies that can accelerate the mass adoption of electrified vehicles. This presentation will highlight the range of ARPA-E's efforts in this area, offering a glimpse into the ARPA-E innovation model and the future of automotive battery technology.

The ARPA-E Innovation Model: A Glimpse into the Future of Automotive Battery Technology

ScienceCinema

Gur, Ilan (Program Director and Senior Advisor, ARPA-E)

2018-02-02

The Department of Energy's Advanced Research Projects Agency-Energy (ARPA-E) focuses on funding game-changing R&D aimed at reducing U.S. foreign energy dependence and emissions. ARPA-E has made a strong commitment to support breakthrough energy storage technologies that can accelerate the mass adoption of electrified vehicles. This presentation will highlight the range of ARPA-E's efforts in this area, offering a glimpse into the ARPA-E innovation model and the future of automotive battery technology.

Coral–algal phase shifts alter fish communities and reduce fisheries production

PubMed Central

Ainsworth, Cameron H; Mumby, Peter J

2015-01-01

Anthropogenic stress has been shown to reduce coral coverage in ecosystems all over the world. A phase shift towards an algae-dominated system may accompany coral loss. In this case, the composition of the reef-associated fish assemblage will change and human communities relying on reef fisheries for income and food security may be negatively impacted. We present a case study based on the Raja Ampat Archipelago in Eastern Indonesia. Using a dynamic food web model, we simulate the loss of coral reefs with accompanied transition towards an algae-dominated state and quantify the likely change in fish populations and fisheries productivity. One set of simulations represents extreme scenarios, including 100% loss of coral. In this experiment, ecosystem changes are driven by coral loss itself and a degree of habitat dependency by reef fish is assumed. An alternative simulation is presented without assumed habitat dependency, where changes to the ecosystem are driven by historical observations of reef fish communities when coral is lost. The coral–algal phase shift results in reduced biodiversity and ecosystem maturity. Relative increases in the biomass of small-bodied fish species mean higher productivity on reefs overall, but much reduced landings of traditionally targeted species. PMID:24953835

Emissions pathways, climate change, and impacts on California

USGS Publications Warehouse

Hayhoe, K.; Cayan, D.; Field, C.B.; Frumhoff, P.C.; Maurer, E.P.; Miller, N.L.; Moser, S.C.; Schneider, S.H.; Cahill, K.N.; Cleland, E.E.; Dale, L.; Drapek, R.; Hanemann, R.M.; Kalkstein, L.S.; Lenihan, J.; Lunch, C.K.; Neilson, R.P.; Sheridan, S.C.; Verville, J.H.

2004-01-01

The magnitude of future climate change depends substantially on the greenhouse gas emission pathways we choose. Here we explore the implications of the highest and lowest Intergovernmental Panel on Climate Change emissions pathways for climate change and associated impacts in California. Based on climate projections from two state-of-the-art climate models with low and medium sensitivity (Parallel Climate Model and Hadley Centre Climate Model, version 3, respectively), we find that annual temperature increases nearly double from the lower B1 to the higher A1fi emissions scenario before 2100. Three of four simulations also show greater increases in summer temperatures as compared with winter. Extreme heat and the associated impacts on a range of temperature-sensitive sectors are substantially greater under the higher emissions scenario, with some interscenario differences apparent before midcentury. By the end of the century under the B1 scenario, heatwaves and extreme heat in Los Angeles quadruple in frequency while heat-related mortality increases two to three times; alpine/subalpine forests are reduced by 50-75%; and Sierra snowpack is reduced 30-70%. Under A1fi, heatwaves in Los Angeles are six to eight times more frequent, with heat-related excess mortality increasing five to seven times; alpine/subalpine forests are reduced by 75-90%; and snowpack declines 73-90%, with cascading impacts on runoff and streamflow that, combined with projected modest declines in winter precipitation, could fundamentally disrupt California's water rights system. Although interscenario differences in climate impacts and costs of adaptation emerge mainly in the second half of the century, they are strongly dependent on emissions from preceding decades.

Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification

PubMed Central

Zhang, Han; Cao, Long

2016-01-01

Ocean uptake of anthropogenic CO2 reduces pH and saturation state of calcium carbonate materials of seawater, which could reduce the calcification rate of some marine organisms, triggering a negative feedback on the growth of atmospheric CO2. We quantify the effect of this CO2-calcification feedback by conducting a series of Earth system model simulations that incorporate different parameterization schemes describing the dependence of calcification rate on saturation state of CaCO3. In a scenario with SRES A2 CO2 emission until 2100 and zero emission afterwards, by year 3500, in the simulation without CO2-calcification feedback, model projects an accumulated ocean CO2 uptake of 1462 PgC, atmospheric CO2 of 612 ppm, and surface pH of 7.9. Inclusion of CO2-calcification feedback increases ocean CO2 uptake by 9 to 285 PgC, reduces atmospheric CO2 by 4 to 70 ppm, and mitigates the reduction in surface pH by 0.003 to 0.06, depending on the form of parameterization scheme used. It is also found that the effect of CO2-calcification feedback on ocean carbon uptake is comparable and could be much larger than the effect from CO2-induced warming. Our results highlight the potentially important role CO2-calcification feedback plays in ocean carbon cycle and projections of future atmospheric CO2 concentrations. PMID:26838480

Effects of afala and antiestrogen ICI 182,780 in the model of hormone-dependent prostate inflammation.

PubMed

Bernoulli, J; Konkol, Y; Vuorikoski, H; Yatkin, E

2014-04-01

In the hormone-dependent prostate inflammation model induced by implantation of slow-releasing pellets (50 mg testosterone and 5 mg estradiol) to Noble male rats, intragastric administration of Afala at a dose of 7.5 ml/kg for 18 weeks reduced the number of inflamed prostatic acini. The effect of afala was comparable with that of antiestrogen ICI 182,780 (3 mg/kg subcutaneously twice a week for 18 weeks). Prolonged treatment with hormones in high doses induced severe inflammation of the prostate tissue, which was not terminated by the test preparations. As differentiated from the antiestrogen ICI 182,780, afala did not induce body weight gain and decrease in pituitary weight in experimental animals in comparison with the control group.

Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons.

PubMed

Alp, Murat; Cucinotta, Francis A

2018-03-01

Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors. We represented dendrites as cylindrical segments of varying diameter with unit aspect ratios, and developed a fast sampling method to consider the stochastic distribution of ED by δ rays (secondary electrons) around the path of heavy ions, to reduce computational times. We introduce probabilistic models with a small number of parameters to describe the induction of precursor lesions that precede dendritic snipping, denoted as snip sites. Predictions for oxygen ( 16 O, 600 MeV/n) and titanium ( 48 Ti, 600 MeV/n) particles with LET of 16.3 and 129 keV/μm, respectively, are considered. Morphometric parameters to quantify changes in neuron morphology are described, including reduction in total dendritic length, number of branch points and branch numbers. Sholl analysis is applied for single neurons to elucidate dose-dependent reductions in dendritic complexity. We predict important differences in measurements from imaging of tissues from brain slices with single neuron cell observations due to the role of neuron death through both soma apoptosis and excessive dendritic length reduction. To further elucidate the role of track structure, random segment excision (snips) models are introduced and a sensitivity study of the effects of the modes of neuron death in predictions of morphometric parameters is described. An important conclusion of this study is that δ rays play a major role in neuron morphological changes due to the large spatial distribution of damage sites, which results in a reduced dependence on LET, including modest difference between 16 O and 48 Ti, compared to damages resulting from ED in localized damage sites.

Preclinical evidence for combining the 5-HT2C receptor agonist lorcaserin and varenicline as a treatment for nicotine dependence.

PubMed

Fletcher, Paul J; Li, Zhaoxia; Silenieks, Leo B; MacMillan, Cam; DeLannoy, Ines; Higgins, Guy A

2018-03-02

Varenicline, a nicotinic acetylcholine receptor partial agonist, is used to treat nicotine dependence. Lorcaserin, a 5-HT 2C receptor agonist has been approved in some countries to treat obesity. Based on preclinical and preliminary clinical evidence, lorcaserin may have potential to treat nicotine dependence. These experiments examined in rats the effects of combining varenicline (0.5 or 1 mg/kg) and lorcaserin (0.3, 0.6 and 1 mg/kg) on nicotine self-administration, reinstatement of nicotine seeking, responding for food and impulsive action. Both drugs alone reduced nicotine self-administration. Combining varenicline and 0.6 mg/kg lorcaserin reduced responding to a greater extent than either drug alone. In a relapse model, extinguished nicotine seeking was reinstated by a priming injection of nicotine and nicotine-associated cues. Reinstatement was reduced by varenicline (1 mg/kg) and by lorcaserin (0.3 mg/kg). Combining lorcaserin (0.3 mg/kg) with varenicline (0.5 or 1 mg/kg) reduced reinstatement to a greater degree than either drug alone. Both drugs had minimal effects on responding for food, alone or in combination. In the five-choice serial reaction time test, varenicline (0.5 or 1 mg/kg) increased impulsivity, measured as increased premature responding. This effect was reduced by lorcaserin (0.3 mg/kg). Plasma levels of varenicline or lorcaserin were not altered by co-administration of the other drug. Varenicline and lorcaserin have additive effects on nicotine self-administration, and on nicotine seeking. Lorcaserin prevents impulsivity induced by varenicline. This pattern of effects suggests that co-administration of varenicline and lorcaserin has potential as a treatment for nicotine dependence that may exceed the value of either drug alone. © 2018 Society for the Study of Addiction.

Polarity effects and apparent ion recombination in microionization chambers

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

Miller, Jessica R., E-mail: miller@humonc.wisc.edu; Hooten, Brian D.; Micka, John A.

Purpose: Microchambers demonstrate anomalous voltage-dependent polarity effects. Existing polarity and ion recombination correction factors do not account for these effects. As a result, many commercial microchamber models do not meet the specification of a reference-class ionization chamber as defined by the American Association of Physicists in Medicine. The purpose of this investigation is to determine the cause of these voltage-dependent polarity effects. Methods: A series of microchamber prototypes were produced to isolate the source of the voltage-dependent polarity effects. Parameters including ionization-chamber collecting-volume size, stem and cable irradiation, chamber assembly, contaminants, high-Z materials, and individual chamber components were investigated. Measurementsmore » were performed with electrodes coated with graphite to isolate electrode conductivity. Chamber response was measured as the potential bias of the guard electrode was altered with respect to the collecting electrode, through the integration of additional power supplies. Ionization chamber models were also simulated using COMSOL Multiphysics software to investigate the effect of a potential difference between electrodes on electric field lines and collecting volume definition. Results: Investigations with microchamber prototypes demonstrated that the significant source of the voltage-dependent polarity effects was a potential difference between the guard and collecting electrodes of the chambers. The voltage-dependent polarity effects for each prototype were primarily isolated to either the guard or collecting electrode. Polarity effects were reduced by coating the isolated electrode with a conductive layer of graphite. Polarity effects were increased by introducing a potential difference between the electrodes. COMSOL simulations further demonstrated that for a given potential difference between electrodes, the collecting volume of the chamber changed as the applied voltage was altered, producing voltage-dependent polarity effects in the chamber response. Ionization chamber measurements and COMSOL simulations demonstrated an inverse relationship between the chamber collecting volume size and the severity of voltage-dependent polarity effects on chamber response. The effect of a given potential difference on chamber polarity effects was roughly ten times greater for microchambers as compared to Farmer-type chambers. Stem and cable irradiations, chamber assembly, contaminants, and high-Z materials were not found to be a significant source of the voltage-dependent polarity effects. Conclusions: A potential difference between the guard and collecting electrodes was found to be the primary source of the voltage-dependent polarity effects demonstrated by microchambers. For a given potential difference between electrodes, the relative change in the collecting volume is smaller for larger-volume chambers, illustrating why these polarity effects are not seen in larger-volume chambers with similar guard and collecting electrode designs. Thus, for small-volume chambers, it is necessary to reduce the potential difference between the guard and collecting electrodes in order to reduce polarity effects for reference dosimetry measurements.« less

A model-reduction approach in micromechanics of materials preserving the variational structure of constitutive relations

NASA Astrophysics Data System (ADS)

Michel, Jean-Claude; Suquet, Pierre

2016-05-01

In 2003 the authors proposed a model-reduction technique, called the Nonuniform Transformation Field Analysis (NTFA), based on a decomposition of the local fields of internal variables on a reduced basis of modes, to analyze the effective response of composite materials. The present study extends and improves on this approach in different directions. It is first shown that when the constitutive relations of the constituents derive from two potentials, this structure is passed to the NTFA model. Another structure-preserving model, the hybrid NTFA model of Fritzen and Leuschner, is analyzed and found to differ (slightly) from the primal NTFA model (it does not exhibit the same variational upper bound character). To avoid the "on-line" computation of local fields required by the hybrid model, new reduced evolution equations for the reduced variables are proposed, based on an expansion to second order (TSO) of the potential of the hybrid model. The coarse dynamics can then be entirely expressed in terms of quantities which can be pre-computed once for all. Roughly speaking, these pre-computed quantities depend only on the average and fluctuations per phase of the modes and of the associated stress fields. The accuracy of the new NTFA-TSO model is assessed by comparison with full-field simulations. The acceleration provided by the new coarse dynamics over the full-field computations (and over the hybrid model) is then spectacular, larger by three orders of magnitude than the acceleration due to the sole reduction of unknowns.

Development of a Reduced-Order Three-Dimensional Flow Model for Thermal Mixing and Stratification Simulation during Reactor Transients

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

Hu, Rui

2017-09-03

Mixing, thermal-stratification, and mass transport phenomena in large pools or enclosures play major roles for the safety of reactor systems. Depending on the fidelity requirement and computational resources, various modeling methods, from the 0-D perfect mixing model to 3-D Computational Fluid Dynamics (CFD) models, are available. Each is associated with its own advantages and shortcomings. It is very desirable to develop an advanced and efficient thermal mixing and stratification modeling capability embedded in a modern system analysis code to improve the accuracy of reactor safety analyses and to reduce modeling uncertainties. An advanced system analysis tool, SAM, is being developedmore » at Argonne National Laboratory for advanced non-LWR reactor safety analysis. While SAM is being developed as a system-level modeling and simulation tool, a reduced-order three-dimensional module is under development to model the multi-dimensional flow and thermal mixing and stratification in large enclosures of reactor systems. This paper provides an overview of the three-dimensional finite element flow model in SAM, including the governing equations, stabilization scheme, and solution methods. Additionally, several verification and validation tests are presented, including lid-driven cavity flow, natural convection inside a cavity, laminar flow in a channel of parallel plates. Based on the comparisons with the analytical solutions and experimental results, it is demonstrated that the developed 3-D fluid model can perform very well for a wide range of flow problems.« less

Modelling of thermal field and point defect dynamics during silicon single crystal growth using CZ technique

NASA Astrophysics Data System (ADS)

Sabanskis, A.; Virbulis, J.

2018-05-01

Mathematical modelling is employed to numerically analyse the dynamics of the Czochralski (CZ) silicon single crystal growth. The model is axisymmetric, its thermal part describes heat transfer by conduction and thermal radiation, and allows to predict the time-dependent shape of the crystal-melt interface. Besides the thermal field, the point defect dynamics is modelled using the finite element method. The considered process consists of cone growth and cylindrical phases, including a short period of a reduced crystal pull rate, and a power jump to avoid large diameter changes. The influence of the thermal stresses on the point defects is also investigated.

The vanishing limit of the square-well fluid: The adhesive hard-sphere model as a reference system

NASA Astrophysics Data System (ADS)

Largo, J.; Miller, M. A.; Sciortino, F.

2008-04-01

We report a simulation study of the gas-liquid critical point for the square-well potential, for values of well width δ as small as 0.005 times the particle diameter σ. For small δ, the reduced second virial coefficient at the critical point B2*c is found to depend linearly on δ. The observed weak linear dependence is not sufficient to produce any significant observable effect if the critical temperature Tc is estimated via a constant B2*c assumption, due to the highly nonlinear transformation between B2*c and Tc. This explains the previously observed validity of the law of corresponding states. The critical density ρc is also found to be constant when measured in units of the cube of the average distance between two bonded particles (1+0.5δ)σ. The possibility of describing the δ →0 dependence with precise functional forms provides improved accurate estimates of the critical parameters of the adhesive hard-sphere model.

The vanishing limit of the square-well fluid: the adhesive hard-sphere model as a reference system.

PubMed

Largo, J; Miller, M A; Sciortino, F

2008-04-07

We report a simulation study of the gas-liquid critical point for the square-well potential, for values of well width delta as small as 0.005 times the particle diameter sigma. For small delta, the reduced second virial coefficient at the critical point B2*c is found to depend linearly on delta. The observed weak linear dependence is not sufficient to produce any significant observable effect if the critical temperature Tc is estimated via a constant B2*c assumption, due to the highly nonlinear transformation between B2*c and Tc. This explains the previously observed validity of the law of corresponding states. The critical density rho c is also found to be constant when measured in units of the cube of the average distance between two bonded particles (1+0.5 delta)sigma. The possibility of describing the delta-->0 dependence with precise functional forms provides improved accurate estimates of the critical parameters of the adhesive hard-sphere model.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans

PubMed Central

Moberg, Christine A.; Bradford, Daniel E.; Kaye, Jesse T.; Curtin, John J.

2017-01-01

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to non-alcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent pre-morbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. PMID:28394145

Impact of Tortuosity on Charge-Carrier Transport in Organic Bulk Heterojunction Blends

NASA Astrophysics Data System (ADS)

Heiber, Michael C.; Kister, Klaus; Baumann, Andreas; Dyakonov, Vladimir; Deibel, Carsten; Nguyen, Thuc-Quyen

2017-11-01

The impact of the tortuosity of the charge-transport pathways through a bulk heterojunction film on the charge-carrier mobility is theoretically investigated using model morphologies and kinetic Monte Carlo simulations. The tortuosity descriptor provides a quantitative metric to characterize the quality of the charge-transport pathways, and model morphologies with controlled domain size and tortuosity are created using an anisotropic domain growth procedure. The tortuosity is found to be dependent on the anisotropy of the domain structure and is highly tunable. Time-of-flight charge-transport simulations on morphologies with a range of tortuosity values reveal that tortuosity can significantly reduce the magnitude of the mobility and the electric-field dependence relative to a neat material. These reductions are found to be further controlled by the energetic disorder and temperature. Most significantly, the sensitivity of the electric-field dependence to the tortuosity can explain the different experimental relationships previously reported, and exploiting this sensitivity could lead to simpler methods for characterizing and optimizing charge transport in organic solar cells.

Pauci ex tanto numero: reduce redundancy in multi-model ensembles

NASA Astrophysics Data System (ADS)

Solazzo, E.; Riccio, A.; Kioutsioukis, I.; Galmarini, S.

2013-08-01

We explicitly address the fundamental issue of member diversity in multi-model ensembles. To date, no attempts in this direction have been documented within the air quality (AQ) community despite the extensive use of ensembles in this field. Common biases and redundancy are the two issues directly deriving from lack of independence, undermining the significance of a multi-model ensemble, and are the subject of this study. Shared, dependant biases among models do not cancel out but will instead determine a biased ensemble. Redundancy derives from having too large a portion of common variance among the members of the ensemble, producing overconfidence in the predictions and underestimation of the uncertainty. The two issues of common biases and redundancy are analysed in detail using the AQMEII ensemble of AQ model results for four air pollutants in two European regions. We show that models share large portions of bias and variance, extending well beyond those induced by common inputs. We make use of several techniques to further show that subsets of models can explain the same amount of variance as the full ensemble with the advantage of being poorly correlated. Selecting the members for generating skilful, non-redundant ensembles from such subsets proved, however, non-trivial. We propose and discuss various methods of member selection and rate the ensemble performance they produce. In most cases, the full ensemble is outscored by the reduced ones. We conclude that, although independence of outputs may not always guarantee enhancement of scores (but this depends upon the skill being investigated), we discourage selecting the members of the ensemble simply on the basis of scores; that is, independence and skills need to be considered disjointly.

Mathematical modeling of Kluyveromyces marxianus growth in solid-state fermentation using a packed-bed bioreactor.

PubMed

Mazutti, Marcio A; Zabot, Giovani; Boni, Gabriela; Skovronski, Aline; de Oliveira, Débora; Di Luccio, Marco; Rodrigues, Maria Isabel; Maugeri, Francisco; Treichel, Helen

2010-04-01

This work investigated the growth of Kluyveromyces marxianus NRRL Y-7571 in solid-state fermentation in a medium composed of sugarcane bagasse, molasses, corn steep liquor and soybean meal within a packed-bed bioreactor. Seven experimental runs were carried out to evaluate the effects of flow rate and inlet air temperature on the following microbial rates: cell mass production, total reducing sugar and oxygen consumption, carbon dioxide and ethanol production, metabolic heat and water generation. A mathematical model based on an artificial neural network was developed to predict the above-mentioned microbial rates as a function of the fermentation time, initial total reducing sugar concentration, inlet and outlet air temperatures. The results showed that the microbial rates were temperature dependent for the range 27-50 degrees C. The proposed model efficiently predicted the microbial rates, indicating that the neural network approach could be used to simulate the microbial growth in SSF.

Calibration of semi-stochastic procedure for simulating high-frequency ground motions

USGS Publications Warehouse

Seyhan, Emel; Stewart, Jonathan P.; Graves, Robert

2013-01-01

Broadband ground motion simulation procedures typically utilize physics-based modeling at low frequencies, coupled with semi-stochastic procedures at high frequencies. The high-frequency procedure considered here combines deterministic Fourier amplitude spectra (dependent on source, path, and site models) with random phase. Previous work showed that high-frequency intensity measures from this simulation methodology attenuate faster with distance and have lower intra-event dispersion than in empirical equations. We address these issues by increasing crustal damping (Q) to reduce distance attenuation bias and by introducing random site-to-site variations to Fourier amplitudes using a lognormal standard deviation ranging from 0.45 for Mw < 7 to zero for Mw 8. Ground motions simulated with the updated parameterization exhibit significantly reduced distance attenuation bias and revised dispersion terms are more compatible with those from empirical models but remain lower at large distances (e.g., > 100 km).

Kinetics of OH + CO reaction under atmospheric conditions

NASA Technical Reports Server (NTRS)

Hynes, A. J.; Wine, P. H.; Ravishankara, A. R.

1986-01-01

A pulsed laser photolysis-pulsed laser-induced fluorescence technique is used to directly measure the temperature, pressure, and H2O concentration dependence on k1 in air. K1 is found to increase linearly with increasing pressure at pressures of not greater than 1 atm, and the pressure dependence of k1 at 299 K is the same in N2 buffer gas as in O2 buffer gas. The rate constant in the low-pressure limit and the slope of the k1 versus pressure dependence are shown to be the same at 262 K as at 299 K. The present results significantly reduce the current atmospheric model uncertainties in the temperature dependence under atmospheric conditions, in the third body efficiency of O2, and in the effect of water vapor on k1.

Density-dependent microbial turnover improves soil carbon model predictions of long-term litter manipulations

NASA Astrophysics Data System (ADS)

Georgiou, Katerina; Abramoff, Rose; Harte, John; Riley, William; Torn, Margaret

2017-04-01

Climatic, atmospheric, and land-use changes all have the potential to alter soil microbial activity via abiotic effects on soil or mediated by changes in plant inputs. Recently, many promising microbial models of soil organic carbon (SOC) decomposition have been proposed to advance understanding and prediction of climate and carbon (C) feedbacks. Most of these models, however, exhibit unrealistic oscillatory behavior and SOC insensitivity to long-term changes in C inputs. Here we diagnose the sources of instability in four models that span the range of complexity of these recent microbial models, by sequentially adding complexity to a simple model to include microbial physiology, a mineral sorption isotherm, and enzyme dynamics. We propose a formulation that introduces density-dependence of microbial turnover, which acts to limit population sizes and reduce oscillations. We compare these models to results from 24 long-term C-input field manipulations, including the Detritus Input and Removal Treatment (DIRT) experiments, to show that there are clear metrics that can be used to distinguish and validate the inherent dynamics of each model structure. We find that widely used first-order models and microbial models without density-dependence cannot readily capture the range of long-term responses observed across the DIRT experiments as a direct consequence of their model structures. The proposed formulation improves predictions of long-term C-input changes, and implies greater SOC storage associated with CO2-fertilization-driven increases in C inputs over the coming century compared to common microbial models. Finally, we discuss our findings in the context of improving microbial model behavior for inclusion in Earth System Models.

Effective information channels for reducing costs of environmentally- friendly technologies: evidence from residential PV markets

NASA Astrophysics Data System (ADS)

Rai, Varun; Robinson, Scott A.

2013-03-01

Realizing the environmental benefits of solar photovoltaics (PV) will require reducing costs associated with perception, informational gaps and technological uncertainties. To identify opportunities to decrease costs associated with residential PV adoption, in this letter we use multivariate regression models to analyze a unique, household-level dataset of PV adopters in Texas (USA) to systematically quantify the effect of different information channels on aspiring PV adopters’ decision-making. We find that the length of the decision period depends on the business model, such as whether the system was bought or leased, and on special opportunities to learn, such as the influence of other PV owners in the neighborhood. This influence accrues passively through merely witnessing PV systems in the neighborhood, increasing confidence and motivation, as well as actively through peer-to-peer communications. Using these insights we propose a new framework to provide public information on PV that could drastically reduce barriers to PV adoption, thereby accelerating its market penetration and environmental benefits. This framework could also serve as a model for other distributed generation technologies.

The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma.

PubMed

Miess, Heike; Dankworth, Beatrice; Gouw, Arvin M; Rosenfeldt, Mathias; Schmitz, Werner; Jiang, Ming; Saunders, Becky; Howell, Michael; Downward, Julian; Felsher, Dean W; Peck, Barrie; Schulze, Almut

2018-06-05

Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis. Moreover, silencing of enzymes of the GSH biosynthesis pathway or glutathione peroxidases, which depend on GSH for the removal of cellular hydroperoxides, selectively reduced viability of ccRCC cells but did not affect the growth of non-malignant renal epithelial cells. Inhibition of GSH synthesis triggered ferroptosis, an iron-dependent form of cell death associated with enhanced lipid peroxidation. VHL is a major tumour suppressor in ccRCC and loss of VHL leads to stabilisation of hypoxia inducible factors HIF-1α and HIF-2α. Restoration of functional VHL via exogenous expression of pVHL reverted ccRCC cells to an oxidative metabolism and rendered them insensitive to the induction of ferroptosis. VHL reconstituted cells also exhibited reduced lipid storage and higher expression of genes associated with oxidiative phosphorylation and fatty acid metabolism. Importantly, inhibition of β-oxidation or mitochondrial ATP-synthesis restored ferroptosis sensitivity in VHL reconstituted cells. We also found that inhibition of GSH synthesis blocked tumour growth in a MYC-dependent mouse model of renal cancer. Together, our data suggest that reduced fatty acid metabolism due to inhibition of β-oxidation renders renal cancer cells highly dependent on the GSH/GPX pathway to prevent lipid peroxidation and ferroptotic cell death.

Deletion of chromosome 9p21 noncoding cardiovascular risk interval in mice alters Smad2 signaling and promotes vascular aneurysm.

PubMed

Loinard, Céline; Basatemur, Gemma; Masters, Leanne; Baker, Lauren; Harrison, James; Figg, Nichola; Vilar, José; Sage, Andrew P; Mallat, Ziad

2014-12-01

Vascular aneurysm is an abnormal local dilatation of an artery that can lead to vessel rupture and sudden death. The only treatment involves surgical or endovascular repair or exclusion. There is currently no approved medical therapy for this condition. Recent data established a strong association between genetic variants in the 9p21 chromosomal region in humans and the presence of cardiovascular diseases, including aneurysms. However, the mechanisms linking this 9p21 DNA variant to cardiovascular risk are still unknown. Here, we show that deletion of the orthologous 70-kb noncoding interval on mouse chromosome 4 (chr4(Δ70kb/Δ70kb) mice) is associated with reduced aortic expression of cyclin-dependent kinase inhibitor genes p19Arf and p15Inkb. Vascular smooth muscle cells from chr4(Δ70kb/Δ70kb) mice show reduced transforming growth factor-β-dependent canonical Smad2 signaling but increased cyclin-dependent kinase-dependent Smad2 phosphorylation at linker sites, a phenotype previously associated with tumor growth and consistent with the mechanistic link between reduced canonical transforming growth factor-β signaling and susceptibility to vascular diseases. We also show that targeted deletion of the 9p21 risk interval promotes susceptibility to aneurysm development and rupture when mice are subjected to a validated model of aneurysm formation. The vascular disease of chr4(Δ70kb/Δ70kb) mice is prevented by treatment with a cyclin-dependent kinase inhibitor. The results establish a direct mechanistic link between 9p21 noncoding risk interval and susceptibility to aneurysm and may have important implications for the understanding and treatment of vascular diseases. © 2014 American Heart Association, Inc.

Using Neural Networks to Improve the Performance of Radiative Transfer Modeling Used for Geometry Dependent LER Calculations

NASA Astrophysics Data System (ADS)

Fasnacht, Z.; Qin, W.; Haffner, D. P.; Loyola, D. G.; Joiner, J.; Krotkov, N. A.; Vasilkov, A. P.; Spurr, R. J. D.

2017-12-01

In order to estimate surface reflectance used in trace gas retrieval algorithms, radiative transfer models (RTM) such as the Vector Linearized Discrete Ordinate Radiative Transfer Model (VLIDORT) can be used to simulate the top of the atmosphere (TOA) radiances with advanced models of surface properties. With large volumes of satellite data, these model simulations can become computationally expensive. Look up table interpolation can improve the computational cost of the calculations, but the non-linear nature of the radiances requires a dense node structure if interpolation errors are to be minimized. In order to reduce our computational effort and improve the performance of look-up tables, neural networks can be trained to predict these radiances. We investigate the impact of using look-up table interpolation versus a neural network trained using the smart sampling technique, and show that neural networks can speed up calculations and reduce errors while using significantly less memory and RTM calls. In future work we will implement a neural network in operational processing to meet growing demands for reflectance modeling in support of high spatial resolution satellite missions.

Quantum Mechanics, Path Integrals and Option Pricing:. Reducing the Complexity of Finance

NASA Astrophysics Data System (ADS)

Baaquie, Belal E.; Corianò, Claudio; Srikant, Marakani

2003-04-01

Quantum Finance represents the synthesis of the techniques of quantum theory (quantum mechanics and quantum field theory) to theoretical and applied finance. After a brief overview of the connection between these fields, we illustrate some of the methods of lattice simulations of path integrals for the pricing of options. The ideas are sketched out for simple models, such as the Black-Scholes model, where analytical and numerical results are compared. Application of the method to nonlinear systems is also briefly overviewed. More general models, for exotic or path-dependent options are discussed.

A coolant flow simulation in fast reactor wire-wrapped assembly

NASA Astrophysics Data System (ADS)

Volkov, V. Yu.; Belova, O. V.; Krutikov, A. A.; Skibin, A. P.

2013-06-01

A CFD model of a 19-rod wire-wrapped fuel assembly is developed. The effect the size of computation mesh in the calculated region and the type of turbulence models have on the pressure drop between the inlet to and outlet from the calculated region is investigated. The possibility of shifting from low-Reynolds to high-Reynolds turbulence models is substantiated. Such a shift allows the mesh size in the calculated region to be reduced by approximately a factor of 18. The obtained results are in good agreement with the empirical dependences and international calculations.

Automatic control algorithm effects on energy production

NASA Technical Reports Server (NTRS)

Mcnerney, G. M.

1981-01-01

A computer model was developed using actual wind time series and turbine performance data to simulate the power produced by the Sandia 17-m VAWT operating in automatic control. The model was used to investigate the influence of starting algorithms on annual energy production. The results indicate that, depending on turbine and local wind characteristics, a bad choice of a control algorithm can significantly reduce overall energy production. The model can be used to select control algorithms and threshold parameters that maximize long term energy production. The results from local site and turbine characteristics were generalized to obtain general guidelines for control algorithm design.

One-dimensional model of inertial pumping

NASA Astrophysics Data System (ADS)

Kornilovitch, Pavel E.; Govyadinov, Alexander N.; Markel, David P.; Torniainen, Erik D.

2013-02-01

A one-dimensional model of inertial pumping is introduced and solved. The pump is driven by a high-pressure vapor bubble generated by a microheater positioned asymmetrically in a microchannel. The bubble is approximated as a short-term impulse delivered to the two fluidic columns inside the channel. Fluid dynamics is described by a Newton-like equation with a variable mass, but without the mass derivative term. Because of smaller inertia, the short column refills the channel faster and accumulates a larger mechanical momentum. After bubble collapse the total fluid momentum is nonzero, resulting in a net flow. Two different versions of the model are analyzed in detail, analytically and numerically. In the symmetrical model, the pressure at the channel-reservoir connection plane is assumed constant, whereas in the asymmetrical model it is reduced by a Bernoulli term. For low and intermediate vapor bubble pressures, both models predict the existence of an optimal microheater location. The predicted net flow in the asymmetrical model is smaller by a factor of about 2. For unphysically large vapor pressures, the asymmetrical model predicts saturation of the effect, while in the symmetrical model net flow increases indefinitely. Pumping is reduced by nonzero viscosity, but to a different degree depending on the microheater location.

One-dimensional model of inertial pumping.

PubMed

Kornilovitch, Pavel E; Govyadinov, Alexander N; Markel, David P; Torniainen, Erik D

2013-02-01

A one-dimensional model of inertial pumping is introduced and solved. The pump is driven by a high-pressure vapor bubble generated by a microheater positioned asymmetrically in a microchannel. The bubble is approximated as a short-term impulse delivered to the two fluidic columns inside the channel. Fluid dynamics is described by a Newton-like equation with a variable mass, but without the mass derivative term. Because of smaller inertia, the short column refills the channel faster and accumulates a larger mechanical momentum. After bubble collapse the total fluid momentum is nonzero, resulting in a net flow. Two different versions of the model are analyzed in detail, analytically and numerically. In the symmetrical model, the pressure at the channel-reservoir connection plane is assumed constant, whereas in the asymmetrical model it is reduced by a Bernoulli term. For low and intermediate vapor bubble pressures, both models predict the existence of an optimal microheater location. The predicted net flow in the asymmetrical model is smaller by a factor of about 2. For unphysically large vapor pressures, the asymmetrical model predicts saturation of the effect, while in the symmetrical model net flow increases indefinitely. Pumping is reduced by nonzero viscosity, but to a different degree depending on the microheater location.

Hydralazine and Organic Nitrates Restore Impaired Excitation-Contraction Coupling by Reducing Calcium Leak Associated with Nitroso-Redox Imbalance*

PubMed Central

Dulce, Raul A.; Yiginer, Omer; Gonzalez, Daniel R.; Goss, Garrett; Feng, Ning; Zheng, Meizi; Hare, Joshua M.

2013-01-01

Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1−/−) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca2+ cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1−/− compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca2+ transient (Δ[Ca2+]i) responses in NOS1−/− cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca2+]i across the range of pacing frequencies and increased myofilament Ca2+ sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca2+ reuptake, and restored SR Ca2+ content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca2+ leak, HYD improves Ca2+ cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling. PMID:23319593

Effectiveness of submerged drains in reducing subsidence of peat soils in agricultural use, and their effects on water management and nutrient loading of surface water: modelling of a case study in the western peat soil area of The Netherlands

NASA Astrophysics Data System (ADS)

Hendriks, Rob F. A.; van den Akker, Jan J. A.

2017-04-01

Effectiveness of submerged drains in reducing subsidence of peat soils in agricultural use, and their effects on water management and nutrient loading of surface water: modelling of a case study in the western peat soil area of The Netherlands In the Netherlands, about 8% of the area is covered by peat soils. Most of these soils are in use for dairy farming and, consequently, are drained. Drainage causes decomposition of peat by oxidation and accordingly leads to surface subsidence and greenhouse gas emission. Submerged drains that enhance submerged infiltration of water from ditches during the dry and warm summer half year were, and are still, studied in The Netherlands as a promising tool for reducing peat decomposition by raising groundwater levels. For this purpose, several pilot field studies in the Western part of the Dutch peat area were conducted. Besides the effectiveness of submerged drains in reducing peat decomposition and subsidence by raising groundwater tables, some other relevant or expected effects of these drains were studied. Most important of these are water management and loading of surface water with nutrients nitrogen, phosphorus and sulphate. Because most of these parameters are not easy to assess and all of them are strongly depending on the meteorological conditions during the field studies some of these studies were modelled. The SWAP model was used for evaluating the hydrological results on groundwater table and water discharge and recharge. Effects of submerged drains were assessed by comparing the results of fields with and without drains. An empirical relation between deepest groundwater table and subsidence was used to convert effects on groundwater table to effects on subsidence. With the SWAP-ANIMO model nutrient loading of surface water was modelled on the basis of field results on nutrient concentrations . Calibrated models were used to assess effects in the present situation, as thirty-year averages, under extreme weather conditions and for two extreme climate scenarios of the Royal Netherlands Meteorological Institute. In this study the model results of one of the pilot studies are presented. The case study 'de Krimpenerwaard' is situated in the peat area in the "Green Heart" between the major cities of Amsterdam, The Hague, Rotterdam and Utrecht. Model results show a halving of soil subsidence, a strong increase of water recharge but a lower increase of water discharge, and generally small to moderate effects on nutrient loading , all depending (strongly) on meteorological conditions.

Assessing the Army Power and Energy Efforts for the Warfighter

DTIC Science & Technology

2011-03-01

forecast some new and unexpected possibilities will emerge. Introduction Armies are dependent on power and energy . When these resources for any...battlefield. This need coincides with the National need for reducing energy dependence on foreign sources. This dependence can be minimized by improving...namely, use less energy by being more efficient, reduce dependence on oil, reduce the cost of energy , and use renewable sources where possible. That

Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

NASA Astrophysics Data System (ADS)

Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

2013-07-01

Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

A specific role for septohippocampal acetylcholine in memory?

PubMed Central

Easton, Alexander; Douchamps, Vincent; Eacott, Madeline; Lever, Colin

2012-01-01

Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the specific role for this neurotransmitter is difficult to identify in human neuropsychology. Here, we review the evidence for a mechanistic model of acetylcholine function within the hippocampus and consider its explanatory power for interpreting effects resulting from both pharmacological anticholinergic manipulations and lesions of the cholinergic input to the hippocampus in animals. We argue that these effects indicate that acetylcholine is necessary for some, but not all, hippocampal-dependent processes. We review recent evidence from lesion, pharmacological and electrophysiological studies to support the view that a primary function of septohippocampal acetylcholine is to reduce interference in the learning process by adaptively timing and separating encoding and retrieval processes. We reinterpret cholinergic-lesion based deficits according to this view and propose that acetylcholine reduces the interference elicited by the movement of salient locations between events. PMID:22884957

Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity.

PubMed

Li, Hua-Fei; Wu, Cong; Chen, Ting; Zhang, Ge; Zhao, He; Ke, Chang-Hong; Xu, Zheng

2015-01-01

The CD20-directed monoclonal antibody rituximab (RTX) established a new era in the treatment of non-Hodgkin lymphoma (NHL); however, suboptimal response and/or resistance to RTX still limit its clinical merits. Although four effector mechanisms are validated to participate in CD20-based immunotherapy, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, caspase-dependent apoptosis, and lysosome-mediated programmed cell death (PCD), they could hardly be synchronously activated by any anti-CD20 mAb or mAb derivative until now. Herein, a novel mAb nanocomb (polyethylenimine polymer-RTX-tositumomab [PPRT nanocomb]) was firstly constructed through mass arming two different anti-CD20 mAbs (RTX and tositumomab) to one polymer by nanotechnology. Comparing with free mAbs, PPRT nanocomb possesses a comparable binding ability and reduced "off-rate" to surface CD20 of NHL cells. When treated by PPRT nanocomb, the caspase-dependent apoptosis was remarkably enhanced except for concurrently eliciting complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and lysosome-mediated PCD. Besides, "cross-cell link"-assisted homotypic adhesion by PPRT nanocomb further enhanced the susceptibility to PCD of lymphoma cells. Pharmacokinetic assays revealed that PPRT nanocomb experienced a relatively reduced clearance from peripheral blood compared with free antibodies. With the cooperation of all the abovementioned superiorities, PPRT nanocomb exhibits exceptionally excellent in vivo antitumor activities in both disseminated and localized human NHL xenotransplant models.

Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity

PubMed Central

Li, Hua-Fei; Wu, Cong; Chen, Ting; Zhang, Ge; Zhao, He; Ke, Chang-Hong; Xu, Zheng

2015-01-01

The CD20-directed monoclonal antibody rituximab (RTX) established a new era in the treatment of non-Hodgkin lymphoma (NHL); however, suboptimal response and/or resistance to RTX still limit its clinical merits. Although four effector mechanisms are validated to participate in CD20-based immunotherapy, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, caspase-dependent apoptosis, and lysosome-mediated programmed cell death (PCD), they could hardly be synchronously activated by any anti-CD20 mAb or mAb derivative until now. Herein, a novel mAb nanocomb (polyethylenimine polymer–RTX–tositumomab [PPRT nanocomb]) was firstly constructed through mass arming two different anti-CD20 mAbs (RTX and tositumomab) to one polymer by nanotechnology. Comparing with free mAbs, PPRT nanocomb possesses a comparable binding ability and reduced “off-rate” to surface CD20 of NHL cells. When treated by PPRT nanocomb, the caspase-dependent apoptosis was remarkably enhanced except for concurrently eliciting complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and lysosome-mediated PCD. Besides, “cross-cell link”-assisted homotypic adhesion by PPRT nanocomb further enhanced the susceptibility to PCD of lymphoma cells. Pharmacokinetic assays revealed that PPRT nanocomb experienced a relatively reduced clearance from peripheral blood compared with free antibodies. With the cooperation of all the abovementioned superiorities, PPRT nanocomb exhibits exceptionally excellent in vivo antitumor activities in both disseminated and localized human NHL xenotransplant models. PMID:26257518

Micromechanics of ice friction

NASA Astrophysics Data System (ADS)

Sammonds, P. R.; Bailey, E.; Lishman, B.; Scourfield, S.

2015-12-01

Frictional mechanics are controlled by the ice micro-structure - surface asperities and flaws - but also the ice fabric and permeability network structure of the contacting blocks. Ice properties are dependent upon the temperature of the bulk ice, on the normal stress and on the sliding velocity and acceleration. This means the shear stress required for sliding is likewise dependent on sliding velocity, acceleration, and temperature. We aim to describe the micro-physics of the contacting surface. We review micro-mechanical models of friction: the elastic and ductile deformation of asperities under normal loads and their shear failure by ductile flow, brittle fracture, or melting and hydrodynamic lubrication. Combinations of these give a total of six rheological models of friction. We present experimental results in ice mechanics and physics from laboratory experiments to understand the mechanical models. We then examine the scaling relations of the slip of ice, to examine how the micro-mechanics of ice friction can be captured simple reduced-parameter models, describing the mechanical state and slip rate of the floes. We aim to capture key elements that they may be incorporated into mid and ocean-basin scale modelling.

Dynamic elementary mode modelling of non-steady state flux data.

PubMed

Folch-Fortuny, Abel; Teusink, Bas; Hoefsloot, Huub C J; Smilde, Age K; Ferrer, Alberto

2018-06-18

A novel framework is proposed to analyse metabolic fluxes in non-steady state conditions, based on the new concept of dynamic elementary mode (dynEM): an elementary mode activated partially depending on the time point of the experiment. Two methods are introduced here: dynamic elementary mode analysis (dynEMA) and dynamic elementary mode regression discriminant analysis (dynEMR-DA). The former is an extension of the recently proposed principal elementary mode analysis (PEMA) method from steady state to non-steady state scenarios. The latter is a discriminant model that permits to identify which dynEMs behave strongly different depending on the experimental conditions. Two case studies of Saccharomyces cerevisiae, with fluxes derived from simulated and real concentration data sets, are presented to highlight the benefits of this dynamic modelling. This methodology permits to analyse metabolic fluxes at early stages with the aim of i) creating reduced dynamic models of flux data, ii) combining many experiments in a single biologically meaningful model, and iii) identifying the metabolic pathways that drive the organism from one state to another when changing the environmental conditions.

A Neurocomputational model of tonic and phasic dopamine in action selection: A comparison with cognitive deficits in Parkinson’s disease

PubMed Central

Guthrie, M.; Myers, C.E.; Gluck, M.A.

2015-01-01

The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson’s disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson’s disease are not solely due to either the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status. PMID:19162084

Data-assisted reduced-order modeling of extreme events in complex dynamical systems

PubMed Central

Koumoutsakos, Petros

2018-01-01

The prediction of extreme events, from avalanches and droughts to tsunamis and epidemics, depends on the formulation and analysis of relevant, complex dynamical systems. Such dynamical systems are characterized by high intrinsic dimensionality with extreme events having the form of rare transitions that are several standard deviations away from the mean. Such systems are not amenable to classical order-reduction methods through projection of the governing equations due to the large intrinsic dimensionality of the underlying attractor as well as the complexity of the transient events. Alternatively, data-driven techniques aim to quantify the dynamics of specific, critical modes by utilizing data-streams and by expanding the dimensionality of the reduced-order model using delayed coordinates. In turn, these methods have major limitations in regions of the phase space with sparse data, which is the case for extreme events. In this work, we develop a novel hybrid framework that complements an imperfect reduced order model, with data-streams that are integrated though a recurrent neural network (RNN) architecture. The reduced order model has the form of projected equations into a low-dimensional subspace that still contains important dynamical information about the system and it is expanded by a long short-term memory (LSTM) regularization. The LSTM-RNN is trained by analyzing the mismatch between the imperfect model and the data-streams, projected to the reduced-order space. The data-driven model assists the imperfect model in regions where data is available, while for locations where data is sparse the imperfect model still provides a baseline for the prediction of the system state. We assess the developed framework on two challenging prototype systems exhibiting extreme events. We show that the blended approach has improved performance compared with methods that use either data streams or the imperfect model alone. Notably the improvement is more significant in regions associated with extreme events, where data is sparse. PMID:29795631

Data-assisted reduced-order modeling of extreme events in complex dynamical systems.

PubMed

Wan, Zhong Yi; Vlachas, Pantelis; Koumoutsakos, Petros; Sapsis, Themistoklis

2018-01-01

The prediction of extreme events, from avalanches and droughts to tsunamis and epidemics, depends on the formulation and analysis of relevant, complex dynamical systems. Such dynamical systems are characterized by high intrinsic dimensionality with extreme events having the form of rare transitions that are several standard deviations away from the mean. Such systems are not amenable to classical order-reduction methods through projection of the governing equations due to the large intrinsic dimensionality of the underlying attractor as well as the complexity of the transient events. Alternatively, data-driven techniques aim to quantify the dynamics of specific, critical modes by utilizing data-streams and by expanding the dimensionality of the reduced-order model using delayed coordinates. In turn, these methods have major limitations in regions of the phase space with sparse data, which is the case for extreme events. In this work, we develop a novel hybrid framework that complements an imperfect reduced order model, with data-streams that are integrated though a recurrent neural network (RNN) architecture. The reduced order model has the form of projected equations into a low-dimensional subspace that still contains important dynamical information about the system and it is expanded by a long short-term memory (LSTM) regularization. The LSTM-RNN is trained by analyzing the mismatch between the imperfect model and the data-streams, projected to the reduced-order space. The data-driven model assists the imperfect model in regions where data is available, while for locations where data is sparse the imperfect model still provides a baseline for the prediction of the system state. We assess the developed framework on two challenging prototype systems exhibiting extreme events. We show that the blended approach has improved performance compared with methods that use either data streams or the imperfect model alone. Notably the improvement is more significant in regions associated with extreme events, where data is sparse.

Group Membership, Group Change, and Intergroup Attitudes: A Recategorization Model Based on Cognitive Consistency Principles.

PubMed

Roth, Jenny; Steffens, Melanie C; Vignoles, Vivian L

2018-01-01

The present article introduces a model based on cognitive consistency principles to predict how new identities become integrated into the self-concept, with consequences for intergroup attitudes. The model specifies four concepts (self-concept, stereotypes, identification, and group compatibility) as associative connections. The model builds on two cognitive principles, balance-congruity and imbalance-dissonance, to predict identification with social groups that people currently belong to, belonged to in the past, or newly belong to. More precisely, the model suggests that the relative strength of self-group associations (i.e., identification) depends in part on the (in)compatibility of the different social groups. Combining insights into cognitive representation of knowledge, intergroup bias, and explicit/implicit attitude change, we further derive predictions for intergroup attitudes. We suggest that intergroup attitudes alter depending on the relative associative strength between the social groups and the self, which in turn is determined by the (in)compatibility between social groups. This model unifies existing models on the integration of social identities into the self-concept by suggesting that basic cognitive mechanisms play an important role in facilitating or hindering identity integration and thus contribute to reducing or increasing intergroup bias.

Group Membership, Group Change, and Intergroup Attitudes: A Recategorization Model Based on Cognitive Consistency Principles

PubMed Central

Roth, Jenny; Steffens, Melanie C.; Vignoles, Vivian L.

2018-01-01

The present article introduces a model based on cognitive consistency principles to predict how new identities become integrated into the self-concept, with consequences for intergroup attitudes. The model specifies four concepts (self-concept, stereotypes, identification, and group compatibility) as associative connections. The model builds on two cognitive principles, balance–congruity and imbalance–dissonance, to predict identification with social groups that people currently belong to, belonged to in the past, or newly belong to. More precisely, the model suggests that the relative strength of self-group associations (i.e., identification) depends in part on the (in)compatibility of the different social groups. Combining insights into cognitive representation of knowledge, intergroup bias, and explicit/implicit attitude change, we further derive predictions for intergroup attitudes. We suggest that intergroup attitudes alter depending on the relative associative strength between the social groups and the self, which in turn is determined by the (in)compatibility between social groups. This model unifies existing models on the integration of social identities into the self-concept by suggesting that basic cognitive mechanisms play an important role in facilitating or hindering identity integration and thus contribute to reducing or increasing intergroup bias. PMID:29681878

A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder.

PubMed

Brown, E Sherwood; Todd, Jackie Peterson; Hu, Lisa T; Schmitz, Joy M; Carmody, Thomas J; Nakamura, Alyson; Sunderajan, Prabha; Rush, A John; Adinoff, Bryon; Bret, Mary Ellen; Holmes, Traci; Lo, Alexander

2015-10-01

Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use. A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale. In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed. Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.

Behavioral and Neural Signatures of Reduced Updating of Alternative Options in Alcohol-Dependent Patients during Flexible Decision-Making.

PubMed

Reiter, Andrea M F; Deserno, Lorenz; Kallert, Thomas; Heinze, Hans-Jochen; Heinz, Andreas; Schlagenhauf, Florian

2016-10-26

Addicted individuals continue substance use despite the knowledge of harmful consequences and often report having no choice but to consume. Computational psychiatry accounts have linked this clinical observation to difficulties in making flexible and goal-directed decisions in dynamic environments via consideration of potential alternative choices. To probe this in alcohol-dependent patients (n = 43) versus healthy volunteers (n = 35), human participants performed an anticorrelated decision-making task during functional neuroimaging. Via computational modeling, we investigated behavioral and neural signatures of inference regarding the alternative option. While healthy control subjects exploited the anticorrelated structure of the task to guide decision-making, alcohol-dependent patients were relatively better explained by a model-free strategy due to reduced inference on the alternative option after punishment. Whereas model-free prediction error signals were preserved, alcohol-dependent patients exhibited blunted medial prefrontal signatures of inference on the alternative option. This reduction was associated with patients' behavioral deficit in updating the alternative choice option and their obsessive-compulsive drinking habits. All results remained significant when adjusting for potential confounders (e.g., neuropsychological measures and gray matter density). A disturbed integration of alternative choice options implemented by the medial prefrontal cortex appears to be one important explanation for the puzzling question of why addicted individuals continue drug consumption despite negative consequences. In addiction, patients maintain substance use despite devastating consequences and often report having no choice but to consume. These clinical observations have been theoretically linked to disturbed mechanisms of inference, for example, to difficulties when learning statistical regularities of the environmental structure to guide decisions. Using computational modeling, we demonstrate disturbed inference on alternative choice options in alcohol addiction. Patients neglecting "what might have happened" was accompanied by blunted coding of inference regarding alternative choice options in the medial prefrontal cortex. An impaired integration of alternative choice options implemented by the medial prefrontal cortex might contribute to ongoing drug consumption in the face of evident negative consequences. Copyright © 2016 the authors 0270-6474/16/3610935-14$15.00/0.

Filling of a Poisson trap by a population of random intermittent searchers.

PubMed

Bressloff, Paul C; Newby, Jay M

2012-03-01

We extend the continuum theory of random intermittent search processes to the case of N independent searchers looking to deliver cargo to a single hidden target located somewhere on a semi-infinite track. Each searcher randomly switches between a stationary state and either a leftward or rightward constant velocity state. We assume that all of the particles start at one end of the track and realize sample trajectories independently generated from the same underlying stochastic process. The hidden target is treated as a partially absorbing trap in which a particle can only detect the target and deliver its cargo if it is stationary and within range of the target; the particle is removed from the system after delivering its cargo. As a further generalization of previous models, we assume that up to n successive particles can find the target and deliver its cargo. Assuming that the rate of target detection scales as 1/N, we show that there exists a well-defined mean-field limit N→∞, in which the stochastic model reduces to a deterministic system of linear reaction-hyperbolic equations for the concentrations of particles in each of the internal states. These equations decouple from the stochastic process associated with filling the target with cargo. The latter can be modeled as a Poisson process in which the time-dependent rate of filling λ(t) depends on the concentration of stationary particles within the target domain. Hence, we refer to the target as a Poisson trap. We analyze the efficiency of filling the Poisson trap with n particles in terms of the waiting time density f(n)(t). The latter is determined by the integrated Poisson rate μ(t)=∫(0)(t)λ(s)ds, which in turn depends on the solution to the reaction-hyperbolic equations. We obtain an approximate solution for the particle concentrations by reducing the system of reaction-hyperbolic equations to a scalar advection-diffusion equation using a quasisteady-state analysis. We compare our analytical results for the mean-field model with Monte Carlo simulations for finite N. We thus determine how the mean first passage time (MFPT) for filling the target depends on N and n.

The Use of Scale-Dependent Precision to Increase Forecast Accuracy in Earth System Modelling

NASA Astrophysics Data System (ADS)

Thornes, Tobias; Duben, Peter; Palmer, Tim

2016-04-01

At the current pace of development, it may be decades before the 'exa-scale' computers needed to resolve individual convective clouds in weather and climate models become available to forecasters, and such machines will incur very high power demands. But the resolution could be improved today by switching to more efficient, 'inexact' hardware with which variables can be represented in 'reduced precision'. Currently, all numbers in our models are represented as double-precision floating points - each requiring 64 bits of memory - to minimise rounding errors, regardless of spatial scale. Yet observational and modelling constraints mean that values of atmospheric variables are inevitably known less precisely on smaller scales, suggesting that this may be a waste of computer resources. More accurate forecasts might therefore be obtained by taking a scale-selective approach whereby the precision of variables is gradually decreased at smaller spatial scales to optimise the overall efficiency of the model. To study the effect of reducing precision to different levels on multiple spatial scales, we here introduce a new model atmosphere developed by extending the Lorenz '96 idealised system to encompass three tiers of variables - which represent large-, medium- and small-scale features - for the first time. In this chaotic but computationally tractable system, the 'true' state can be defined by explicitly resolving all three tiers. The abilities of low resolution (single-tier) double-precision models and similar-cost high resolution (two-tier) models in mixed-precision to produce accurate forecasts of this 'truth' are compared. The high resolution models outperform the low resolution ones even when small-scale variables are resolved in half-precision (16 bits). This suggests that using scale-dependent levels of precision in more complicated real-world Earth System models could allow forecasts to be made at higher resolution and with improved accuracy. If adopted, this new paradigm would represent a revolution in numerical modelling that could be of great benefit to the world.

Impact of Langmuir Turbulence on Upper Ocean Response to Hurricane Edouard: Model and Observations

NASA Astrophysics Data System (ADS)

Blair, A.; Ginis, I.; Hara, T.; Ulhorn, E.

2017-12-01

Tropical cyclone intensity is strongly affected by the air-sea heat flux beneath the storm. When strong storm winds enhance upper ocean turbulent mixing and entrainment of colder water from below the thermocline, the resulting sea surface temperature cooling may reduce the heat flux to the storm and weaken the storm. Recent studies suggest that this upper ocean turbulence is strongly affected by different sea states (Langmuir turbulence), which are highly complex and variable in tropical cyclone conditions. In this study, the upper ocean response under Hurricane Edouard (2014) is investigated using a coupled ocean-wave model with and without an explicit sea state dependent Langmuir turbulence parameterization. The results are compared with in situ observations of sea surface temperature and mixed layer depth from AXBTs, as well as satellite sea surface temperature observations. Overall, the model results of mixed layer deepening and sea surface temperature cooling under and behind the storm are consistent with observations. The model results show that the effects of sea state dependent Langmuir turbulence can be significant, particularly on the mixed layer depth evolution. Although available observations are not sufficient to confirm such effects, some observed trends suggest that the sea state dependent parameterization might be more accurate than the traditional (sea state independent) parameterization.

A thermodynamic approach to model the caloric properties of semicrystalline polymers

NASA Astrophysics Data System (ADS)

Lion, Alexander; Johlitz, Michael

2016-05-01

It is well known that the crystallisation and melting behaviour of semicrystalline polymers depends in a pronounced manner on the temperature history. If the polymer is in the liquid state above the melting point, and the temperature is reduced to a level below the glass transition, the final degree of crystallinity, the amount of the rigid amorphous phase and the configurational state of the mobile amorphous phase strongly depend on the cooling rate. If the temperature is increased afterwards, the extents of cold crystallisation and melting are functions of the heating rate. Since crystalline and amorphous phases exhibit different densities, the specific volume depends also on the temperature history. In this article, a thermodynamically based phenomenological approach is developed which allows for the constitutive representation of these phenomena in the time domain. The degree of crystallinity and the configuration of the amorphous phase are represented by two internal state variables whose evolution equations are formulated under consideration of the second law of thermodynamics. The model for the specific Gibbs free energy takes the chemical potentials of the different phases and the mixture entropy into account. For simplification, it is assumed that the amount of the rigid amorphous phase is proportional to the degree of crystallinity. An essential outcome of the model is an equation in closed form for the equilibrium degree of crystallinity in dependence on pressure and temperature. Numerical simulations demonstrate that the process dependences of crystallisation and melting under consideration of the glass transition are represented.

Size, History-Dependent, Activation and Three-Dimensional Effects on the Work and Power Produced During Cyclic Muscle Contractions.

PubMed

Ross, Stephanie A; Ryan, David S; Dominguez, Sebastian; Nigam, Nilima; Wakeling, James M

2018-05-03

Muscles undergo cycles of length change and force development during locomotion, and these contribute to their work and power production to drive body motion. Muscle fibres are typically considered to be linear actuators whose stress depends on their length, velocity, and activation state, and whose properties can be scaled up to explain the function of whole muscles. However, experimental and modelling studies have shown that a muscle's stress additionally depends on inactive and passive tissues within the muscle, the muscle's size, and its previous contraction history. These effects have not been tested under common sets of contraction conditions, especially the cyclic contractions that are typical of locomotion. Here we evaluate the relative effects of size, history-dependent, activation and three-dimensional effects on the work and power produced during cyclic contractions of muscle models. Simulations of muscle contraction were optimized to generate high power outputs: this resulted in the muscle models being largely active during shortening, and inactive during lengthening. As such, the history-dependent effects were dominated by force depression during simulated active shortening rather than force enhancement during active stretch. Internal work must be done to deform the muscle tissue, and to accelerate the internal muscle mass, resulting in reduced power and work that can be done on an external load. The effect of the muscle mass affects the scaling of muscle properties, with the inertial costs of contraction being relatively greater at larger sizes and lower activation levels.

Carbon tradeoffs of restoration and provision of endangered species habitat in a fire-maintained forest

Treesearch

Katherine L. Martin; Matthew D. Hurteau; Bruce A. Hungate; George W. Koch; Malcolm P. North

2015-01-01

Forests are a significant part of the global carbon cycle and are increasingly viewed as tools for mitigating climate change. Natural disturbances, such as fire, can reduce carbon storage. However, many forests and dependent species evolved with frequent fire as an integral ecosystem process. We used a landscape forest simulation model to evaluate the effects of...

Modeling relationships among 217 fires using remote sensing of burn severity in southern pine forests

Treesearch

Sparkle L. Malone; Leda N. Kobziar; Christina L. Staudhammer; Amr Abd-Elrahman

2011-01-01

Pine flatwoods forests in the southeastern US have experienced severe wildfires over the past few decades, often attributed to fuel load build-up. These forest communities are fire dependent and require regular burning for ecosystem maintenance and health. Although prescribed fire has been used to reduce wildfire risk and maintain ecosystem integrity, managers are...

Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

NASA Astrophysics Data System (ADS)

Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Eui-Baek; Lee, Soo-Young; Kang, Il-Jun; Byun, Myung-Woo

2007-11-01

Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN- γ level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice.

The Selective Tie2 Inhibitor Rebastinib Blocks Recruitment and Function of Tie2Hi Macrophages in Breast Cancer and Pancreatic Neuroendocrine Tumors.

PubMed

Harney, Allison S; Karagiannis, George S; Pignatelli, Jeanine; Smith, Bryan D; Kadioglu, Ece; Wise, Scott C; Hood, Molly M; Kaufman, Michael D; Leary, Cynthia B; Lu, Wei-Ping; Al-Ani, Gada; Chen, Xiaoming; Entenberg, David; Oktay, Maja H; Wang, Yarong; Chun, Lawrence; De Palma, Michele; Jones, Joan G; Flynn, Daniel L; Condeelis, John S

2017-11-01

Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation, and metastasis, which can offset the effects of chemotherapy, radiation, and antiangiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and protumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2 + myeloid cell infiltration, antiangiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2 Hi /Vegf-A Hi macrophages in the tumor microenvironment of metastasis (TMEM). The antitumor effects of rebastinib enhance the efficacy of microtubule inhibiting chemotherapeutic agents, either eribulin or paclitaxel, by reducing tumor volume, metastasis, and improving overall survival. Rebastinib inhibition of angiopoietin/Tie2 signaling impairs multiple pathways in tumor progression mediated by protumoral Tie2 + macrophages, including TMEM-dependent dissemination and angiopoietin/Tie2-dependent angiogenesis. Rebastinib is a promising therapy for achieving Tie2 inhibition in cancer patients. Mol Cancer Ther; 16(11); 2486-501. ©2017 AACR . ©2017 American Association for Cancer Research.

Concurrent hyperthermia estimation schemes based on extended Kalman filtering and reduced-order modelling.

PubMed

Potocki, J K; Tharp, H S

1993-01-01

The success of treating cancerous tissue with heat depends on the temperature elevation, the amount of tissue elevated to that temperature, and the length of time that the tissue temperature is elevated. In clinical situations the temperature of most of the treated tissue volume is unknown, because only a small number of temperature sensors can be inserted into the tissue. A state space model based on a finite difference approximation of the bioheat transfer equation (BHTE) is developed for identification purposes. A full-order extended Kalman filter (EKF) is designed to estimate both the unknown blood perfusion parameters and the temperature at unmeasured locations. Two reduced-order estimators are designed as computationally less intensive alternatives to the full-order EKF. Simulation results show that the success of the estimation scheme depends strongly on the number and location of the temperature sensors. Superior results occur when a temperature sensor exists in each unknown blood perfusion zone, and the number of sensors is at least as large as the number of unknown perfusion zones. Unacceptable results occur when there are more unknown perfusion parameters than temperature sensors, or when the sensors are placed in locations that do not sample the unknown perfusion information.

Troubled times, troubled relationships: how economic resources, gender beliefs, and neighborhood disadvantage influence intimate partner violence.

PubMed

Golden, Shelley D; Perreira, Krista M; Durrance, Christine Piette

2013-07-01

We evaluate race/ethnicity and nativity-based disparities in three different types of intimate partner violence (IPV) and examine how economic hardship, maternal economic dependency, maternal gender beliefs, and neighborhood disadvantage influence these disparities. Using nationally representative data from urban mothers of young children who are living with their intimate partners (N = 1,886), we estimate a series of unadjusted and adjusted logit models on mothers' reports of physical assault, emotional abuse, and coercion. When their children were age 3, more than one in five mothers were living with a partner who abused them. The prevalence of any IPV was highest among Hispanic (26%) and foreign-born (35%) mothers. Economic hardship, economic dependency on a romantic partner, and traditional gender beliefs each increased women's risk for exposure to one or more types of IPV, whereas neighborhood conditions were not significantly related to IPV in adjusted models. These factors also explained most of the racial/ethnic and nativity disparities in IPV. Policies and programs that reduce economic hardship among women with young children, promote women's economic independence, and foster gender equity in romantic partnerships can potentially reduce multiple forms of IPV.

Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro✩

PubMed Central

Secor, Eric R.; Singh, Anurag; Guernsey, Linda A.; McNamara, Jeff T.; Zhan, Lijun; Maulik, Nilanjana; Thrall, Roger S.

2009-01-01

Bromelain (Br), an extract from pineapple stem with cysteine protease activity, exerts anti-inflammatory effects in a number of inflammatory models. We have previously shown that Br treatment decreased activated CD4+ T cells and has a therapeutic role in an ovalbumin-induced murine model of allergic airway disease. The current study was designed to determine the effect of Br on CD4+ T cell activation, specifically the expression of CD25 in vitro. CD25 is up regulated upon T cell activation, found as a soluble fraction (sCD25) and is a therapeutic target in inflammation, autoimmunity and allergy. Br treatment of anti-CD3 stimulated CD4+ T cells reduced CD25 expression in a dose and time dependent manner. This reduction of CD25 was dependent on the proteolytic action of Br as the addition of E64 (a cysteine protease inhibitor) abrogated this response. The concentration of sCD25 was increased in supernatants of Br treated activated CD4+ T cells as compared to control cells, suggesting that Br proteolytically cleaved cell-surface CD25. This novel mechanism of action identifies how Br may exert its therapeutic benefits in inflammatory conditions. PMID:19162239

Relationships between nonlinear normal modes and response to random inputs

NASA Astrophysics Data System (ADS)

Schoneman, Joseph D.; Allen, Matthew S.; Kuether, Robert J.

2017-02-01

The ability to model nonlinear structures subject to random excitation is of key importance in designing hypersonic aircraft and other advanced aerospace vehicles. When a structure is linear, superposition can be used to construct its response to a known spectrum in terms of its linear modes. Superposition does not hold for a nonlinear system, but several works have shown that a system's dynamics can still be understood qualitatively in terms of its nonlinear normal modes (NNMs). This work investigates the connection between a structure's undamped nonlinear normal modes and the spectrum of its response to high amplitude random forcing. Two examples are investigated: a spring-mass system and a clamped-clamped beam modeled within a geometrically nonlinear finite element package. In both cases, an intimate connection is observed between the smeared peaks in the response spectrum and the frequency-energy dependence of the nonlinear normal modes. In order to understand the role of coupling between the underlying linear modes, reduced order models with and without modal coupling terms are used to separate the effect of each NNM's backbone from the nonlinear couplings that give rise to internal resonances. In the cases shown here, uncoupled, single-degree-of-freedom nonlinear models are found to predict major features in the response with reasonable accuracy; a highly inexpensive approximation such as this could be useful in design and optimization studies. More importantly, the results show that a reduced order model can be expected to give accurate results only if it is also capable of accurately predicting the frequency-energy dependence of the nonlinear modes that are excited.

A novel heart rate control model provides insights linking LF-HRV behavior to the open-loop gain.

PubMed

Dvir, Hila; Bobrovsky, Ben Zion; Gabbay, Uri

2013-09-20

Low-frequency heart rate variability (LF-HRV) at rest has already been successfully modeled as self-sustained oscillations in a nonlinear control loop, but these models fail to simulate LF-HRV decreases either during aerobic exercise or in heart failure patients. Following control engineering practices, we assume the existence of a biological excitation (dither) within the heart rate control loop that softens the nonlinearity and studied LF-HRV behavior in a dither-embedded model. We adopted the Ottesen model with some revisions and induced a dither of high-frequency stochastic perturbations. We simulated scenarios of a healthy subject at rest and during aerobic exercise (by decreasing peripheral vascular resistance) and a heart failure patient (by decreasing stroke volume). The simulations resembled physiological LF-HRV behavior, i.e., LF-HRV decreased during aerobic exercise and in the heart failure patient. The simulations exhibited LF-HRV dependency on the open-loop gain, which is related to the product of the feedback gain and the feed forward gain. We are the first to demonstrate that LF-HRV may be dependent on the open-loop gain. Accordingly, reduced open-loop gain results in decreased LF-HRV, and vice versa. Our findings explain a well-known but unexplained observed phenomenon of reduced LF-HRV both in heart failure patients and in healthy subjects performing aerobic exercise. These findings have implications on how changes in LF-HRV can be interpreted physiologically, a necessary step towards the clinical utilization of LF-HRV. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Determination of critical nucleation number for a single nucleation amyloid-β aggregation model.

PubMed

Ghosh, Preetam; Vaidya, Ashwin; Kumar, Amit; Rangachari, Vijayaraghavan

2016-03-01

Aggregates of amyloid-β (Aβ) peptide are known to be the key pathological agents in Alzheimer disease (AD). Aβ aggregates to form large, insoluble fibrils that deposit as senile plaques in AD brains. The process of aggregation is nucleation-dependent in which the formation of a nucleus is the rate-limiting step, and controls the physiochemical fate of the aggregates formed. Therefore, understanding the properties of nucleus and pre-nucleation events will be significant in reducing the existing knowledge-gap in AD pathogenesis. In this report, we have determined the plausible range of critical nucleation number (n(*)), the number of monomers associated within the nucleus for a homogenous aggregation model with single unique nucleation event, by two independent methods: A reduced-order stability analysis and ordinary differential equation based numerical analysis, supported by experimental biophysics. The results establish that the most likely range of n(*) is between 7 and 14 and within, this range, n(*) = 12 closely supports the experimental data. These numbers are in agreement with those previously reported, and importantly, the report establishes a new modeling framework using two independent approaches towards a convergent solution in modeling complex aggregation reactions. Our model also suggests that the formation of large protofibrils is dependent on the nature of n(*), further supporting the idea that pre-nucleation events are significant in controlling the fate of larger aggregates formed. This report has re-opened an old problem with a new perspective and holds promise towards revealing the molecular events in amyloid pathologies in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Anxiety: towards a decision-theoretic perspective.

PubMed

Shechter, M; Zeidner, M

1990-05-01

This paper sets out to illustrate how anxiety may be incorporated into a formal decision theoretic utility model of choice, and to suggest several measurement procedures towards that end. The major propositions derived and posited in this paper lend considerable support to intuitive notions with respect to the effects of anxiety on human behaviour in risky decision situations. Namely, that the willingness of an individual to pay to reduce health risks (an economic indicator of individual welfare associated with reduced morbidity or increased longevity) tends to be positive and higher when anxiety is present than when it is not. The formal results of the analysis show that when psychological considerations are incorporated into a state-dependent utility model, the normative results customarily obtained concerning value-of-life need to be qualified.

Electrochemical state and internal variables estimation using a reduced-order physics-based model of a lithium-ion cell and an extended Kalman filter

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

Stetzel, KD; Aldrich, LL; Trimboli, MS

2015-03-15

This paper addresses the problem of estimating the present value of electrochemical internal variables in a lithium-ion cell in real time, using readily available measurements of cell voltage, current, and temperature. The variables that can be estimated include any desired set of reaction flux and solid and electrolyte potentials and concentrations at any set of one-dimensional spatial locations, in addition to more standard quantities such as state of charge. The method uses an extended Kalman filter along with a one-dimensional physics-based reduced-order model of cell dynamics. Simulations show excellent and robust predictions having dependable error bounds for most internal variables.more » (C) 2014 Elsevier B.V. All rights reserved.« less

Sleep-Dependent Modulation of Metabolic Rate in Drosophila.

PubMed

Stahl, Bethany A; Slocumb, Melissa E; Chaitin, Hersh; DiAngelo, Justin R; Keene, Alex C

2017-08-01

Dysregulation of sleep is associated with metabolic diseases, and metabolic rate (MR) is acutely regulated by sleep-wake behavior. In humans and rodent models, sleep loss is associated with obesity, reduced metabolic rate, and negative energy balance, yet little is known about the neural mechanisms governing interactions between sleep and metabolism. We have developed a system to simultaneously measure sleep and MR in individual Drosophila, allowing for interrogation of neural systems governing interactions between sleep and metabolic rate. Like mammals, MR in flies is reduced during sleep and increased during sleep deprivation suggesting sleep-dependent regulation of MR is conserved across phyla. The reduction of MR during sleep is not simply a consequence of inactivity because MR is reduced ~30 minutes following the onset of sleep, raising the possibility that CO2 production provides a metric to distinguish different sleep states in the fruit fly. To examine the relationship between sleep and metabolism, we determined basal and sleep-dependent changes in MR is reduced in starved flies, suggesting that starvation inhibits normal sleep-associated effects on metabolic rate. Further, translin mutant flies that fail to suppress sleep during starvation demonstrate a lower basal metabolic rate, but this rate was further reduced in response to starvation, revealing that regulation of starvation-induced changes in MR and sleep duration are genetically distinct. Therefore, this system provides the unique ability to simultaneously measure sleep and oxidative metabolism, providing novel insight into the physiological changes associated with sleep and wakefulness in the fruit fly. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

VR-SCOSMO: A smooth conductor-like screening model with charge-dependent radii for modeling chemical reactions.

PubMed

Kuechler, Erich R; Giese, Timothy J; York, Darrin M

2016-04-28

To better represent the solvation effects observed along reaction pathways, and of ionic species in general, a charge-dependent variable-radii smooth conductor-like screening model (VR-SCOSMO) is developed. This model is implemented and parameterized with a third order density-functional tight binding quantum model, DFTB3/3OB-OPhyd, a quantum method which was developed for organic and biological compounds, utilizing a specific parameterization for phosphate hydrolysis reactions. Unlike most other applications with the DFTB3/3OB model, an auxiliary set of atomic multipoles is constructed from the underlying DFTB3 density matrix which is used to interact the solute with the solvent response surface. The resulting method is variational, produces smooth energies, and has analytic gradients. As a baseline, a conventional SCOSMO model with fixed radii is also parameterized. The SCOSMO and VR-SCOSMO models shown have comparable accuracy in reproducing neutral-molecule absolute solvation free energies; however, the VR-SCOSMO model is shown to reduce the mean unsigned errors (MUEs) of ionic compounds by half (about 2-3 kcal/mol). The VR-SCOSMO model presents similar accuracy as a charge-dependent Poisson-Boltzmann model introduced by Hou et al. [J. Chem. Theory Comput. 6, 2303 (2010)]. VR-SCOSMO is then used to examine the hydrolysis of trimethylphosphate and seven other phosphoryl transesterification reactions with different leaving groups. Two-dimensional energy landscapes are constructed for these reactions and calculated barriers are compared to those obtained from ab initio polarizable continuum calculations and experiment. Results of the VR-SCOSMO model are in good agreement in both cases, capturing the rate-limiting reaction barrier and the nature of the transition state.

Trust Model of Wireless Sensor Networks and Its Application in Data Fusion

PubMed Central

Chen, Zhenguo; Tian, Liqin; Lin, Chuang

2017-01-01

In order to ensure the reliability and credibility of the data in wireless sensor networks (WSNs), this paper proposes a trust evaluation model and data fusion mechanism based on trust. First of all, it gives the model structure. Then, the calculation rules of trust are given. In the trust evaluation model, comprehensive trust consists of three parts: behavior trust, data trust, and historical trust. Data trust can be calculated by processing the sensor data. Based on the behavior of nodes in sensing and forwarding, the behavior trust is obtained. The initial value of historical trust is set to the maximum and updated with comprehensive trust. Comprehensive trust can be obtained by weighted calculation, and then the model is used to construct the trust list and guide the process of data fusion. Using the trust model, simulation results indicate that energy consumption can be reduced by an average of 15%. The detection rate of abnormal nodes is at least 10% higher than that of the lightweight and dependable trust system (LDTS) model. Therefore, this model has good performance in ensuring the reliability and credibility of the data. Moreover, the energy consumption of transmitting was greatly reduced. PMID:28350347

A model of plant isoprene emission based on available reducing power captures responses to atmospheric CO₂.

PubMed

Morfopoulos, Catherine; Sperlich, Dominik; Peñuelas, Josep; Filella, Iolanda; Llusià, Joan; Medlyn, Belinda E; Niinemets, Ülo; Possell, Malcolm; Sun, Zhihong; Prentice, Iain Colin

2014-07-01

We present a unifying model for isoprene emission by photosynthesizing leaves based on the hypothesis that isoprene biosynthesis depends on a balance between the supply of photosynthetic reducing power and the demands of carbon fixation. We compared the predictions from our model, as well as from two other widely used models, with measurements of isoprene emission from leaves of Populus nigra and hybrid aspen (Populus tremula × P. tremuloides) in response to changes in leaf internal CO2 concentration (C(i)) and photosynthetic photon flux density (PPFD) under diverse ambient CO2 concentrations (C(a)). Our model reproduces the observed changes in isoprene emissions with C(i) and PPFD, and also reproduces the tendency for the fraction of fixed carbon allocated to isoprene to increase with increasing PPFD. It also provides a simple mechanism for the previously unexplained decrease in the quantum efficiency of isoprene emission with increasing C(a). Experimental and modelled results support our hypothesis. Our model can reproduce the key features of the observations and has the potential to improve process-based modelling of isoprene emissions by land vegetation at the ecosystem and global scales. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Increased Extracellular Glutamate In the Nucleus Accumbens Promotes Excessive Ethanol Drinking in Ethanol Dependent Mice

PubMed Central

Griffin III, William C; Haun, Harold L; Hazelbaker, Callan L; Ramachandra, Vorani S; Becker, Howard C

2014-01-01

Using a well-established model of ethanol dependence and relapse, this study examined adaptations in glutamatergic transmission in the nucleus accumbens (NAc) and their role in regulating voluntary ethanol drinking. Mice were first trained to drink ethanol in a free-choice, limited access (2 h/day) paradigm. One group (EtOH mice) received repeated weekly cycles of chronic intermittent ethanol (CIE) exposure with intervening weeks of test drinking sessions, whereas the remaining mice (CTL mice) were similarly treated but did not receive CIE treatment. Over repeated cycles of CIE exposure, EtOH mice exhibited significant escalation in drinking (up to ∼3.5 g/kg), whereas drinking remained relatively stable at baseline levels (2–2.5 g/kg) in CTL mice. Using in vivo microdialysis procedures, extracellular glutamate (GLUEX) levels in the NAc were increased approximately twofold in EtOH mice compared with CTL mice, and this difference was observed 7 days after final CIE exposure, indicating that this hyperglutamatergic state persisted beyond acute withdrawal. This finding prompted additional studies examining the effects of pharmacologically manipulating GLUEX in the NAc on ethanol drinking in the CIE model. The non-selective glutamate reuptake antagonist, threo-β-benzyloxyaspartate (TBOA), was bilaterally microinjected into the NAc and found to dose-dependently increase drinking in nondependent (CTL) mice to levels attained by dependent (EtOH) mice. TBOA also further increased drinking in EtOH mice. In contrast, reducing glutamatergic transmission in the NAc via bilateral injections of the metabotropic glutamate receptor-2/3 agonist LY379268 reduced drinking in dependent (EtOH) mice to nondependent (CTL) levels, whereas having a more modest effect in decreasing ethanol consumption in CTL mice. Taken together, these data support an important role of glutamatergic transmission in the NAc in regulating ethanol drinking. Additionally, these results indicate that ethanol dependence produces adaptations that favor elevated glutamate activity in the NAc which, in turn, promote excessive levels of ethanol consumption associated with dependence. PMID:24067300

An intervention to stop smoking among patients suspected of TB--evaluation of an integrated approach.

PubMed

Siddiqi, Kamran; Khan, Amir; Ahmad, Maqsood; Shafiq-ur-Rehman

2010-03-25

In many low- and middle-income countries, where tobacco use is common, tuberculosis is also a major problem. Tobacco use increases the risk of developing tuberculosis, secondary mortality, poor treatment compliance and relapses. In countries with TB epidemic, even a modest relative risk leads to a significant attributable risk. Treating tobacco dependence, therefore, is likely to have benefits for controlling tuberculosis in addition to reducing the non-communicable disease burden associated with smoking. In poorly resourced health systems which face a dual burden of disease secondary to tuberculosis and tobacco, an integrated approach to tackle tobacco dependence in TB control could be economically desirable. During TB screening, health professionals come across large numbers of patients with respiratory symptoms, a significant proportion of which are likely to be tobacco users. These clinical encounters, considered to be "teachable moments", provide a window of opportunity to offer treatment for tobacco dependence. We aim to develop and trial a complex intervention to reduce tobacco dependence among TB suspects based on the WHO 'five steps to quit' model. This model relies on assessing personal motivation to quit tobacco use and uses it as the basis for assessing suitability for the different therapeutic options for tobacco dependence.We will use the Medical Research Council framework approach for evaluating complex interventions to: (a) design an evidence-based treatment package (likely to consist of training materials for health professionals and education tools for patients); (b) pilot the package to determine the delivery modalities in TB programme (c) assess the incremental cost-effectiveness of the package compared to usual care using a cluster RCT design; (d) to determine barriers and drivers to the provision of treatment of tobacco dependence within TB programmes; and (e) support long term implementation. The main outcomes to assess the effectiveness would be point abstinence at 4 weeks and continuous abstinence up to 6 months. This work will be carried out in Pakistan and is expected to have relevance for other low and middle income countries with high tobacco use and TB incidence. This will enhance our knowledge of the cost-effectiveness of treating tobacco dependence in patients suspected of TB. ISRCTN08829879.

Heat reversal of activity-based anorexia: implications for the treatment of anorexia nervosa.

PubMed

Gutierrez, Emilio; Cerrato, María; Carrera, Olaia; Vazquez, Reyes

2008-11-01

Activity-based anorexia (ABA) provides an animal model of anorexia nervosa (AN). In this model, rats given restricted access to food but unrestricted access to activity wheels, run excessively while reducing food intake, lose a sizeable percentage of body weight, become hypothermic, and can fail to recover unless removed from these conditions. Once rats had lost 20% of body weight under standard ABA conditions, they were assigned to one of two ambient temperature (AT) conditions. Increased AT reduced running rates and led to weight gain in active rats. The effect of increasing AT on food intake was dependent on whether the rats were sedentary or active. Although warming reduced food intake in the sedentary rats their body weight remained stable, whereas in active rats increased AT did not reduce food intake and weight gain gradually rose. From a translational perspective, these findings offer a fresh perspective to the disorder, and underscore the need for further studies to assess the effects of heat treatment in patients as an innovative adjunctive treatment for anorexia nervosa.

Modelling of subsonic COIL with an arbitrary magnetic modulation

NASA Astrophysics Data System (ADS)

Beránek, Jaroslav; Rohlena, Karel

2007-05-01

The concept of 1D subsonic COIL model with a mixing length was generalized to include the influence of a variable magnetic field on the stimulated emission cross-section. Equations describing the chemical kinetics were solved taking into account together with the gas temperature also a simplified mixing model of oxygen and iodine molecules. With the external time variable magnetic field the model is no longer stationary. A transformation in the system moving with the mixture reduces partial differential equations to ordinary equations in time with initial conditions given either by the stationary flow at the moment when the magnetic field is switched on combined with the boundary conditions at the injector. Advantage of this procedure is a possibility to consider an arbitrary temporal dependence of the imposed magnetic field and to calculate directly the response of the laser output. The method was applied to model the experimental data measured with the subsonic version of the COIL device in the Institute of Physics, Prague, where the applied magnetic field had a saw-tooth dependence. We found that various values characterizing the laser performance, such as the power density distribution over the active zone cross-section, may have a fairly complicated structure given by combined effects of the delayed reaction to the magnetic switching and the flow velocity. This is necessarily translated in a time dependent spatial inhomogeneity of output beam intensity profile.

Analysis of signal-dependent sensor noise on JPEG 2000-compressed Sentinel-2 multi-spectral images

NASA Astrophysics Data System (ADS)

Uss, M.; Vozel, B.; Lukin, V.; Chehdi, K.

2017-10-01

The processing chain of Sentinel-2 MultiSpectral Instrument (MSI) data involves filtering and compression stages that modify MSI sensor noise. As a result, noise in Sentinel-2 Level-1C data distributed to users becomes processed. We demonstrate that processed noise variance model is bivariate: noise variance depends on image intensity (caused by signal-dependency of photon counting detectors) and signal-to-noise ratio (SNR; caused by filtering/compression). To provide information on processed noise parameters, which is missing in Sentinel-2 metadata, we propose to use blind noise parameter estimation approach. Existing methods are restricted to univariate noise model. Therefore, we propose extension of existing vcNI+fBm blind noise parameter estimation method to multivariate noise model, mvcNI+fBm, and apply it to each band of Sentinel-2A data. Obtained results clearly demonstrate that noise variance is affected by filtering/compression for SNR less than about 15. Processed noise variance is reduced by a factor of 2 - 5 in homogeneous areas as compared to noise variance for high SNR values. Estimate of noise variance model parameters are provided for each Sentinel-2A band. Sentinel-2A MSI Level-1C noise models obtained in this paper could be useful for end users and researchers working in a variety of remote sensing applications.

Fault-Tolerant and Elastic Streaming MapReduce with Decentralized Coordination

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

Kumbhare, Alok; Frincu, Marc; Simmhan, Yogesh

2015-06-29

The MapReduce programming model, due to its simplicity and scalability, has become an essential tool for processing large data volumes in distributed environments. Recent Stream Processing Systems (SPS) extend this model to provide low-latency analysis of high-velocity continuous data streams. However, integrating MapReduce with streaming poses challenges: first, the runtime variations in data characteristics such as data-rates and key-distribution cause resource overload, that inturn leads to fluctuations in the Quality of the Service (QoS); and second, the stateful reducers, whose state depends on the complete tuple history, necessitates efficient fault-recovery mechanisms to maintain the desired QoS in the presence ofmore » resource failures. We propose an integrated streaming MapReduce architecture leveraging the concept of consistent hashing to support runtime elasticity along with locality-aware data and state replication to provide efficient load-balancing with low-overhead fault-tolerance and parallel fault-recovery from multiple simultaneous failures. Our evaluation on a private cloud shows up to 2:8 improvement in peak throughput compared to Apache Storm SPS, and a low recovery latency of 700 -1500 ms from multiple failures.« less

Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury.

PubMed

Martin, W J

1984-08-01

Neutrophil-mediated injury to lung parenchymal cells has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. As an in vitro model of neutrophil-mediated injury, this study used activated human neutrophils as effector cells in an 18-h cytotoxicity assay with 51Cr-labeled bovine pulmonary artery endothelial cells serving as target cells. Neutrophils effectively injured pulmonary endothelial cells, expressed as cytotoxic index (CI), of 63.8 +/- 5.4, and this injury could be significantly reduced by several agents, including 1% dimethyl sulfoxide (CI, 51.3 +/- 3.7), 50 micrograms/ml ascorbic acid (CI, 40.8 +/- 4.7), and especially 1,100 U/ml catalase (CI, 14.3 +/- 4.1). As cell-free models of neutrophil-mediated endothelial cell injury, H2O2 (30 microM), O2- (generated by 0.5 mU xanthine oxidase), and the myeloperoxidase-dependent (0.32 U) hypohalite ion were each capable of injuring the target cells with CI of 6.21 +/- 2.8, 53.6 +/- 5.3, and 21.2 +/- 1.5, respectively. Catalase was effective in reducing the injurious effect of each of these oxidant-generating systems (p less than 0.01, all comparisons), confirming the important role for H2O2 in the mediation of this injury. The data indicate that neutrophils are capable of killing pulmonary endothelial cells by a pathway largely dependent on the generation of H2O2, and suggest the possibility that removal of H2O2 from the alveolar structures in subjects with these disorder might be an effective future therapeutic approach.

Factors controlling nitrate fluxes in groundwater in agricultural areas

USGS Publications Warehouse

Liao, Lixia; Green, Christopher T.; Bekins, Barbara A.; Böhlke, J.K.

2012-01-01

The impact of agricultural chemicals on groundwater quality depends on the interactions of biogeochemical and hydrologic factors. To identify key processes affecting distribution of agricultural nitrate in groundwater, a parsimonious transport model was applied at 14 sites across the U.S. Simulated vertical profiles of NO3-, N2 from denitrification, O2, Cl-, and environmental tracers of groundwater age were matched to observations by adjusting the parameters for recharge rate, unsaturated zone travel time, fractions of N and Cl- inputs leached to groundwater, O2 reduction rate, O2 threshold for denitrification, and denitrification rate. Model results revealed important interactions among biogeochemical and physical factors. Chloride fluxes decreased between the land surface and water table possibly because of Cl- exports in harvested crops (averaging 22% of land-surface Cl- inputs). Modeled zero-order rates of O2 reduction and denitrification were correlated. Denitrification rates at depth commonly exceeded overlying O2 reduction rates, likely because shallow geologic sources of reactive electron donors had been depleted. Projections indicated continued downward migration of NO3- fronts at sites with denitrification rates -1 yr-1. The steady state depth of NO3- depended to a similar degree on application rate, leaching fraction, recharge, and NO3- and O2 reaction rates. Steady state total mass in each aquifer depended primarily on the N application rate. In addition to managing application rates at land surface, efficient water use may reduce the depth and mass of N in groundwater because lower recharge was associated with lower N fraction leached. Management actions to reduce N leaching could be targeted over aquifers with high-recharge and low-denitrification rates.

Landscape pattern and car use: Linking household data with satellite imagery

NASA Astrophysics Data System (ADS)

Keller, R.; Vance, C.

2013-12-01

Landscape pattern has long been hypothesized to influence automobile dependency. Because choices about land development tend to have long-lasting impacts that span over decades, understanding the magnitude of this influence is critical to the design of policies to reduce emissions and other negative externalities associated with car use. Combining household survey data from Germany with satellite imagery and other geo-referenced data sources, we undertake an econometric analysis of the relation between landscape pattern and automobile dependency. Specifically, we employ a two-part model to investigate two dimensions of car use, the discrete decision to own a car and, conditional upon ownership, the continuous decision of how far to drive. Results indicate that landscape pattern, as captured by measures of both land cover (e.g. the extent of open space and landscape diversity) and land use (e.g. the density of regional businesses) are important predictors of car ownership and use. Other policy-relevant variables, such as fuel prices and public transit infrastructure, are also identified as correlates. Based on the magnitude of our estimates, we conclude that carefully considered land development and zoning measures - ones that encourage dense development, diverse land cover and mixed land use - can have beneficial impacts in reducing car dependency that extend far into the future. Key terms: Landscape pattern, Satellite imagery, Germany, Two-part model Figure 1. Distribution of Elasticities of Landscape and Social Effects on German Household Weekly Car Use Results from Two Part Model N = 13,089 (probit) N = 10,987 (OLS)Robust standard errors in parentheses***, **, and *, denotes significance at the 0.01, 0.05, and 0.1 levels

The Research and Application of Information Platform About Community Support Intervention for Patients with Alcohol Dependence.

PubMed

Yang, Liqun

2016-01-01

Through the establishment of electronic health records, health education and measures such as regional information sharing platform, we explored the management of patients with alcohol dependence living in communities and established a medical information resource sharing model between mental hospital-community to strengthen the supportive intervention management of patients with alcohol dependence, improve the effect of intervention and reduce the rate of compound drink. To design the questionnaire of health state for patients with alcohol dependence. After data collection. We should establish electronic health records and community support intervention, make medical health card with terminal configuration card reader in both mental hospitals and community, develop information platform, establish a variety of supporting interventions and the service function modules, unblock information sharing between hospitals and community to make full use of the platform to carry out health education and health intervention management. The effectives of community supportive intervention are improved, rehabilitation rate of patients is reduced greatly, bad ways of life behavior are better. Establishing electronic health records is an important mean of community supportive interventions which is good for Real-time, dynamic management and promoting self-management skills making the dream of medical information resource between hospital-community sharing come true.

Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study.

PubMed

Adejumo, Adeyinka Charles; Alliu, Samson; Ajayi, Tokunbo Opeyemi; Adejumo, Kelechi Lauretta; Adegbala, Oluwole Muyiwa; Onyeakusi, Nnaemeka Egbuna; Akinjero, Akintunde Micheal; Durojaiye, Modupeoluwa; Bukong, Terence Ndonyi

2017-01-01

Cannabis use is associated with reduced prevalence of obesity and diabetes mellitus (DM) in humans and mouse disease models. Obesity and DM are a well-established independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most prevalent liver disease globally. The effects of cannabis use on NAFLD prevalence in humans remains ill-defined. Our objective is to determine the relationship between cannabis use and the prevalence of NAFLD in humans. We conducted a population-based case-control study of 5,950,391 patients using the 2014 Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Survey (NIS) discharge records of patients 18 years and older. After identifying patients with NAFLD (1% of all patients), we next identified three exposure groups: non-cannabis users (98.04%), non-dependent cannabis users (1.74%), and dependent cannabis users (0.22%). We adjusted for potential demographics and patient related confounders and used multivariate logistic regression (SAS 9.4) to determine the odds of developing NAFLD with respects to cannabis use. Our findings revealed that cannabis users (dependent and non-dependent) showed significantly lower NAFLD prevalence compared to non-users (AOR: 0.82[0.76-0.88]; p<0.0001). The prevalence of NAFLD was 15% lower in non-dependent users (AOR: 0.85[0.79-0.92]; p<0.0001) and 52% lower in dependent users (AOR: 0.49[0.36-0.65]; p<0.0001). Among cannabis users, dependent patients had 43% significantly lower prevalence of NAFLD compared to non-dependent patients (AOR: 0.57[0.42-0.77]; p<0.0001). Our observations suggest that cannabis use is associated with lower prevalence of NAFLD in patients. These novel findings suggest additional molecular mechanistic studies to explore the potential role of cannabis use in NAFLD development.

Electro-mechanical analysis of composite and sandwich multilayered structures by shell elements with node-dependent kinematics

NASA Astrophysics Data System (ADS)

Carrera; Valvano; Kulikov

2018-01-01

In this work, a new class of finite elements for the analysis of composite and sandwich shells embedding piezoelectric skins and patches is proposed. The main idea of models coupling is developed by presenting the concept of nodal dependent kinematics where the same finite element can present at each node a different approximation of the main unknowns by setting a node-wise through-the-thickness approximation base. In a global/local approach scenario, the computational costs can be reduced drastically by assuming refined theories only in those zones/nodes of the structural domain where the resulting strain and stress states, and their electro-mechanical coupling present a complex distribution. Several numerical investigations are carried out to validate the accuracy and efficiency of the present shell element. An accurate representation of mechanical stresses and electric displacements in localized zones is possible with reduction of the computational costs if an accurate distribution of the higher-order kinematic capabilities is performed. On the contrary, the accuracy of the solution in terms of mechanical displacements and electric potential values depends on the global approximation over the whole structure. The efficacy of the present node-dependent variable kinematic models, thus, depends on the characteristics of the problem under consideration as well as on the required analysis type.

Dynamics in a Maximally Symmetric Universe

NASA Astrophysics Data System (ADS)

Bewketu, Asnakew

2016-03-01

Our present understanding of the evolution of the universe relies upon the Friedmann- Robertson- Walker cosmological models. This model is so successful that it is now being considered as the Standard Model of Cosmology. So in this work we derive the Fried- mann equations using the Friedmann-Robertson-Walker metric together with Einstein field equation and then we give a simple method to reduce Friedmann equations to a second order linear differential equation when it is supplemented with a time dependent equation of state. Furthermore, as illustrative examples, we solve this equation for some specific time dependent equation of states. And also by using the Friedmann equations with some time dependent equation of state we try to determine the cosmic scale factor(the rate at which the universe expands) and age of the Friedmann universe, for the matter dominated era, radiation dominated era and for both matter and radiation dominated era by considering different cases. We have finally discussed the observable quantities that can be evidences for the accelerated expansion of the Friedmann universe. I would like to acknowledge Addis Ababa University for its financial and material support to my work on the title mentioned above.

A 2D mechanical-magneto-thermal model for direction-dependent magnetoelectric effect in laminates

NASA Astrophysics Data System (ADS)

Zhang, Shunzu; Yao, Hong; Gao, Yuanwen

2017-04-01

A two dimensional (2D) mechanical-magneto-thermal model of direction-dependent magnetoelectric (ME) effect in Terfenol-D/PZT/Terfenol-D laminated composites is established. The expressions of ME coefficient at low and resonance frequencies are derived by the average field method, respectively. The prediction of theoretical model presents a good agreement with the experimental data. The combined effect of orientation-dependent stress and magnetic fields, as well as operating temperature on ME coefficient is discussed. It is shown that ME effect presents a significantly nonlinear change with the increasing pre-stress under different loading angles. There exists an optimal angle and value of pre-stress corresponding to the best ME effect, improving the angle of pre-stress can get more prominent ME coupling than in x axis state. Note that an optimal angle of magnetic field gradually increases with the rise of pre-stress, which can further lead to the enhancement of ME coefficient. Meanwhile, reducing the operating temperature can enhance ME coefficient. Furthermore, resonance frequency, affected by pre-stress, magnetic field and temperature via " ΔE effect", can enhance ME coefficient about 100 times than that at low frequency.

Games of age-dependent prevention of chronic infections by social distancing.

PubMed

Reluga, Timothy C; Li, Jing

2013-06-01

Epidemiological games combine epidemic modelling with game theory to assess strategic choices in response to risks from infectious diseases. In most epidemiological games studied thus-far, the strategies of an individual are represented with a single choice parameter. There are many natural situations where strategies can not be represented by a single dimension, including situations where individuals can change their behavior as they age. To better understand how age-dependent variations in behavior can help individuals deal with infection risks, we study an epidemiological game in an SI model with two life-history stages where social distancing behaviors that reduce exposure rates are age-dependent. When considering a special case of the general model, we show that there is a unique Nash equilibrium when the infection pressure is a monotone function of aggregate exposure rates, but non-monotone effects can appear even in our special case. The non-monotone effects sometimes result in three Nash equilibria, two of which have local invasion potential simultaneously. Returning to a general case, we also describe a game with continuous age-structure using partial-differential equations, numerically identify some Nash equilibria, and conjecture about uniqueness.

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

PubMed Central

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; Bourassa, Megan W.; Sleiman, Sama F.; John, Roseleen; Thinnes, Cyrille C.; Yeh, Tzu-Lan; Demetriades, Marina; Neitemeier, Sandra; Cruz, Dana; Gazaryan, Irina; Killilea, David W.; Morgenstern, Lewis; Xi, Guohua; Keep, Richard F.; Schallert, Timothy; Tappero, Ryan V.; Zhong, Jian; Cho, Sunghee; Maxfield, Frederick R.; Holman, Theodore R.; Culmsee, Carsten; Fong, Guo-Hua; Su, Yijing; Ming, Guo-li; Song, Hongjun; Cave, John W.; Schofield, Christopher J.; Colbourne, Frederick; Coppola, Giovanni; Ratan, Rajiv R.

2017-01-01

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) family of iron-dependent, oxygen-sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in the mouse striatum improved functional recovery after ICH. A low-molecular-weight hydroxyquinoline inhibitor of the HIF-PHD enzymes, adaptaquin, reduced neuronal death and behavioral deficits after ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of activity of the prodeath factor ATF4 rather than activation of an HIF-dependent prosurvival pathway. Together, these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier-permeable inhibitor adaptaquin can improve functional outcomes after ICH in several rodent models. PMID:26936506

Synthetic Modeling of Autonomous Learning with a Chaotic Neural Network

NASA Astrophysics Data System (ADS)

Funabashi, Masatoshi

We investigate the possible role of intermittent chaotic dynamics called chaotic itinerancy, in interaction with nonsupervised learnings that reinforce and weaken the neural connection depending on the dynamics itself. We first performed hierarchical stability analysis of the Chaotic Neural Network model (CNN) according to the structure of invariant subspaces. Irregular transition between two attractor ruins with positive maximum Lyapunov exponent was triggered by the blowout bifurcation of the attractor spaces, and was associated with riddled basins structure. We secondly modeled two autonomous learnings, Hebbian learning and spike-timing-dependent plasticity (STDP) rule, and simulated the effect on the chaotic itinerancy state of CNN. Hebbian learning increased the residence time on attractor ruins, and produced novel attractors in the minimum higher-dimensional subspace. It also augmented the neuronal synchrony and established the uniform modularity in chaotic itinerancy. STDP rule reduced the residence time on attractor ruins, and brought a wide range of periodicity in emerged attractors, possibly including strange attractors. Both learning rules selectively destroyed and preserved the specific invariant subspaces, depending on the neuron synchrony of the subspace where the orbits are situated. Computational rationale of the autonomous learning is discussed in connectionist perspective.

Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms

PubMed Central

Li, Jing; Tian, Yanxin; Guo, Shimeng; Gu, Haifeng; Yuan, Qianting; Xie, Xin

2018-01-01

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies. PMID:29351556

Real-time characterization of partially observed epidemics using surrogate models.

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

Safta, Cosmin; Ray, Jaideep; Lefantzi, Sophia

We present a statistical method, predicated on the use of surrogate models, for the 'real-time' characterization of partially observed epidemics. Observations consist of counts of symptomatic patients, diagnosed with the disease, that may be available in the early epoch of an ongoing outbreak. Characterization, in this context, refers to estimation of epidemiological parameters that can be used to provide short-term forecasts of the ongoing epidemic, as well as to provide gross information on the dynamics of the etiologic agent in the affected population e.g., the time-dependent infection rate. The characterization problem is formulated as a Bayesian inverse problem, and epidemiologicalmore » parameters are estimated as distributions using a Markov chain Monte Carlo (MCMC) method, thus quantifying the uncertainty in the estimates. In some cases, the inverse problem can be computationally expensive, primarily due to the epidemic simulator used inside the inversion algorithm. We present a method, based on replacing the epidemiological model with computationally inexpensive surrogates, that can reduce the computational time to minutes, without a significant loss of accuracy. The surrogates are created by projecting the output of an epidemiological model on a set of polynomial chaos bases; thereafter, computations involving the surrogate model reduce to evaluations of a polynomial. We find that the epidemic characterizations obtained with the surrogate models is very close to that obtained with the original model. We also find that the number of projections required to construct a surrogate model is O(10)-O(10{sup 2}) less than the number of samples required by the MCMC to construct a stationary posterior distribution; thus, depending upon the epidemiological models in question, it may be possible to omit the offline creation and caching of surrogate models, prior to their use in an inverse problem. The technique is demonstrated on synthetic data as well as observations from the 1918 influenza pandemic collected at Camp Custer, Michigan.« less

Application of physiologically based absorption modeling to formulation development of a low solubility, low permeability weak base: mechanistic investigation of food effect.

PubMed

Zhang, Hefei; Xia, Binfeng; Sheng, Jennifer; Heimbach, Tycho; Lin, Tsu-Han; He, Handan; Wang, Yanfeng; Novick, Steven; Comfort, Ann

2014-04-01

Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the underlying mechanisms of the observed positive food effect of compound X (cpd X) and to strategically explore the feasible approaches to mitigate the food effect. Cpd X is a weak base with pH-dependent solubility; the compound displays significant and dose-dependent food effect in humans, leading to a nonadherence of drug administration. A GastroPlus Opt logD Model was selected for pharmacokinetic simulation under both fasted and fed conditions, where the biopharmaceutic parameters (e.g., solubility and permeability) for cpd X were determined in vitro, and human pharmacokinetic disposition properties were predicted from preclinical data and then optimized with clinical pharmacokinetic data. A parameter sensitivity analysis was performed to evaluate the effect of particle size on the cpd X absorption. A PBPK model was successfully developed for cpd X; its pharmacokinetic parameters (e.g., C max, AUCinf, and t max) predicted at different oral doses were within ±25% of the observed mean values. The in vivo solubility (in duodenum) and mean precipitation time under fed conditions were estimated to be 7.4- and 3.4-fold higher than those under fasted conditions, respectively. The PBPK modeling analysis provided a reasonable explanation for the underlying mechanism for the observed positive food effect of the cpd X in humans. Oral absorption of the cpd X can be increased by reducing the particle size (<100 nm) of an active pharmaceutical ingredient under fasted conditions and therefore, reduce the cpd X food effect correspondingly.

Modeling shifts in the rate and pattern of subthalamopallidal network activity during deep brain stimulation.

PubMed

Hahn, Philip J; McIntyre, Cameron C

2010-06-01

Deep brain stimulation (DBS) of the subthlamic nucleus (STN) represents an effective treatment for medically refractory Parkinson's disease; however, understanding of its effects on basal ganglia network activity remains limited. We constructed a computational model of the subthalamopallidal network, trained it to fit in vivo recordings from parkinsonian monkeys, and evaluated its response to STN DBS. The network model was created with synaptically connected single compartment biophysical models of STN and pallidal neurons, and stochastically defined inputs driven by cortical beta rhythms. A least mean square error training algorithm was developed to parameterize network connections and minimize error when compared to experimental spike and burst rates in the parkinsonian condition. The output of the trained network was then compared to experimental data not used in the training process. We found that reducing the influence of the cortical beta input on the model generated activity that agreed well with recordings from normal monkeys. Further, during STN DBS in the parkinsonian condition the simulations reproduced the reduction in GPi bursting found in existing experimental data. The model also provided the opportunity to greatly expand analysis of GPi bursting activity, generating three major predictions. First, its reduction was proportional to the volume of STN activated by DBS. Second, GPi bursting decreased in a stimulation frequency dependent manner, saturating at values consistent with clinically therapeutic DBS. And third, ablating STN neurons, reported to generate similar therapeutic outcomes as STN DBS, also reduced GPi bursting. Our theoretical analysis of stimulation induced network activity suggests that regularization of GPi firing is dependent on the volume of STN tissue activated and a threshold level of burst reduction may be necessary for therapeutic effect.

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

Bean, Bruce Palmer

The effects of ether and halothane on membrane currents in the voltage clamped crayfish giant axon membrane were investigated. Concentrations of ether up to 300 mM and of halothane up to 32 mM had no effect on resting potential or leakage conductance. Ether and halothane reduced the size of sodium currents without changing the voltage dependence of the peak currents or their reversal potential. Ether and halothane also produced a reversible, dose-dependent speeding of sodium current decay at all membrane potentials. Ether reduced the time constants for inactivation, and also shifted the midpoint of the steady-state inactivation curve in themore » hyperpolarizing direction. Potassium currents were smaller with ether present, with no change in the voltage dependence of steady-state currents. The activation of potassium channels was faster with ether present. There was no apparent change in the capacitance of the crayfish giant axon membrane with ether concentrations of up to 100 mM. Experiments on sodium channel inactivation kinetics were performed using 4-aminopyridine to block potassium currents. Sodium currents decayed with a time course generally fit well by a single exponential. The time constant of decay was a steep function of voltage, especially in the negative resistance region of the peak current vs voltage relation.The time course of inactivation was very similar to that of the decay of the current at the same potential. The measurement of steady-state inactivation curves with different test pulses showed no shifts along the voltage asix. The voltage-dependence of the integral of sodium conductance was measured to test models of sodium channel inactivation in which channels must open before inactivating; the results appear inconsistent with some of the simplest cases of such models.« less

Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms

PubMed Central

Tian, Jihua; Wang, Yanhong; Liu, Xinyan; Zhou, Xiaoshuang

2014-01-01

IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27Kip1, p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclin-dependent kinase 2. However, rapamycin upregulated p27Kip1 at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN. PMID:25349217

Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms.

PubMed

Tian, Jihua; Wang, Yanhong; Liu, Xinyan; Zhou, Xiaoshuang; Li, Rongshan

2015-07-01

IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27(Kip1), p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclin-dependent kinase 2. However, rapamycin upregulated p27(Kip1) at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN. © 2014 by the Society for Experimental Biology and Medicine.

Vulnerability to shocks in the global seafood trade network

NASA Astrophysics Data System (ADS)

Gephart, Jessica A.; Rovenskaya, Elena; Dieckmann, Ulf; Pace, Michael L.; Brännström, Åke

2016-03-01

Trade can allow countries to overcome local or regional losses (shocks) to their food supply, but reliance on international food trade also exposes countries to risks from external perturbations. Countries that are nutritionally or economically dependent on international trade of a commodity may be adversely affected by such shocks. While exposure to shocks has been studied in financial markets, communication networks, and some infrastructure systems, it has received less attention in food-trade networks. Here, we develop a forward shock-propagation model to quantify how trade flows are redistributed under a range of shock scenarios and assess the food-security outcomes by comparing changes in national fish supplies to indices of each country’s nutritional fish dependency. Shock propagation and distribution among regions are modeled on a network of historical bilateral seafood trade data from UN Comtrade using 205 reporting territories grouped into 18 regions. In our model exposure to shocks increases with total imports and the number of import partners. We find that Central and West Africa are the most vulnerable to shocks, with their vulnerability increasing when a willingness-to-pay proxy is included. These findings suggest that countries can reduce their overall vulnerability to shocks by reducing reliance on imports and diversifying food sources. As international seafood trade grows, identifying these types of potential risks and vulnerabilities is important to build a more resilient food system.

Fluid-structure coupling for an oscillating hydrofoil

NASA Astrophysics Data System (ADS)

Münch, C.; Ausoni, P.; Braun, O.; Farhat, M.; Avellan, F.

2010-08-01

Fluid-structure investigations in hydraulic machines using coupled simulations are particularly time-consuming. In this study, an alternative method is presented that linearizes the hydrodynamic load of a rigid, oscillating hydrofoil. The hydrofoil, which is surrounded by incompressible, turbulent flow, is modeled with forced and free pitching motions, where the mean incidence angle is 0° with a maximum angle amplitude of 2°. Unsteady simulations of the flow, performed with ANSYS CFX, are presented and validated with experiments which were carried out in the EPFL High-Speed Cavitation Tunnel. First, forced motion is investigated for reduced frequencies ranging from 0.02 to 100. The hydrodynamic load is modeled as a simple combination of inertia, damping and stiffness effects. As expected, the potential flow analysis showed the added moment of inertia is constant, while the fluid damping and the fluid stiffness coefficients depend on the reduced frequency of the oscillation motion. Behavioral patterns were observed and two cases were identified depending on if vortices did or did not develop in the hydrofoil wake. Using the coefficients identified in the forced motion case, the time history of the profile incidence is then predicted analytically for the free motion case and excellent agreement is found for the results from coupled fluid-structure simulations. The model is validated and may be extended to more complex cases, such as blade grids in hydraulic machinery.

Density functional theory of electron transfer beyond the Born-Oppenheimer approximation: Case study of LiF.

PubMed

Li, Chen; Requist, Ryan; Gross, E K U

2018-02-28

We perform model calculations for a stretched LiF molecule, demonstrating that nonadiabatic charge transfer effects can be accurately and seamlessly described within a density functional framework. In alkali halides like LiF, there is an abrupt change in the ground state electronic distribution due to an electron transfer at a critical bond length R = R c , where an avoided crossing of the lowest adiabatic potential energy surfaces calls the validity of the Born-Oppenheimer approximation into doubt. Modeling the R-dependent electronic structure of LiF within a two-site Hubbard model, we find that nonadiabatic electron-nuclear coupling produces a sizable elongation of the critical R c by 0.5 bohr. This effect is very accurately captured by a simple and rigorously derived correction, with an M -1 prefactor, to the exchange-correlation potential in density functional theory, M = reduced nuclear mass. Since this nonadiabatic term depends on gradients of the nuclear wave function and conditional electronic density, ∇ R χ(R) and ∇ R n(r, R), it couples the Kohn-Sham equations at neighboring R points. Motivated by an observed localization of nonadiabatic effects in nuclear configuration space, we propose a local conditional density approximation-an approximation that reduces the search for nonadiabatic density functionals to the search for a single function y(n).

Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid secretion in airway epithelia

PubMed Central

Turner, Mark J.; Saint‐Criq, Vinciane; Patel, Waseema; Ibrahim, Salam H.; Verdon, Bernard; Ward, Christopher; Garnett, James P.; Tarran, Robert; Cann, Martin J.

2015-01-01

Key points Raised arterial blood CO2 (hypercapnia) is a feature of many lung diseases.CO2 has been shown to act as a cell signalling molecule in human cells, notably by influencing the levels of cell signalling second messengers: cAMP and Ca2+.Hypercapnia reduced cAMP‐stimulated cystic fibrosis transmembrane conductance regulator‐dependent anion and fluid transport in Calu‐3 cells and primary human airway epithelia but did not affect cAMP‐regulated HCO3 − transport via pendrin or Na+/HCO3 − cotransporters.These results further support the role of CO2 as a cell signalling molecule and suggests CO2‐induced reductions in airway anion and fluid transport may impair innate defence mechanisms of the lungs. Abstract Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist‐stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP‐regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin‐stimulated elevations in intracellular cAMP as well as both adenosine‐ and forskolin‐stimulated increases in CFTR‐dependent transepithelial short‐circuit current, in polarised cultures of Calu‐3 human airway cells. This CO2‐induced reduction in anion secretion was not due to a decrease in HCO3 − transport given that neither a change in CFTR‐dependent HCO3 − efflux nor Na+/HCO3 − cotransporter‐dependent HCO3 − influx were CO2‐sensitive. Hypercapnia also reduced the volume of forskolin‐stimulated fluid secretion over 24 h, yet had no effect on the HCO3 − content of the secreted fluid. Our data reveal that hypercapnia reduces CFTR‐dependent, electrogenic Cl− and fluid secretion, but not CFTR‐dependent HCO3 − secretion, which highlights a differential sensitivity of Cl− and HCO3 − transporters to raised CO2 in Calu‐3 cells. Hypercapnia also reduced forskolin‐stimulated CFTR‐dependent anion secretion in primary human airway epithelia. Based on current models of airways biology, a reduction in fluid secretion, associated with hypercapnia, would be predicted to have important consequences for airways hydration and the innate defence mechanisms of the lungs. PMID:26574187

The piecewise-linear dynamic attenuator reduces the impact of count rate loss with photon-counting detectors

NASA Astrophysics Data System (ADS)

Hsieh, Scott S.; Pelc, Norbert J.

2014-06-01

Photon counting x-ray detectors (PCXDs) offer several advantages compared to standard energy-integrating x-ray detectors, but also face significant challenges. One key challenge is the high count rates required in CT. At high count rates, PCXDs exhibit count rate loss and show reduced detective quantum efficiency in signal-rich (or high flux) measurements. In order to reduce count rate requirements, a dynamic beam-shaping filter can be used to redistribute flux incident on the patient. We study the piecewise-linear attenuator in conjunction with PCXDs without energy discrimination capabilities. We examined three detector models: the classic nonparalyzable and paralyzable detector models, and a ‘hybrid’ detector model which is a weighted average of the two which approximates an existing, real detector (Taguchi et al 2011 Med. Phys. 38 1089-102 ). We derive analytic expressions for the variance of the CT measurements for these detectors. These expressions are used with raw data estimated from DICOM image files of an abdomen and a thorax to estimate variance in reconstructed images for both the dynamic attenuator and a static beam-shaping (‘bowtie’) filter. By redistributing flux, the dynamic attenuator reduces dose by 40% without increasing peak variance for the ideal detector. For non-ideal PCXDs, the impact of count rate loss is also reduced. The nonparalyzable detector shows little impact from count rate loss, but with the paralyzable model, count rate loss leads to noise streaks that can be controlled with the dynamic attenuator. With the hybrid model, the characteristic count rates required before noise streaks dominate the reconstruction are reduced by a factor of 2 to 3. We conclude that the piecewise-linear attenuator can reduce the count rate requirements of the PCXD in addition to improving dose efficiency. The magnitude of this reduction depends on the detector, with paralyzable detectors showing much greater benefit than nonparalyzable detectors.

The Impact of the Good Behavior Game, a Universal Classroom-Based Preventive Intervention in First and Second Grades, on High-Risk Sexual Behaviors and Drug Abuse and Dependence Disorders into Young Adulthood

PubMed Central

Wang, Wei; Mackenzie, Amelia C. L.; Brown, C. Hendricks; Ompad, Danielle C.; Or, Flora; Ialongo, Nicholas S.; Poduska, Jeanne M.; Windham, Amy

2013-01-01

The Good Behavior Game (GBG), a method of teacher classroom behavior management, was tested in first-and second-grade classrooms in 19 Baltimore City Public Schools beginning in the 1985–1986 school year. The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive, disruptive behaviors, confirmed antecedents of a profile of externalizing problem outcomes. This article reports on the GBG impact on the courses and interrelationships among aggressive, disruptive behavior through middle school, risky sexual behaviors, and drug abuse and dependence disorders through ages 19–21. In five poor to lower-middle class, mainly African American urban areas, classrooms within matched schools were assigned randomly to either the GBG intervention or the control condition. Balanced assignment of children to classrooms was made, and teachers were randomly assigned to intervention or control. Analyses involved multilevel growth mixture modeling. By young adulthood, significant GBG impact was found in terms of reduced high-risk sexual behaviors and drug abuse and dependence disorders among males who in first grade and through middle school were more aggressive, disruptive. A replication with the next cohort of first-grade children with the same teachers occurred during the following school year, but with minimal teacher mentoring and monitoring. Findings were not significant but generally in the predicted direction. A universal classroom-based prevention intervention in first- and second-grade classrooms can reduce drug abuse and dependence disorders and risky sexual behaviors. PMID:23070695

The impact of the Good Behavior Game, a universal classroom-based preventive intervention in first and second grades, on high-risk sexual behaviors and drug abuse and dependence disorders into young adulthood.

PubMed

Kellam, Sheppard G; Wang, Wei; Mackenzie, Amelia C L; Brown, C Hendricks; Ompad, Danielle C; Or, Flora; Ialongo, Nicholas S; Poduska, Jeanne M; Windham, Amy

2014-02-01

The Good Behavior Game (GBG), a method of teacher classroom behavior management, was tested in first- and second-grade classrooms in 19 Baltimore City Public Schools beginning in the 1985-1986 school year. The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive, disruptive behaviors, confirmed antecedents of a profile of externalizing problem outcomes. This article reports on the GBG impact on the courses and interrelationships among aggressive, disruptive behavior through middle school, risky sexual behaviors, and drug abuse and dependence disorders through ages 19-21. In five poor to lower-middle class, mainly African American urban areas, classrooms within matched schools were assigned randomly to either the GBG intervention or the control condition. Balanced assignment of children to classrooms was made, and teachers were randomly assigned to intervention or control. Analyses involved multilevel growth mixture modeling. By young adulthood, significant GBG impact was found in terms of reduced high-risk sexual behaviors and drug abuse and dependence disorders among males who in first grade and through middle school were more aggressive, disruptive. A replication with the next cohort of first-grade children with the same teachers occurred during the following school year, but with minimal teacher mentoring and monitoring. Findings were not significant but generally in the predicted direction. A universal classroom-based prevention intervention in first- and second-grade classrooms can reduce drug abuse and dependence disorders and risky sexual behaviors.

Kinetic study of the inactivation of ascorbate peroxidase by hydrogen peroxide.

PubMed Central

Hiner, A N; Rodríguez-López, J N; Arnao, M B; Lloyd Raven, E; García-Cánovas, F; Acosta, M

2000-01-01

The activity of ascorbate peroxidase (APX) has been studied with H(2)O(2) and various reducing substrates. The activity decreased in the order pyrogallol>ascorbate>guaiacol>2, 2'-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS). The inactivation of APX with H(2)O(2) as the sole substrate was studied. The number of H(2)O(2) molecules required for maximal inactivation of the enzyme was determined as approx. 2.5. Enzymic activity of approx. 20% of the original remained at the end of the inactivation process (i.e. approx. 20% resistance) when ascorbate or ABTS was used as the substrate in activity assays. With pyrogallol or guaiacol no resistance was seen. Inactivation by H(2)O(2) followed over time with ascorbate or pyrogallol assays exhibited single-exponential decreases in enzymic activity. Hyperbolic saturation kinetics were observed in both assay systems; a similar dissociation constant (0.8 microM) for H(2)O(2) was obtained in each case. However, the maximum rate constant (lambda(max)) obtained from the plots differed depending on the assay substrate. The presence of reducing substrate in addition to H(2)O(2) partly or completely protected the enzyme from inactivation, depending on how many molar equivalents of reducing substrate were added. An oxygen electrode system has been used to confirm that APX does not exhibit a catalase-like oxygen-releasing reaction. A kinetic model was developed to interpret the experimental results; both the results and the model are compared and contrasted with previously obtained results for horseradish peroxidase C. The kinetic model has led us to the conclusion that the inactivation of APX by H(2)O(2) represents an unusual situation in which no enzyme turnover occurs but there is a partition of the enzyme between two forms, one inactive and the other with activity towards reducing substrates such as ascorbate and ABTS only. The partition ratio is less than 1. PMID:10816425

60 years of UK visibility measurements: impact of meteorology and atmospheric pollutants on visibility

NASA Astrophysics Data System (ADS)

Singh, Ajit; Bloss, William J.; Pope, Francis D.

2017-02-01

Reduced visibility is an indicator of poor air quality. Moreover, degradation in visibility can be hazardous to human safety; for example, low visibility can lead to road, rail, sea and air accidents. In this paper, we explore the combined influence of atmospheric aerosol particle and gas characteristics, and meteorology, on long-term visibility. We use visibility data from eight meteorological stations, situated in the UK, which have been running since the 1950s. The site locations include urban, rural and marine environments. Most stations show a long-term trend of increasing visibility, which is indicative of reductions in air pollution, especially in urban areas. Additionally, the visibility at all sites shows a very clear dependence on relative humidity, indicating the importance of aerosol hygroscopicity on the ability of aerosol particles to scatter radiation. The dependence of visibility on other meteorological parameters, such as wind speed and wind direction, is also investigated. Most stations show long-term increases in temperature which can be ascribed to climate change, land-use changes (e.g. urban heat island effects) or a combination of both; the observed effect is greatest in urban areas. The impact of this temperature change upon local relative humidity is discussed. To explain the long-term visibility trends and their dependence on meteorological conditions, the measured data were fitted to a newly developed light-extinction model to generate predictions of historic aerosol and gas scattering and absorbing properties. In general, an excellent fit was achieved between measured and modelled visibility for all eight sites. The model incorporates parameterizations of aerosol hygroscopicity, particle concentration, particle scattering, and particle and gas absorption. This new model should be applicable and is easily transferrable to other data sets worldwide. Hence, historical visibility data can be used to assess trends in aerosol particle properties. This approach may help constrain global model simulations which attempt to generate aerosol fields for time periods when observational data are scarce or non-existent. Both the measured visibility and the modelled aerosol properties reported in this paper highlight the success of the UK's Clean Air Act, which was passed in 1956, in cleaning the atmosphere of visibility-reducing pollutants.