A Global 3D P-Velocity Model of the Earth’s Crust and Mantle for Improved Event Location -- SALSA3D

DTIC Science & Technology

2010-09-01

incorporates variable resolution in both the geographic and radial dimensions. For our starting model, we use a simplified two layer crustal model derived from... crustal model derived from the Crust 2.0 model over a uniform AK135 mantle. Sufficient damping is used to reduce velocity adjustments so that ray path...upper mantle, and a third tessellation with variable resolution to all crustal layers. The crustal tessellation (not shown) has 2° triangles in oceanic

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

PubMed

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

2016-12-01

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

Anisotropic inflation with derivative couplings

NASA Astrophysics Data System (ADS)

Holland, Jonathan; Kanno, Sugumi; Zavala, Ivonne

2018-05-01

We study anisotropic power-law inflationary solutions when the inflaton and its derivative couple to a vector field. This type of coupling is motivated by D-brane inflationary models, in which the inflaton, and a vector field living on the D-brane, couple disformally (derivatively). We start by studying a phenomenological model where we show the existence of anisotropic solutions and demonstrate their stability via a dynamical system analysis. Compared to the case without a derivative coupling, the anisotropy is reduced and thus can be made consistent with current limits, while the value of the slow-roll parameter remains almost unchanged. We also discuss solutions for more general cases, including D-brane-like couplings.

Parametric reduced models for the nonlinear Schrödinger equation

NASA Astrophysics Data System (ADS)

Harlim, John; Li, Xiantao

2015-05-01

Reduced models for the (defocusing) nonlinear Schrödinger equation are developed. In particular, we develop reduced models that only involve the low-frequency modes given noisy observations of these modes. The ansatz of the reduced parametric models are obtained by employing a rational approximation and a colored-noise approximation, respectively, on the memory terms and the random noise of a generalized Langevin equation that is derived from the standard Mori-Zwanzig formalism. The parameters in the resulting reduced models are inferred from noisy observations with a recently developed ensemble Kalman filter-based parametrization method. The forecasting skill across different temperature regimes are verified by comparing the moments up to order four, a two-time correlation function statistics, and marginal densities of the coarse-grained variables.

Parametric reduced models for the nonlinear Schrödinger equation.

PubMed

Harlim, John; Li, Xiantao

2015-05-01

Reduced models for the (defocusing) nonlinear Schrödinger equation are developed. In particular, we develop reduced models that only involve the low-frequency modes given noisy observations of these modes. The ansatz of the reduced parametric models are obtained by employing a rational approximation and a colored-noise approximation, respectively, on the memory terms and the random noise of a generalized Langevin equation that is derived from the standard Mori-Zwanzig formalism. The parameters in the resulting reduced models are inferred from noisy observations with a recently developed ensemble Kalman filter-based parametrization method. The forecasting skill across different temperature regimes are verified by comparing the moments up to order four, a two-time correlation function statistics, and marginal densities of the coarse-grained variables.

Adjusting lidar-derived digital terrain models in coastal marshes based on estimated aboveground biomass density

DOE PAGES

Medeiros, Stephen; Hagen, Scott; Weishampel, John; ...

2015-03-25

Digital elevation models (DEMs) derived from airborne lidar are traditionally unreliable in coastal salt marshes due to the inability of the laser to penetrate the dense grasses and reach the underlying soil. To that end, we present a novel processing methodology that uses ASTER Band 2 (visible red), an interferometric SAR (IfSAR) digital surface model, and lidar-derived canopy height to classify biomass density using both a three-class scheme (high, medium and low) and a two-class scheme (high and low). Elevation adjustments associated with these classes using both median and quartile approaches were applied to adjust lidar-derived elevation values closer tomore » true bare earth elevation. The performance of the method was tested on 229 elevation points in the lower Apalachicola River Marsh. The two-class quartile-based adjusted DEM produced the best results, reducing the RMS error in elevation from 0.65 m to 0.40 m, a 38% improvement. The raw mean errors for the lidar DEM and the adjusted DEM were 0.61 ± 0.24 m and 0.32 ± 0.24 m, respectively, thereby reducing the high bias by approximately 49%.« less

Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200Rlow Monocyte-Derived Cells in Periodontitis.

PubMed

Björnfot Holmström, Sofia; Clark, Reuben; Zwicker, Stephanie; Bureik, Daniela; Kvedaraite, Egle; Bernasconi, Eric; Nguyen Hoang, Anh Thu; Johannsen, Gunnar; Marsland, Benjamin J; Boström, Elisabeth A; Svensson, Mattias

2017-12-15

Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD. Copyright © 2017 by The American Association of Immunologists, Inc.

The prediction of the flash point for binary aqueous-organic solutions.

PubMed

Liaw, Horng-Jang; Chiu, Yi-Yu

2003-07-18

A mathematical model, which may be used for predicting the flash point of aqueous-organic solutions, has been proposed and subsequently verified by experimentally-derived data. The results reveal that this model is able to precisely predict the flash point over the entire composition range of binary aqueous-organic solutions by way of utilizing the flash point data pertaining to the flammable component. The derivative of flash point with respect to composition (solution composition effect upon flash point) can be applied to process safety design/operation in order to identify as to whether the dilution of a flammable liquid solution with water is effective in reducing the fire and explosion hazard of the solution at a specified composition. Such a derivative equation was thus derived based upon the flash point prediction model referred to above and then verified by the application of experimentally-derived data.

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line.

PubMed

Terawaki, Kiyoshi; Sawada, Yumi; Kashiwase, Yohei; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Suzuki, Masami; Miyano, Kanako; Sudo, Yuka; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

2014-02-15

Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

Constraints on scattering amplitudes in multistate Landau-Zener theory

NASA Astrophysics Data System (ADS)

Sinitsyn, Nikolai A.; Lin, Jeffmin; Chernyak, Vladimir Y.

2017-01-01

We derive a set of constraints, which we will call hierarchy constraints, on scattering amplitudes of an arbitrary multistate Landau-Zener model (MLZM). The presence of additional symmetries can transform such constraints into nontrivial relations between elements of the transition probability matrix. This observation can be used to derive complete solutions of some MLZMs or, for models that cannot be solved completely, to reduce the number of independent elements of the transition probability matrix.

Two degree of freedom internal model control-PID design for LFC of power systems via logarithmic approximations.

PubMed

Singh, Jay; Chattterjee, Kalyan; Vishwakarma, C B

2018-01-01

Load frequency controller has been designed for reduced order model of single area and two-area reheat hydro-thermal power system through internal model control - proportional integral derivative (IMC-PID) control techniques. The controller design method is based on two degree of freedom (2DOF) internal model control which combines with model order reduction technique. Here, in spite of taking full order system model a reduced order model has been considered for 2DOF-IMC-PID design and the designed controller is directly applied to full order system model. The Logarithmic based model order reduction technique is proposed to reduce the single and two-area high order power systems for the application of controller design.The proposed IMC-PID design of reduced order model achieves good dynamic response and robustness against load disturbance with the original high order system. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

A biophysical observation model for field potentials of networks of leaky integrate-and-fire neurons.

PubMed

Beim Graben, Peter; Rodrigues, Serafim

2012-01-01

We present a biophysical approach for the coupling of neural network activity as resulting from proper dipole currents of cortical pyramidal neurons to the electric field in extracellular fluid. Starting from a reduced three-compartment model of a single pyramidal neuron, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential (DFP) that contributes to the local field potential (LFP) of a neural population. This work aligns and satisfies the widespread dipole assumption that is motivated by the "open-field" configuration of the DFP around cortical pyramidal cells. Our reduced three-compartment scheme allows to derive networks of leaky integrate-and-fire (LIF) models, which facilitates comparison with existing neural network and observation models. In particular, by means of numerical simulations we compare our approach with an ad hoc model by Mazzoni et al. (2008), and conclude that our biophysically motivated approach yields substantial improvement.

A Critique of a Phenomenological Fiber Breakage Model for Stress Rupture of Composite Materials

NASA Technical Reports Server (NTRS)

Reeder, James R.

2010-01-01

Stress rupture is not a critical failure mode for most composite structures, but there are a few applications where it can be critical. One application where stress rupture can be a critical design issue is in Composite Overwrapped Pressure Vessels (COPV's), where the composite material is highly and uniformly loaded for long periods of time and where very high reliability is required. COPV's are normally required to be proof loaded before being put into service to insure strength, but it is feared that the proof load may cause damage that reduces the stress rupture reliability. Recently, a fiber breakage model was proposed specifically to estimate a reduced reliability due to proof loading. The fiber breakage model attempts to model physics believed to occur at the microscopic scale, but validation of the model has not occurred. In this paper, the fiber breakage model is re-derived while highlighting assumptions that were made during the derivation. Some of the assumptions are examined to assess their effect on the final predicted reliability.

A biophysical observation model for field potentials of networks of leaky integrate-and-fire neurons

PubMed Central

beim Graben, Peter; Rodrigues, Serafim

2013-01-01

We present a biophysical approach for the coupling of neural network activity as resulting from proper dipole currents of cortical pyramidal neurons to the electric field in extracellular fluid. Starting from a reduced three-compartment model of a single pyramidal neuron, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential (DFP) that contributes to the local field potential (LFP) of a neural population. This work aligns and satisfies the widespread dipole assumption that is motivated by the “open-field” configuration of the DFP around cortical pyramidal cells. Our reduced three-compartment scheme allows to derive networks of leaky integrate-and-fire (LIF) models, which facilitates comparison with existing neural network and observation models. In particular, by means of numerical simulations we compare our approach with an ad hoc model by Mazzoni et al. (2008), and conclude that our biophysically motivated approach yields substantial improvement. PMID:23316157

Bifurcations of large networks of two-dimensional integrate and fire neurons.

PubMed

Nicola, Wilten; Campbell, Sue Ann

2013-08-01

Recently, a class of two-dimensional integrate and fire models has been used to faithfully model spiking neurons. This class includes the Izhikevich model, the adaptive exponential integrate and fire model, and the quartic integrate and fire model. The bifurcation types for the individual neurons have been thoroughly analyzed by Touboul (SIAM J Appl Math 68(4):1045-1079, 2008). However, when the models are coupled together to form networks, the networks can display bifurcations that an uncoupled oscillator cannot. For example, the networks can transition from firing with a constant rate to burst firing. This paper introduces a technique to reduce a full network of this class of neurons to a mean field model, in the form of a system of switching ordinary differential equations. The reduction uses population density methods and a quasi-steady state approximation to arrive at the mean field system. Reduced models are derived for networks with different topologies and different model neurons with biologically derived parameters. The mean field equations are able to qualitatively and quantitatively describe the bifurcations that the full networks display. Extensions and higher order approximations are discussed.

MHD-model for low-frequency waves in a tokamak with toroidal plasma rotation and problem of existence of global geodesic acoustic modes

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

Lakhin, V. P.; Sorokina, E. A., E-mail: sorokina.ekaterina@gmail.com, E-mail: vilkiae@gmail.com; Ilgisonis, V. I.

2015-12-15

A set of reduced linear equations for the description of low-frequency perturbations in toroidally rotating plasma in axisymmetric tokamak is derived in the framework of ideal magnetohydrodynamics. The model suitable for the study of global geodesic acoustic modes (GGAMs) is designed. An example of the use of the developed model for derivation of the integral conditions for GGAM existence and of the corresponding dispersion relation is presented. The paper is dedicated to the memory of academician V.D. Shafranov.

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Constraints on scattering amplitudes in multistate Landau-Zener theory

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

Sinitsyn, Nikolai A.; Lin, Jeffmin; Chernyak, Vladimir Y.

2017-01-30

Here, we derive a set of constraints, which we will call hierarchy constraints, on scattering amplitudes of an arbitrary multistate Landau-Zener model (MLZM). The presence of additional symmetries can transform such constraints into nontrivial relations between elements of the transition probability matrix. This observation can be used to derive complete solutions of some MLZMs or, for models that cannot be solved completely, to reduce the number of independent elements of the transition probability matrix.

Multimedia Model for Polycyclic Aromatic Hydrocarbons (PAHs) and Nitro-PAHs in Lake Michigan

PubMed Central

2015-01-01

Polycyclic aromatic hydrocarbon (PAH) contamination in the U.S. Great Lakes has long been of concern, but information regarding the current sources, distribution, and fate of PAH contamination is lacking, and very little information exists for the potentially more toxic nitro-derivatives of PAHs (NPAHs). This study uses fugacity, food web, and Monte Carlo models to examine 16 PAHs and five NPAHs in Lake Michigan, and to derive PAH and NPAH emission estimates. Good agreement was found between predicted and measured PAH concentrations in air, but concentrations in water and sediment were generally under-predicted, possibly due to incorrect parameter estimates for degradation rates, discharges to water, or inputs from tributaries. The food web model matched measurements of heavier PAHs (≥5 rings) in lake trout, but lighter PAHs (≤4 rings) were overpredicted, possibly due to overestimates of metabolic half-lives or gut/gill absorption efficiencies. Derived PAH emission rates peaked in the 1950s, and rates now approach those in the mid-19th century. The derived emission rates far exceed those in the source inventories, suggesting the need to reconcile differences and reduce uncertainties. Although additional measurements and physiochemical data are needed to reduce uncertainties and for validation purposes, the models illustrate the behavior of PAHs and NPAHs in Lake Michigan, and they provide useful and potentially diagnostic estimates of emission rates. PMID:25373871

Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy

PubMed Central

James, Mark I.; Iwuji, Chinenye; Irving, Glen; Karmokar, Ankur; Higgins, Jennifer A.; Griffin-Teal, Nicola; Thomas, Anne; Greaves, Peter; Cai, Hong; Patel, Samita R.; Morgan, Bruno; Dennison, Ashley; Metcalfe, Matthew; Garcea, Giuseppe; Lloyd, David M.; Berry, David P.; Steward, William P.; Howells, Lynne M.; Brown, Karen

2015-01-01

In vitro and pre-clinical studies have suggested that addition of the diet-derived agent curcumin may provide a suitable adjunct to enhance efficacy of chemotherapy in models of colorectal cancer. However, the majority of evidence for this currently derives from established cell lines. Here, we utilised patient-derived colorectal liver metastases (CRLM) to assess whether curcumin may provide added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in cancer stem cell (CSC) models. Combination of curcumin with FOLFOX chemotherapy was then assessed clinically in a phase I dose escalation study. Curcumin alone and in combination significantly reduced spheroid number in CRLM CSC models, and decreased the number of cells with high aldehyde dehydrogenase activity (ALDHhigh/CD133−). Addition of curcumin to oxaliplatin/5-FU enhanced anti-proliferative and pro-apoptotic effects in a proportion of patient-derived explants, whilst reducing expression of stem cell-associated markers ALDH and CD133. The phase I dose escalation study revealed curcumin to be a safe and tolerable adjunct to FOLFOX chemotherapy in patients with CRLM (n = 12) at doses up to 2 grams daily. Curcumin may provide added benefit in subsets of patients when administered with FOLFOX, and is a well-tolerated chemotherapy adjunct. PMID:25979230

Forced Oscillation Wind Tunnel Testing for FASER Flight Research Aircraft

NASA Technical Reports Server (NTRS)

Hoe, Garrison; Owens, Donald B.; Denham, Casey

2012-01-01

As unmanned air vehicles (UAVs) continue to expand their flight envelopes into areas of high angular rate and high angle of attack, modeling the complex unsteady aerodynamics for simulation in these regimes has become more difficult using traditional methods. The goal of this experiment was to improve the current six degree-of-freedom aerodynamic model of a small UAV by replacing the analytically derived damping derivatives with experimentally derived values. The UAV is named the Free-flying Aircraft for Sub-scale Experimental Research, FASER, and was tested in the NASA Langley Research Center 12- Foot Low-Speed Tunnel. The forced oscillation wind tunnel test technique was used to measure damping in the roll and yaw axes. By imparting a variety of sinusoidal motions, the effects of non-dimensional angular rate and reduced frequency were examined over a large range of angle of attack and side-slip combinations. Tests were performed at angles of attack from -5 to 40 degrees, sideslip angles of -30 to 30 degrees, oscillation amplitudes from 5 to 30 degrees, and reduced frequencies from 0.010 to 0.133. Additionally, the effect of aileron or elevator deflection on the damping coefficients was examined. Comparisons are made of two different data reduction methods used to obtain the damping derivatives. The results show that the damping derivatives are mainly a function of angle of attack and have dependence on the non-dimensional rate and reduced frequency only in the stall/post-stall regime

The cost-effectiveness and consumer acceptability of taxation strategies to reduce rates of overweight and obesity among children in Australia: study protocol.

PubMed

Comans, Tracy A; Whitty, Jennifer A; Hills, Andrew P; Kendall, Elizabeth; Turkstra, Erika; Gordon, Louisa G; Byrnes, Josh M; Scuffham, Paul A

2013-12-14

Childhood obesity is a recognised public health problem and around 25% of Australian children are overweight or obese. A major contributor is the obesogenic environment which encourages over consumption of energy dense nutrient poor food. Taxation is commonly proposed as a mechanism to reduce consumption of poor food choices and hence reduce rates of obesity and overweight in the community. An economic model will be developed to assess the lifetime benefits and costs to a cohort of Australian children by reducing energy dense nutrient poor food consumption through taxation mechanisms. The model inputs will be derived from a series of smaller studies. Food options for taxation will be derived from literature and expert opinion, the acceptability and impact of price changes will be explored through a Citizen's Jury and a discrete choice experiment and price elasticities will be derived from the discrete choice experiment and consumption data. The health care costs of managing rising levels of obesity are a challenge for all governments. This study will provide a unique contribution to the international knowledge base by engaging a variety of robust research techniques, with a multidisciplinary focus and be responsive to consumers from diverse socio-economic backgrounds.

The cost-effectiveness and consumer acceptability of taxation strategies to reduce rates of overweight and obesity among children in Australia: study protocol

PubMed Central

2013-01-01

Background Childhood obesity is a recognised public health problem and around 25% of Australian children are overweight or obese. A major contributor is the obesogenic environment which encourages over consumption of energy dense nutrient poor food. Taxation is commonly proposed as a mechanism to reduce consumption of poor food choices and hence reduce rates of obesity and overweight in the community. Methods/Design An economic model will be developed to assess the lifetime benefits and costs to a cohort of Australian children by reducing energy dense nutrient poor food consumption through taxation mechanisms. The model inputs will be derived from a series of smaller studies. Food options for taxation will be derived from literature and expert opinion, the acceptability and impact of price changes will be explored through a Citizen’s Jury and a discrete choice experiment and price elasticities will be derived from the discrete choice experiment and consumption data. Discussion The health care costs of managing rising levels of obesity are a challenge for all governments. This study will provide a unique contribution to the international knowledge base by engaging a variety of robust research techniques, with a multidisciplinary focus and be responsive to consumers from diverse socio-economic backgrounds. PMID:24330325

A reduced-form intensity-based model under fuzzy environments

NASA Astrophysics Data System (ADS)

Wu, Liang; Zhuang, Yaming

2015-05-01

The external shocks and internal contagion are the important sources of default events. However, the external shocks and internal contagion effect on the company is not observed, we cannot get the accurate size of the shocks. The information of investors relative to the default process exhibits a certain fuzziness. Therefore, using randomness and fuzziness to study such problems as derivative pricing or default probability has practical needs. But the idea of fuzzifying credit risk models is little exploited, especially in a reduced-form model. This paper proposes a new default intensity model with fuzziness and presents a fuzzy default probability and default loss rate, and puts them into default debt and credit derivative pricing. Finally, the simulation analysis verifies the rationality of the model. Using fuzzy numbers and random analysis one can consider more uncertain sources in the default process of default and investors' subjective judgment on the financial markets in a variety of fuzzy reliability so as to broaden the scope of possible credit spreads.

A Control Concept for Large Flexible Spacecraft Using Order Reduction Techniques

NASA Technical Reports Server (NTRS)

Thieme, G.; Roth, H.

1985-01-01

Results found during the investigation of control problems of large flexible spacecraft are given. A triple plate configuration of such a spacecraft is defined and studied. The model is defined by modal data derived from infinite element modeling. The order reduction method applied is briefly described. An attitude control concept with low and high authority control has been developed to design an attitude controller for the reduced model. The stability and response of the original system together with the reduced controller is analyzed.

Shear Modulus for Nonisotropic, Open-Celled Foams Using a General Elongated Kelvin Foam Model

NASA Technical Reports Server (NTRS)

Sullivan, Roy M.; Ghosn, Louis J.

2008-01-01

An equation for the shear modulus for nonisotropic, open-celled foams in the plane transverse to the elongation (rise) direction is derived using an elongated Kelvin foam model with the most general geometric description. The shear modulus was found to be a function of the unit cell dimensions, the solid material properties, and the cell edge cross-section properties. The shear modulus equation reduces to the relation derived by others for isotropic foams when the unit cell is equiaxed.

An Optimization Principle for Deriving Nonequilibrium Statistical Models of Hamiltonian Dynamics

NASA Astrophysics Data System (ADS)

Turkington, Bruce

2013-08-01

A general method for deriving closed reduced models of Hamiltonian dynamical systems is developed using techniques from optimization and statistical estimation. Given a vector of resolved variables, selected to describe the macroscopic state of the system, a family of quasi-equilibrium probability densities on phase space corresponding to the resolved variables is employed as a statistical model, and the evolution of the mean resolved vector is estimated by optimizing over paths of these densities. Specifically, a cost function is constructed to quantify the lack-of-fit to the microscopic dynamics of any feasible path of densities from the statistical model; it is an ensemble-averaged, weighted, squared-norm of the residual that results from submitting the path of densities to the Liouville equation. The path that minimizes the time integral of the cost function determines the best-fit evolution of the mean resolved vector. The closed reduced equations satisfied by the optimal path are derived by Hamilton-Jacobi theory. When expressed in terms of the macroscopic variables, these equations have the generic structure of governing equations for nonequilibrium thermodynamics. In particular, the value function for the optimization principle coincides with the dissipation potential that defines the relation between thermodynamic forces and fluxes. The adjustable closure parameters in the best-fit reduced equations depend explicitly on the arbitrary weights that enter into the lack-of-fit cost function. Two particular model reductions are outlined to illustrate the general method. In each example the set of weights in the optimization principle contracts into a single effective closure parameter.

Model improvements and validation of TerraSAR-X precise orbit determination

NASA Astrophysics Data System (ADS)

Hackel, S.; Montenbruck, O.; Steigenberger, P.; Balss, U.; Gisinger, C.; Eineder, M.

2017-05-01

The radar imaging satellite mission TerraSAR-X requires precisely determined satellite orbits for validating geodetic remote sensing techniques. Since the achieved quality of the operationally derived, reduced-dynamic (RD) orbit solutions limits the capabilities of the synthetic aperture radar (SAR) validation, an effort is made to improve the estimated orbit solutions. This paper discusses the benefits of refined dynamical models on orbit accuracy as well as estimated empirical accelerations and compares different dynamic models in a RD orbit determination. Modeling aspects discussed in the paper include the use of a macro-model for drag and radiation pressure computation, the use of high-quality atmospheric density and wind models as well as the benefit of high-fidelity gravity and ocean tide models. The Sun-synchronous dusk-dawn orbit geometry of TerraSAR-X results in a particular high correlation of solar radiation pressure modeling and estimated normal-direction positions. Furthermore, this mission offers a unique suite of independent sensors for orbit validation. Several parameters serve as quality indicators for the estimated satellite orbit solutions. These include the magnitude of the estimated empirical accelerations, satellite laser ranging (SLR) residuals, and SLR-based orbit corrections. Moreover, the radargrammetric distance measurements of the SAR instrument are selected for assessing the quality of the orbit solutions and compared to the SLR analysis. The use of high-fidelity satellite dynamics models in the RD approach is shown to clearly improve the orbit quality compared to simplified models and loosely constrained empirical accelerations. The estimated empirical accelerations are substantially reduced by 30% in tangential direction when working with the refined dynamical models. Likewise the SLR residuals are reduced from -3 ± 17 to 2 ± 13 mm, and the SLR-derived normal-direction position corrections are reduced from 15 to 6 mm, obtained from the 2012-2014 period. The radar range bias is reduced from -10.3 to -6.1 mm with the updated orbit solutions, which coincides with the reduced standard deviation of the SLR residuals. The improvements are mainly driven by the satellite macro-model for the purpose of solar radiation pressure modeling, improved atmospheric density models, and the use of state-of-the-art gravity field models.

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.

An improved rotated staggered-grid finite-difference method with fourth-order temporal accuracy for elastic-wave modeling in anisotropic media

DOE PAGES

Gao, Kai; Huang, Lianjie

2017-08-31

The rotated staggered-grid (RSG) finite-difference method is a powerful tool for elastic-wave modeling in 2D anisotropic media where the symmetry axes of anisotropy are not aligned with the coordinate axes. We develop an improved RSG scheme with fourth-order temporal accuracy to reduce the numerical dispersion associated with prolonged wave propagation or a large temporal step size. The high-order temporal accuracy is achieved by including high-order temporal derivatives, which can be converted to high-order spatial derivatives to reduce computational cost. Dispersion analysis and numerical tests show that our method exhibits very low temporal dispersion even with a large temporal step sizemore » for elastic-wave modeling in complex anisotropic media. Using the same temporal step size, our method is more accurate than the conventional RSG scheme. In conclusion, our improved RSG scheme is therefore suitable for prolonged modeling of elastic-wave propagation in 2D anisotropic media.« less

An improved rotated staggered-grid finite-difference method with fourth-order temporal accuracy for elastic-wave modeling in anisotropic media

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

Gao, Kai; Huang, Lianjie

The rotated staggered-grid (RSG) finite-difference method is a powerful tool for elastic-wave modeling in 2D anisotropic media where the symmetry axes of anisotropy are not aligned with the coordinate axes. We develop an improved RSG scheme with fourth-order temporal accuracy to reduce the numerical dispersion associated with prolonged wave propagation or a large temporal step size. The high-order temporal accuracy is achieved by including high-order temporal derivatives, which can be converted to high-order spatial derivatives to reduce computational cost. Dispersion analysis and numerical tests show that our method exhibits very low temporal dispersion even with a large temporal step sizemore » for elastic-wave modeling in complex anisotropic media. Using the same temporal step size, our method is more accurate than the conventional RSG scheme. In conclusion, our improved RSG scheme is therefore suitable for prolonged modeling of elastic-wave propagation in 2D anisotropic media.« less

Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

PubMed

Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

2009-01-01

Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

Modal Test/Analysis Correlation of Space Station Structures Using Nonlinear Sensitivity

NASA Technical Reports Server (NTRS)

Gupta, Viney K.; Newell, James F.; Berke, Laszlo; Armand, Sasan

1992-01-01

The modal correlation problem is formulated as a constrained optimization problem for validation of finite element models (FEM's). For large-scale structural applications, a pragmatic procedure for substructuring, model verification, and system integration is described to achieve effective modal correlation. The space station substructure FEM's are reduced using Lanczos vectors and integrated into a system FEM using Craig-Bampton component modal synthesis. The optimization code is interfaced with MSC/NASTRAN to solve the problem of modal test/analysis correlation; that is, the problem of validating FEM's for launch and on-orbit coupled loads analysis against experimentally observed frequencies and mode shapes. An iterative perturbation algorithm is derived and implemented to update nonlinear sensitivity (derivatives of eigenvalues and eigenvectors) during optimizer iterations, which reduced the number of finite element analyses.

Modal test/analysis correlation of Space Station structures using nonlinear sensitivity

NASA Technical Reports Server (NTRS)

Gupta, Viney K.; Newell, James F.; Berke, Laszlo; Armand, Sasan

1992-01-01

The modal correlation problem is formulated as a constrained optimization problem for validation of finite element models (FEM's). For large-scale structural applications, a pragmatic procedure for substructuring, model verification, and system integration is described to achieve effective modal correlations. The space station substructure FEM's are reduced using Lanczos vectors and integrated into a system FEM using Craig-Bampton component modal synthesis. The optimization code is interfaced with MSC/NASTRAN to solve the problem of modal test/analysis correlation; that is, the problem of validating FEM's for launch and on-orbit coupled loads analysis against experimentally observed frequencies and mode shapes. An iterative perturbation algorithm is derived and implemented to update nonlinear sensitivity (derivatives of eigenvalues and eigenvectors) during optimizer iterations, which reduced the number of finite element analyses.

Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

PubMed

Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

2013-10-01

Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

Comparison of stellar population model predictions using optical and infrared spectroscopy

NASA Astrophysics Data System (ADS)

Baldwin, C.; McDermid, R. M.; Kuntschner, H.; Maraston, C.; Conroy, C.

2018-02-01

We present Gemini/GNIRS cross-dispersed near-infrared spectra of 12 nearby early-type galaxies, with the aim of testing commonly used stellar population synthesis models. We select a subset of galaxies from the ATLAS3D sample which span a wide range of ages (single stellar population equivalent ages of 1-15 Gyr) at approximately solar metallicity. We derive star formation histories using four different stellar population synthesis models, namely those of Bruzual & Charlot, Conroy, Gunn & White, Maraston & Strömbäck and Vazdekis et al. We compare star formation histories derived from near-infrared spectra with those derived from optical spectra using the same models. We find that while all models agree in the optical, the derived star formation histories vary dramatically from model to model in the near-infrared. We find that this variation is largely driven by the choice of stellar spectral library, such that models including high-quality spectral libraries provide the best fits to the data, and are the most self-consistent when comparing optically derived properties with near-infrared ones. We also find the impact of age variation in the near-infrared to be subtle, and largely encoded in the shape of the continuum, meaning that the common approach of removing continuum information with a high-order polynomial greatly reduces our ability to constrain ages in the near-infrared.

Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

PubMed

Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

2015-09-29

The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Assessment of some straw-derived materials for reducing the leaching potential of Metribuzin residues in the soil

NASA Astrophysics Data System (ADS)

Cara, Irina Gabriela; Trincă, Lucia Carmen; Trofin, Alina Elena; Cazacu, Ana; Ţopa, Denis; Peptu, Cătălina Anişoara; Jităreanu, Gerard

2015-12-01

Biomass (straw waste) can be used as raw to obtain materials for herbicide removal from wastewater. These by-products have some important advantages, being environmentally friendly, easily available, presenting low costs, and requiring little processing to increase their adsorptive capacity. In the present study, some materials derived from agricultural waste (wheat, corn and soybean straw) were investigated as potential adsorbents for metribuzin removal from aqueous solutions. The straw wastes were processed by grinding, mineralisation (850 °C) and KOH activation in order to improve their functional surface activity. The materials surface characteristics were investigated by scanning electron microscopy, energy dispersive X-ray spectroscopy and atomic force microscopy. The adsorbents capacity was evaluated using batch sorption tests and liquid chromatography coupled with mass spectrometry for herbicide determination. For adsorption isotherms, the equilibrium time considered was 3 h. The experimental adsorption data were modelled by Freundlich and Langmuir models. The activated straw and ash-derived materials from wheat, corn and soybean increased the adsorption capacity of metribuzin with an asymmetrical behaviour. Overall, our results sustain that activated ash-derived from straw and activated straw materials can be a valuable solution for reducing the leaching potential of metribuzin through soil.

Deriving video content type from HEVC bitstream semantics

NASA Astrophysics Data System (ADS)

Nightingale, James; Wang, Qi; Grecos, Christos; Goma, Sergio R.

2014-05-01

As network service providers seek to improve customer satisfaction and retention levels, they are increasingly moving from traditional quality of service (QoS) driven delivery models to customer-centred quality of experience (QoE) delivery models. QoS models only consider metrics derived from the network however, QoE models also consider metrics derived from within the video sequence itself. Various spatial and temporal characteristics of a video sequence have been proposed, both individually and in combination, to derive methods of classifying video content either on a continuous scale or as a set of discrete classes. QoE models can be divided into three broad categories, full reference, reduced reference and no-reference models. Due to the need to have the original video available at the client for comparison, full reference metrics are of limited practical value in adaptive real-time video applications. Reduced reference metrics often require metadata to be transmitted with the bitstream, while no-reference metrics typically operate in the decompressed domain at the client side and require significant processing to extract spatial and temporal features. This paper proposes a heuristic, no-reference approach to video content classification which is specific to HEVC encoded bitstreams. The HEVC encoder already makes use of spatial characteristics to determine partitioning of coding units and temporal characteristics to determine the splitting of prediction units. We derive a function which approximates the spatio-temporal characteristics of the video sequence by using the weighted averages of the depth at which the coding unit quadtree is split and the prediction mode decision made by the encoder to estimate spatial and temporal characteristics respectively. Since the video content type of a sequence is determined by using high level information parsed from the video stream, spatio-temporal characteristics are identified without the need for full decoding and can be used in a timely manner to aid decision making in QoE oriented adaptive real time streaming.

Analytical properties of a three-compartmental dynamical demographic model

NASA Astrophysics Data System (ADS)

Postnikov, E. B.

2015-07-01

The three-compartmental demographic model by Korotaeyv-Malkov-Khaltourina, connecting population size, economic surplus, and education level, is considered from the point of view of dynamical systems theory. It is shown that there exist two integrals of motion, which enables the system to be reduced to one nonlinear ordinary differential equation. The study of its structure provides analytical criteria for the dominance ranges of the dynamics of Malthus and Kremer. Additionally, the particular ranges of parameters enable the derived general ordinary differential equations to be reduced to the models of Gompertz and Thoularis-Wallace.

Multi-site assimilation of a terrestrial biosphere model (BETHY) using satellite derived soil moisture data

NASA Astrophysics Data System (ADS)

Wu, Mousong; Sholze, Marko

2017-04-01

We investigated the importance of soil moisture data on assimilation of a terrestrial biosphere model (BETHY) for a long time period from 2010 to 2015. Totally, 101 parameters related to carbon turnover, soil respiration, as well as soil texture were selected for optimization within a carbon cycle data assimilation system (CCDAS). Soil moisture data from Soil Moisture and Ocean Salinity (SMOS) product was derived for 10 sites representing different plant function types (PFTs) as well as different climate zones. Uncertainty of SMOS soil moisture data was also estimated using triple collocation analysis (TCA) method by comparing with ASCAT dataset and BETHY forward simulation results. Assimilation of soil moisture to the system improved soil moisture as well as net primary productivity(NPP) and net ecosystem productivity (NEP) when compared with soil moisture derived from in-situ measurements and fluxnet datasets. Parameter uncertainties were largely reduced relatively to prior values. Using SMOS soil moisture data for assimilation of a terrestrial biosphere model proved to be an efficient approach in reducing uncertainty in ecosystem fluxes simulation. It could be further used in regional an global assimilation work to constrain carbon dioxide concentration simulation by combining with other sources of measurements.

The effects of plastic waves on the numerical convergence of the viscous-plastic and elastic-viscous-plastic sea-ice models

NASA Astrophysics Data System (ADS)

Williams, James; Tremblay, L. Bruno; Lemieux, Jean-François

2017-07-01

The plastic wave speed is derived from the linearized 1-D version of the widely used viscous-plastic (VP) and elastic-viscous-plastic (EVP) sea-ice models. Courant-Friedrichs-Lewy (CFL) conditions are derived using the propagation speed of the wave. 1-D numerical experiments of the VP, EVP and EVP* models successfully recreate a reference solution when the CFL conditions are satisfied, in agreement with the theory presented. The IMplicit-EXplicit (IMEX) method is shown to effectively alleviate the plastic wave CFL constraint on the timestep in the implicitly solved VP model in both 1-D and 2-D. In 2-D, the EVP and EVP* models show first order error in the simulated velocity field when the plastic wave is not resolved. EVP simulations are performed with various advective timestep, number of subcycles, and elastic-wave damping timescales. It is found that increasing the number of subcycles beyond that needed to resolve the elastic wave does not improve the quality of the solution. It is found that reducing the elastic wave damping timescale reduces the spatial extent of first order errors cause by the unresolved plastic wave. Reducing the advective timestep so that the plastic wave is resolved also reduces the velocity error in terms of magnitude and spatial extent. However, the parameter set required for convergence to within the error bars of satellite (RGPS) deformation fields is impractical for use in climate model simulations. The behavior of the EVP* method is analogous to that of the EVP method except that it is not possible to reduce the damping timescale with α = β.

CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability.

PubMed

Meng, Jinhong; Muntoni, Francesco; Morgan, Jennifer

2018-05-12

Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the missing dystrophin protein, thus improving muscle function. CD133+ cells derived from normal human skeletal muscle contribute to regenerated muscle fibres and form muscle stem cells after their intra-muscular transplantation into an immunodeficient mouse model. But it is not known whether CD133+ cells derived from DMD patient muscles have compromised muscle regenerative function. To test this, we compared CD133+ cells derived from DMD and normal human muscles. DMD CD133+ cells had a reduced capacity to undergo myogenic differentiation in vitro compared with CD133+ cells derived from normal muscle. In contrast to CD133+ cells derived from normal human muscle, those derived from DMD muscle formed no satellite cells and gave rise to significantly fewer muscle fibres of donor origin, after their intra-muscular transplantation into an immunodeficient, non-dystrophic, mouse muscle. DMD CD133+ cells gave rise to more clones of smaller size and more clones that were less myogenic than did CD133+ cells derived from normal muscle. The heterogeneity of the progeny of CD133+ cells, combined with the reduced proliferation and myogenicity of DMD compared to normal CD133+ cells, may explain the reduced regenerative capacity of DMD CD133+ cells. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

PubMed

Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

2013-04-01

Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

Experimental investigation of elastic mode control on a model of a transport aircraft

NASA Technical Reports Server (NTRS)

Abramovitz, M.; Heimbaugh, R. M.; Nomura, J. K.; Pearson, R. M.; Shirley, W. A.; Stringham, R. H.; Tescher, E. L.; Zoock, I. E.

1981-01-01

A 4.5 percent DC-10 derivative flexible model with active controls is fabricated, developed, and tested to investigate the ability to suppress flutter and reduce gust loads with active controlled surfaces. The model is analyzed and tested in both semispan and complete model configuration. Analytical methods are refined and control laws are developed and successfully tested on both versions of the model. A 15 to 25 percent increase in flutter speed due to the active system is demonstrated. The capability of an active control system to significantly reduce wing bending moments due to turbulence is demonstrated. Good correlation is obtained between test and analytical prediction.

Fetal Alcohol Spectrum Disorder-associated depression: evidence for reductions in the levels of brain-derived neurotrophic factor in a mouse model

PubMed Central

Caldwell, Kevin K.; Sheema, S.; Paz, Rodrigo D; Samudio-Ruiz, Sabrina L.; Laughlin, Mary H.; Spence, Nathan E.; Roehlk, Michael J; Alcon, Sara N.; Allan, Andrea M.

2009-01-01

Prenatal ethanol exposure is associated with an increased incidence of depressive disorders in patient populations. However, the mechanisms that link prenatal ethanol exposure and depression are unknown. Several recent studies have implicated reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampal formation and frontal cortex as important contributors to the etiology of depression. In the present studies, we sought to determine whether prenatal ethanol exposure is associated with behaviors that model depression, as well as with reduced BDNF levels in the hippocampal formation and/or medial frontal cortex, in a mouse model of fetal alcohol spectrum disorder (FASD). Compared to control adult mice, prenatal ethanol-exposed adult mice displayed increased learned helplessness behavior and increased immobility in the Porsolt forced swim test. Prenatal ethanol exposure was associated with decreased BDNF protein levels in the medial frontal cortex, but not the hippocampal formation, while total BDNF mRNA and BDNF transcripts containing exon III, IV or VI were reduced in both the medial frontal cortex and the hippocampal formation of prenatal ethanol-exposed mice. These results identify reduced BDNF levels in the medial frontal cortex and hippocampal formation as potential mediators of depressive disorders associated with FASD. PMID:18558427

Low rank approach to computing first and higher order derivatives using automatic differentiation

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

Reed, J. A.; Abdel-Khalik, H. S.; Utke, J.

2012-07-01

This manuscript outlines a new approach for increasing the efficiency of applying automatic differentiation (AD) to large scale computational models. By using the principles of the Efficient Subspace Method (ESM), low rank approximations of the derivatives for first and higher orders can be calculated using minimized computational resources. The output obtained from nuclear reactor calculations typically has a much smaller numerical rank compared to the number of inputs and outputs. This rank deficiency can be exploited to reduce the number of derivatives that need to be calculated using AD. The effective rank can be determined according to ESM by computingmore » derivatives with AD at random inputs. Reduced or pseudo variables are then defined and new derivatives are calculated with respect to the pseudo variables. Two different AD packages are used: OpenAD and Rapsodia. OpenAD is used to determine the effective rank and the subspace that contains the derivatives. Rapsodia is then used to calculate derivatives with respect to the pseudo variables for the desired order. The overall approach is applied to two simple problems and to MATWS, a safety code for sodium cooled reactors. (authors)« less

Potential formulation of sleep dynamics

NASA Astrophysics Data System (ADS)

Phillips, A. J. K.; Robinson, P. A.

2009-02-01

A physiologically based model of the mechanisms that control the human sleep-wake cycle is formulated in terms of an equivalent nonconservative mechanical potential. The potential is analytically simplified and reduced to a quartic two-well potential, matching the bifurcation structure of the original model. This yields a dynamics-based model that is analytically simpler and has fewer parameters than the original model, allowing easier fitting to experimental data. This model is first demonstrated to semiquantitatively match the dynamics of the physiologically based model from which it is derived, and is then fitted directly to a set of experimentally derived criteria. These criteria place rigorous constraints on the parameter values, and within these constraints the model is shown to reproduce normal sleep-wake dynamics and recovery from sleep deprivation. Furthermore, this approach enables insights into the dynamics by direct analogies to phenomena in well studied mechanical systems. These include the relation between friction in the mechanical system and the timecourse of neurotransmitter action, and the possible relation between stochastic resonance and napping behavior. The model derived here also serves as a platform for future investigations of sleep-wake phenomena from a dynamical perspective.

Emissions databases for polycyclic aromatic compounds in the Canadian Athabasca oil sands region - development using current knowledge and evaluation with passive sampling and air dispersion modelling data

NASA Astrophysics Data System (ADS)

Qiu, Xin; Cheng, Irene; Yang, Fuquan; Horb, Erin; Zhang, Leiming; Harner, Tom

2018-03-01

Two speciated and spatially resolved emissions databases for polycyclic aromatic compounds (PACs) in the Athabasca oil sands region (AOSR) were developed. The first database was derived from volatile organic compound (VOC) emissions data provided by the Cumulative Environmental Management Association (CEMA) and the second database was derived from additional data collected within the Joint Canada-Alberta Oil Sands Monitoring (JOSM) program. CALPUFF modelling results for atmospheric polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, and dibenzothiophenes (DBTs), obtained using each of the emissions databases, are presented and compared with measurements from a passive air monitoring network. The JOSM-derived emissions resulted in better model-measurement agreement in the total PAH concentrations and for most PAH species concentrations compared to results using CEMA-derived emissions. At local sites near oil sands mines, the percent error of the model compared to observations decreased from 30 % using the CEMA-derived emissions to 17 % using the JOSM-derived emissions. The improvement at local sites was likely attributed to the inclusion of updated tailings pond emissions estimated from JOSM activities. In either the CEMA-derived or JOSM-derived emissions scenario, the model underestimated PAH concentrations by a factor of 3 at remote locations. Potential reasons for the disagreement include forest fire emissions, re-emissions of previously deposited PAHs, and long-range transport not considered in the model. Alkylated PAH and DBT concentrations were also significantly underestimated. The CALPUFF model is expected to predict higher concentrations because of the limited chemistry and deposition modelling. Thus the model underestimation of PACs is likely due to gaps in the emissions database for these compounds and uncertainties in the methodology for estimating the emissions. Future work is required that focuses on improving the PAC emissions estimation and speciation methodologies and reducing the uncertainties in VOC emissions which are subsequently used in PAC emissions estimation.

Reducing calibration parameters to increase insight in catchment organization and similarity

NASA Astrophysics Data System (ADS)

Skaugen, Thomas; Onof, Christian

2013-04-01

Ideally, hydrological models should be built from equations parameterised from observed catchment characteristics and data. This state of affairs may never be reached, but a governing principle in hydrological modelling should be to keep the number of calibration parameters to a minimum. A reduced number of parameters to be calibrated, while maintaining the accuracy and detail required by modern hydrological models, will reduce parameter and model structure uncertainty and improve model diagnostics. The dynamics of runoff for small catchments are derived from the distribution of distances from points in the catchments to the nearest stream in a catchment. This distribution is unique for each catchment and can be determined from a geographical information system (GIS). The distribution of distances, will, when a celerity of (subsurface) flow is introduced, provide a distribution of travel times, or a unit hydrograph (UH). For spatially varying levels of saturation deficit we have different celerities and, hence, different UHs. Runoff is derived from the super-positioning of the different UHs. This study shows how celerities can be estimated if we assume that recession events represent the superpositioned UH for different levels of saturation deficit. The performance of the DDD (Distance Distribution Dynamics) model is compared to that of the Swedish HBV model and is found to perform equally well for eight Norwegian catchments although the number of parameters to be calibrated in the module concerning soil moisture and runoff dynamics is reduced from 7 in the HBV model to 1 in the DDD model. It is also shown that the DDD model has a more realistic representation of the subsurface hydrology. The transparency of the DDD model makes model diagnostics more easy and experience with DDD shows that differences in model performance may be related to differences in catchment characteristics. More specifically, it appears that the hydrological dynamics of bogs have to be taken especially into account when modelling Norwegian catchments.

The Use of Neural Networks in Identifying Error Sources in Satellite-Derived Tropical SST Estimates

PubMed Central

Lee, Yung-Hsiang; Ho, Chung-Ru; Su, Feng-Chun; Kuo, Nan-Jung; Cheng, Yu-Hsin

2011-01-01

An neural network model of data mining is used to identify error sources in satellite-derived tropical sea surface temperature (SST) estimates from thermal infrared sensors onboard the Geostationary Operational Environmental Satellite (GOES). By using the Back Propagation Network (BPN) algorithm, it is found that air temperature, relative humidity, and wind speed variation are the major factors causing the errors of GOES SST products in the tropical Pacific. The accuracy of SST estimates is also improved by the model. The root mean square error (RMSE) for the daily SST estimate is reduced from 0.58 K to 0.38 K and mean absolute percentage error (MAPE) is 1.03%. For the hourly mean SST estimate, its RMSE is also reduced from 0.66 K to 0.44 K and the MAPE is 1.3%. PMID:22164030

Hamiltonian closures in fluid models for plasmas

NASA Astrophysics Data System (ADS)

Tassi, Emanuele

2017-11-01

This article reviews recent activity on the Hamiltonian formulation of fluid models for plasmas in the non-dissipative limit, with emphasis on the relations between the fluid closures adopted for the different models and the Hamiltonian structures. The review focuses on results obtained during the last decade, but a few classical results are also described, in order to illustrate connections with the most recent developments. With the hope of making the review accessible not only to specialists in the field, an introduction to the mathematical tools applied in the Hamiltonian formalism for continuum models is provided. Subsequently, we review the Hamiltonian formulation of models based on the magnetohydrodynamics description, including those based on the adiabatic and double adiabatic closure. It is shown how Dirac's theory of constrained Hamiltonian systems can be applied to impose the incompressibility closure on a magnetohydrodynamic model and how an extended version of barotropic magnetohydrodynamics, accounting for two-fluid effects, is amenable to a Hamiltonian formulation. Hamiltonian reduced fluid models, valid in the presence of a strong magnetic field, are also reviewed. In particular, reduced magnetohydrodynamics and models assuming cold ions and different closures for the electron fluid are discussed. Hamiltonian models relaxing the cold-ion assumption are then introduced. These include models where finite Larmor radius effects are added by means of the gyromap technique, and gyrofluid models. Numerical simulations of Hamiltonian reduced fluid models investigating the phenomenon of magnetic reconnection are illustrated. The last part of the review concerns recent results based on the derivation of closures preserving a Hamiltonian structure, based on the Hamiltonian structure of parent kinetic models. Identification of such closures for fluid models derived from kinetic systems based on the Vlasov and drift-kinetic equations are presented, and connections with previously discussed fluid models are pointed out.

Impact of sensor's point spread function on land cover characterization: Assessment and deconvolution

USGS Publications Warehouse

Huang, C.; Townshend, J.R.G.; Liang, S.; Kalluri, S.N.V.; DeFries, R.S.

2002-01-01

Measured and modeled point spread functions (PSF) of sensor systems indicate that a significant portion of the recorded signal of each pixel of a satellite image originates from outside the area represented by that pixel. This hinders the ability to derive surface information from satellite images on a per-pixel basis. In this study, the impact of the PSF of the Moderate Resolution Imaging Spectroradiometer (MODIS) 250 m bands was assessed using four images representing different landscapes. Experimental results showed that though differences between pixels derived with and without PSF effects were small on the average, the PSF generally brightened dark objects and darkened bright objects. This impact of the PSF lowered the performance of a support vector machine (SVM) classifier by 5.4% in overall accuracy and increased the overall root mean square error (RMSE) by 2.4% in estimating subpixel percent land cover. An inversion method based on the known PSF model reduced the signals originating from surrounding areas by as much as 53%. This method differs from traditional PSF inversion deconvolution methods in that the PSF was adjusted with lower weighting factors for signals originating from neighboring pixels than those specified by the PSF model. By using this deconvolution method, the lost classification accuracy due to residual impact of PSF effects was reduced to only 1.66% in overall accuracy. The increase in the RMSE of estimated subpixel land cover proportions due to the residual impact of PSF effects was reduced to 0.64%. Spatial aggregation also effectively reduced the errors in estimated land cover proportion images. About 50% of the estimation errors were removed after applying the deconvolution method and aggregating derived proportion images to twice their dimensional pixel size. ?? 2002 Elsevier Science Inc. All rights reserved.

A spatially explicit model for an Allee effect: why wolves recolonize so slowly in Greater Yellowstone.

PubMed

Hurford, Amy; Hebblewhite, Mark; Lewis, Mark A

2006-11-01

A reduced probability of finding mates at low densities is a frequently hypothesized mechanism for a component Allee effect. At low densities dispersers are less likely to find mates and establish new breeding units. However, many mathematical models for an Allee effect do not make a distinction between breeding group establishment and subsequent population growth. Our objective is to derive a spatially explicit mathematical model, where dispersers have a reduced probability of finding mates at low densities, and parameterize the model for wolf recolonization in the Greater Yellowstone Ecosystem (GYE). In this model, only the probability of establishing new breeding units is influenced by the reduced probability of finding mates at low densities. We analytically and numerically solve the model to determine the effect of a decreased probability in finding mates at low densities on population spread rate and density. Our results suggest that a reduced probability of finding mates at low densities may slow recolonization rate.

Reduced Complexity Modelling of Urban Floodplain Inundation

NASA Astrophysics Data System (ADS)

McMillan, H. K.; Brasington, J.; Mihir, M.

2004-12-01

Significant recent advances in floodplain inundation modelling have been achieved by directly coupling 1d channel hydraulic models with a raster storage cell approximation for floodplain flows. The strengths of this reduced-complexity model structure derive from its explicit dependence on a digital elevation model (DEM) to parameterize flows through riparian areas, providing a computationally efficient algorithm to model heterogeneous floodplains. Previous applications of this framework have generally used mid-range grid scales (101-102 m), showing the capacity of the models to simulate long reaches (103-104 m). However, the increasing availability of precision DEMs derived from airborne laser altimetry (LIDAR) enables their use at very high spatial resolutions (100-101 m). This spatial scale offers the opportunity to incorporate the complexity of the built environment directly within the floodplain DEM and simulate urban flooding. This poster describes a series of experiments designed to explore model functionality at these reduced scales. Important questions are considered, raised by this new approach, about the reliability and representation of the floodplain topography and built environment, and the resultant sensitivity of inundation forecasts. The experiments apply a raster floodplain model to reconstruct a 1:100 year flood event on the River Granta in eastern England, which flooded 72 properties in the town of Linton in October 2001. The simulations use a nested-scale model to maintain efficiency. A 2km by 4km urban zone is represented by a high-resolution DEM derived from single-pulse LIDAR data supplied by the UK Environment Agency, together with surveyed data and aerial photography. Novel methods of processing the raw data to provide the individual structure detail required are investigated and compared. This is then embedded within a lower-resolution model application at the reach scale which provides boundary conditions based on recorded flood stage. The high resolution predictions on a scale commensurate with urban structures make possible a multi-criteria validation which combines verification of reach-scale characteristics such as downstream flow and inundation extent with internal validation of flood depth at individual sites.

Development of Detailed and Reduced Kinetics Mechanisms for Surrogates of Petroleum-Derived and Synthetic Jet Fuels

DTIC Science & Technology

2014-12-04

is determined with an on-line, continuous NDIR analyzer and O2 is measured using an electrochemical oxygen sensor . 8 3.1.2 Modelling Approach...hydrocarbons were discussed. Additionally, the possibility to extend the reach of JetSurF model and apply it for models of soot formation in gas turbine engines was addressed.

Potential uncertainty reduction in model-averaged benchmark dose estimates informed by an additional dose study.

PubMed

Shao, Kan; Small, Mitchell J

2011-10-01

A methodology is presented for assessing the information value of an additional dosage experiment in existing bioassay studies. The analysis demonstrates the potential reduction in the uncertainty of toxicity metrics derived from expanded studies, providing insights for future studies. Bayesian methods are used to fit alternative dose-response models using Markov chain Monte Carlo (MCMC) simulation for parameter estimation and Bayesian model averaging (BMA) is used to compare and combine the alternative models. BMA predictions for benchmark dose (BMD) are developed, with uncertainty in these predictions used to derive the lower bound BMDL. The MCMC and BMA results provide a basis for a subsequent Monte Carlo analysis that backcasts the dosage where an additional test group would have been most beneficial in reducing the uncertainty in the BMD prediction, along with the magnitude of the expected uncertainty reduction. Uncertainty reductions are measured in terms of reduced interval widths of predicted BMD values and increases in BMDL values that occur as a result of this reduced uncertainty. The methodology is illustrated using two existing data sets for TCDD carcinogenicity, fitted with two alternative dose-response models (logistic and quantal-linear). The example shows that an additional dose at a relatively high value would have been most effective for reducing the uncertainty in BMA BMD estimates, with predicted reductions in the widths of uncertainty intervals of approximately 30%, and expected increases in BMDL values of 5-10%. The results demonstrate that dose selection for studies that subsequently inform dose-response models can benefit from consideration of how these models will be fit, combined, and interpreted. © 2011 Society for Risk Analysis.

Parameterized reduced order models from a single mesh using hyper-dual numbers

NASA Astrophysics Data System (ADS)

Brake, M. R. W.; Fike, J. A.; Topping, S. D.

2016-06-01

In order to assess the predicted performance of a manufactured system, analysts must consider random variations (both geometric and material) in the development of a model, instead of a single deterministic model of an idealized geometry with idealized material properties. The incorporation of random geometric variations, however, potentially could necessitate the development of thousands of nearly identical solid geometries that must be meshed and separately analyzed, which would require an impractical number of man-hours to complete. This research advances a recent approach to uncertainty quantification by developing parameterized reduced order models. These parameterizations are based upon Taylor series expansions of the system's matrices about the ideal geometry, and a component mode synthesis representation for each linear substructure is used to form an efficient basis with which to study the system. The numerical derivatives required for the Taylor series expansions are obtained via hyper-dual numbers, and are compared to parameterized models constructed with finite difference formulations. The advantage of using hyper-dual numbers is two-fold: accuracy of the derivatives to machine precision, and the need to only generate a single mesh of the system of interest. The theory is applied to a stepped beam system in order to demonstrate proof of concept. The results demonstrate that the hyper-dual number multivariate parameterization of geometric variations, which largely are neglected in the literature, are accurate for both sensitivity and optimization studies. As model and mesh generation can constitute the greatest expense of time in analyzing a system, the foundation to create a parameterized reduced order model based off of a single mesh is expected to reduce dramatically the necessary time to analyze multiple realizations of a component's possible geometry.

Constraining the Sensitivity of Amazonian Rainfall with Observations of Surface Temperature

NASA Astrophysics Data System (ADS)

Dolman, A. J.; von Randow, C.; de Oliveira, G. S.; Martins, G.; Nobre, C. A.

2016-12-01

Earth System models generally do a poor job in predicting Amazonian rainfall, necessitating the need to look for observational constraints on their predictability. We use observed surface temperature and precipitation of the Amazon and a set of 21 CMIP5 models to derive an observational constraint of the sensitivity of rainfall to surface temperature (dP/dT). From first principles such a relation between the surface temperature of the earth and the amount of precipitation through the surface energy balance should exist, particularly in the tropics. When de-trended anomalies in surface temperature and precipitation from a set of datasets are plotted, a clear linear relation between surface temperature and precipitation appears. CMIP5 models show a similar relation with relatively cool models having a larger sensitivity, producing more rainfall. Using the ensemble of models and the observed surface temperature we were able to derive an emerging constraint, reducing the dPdt sensitivity of the CMIP5 model from -0.75 mm day-1 0C-1 (+/- 0.54 SD) to -0.77 mm day-1 0C-1 with a reduced uncertainty of about a factor 5. dPdT from the observation is -0.89 mm day-1 0C-1 . We applied the method to wet and dry season separately noticing that in the wet season we shifted the mean and reduced uncertainty, while in the dry season we very much reduced uncertainty only. The method can be applied to other model simulations such as specific deforestation scenarios to constrain the sensitivity of rainfall to surface temperature. We discuss the implications of the constrained sensitivity for future Amazonian predictions.

Change in attitudes about employed mothers: exposure, interests, and gender ideology discrepancies.

PubMed

Kroska, Amy; Elman, Cheryl

2009-06-01

Using a sample of continuously-married individuals (793 women and 847 men) and their spouses drawn from the first two waves of the NSFH, we examine change in individuals' attitudes about mothers' employment. We investigate hypotheses derived from three models of attitude change: the exposure model, the interest-based model, and the control model. We find support for hypotheses derived from all three. Consistent with exposure hypotheses, the adoption of fundamentalist beliefs reduces egalitarianism, while spouses' egalitarianism and spouses' education are positively related to individuals' own egalitarianism. As predicted in both exposure and interest hypotheses, women's entry into employment is positively related to women's egalitarianism, while wives' occupational prestige is positively related to men's egalitarianism. Congruent with the interest model, the presence of a young child is positively associated with women's egalitarianism. Consistent with the exposure model, the number of children in the home reduces men's egalitarianism, and a traditional division of housework decreases women's egalitarianism. Finally, consistent with the gender ideology discrepancy hypothesis, derived from the control model, individuals whose background, work, and family life are inconsistent with their gender ideology at wave 1 shift their gender ideology at wave 2 in a direction that is more compatible with their background, work, and family life: egalitarians with traditional life patterns at wave 1 are more traditional in their gender ideology at wave 2, and traditionals with egalitarian life patterns at wave 1 are more egalitarian at wave 2. We discuss the implications of these patterns for larger scale change in gender ideology.

Wigner distribution functions for complex dynamical systems: the emergence of the Wigner-Boltzmann equation.

PubMed

Sels, Dries; Brosens, Fons

2013-10-01

The equation of motion for the reduced Wigner function of a system coupled to an external quantum system is presented for the specific case when the external quantum system can be modeled as a set of harmonic oscillators. The result is derived from the Wigner function formulation of the Feynman-Vernon influence functional theory. It is shown how the true self-energy for the equation of motion is connected with the influence functional for the path integral. Explicit expressions are derived in terms of the bare Wigner propagator. Finally, we show under which approximations the resulting equation of motion reduces to the Wigner-Boltzmann equation.

Pharmacokinetic and pharmacodynamic modelling of the novel human granulocyte colony-stimulating factor derivative Maxy-G34 and pegfilgrastim in rats.

PubMed

Scholz, M; Engel, C; Apt, D; Sankar, S L; Goldstein, E; Loeffler, M

2009-12-01

This study aims to compare pharmacokinetics and pharmacodynamics of pegfilgrastim, a pharmaceutical recombinant human granulocyte colony-stimulating factor (rhG-CSF), with that of a newly developed reagent, Maxy-G34. This comparison was performed using rat experiments and biomathematical modelling of granulopoiesis. Healthy rats and those with cyclophosphamide-induced neutropenia were treated with either pegfilgrastim or Maxy-G34 under various schedules. Time courses of absolute neutrophil count (ANC) and G-CSF serum level were measured and we constructed a combined pharmacokinetic/pharmacodynamic model of both drugs. Neutropenic episodes were assessed by experimental data and model simulations. Both Pegfilgrastim and Maxy-G34 showed strong dose-dependent efficacy in reducing neutropenic episodes. However, time courses of ANC and G-CSF serum levels were markedly different. The biomathematical model showed good agreement with these data. We estimated that differences between the two drugs could be explained by lower bioavailability and reduced elimination of Maxy-G34. Based on the data and model interpolations, we estimated that Maxy-G34 is superior in reducing neutropenic episodes. Also, we predicted that G-CSF administration 48 h after cyclophosphamide would be superior to its administration after 2 or 24 h, for both derivatives. Maxy-G34 is a highly potent drug for stimulation of neutrophil production in rats. By our modelling approach, we quantified differences between Maxy-G34 and pegfilgrastim, related to pharmacokinetic parameters. Model simulations can be used to estimate optimal dosing and timing options in the present preclinical rat model.

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…

Comparison of risk estimates using life-table methods.

PubMed

Sullivan, R E; Weng, P S

1987-08-01

Risk estimates promulgated by various radiation protection authorities in recent years have become increasingly more complex. Early "integral" estimates in the form of health effects per 0.01 person-Gy (per person-rad) or per 10(4) person-Gy (per 10(6) person-rad) have tended to be replaced by "differential" estimates which are age- and sex-dependent and specify both minimum induction (latency) and duration of risk expression (plateau) periods. These latter types of risk estimate must be used in conjunction with a life table in order to reduce them to integral form. In this paper, the life table has been used to effect a comparison of the organ and tissue risk estimates derived in several recent reports. In addition, a brief review of life-table methodology is presented and some features of the models used in deriving differential coefficients are discussed. While the great number of permutations possible with dose-response models, detailed risk estimates and proposed projection models precludes any unique result, the reduced integral coefficients are required to conform to the linear, absolute-risk model recommended for use with the integral risk estimates reviewed.

Eliminating time dispersion from seismic wave modeling

NASA Astrophysics Data System (ADS)

Koene, Erik F. M.; Robertsson, Johan O. A.; Broggini, Filippo; Andersson, Fredrik

2018-04-01

We derive an expression for the error introduced by the second-order accurate temporal finite-difference (FD) operator, as present in the FD, pseudospectral and spectral element methods for seismic wave modeling applied to time-invariant media. The `time-dispersion' error speeds up the signal as a function of frequency and time step only. Time dispersion is thus independent of the propagation path, medium or spatial modeling error. We derive two transforms to either add or remove time dispersion from synthetic seismograms after a simulation. The transforms are compared to previous related work and demonstrated on wave modeling in acoustic as well as elastic media. In addition, an application to imaging is shown. The transforms enable accurate computation of synthetic seismograms at reduced cost, benefitting modeling applications in both exploration and global seismology.

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.

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair.

PubMed

Crompton, Rachel; Williams, Helen; Ansell, David; Campbell, Laura; Holden, Kirsty; Cruickshank, Sheena; Hardman, Matthew J

2016-04-01

Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.

Covariant diagrams for one-loop matching

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

Zhang, Zhengkang

Here, we present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gauge-covariant quantities and are thus dubbed "covariant diagrams." The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We also show how such derivation canmore » be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.« less

Covariant diagrams for one-loop matching

DOE PAGES

Zhang, Zhengkang

2017-05-30

Here, we present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gauge-covariant quantities and are thus dubbed "covariant diagrams." The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We also show how such derivation canmore » be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.« less

Interpretable Topic Features for Post-ICU Mortality Prediction.

PubMed

Luo, Yen-Fu; Rumshisky, Anna

2016-01-01

Electronic health records provide valuable resources for understanding the correlation between various diseases and mortality. The analysis of post-discharge mortality is critical for healthcare professionals to follow up potential causes of death after a patient is discharged from the hospital and give prompt treatment. Moreover, it may reduce the cost derived from readmissions and improve the quality of healthcare. Our work focused on post-discharge ICU mortality prediction. In addition to features derived from physiological measurements, we incorporated ICD-9-CM hierarchy into Bayesian topic model learning and extracted topic features from medical notes. We achieved highest AUCs of 0.835 and 0.829 for 30-day and 6-month post-discharge mortality prediction using baseline and topic proportions derived from Labeled-LDA. Moreover, our work emphasized the interpretability of topic features derived from topic model which may facilitates the understanding and investigation of the complexity between mortality and diseases.

Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury.

PubMed

Haga, Hiroaki; Yan, Irene K; Borrelli, David A; Matsuda, Akiko; Parasramka, Mansi; Shukla, Neha; Lee, David D; Patel, Tushar

2017-06-01

Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from mesenchymal stem cells (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow-derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross-clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of up to 6 hours. Compared with controls, intravenous administration of MSC-EV 30 minutes prior to IRI dramatically reduced the extent of tissue necrosis, decreased caspase 3-positive and apoptotic cells, and reduced serum aminotransferase levels. MSC-EV increased hepatic messenger RNA (mRNA) expression of NACHT, LRR, and PYD domains-containing protein 12, and the chemokine (C-X-C motif) ligand 1, and reduced mRNA expression of several inflammatory cytokines such as interleukin 6 during IRI. MSC-EV increased cell viability and suppressed both oxidative injury and nuclear factor kappa B activity in murine hepatocytes in vitro. In conclusion, the administration of extracellular vesicles derived from bone marrow-derived MSCs may ameliorate hepatic IRI by reducing hepatic injury through modulation of the inflammatory response.Liver Transplantation 23 791-803 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Docking studies on a new human immunodeficiency virus integrase-Mg-DNA complex: phenyl ring exploration and synthesis of 1H-benzylindole derivatives through fluorine substitutions.

PubMed

Ferro, Stefania; De Luca, Laura; Barreca, Maria Letizia; Iraci, Nunzio; De Grazia, Sara; Christ, Frauke; Witvrouw, Myriam; Debyser, Zeger; Chimirri, Alba

2009-01-22

A new model of HIV-1 integrase-Mg-DNA complex that is useful for docking experiments has been built. It was used to study the binding mode of integrase strand transfer inhibitor 1 (CHI-1043) and other fluorine analogues. Molecular modeling results prompted us to synthesize the designed derivatives which showed potent enzymatic inhibition at nanomolar concentration, high antiviral activity, and low toxicity. Microwave assisted organic synthesis (MAOS) was employed in several steps of the synthetic pathway, thus reducing reaction times and improving yields.

Fractals, malware, and data models

NASA Astrophysics Data System (ADS)

Jaenisch, Holger M.; Potter, Andrew N.; Williams, Deborah; Handley, James W.

2012-06-01

We examine the hypothesis that the decision boundary between malware and non-malware is fractal. We introduce a novel encoding method derived from text mining for converting disassembled programs first into opstrings and then filter these into a reduced opcode alphabet. These opcodes are enumerated and encoded into real floating point number format and used for characterizing frequency of occurrence and distribution properties of malware functions to compare with non-malware functions. We use the concept of invariant moments to characterize the highly non-Gaussian structure of the opcode distributions. We then derive Data Model based classifiers from identified features and interpolate and extrapolate the parameter sample space for the derived Data Models. This is done to examine the nature of the parameter space classification boundary between families of malware and the general non-malware category. Preliminary results strongly support the fractal boundary hypothesis, and a summary of our methods and results are presented here.

Validation of Infrared Azimuthal Model as Applied to GOES Data Over the ARM SGP

NASA Technical Reports Server (NTRS)

Gambheer, Arvind V.; Doelling, David R.; Spangenberg, Douglas A.; Minnis, Patrick

2004-01-01

The goal of this research is to identify and reduce the GOES-8 IR temperature biases, induced by a fixed geostationary position, during the course of a day. In this study, the same CERES LW window channel model is applied to GOES-8 IR temperatures during clear days over the Atmospheric Radiation Measurement-Southern Great Plains Central Facility (SCF). The model-adjusted and observed IR temperatures are compared with topof- the-atmosphere (TOA) estimated temperatures derived from a radiative transfer algorithm based on the atmospheric profile and surface radiometer measurements. This algorithm can then be incorporated to derive more accurate Ts from real-time satellite operational products.

A computer code for calculations in the algebraic collective model of the atomic nucleus

NASA Astrophysics Data System (ADS)

Welsh, T. A.; Rowe, D. J.

2016-03-01

A Maple code is presented for algebraic collective model (ACM) calculations. The ACM is an algebraic version of the Bohr model of the atomic nucleus, in which all required matrix elements are derived by exploiting the model's SU(1 , 1) × SO(5) dynamical group. This paper reviews the mathematical formulation of the ACM, and serves as a manual for the code. The code enables a wide range of model Hamiltonians to be analysed. This range includes essentially all Hamiltonians that are rational functions of the model's quadrupole moments qˆM and are at most quadratic in the corresponding conjugate momenta πˆN (- 2 ≤ M , N ≤ 2). The code makes use of expressions for matrix elements derived elsewhere and newly derived matrix elements of the operators [ π ˆ ⊗ q ˆ ⊗ π ˆ ] 0 and [ π ˆ ⊗ π ˆ ] LM. The code is made efficient by use of an analytical expression for the needed SO(5)-reduced matrix elements, and use of SO(5) ⊃ SO(3) Clebsch-Gordan coefficients obtained from precomputed data files provided with the code.

Generalized Fractional Derivative Anisotropic Viscoelastic Characterization.

PubMed

Hilton, Harry H

2012-01-18

Isotropic linear and nonlinear fractional derivative constitutive relations are formulated and examined in terms of many parameter generalized Kelvin models and are analytically extended to cover general anisotropic homogeneous or non-homogeneous as well as functionally graded viscoelastic material behavior. Equivalent integral constitutive relations, which are computationally more powerful, are derived from fractional differential ones and the associated anisotropic temperature-moisture-degree-of-cure shift functions and reduced times are established. Approximate Fourier transform inversions for fractional derivative relations are formulated and their accuracy is evaluated. The efficacy of integer and fractional derivative constitutive relations is compared and the preferential use of either characterization in analyzing isotropic and anisotropic real materials must be examined on a case-by-case basis. Approximate protocols for curve fitting analytical fractional derivative results to experimental data are formulated and evaluated.

Effects of Reduced Terrestrial LiDAR Point Density on High-Resolution Grain Crop Surface Models in Precision Agriculture

PubMed Central

Hämmerle, Martin; Höfle, Bernhard

2014-01-01

3D geodata play an increasingly important role in precision agriculture, e.g., for modeling in-field variations of grain crop features such as height or biomass. A common data capturing method is LiDAR, which often requires expensive equipment and produces large datasets. This study contributes to the improvement of 3D geodata capturing efficiency by assessing the effect of reduced scanning resolution on crop surface models (CSMs). The analysis is based on high-end LiDAR point clouds of grain crop fields of different varieties (rye and wheat) and nitrogen fertilization stages (100%, 50%, 10%). Lower scanning resolutions are simulated by keeping every n-th laser beam with increasing step widths n. For each iteration step, high-resolution CSMs (0.01 m2 cells) are derived and assessed regarding their coverage relative to a seamless CSM derived from the original point cloud, standard deviation of elevation and mean elevation. Reducing the resolution to, e.g., 25% still leads to a coverage of >90% and a mean CSM elevation of >96% of measured crop height. CSM types (maximum elevation or 90th-percentile elevation) react differently to reduced scanning resolutions in different crops (variety, density). The results can help to assess the trade-off between CSM quality and minimum requirements regarding equipment and capturing set-up. PMID:25521383

Reduced linear noise approximation for biochemical reaction networks with time-scale separation: The stochastic tQSSA+

NASA Astrophysics Data System (ADS)

Herath, Narmada; Del Vecchio, Domitilla

2018-03-01

Biochemical reaction networks often involve reactions that take place on different time scales, giving rise to "slow" and "fast" system variables. This property is widely used in the analysis of systems to obtain dynamical models with reduced dimensions. In this paper, we consider stochastic dynamics of biochemical reaction networks modeled using the Linear Noise Approximation (LNA). Under time-scale separation conditions, we obtain a reduced-order LNA that approximates both the slow and fast variables in the system. We mathematically prove that the first and second moments of this reduced-order model converge to those of the full system as the time-scale separation becomes large. These mathematical results, in particular, provide a rigorous justification to the accuracy of LNA models derived using the stochastic total quasi-steady state approximation (tQSSA). Since, in contrast to the stochastic tQSSA, our reduced-order model also provides approximations for the fast variable stochastic properties, we term our method the "stochastic tQSSA+". Finally, we demonstrate the application of our approach on two biochemical network motifs found in gene-regulatory and signal transduction networks.

Using Human iPSC-Derived Neurons to Model TAU Aggregation

PubMed Central

Verheyen, An; Diels, Annick; Dijkmans, Joyce; Oyelami, Tutu; Meneghello, Giulia; Mertens, Liesbeth; Versweyveld, Sofie; Borgers, Marianne; Buist, Arjan; Peeters, Pieter; Cik, Miroslav

2015-01-01

Alzheimer’s disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation. PMID:26720731

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats.

PubMed

Jung, Kyung Hee; Song, Sun U; Yi, Tacghee; Jeon, Myung-Shin; Hong, Sang-Won; Zheng, Hong-Mei; Lee, Hee-Seung; Choi, Myung-Joo; Lee, Don-Haeng; Hong, Soon-Sun

2011-03-01

Acute pancreatitis (AP) has a high mortality rate; repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunoregulatory effects and reduce inflammation. We developed a protocol to isolate human bone marrow-derived clonal MSCs (hcMSCs) from bone marrow aspirate and investigated the effects of these cells in rat models of mild and severe AP. Mild AP was induced in Sprague-Dawley rats by 3 intraperitoneal injections of cerulein (100 μg/kg), given at 2-hour intervals; severe AP was induced by intraparenchymal injection of 3% sodium taurocholate solution. hcMSCs were labeled with CM-1,1'-dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchloride and administered to rats through the tail vein. hcMSCs underwent self-renewal and had multipotent differentiation capacities and immunoregulatory functions. Greater numbers of infused hcMSCs were detected in pancreas of rats with mild and severe AP than of control rats. Infused hcMSCs reduced acinar-cell degeneration, pancreatic edema, and inflammatory cell infiltration in each model of pancreatitis. The hcMSCs reduced expression of inflammation mediators and cytokines in rats with mild and severe AP. hcMSCs suppressed the mixed lymphocyte reaction and increased expression of Foxp3(+) (a marker of regulatory T cells) in cultured rat lymph node cells. Rats with mild or severe AP that were given infusions of hcMSCs had reduced numbers of CD3(+) T cells and increased expression of Foxp3(+) in pancreas tissues. hcMSCs reduced inflammation and damage to pancreatic tissue in a rat model of AP; they reduced levels of cytokines and induced numbers of Foxp3(+) regulatory T cells. hcMSCs might be developed as a cell therapy for pancreatitis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

PubMed

Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

2012-12-01

Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

Parameterized reduced-order models using hyper-dual numbers.

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

Fike, Jeffrey A.; Brake, Matthew Robert

2013-10-01

The goal of most computational simulations is to accurately predict the behavior of a real, physical system. Accurate predictions often require very computationally expensive analyses and so reduced order models (ROMs) are commonly used. ROMs aim to reduce the computational cost of the simulations while still providing accurate results by including all of the salient physics of the real system in the ROM. However, real, physical systems often deviate from the idealized models used in simulations due to variations in manufacturing or other factors. One approach to this issue is to create a parameterized model in order to characterize themore » effect of perturbations from the nominal model on the behavior of the system. This report presents a methodology for developing parameterized ROMs, which is based on Craig-Bampton component mode synthesis and the use of hyper-dual numbers to calculate the derivatives necessary for the parameterization.« less

Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1-Stat3.

PubMed

Wu, Chuan Xing; Xu, Aimin; Zhang, Cathy C; Olson, Peter; Chen, Lin; Lee, Terence K; Cheung, Tan To; Lo, Chung Mau; Wang, Xiao Qi

2017-08-01

Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma, indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in hepatocellular carcinoma. Hepatocellular carcinoma spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells. PF-03084014 reduced the hepatocellular carcinoma sphere-derived orthotopic tumor and blocked the hepatocellular carcinoma tumor liver to lung metastasis. We further tested the PF-03084014 in PDX models and confirmed the inhibition tumor growth effect. In addition, a low dose of PF-03084014 induced hepatocellular carcinoma sphere differentiation, resulting in chemosensitization. Antitumor activity was associated with PF-03084014-induced suppression of Notch1 activity, decreased Stat3 activation and phosphorylation of the Akt signaling pathway, and reduced epithelial-mesenchymal transition. These are the key contributors to the maintenance of cancer stemness and the promotion of cancer metastasis. Moreover, the Notch-Stat3 association was implicated in the clinical hepatocellular carcinoma prognosis. Collectively, PF-03084014 revealed antitumor and antimetastatic effects in hepatocellular carcinoma, providing evidence for the potential use of gamma-secretase inhibitors as a therapeutic option for the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1531-43. ©2017 AACR . ©2017 American Association for Cancer Research.

Transport coefficient computation based on input/output reduced order models

NASA Astrophysics Data System (ADS)

Hurst, Joshua L.

The guiding purpose of this thesis is to address the optimal material design problem when the material description is a molecular dynamics model. The end goal is to obtain a simplified and fast model that captures the property of interest such that it can be used in controller design and optimization. The approach is to examine model reduction analysis and methods to capture a specific property of interest, in this case viscosity, or more generally complex modulus or complex viscosity. This property and other transport coefficients are defined by a input/output relationship and this motivates model reduction techniques that are tailored to preserve input/output behavior. In particular Singular Value Decomposition (SVD) based methods are investigated. First simulation methods are identified that are amenable to systems theory analysis. For viscosity, these models are of the Gosling and Lees-Edwards type. They are high order nonlinear Ordinary Differential Equations (ODEs) that employ Periodic Boundary Conditions. Properties can be calculated from the state trajectories of these ODEs. In this research local linear approximations are rigorously derived and special attention is given to potentials that are evaluated with Periodic Boundary Conditions (PBC). For the Gosling description LTI models are developed from state trajectories but are found to have limited success in capturing the system property, even though it is shown that full order LTI models can be well approximated by reduced order LTI models. For the Lees-Edwards SLLOD type model nonlinear ODEs will be approximated by a Linear Time Varying (LTV) model about some nominal trajectory and both balanced truncation and Proper Orthogonal Decomposition (POD) will be used to assess the plausibility of reduced order models to this system description. An immediate application of the derived LTV models is Quasilinearization or Waveform Relaxation. Quasilinearization is a Newton's method applied to the ODE operator equation. Its a recursive method that solves nonlinear ODE's by solving a LTV systems at each iteration to obtain a new closer solution. LTV models are derived for both Gosling and Lees-Edwards type models. Particular attention is given to SLLOD Lees-Edwards models because they are in a form most amenable to performing Taylor series expansion, and the most commonly used model to examine viscosity. With linear models developed a method is presented to calculate viscosity based on LTI Gosling models but is shown to have some limitations. To address these issues LTV SLLOD models are analyzed with both Balanced Truncation and POD and both show that significant order reduction is possible. By examining the singular values of both techniques it is shown that Balanced Truncation has a potential to offer greater reduction, which should be expected as it is based on the input/output mapping instead of just the state information as in POD. Obtaining reduced order systems that capture the property of interest is challenging. For Balanced Truncation reduced order models for 1-D LJ and FENE systems are obtained and are shown to capture the output of interest fairly well. However numerical challenges currently limit this analysis to small order systems. Suggestions are presented to extend this method to larger systems. In addition reduced 2nd order systems are obtained from POD. Here the challenge is extending the solution beyond the original period used for the projection, in particular identifying the manifold the solution travels along. The remaining challenges are presented and discussed.

Modeling the influence of a reduced equator-to-pole sea surface temperature gradient on the distribution of water isotopes in the Eocene

NASA Astrophysics Data System (ADS)

Speelman, E. N.; Sewall, J. O.; Noone, D. C.; Huber, M.; Sinninghe Damsté, J. S.; Reichart, G.

2009-12-01

Proxy-based climate reconstructions suggest the existence of a strongly reduced equator-to-pole temperature gradient during most of the Early Eocene. With the realization that the Eocene Arctic Ocean was covered with enormous quantities of the free floating freshwater fern Azolla, new questions related to Eocene (global) hydrological cycling facilitating these blooms arose. Changes in hydrological cycling, as a consequence of a reduced temperature gradient, are expected to be most clearly reflected in the isotopic composition (D, 18O) of precipitation. The interpretation of water isotopic records to quantitatively estimate past precipitation patterns is, however, hampered by the lack of detailed information on changes in their spatial and temporal distribution. Using the isotope-enabled global circulation model, Community Atmosphere Model v.3 (isoCAM3), relationships between water isotopes and past climates can be simulated. Here we examine the influence of a reduced meridional sea surface temperature gradient on the spatial distribution of precipitation and its isotopic composition in an Eocene setting. Overall, our combination of Eocene climate forcings, with superimposed TEX86-derived SST estimates and elevated pCO2 concentrations, produces a climate that agrees well with proxy data in locations around the globe. It shows the presence of an intensified hydrological cycle with precipitation exceeding evaporation in the Arctic region. The Eocene model runs with a significantly reduced equator-to-pole temperature gradient in a warmer more humid world predict occurrence of less depleted precipitation, with δD values ranging only between 0 and -140‰ (as opposed to the present-day range of 0 to -300‰). Combining new results obtained from compound specific isotope analyses on terrestrially derived n-alkanes extracted from Eocene sediments, and model calculations, shows that the model not only captures the main features, but reproduces isotopic values quantitatively as well. This combination of modeling outcomes and independent stable isotope records thus confirms independently the validity of the earlier, proxy-based, inferred reduced meridional temperature gradient.

Analysis of Wind Tunnel Oscillatory Data of the X-31A Aircraft

NASA Technical Reports Server (NTRS)

Smith, Mark S.

1999-01-01

Wind tunnel oscillatory tests in pitch, roll, and yaw were performed on a 19%-scale model of the X-31A aircraft. These tests were used to study the aerodynamic characteristics of the X-31A in response to harmonic oscillations at six frequencies. In-phase and out-of-phase components of the aerodynamic coefficients were obtained over a range of angles of attack from 0 to 90 deg. To account for the effect of frequency on the data, mathematical models with unsteady terms were formulated by use of two different indicial functions. Data from a reduced set of frequencies were used to estimate model parameters, including steady-state static and dynamic stability derivatives. Both models showed good prediction capability and the ability to accurately fit the measured data. Estimated static stability derivatives compared well with those obtained from static wind tunnel tests. The roll and yaw rate derivative estimates were compared with rotary-balanced wind tunnel data and theoretical predictions. The estimates and theoretical predictions were in agreement at small angles of attack. The rotary-balance data showed, in general, acceptable agreement with the steady-state derivative estimates.

Computational Thermochemistry: Scale Factor Databases and Scale Factors for Vibrational Frequencies Obtained from Electronic Model Chemistries.

PubMed

Alecu, I M; Zheng, Jingjing; Zhao, Yan; Truhlar, Donald G

2010-09-14

Optimized scale factors for calculating vibrational harmonic and fundamental frequencies and zero-point energies have been determined for 145 electronic model chemistries, including 119 based on approximate functionals depending on occupied orbitals, 19 based on single-level wave function theory, three based on the neglect-of-diatomic-differential-overlap, two based on doubly hybrid density functional theory, and two based on multicoefficient correlation methods. Forty of the scale factors are obtained from large databases, which are also used to derive two universal scale factor ratios that can be used to interconvert between scale factors optimized for various properties, enabling the derivation of three key scale factors at the effort of optimizing only one of them. A reduced scale factor optimization model is formulated in order to further reduce the cost of optimizing scale factors, and the reduced model is illustrated by using it to obtain 105 additional scale factors. Using root-mean-square errors from the values in the large databases, we find that scaling reduces errors in zero-point energies by a factor of 2.3 and errors in fundamental vibrational frequencies by a factor of 3.0, but it reduces errors in harmonic vibrational frequencies by only a factor of 1.3. It is shown that, upon scaling, the balanced multicoefficient correlation method based on coupled cluster theory with single and double excitations (BMC-CCSD) can lead to very accurate predictions of vibrational frequencies. With a polarized, minimally augmented basis set, the density functionals with zero-point energy scale factors closest to unity are MPWLYP1M (1.009), τHCTHhyb (0.989), BB95 (1.012), BLYP (1.013), BP86 (1.014), B3LYP (0.986), MPW3LYP (0.986), and VSXC (0.986).

Finite element formulation of viscoelastic sandwich beams using fractional derivative operators

NASA Astrophysics Data System (ADS)

Galucio, A. C.; Deü, J.-F.; Ohayon, R.

This paper presents a finite element formulation for transient dynamic analysis of sandwich beams with embedded viscoelastic material using fractional derivative constitutive equations. The sandwich configuration is composed of a viscoelastic core (based on Timoshenko theory) sandwiched between elastic faces (based on Euler-Bernoulli assumptions). The viscoelastic model used to describe the behavior of the core is a four-parameter fractional derivative model. Concerning the parameter identification, a strategy to estimate the fractional order of the time derivative and the relaxation time is outlined. Curve-fitting aspects are focused, showing a good agreement with experimental data. In order to implement the viscoelastic model into the finite element formulation, the Grünwald definition of the fractional operator is employed. To solve the equation of motion, a direct time integration method based on the implicit Newmark scheme is used. One of the particularities of the proposed algorithm lies in the storage of displacement history only, reducing considerably the numerical efforts related to the non-locality of fractional operators. After validations, numerical applications are presented in order to analyze truncation effects (fading memory phenomena) and solution convergence aspects.

Parallelization of a hydrological model using the message passing interface

USGS Publications Warehouse

Wu, Yiping; Li, Tiejian; Sun, Liqun; Chen, Ji

2013-01-01

With the increasing knowledge about the natural processes, hydrological models such as the Soil and Water Assessment Tool (SWAT) are becoming larger and more complex with increasing computation time. Additionally, other procedures such as model calibration, which may require thousands of model iterations, can increase running time and thus further reduce rapid modeling and analysis. Using the widely-applied SWAT as an example, this study demonstrates how to parallelize a serial hydrological model in a Windows® environment using a parallel programing technology—Message Passing Interface (MPI). With a case study, we derived the optimal values for the two parameters (the number of processes and the corresponding percentage of work to be distributed to the master process) of the parallel SWAT (P-SWAT) on an ordinary personal computer and a work station. Our study indicates that model execution time can be reduced by 42%–70% (or a speedup of 1.74–3.36) using multiple processes (two to five) with a proper task-distribution scheme (between the master and slave processes). Although the computation time cost becomes lower with an increasing number of processes (from two to five), this enhancement becomes less due to the accompanied increase in demand for message passing procedures between the master and all slave processes. Our case study demonstrates that the P-SWAT with a five-process run may reach the maximum speedup, and the performance can be quite stable (fairly independent of a project size). Overall, the P-SWAT can help reduce the computation time substantially for an individual model run, manual and automatic calibration procedures, and optimization of best management practices. In particular, the parallelization method we used and the scheme for deriving the optimal parameters in this study can be valuable and easily applied to other hydrological or environmental models.

Estimating thermal performance curves from repeated field observations

USGS Publications Warehouse

Childress, Evan; Letcher, Benjamin H.

2017-01-01

Estimating thermal performance of organisms is critical for understanding population distributions and dynamics and predicting responses to climate change. Typically, performance curves are estimated using laboratory studies to isolate temperature effects, but other abiotic and biotic factors influence temperature-performance relationships in nature reducing these models' predictive ability. We present a model for estimating thermal performance curves from repeated field observations that includes environmental and individual variation. We fit the model in a Bayesian framework using MCMC sampling, which allowed for estimation of unobserved latent growth while propagating uncertainty. Fitting the model to simulated data varying in sampling design and parameter values demonstrated that the parameter estimates were accurate, precise, and unbiased. Fitting the model to individual growth data from wild trout revealed high out-of-sample predictive ability relative to laboratory-derived models, which produced more biased predictions for field performance. The field-based estimates of thermal maxima were lower than those based on laboratory studies. Under warming temperature scenarios, field-derived performance models predicted stronger declines in body size than laboratory-derived models, suggesting that laboratory-based models may underestimate climate change effects. The presented model estimates true, realized field performance, avoiding assumptions required for applying laboratory-based models to field performance, which should improve estimates of performance under climate change and advance thermal ecology.

Application of time-variable process noise in terrestrial reference frames determined from VLBI data

NASA Astrophysics Data System (ADS)

Soja, Benedikt; Gross, Richard S.; Abbondanza, Claudio; Chin, Toshio M.; Heflin, Michael B.; Parker, Jay W.; Wu, Xiaoping; Balidakis, Kyriakos; Nilsson, Tobias; Glaser, Susanne; Karbon, Maria; Heinkelmann, Robert; Schuh, Harald

2018-05-01

In recent years, Kalman filtering has emerged as a suitable technique to determine terrestrial reference frames (TRFs), a prime example being JTRF2014. The time series approach allows variations of station coordinates that are neither reduced by observational corrections nor considered in the functional model to be taken into account. These variations are primarily due to non-tidal geophysical loading effects that are not reduced according to the current IERS Conventions (2010). It is standard practice that the process noise models applied in Kalman filter TRF solutions are derived from time series of loading displacements and account for station dependent differences. So far, it has been assumed that the parameters of these process noise models are constant over time. However, due to the presence of seasonal and irregular variations, this assumption does not truly reflect reality. In this study, we derive a station coordinate process noise model allowing for such temporal variations. This process noise model and one that is a parameterized version of the former are applied in the computation of TRF solutions based on very long baseline interferometry data. In comparison with a solution based on a constant process noise model, we find that the station coordinates are affected at the millimeter level.

Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived tumor xenograft models

PubMed Central

Yang, Cheng-Yu; Lin, Chih-Kung; Tsao, Chang-Huei; Hsieh, Cheng-Chih; Lin, Gu-Jiun; Ma, Kuo-Hsing; Shieh, Yi-Shing; Sytwu, Huey-Kang; Chen, Yuan-Wu

2017-01-01

Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we examined whether aberrant LSD1 overexpression in OSCC is associated with poor prognosis. We also evaluated the action mechanism of melatonin against OSCC with lymphatic metastases by using the PDTX models. Our results indicated that melatonin, at pharmacological concentrations, significantly suppresses cell proliferation in a dose- and time-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that the beneficial effects of melatonin in reducing oral cancer cell proliferation are associated with reduced LSD1 expression in vivo and in vitro. PMID:28422711

Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model.

PubMed

Choi, In Young; Lim, HoTae; Estrellas, Kenneth; Mula, Jyothi; Cohen, Tatiana V; Zhang, Yuanfan; Donnelly, Christopher J; Richard, Jean-Philippe; Kim, Yong Jun; Kim, Hyesoo; Kazuki, Yasuhiro; Oshimura, Mitsuo; Li, Hongmei Lisa; Hotta, Akitsu; Rothstein, Jeffrey; Maragakis, Nicholas; Wagner, Kathryn R; Lee, Gabsang

2016-06-07

Duchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs). Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our "chemical-compound-based" strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological "dual-SMAD" inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form "rescued" multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human "DMD-in-a-dish" model using hiPSC-based disease modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Reducing fertilizer-nitrogen losses from rowcrop landscapes: Insights and implications from a spatially explicit watershed model

USGS Publications Warehouse

McLellan, Eileen; Schilling, Keith; Robertson, Dale M.

2015-01-01

We present conceptual and quantitative models that predict changes in fertilizer-derived nitrogen delivery from rowcrop landscapes caused by agricultural conservation efforts implemented to reduce nutrient inputs and transport and increase nutrient retention in the landscape. To evaluate the relative importance of changes in the sources, transport, and sinks of fertilizer-derived nitrogen across a region, we use the spatially explicit SPAtially Referenced Regression On Watershed attributes watershed model to map the distribution, at the small watershed scale within the Upper Mississippi-Ohio River Basin (UMORB), of: (1) fertilizer inputs; (2) nutrient attenuation during delivery of those inputs to the UMORB outlet; and (3) nitrogen export from the UMORB outlet. Comparing these spatial distributions suggests that the amount of fertilizer input and degree of nutrient attenuation are both important in determining the extent of nitrogen export. From a management perspective, this means that agricultural conservation efforts to reduce nitrogen export would benefit by: (1) expanding their focus to include activities that restore and enhance nutrient processing in these highly altered landscapes; and (2) targeting specific types of best management practices to watersheds where they will be most valuable. Doing so successfully may result in a shift in current approaches to conservation planning, outreach, and funding.

Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

PubMed

Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

2017-06-01

Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

A two-fluid model for avalanche and debris flows.

PubMed

Pitman, E Bruce; Le, Long

2005-07-15

Geophysical mass flows--debris flows, avalanches, landslides--can contain O(10(6)-10(10)) m(3) or more of material, often a mixture of soil and rocks with a significant quantity of interstitial fluid. These flows can be tens of meters in depth and hundreds of meters in length. The range of scales and the rheology of this mixture presents significant modelling and computational challenges. This paper describes a depth-averaged 'thin layer' model of geophysical mass flows containing a mixture of solid material and fluid. The model is derived from a 'two-phase' or 'two-fluid' system of equations commonly used in engineering research. Phenomenological modelling and depth averaging combine to yield a tractable set of equations, a hyperbolic system that describes the motion of the two constituent phases. If the fluid inertia is small, a reduced model system that is easier to solve may be derived.

Using model order tests to determine sensory inputs in a motion study

NASA Technical Reports Server (NTRS)

Repperger, D. W.; Junker, A. M.

1977-01-01

In the study of motion effects on tracking performance, a problem of interest is the determination of what sensory inputs a human uses in controlling his tracking task. In the approach presented here a simple canonical model (FID or a proportional, integral, derivative structure) is used to model the human's input-output time series. A study of significant changes in reduction of the output error loss functional is conducted as different permutations of parameters are considered. Since this canonical model includes parameters which are related to inputs to the human (such as the error signal, its derivatives and integration), the study of model order is equivalent to the study of which sensory inputs are being used by the tracker. The parameters are obtained which have the greatest effect on reducing the loss function significantly. In this manner the identification procedure converts the problem of testing for model order into the problem of determining sensory inputs.

On the Development of Parameterized Linear Analytical Longitudinal Airship Models

NASA Technical Reports Server (NTRS)

Kulczycki, Eric A.; Johnson, Joseph R.; Bayard, David S.; Elfes, Alberto; Quadrelli, Marco B.

2008-01-01

In order to explore Titan, a moon of Saturn, airships must be able to traverse the atmosphere autonomously. To achieve this, an accurate model and accurate control of the vehicle must be developed so that it is understood how the airship will react to specific sets of control inputs. This paper explains how longitudinal aircraft stability derivatives can be used with airship parameters to create a linear model of the airship solely by combining geometric and aerodynamic airship data. This method does not require system identification of the vehicle. All of the required data can be derived from computational fluid dynamics and wind tunnel testing. This alternate method of developing dynamic airship models will reduce time and cost. Results are compared to other stable airship dynamic models to validate the methods. Future work will address a lateral airship model using the same methods.

N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.

PubMed

Chang, Chia-Yu; Chen, Sheng-Mei; Lu, Huai-En; Lai, Syu-Ming; Lai, Ping-Shan; Shen, Po-Wen; Chen, Pei-Ying; Shen, Ching-I; Harn, Horng-Jyh; Lin, Shinn-Zong; Hwang, Shiaw-Min; Su, Hong-Lin

2015-03-04

Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.

Seeing through the Canopy: Relationship between Coarse Woody Debris and Forest Structure measured by Airborne Lidar in the Brazilian Amazon

NASA Astrophysics Data System (ADS)

Scaranello, M. A., Sr.; Keller, M. M.; dos-Santos, M. N.; Longo, M.; Pinagé, E. R.; Leitold, V.

2016-12-01

Coarse woody debris is an important but infrequently quantified carbon pool in tropical forests. Based on studies at 12 sites spread across the Brazilian Amazon, we quantified coarse woody debris stocks in intact forests and forests affected by different intensities of degradation by logging and/or fire. Measurement were made in-situ and for the first time field measurements of coarse woody debris were related to structural metrics derived from airborne lidar. Using the line-intercept method we established 84 transects for sampling fallen coarse woody debris and associated inventory plots for sampling standing dead wood in intact, conventional logging, reduced impact logging, burned and burned after logging forests. Overall mean and standard deviation of total coarse woody debris were 50.0 Mg ha-1 and 26.4 Mg ha-1 respectively. Forest degradation increased coarse woody debris stocks compared to intact forests by a factor of 1.7 in reduced impact logging forests and up to 3-fold in burned forests, in a side-by-side comparison of nearby areas. The ratio between coarse woody debris and biomass increased linearly with number of degradation events (R²: 0.67, p<0.01). Individual lidar-derived structural variables strongly correlated with coarse woody debris in intact and reduced impact logging forests: the 5th percentile of last returns for in intact forests (R²: 0.78, p<0.01) and forest gap area, mapped using lidar-derived canopy height model, for reduced impact logging forests (R²: 0.63, p<0.01). Individual gap area also played a weak but significant role in determining coarse woody debris in burned forests (R2: 0.21, p<0.05), but with contrasting trend. Both degradation-specific and general multiple models using lidar-derived variables were good predictor of coarse woody debris stocks in different degradation levels in the Brazilian Amazon. The strong relation of coarse woody debris with lidar derived structural variables suggests an approach for quantifying infrequently measured coarse woody debris over large areas.

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.

Landslides Identification Using Airborne Laser Scanning Data Derived Topographic Terrain Attributes and Support Vector Machine Classification

NASA Astrophysics Data System (ADS)

Pawłuszek, Kamila; Borkowski, Andrzej

2016-06-01

Since the availability of high-resolution Airborne Laser Scanning (ALS) data, substantial progress in geomorphological research, especially in landslide analysis, has been carried out. First and second order derivatives of Digital Terrain Model (DTM) have become a popular and powerful tool in landslide inventory mapping. Nevertheless, an automatic landslide mapping based on sophisticated classifiers including Support Vector Machine (SVM), Artificial Neural Network or Random Forests is often computationally time consuming. The objective of this research is to deeply explore topographic information provided by ALS data and overcome computational time limitation. For this reason, an extended set of topographic features and the Principal Component Analysis (PCA) were used to reduce redundant information. The proposed novel approach was tested on a susceptible area affected by more than 50 landslides located on Rożnów Lake in Carpathian Mountains, Poland. The initial seven PCA components with 90% of the total variability in the original topographic attributes were used for SVM classification. Comparing results with landslide inventory map, the average user's accuracy (UA), producer's accuracy (PA), and overall accuracy (OA) were calculated for two models according to the classification results. Thereby, for the PCA-feature-reduced model UA, PA, and OA were found to be 72%, 76%, and 72%, respectively. Similarly, UA, PA, and OA in the non-reduced original topographic model, was 74%, 77% and 74%, respectively. Using the initial seven PCA components instead of the twenty original topographic attributes does not significantly change identification accuracy but reduce computational time.

Cerebral Aneurysm Clipping Surgery Simulation Using Patient-Specific 3D Printing and Silicone Casting.

PubMed

Ryan, Justin R; Almefty, Kaith K; Nakaji, Peter; Frakes, David H

2016-04-01

Neurosurgery simulator development is growing as practitioners recognize the need for improved instructional and rehearsal platforms to improve procedural skills and patient care. In addition, changes in practice patterns have decreased the volume of specific cases, such as aneurysm clippings, which reduces the opportunity for operating room experience. The authors developed a hands-on, dimensionally accurate model for aneurysm clipping using patient-derived anatomic data and three-dimensional (3D) printing. Design of the model focused on reproducibility as well as adaptability to new patient geometry. A modular, reproducible, and patient-derived medical simulacrum was developed for medical learners to practice aneurysmal clipping procedures. Various forms of 3D printing were used to develop a geometrically accurate cranium and vascular tree featuring 9 patient-derived aneurysms. 3D printing in conjunction with elastomeric casting was leveraged to achieve a patient-derived brain model with tactile properties not yet available from commercial 3D printing technology. An educational pilot study was performed to gauge simulation efficacy. Through the novel manufacturing process, a patient-derived simulacrum was developed for neurovascular surgical simulation. A follow-up qualitative study suggests potential to enhance current educational programs; assessments support the efficacy of the simulacrum. The proposed aneurysm clipping simulator has the potential to improve learning experiences in surgical environment. 3D printing and elastomeric casting can produce patient-derived models for a dynamic learning environment that add value to surgical training and preparation. Copyright © 2016 Elsevier Inc. All rights reserved.

Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis.

PubMed

Sun, Xuejiao; Liu, Yi; Li, Cheng; Wang, Xiting; Zhu, Ruyuan; Liu, Chenyue; Liu, Haixia; Wang, Lili; Ma, Rufeng; Fu, Min; Zhang, Dongwei; Li, Yu

2017-01-01

Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF- κ B, TNF- α , IL-1 β , COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF- β /Smads, MAPK/ERK, and PPAR- γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

PubMed

Hou, Chen; Peng, Danyi; Gao, Li; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Chen, Hong; Zou, Lin; Fu, Zhou

2018-01-08

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O 2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation. Copyright © 2017. Published by Elsevier Inc.

The neglected tool in the Bayesian ecologist's shed: a case study testing informative priors' effect on model accuracy

PubMed Central

Morris, William K; Vesk, Peter A; McCarthy, Michael A; Bunyavejchewin, Sarayudh; Baker, Patrick J

2015-01-01

Despite benefits for precision, ecologists rarely use informative priors. One reason that ecologists may prefer vague priors is the perception that informative priors reduce accuracy. To date, no ecological study has empirically evaluated data-derived informative priors' effects on precision and accuracy. To determine the impacts of priors, we evaluated mortality models for tree species using data from a forest dynamics plot in Thailand. Half the models used vague priors, and the remaining half had informative priors. We found precision was greater when using informative priors, but effects on accuracy were more variable. In some cases, prior information improved accuracy, while in others, it was reduced. On average, models with informative priors were no more or less accurate than models without. Our analyses provide a detailed case study on the simultaneous effect of prior information on precision and accuracy and demonstrate that when priors are specified appropriately, they lead to greater precision without systematically reducing model accuracy. PMID:25628867

The neglected tool in the Bayesian ecologist's shed: a case study testing informative priors' effect on model accuracy.

PubMed

Morris, William K; Vesk, Peter A; McCarthy, Michael A; Bunyavejchewin, Sarayudh; Baker, Patrick J

2015-01-01

Despite benefits for precision, ecologists rarely use informative priors. One reason that ecologists may prefer vague priors is the perception that informative priors reduce accuracy. To date, no ecological study has empirically evaluated data-derived informative priors' effects on precision and accuracy. To determine the impacts of priors, we evaluated mortality models for tree species using data from a forest dynamics plot in Thailand. Half the models used vague priors, and the remaining half had informative priors. We found precision was greater when using informative priors, but effects on accuracy were more variable. In some cases, prior information improved accuracy, while in others, it was reduced. On average, models with informative priors were no more or less accurate than models without. Our analyses provide a detailed case study on the simultaneous effect of prior information on precision and accuracy and demonstrate that when priors are specified appropriately, they lead to greater precision without systematically reducing model accuracy.

Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma.

PubMed

Wu, Aiguo; Ying, Zhe; Schubert, David; Gomez-Pinilla, Fernando

2011-05-01

In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress-related molecules (SOD, Sir2). These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.

Cigarette Smoke Inhibits Recruitment of Bone-Marrow-Derived Stem cells to The Uterus

PubMed Central

Zhou, Yuping; Gan, Ye; Taylor, Hugh S.

2011-01-01

Cigarette smoking leads to female infertility and a decreased incidence of endometriosis. Bone marrow derived stem cells are recruited to uterine endometrium and endometriosis. The effect of cigarette smoking on stem cell recruitment to any organ is uncharacterized. We hypothesized that bone marrow-derived mesenchymal stem cell recruitment to the uterus and differentiation would be diminished by cigarette smoke. We used human mesenchymal stem cells (hMSC) in vitro and a mouse model of cigarette smoke exposure. After myeloablation female C57BL/6J received bone marrow cells from males. Mice were exposed to room air or smoke from unfiltered cigarettes. Immunofluorescence and Y-FISH was performed on uterine sections. In vitro hMSCs were treated with 8-Br-cAMP to induce endometrial cell differentiation with or without cigarette smoke extract (CSE) and decidualization assessed morphologically and by prolactin expression. After 4 weeks the total number of Y-chromosome cells in the uterus was reduced by 68% in the smoke exposed mice. Both leukocytes and bone marrow derived endometrial cells were reduced by 60% and 73%, respectively. Differentiation of bone marrow derived cell to endometrial epithelial cells was reduced by 84%. hMSC treated with CSE failed to show cytological characteristics of decidualization. mRNA levels of the decidualization marker prolactin were decreased by 90% in CSE treated cells. Smoking inhibits both recruitment of bone marrow derived stem cells to uterus and stem cell differentiation. Inhibition of stem cells recruitment may be a general mechanism by which smoking leads to long term organ damage through inability to repair or regenerate multiple tissues. PMID:20955787

PP/PS anisotropic stereotomography

NASA Astrophysics Data System (ADS)

Nag, Steinar; Alerini, Mathias; Ursin, Bjørn

2010-04-01

Stereotomography is a slope tomographic method which gives good results for background velocity model estimation in 2-D isotropic media. We develop here the extension of the method to 3-D general anisotropic media for PP and PS events. We do not take into account the issue of shear wave degeneracy. As in isotropic media, the sensitivity matrix of the inversion can be computed by paraxial ray tracing. We introduce a `constant Z stereotomography' approach, which can reduce the size of the sensitivity matrix. Based on ray perturbation theory, we give all the derivatives of stereotomography data parameters with respect to model parameters in a 3-D general anisotropic medium. These general formulas for the derivatives can also be used in other applications that rely on anisotropic ray perturbation theory. In particular, we obtain derivatives of the phase velocity with respect to position, phase angle and elastic medium parameters, all for general anisotropic media. The derivatives are expressed using the Voigt notation for the elastic medium parameters. We include a Jacobian that allows to change the model parametrization from Voigt to Thomsen parameters. Explicit expressions for the derivatives of the data are given for the case of 2-D tilted transversely isotropic (TTI) media. We validate the method by single-parameter estimation of each Thomsen parameter field of a 2-D TTI synthetic model, where data are modelled by ray tracing. For each Thomsen parameter, the estimated velocity field fits well with the true velocity field.

Three-Dimensional Human Tissue Models That Incorporate Diabetic Foot Ulcer-Derived Fibroblasts Mimic In Vivo Features of Chronic Wounds

PubMed Central

Maione, Anna G.; Brudno, Yevgeny; Stojadinovic, Olivera; Park, Lara K.; Smith, Avi; Tellechea, Ana; Leal, Ermelindo C.; Kearney, Cathal J.; Veves, Aristidis; Tomic-Canic, Marjana; Mooney, David J.

2015-01-01

Diabetic foot ulcers (DFU) are a major, debilitating complication of diabetes mellitus. Unfortunately, many DFUs are refractory to existing treatments and frequently lead to amputation. The development of more effective therapies has been hampered by the lack of predictive in vitro methods to investigate the mechanisms underlying impaired healing. To address this need for realistic wound-healing models, we established patient-derived fibroblasts from DFUs and site-matched controls and used them to construct three-dimensional (3D) models of chronic wound healing. Incorporation of DFU-derived fibroblasts into these models accurately recapitulated the following key aspects of chronic ulcers: reduced stimulation of angiogenesis, increased keratinocyte proliferation, decreased re-epithelialization, and impaired extracellular matrix deposition. In addition to reflecting clinical attributes of DFUs, the wound-healing potential of DFU fibroblasts demonstrated in this suite of models correlated with in vivo wound closure in mice. Thus, the reported panel of 3D DFU models provides a more biologically relevant platform for elucidating the cell–cell and cell–matrix-related mechanisms responsible for chronic wound pathogenesis and may improve translation of in vitro findings into efficacious clinical applications. PMID:25343343

A methodology for reduced order modeling and calibration of the upper atmosphere

NASA Astrophysics Data System (ADS)

Mehta, Piyush M.; Linares, Richard

2017-10-01

Atmospheric drag is the largest source of uncertainty in accurately predicting the orbit of satellites in low Earth orbit (LEO). Accurately predicting drag for objects that traverse LEO is critical to space situational awareness. Atmospheric models used for orbital drag calculations can be characterized either as empirical or physics-based (first principles based). Empirical models are fast to evaluate but offer limited real-time predictive/forecasting ability, while physics based models offer greater predictive/forecasting ability but require dedicated parallel computational resources. Also, calibration with accurate data is required for either type of models. This paper presents a new methodology based on proper orthogonal decomposition toward development of a quasi-physical, predictive, reduced order model that combines the speed of empirical and the predictive/forecasting capabilities of physics-based models. The methodology is developed to reduce the high dimensionality of physics-based models while maintaining its capabilities. We develop the methodology using the Naval Research Lab's Mass Spectrometer Incoherent Scatter model and show that the diurnal and seasonal variations can be captured using a small number of modes and parameters. We also present calibration of the reduced order model using the CHAMP and GRACE accelerometer-derived densities. Results show that the method performs well for modeling and calibration of the upper atmosphere.

Impact of Satellite Viewing-Swath Width on Global and Regional Aerosol Optical Thickness Statistics and Trends

NASA Technical Reports Server (NTRS)

Colarco, P. R.; Kahn, R. A.; Remer, L. A.; Levy, R. C.

2014-01-01

We use the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite aerosol optical thickness (AOT) product to assess the impact of reduced swath width on global and regional AOT statistics and trends. Alongtrack and across-track sampling strategies are employed, in which the full MODIS data set is sub-sampled with various narrow-swath (approximately 400-800 km) and single pixel width (approximately 10 km) configurations. Although view-angle artifacts in the MODIS AOT retrieval confound direct comparisons between averages derived from different sub-samples, careful analysis shows that with many portions of the Earth essentially unobserved, spatial sampling introduces uncertainty in the derived seasonal-regional mean AOT. These AOT spatial sampling artifacts comprise up to 60%of the full-swath AOT value under moderate aerosol loading, and can be as large as 0.1 in some regions under high aerosol loading. Compared to full-swath observations, narrower swath and single pixel width sampling exhibits a reduced ability to detect AOT trends with statistical significance. On the other hand, estimates of the global, annual mean AOT do not vary significantly from the full-swath values as spatial sampling is reduced. Aggregation of the MODIS data at coarse grid scales (10 deg) shows consistency in the aerosol trends across sampling strategies, with increased statistical confidence, but quantitative errors in the derived trends are found even for the full-swath data when compared to high spatial resolution (0.5 deg) aggregations. Using results of a model-derived aerosol reanalysis, we find consistency in our conclusions about a seasonal-regional spatial sampling artifact in AOT Furthermore, the model shows that reduced spatial sampling can amount to uncertainty in computed shortwave top-ofatmosphere aerosol radiative forcing of 2-3 W m(sup-2). These artifacts are lower bounds, as possibly other unconsidered sampling strategies would perform less well. These results suggest that future aerosol satellite missions having significantly less than full-swath viewing are unlikely to sample the true AOT distribution well enough to obtain the statistics needed to reduce uncertainty in aerosol direct forcing of climate.

Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases.

PubMed

Santana, Fernanda Paula R; Pinheiro, Nathalia M; Mernak, Márcia Isabel B; Righetti, Renato F; Martins, Mílton A; Lago, João H G; Lopes, Fernanda D T Q Dos Santos; Tibério, Iolanda F L C; Prado, Carla M

2016-01-01

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.

An integrated physiology model to study regional lung damage effects and the physiologic response

PubMed Central

2014-01-01

Background This work expands upon a previously developed exercise dynamic physiology model (DPM) with the addition of an anatomic pulmonary system in order to quantify the impact of lung damage on oxygen transport and physical performance decrement. Methods A pulmonary model is derived with an anatomic structure based on morphometric measurements, accounting for heterogeneous ventilation and perfusion observed experimentally. The model is incorporated into an existing exercise physiology model; the combined system is validated using human exercise data. Pulmonary damage from blast, blunt trauma, and chemical injury is quantified in the model based on lung fluid infiltration (edema) which reduces oxygen delivery to the blood. The pulmonary damage component is derived and calibrated based on published animal experiments; scaling laws are used to predict the human response to lung injury in terms of physical performance decrement. Results The augmented dynamic physiology model (DPM) accurately predicted the human response to hypoxia, altitude, and exercise observed experimentally. The pulmonary damage parameters (shunt and diffusing capacity reduction) were fit to experimental animal data obtained in blast, blunt trauma, and chemical damage studies which link lung damage to lung weight change; the model is able to predict the reduced oxygen delivery in damage conditions. The model accurately estimates physical performance reduction with pulmonary damage. Conclusions We have developed a physiologically-based mathematical model to predict performance decrement endpoints in the presence of thoracic damage; simulations can be extended to estimate human performance and escape in extreme situations. PMID:25044032

Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

PubMed

Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

2018-05-10

Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Mathematical Model with Quarantine States for the Dynamics of Ebola Virus Disease in Human Populations.

PubMed

Ngwa, Gideon A; Teboh-Ewungkem, Miranda I

2016-01-01

A deterministic ordinary differential equation model for the dynamics and spread of Ebola Virus Disease is derived and studied. The model contains quarantine and nonquarantine states and can be used to evaluate transmission both in treatment centres and in the community. Possible sources of exposure to infection, including cadavers of Ebola Virus victims, are included in the model derivation and analysis. Our model's results show that there exists a threshold parameter, R 0, with the property that when its value is above unity, an endemic equilibrium exists whose value and size are determined by the size of this threshold parameter, and when its value is less than unity, the infection does not spread into the community. The equilibrium state, when it exists, is locally and asymptotically stable with oscillatory returns to the equilibrium point. The basic reproduction number, R 0, is shown to be strongly dependent on the initial response of the emergency services to suspected cases of Ebola infection. When intervention measures such as quarantining are instituted fully at the beginning, the value of the reproduction number reduces and any further infections can only occur at the treatment centres. Effective control measures, to reduce R 0 to values below unity, are discussed.

A Mathematical Model with Quarantine States for the Dynamics of Ebola Virus Disease in Human Populations

PubMed Central

Ngwa, Gideon A.

2016-01-01

A deterministic ordinary differential equation model for the dynamics and spread of Ebola Virus Disease is derived and studied. The model contains quarantine and nonquarantine states and can be used to evaluate transmission both in treatment centres and in the community. Possible sources of exposure to infection, including cadavers of Ebola Virus victims, are included in the model derivation and analysis. Our model's results show that there exists a threshold parameter, R 0, with the property that when its value is above unity, an endemic equilibrium exists whose value and size are determined by the size of this threshold parameter, and when its value is less than unity, the infection does not spread into the community. The equilibrium state, when it exists, is locally and asymptotically stable with oscillatory returns to the equilibrium point. The basic reproduction number, R 0, is shown to be strongly dependent on the initial response of the emergency services to suspected cases of Ebola infection. When intervention measures such as quarantining are instituted fully at the beginning, the value of the reproduction number reduces and any further infections can only occur at the treatment centres. Effective control measures, to reduce R 0 to values below unity, are discussed. PMID:27579053

Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo.

PubMed

Mezouar, Soraya; Darbousset, Roxane; Dignat-George, Françoise; Panicot-Dubois, Laurence; Dubois, Christophe

2015-01-15

Venous thromboembolism constitutes one of the main causes of death during the progression of a cancer. We previously demonstrated that tissue factor (TF)-bearing cancer cell-derived microparticles accumulate at the site of injury in mice developing a pancreatic cancer. The presence of these microparticles at the site of thrombosis correlates with the size of the platelet-rich thrombus. The objective of this study was to determine the involvement of TF expressed by cancer cell-derived microparticles on thrombosis associated with cancer. We observed that pancreatic cancer cell derived microparticles expressed TF, its inhibitor tissue factor pathway inhibitor (TFPI) as well as the integrins αvβ1 and αvβ3. In mice bearing a tumor under-expressing TF, a significant decrease in circulating TF activity associated with an increase bleeding time and a 100-fold diminished fibrin generation and platelet accumulation at the site of injury were observed. This was mainly due to the interaction of circulating cancer cell-derived microparticles expressing TFPI with activated platelets and fibrinogen. In an ectopic model of cancer, treatment of mice with Clopidogrel, an anti-platelet drug, decreased the size of the tumors and restored hemostasis by preventing the accumulation of cancer cell-derived microparticles at the site of thrombosis. In a syngeneic orthotopic model of pancreatic cancer Clopidogrel also significantly inhibited the development of metastases. Together, these results indicate that an anti-platelet strategy may efficiently treat thrombosis associated with cancer and reduce the progression of pancreatic cancer in mice. © 2014 UICC.

Multidisciplinary optimization of aeroservoelastic systems using reduced-size models

NASA Technical Reports Server (NTRS)

Karpel, Mordechay

1992-01-01

Efficient analytical and computational tools for simultaneous optimal design of the structural and control components of aeroservoelastic systems are presented. The optimization objective is to achieve aircraft performance requirements and sufficient flutter and control stability margins with a minimal weight penalty and without violating the design constraints. Analytical sensitivity derivatives facilitate an efficient optimization process which allows a relatively large number of design variables. Standard finite element and unsteady aerodynamic routines are used to construct a modal data base. Minimum State aerodynamic approximations and dynamic residualization methods are used to construct a high accuracy, low order aeroservoelastic model. Sensitivity derivatives of flutter dynamic pressure, control stability margins and control effectiveness with respect to structural and control design variables are presented. The performance requirements are utilized by equality constraints which affect the sensitivity derivatives. A gradient-based optimization algorithm is used to minimize an overall cost function. A realistic numerical example of a composite wing with four controls is used to demonstrate the modeling technique, the optimization process, and their accuracy and efficiency.

Magnetic field of longitudinal gradient bend

NASA Astrophysics Data System (ADS)

Aiba, Masamitsu; Böge, Michael; Ehrlichman, Michael; Streun, Andreas

2018-06-01

The longitudinal gradient bend is an effective method for reducing the natural emittance in light sources. It is, however, not a common element. We have analyzed its magnetic field and derived a set of formulae. Based on the derivation, we discuss how to model the longitudinal gradient bend in accelerator codes that are used for designing electron storage rings. Strengths of multipole components can also be evaluated from the formulae, and we investigate the impact of higher order multipole components in a very low emittance lattice.

Imatinib mesylate (Glivec) inhibits Schwann cell viability and reduces the size of human plexiform neurofibroma in a xenograft model.

PubMed

Demestre, Maria; Herzberg, Jan; Holtkamp, Nikola; Hagel, Christian; Reuss, David; Friedrich, Reinhard E; Kluwe, Lan; Von Deimling, Andreas; Mautner, Victor-F; Kurtz, Andreas

2010-05-01

Plexiform neurofibromas (PNF), one of the major features of neurofibromatosis type 1 (NF1), are characterized by complex cellular composition and mostly slow but variable growth patterns. In this study, we examined the effect of imatinib mesylate, a receptor tyrosine kinase inhibitor, on PNF-derived Schwann cells and PNF tumour growth in vitro and in vivo. In vitro, PNF-derived primary Schwann cells express platelet-derived growth factors receptors (PDGFR) alpha and beta, both targets of imatinib, and cell viability was reduced by imatinib mesylate, with 50% inhibition concentration (IC(50)) of 10 microM. For in vivo studies, PNF tumour fragments xenografted onto the sciatic nerve of athymic nude mice were first characterized. The tumours persisted for at least 63 days and maintained typical characteristics of PNFs such as complex cellular composition, low proliferation rate and angiogenesis. A transient enlargement of the graft size was due to inflammation by host cells. Treatment with imatinib mesylate at a daily dose of 75 mg/kg for 4 weeks reduced the graft size by an average of 80% (n = 8), significantly different from the original sizes within the group and from sizes of the grafts in 11 untreated mice in the control group (P < 0.001). We demonstrated that grafting human PNF tumour fragments into nude mice provides an adequate in vivo model for drug testing. Our results provide in vivo and in vitro evidence for efficacy of imatinib mesylate for PNF.

Reduced-Order Structure-Preserving Model for Parallel-Connected Three-Phase Grid-Tied Inverters

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

Johnson, Brian B; Purba, Victor; Jafarpour, Saber

Next-generation power networks will contain large numbers of grid-connected inverters satisfying a significant fraction of system load. Since each inverter model has a relatively large number of dynamic states, it is impractical to analyze complex system models where the full dynamics of each inverter are retained. To address this challenge, we derive a reduced-order structure-preserving model for parallel-connected grid-tied three-phase inverters. Here, each inverter in the system is assumed to have a full-bridge topology, LCL filter at the point of common coupling, and the control architecture for each inverter includes a current controller, a power controller, and a phase-locked loopmore » for grid synchronization. We outline a structure-preserving reduced-order inverter model with lumped parameters for the setting where the parallel inverters are each designed such that the filter components and controller gains scale linearly with the power rating. By structure preserving, we mean that the reduced-order three-phase inverter model is also composed of an LCL filter, a power controller, current controller, and PLL. We show that the system of parallel inverters can be modeled exactly as one aggregated inverter unit and this equivalent model has the same number of dynamical states as any individual inverter in the system. Numerical simulations validate the reduced-order model.« less

Advanced Control Considerations for Turbofan Engine Design

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Csank, Jeffrey T.; Chicatelli, Amy

2016-01-01

This paper covers the application of a model-based engine control (MBEC) methodology featuring a self tuning on-board model for an aircraft turbofan engine simulation. The nonlinear engine model is capable of modeling realistic engine performance, allowing for a verification of the advanced control methodology over a wide range of operating points and life cycle conditions. The on-board model is a piece-wise linear model derived from the nonlinear engine model and updated using an optimal tuner Kalman Filter estimation routine, which enables the on-board model to self-tune to account for engine performance variations. MBEC is used here to show how advanced control architectures can improve efficiency during the design phase of a turbofan engine by reducing conservative operability margins. The operability margins that can be reduced, such as stall margin, can expand the engine design space and offer potential for efficiency improvements. Application of MBEC architecture to a nonlinear engine simulation is shown to reduce the thrust specific fuel consumption by approximately 1% over the baseline design, while maintaining safe operation of the engine across the flight envelope.

Investigation of approximate models of experimental temperature characteristics of machines

NASA Astrophysics Data System (ADS)

Parfenov, I. V.; Polyakov, A. N.

2018-05-01

This work is devoted to the investigation of various approaches to the approximation of experimental data and the creation of simulation mathematical models of thermal processes in machines with the aim of finding ways to reduce the time of their field tests and reducing the temperature error of the treatments. The main methods of research which the authors used in this work are: the full-scale thermal testing of machines; realization of various approaches at approximation of experimental temperature characteristics of machine tools by polynomial models; analysis and evaluation of modelling results (model quality) of the temperature characteristics of machines and their derivatives up to the third order in time. As a result of the performed researches, rational methods, type, parameters and complexity of simulation mathematical models of thermal processes in machine tools are proposed.

Creating Aerosol Types from CHemistry (CATCH): A New Algorithm to Extend the Link Between Remote Sensing and Models

NASA Astrophysics Data System (ADS)

Dawson, K. W.; Meskhidze, N.; Burton, S. P.; Johnson, M. S.; Kacenelenbogen, M. S.; Hostetler, C. A.; Hu, Y.

2017-11-01

Current remote sensing methods can identify aerosol types within an atmospheric column, presenting an opportunity to incrementally bridge the gap between remote sensing and models. Here a new algorithm was designed for Creating Aerosol Types from CHemistry (CATCH). CATCH-derived aerosol types—dusty mix, maritime, urban, smoke, and fresh smoke—are based on first-generation airborne High Spectral Resolution Lidar (HSRL-1) retrievals during the Ship-Aircraft Bio-Optical Research (SABOR) campaign, July/August 2014. CATCH is designed to derive aerosol types from model output of chemical composition. CATCH-derived aerosol types are determined by multivariate clustering of model-calculated variables that have been trained using retrievals of aerosol types from HSRL-1. CATCH-derived aerosol types (with the exception of smoke) compare well with HSRL-1 retrievals during SABOR with an average difference in aerosol optical depth (AOD) <0.03. Data analysis shows that episodic free tropospheric transport of smoke is underpredicted by the Goddard Earth Observing System- with Chemistry (GEOS-Chem) model. Spatial distributions of CATCH-derived aerosol types for the North American model domain during July/August 2014 show that aerosol type-specific AOD values occurred over representative locations: urban over areas with large population, maritime over oceans, smoke, and fresh smoke over typical biomass burning regions. This study demonstrates that model-generated information on aerosol chemical composition can be translated into aerosol types analogous to those retrieved from remote sensing methods. In the future, spaceborne HSRL-1 and CATCH can be used to gain insight into chemical composition of aerosol types, reducing uncertainties in estimates of aerosol radiative forcing.

Reducing uncertainty and increasing consistency: technical improvements to forest carbon pool estimation using the national forest inventory of the US

Treesearch

C.W. Woodall; G.M. Domke; J. Coulston; M.B. Russell; J.A. Smith; C.H. Perry; S.M. Ogle; S. Healey; A. Gray

2015-01-01

The FIA program does not directly measure forest C stocks. Instead, a combination of empirically derived C estimates (e.g., standing live and dead trees) and models (e.g., understory C stocks related to stand age and forest type) are used to estimate forest C stocks. A series of recent refinements in FIA estimation procedures have sought to reduce the uncertainty...

Hybrid 3D printing: a game-changer in personalized cardiac medicine?

PubMed

Kurup, Harikrishnan K N; Samuel, Bennett P; Vettukattil, Joseph J

2015-12-01

Three-dimensional (3D) printing in congenital heart disease has the potential to increase procedural efficiency and patient safety by improving interventional and surgical planning and reducing radiation exposure. Cardiac magnetic resonance imaging and computed tomography are usually the source datasets to derive 3D printing. More recently, 3D echocardiography has been demonstrated to derive 3D-printed models. The integration of multiple imaging modalities for hybrid 3D printing has also been shown to create accurate printed heart models, which may prove to be beneficial for interventional cardiologists, cardiothoracic surgeons, and as an educational tool. Further advancements in the integration of different imaging modalities into a single platform for hybrid 3D printing and virtual 3D models will drive the future of personalized cardiac medicine.

A parameterization of the passive layer of a quasigeostrophic flow in a continuously-stratified ocean

NASA Astrophysics Data System (ADS)

Benilov, E. S.

2018-05-01

This paper examines quasigeostrophic flows in an ocean that can be subdivided into an upper active layer (AL) and a lower passive layer (PL), with the flow and density stratification mainly confined to the former. Under this assumption, an asymptotic model is derived parameterizing the effect of the PL on the AL. The model depends only on the PL's depth, whereas its Väisälä-Brunt frequency turns out to be unimportant (as long as it is small). Under an additional assumption-that the potential vorticity field in the PL is well-diffused and, thus, uniform-the derived model reduces to a simple boundary condition. This condition is to be applied at the AL/PL interface, after which the PL can be excluded from consideration.

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.

Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment

PubMed Central

2013-01-01

Background Stress and anxiety-related behaviors are seen in many organisms. Studies have shown that in humans and other animals, treatment with selective serotonin reuptake inhibitors (e.g. fluoxetine) can reduce anxiety and anxiety-related behaviors. The efficacies and side effects, however, can vary between individuals. Fluoxetine can modulate anxiety in a stereospecific manner or with equal efficacy regardless of stereoisomer depending on the mechanism of action (e.g. serotonergic or GABAergic effects). Zebrafish are an emerging and valuable translational model for understanding human health related issues such as anxiety. In this study we present data showing the behavioral and whole brain transcriptome changes with fluoxetine treatment in wild-derived zebrafish and suggest additional molecular mechanisms of this widely-prescribed drug. Results We used automated behavioral analyses to assess the effects of racemic and stereoisomeric fluoxetine on male wild-derived zebrafish. Both racemic and the individual isomers of fluoxetine reduced anxiety-related behaviors relative to controls and we did not observe stereospecific fluoxetine effects. Using RNA-sequencing of the whole brain, we identified 411 genes showing differential expression with racemic fluoxetine treatment. Several neuropeptides (neuropeptide Y, isotocin, urocortin 3, prolactin) showed consistent expression patterns with the alleviation of stress and anxiety when anxiety-related behavior was reduced with fluoxetine treatment. With gene ontology and KEGG pathway analyses, we identified lipid and amino acid metabolic processes, and steroid biosynthesis among other terms to be over-enriched. Conclusion Our results demonstrate that fluoxetine reduces anxiety-related behaviors in wild-derived zebrafish and alters their neurogenomic state. We identify two biological processes, lipid and amino acid metabolic synthesis that characterize differences in the fluoxetine treated fish. Fluoxetine may be acting on several different molecular pathways to reduce anxiety-related behaviors in wild-derived zebrafish. This study provides data that could help identify common molecular mechanisms of fluoxetine action across animal taxa. PMID:23706039

Updated reduced CMB data and constraints on cosmological parameters

NASA Astrophysics Data System (ADS)

Cai, Rong-Gen; Guo, Zong-Kuan; Tang, Bo

2015-07-01

We obtain the reduced CMB data {lA, R, z∗} from WMAP9, WMAP9+BKP, Planck+WP and Planck+WP+BKP for the ΛCDM and wCDM models with or without spatial curvature. We then use these reduced CMB data in combination with low-redshift observations to put constraints on cosmological parameters. We find that including BKP results in a higher value of the Hubble constant especially when the equation of state (EOS) of dark energy and curvature are allowed to vary. For the ΛCDM model with curvature, the estimate of the Hubble constant with Planck+WP+Lensing is inconsistent with the one derived from Planck+WP+BKP at about 1.2σ confidence level (CL).

Low-dimensional spike rate models derived from networks of adaptive integrate-and-fire neurons: Comparison and implementation.

PubMed

Augustin, Moritz; Ladenbauer, Josef; Baumann, Fabian; Obermayer, Klaus

2017-06-01

The spiking activity of single neurons can be well described by a nonlinear integrate-and-fire model that includes somatic adaptation. When exposed to fluctuating inputs sparsely coupled populations of these model neurons exhibit stochastic collective dynamics that can be effectively characterized using the Fokker-Planck equation. This approach, however, leads to a model with an infinite-dimensional state space and non-standard boundary conditions. Here we derive from that description four simple models for the spike rate dynamics in terms of low-dimensional ordinary differential equations using two different reduction techniques: one uses the spectral decomposition of the Fokker-Planck operator, the other is based on a cascade of two linear filters and a nonlinearity, which are determined from the Fokker-Planck equation and semi-analytically approximated. We evaluate the reduced models for a wide range of biologically plausible input statistics and find that both approximation approaches lead to spike rate models that accurately reproduce the spiking behavior of the underlying adaptive integrate-and-fire population. Particularly the cascade-based models are overall most accurate and robust, especially in the sensitive region of rapidly changing input. For the mean-driven regime, when input fluctuations are not too strong and fast, however, the best performing model is based on the spectral decomposition. The low-dimensional models also well reproduce stable oscillatory spike rate dynamics that are generated either by recurrent synaptic excitation and neuronal adaptation or through delayed inhibitory synaptic feedback. The computational demands of the reduced models are very low but the implementation complexity differs between the different model variants. Therefore we have made available implementations that allow to numerically integrate the low-dimensional spike rate models as well as the Fokker-Planck partial differential equation in efficient ways for arbitrary model parametrizations as open source software. The derived spike rate descriptions retain a direct link to the properties of single neurons, allow for convenient mathematical analyses of network states, and are well suited for application in neural mass/mean-field based brain network models.

Low-dimensional spike rate models derived from networks of adaptive integrate-and-fire neurons: Comparison and implementation

PubMed Central

Baumann, Fabian; Obermayer, Klaus

2017-01-01

The spiking activity of single neurons can be well described by a nonlinear integrate-and-fire model that includes somatic adaptation. When exposed to fluctuating inputs sparsely coupled populations of these model neurons exhibit stochastic collective dynamics that can be effectively characterized using the Fokker-Planck equation. This approach, however, leads to a model with an infinite-dimensional state space and non-standard boundary conditions. Here we derive from that description four simple models for the spike rate dynamics in terms of low-dimensional ordinary differential equations using two different reduction techniques: one uses the spectral decomposition of the Fokker-Planck operator, the other is based on a cascade of two linear filters and a nonlinearity, which are determined from the Fokker-Planck equation and semi-analytically approximated. We evaluate the reduced models for a wide range of biologically plausible input statistics and find that both approximation approaches lead to spike rate models that accurately reproduce the spiking behavior of the underlying adaptive integrate-and-fire population. Particularly the cascade-based models are overall most accurate and robust, especially in the sensitive region of rapidly changing input. For the mean-driven regime, when input fluctuations are not too strong and fast, however, the best performing model is based on the spectral decomposition. The low-dimensional models also well reproduce stable oscillatory spike rate dynamics that are generated either by recurrent synaptic excitation and neuronal adaptation or through delayed inhibitory synaptic feedback. The computational demands of the reduced models are very low but the implementation complexity differs between the different model variants. Therefore we have made available implementations that allow to numerically integrate the low-dimensional spike rate models as well as the Fokker-Planck partial differential equation in efficient ways for arbitrary model parametrizations as open source software. The derived spike rate descriptions retain a direct link to the properties of single neurons, allow for convenient mathematical analyses of network states, and are well suited for application in neural mass/mean-field based brain network models. PMID:28644841

Modeling the atmospheric chemistry of TICs

NASA Astrophysics Data System (ADS)

Henley, Michael V.; Burns, Douglas S.; Chynwat, Veeradej; Moore, William; Plitz, Angela; Rottmann, Shawn; Hearn, John

2009-05-01

An atmospheric chemistry model that describes the behavior and disposition of environmentally hazardous compounds discharged into the atmosphere was coupled with the transport and diffusion model, SCIPUFF. The atmospheric chemistry model was developed by reducing a detailed atmospheric chemistry mechanism to a simple empirical effective degradation rate term (keff) that is a function of important meteorological parameters such as solar flux, temperature, and cloud cover. Empirically derived keff functions that describe the degradation of target toxic industrial chemicals (TICs) were derived by statistically analyzing data generated from the detailed chemistry mechanism run over a wide range of (typical) atmospheric conditions. To assess and identify areas to improve the developed atmospheric chemistry model, sensitivity and uncertainty analyses were performed to (1) quantify the sensitivity of the model output (TIC concentrations) with respect to changes in the input parameters and (2) improve, where necessary, the quality of the input data based on sensitivity results. The model predictions were evaluated against experimental data. Chamber data were used to remove the complexities of dispersion in the atmosphere.

Computer-aided diagnosis of prostate cancer using multi-parametric MRI: comparison between PUN and Tofts models

NASA Astrophysics Data System (ADS)

Mazzetti, S.; Giannini, V.; Russo, F.; Regge, D.

2018-05-01

Computer-aided diagnosis (CAD) systems are increasingly being used in clinical settings to report multi-parametric magnetic resonance imaging (mp-MRI) of the prostate. Usually, CAD systems automatically highlight cancer-suspicious regions to the radiologist, reducing reader variability and interpretation errors. Nevertheless, implementing this software requires the selection of which mp-MRI parameters can best discriminate between malignant and non-malignant regions. To exploit functional information, some parameters are derived from dynamic contrast-enhanced (DCE) acquisitions. In particular, much CAD software employs pharmacokinetic features, such as K trans and k ep, derived from the Tofts model, to estimate a likelihood map of malignancy. However, non-pharmacokinetic models can be also used to describe DCE-MRI curves, without any requirement for prior knowledge or measurement of the arterial input function, which could potentially lead to large errors in parameter estimation. In this work, we implemented an empirical function derived from the phenomenological universalities (PUN) class to fit DCE-MRI. The parameters of the PUN model are used in combination with T2-weighted and diffusion-weighted acquisitions to feed a support vector machine classifier to produce a voxel-wise malignancy likelihood map of the prostate. The results were all compared to those for a CAD system based on Tofts pharmacokinetic features to describe DCE-MRI curves, using different quality aspects of image segmentation, while also evaluating the number and size of false positive (FP) candidate regions. This study included 61 patients with 70 biopsy-proven prostate cancers (PCa). The metrics used to evaluate segmentation quality between the two CAD systems were not statistically different, although the PUN-based CAD reported a lower number of FP, with reduced size compared to the Tofts-based CAD. In conclusion, the CAD software based on PUN parameters is a feasible means with which to detect PCa, without affecting segmentation quality, and hence it could be successfully applied in clinical settings, improving the automated diagnosis process and reducing computational complexity.

PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia.

PubMed

Parrella, Edoardo; Porrini, Vanessa; Iorio, Rosa; Benarese, Marina; Lanzillotta, Annamaria; Mota, Mariana; Fusco, Mariella; Tonin, Paolo; Spano, PierFranco; Pizzi, Marina

2016-10-01

The combination of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines, and the flavonoid luteolin has been found to exert neuroprotective activities in a variety of mouse models of neurological disorders, including brain ischemia. Indirect findings suggest that the two molecules can reduce the activation of mastocytes in brain ischemia, thus modulating crucial cells that trigger the inflammatory cascade. Though, no evidence exists about a direct effect of PEA and luteolin on mast cells in experimental models of brain ischemia, either used separately or in combination. In order to fill this gap, we developed a novel cell-based model of severe brain ischemia consisting of primary mouse cortical neurons and cloned mast cells derived from mouse fetal liver (MC/9 cells) subjected to oxygen and glucose deprivation (OGD). OGD exposure promoted both mast cell degranulation and the release of lactate dehydrogenase (LDH) in a time-dependent fashion. MC/9 cells exacerbated neuronal damage in neuron-mast cells co-cultures exposed to OGD. Likewise, the conditioned medium derived from OGD-exposed MC/9 cells induced significant neurotoxicity in control primary neurons. PEA and luteolin pre-treatment synergistically prevented the OGD-induced degranulation of mast cells and reduced the neurotoxic potential of MC/9 cells conditioned medium. Finally, the association of the two drugs promoted a direct synergistic neuroprotection even in pure cortical neurons exposed to OGD. In summary, our results indicate that mast cells release neurotoxic factors upon OGD-induced activation. The association PEA-luteolin actively reduces mast cell-mediated neurotoxicity as well as pure neurons susceptibility to OGD. Copyright © 2016 Elsevier B.V. All rights reserved.

Ground-Based Telescope Parametric Cost Model

NASA Technical Reports Server (NTRS)

Stahl, H. Philip; Rowell, Ginger Holmes

2004-01-01

A parametric cost model for ground-based telescopes is developed using multi-variable statistical analysis, The model includes both engineering and performance parameters. While diameter continues to be the dominant cost driver, other significant factors include primary mirror radius of curvature and diffraction limited wavelength. The model includes an explicit factor for primary mirror segmentation and/or duplication (i.e.. multi-telescope phased-array systems). Additionally, single variable models based on aperture diameter are derived. This analysis indicates that recent mirror technology advances have indeed reduced the historical telescope cost curve.

Effectively-truncated large-scale shell-model calculations and nuclei around 100Sn

NASA Astrophysics Data System (ADS)

Gargano, A.; Coraggio, L.; Itaco, N.

2017-09-01

This paper presents a short overview of a procedure we have recently introduced, dubbed the double-step truncation method, which is aimed to reduce the computational complexity of large-scale shell-model calculations. Within this procedure, one starts with a realistic shell-model Hamiltonian defined in a large model space, and then, by analyzing the effective single particle energies of this Hamiltonian as a function of the number of valence protons and/or neutrons, reduced model spaces are identified containing only the single-particle orbitals relevant to the description of the spectroscopic properties of a certain class of nuclei. As a final step, new effective shell-model Hamiltonians defined within the reduced model spaces are derived by way of a unitary transformation of the original large-scale Hamiltonian. A detailed account of this transformation is given and the merit of the double-step truncation method is illustrated by discussing few selected results for 96Mo, described as four protons and four neutrons outside 88Sr. Some new preliminary results for light odd-tin isotopes from A = 101 to 107 are also reported.

In defense of derivations

NASA Astrophysics Data System (ADS)

Mungan, Carl E.

2016-05-01

At the 2015 AAPT Summer Meeting, I presented four derivations of the formula for motional emf. Such physics derivations involve the construction of explanatory frameworks involving diagrams and mathematical models. Although textbooks devote considerable space to such explanations, many teachers and students spend their time on worksheets, end-of-chapter problems, and the like. The book is reduced to a bank of solved (i.e., example) and unsolved (i.e., homework) questions, along with equations in colored boxes that presumably are to be used to answer those questions. Such an approach encourages fragmentation of knowledge, the view that there is only one right answer to a problem with the goal of physics being to find that answer (neatly boxed of course), and the inability to reason about even a slightly different (much less a novel) situation. If we are to develop scientific literacy, significant course time must be devoted to explaining the structure of and support for the models and equations we use.

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

PubMed Central

Lotti, Roberta; Palazzo, Elisabetta; Petrachi, Tiziana; Dallaglio, Katiuscia; Saltari, Annalisa; Truzzi, Francesca; Quadri, Marika; Puviani, Mario; Maiorana, Antonino; Marconi, Alessandra; Pincelli, Carlo

2016-01-01

Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development. PMID:26771605

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

Ramos-Solano, Moisés, E-mail: mrsolano84@gmail.com; Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud; Meza-Canales, Ivan D., E-mail: imezacanales@ice.mpg.de

According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviralmore » gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. - Highlights: • WNT7A is expressed in normal keratinocytes or cervical cells without lesion. • WNT7A is significantly reduced in cervical cancer-derived cells. • Restoration of WNT7A expression in HeLa decreases proliferation and cell migration. • Silencing of WNT7A in HaCaT induces an increased proliferation and migration rate. • Decreased WNT7A expression in this model is due to hypermethylation.« less

Mesenchymal Stem Cells Suppress Chronic Rejection in Heterotopic Small Intestine Transplant Rat Models Via Inhibition of CD68, Transforming Growth Factor- β1, and Platelet-Derived Growth Factor Expression.

PubMed

Li, Fuxin; Cao, Jisen; Zhao, Zhicheng; Li, Chuan; Qi, Feng; Liu, Tong

2017-04-01

Mesenchymal stem cells are easy to obtain and expand, with characteristics of low immunogenicity and strong tissue repair capacity. In this study, our aim was to investigate the role of mesenchymal stem cells in chronic immune rejection of heterotopic small intestine transplant in rats. After successfully constructing a rat chronic immune rejection model of heterotopic small intestine transplant, we infused mesenchymal stem cells into the animal recipients. We observed mesenchymal stem cell location in the recipients, recipient survival, pathology changes, and the expression of CD68, transforming growth factor β1, and platelet-derived growth factor C in the donor intestine. Mesenchymal stem cells inhibited the lymphocyte proliferation caused by concanavalin A in vitro. After stem cells were infused into recipients, they were mainly located in the donor intestine, as well as in the spleen and thymus. Recovery after transplant and pathology changes of the donor intestine in rats with stem cell infusion were better than in the control group; however, we observed no differences in survival time, accompanied by downregulated expression of CD68, transforming growth factor β1, and platelet-derived growth factor C. Mesenchymal stem cells, to a certain extent, could inhibit the process of chronic rejection. The mechanisms may include the inhibited function of these cells on lymphocyte proliferation, reduced infiltration of macrophages, and reduced expression of transforming growth factor β1 and platelet-derived growth factor C.

Use of thermodynamic sorption models to derive radionuclide Kd values for performance assessment: Selected results and recommendations of the NEA sorption project

USGS Publications Warehouse

Ochs, M.; Davis, J.A.; Olin, M.; Payne, T.E.; Tweed, C.J.; Askarieh, M.M.; Altmann, S.

2006-01-01

For the safe final disposal and/or long-term storage of radioactive wastes, deep or near-surface underground repositories are being considered world-wide. A central safety feature is the prevention, or sufficient retardation, of radionuclide (RN) migration to the biosphere. To this end, radionuclide sorption is one of the most important processes. Decreasing the uncertainty in radionuclide sorption may contribute significantly to reducing the overall uncertainty of a performance assessment (PA). For PA, sorption is typically characterised by distribution coefficients (Kd values). The conditional nature of Kd requires different estimates of this parameter for each set of geochemical conditions of potential relevance in a RN's migration pathway. As it is not feasible to measure sorption for every set of conditions, the derivation of Kd for PA must rely on data derived from representative model systems. As a result, uncertainty in Kd is largely caused by the need to derive values for conditions not explicitly addressed in experiments. The recently concluded NEA Sorption Project [1] showed that thermodynamic sorption models (TSMs) are uniquely suited to derive K d as a function of conditions, because they allow a direct coupling of sorption with variable solution chemistry and mineralogy in a thermodynamic framework. The results of the project enable assessment of the suitability of various TSM approaches for PA-relevant applications as well as of the potential and limitations of TSMs to model RN sorption in complex systems. ?? by Oldenbourg Wissenschaftsverlag.

Extracellular Vesicles from Bone Marrow‐Derived Mesenchymal Stem Cells Improve Survival from Lethal Hepatic Failure in Mice

PubMed Central

Haga, Hiroaki; Yan, Irene K.; Takahashi, Kenji; Matsuda, Akiko

2017-01-01

Abstract Stem cell‐based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell‐based therapies. Therapeutic effects of bone‐marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d‐galactosamine/tumor necrosis factor‐α (TNF‐α). Systemically administered EV derived from MSC accumulated within the injured liver following systemic administration, reduced hepatic injury, and modulated cytokine expression. Moreover, survival was dramatically increased by EV derived from either murine or human MSC. Similar results were observed with the use of cryopreserved mMSC‐EV after 3 months. Y‐RNA‐1 was identified as a highly enriched noncoding RNA within hMSC‐EV compared to cells of origin. Moreover, siRNA mediated knockdown of Y‐RNA‐1 reduced the protective effects of MSC‐EV on TNF‐α/ActD‐mediated hepatocyte apoptosis in vitro. These data support a critical role for MSC‐derived EV in mediating reparative responses following hepatic injury, and provide compelling evidence to support the therapeutic use of MSC‐derived EV in fulminant hepatic failure. Stem Cells Translational Medicine 2017;6:1262–1272 PMID:28213967

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

Systematic development of reduced reaction mechanisms for dynamic modeling

NASA Technical Reports Server (NTRS)

Frenklach, M.; Kailasanath, K.; Oran, E. S.

1986-01-01

A method for systematically developing a reduced chemical reaction mechanism for dynamic modeling of chemically reactive flows is presented. The method is based on the postulate that if a reduced reaction mechanism faithfully describes the time evolution of both thermal and chain reaction processes characteristic of a more complete mechanism, then the reduced mechanism will describe the chemical processes in a chemically reacting flow with approximately the same degree of accuracy. Here this postulate is tested by producing a series of mechanisms of reduced accuracy, which are derived from a full detailed mechanism for methane-oxygen combustion. These mechanisms were then tested in a series of reactive flow calculations in which a large-amplitude sinusoidal perturbation is applied to a system that is initially quiescent and whose temperature is high enough to start ignition processes. Comparison of the results for systems with and without convective flow show that this approach produces reduced mechanisms that are useful for calculations of explosions and detonations. Extensions and applicability to flames are discussed.

Spectral Generation from the Ames Mars GCM for the Study of Martian Clouds

NASA Astrophysics Data System (ADS)

Klassen, David R.; Kahre, Melinda A.; Wolff, Michael J.; Haberle, Robert; Hollingsworth, Jeffery L.

2017-10-01

Studies of martian clouds come from two distinct groups of researchers: those modeling the martian system from first principles and those observing Mars from ground-based and orbital platforms. The model-view begins with global circulation models (GCMs) or mesoscale models to track a multitude of state variables over a prescribed set of spatial and temporal resolutions. The state variables can then be processed into distinct maps of derived product variables, such as integrated optical depth of aerosol (e.g., water ice cloud, dust) or column integrated water vapor for comparison to observational results. The observer view begins, typically, with spectral images or imaging spectra, calibrated to some form of absolute units then run through some form of radiative transfer model to also produce distinct maps of derived product variables. Both groups of researchers work to adjust model parameters and assumptions until some level of agreement in derived product variables is achieved. While this system appears to work well, it is in some sense only an implicit confirmation of the model assumptions that attribute to the work from both sides. We have begun a project of testing the NASA Ames Mars GCM and key aerosol model assumptions more directly by taking the model output and creating synthetic TES-spectra from them for comparison to actual raw-reduced TES spectra. We will present some preliminary generated GCM spectra and TES comparisons.

Comparison of constitutive flow resistance equations based on the Manning and Chezy equations applied to natural rivers

USGS Publications Warehouse

Bjerklie, David M.; Dingman, S. Lawrence; Bolster, Carl H.

2005-01-01

A set of conceptually derived in‐bank river discharge–estimating equations (models), based on the Manning and Chezy equations, are calibrated and validated using a database of 1037 discharge measurements in 103 rivers in the United States and New Zealand. The models are compared to a multiple regression model derived from the same data. The comparison demonstrates that in natural rivers, using an exponent on the slope variable of 0.33 rather than the traditional value of 0.5 reduces the variance associated with estimating flow resistance. Mean model uncertainty, assuming a constant value for the conductance coefficient, is less than 5% for a large number of estimates, and 67% of the estimates would be accurate within 50%. The models have potential application where site‐specific flow resistance information is not available and can be the basis for (1) a general approach to estimating discharge from remotely sensed hydraulic data, (2) comparison to slope‐area discharge estimates, and (3) large‐scale river modeling.

Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer

PubMed Central

Qu, Sifeng; Ci, Xinpei; Xue, Hui; Dong, Xin; Hao, Jun; Lin, Dong; Clermont, Pier-Luc; Wu, Rebecca; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

2018-01-01

Background: Docetaxel used for first-line treatment of advanced prostate cancer (PCa) is only marginally effective. We previously showed, using the LTL-313H subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to marked synergistic tumour growth inhibition. Here, we investigated the effect of docetaxel+Aneustat on metastasis. Methods: C4-2 cells were incubated with docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration. The LTL-313H model, similarly treated, was analysed for effects on lung micro-metastasis and kidney invasion. The LTL-313H gene expression profile was compared with profiles of PCa patients (obtained from Oncomine) and subjected to IPA to determine involvement of cancer driver genes. Results: Docetaxel+Aneustat markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney invasion. Oncomine analysis indicated that treatment with docetaxel+Aneustat was associated with improved patient outcome. The drug combination markedly downregulated expression of cancer driver genes such as FOXM1 (and FOXM1-target genes). FOXM1 overexpression reduced the anti-metastatic activity of docetaxel+Aneustat. Conclusions: Docetaxel+Aneustat can inhibit PCa tissue invasion and metastasis. This activity appears to be based on reduced expression of cancer driver genes such as FOXM1. Use of docetaxel+Aneustat may provide a new, more effective regimen for therapy of metastatic PCa. PMID:29381682

Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure of the rabbit.

PubMed

ElSohly, M A; Harland, E C; Benigni, D A; Waller, C W

1984-06-01

Thirty-two different cannabinoids were tested for their ability to reduce intraocular pressure (IOP) in the rabbit. These included many of delta 9- and delta 8-THC derivatives and metabolites along with other natural and synthetic cannabinoids. In addition, some non-cannabinoid constituents of Cannabis were screened using the same model. All compounds were administered intravenously, while only a few were tested topically in mineral oil. Water soluble derivatives of delta 9- and delta 8-THC were prepared and tested topically in aqueous solution. The data revealed that certain derivatives of delta 9-and delta 8-THC were more active in lowering IOP than the parent cannabinoids. In addition, compounds other than delta 9- and delta 8-THC and their derivatives were shown to have activity.

A model of free-living gait: A factor analysis in Parkinson's disease.

PubMed

Morris, Rosie; Hickey, Aodhán; Del Din, Silvia; Godfrey, Alan; Lord, Sue; Rochester, Lynn

2017-02-01

Gait is a marker of global health, cognition and falls risk. Gait is complex, comprised of multiple characteristics sensitive to survival, age and pathology. Due to covariance amongst characteristics, conceptual gait models have been established to reduce redundancy and aid interpretation. Previous models have been derived from laboratory gait assessments which are costly in equipment and time. Body-worn monitors (BWM) allow for free-living, low-cost and continuous gait measurement and produce similar covariant gait characteristics. A BWM gait model from both controlled and free-living measurement has not yet been established, limiting utility. 103 control and 67 PD participants completed a controlled laboratory assessment; walking for two minutes around a circuit wearing a BWM. 89 control and 58 PD participants were assessed in free-living, completing normal activities for 7 days wearing a BWM. Fourteen gait characteristics were derived from the BWM, selected according to a previous model. Principle component analysis derived factor loadings of gait characteristics. Four gait domains were derived for both groups and conditions; pace, rhythm, variability and asymmetry. Domains totalled 84.84% and 88.43% of variance for controlled and 90.00% and 93.03% of variance in free-living environments for control and PD participants respectively. Gait characteristic loading was unambiguous for all characteristics apart from gait variability which demonstrated cross-loading for both groups and environments. The model was highly congruent with the original model. The conceptual gait models remained stable using a BWM in controlled and free-living environments. The model became more discrete supporting utility of the gait model for free-living gait. Copyright © 2016 Elsevier B.V. All rights reserved.

Computational Discovery of Niclosamide Ethanolamine, a Repurposed Drug Candidate That Reduces Growth of Hepatocellular Carcinoma Cells In Vitro and in Mice by Inhibiting Cell Division Cycle 37 Signaling.

PubMed

Chen, Bin; Wei, Wei; Ma, Li; Yang, Bin; Gill, Ryan M; Chua, Mei-Sze; Butte, Atul J; So, Samuel

2017-06-01

Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). We searched public databases of messenger RNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are down-regulated in HCCs and reduce expression of genes up-regulated in HCCs using a nonparametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic. We evaluated the anti-tumor activity of niclosamide and its ethanolamine salt (NEN) in HCC cell lines (HepG2, Huh7, Hep3B, Hep40, and PLC/PRF/5), primary human hepatocytes, and 2 mouse models of HCC. In one model of HCC, liver tumor development was induced by hydrodynamic delivery of a sleeping beauty transposon expressing an activated form of Ras (v12) and truncated β-catenin (N90). In another mouse model, patient-derived xenografts were established by implanting HCC cells from patients into livers of immunocompromised mice. Tumor growth was monitored by bioluminescence imaging. Tumor-bearing mice were fed a regular chow diet or a chow diet containing niclosamide or NEN. In a separate experiment using patient-derived xenografts, tumor-bearing mice were given sorafenib (the standard of care for patients with advanced HCC), NEN, or niclosamide alone; a combination of sorafenib and NEN; or a combination sorafenib and niclosamide in their drinking water, or regular water (control), and tumor growth was monitored. Based on gene expression signatures, we identified 3 anthelmintics that significantly altered the expression of genes that are up- or down-regulated in HCCs. Niclosamide and NEN specifically reduced the viability of HCC cells: the agents were at least 7-fold more cytotoxic to HCCs than primary hepatocytes. Oral administration of NEN to mice significantly slowed growth of genetically induced liver tumors and patient-derived xenografts, whereas niclosamide did not, coinciding with the observed greater bioavailability of NEN compared with niclosamide. The combination of NEN and sorafenib was more effective at slowing growth of patient-derived xenografts than either agent alone. In HepG2 cells and in patient-derived xenografts, administration of niclosamide or NEN increased expression of 20 genes down-regulated in HCC and reduced expression of 29 genes up-regulated in the 274-gene HCC signature. Administration of NEN to mice with patient-derived xenografts reduced expression of proteins in the Wnt-β-catenin, signal transducer and activator of transcription 3, AKT-mechanistic target of rapamycin, epidermal growth factor receptor-Ras-Raf signaling pathways. Using immunoprecipitation assays, we found NEN to bind cell division cycle 37 protein and disrupt its interaction with heat shock protein 90. In a bioinformatics search for agents that alter the HCC-specific gene expression pattern, we identified the anthelmintic niclosamide as a potential anti-tumor agent. Its ethanolamine salt, with greater bioavailability, was more effective than niclosamide at slowing the growth of genetically induced liver tumors and patient-derived xenografts in mice. Both agents disrupted interaction between cell division cycle 37 and heat shock protein 90 in HCC cells, with concomitant inhibition of their downstream signaling pathways. NEN might be effective for treatment of patients with HCC. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Linear Algebraic Modeling of Power Flow in the HMPT500-3 Transmission

DTIC Science & Technology

2012-08-01

BFV ) family and Multiple Launch Rocket System (MLRS). It is also proposed for use in the Paladin Integrated Management (PIM) self-propelled...howitzer and BFV derived Armored Multipurpose Vehicle (AMPV). Weight growth of these vehicles is exceeding the capacity of the current HMPT500-3...reduce the heat-rejection burden to the cooling system also makes efficiency improvements desirable. Automotive performance models of the BFV to

Linear Algebraic Modeling of Power Flow in the HMP500-3 Transmission

DTIC Science & Technology

2012-08-01

BFV ) family and Multiple Launch Rocket System (MLRS). It is also proposed for use in the Paladin Integrated Management (PIM) self-propelled...howitzer and BFV derived Armored Multipurpose Vehicle (AMPV). Weight growth of these vehicles is exceeding the capacity of the current HMPT500-3...reduce the heat-rejection burden to the cooling system also makes efficiency improvements desirable. Automotive performance models of the BFV to date

Visco-elastic controlled-source full waveform inversion without surface waves

NASA Astrophysics Data System (ADS)

Paschke, Marco; Krause, Martin; Bleibinhaus, Florian

2016-04-01

We developed a frequency-domain visco-elastic full waveform inversion for onshore seismic experiments with topography. The forward modeling is based on a finite-difference time-domain algorithm by Robertsson that uses the image-method to ensure a stress-free condition at the surface. The time-domain data is Fourier-transformed at every point in the model space during the forward modeling for a given set of frequencies. The motivation for this approach is the reduced amount of memory when computing kernels, and the straightforward implementation of the multiscale approach. For the inversion, we calculate the Frechet derivative matrix explicitly, and we implement a Levenberg-Marquardt scheme that allows for computing the resolution matrix. To reduce the size of the Frechet derivative matrix, and to stabilize the inversion, an adapted inverse mesh is used. The node spacing is controlled by the velocity distribution and the chosen frequencies. To focus the inversion on body waves (P, P-coda, and S) we mute the surface waves from the data. Consistent spatiotemporal weighting factors are applied to the wavefields during the Fourier transform to obtain the corresponding kernels. We test our code with a synthetic study using the Marmousi model with arbitrary topography. This study also demonstrates the importance of topography and muting surface waves in controlled-source full waveform inversion.

18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.

PubMed

Wang, Di; Zhang, Yongfeng; Wang, Chunyue; Jia, Dongxu; Cai, Guangsheng; Lu, Jiahui; Wang, Di; Zhang, Zhang-Jin

2016-09-01

The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.

Effect of Whey Supplementation on Circulating C-Reactive Protein: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Zhou, Ling-Mei; Xu, Jia-Ying; Rao, Chun-Ping; Han, Shufen; Wan, Zhongxiao; Qin, Li-Qiang

2015-01-01

Whey supplementation is beneficial for human health, possibly by reducing the circulating C-reactive protein (CRP) level, a sensitive marker of inflammation. Thus, a meta-analysis of randomized controlled trials was conducted to evaluate their relationship. A systematic literature search was conducted in July, 2014, to identify eligible studies. Either a fixed-effects model or a random-effects model was used to calculate pooled effects. The meta-analysis results of nine trials showed a slight, but no significant, reduction of 0.42 mg/L (95% CI −0.96, 0.13) in CRP level with the supplementation of whey protein and its derivates. Relatively high heterogeneity across studies was observed. Subgroup analyses showed that whey significantly lowered CRP by 0.72 mg/L (95% CI −0.97, −0.47) among trials with a daily whey dose ≥20 g/day and by 0.67 mg/L (95% CI −1.21, −0.14) among trials with baseline CRP ≥3 mg/L. Meta-regression analysis revealed that the baseline CRP level was a potential effect modifier of whey supplementation in reducing CRP. In conclusion, our meta-analysis did not find sufficient evidence that whey and its derivates elicited a beneficial effect in reducing circulating CRP. However, they may significantly reduce CRP among participants with highly supplemental doses or increased baseline CRP levels. PMID:25671415

THE ROLE OF SPECTRAL IMAGERY FOR MONITORING & MODELING TRANSGENIC CROP-PEST INTERACTIONS

EPA Science Inventory

Crops bioengineered to contain toxins derived from Bacillus thuringensis (Bt) are under regulatory scrutiny by USEPA under the FIFRA legislation. The agency has declared these crops to be "in the public good" based on the reduced use of pesticides required for management of these...

Analytical skin friction and heat transfer formula for compressible internal flows

NASA Technical Reports Server (NTRS)

Dechant, Lawrence J.; Tattar, Marc J.

1994-01-01

An analytic, closed-form friction formula for turbulent, internal, compressible, fully developed flow was derived by extending the incompressible law-of-the-wall relation to compressible cases. The model is capable of analyzing heat transfer as a function of constant surface temperatures and surface roughness as well as analyzing adiabatic conditions. The formula reduces to Prandtl's law of friction for adiabatic, smooth, axisymmetric flow. In addition, the formula reduces to the Colebrook equation for incompressible, adiabatic, axisymmetric flow with various roughnesses. Comparisons with available experiments show that the model averages roughly 12.5 percent error for adiabatic flow and 18.5 percent error for flow involving heat transfer.

Influence of model reduction on uncertainty of flood inundation predictions

NASA Astrophysics Data System (ADS)

Romanowicz, R. J.; Kiczko, A.; Osuch, M.

2012-04-01

Derivation of flood risk maps requires an estimation of the maximum inundation extent for a flood with an assumed probability of exceedence, e.g. a 100 or 500 year flood. The results of numerical simulations of flood wave propagation are used to overcome the lack of relevant observations. In practice, deterministic 1-D models are used for flow routing, giving a simplified image of a flood wave propagation process. The solution of a 1-D model depends on the simplifications to the model structure, the initial and boundary conditions and the estimates of model parameters which are usually identified using the inverse problem based on the available noisy observations. Therefore, there is a large uncertainty involved in the derivation of flood risk maps. In this study we examine the influence of model structure simplifications on estimates of flood extent for the urban river reach. As the study area we chose the Warsaw reach of the River Vistula, where nine bridges and several dikes are located. The aim of the study is to examine the influence of water structures on the derived model roughness parameters, with all the bridges and dikes taken into account, with a reduced number and without any water infrastructure. The results indicate that roughness parameter values of a 1-D HEC-RAS model can be adjusted for the reduction in model structure. However, the price we pay is the model robustness. Apart from a relatively simple question regarding reducing model structure, we also try to answer more fundamental questions regarding the relative importance of input, model structure simplification, parametric and rating curve uncertainty to the uncertainty of flood extent estimates. We apply pseudo-Bayesian methods of uncertainty estimation and Global Sensitivity Analysis as the main methodological tools. The results indicate that the uncertainties have a substantial influence on flood risk assessment. In the paper we present a simplified methodology allowing the influence of that uncertainty to be assessed. This work was supported by National Science Centre of Poland (grant 2011/01/B/ST10/06866).

Comparison of different models for non-invasive FFR estimation

NASA Astrophysics Data System (ADS)

Mirramezani, Mehran; Shadden, Shawn

2017-11-01

Coronary artery disease is a leading cause of death worldwide. Fractional flow reserve (FFR), derived from invasively measuring the pressure drop across a stenosis, is considered the gold standard to diagnose disease severity and need for treatment. Non-invasive estimation of FFR has gained recent attention for its potential to reduce patient risk and procedural cost versus invasive FFR measurement. Non-invasive FFR can be obtained by using image-based computational fluid dynamics to simulate blood flow and pressure in a patient-specific coronary model. However, 3D simulations require extensive effort for model construction and numerical computation, which limits their routine use. In this study we compare (ordered by increasing computational cost/complexity): reduced-order algebraic models of pressure drop across a stenosis; 1D, 2D (multiring) and 3D CFD models; as well as 3D FSI for the computation of FFR in idealized and patient-specific stenosis geometries. We demonstrate the ability of an appropriate reduced order algebraic model to closely predict FFR when compared to FFR from a full 3D simulation. This work was supported by the NIH, Grant No. R01-HL103419.

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

PubMed Central

Monsma, David J; Cherba, David M; Eugster, Emily E; Dylewski, Dawna L; Davidson, Paula T; Peterson, Chelsea A; Borgman, Andrew S; Winn, Mary E; Dykema, Karl J; Webb, Craig P; MacKeigan, Jeffrey P; Duesbery, Nicholas S; Nickoloff, Brian J; Monks, Noel R

2015-01-01

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAFV600E models showed acquired drug resistance, one BRAFV600E model had a complete and durable response, and a BRAFV600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations. PMID:26101714

Application of adipose-derived stem cells on scleral contact lens carrier in an animal model of severe acute alkaline burn.

PubMed

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2014-07-01

To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits.

Application of Adipose-Derived Stem Cells on Scleral Contact Lens Carrier in an Animal Model of Severe Acute Alkaline Burn

PubMed Central

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2015-01-01

Purpose To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. Materials and Methods After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Results Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Conclusion Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits. PMID:24901976

Occurrence of urea-based soluble epoxide hydrolase inhibitors from the plants in the order Brassicales

PubMed Central

Kitamura, Seiya; Morisseau, Christophe; Harris, Todd R.; Inceoglu, Bora

2017-01-01

Recently, dibenzylurea-based potent soluble epoxide hydrolase (sEH) inhibitors were identified in Pentadiplandra brazzeana, a plant in the order Brassicales. In an effort to generalize the concept, we hypothesized that plants that produce benzyl glucosinolates and corresponding isothiocyanates also produce these dibenzylurea derivatives. Our overall aim here was to examine the occurrence of urea derivatives in Brassicales, hoping to find biologically active urea derivatives from plants. First, plants in the order Brassicales were analyzed for the presence of 1, 3-dibenzylurea (compound 1), showing that three additional plants in the order Brassicales produce the urea derivatives. Based on the hypothesis, three dibenzylurea derivatives with sEH inhibitory activity were isolated from maca (Lepidium meyenii) roots. Topical application of one of the identified compounds (compound 3, human sEH IC50 = 222 nM) effectively reduced pain in rat inflammatory pain model, and this compound was bioavailable after oral administration in mice. The biosynthetic pathway of these urea derivatives was investigated using papaya (Carica papaya) seed as a model system. Finally, a small collection of plants from the Brassicales order was grown, collected, extracted and screened for sEH inhibitory activity. Results show that several plants of the Brassicales order could be potential sources of urea-based sEH inhibitors. PMID:28472063

The Preventive Control of a Dengue Disease Using Pontryagin Minimum Principal

NASA Astrophysics Data System (ADS)

Ratna Sari, Eminugroho; Insani, Nur; Lestari, Dwi

2017-06-01

Behaviour analysis for host-vector model without control of dengue disease is based on the value of basic reproduction number obtained using next generation matrices. Furthermore, the model is further developed involving a preventive control to minimize the contact between host and vector. The purpose is to obtain an optimal preventive strategy with minimal cost. The Pontryagin Minimum Principal is used to find the optimal control analytically. The derived optimality model is then solved numerically to investigate control effort to reduce infected class.

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.

Mapping of the DLQI scores to EQ-5D utility values using ordinal logistic regression.

PubMed

Ali, Faraz Mahmood; Kay, Richard; Finlay, Andrew Y; Piguet, Vincent; Kupfer, Joerg; Dalgard, Florence; Salek, M Sam

2017-11-01

The Dermatology Life Quality Index (DLQI) and the European Quality of Life-5 Dimension (EQ-5D) are separate measures that may be used to gather health-related quality of life (HRQoL) information from patients. The EQ-5D is a generic measure from which health utility estimates can be derived, whereas the DLQI is a specialty-specific measure to assess HRQoL. To reduce the burden of multiple measures being administered and to enable a more disease-specific calculation of health utility estimates, we explored an established mathematical technique known as ordinal logistic regression (OLR) to develop an appropriate model to map DLQI data to EQ-5D-based health utility estimates. Retrospective data from 4010 patients were randomly divided five times into two groups for the derivation and testing of the mapping model. Split-half cross-validation was utilized resulting in a total of ten ordinal logistic regression models for each of the five EQ-5D dimensions against age, sex, and all ten items of the DLQI. Using Monte Carlo simulation, predicted health utility estimates were derived and compared against those observed. This method was repeated for both OLR and a previously tested mapping methodology based on linear regression. The model was shown to be highly predictive and its repeated fitting demonstrated a stable model using OLR as well as linear regression. The mean differences between OLR-predicted health utility estimates and observed health utility estimates ranged from 0.0024 to 0.0239 across the ten modeling exercises, with an average overall difference of 0.0120 (a 1.6% underestimate, not of clinical importance). This modeling framework developed in this study will enable researchers to calculate EQ-5D health utility estimates from a specialty-specific study population, reducing patient and economic burden.

Reduced-Order Structure-Preserving Model for Parallel-Connected Three-Phase Grid-Tied Inverters: Preprint

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

Johnson, Brian B; Purba, Victor; Jafarpour, Saber

Given that next-generation infrastructures will contain large numbers of grid-connected inverters and these interfaces will be satisfying a growing fraction of system load, it is imperative to analyze the impacts of power electronics on such systems. However, since each inverter model has a relatively large number of dynamic states, it would be impractical to execute complex system models where the full dynamics of each inverter are retained. To address this challenge, we derive a reduced-order structure-preserving model for parallel-connected grid-tied three-phase inverters. Here, each inverter in the system is assumed to have a full-bridge topology, LCL filter at the pointmore » of common coupling, and the control architecture for each inverter includes a current controller, a power controller, and a phase-locked loop for grid synchronization. We outline a structure-preserving reduced-order inverter model for the setting where the parallel inverters are each designed such that the filter components and controller gains scale linearly with the power rating. By structure preserving, we mean that the reduced-order three-phase inverter model is also composed of an LCL filter, a power controller, current controller, and PLL. That is, we show that the system of parallel inverters can be modeled exactly as one aggregated inverter unit and this equivalent model has the same number of dynamical states as an individual inverter in the paralleled system. Numerical simulations validate the reduced-order models.« less

Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma.

PubMed

Andersen, Nicholas J; Nickoloff, Brian J; Dykema, Karl J; Boguslawski, Elissa A; Krivochenitser, Roman I; Froman, Roe E; Dawes, Michelle J; Baker, Laurence H; Thomas, Dafydd G; Kamstock, Debra A; Kitchell, Barbara E; Furge, Kyle A; Duesbery, Nicholas S

2013-09-01

Angiosarcoma is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human angiosarcoma, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive extracellular signal-regulated kinase (ERK) activation. The mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multireceptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human angiosarcoma, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was upregulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human angiosarcoma. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human angiosarcoma, and it highlights the use of spontaneous canine cancers as a model of human disease.

Calibration of GOES-derived solar radiation data using a distributed network of surface measurements in Florida, USA

USGS Publications Warehouse

Sumner, David M.; Pathak, Chandra S.; Mecikalski, John R.; Paech, Simon J.; Wu, Qinglong; Sangoyomi, Taiye; Babcock, Roger W.; Walton, Raymond

2008-01-01

Solar radiation data are critically important for the estimation of evapotranspiration. Analysis of visible-channel data derived from Geostationary Operational Environmental Satellites (GOES) using radiative transfer modeling has been used to produce spatially- and temporally-distributed datasets of solar radiation. An extensive network of (pyranometer) surface measurements of solar radiation in the State of Florida has allowed refined calibration of a GOES-derived daily integrated radiation data product. This refinement of radiation data allowed for corrections of satellite sensor drift, satellite generational change, and consideration of the highly-variable cloudy conditions that are typical of Florida. To aid in calibration of a GOES-derived radiation product, solar radiation data for the period 1995–2004 from 58 field stations that are located throughout the State were compiled. The GOES radiation product was calibrated by way of a three-step process: 1) comparison with ground-based pyranometer measurements on clear reference days, 2) correcting for a bias related to cloud cover, and 3) deriving month-by-month bias correction factors. Pre-calibration results indicated good model performance, with a station-averaged model error of 2.2 MJ m–2 day–1 (13 percent). Calibration reduced errors to 1.7 MJ m–2 day–1 (10 percent) and also removed time- and cloudiness-related biases. The final dataset has been used to produce Statewide evapotranspiration estimates.

Reducing computation in an i-vector speaker recognition system using a tree-structured universal background model

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

McClanahan, Richard; De Leon, Phillip L.

The majority of state-of-the-art speaker recognition systems (SR) utilize speaker models that are derived from an adapted universal background model (UBM) in the form of a Gaussian mixture model (GMM). This is true for GMM supervector systems, joint factor analysis systems, and most recently i-vector systems. In all of the identified systems, the posterior probabilities and sufficient statistics calculations represent a computational bottleneck in both enrollment and testing. We propose a multi-layered hash system, employing a tree-structured GMM–UBM which uses Runnalls’ Gaussian mixture reduction technique, in order to reduce the number of these calculations. Moreover, with this tree-structured hash, wemore » can trade-off reduction in computation with a corresponding degradation of equal error rate (EER). As an example, we also reduce this computation by a factor of 15× while incurring less than 10% relative degradation of EER (or 0.3% absolute EER) when evaluated with NIST 2010 speaker recognition evaluation (SRE) telephone data.« less

Reducing computation in an i-vector speaker recognition system using a tree-structured universal background model

DOE PAGES

McClanahan, Richard; De Leon, Phillip L.

2014-08-20

The majority of state-of-the-art speaker recognition systems (SR) utilize speaker models that are derived from an adapted universal background model (UBM) in the form of a Gaussian mixture model (GMM). This is true for GMM supervector systems, joint factor analysis systems, and most recently i-vector systems. In all of the identified systems, the posterior probabilities and sufficient statistics calculations represent a computational bottleneck in both enrollment and testing. We propose a multi-layered hash system, employing a tree-structured GMM–UBM which uses Runnalls’ Gaussian mixture reduction technique, in order to reduce the number of these calculations. Moreover, with this tree-structured hash, wemore » can trade-off reduction in computation with a corresponding degradation of equal error rate (EER). As an example, we also reduce this computation by a factor of 15× while incurring less than 10% relative degradation of EER (or 0.3% absolute EER) when evaluated with NIST 2010 speaker recognition evaluation (SRE) telephone data.« less

An error bound for a discrete reduced order model of a linear multivariable system

NASA Technical Reports Server (NTRS)

Al-Saggaf, Ubaid M.; Franklin, Gene F.

1987-01-01

The design of feasible controllers for high dimension multivariable systems can be greatly aided by a method of model reduction. In order for the design based on the order reduction to include a guarantee of stability, it is sufficient to have a bound on the model error. Previous work has provided such a bound for continuous-time systems for algorithms based on balancing. In this note an L-infinity bound is derived for model error for a method of order reduction of discrete linear multivariable systems based on balancing.

Arundinosides A-G, new glucosyloxybenzyl 2R-benzylmalate derivatives from the aerial parts of Arundina graminifolia.

PubMed

Auberon, Florence; Olatunji, Opeyemi Joshua; Krisa, Stéphanie; Herbette, Gaëtan; Antheaume, Cyril; Bonté, Frédéric; Mérillon, Jean-Michel; Lobstein, Annelise

2018-03-01

Seven new glucosyloxybenzyl 2R-benzylmalate derivatives, arundinosides A-G (1-7) were isolated from the aerial parts of the bamboo orchid Arundina graminifolia. This is the first occurrence of this class of compounds in the genus Arundina. Their planar structures and absolute configuration were determined by extensive NMR spectroscopic data as well as chemical conversion. Their neuroprotective properties were also evaluated on their potential ability to reduce the beta amyloid damage on PC12 cell model. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel metastatic models of esophageal adenocarcinoma derived from FLO-1 cells highlight the importance of E-cadherin in cancer metastasis.

PubMed

Liu, David S; Hoefnagel, Sanne J M; Fisher, Oliver M; Krishnadath, Kausilia K; Montgomery, Karen G; Busuttil, Rita A; Colebatch, Andrew J; Read, Matthew; Duong, Cuong P; Phillips, Wayne A; Clemons, Nicholas J

2016-12-13

There is currently a paucity of preclinical models available to study the metastatic process in esophageal cancer. Here we report FLO-1, and its isogenic derivative FLO-1LM, as two spontaneously metastatic cell line models of human esophageal adenocarcinoma. We show that FLO-1 has undergone epithelial-mesenchymal transition and metastasizes following subcutaneous injection in mice. FLO-1LM, derived from a FLO-1 liver metastasis, has markedly enhanced proliferative, clonogenic, anti-apoptotic, invasive, immune-tolerant and metastatic potential. Genome-wide RNAseq profiling revealed a significant enrichment of metastasis-related pathways in FLO-1LM cells. Moreover, CDH1, which encodes the adhesion molecule E-cadherin, was the most significantly downregulated gene in FLO-1LM compared to FLO-1. Consistent with this, repression of E-cadherin expression in FLO-1 cells resulted in increased metastatic activity. Importantly, reduced E-cadherin expression is commonly reported in esophageal adenocarcinoma and independently predicts poor patient survival. Collectively, these findings highlight the biological importance of E-cadherin activity in the pathogenesis of metastatic esophageal adenocarcinoma and validate the utility of FLO-1 parental and FLO-1LM cells as preclinical models of metastasis in this disease.

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.

Efficient minimization of multipole electrostatic potentials in torsion space

PubMed Central

Bodmer, Nicholas K.

2018-01-01

The development of models of macromolecular electrostatics capable of delivering improved fidelity to quantum mechanical calculations is an active field of research in computational chemistry. Most molecular force field development takes place in the context of models with full Cartesian coordinate degrees of freedom. Nevertheless, a number of macromolecular modeling programs use a reduced set of conformational variables limited to rotatable bonds. Efficient algorithms for minimizing the energies of macromolecular systems with torsional degrees of freedom have been developed with the assumption that all atom-atom interaction potentials are isotropic. We describe novel modifications to address the anisotropy of higher order multipole terms while retaining the efficiency of these approaches. In addition, we present a treatment for obtaining derivatives of atom-centered tensors with respect to torsional degrees of freedom. We apply these results to enable minimization of the Amoeba multipole electrostatics potential in a system with torsional degrees of freedom, and validate the correctness of the gradients by comparison to finite difference approximations. In the interest of enabling a complete model of electrostatics with implicit treatment of solvent-mediated effects, we also derive expressions for the derivative of solvent accessible surface area with respect to torsional degrees of freedom. PMID:29641557

Anti-fibrotic effect of pirfenidone in muscle derived-fibroblasts from Duchenne muscular dystrophy patients.

PubMed

Zanotti, Simona; Bragato, Cinzia; Zucchella, Andrea; Maggi, Lorenzo; Mantegazza, Renato; Morandi, Lucia; Mora, Marina

2016-01-15

Tissue fibrosis, characterized by excessive deposition of extracellular matrix proteins, is the end point of diseases affecting the kidney, bladder, liver, lung, gut, skin, heart and muscle. In Duchenne muscular dystrophy (DMD), connective fibrotic tissue progressively substitutes muscle fibers. So far no specific pharmacological treatment is available for muscle fibrosis. Among promising anti-fibrotic molecules, pirfenidone has shown anti-fibrotic and anti-inflammatory activity in animal and cell models, and has already been employed in clinical trials. Therefore we tested pirfenidone anti-fibrotic properties in an in vitro model of muscle fibrosis. We evaluated effect of pirfenidone on fibroblasts isolated from DMD muscle biopsies. These cells have been previously characterized as having a pro-fibrotic phenotype. We tested cell proliferation and migration, secretion of soluble collagens, intracellular levels of collagen type I and fibronectin, and diameter of 3D fibrotic nodules. We found that pirfenidone significantly reduced proliferation and cell migration of control and DMD muscle-derived fibroblasts, decreased extracellular secretion of soluble collagens by control and DMD fibroblasts, as well as levels of collagen type I and fibronectin, and, in DMD fibroblasts only, reduced synthesis and deposition of intracellular collagen. Furthermore, pirfenidone was able to reduce the diameter of fibrotic-nodules in our 3D model of in vitro fibrosis. These pre-clinical results indicate that pirfenidone has potential anti-fibrotic effects also in skeletal muscle fibrosis, urging further studies in in vivo animal models of muscular dystrophy in order to translate the drug into the treatment of muscle fibrosis in DMD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of patients at high risk for Clostridium difficile infection: development and validation of a risk prediction model in hospitalized patients treated with antibiotics.

PubMed

van Werkhoven, C H; van der Tempel, J; Jajou, R; Thijsen, S F T; Diepersloot, R J A; Bonten, M J M; Postma, D F; Oosterheert, J J

2015-08-01

To develop and validate a prediction model for Clostridium difficile infection (CDI) in hospitalized patients treated with systemic antibiotics, we performed a case-cohort study in a tertiary (derivation) and secondary care hospital (validation). Cases had a positive Clostridium test and were treated with systemic antibiotics before suspicion of CDI. Controls were randomly selected from hospitalized patients treated with systemic antibiotics. Potential predictors were selected from the literature. Logistic regression was used to derive the model. Discrimination and calibration of the model were tested in internal and external validation. A total of 180 cases and 330 controls were included for derivation. Age >65 years, recent hospitalization, CDI history, malignancy, chronic renal failure, use of immunosuppressants, receipt of antibiotics before admission, nonsurgical admission, admission to the intensive care unit, gastric tube feeding, treatment with cephalosporins and presence of an underlying infection were independent predictors of CDI. The area under the receiver operating characteristic curve of the model in the derivation cohort was 0.84 (95% confidence interval 0.80-0.87), and was reduced to 0.81 after internal validation. In external validation, consisting of 97 cases and 417 controls, the model area under the curve was 0.81 (95% confidence interval 0.77-0.85) and model calibration was adequate (Brier score 0.004). A simplified risk score was derived. Using a cutoff of 7 points, the positive predictive value, sensitivity and specificity were 1.0%, 72% and 73%, respectively. In conclusion, a risk prediction model was developed and validated, with good discrimination and calibration, that can be used to target preventive interventions in patients with increased risk of CDI. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Applying Statistical Models and Parametric Distance Measures for Music Similarity Search

NASA Astrophysics Data System (ADS)

Lukashevich, Hanna; Dittmar, Christian; Bastuck, Christoph

Automatic deriving of similarity relations between music pieces is an inherent field of music information retrieval research. Due to the nearly unrestricted amount of musical data, the real-world similarity search algorithms have to be highly efficient and scalable. The possible solution is to represent each music excerpt with a statistical model (ex. Gaussian mixture model) and thus to reduce the computational costs by applying the parametric distance measures between the models. In this paper we discuss the combinations of applying different parametric modelling techniques and distance measures and weigh the benefits of each one against the others.

True covariance simulation of the EUVE update filter

NASA Technical Reports Server (NTRS)

Bar-Itzhack, Itzhack Y.; Harman, R. R.

1989-01-01

A covariance analysis of the performance and sensitivity of the attitude determination Extended Kalman Filter (EKF) used by the On Board Computer (OBC) of the Extreme Ultra Violet Explorer (EUVE) spacecraft is presented. The linearized dynamics and measurement equations of the error states are derived which constitute the truth model describing the real behavior of the systems involved. The design model used by the OBC EKF is then obtained by reducing the order of the truth model. The covariance matrix of the EKF which uses the reduced order model is not the correct covariance of the EKF estimation error. A true covariance analysis has to be carried out in order to evaluate the correct accuracy of the OBC generated estimates. The results of such analysis are presented which indicate both the performance and the sensitivity of the OBC EKF.

Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease

PubMed Central

Jiao, S-S; Shen, L-L; Zhu, C; Bu, X-L; Liu, Y-H; Liu, C-H; Yao, X-Q; Zhang, L-L; Zhou, H-D; Walker, D G; Tan, J; Götz, J; Zhou, X-F; Wang, Y-J

2016-01-01

Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy. PMID:27701410

Spectra of eigenstates in fermionic tensor quantum mechanics

NASA Astrophysics Data System (ADS)

Klebanov, Igor R.; Milekhin, Alexey; Popov, Fedor; Tarnopolsky, Grigory

2018-05-01

We study the O (N1)×O (N2)×O (N3) symmetric quantum mechanics of 3-index Majorana fermions. When the ranks Ni are all equal, this model has a large N limit which is dominated by the melonic Feynman diagrams. We derive an integral formula which computes the number of group invariant states for any set of Ni. It is non-vanishing only when each Ni is even. For equal ranks the number of singlets exhibits rapid growth with N : it jumps from 36 in the O (4 )3 model to 595 354 780 in the O (6 )3 model. We derive bounds on the values of energy, which show that they scale at most as N3 in the large N limit, in agreement with expectations. We also show that the splitting between the lowest singlet and non-singlet states is of order 1 /N . For N3=1 the tensor model reduces to O (N1)×O (N2) fermionic matrix quantum mechanics, and we find a simple expression for the Hamiltonian in terms of the quadratic Casimir operators of the symmetry group. A similar expression is derived for the complex matrix model with S U (N1)×S U (N2)×U (1 ) symmetry. Finally, we study the N3=2 case of the tensor model, which gives a more intricate complex matrix model whose symmetry is only O (N1)×O (N2)×U (1 ). All energies are again integers in appropriate units, and we derive a concise formula for the spectrum. The fermionic matrix models we studied possess standard 't Hooft large N limits where the ground state energies are of order N2, while the energy gaps are of order 1.

Kinematics of our Galaxy from the PMA and TGAS catalogues

NASA Astrophysics Data System (ADS)

Velichko, Anna B.; Akhmetov, Volodymyr S.; Fedorov, Peter N.

2018-04-01

We derive and compare kinematic parameters of the Galaxy using the PMA and Gaia TGAS data. Two methods are used in calculations: evaluation of the Ogorodnikov-Milne model (OMM) parameters by the least square method (LSM) and a decomposition on a set of vector spherical harmonics (VSH). We trace dependencies on the distance of the derived parameters including the Oort constants A and B and the rotational velocity of the Galaxy V rot at the Solar distance for the common sample of stars of mixed spectral composition of the PMA and TGAS catalogues. The distances were obtained from the TGAS parallaxes or from reduced proper motions for fainter stars. The A, B and V rot parameters derived from proper motions of both catalogues used show identical behaviour but the values are systematically shifted by about 0.5 mas/yr. The Oort B parameter derived from the PMA sample of red giants shows gradual decrease with increasing the distance while the Oort A has a minimum at about 2 kpc and then gradually increases. As for models chosen for calculations, first, we confirm conclusions of other authors about the existence of extra-model harmonics in the stellar velocity field. Secondly, not all parameters of the OMM are statistically significant, and the set of parameters depends on the stellar sample used.

A Moisture Function of Soil Heterotrophic Respiration Derived from Pore-scale Mechanisms

NASA Astrophysics Data System (ADS)

Yan, Z.; Todd-Brown, K. E.; Bond-Lamberty, B. P.; Bailey, V.; Liu, C.

2017-12-01

Soil heterotrophic respiration (HR) is an important process controlling carbon (C) flux, but its response to changes in soil water content (θ) is poorly understood. Earth system models (ESMs) use empirical moisture functions developed from specific sites to describe the HR-θ relationship in soils, introducing significant uncertainty. Generalized models derived from mechanisms that control substrate availability and microbial respiration are thus urgently needed. Here we derive, present, and test a novel moisture function fp developed from pore-scale mechanisms. This fp encapsulates primary physicochemical and biological processes controlling HR response to moisture variation in soils. We tested fp against a wide range of published data for different soil types, and found that fp reliably predicted diverse HR- relationships. The mathematical relationship between the parameters in fp and macroscopic soil properties such as porosity and organic C content was also established, enabling to estimate fp using soil properties. Compared with empirical moisture functions used in ESMs, this derived fp could reduce uncertainty in predicting the response of soil organic C stock to climate changes. In addition, this work is one of the first studies to upscale a mechanistic soil HR model based on pore-scale processes, thus linking the pore-scale mechanisms with macroscale observations.

Compatibility of Segments of Thermoelectric Generators

NASA Technical Reports Server (NTRS)

Snyder, G. Jeffrey; Ursell, Tristan

2009-01-01

A method of calculating (usually for the purpose of maximizing) the power-conversion efficiency of a segmented thermoelectric generator is based on equations derived from the fundamental equations of thermoelectricity. Because it is directly traceable to first principles, the method provides physical explanations in addition to predictions of phenomena involved in segmentation. In comparison with the finite-element method used heretofore to predict (without being able to explain) the behavior of a segmented thermoelectric generator, this method is much simpler to implement in practice: in particular, the efficiency of a segmented thermoelectric generator can be estimated by evaluating equations using only hand-held calculator with this method. In addition, the method provides for determination of cascading ratios. The concept of cascading is illustrated in the figure and the definition of the cascading ratio is defined in the figure caption. An important aspect of the method is its approach to the issue of compatibility among segments, in combination with introduction of the concept of compatibility within a segment. Prior approaches involved the use of only averaged material properties. Two materials in direct contact could be examined for compatibility with each other, but there was no general framework for analysis of compatibility. The present method establishes such a framework. The mathematical derivation of the method begins with the definition of reduced efficiency of a thermoelectric generator as the ratio between (1) its thermal-to-electric power-conversion efficiency and (2) its Carnot efficiency (the maximum efficiency theoretically attainable, given its hot- and cold-side temperatures). The derivation involves calculation of the reduced efficiency of a model thermoelectric generator for which the hot-side temperature is only infinitesimally greater than the cold-side temperature. The derivation includes consideration of the ratio (u) between the electric current and heat-conduction power and leads to the concept of compatibility factor (s) for a given thermoelectric material, defined as the value of u that maximizes the reduced efficiency of the aforementioned model thermoelectric generator.

75 FR 71397 - Regulations Establishing and Governing the Duties of Swap Dealers and Major Swap Participants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

... risks associated with the use of models to derive market valuations or otherwise calculate or evaluate... swap dealers and major swap participants registered with the Commission with regard to: Risk management...) \\3\\ to establish a comprehensive regulatory framework to reduce risk, increase transparency, and...

Paricalcitol, a Vitamin D Receptor Activator, Inhibits Tumor Formation in a Murine Model of Uterine Fibroids

PubMed Central

Halder, Sunil K.; Sharan, Chakradhari; Al-Hendy, Omar

2014-01-01

We examined the antitumor and therapeutic potentials of paricalcitol, an analog of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid cells and animal models. We found that paricalcitol has potential to reduce the proliferation of the immortalized human uterine fibroid cells. For the in vivo study, we generated subcutaneous tumors by injecting the Eker rat-derived uterine leiomyoma cell line (ELT-3) rat uterine fibroid-derived cell line in athymic nude mice supplemented with estrogen pellets. These mice were administered with vehicle versus paricalcitol (300 ng/kg/d) or 1,25-dihydroxyvitamin D3 (500 ng/kg/d) for 4 consecutive weeks, and the data were analyzed. We found that while both paricalcitol and 1,25-dihydroxyvitamin D3 significantly reduced fibroid tumor size, the shrinkage was slightly higher in the paricalcitol-treated group. Together, our results suggest that paricalcitol may be a potential candidate for effective, safe, and noninvasive medical treatment option for uterine fibroids. PMID:24925855

Intermittency in small-scale turbulence: a velocity gradient approach

NASA Astrophysics Data System (ADS)

Meneveau, Charles; Johnson, Perry

2017-11-01

Intermittency of small-scale motions is an ubiquitous facet of turbulent flows, and predicting this phenomenon based on reduced models derived from first principles remains an important open problem. Here, a multiple-time scale stochastic model is introduced for the Lagrangian evolution of the full velocity gradient tensor in fluid turbulence at arbitrarily high Reynolds numbers. This low-dimensional model differs fundamentally from prior shell models and other empirically-motivated models of intermittency because the nonlinear gradient self-stretching and rotation A2 term vital to the energy cascade and intermittency development is represented exactly from the Navier-Stokes equations. With only one adjustable parameter needed to determine the model's effective Reynolds number, numerical solutions of the resulting set of stochastic differential equations show that the model predicts anomalous scaling for moments of the velocity gradient components and negative derivative skewness. It also predicts signature topological features of the velocity gradient tensor such as vorticity alignment trends with the eigen-directions of the strain-rate. This research was made possible by a graduate Fellowship from the National Science Foundation and by a Grant from The Gulf of Mexico Research Initiative.

QSPR models for predicting generator-column-derived octanol/water and octanol/air partition coefficients of polychlorinated biphenyls.

PubMed

Yuan, Jintao; Yu, Shuling; Zhang, Ting; Yuan, Xuejie; Cao, Yunyuan; Yu, Xingchen; Yang, Xuan; Yao, Wu

2016-06-01

Octanol/water (K(OW)) and octanol/air (K(OA)) partition coefficients are two important physicochemical properties of organic substances. In current practice, K(OW) and K(OA) values of some polychlorinated biphenyls (PCBs) are measured using generator column method. Quantitative structure-property relationship (QSPR) models can serve as a valuable alternative method of replacing or reducing experimental steps in the determination of K(OW) and K(OA). In this paper, two different methods, i.e., multiple linear regression based on dragon descriptors and hologram quantitative structure-activity relationship, were used to predict generator-column-derived log K(OW) and log K(OA) values of PCBs. The predictive ability of the developed models was validated using a test set, and the performances of all generated models were compared with those of three previously reported models. All results indicated that the proposed models were robust and satisfactory and can thus be used as alternative models for the rapid assessment of the K(OW) and K(OA) of PCBs. Copyright © 2016 Elsevier Inc. All rights reserved.

Rumor Spreading Model with Trust Mechanism in Complex Social Networks

NASA Astrophysics Data System (ADS)

Wang, Ya-Qi; Yang, Xiao-Yuan; Han, Yi-Liang; Wang, Xu-An

2013-04-01

In this paper, to study rumor spreading, we propose a novel susceptible-infected-removed (SIR) model by introducing the trust mechanism. We derive mean-field equations that describe the dynamics of the SIR model on homogeneous networks and inhomogeneous networks. Then a steady-state analysis is conducted to investigate the critical threshold and the final size of the rumor spreading. We show that the introduction of trust mechanism reduces the final rumor size and the velocity of rumor spreading, but increases the critical thresholds on both networks. Moreover, the trust mechanism not only greatly reduces the maximum rumor influence, but also postpones the rumor terminal time, which provides us with more time to take measures to control the rumor spreading. The theoretical results are confirmed by sufficient numerical simulations.

Can hydraulic-modelled rating curves reduce uncertainty in high flow data?

NASA Astrophysics Data System (ADS)

Westerberg, Ida; Lam, Norris; Lyon, Steve W.

2017-04-01

Flood risk assessments rely on accurate discharge data records. Establishing a reliable rating curve for calculating discharge from stage at a gauging station normally takes years of data collection efforts. Estimation of high flows is particularly difficult as high flows occur rarely and are often practically difficult to gauge. Hydraulically-modelled rating curves can be derived based on as few as two concurrent stage-discharge and water-surface slope measurements at different flow conditions. This means that a reliable rating curve can, potentially, be derived much faster than a traditional rating curve based on numerous stage-discharge gaugings. In this study we compared the uncertainty in discharge data that resulted from these two rating curve modelling approaches. We applied both methods to a Swedish catchment, accounting for uncertainties in the stage-discharge gauging and water-surface slope data for the hydraulic model and in the stage-discharge gauging data and rating-curve parameters for the traditional method. We focused our analyses on high-flow uncertainty and the factors that could reduce this uncertainty. In particular, we investigated which data uncertainties were most important, and at what flow conditions the gaugings should preferably be taken. First results show that the hydraulically-modelled rating curves were more sensitive to uncertainties in the calibration measurements of discharge than water surface slope. The uncertainty of the hydraulically-modelled rating curves were lowest within the range of the three calibration stage-discharge gaugings (i.e. between median and two-times median flow) whereas uncertainties were higher outside of this range. For instance, at the highest observed stage of the 24-year stage record, the 90% uncertainty band was -15% to +40% of the official rating curve. Additional gaugings at high flows (i.e. four to five times median flow) would likely substantially reduce those uncertainties. These first results show the potential of the hydraulically-modelled curves, particularly where the calibration gaugings are of high quality and cover a wide range of flow conditions.

Separation of atmospheric, oceanic and hydrological polar motion excitation mechanisms based on a combination of geometric and gravimetric space observations

NASA Astrophysics Data System (ADS)

Göttl, F.; Schmidt, M.; Seitz, F.; Bloßfeld, M.

2015-04-01

The goal of our study is to determine accurate time series of geophysical Earth rotation excitations to learn more about global dynamic processes in the Earth system. For this purpose, we developed an adjustment model which allows to combine precise observations from space geodetic observation systems, such as Satellite Laser Ranging (SLR), Global Navigation Satellite Systems, Very Long Baseline Interferometry, Doppler Orbit determination and Radiopositioning Integrated on Satellite, satellite altimetry and satellite gravimetry in order to separate geophysical excitation mechanisms of Earth rotation. Three polar motion time series are applied to derive the polar motion excitation functions (integral effect). Furthermore we use five time variable gravity field solutions from Gravity Recovery and Climate Experiment to determine not only the integral mass effect but also the oceanic and hydrological mass effects by applying suitable filter techniques and a land-ocean mask. For comparison the integral mass effect is also derived from degree 2 potential coefficients that are estimated from SLR observations. The oceanic mass effect is also determined from sea level anomalies observed by satellite altimetry by reducing the steric sea level anomalies derived from temperature and salinity fields of the oceans. Due to the combination of all geodetic estimated excitations the weaknesses of the individual processing strategies can be reduced and the technique-specific strengths can be accounted for. The formal errors of the adjusted geodetic solutions are smaller than the RMS differences of the geophysical model solutions. The improved excitation time series can be used to improve the geophysical modeling.

Edible Ginger-Derived Nanoparticles: A Novel Therapeutic Approach for the Prevention and Treatment of Inflammatory Bowel Disease and Colitis-Associated Cancer

PubMed Central

Zhang, Mingzhen; Viennois, Emilie; Prasad, Meena; Zhang, Yunchen; Wang, Lixin; Zhang, Zhan; Han, Moon Kwon; Xiao, Bo; Xu, Changlong; Srinivasan, Shanthi; Merlin, Didier

2016-01-01

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ~230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ~125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles. PMID:27318094

Electrical conductivity of the Earth's mantle from the first Swarm magnetic field measurements

NASA Astrophysics Data System (ADS)

Civet, F.; Thébault, E.; Verhoeven, O.; Langlais, B.; Saturnino, D.

2015-05-01

We present a 1-D electrical conductivity profile of the Earth's mantle down to 2000 km derived from L1b Swarm satellite magnetic field measurements from November 2013 to September 2014. We first derive a model for the main magnetic field, correct the data for a lithospheric field model, and additionally select the data to reduce the contributions of the ionospheric field. We then model the primary and induced magnetospheric fields for periods between 2 and 256 days and perform a Bayesian inversion to obtain the probability density function for the electrical conductivity as function of depth. The conductivity increases by 3 orders of magnitude in the 400-900 km depth range. Assuming a pyrolitic mantle composition, this profile is interpreted in terms of temperature variations leading to a temperature gradient in the lower mantle that is close to adiabatic.

Curvature-driven morphing of non-Euclidean shells

NASA Astrophysics Data System (ADS)

Pezzulla, Matteo; Stoop, Norbert; Jiang, Xin; Holmes, D. P.

2017-05-01

We investigate how thin structures change their shape in response to non-mechanical stimuli that can be interpreted as variations in the structure's natural curvature. Starting from the theory of non-Euclidean plates and shells, we derive an effective model that reduces a three-dimensional stimulus to the natural fundamental forms of the mid-surface of the structure, incorporating expansion, or growth, in the thickness. Then, we apply the model to a variety of thin bodies, from flat plates to spherical shells, obtaining excellent agreement between theory and numerics. We show how cylinders and cones can either bend more or unroll, and eventually snap and rotate. We also study the nearly isometric deformations of a spherical shell and describe how this shape change is ruled by the geometry of a spindle. As the derived results stem from a purely geometrical model, they are general and scalable.

Modeling of the reburning process using sewage sludge-derived syngas.

PubMed

Werle, Sebastian

2012-04-01

Gasification of sewage sludge can provide clean and effective reburning fuel for combustion applications. The motivation of this work was to define the reburning potential of the sewage sludge gasification gas (syngas). A numerical simulation of the co-combustion process of syngas in a hard coal-fired boiler was done. All calculations were performed using the Chemkin programme and a plug-flow reactor model was used. The calculations were modelled using the GRI-Mech 2.11 mechanism. The highest conversions for nitric oxide (NO) were obtained at temperatures of approximately 1000-1200K. The combustion of hard coal with sewage sludge-derived syngas reduces NO emissions. The highest reduction efficiency (>90%) was achieved when the molar flow ratio of the syngas was 15%. Calculations show that the analysed syngas can provide better results than advanced reburning (connected with ammonia injection), which is more complicated process. Copyright © 2011 Elsevier Ltd. All rights reserved.

Self-gravitating static non-critical black holes in 4 D Einstein-Klein-Gordon system with nonminimal derivative coupling

NASA Astrophysics Data System (ADS)

Gunara, Bobby Eka; Yaqin, Ainol

2018-06-01

We study static non-critical hairy black holes of four dimensional gravitational model with nonminimal derivative coupling and a scalar potential turned on. By taking an ansatz, namely, the first derivative of the scalar field is proportional to square root of a metric function, we reduce the Einstein field equation and the scalar field equation of motions into a single highly nonlinear differential equation. This setup implies that the hair is secondary-like since the scalar charge-like depends on the non-constant mass-like quantity in the asymptotic limit. Then, we show that near boundaries the solution is not the critical point of the scalar potential and the effective geometries become spaces of constant scalar curvature.

Signal processing using sparse derivatives with applications to chromatograms and ECG

NASA Astrophysics Data System (ADS)

Ning, Xiaoran

In this thesis, we investigate the sparsity exist in the derivative domain. Particularly, we focus on the type of signals which posses up to Mth (M > 0) order sparse derivatives. Efforts are put on formulating proper penalty functions and optimization problems to capture properties related to sparse derivatives, searching for fast, computationally efficient solvers. Also the effectiveness of these algorithms are applied to two real world applications. In the first application, we provide an algorithm which jointly addresses the problems of chromatogram baseline correction and noise reduction. The series of chromatogram peaks are modeled as sparse with sparse derivatives, and the baseline is modeled as a low-pass signal. A convex optimization problem is formulated so as to encapsulate these non-parametric models. To account for the positivity of chromatogram peaks, an asymmetric penalty function is also utilized with symmetric penalty functions. A robust, computationally efficient, iterative algorithm is developed that is guaranteed to converge to the unique optimal solution. The approach, termed Baseline Estimation And Denoising with Sparsity (BEADS), is evaluated and compared with two state-of-the-art methods using both simulated and real chromatogram data. Promising result is obtained. In the second application, a novel Electrocardiography (ECG) enhancement algorithm is designed also based on sparse derivatives. In the real medical environment, ECG signals are often contaminated by various kinds of noise or artifacts, for example, morphological changes due to motion artifact, non-stationary noise due to muscular contraction (EMG), etc. Some of these contaminations severely affect the usefulness of ECG signals, especially when computer aided algorithms are utilized. By solving the proposed convex l1 optimization problem, artifacts are reduced by modeling the clean ECG signal as a sum of two signals whose second and third-order derivatives (differences) are sparse respectively. At the end, the algorithm is applied to a QRS detection system and validated using the MIT-BIH Arrhythmia database (109452 anotations), resulting a sensitivity of Se = 99.87%$ and a positive prediction of +P = 99.88%.

Impact of different satellite soil moisture products on the predictions of a continuous distributed hydrological model

NASA Astrophysics Data System (ADS)

Laiolo, P.; Gabellani, S.; Campo, L.; Silvestro, F.; Delogu, F.; Rudari, R.; Pulvirenti, L.; Boni, G.; Fascetti, F.; Pierdicca, N.; Crapolicchio, R.; Hasenauer, S.; Puca, S.

2016-06-01

The reliable estimation of hydrological variables in space and time is of fundamental importance in operational hydrology to improve the flood predictions and hydrological cycle description. Nowadays remotely sensed data can offer a chance to improve hydrological models especially in environments with scarce ground based data. The aim of this work is to update the state variables of a physically based, distributed and continuous hydrological model using four different satellite-derived data (three soil moisture products and a land surface temperature measurement) and one soil moisture analysis to evaluate, even with a non optimal technique, the impact on the hydrological cycle. The experiments were carried out for a small catchment, in the northern part of Italy, for the period July 2012-June 2013. The products were pre-processed according to their own characteristics and then they were assimilated into the model using a simple nudging technique. The benefits on the model predictions of discharge were tested against observations. The analysis showed a general improvement of the model discharge predictions, even with a simple assimilation technique, for all the assimilation experiments; the Nash-Sutcliffe model efficiency coefficient was increased from 0.6 (relative to the model without assimilation) to 0.7, moreover, errors on discharge were reduced up to the 10%. An added value to the model was found in the rainfall season (autumn): all the assimilation experiments reduced the errors up to the 20%. This demonstrated that discharge prediction of a distributed hydrological model, which works at fine scale resolution in a small basin, can be improved with the assimilation of coarse-scale satellite-derived data.

Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents.

PubMed

Sashidhara, Koneni V; Rao, K Bhaskara; Singh, Seema; Modukuri, Ram K; Aruna Teja, G; Chandasana, Hardik; Shukla, Shubha; Bhatta, Rabi S

2014-10-15

A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space. Copyright © 2014 Elsevier Ltd. All rights reserved.

An implicit spatial and high-order temporal finite difference scheme for 2D acoustic modelling

NASA Astrophysics Data System (ADS)

Wang, Enjiang; Liu, Yang

2018-01-01

The finite difference (FD) method exhibits great superiority over other numerical methods due to its easy implementation and small computational requirement. We propose an effective FD method, characterised by implicit spatial and high-order temporal schemes, to reduce both the temporal and spatial dispersions simultaneously. For the temporal derivative, apart from the conventional second-order FD approximation, a special rhombus FD scheme is included to reach high-order accuracy in time. Compared with the Lax-Wendroff FD scheme, this scheme can achieve nearly the same temporal accuracy but requires less floating-point operation times and thus less computational cost when the same operator length is adopted. For the spatial derivatives, we adopt the implicit FD scheme to improve the spatial accuracy. Apart from the existing Taylor series expansion-based FD coefficients, we derive the least square optimisation based implicit spatial FD coefficients. Dispersion analysis and modelling examples demonstrate that, our proposed method can effectively decrease both the temporal and spatial dispersions, thus can provide more accurate wavefields.

Data Analysis of the Floating Potential Measurement Unit aboard the International Space Station

NASA Technical Reports Server (NTRS)

Barjatya, Aroh; Swenson, Charles M.; Thompson, Donald C.; Wright, Kenneth H., Jr.

2009-01-01

We present data from the Floating Potential Measurement Unit (FPMU), that is deployed on the starboard (S1) truss of the International Space Station. The FPMU is a suite of instruments capable of redundant measurements of various plasma parameters. The instrument suite consists of: a Floating Potential Probe, a Wide-sweeping spherical Langmuir probe, a Narrow-sweeping cylindrical Langmuir Probe, and a Plasma Impedance Probe. This paper gives a brief overview of the instrumentation and the received data quality, and then presents the algorithm used to reduce I-V curves to plasma parameters. Several hours of data is presented from August 5th, 2006 and March 3rd, 2007. The FPMU derived plasma density and temperatures are compared with the International Reference Ionosphere (IRI) and USU-Global Assimilation of Ionospheric Measurement (USU-GAIM) models. Our results show that the derived in-situ density matches the USU-GAIM model better than the IRI, and the derived in-situ temperatures are comparable to the average temperatures given by the IRI.

Reduced Stress Tensor and Dissipation and the Transport of Lamb Vector

NASA Technical Reports Server (NTRS)

Wu, Jie-Zhi; Zhou, Ye; Wu, Jian-Ming

1996-01-01

We develop a methodology to ensure that the stress tensor, regardless of its number of independent components, can be reduced to an exactly equivalent one which has the same number of independent components as the surface force. It is applicable to the momentum balance if the shear viscosity is constant. A direct application of this method to the energy balance also leads to a reduction of the dissipation rate of kinetic energy. Following this procedure, significant saving in analysis and computation may be achieved. For turbulent flows, this strategy immediately implies that a given Reynolds stress model can always be replaced by a reduced one before putting it into computation. Furthermore, we show how the modeling of Reynolds stress tensor can be reduced to that of the mean turbulent Lamb vector alone, which is much simpler. As a first step of this alternative modeling development, we derive the governing equations for the Lamb vector and its square. These equations form a basis of new second-order closure schemes and, we believe, should be favorably compared to that of traditional Reynolds stress transport equation.

Electroneutral models for dynamic Poisson-Nernst-Planck systems

NASA Astrophysics Data System (ADS)

Song, Zilong; Cao, Xiulei; Huang, Huaxiong

2018-01-01

The Poisson-Nernst-Planck (PNP) system is a standard model for describing ion transport. In many applications, e.g., ions in biological tissues, the presence of thin boundary layers poses both modeling and computational challenges. In this paper, we derive simplified electroneutral (EN) models where the thin boundary layers are replaced by effective boundary conditions. There are two major advantages of EN models. First, it is much cheaper to solve them numerically. Second, EN models are easier to deal with compared to the original PNP system; therefore, it would also be easier to derive macroscopic models for cellular structures using EN models. Even though the approach used here is applicable to higher-dimensional cases, this paper mainly focuses on the one-dimensional system, including the general multi-ion case. Using systematic asymptotic analysis, we derive a variety of effective boundary conditions directly applicable to the EN system for the bulk region. This EN system can be solved directly and efficiently without computing the solution in the boundary layer. The derivation is based on matched asymptotics, and the key idea is to bring back higher-order contributions into the effective boundary conditions. For Dirichlet boundary conditions, the higher-order terms can be neglected and the classical results (continuity of electrochemical potential) are recovered. For flux boundary conditions, higher-order terms account for the accumulation of ions in boundary layer and neglecting them leads to physically incorrect solutions. To validate the EN model, numerical computations are carried out for several examples. Our results show that solving the EN model is much more efficient than the original PNP system. Implemented with the Hodgkin-Huxley model, the computational time for solving the EN model is significantly reduced without sacrificing the accuracy of the solution due to the fact that it allows for relatively large mesh and time-step sizes.

Development of a Salmonella cross-protective vaccine for food animal production systems.

PubMed

Heithoff, Douglas M; House, John K; Thomson, Peter C; Mahan, Michael J

2015-01-01

Intensive livestock production is associated with increased Salmonella exposure, transmission, animal disease, and contamination of food and water supplies. Modified live Salmonella enterica vaccines that lack a functional DNA adenine methylase (Dam) confer cross-protection to a diversity of salmonellae in experimental models of murine, avian, ovine, and bovine models of salmonellosis. However, the commercial success of any vaccine is dependent upon the therapeutic index, the ratio of safety/efficacy. Herein, secondary virulence-attenuating mutations targeted to genes involved in intracellular and/or systemic survival were introduced into Salmonella dam vaccines to screen for vaccine candidates that were safe in the animal and the environment, while maintaining the capacity to confer cross-protective immunity to pathogenic salmonellae serotypes. Salmonella dam mgtC, dam sifA, and dam spvB vaccine strains exhibited significantly improved vaccine safety as evidenced by the failure to give rise to virulent revertants during the infective process, contrary to the parental Salmonella dam vaccine. Further, these vaccines exhibited a low grade persistence in host tissues that was associated with reduced vaccine shedding, reduced environmental persistence, and induction of cross-protective immunity to pathogenic serotypes derived from infected livestock. These data indicate that Salmonella dam double mutant vaccines are suitable for commercial applications against salmonellosis in livestock production systems. Reducing pre-harvest salmonellae load through vaccination will promote the health and productivity of livestock and reduce contamination of livestock-derived food products, while enhancing overall food safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

PubMed

Schwab, Andrew J; Ebert, Allison D

2014-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

Nonlinear feedback control for high alpha flight

NASA Technical Reports Server (NTRS)

Stalford, Harold

1990-01-01

Analytical aerodynamic models are derived from a high alpha 6 DOF wind tunnel model. One detail model requires some interpolation between nonlinear functions of alpha. One analytical model requires no interpolation and as such is a completely continuous model. Flight path optimization is conducted on the basic maneuvers: half-loop, 90 degree pitch-up, and level turn. The optimal control analysis uses the derived analytical model in the equations of motion and is based on both moment and force equations. The maximum principle solution for the half-loop is poststall trajectory performing the half-loop in 13.6 seconds. The agility induced by thrust vectoring capability provided a minimum effect on reducing the maneuver time. By means of thrust vectoring control the 90 degrees pitch-up maneuver can be executed in a small place over a short time interval. The agility capability of thrust vectoring is quite beneficial for pitch-up maneuvers. The level turn results are based currently on only outer layer solutions of singular perturbation. Poststall solutions provide high turn rates but generate higher losses of energy than that of classical sustained solutions.

Hollow-Fiber Cartridges: Model Systems for Virus Removal from Blood

NASA Astrophysics Data System (ADS)

Jacobitz, Frank; Menon, Jeevan

2005-11-01

Aethlon Medical is developing a hollow-fiber hemodialysis device designed to remove viruses and toxins from blood. Possible target viruses include HIV and pox-viruses. The filter could reduce virus and viral toxin concentration in the patient's blood, delaying illness so the patient's immune system can fight off the virus. In order to optimize the design of such a filter, the fluid mechanics of the device is both modeled analytically and investigated experimentally. The flow configuration of the proposed device is that of Starling flow. Polysulfone hollow-fiber dialysis cartridges were used. The cartridges are charged with water as a model fluid for blood and fluorescent latex beads are used in the experiments as a model for viruses. In the experiments, properties of the flow through the cartridge are determined through pressure and volume flow rate measurements of water. The removal of latex beads, which are captured in the porous walls of the fibers, was measured spectrophotometrically. Experimentally derived coefficients derived from these experiments are used in the analytical model of the flow and removal predictions from the model are compared to those obtained from the experiments.

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.

Transition between inverse and direct energy cascades in multiscale optical turbulence.

PubMed

Malkin, V M; Fisch, N J

2018-03-01

Multiscale turbulence naturally develops and plays an important role in many fluid, gas, and plasma phenomena. Statistical models of multiscale turbulence usually employ Kolmogorov hypotheses of spectral locality of interactions (meaning that interactions primarily occur between pulsations of comparable scales) and scale-invariance of turbulent pulsations. However, optical turbulence described by the nonlinear Schrodinger equation exhibits breaking of both the Kolmogorov locality and scale-invariance. A weaker form of spectral locality that holds for multi-scale optical turbulence enables a derivation of simplified evolution equations that reduce the problem to a single scale modeling. We present the derivation of these equations for Kerr media with random inhomogeneities. Then, we find the analytical solution that exhibits a transition between inverse and direct energy cascades in optical turbulence.

Transition between inverse and direct energy cascades in multiscale optical turbulence

NASA Astrophysics Data System (ADS)

Malkin, V. M.; Fisch, N. J.

2018-03-01

Multiscale turbulence naturally develops and plays an important role in many fluid, gas, and plasma phenomena. Statistical models of multiscale turbulence usually employ Kolmogorov hypotheses of spectral locality of interactions (meaning that interactions primarily occur between pulsations of comparable scales) and scale-invariance of turbulent pulsations. However, optical turbulence described by the nonlinear Schrodinger equation exhibits breaking of both the Kolmogorov locality and scale-invariance. A weaker form of spectral locality that holds for multi-scale optical turbulence enables a derivation of simplified evolution equations that reduce the problem to a single scale modeling. We present the derivation of these equations for Kerr media with random inhomogeneities. Then, we find the analytical solution that exhibits a transition between inverse and direct energy cascades in optical turbulence.

On the recovery of gravity anomalies from high precision altimeter data

NASA Technical Reports Server (NTRS)

Lelgemann, D.

1976-01-01

A model for the recovery of gravity anomalies from high precision altimeter data is derived which consists of small correction terms to the inverse Stokes' formula. The influence of unknown sea surface topography in the case of meandering currents such as the Gulf Stream is discussed. A formula was derived in order to estimate the accuracy of the gravity anomalies from the known accuracy of the altimeter data. It is shown that for the case of known harmonic coefficients of lower order the range of integration in Stokes inverse formula can be reduced very much.

Observations of the Mf ocean tide from Geosat altimetry

NASA Technical Reports Server (NTRS)

Cartwright, David E.; Ray, Richard D.

1990-01-01

Zonal averages of the 13.66-day Mf tide are derived from one year of Geosat altimetry records. The orbit errors are reduced by 1/revolution corrections taken over long (several day) arcs. The short-period tides are removed using a model previously derived from the same data. The Mf zonal averages indicate definite nonequilibrium character at nearly all latitudes. The imaginary admittances indicate a Q of at least 8; such a value is consistent with a simplified theory of coupled gravitational and vorticity modes and suggests a value for Proudman's 'friction period' about 123 days.

The phonon-coupling model for Skyrme forces

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

Lyutorovich, N.; Tselyaev, V.; Speth, J., E-mail: J.Speth@fz-juelich.de

2016-11-15

A short review on the self-consistent RPA based on the energy-density functional of the Skyrme type is given. We also present an extension of the RPA where the coupling of phonons to the single-particle states is considered. Within this approach we present numerical results which are compared with data. The self-consistent approach is compared with the Landau–Migdal theory. Here we derive from the self-consistent ph interaction, the Landau–Migdal parameters as well as their density dependence. In the Appendix a new derivation of the reduced matrix elements of the ph interaction is presented.

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.

Sediment on Mars: settling faster, moving slower

NASA Astrophysics Data System (ADS)

Kuhn, N. J.

2013-12-01

Using empirical approaches developed on Earth to assess Martian hydrology based on conglomerates such as those found at Gale crater may deliver false results because Martian gravity potentially alters flow-sediment interaction compared to Earth. In this study, we report the results of our Mars Sedimentation Experiments (MarsSedEx I and II) which used settling tubes during reduced gravity flights in November 2012 (and scheduled for November 2013) on board Zero g's G-Force 1. The settling velocity data collected during the flights are compared to several models for terrestrial settling velocities. The results indicate that settling velocities on Mars are underestimated by up to 30 to 50%, depending on the selected model. As a consequence, transport distances of sediment particles increase by a similar proportion in a given flow. We suspect that the underestimation of settling velocity is caused by poor capture of flow hydraulics under reduced gravity. While MarsSedEx I (and II) results are only very preliminary, they indicate that applying empirically derived models for Earth to conglomerates such as those found at Garle crater to derive properties of surface runoff carries the risk of significantly misjudging flow depth and velocities. In the light of the potentially strong influence of topography on runoff generation on Mars, we may therefore end up looking for water in the wrong place.

Hidden Markov induced Dynamic Bayesian Network for recovering time evolving gene regulatory networks

NASA Astrophysics Data System (ADS)

Zhu, Shijia; Wang, Yadong

2015-12-01

Dynamic Bayesian Networks (DBN) have been widely used to recover gene regulatory relationships from time-series data in computational systems biology. Its standard assumption is ‘stationarity’, and therefore, several research efforts have been recently proposed to relax this restriction. However, those methods suffer from three challenges: long running time, low accuracy and reliance on parameter settings. To address these problems, we propose a novel non-stationary DBN model by extending each hidden node of Hidden Markov Model into a DBN (called HMDBN), which properly handles the underlying time-evolving networks. Correspondingly, an improved structural EM algorithm is proposed to learn the HMDBN. It dramatically reduces searching space, thereby substantially improving computational efficiency. Additionally, we derived a novel generalized Bayesian Information Criterion under the non-stationary assumption (called BWBIC), which can help significantly improve the reconstruction accuracy and largely reduce over-fitting. Moreover, the re-estimation formulas for all parameters of our model are derived, enabling us to avoid reliance on parameter settings. Compared to the state-of-the-art methods, the experimental evaluation of our proposed method on both synthetic and real biological data demonstrates more stably high prediction accuracy and significantly improved computation efficiency, even with no prior knowledge and parameter settings.

SDF-1 is both necessary and sufficient to promote proliferative retinopathy

PubMed Central

Butler, Jason M.; Guthrie, Steven M.; Koc, Mehmet; Afzal, Aqeela; Caballero, Sergio; Brooks, H. Logan; Mames, Robert N.; Segal, Mark S.; Grant, Maria B.; Scott, Edward W.

2005-01-01

Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell–derived factor–1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen–4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell–derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy. PMID:15630447

Simulation of ground-water flow in the St. Peter aquifer in an area contaminated by coal-tar derivatives, St. Louis Park, Minnesota. Water Resources Investigation

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

Lorenz, D.L.; Stark, J.R.

1990-01-01

A model constructed to simulate ground-water flow in part of the Prairie du Chien-Jordan and St. Peter aquifers, St. Louis Park, Minnesota, was used to test hypotheses about the movement of ground water contaminated with coal-tar derivatives and to simulate alternatives for reducing the downgradient movement of contamination in the St. Peter aquifer. The model, constructed for a previous study, was applied to simulate the effects of current ground-water withdrawals on the potentiometric surface of the St. Peter aquifer. Model simulations predict that the multiaquifer wells have the potential to limit downgradient migration of contaminants in the St. Peter aquifermore » caused by cones of depression created around the multiaquifer wells. Differences in vertical leakage to the St. Peter aquifer may exist in areas of bedrock valleys. Model simulations indicate that these differences are not likely to affect significantly the general patterns of ground-water flow.« less

Content-Aware Video Adaptation under Low-Bitrate Constraint

NASA Astrophysics Data System (ADS)

Hsiao, Ming-Ho; Chen, Yi-Wen; Chen, Hua-Tsung; Chou, Kuan-Hung; Lee, Suh-Yin

2007-12-01

With the development of wireless network and the improvement of mobile device capability, video streaming is more and more widespread in such an environment. Under the condition of limited resource and inherent constraints, appropriate video adaptations have become one of the most important and challenging issues in wireless multimedia applications. In this paper, we propose a novel content-aware video adaptation in order to effectively utilize resource and improve visual perceptual quality. First, the attention model is derived from analyzing the characteristics of brightness, location, motion vector, and energy features in compressed domain to reduce computation complexity. Then, through the integration of attention model, capability of client device and correlational statistic model, attractive regions of video scenes are derived. The information object- (IOB-) weighted rate distortion model is used for adjusting the bit allocation. Finally, the video adaptation scheme dynamically adjusts video bitstream in frame level and object level. Experimental results validate that the proposed scheme achieves better visual quality effectively and efficiently.

Modeling the Distribution of Geodia Sponges and Sponge Grounds in the Northwest Atlantic

PubMed Central

Knudby, Anders; Kenchington, Ellen; Murillo, Francisco Javier

2013-01-01

Deep-sea sponge grounds provide structurally complex habitat for fish and invertebrates and enhance local biodiversity. They are also vulnerable to bottom-contact fisheries and prime candidates for Vulnerable Marine Ecosystem designation and related conservation action. This study uses species distribution modeling, based on presence and absence observations of Geodia spp. and sponge grounds derived from research trawl catches, as well as spatially continuous data on the physical and biological ocean environment derived from satellite data and oceanographic models, to model the distribution of Geodia sponges and sponge grounds in the Northwest Atlantic. Most models produce excellent fits with validation data although fits are reduced when models are extrapolated to new areas, especially when oceanographic regimes differ between areas. Depth and minimum bottom salinity were important predictors in most models, and a Geodia spp. minimum bottom salinity tolerance threshold in the 34.3-34.8 psu range was hypothesized on the basis of model structure. The models indicated two currently unsampled regions within the study area, the deeper parts of Baffin Bay and the Newfoundland and Labrador slopes, where future sponge grounds are most likely to be found. PMID:24324768

Modifying Taper-Derived Merchantable Height Estimates to Account for Tree Characteristics

Treesearch

James A. Westfall

2006-01-01

The U.S. Department of Agriculture Forest Service Northeastern Forest Inventory and Analysis program (NE-FIA) is developing regionwide tree-taper equations. Unlike most previous work on modeling tree form, this effort necessarily includes a wide array of tree species. For some species, branching patterns can produce undesirable tree form that reduces the merchantable...

Isosinglet approximation for nonelastic reactions

NASA Technical Reports Server (NTRS)

Wilson, J. W.

1972-01-01

Group theoretic relations are derived between different combinations of projectile and secondary particles which appear to have a broad range of application in spacecraft shielding or radiation damage studies. These relations are used to reduce the experimental effort required to obtain nuclear reaction data for transport calculations. Implications for theoretical modeling are also noted, especially for heavy-heavy reactions.

Machine learning and hurdle models for improving regional predictions of stream water acid neutralizing capacity

Treesearch

Nicholas A. Povak; Paul F. Hessburg; Keith M. Reynolds; Timothy J. Sullivan; Todd C. McDonnell; R. Brion Salter

2013-01-01

In many industrialized regions of the world, atmospherically deposited sulfur derived from industrial, nonpoint air pollution sources reduces stream water quality and results in acidic conditions that threaten aquatic resources. Accurate maps of predicted stream water acidity are an essential aid to managers who must identify acid-sensitive streams, potentially...

A reduced-order model from high-dimensional frictional hysteresis

PubMed Central

Biswas, Saurabh; Chatterjee, Anindya

2014-01-01

Hysteresis in material behaviour includes both signum nonlinearities as well as high dimensionality. Available models for component-level hysteretic behaviour are empirical. Here, we derive a low-order model for rate-independent hysteresis from a high-dimensional massless frictional system. The original system, being given in terms of signs of velocities, is first solved incrementally using a linear complementarity problem formulation. From this numerical solution, to develop a reduced-order model, basis vectors are chosen using the singular value decomposition. The slip direction in generalized coordinates is identified as the minimizer of a dissipation-related function. That function includes terms for frictional dissipation through signum nonlinearities at many friction sites. Luckily, it allows a convenient analytical approximation. Upon solution of the approximated minimization problem, the slip direction is found. A final evolution equation for a few states is then obtained that gives a good match with the full solution. The model obtained here may lead to new insights into hysteresis as well as better empirical modelling thereof. PMID:24910522

A time-dependent neutron transport method of characteristics formulation with time derivative propagation

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

Hoffman, Adam J., E-mail: adamhoff@umich.edu; Lee, John C., E-mail: jcl@umich.edu

2016-02-15

A new time-dependent Method of Characteristics (MOC) formulation for nuclear reactor kinetics was developed utilizing angular flux time-derivative propagation. This method avoids the requirement of storing the angular flux at previous points in time to represent a discretized time derivative; instead, an equation for the angular flux time derivative along 1D spatial characteristics is derived and solved concurrently with the 1D transport characteristic equation. This approach allows the angular flux time derivative to be recast principally in terms of the neutron source time derivatives, which are approximated to high-order accuracy using the backward differentiation formula (BDF). This approach, called Sourcemore » Derivative Propagation (SDP), drastically reduces the memory requirements of time-dependent MOC relative to methods that require storing the angular flux. An SDP method was developed for 2D and 3D applications and implemented in the computer code DeCART in 2D. DeCART was used to model two reactor transient benchmarks: a modified TWIGL problem and a C5G7 transient. The SDP method accurately and efficiently replicated the solution of the conventional time-dependent MOC method using two orders of magnitude less memory.« less

Estimation of debris flow critical rainfall thresholds by a physically-based model

NASA Astrophysics Data System (ADS)

Papa, M. N.; Medina, V.; Ciervo, F.; Bateman, A.

2012-11-01

Real time assessment of debris flow hazard is fundamental for setting up warning systems that can mitigate its risk. A convenient method to assess the possible occurrence of a debris flow is the comparison of measured and forecasted rainfall with rainfall threshold curves (RTC). Empirical derivation of the RTC from the analysis of rainfall characteristics of past events is not possible when the database of observed debris flows is poor or when the environment changes with time. For landslides triggered debris flows, the above limitations may be overcome through the methodology here presented, based on the derivation of RTC from a physically based model. The critical RTC are derived from mathematical and numerical simulations based on the infinite-slope stability model in which land instability is governed by the increase in groundwater pressure due to rainfall. The effect of rainfall infiltration on landside occurrence is modelled trough a reduced form of the Richards equation. The simulations are performed in a virtual basin, representative of the studied basin, taking into account the uncertainties linked with the definition of the characteristics of the soil. A large number of calculations are performed combining different values of the rainfall characteristics (intensity and duration of event rainfall and intensity of antecedent rainfall). For each combination of rainfall characteristics, the percentage of the basin that is unstable is computed. The obtained database is opportunely elaborated to derive RTC curves. The methodology is implemented and tested on a small basin of the Amalfi Coast (South Italy).

Treatment of hypoxic-ischemic encephalopathy in mouse by transplantation of embryonic stem cell-derived cells.

PubMed

Ma, Jie; Wang, Yu; Yang, Jianhua; Yang, Min; Chang, Keun-A; Zhang, Linhua; Jiang, Feng; Li, Yi; Zhang, Zhonggong; Heo, Chaejeong; Suh, Yoo-Hun

2007-07-01

A 7-day-old hypoxic-ischemic encephalopathy (HIE) mouse model was used to study the effect of transplantation of embryonic stem (ES) cell-derived cells on the HIE. After the inducement in vitro, the ES cell-derived cells expressed Nestin and MAP-2, rather than GFAP mRNA. After transplantation, ES cell-derived cells can survive, migrate into the injury site, and specifically differentiate into neurons, showing improvement of the learning ability and memory of the HIE mouse at 8 months post-transplantation. The non-grafted HIE mouse brain showed typical pathological changes in the hippocampus and cerebral cortex, where the number of neurons was reduced, while in the cell graft group, number of the neurons increased in the same regions. Although further study is necessary to elucidate the precise mechanisms responsible for this functional recovery, we believe that ES cells have advantages for use as a donor source in HIE.

A Methodology to Validate the InSAR Derived Displacement Field of the September 7th, 1999 Athens Earthquake Using Terrestrial Surveying. Improvement of the Assessed Deformation Field by Interferometric Stacking.

PubMed

Kotsis, Ioannis; Kontoes, Charalabos; Paradissis, Dimitrios; Karamitsos, Spyros; Elias, Panagiotis; Papoutsis, Ioannis

2008-06-10

The primary objective of this paper is the evaluation of the InSAR derived displacement field caused by the 07/09/1999 Athens earthquake, using as reference an external data source provided by terrestrial surveying along the Mornos river open aqueduct. To accomplish this, a processing chain to render comparable the leveling measurements and the interferometric derived measurements has been developed. The distinct steps proposed include a solution for reducing the orbital and atmospheric interferometric fringes and an innovative method to compute the actual InSAR estimated vertical ground subsidence, for direct comparison with the leveling data. Results indicate that the modeled deformation derived from a series of stacked interferograms, falls entirely within the confidence interval assessed for the terrestrial surveying data.

A Methodology to Validate the InSAR Derived Displacement Field of the September 7th, 1999 Athens Earthquake Using Terrestrial Surveying. Improvement of the Assessed Deformation Field by Interferometric Stacking

PubMed Central

Kotsis, Ioannis; Kontoes, Charalabos; Paradissis, Dimitrios; Karamitsos, Spyros; Elias, Panagiotis; Papoutsis, Ioannis

2008-01-01

The primary objective of this paper is the evaluation of the InSAR derived displacement field caused by the 07/09/1999 Athens earthquake, using as reference an external data source provided by terrestrial surveying along the Mornos river open aqueduct. To accomplish this, a processing chain to render comparable the leveling measurements and the interferometric derived measurements has been developed. The distinct steps proposed include a solution for reducing the orbital and atmospheric interferometric fringes and an innovative method to compute the actual InSAR estimated vertical ground subsidence, for direct comparison with the leveling data. Results indicate that the modeled deformation derived from a series of stacked interferograms, falls entirely within the confidence interval assessed for the terrestrial surveying data. PMID:27879926

The Effects of Insulin Resistance on Individual Tissues: An Application of a Mathematical Model of Metabolism in Humans.

PubMed

Pearson, Taliesin; Wattis, Jonathan A D; King, John R; MacDonald, Ian A; Mazzatti, Dawn J

2016-06-01

Whilst the human body expends energy constantly, the human diet consists of a mix of carbohydrates and fats delivered in a discontinuous manner. To deal with this sporadic supply of energy, there are transport, storage and utilisation mechanisms, for both carbohydrates and fats, around all tissues of the body. Insulin-resistant states such as type 2 diabetes and obesity are characterised by reduced efficiency of these mechanisms. Exactly how these insulin-resistant states develop, for example whether there is an order in which tissues become insulin resistant, is an active area of research with the hope of gaining a better overall understanding of insulin resistance. In this paper, we use a previously derived system of 12 first-order coupled differential equations that describe the transport between, and storage in, different tissues of the human body. We briefly revisit the derivation of the model before parametrising the model to account for insulin resistance. We then solve the model numerically, separately simulating each individual tissue as insulin resistant, and discuss and compare these results, drawing three main conclusions. The implications of these results are in accordance with biological intuition. First, insulin resistance in a tissue creates a knock-on effect on the other tissues in the body, whereby they attempt to compensate for the reduced efficiency of the insulin-resistant tissue. Second, insulin resistance causes a fatty liver, and the insulin resistance of tissues other than the liver can cause fat to accumulate in the liver. Finally, although insulin resistance in individual tissues can cause slightly reduced skeletal muscle metabolic flexibility, it is when the whole body is insulin resistant that the biggest effect on skeletal muscle flexibility is seen.

EGAR, A Food Protein-Derived Tetrapeptide, Reduces Seizure Activity in Pentylenetetrazole-Induced Epilepsy Models Through α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate Receptors.

PubMed

Cai, Song; Ling, Chuwen; Lu, Jun; Duan, Songwei; Wang, Yingzhao; Zhu, Huining; Lin, Ruibang; Chen, Liang; Pan, Xingchang; Cai, Muyi; Gu, Huaiyu

2017-01-01

A primary pathogeny of epilepsy is excessive activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs). To find potential molecules to inhibit AMPARs, high-throughput screening was performed in a library of tetrapeptides in silico. Computational results suggest that some tetrapeptides bind stably to the AMPAR. We aligned these sequences of tetrapeptide candidates with those from in vitro digestion of the trout skin protein. Among salmon-derived products, Glu-Gly-Ala-Arg (EGAR) showed a high biological affinity toward AMPAR when tested in silico. Accordingly, natural EGAR was hypothesized to have anticonvulsant activity, and in vitro experiments showed that EGAR selectively inhibited AMPAR-mediated synaptic transmission without affecting the electrophysiological properties of hippocampal pyramidal neurons. In addition, EGAR reduced neuronal spiking in an in vitro seizure model. Moreover, the ability of EGAR to reduce seizures was evaluated in a rodent epilepsy model. Briefer and less severe seizures versus controls were shown after mice were treated with EGAR. In conclusion, the promising experimental results suggest that EGAR inhibitor against AMPARs may be a target for antiepilepsy pharmaceuticals. Epilepsy is a common brain disorder characterized by the occurrence of recurring, unprovoked seizures. Twenty to 30 % of persons with epilepsy do not achieve adequate seizure control with any drug. Here we provide a possibility in which a natural and edible tetrapeptide, EGAR, can act as an antiepileptic agent. We have combined computation with in vitro experiments to show how EGAR modulates epilepsy. We also used an animal model of epilepsy to prove that EGAR can inhibit seizures in vivo. This study suggests EGAR as a potential pharmaceutical for the treatment of epilepsy.

Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response.

PubMed

Jayakumar, Asha; Bothwell, Alfred L M

2017-08-01

Intestinal tumorigenesis in the ApcMin/+ model is initiated by aberrant activation of Wnt pathway. Increased IL-4 expression in human colorectal cancer tissue and growth of colon cancer cell lines implied that IL-4-induced Stat6-mediated tumorigenic signaling likely contributes to intestinal tumor progression in ApcMin/+ mice. Stat6 also appears to promote expansion of myeloid-derived suppressor cells (MDSCs) cells. MDSCs promote polyp formation in the ApcMin/+ model. Hence, Stat6 could have a broad role in coordinating both polyp cell proliferation and MDSC expansion. We found that IL-4-induced Stat6-mediated proliferation of intestinal epithelial cells is augmented by platelet-derived growth factor-BB, a tumor-promoting growth factor. To determine whether polyp progression in ApcMin/+ mice is dependent on Stat6 signaling, we disrupted Stat6 in this model. Total polyps in the small intestine were fewer in ApcMin/+ mice lacking Stat6. Furthermore, proliferation of polyp epithelial cells was reduced, indicating that Stat6 in part controlled polyp formation. Stat6 also promoted expansion of MDSCs in the spleen and lamina propria of ApcMin/+ mice, implying regulation of antitumor T-cell response. More CD8 cells and reduced PD-1 expression on CD4 cells correlated with reduced polyps. In addition, a strong CD8-mediated cytotoxic response led to killing of tumor cells in Stat6-deficient ApcMin/+ mice. Therefore, these findings show that Stat6 has an oncogenic role in intestinal tumorigenesis by promoting polyp cell proliferation and immunosuppressive mediators, and preventing an active cytotoxic process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A model for longitudinal and shear wave propagation in viscoelastic media

PubMed

Szabo; Wu

2000-05-01

Relaxation models fail to predict and explain loss characteristics of many viscoelastic materials which follow a frequency power law. A model based on a time-domain statement of causality is presented that describes observed power-law behavior of many viscoelastic materials. A Hooke's law is derived from power-law loss characteristics; it reduces to the Hooke's law for the Voigt model for the specific case of quadratic frequency loss. Broadband loss and velocity data for both longitudinal and shear elastic types of waves agree well with predictions. These acoustic loss models are compared to theories for loss mechanisms in dielectrics based on isolated polar molecules and cooperative interactions.

MRAC Control with Prior Model Knowledge for Asymmetric Damaged Aircraft

PubMed Central

Zhang, Jing

2015-01-01

This paper develops a novel state-tracking multivariable model reference adaptive control (MRAC) technique utilizing prior knowledge of plant models to recover control performance of an asymmetric structural damaged aircraft. A modification of linear model representation is given. With prior knowledge on structural damage, a polytope linear parameter varying (LPV) model is derived to cover all concerned damage conditions. An MRAC method is developed for the polytope model, of which the stability and asymptotic error convergence are theoretically proved. The proposed technique reduces the number of parameters to be adapted and thus decreases computational cost and requires less input information. The method is validated by simulations on NASA generic transport model (GTM) with damage. PMID:26180839

Comparing geological and statistical approaches for element selection in sediment tracing research

NASA Astrophysics Data System (ADS)

Laceby, J. Patrick; McMahon, Joe; Evrard, Olivier; Olley, Jon

2015-04-01

Elevated suspended sediment loads reduce reservoir capacity and significantly increase the cost of operating water treatment infrastructure, making the management of sediment supply to reservoirs of increasingly importance. Sediment fingerprinting techniques can be used to determine the relative contributions of different sources of sediment accumulating in reservoirs. The objective of this research is to compare geological and statistical approaches to element selection for sediment fingerprinting modelling. Time-integrated samplers (n=45) were used to obtain source samples from four major subcatchments flowing into the Baroon Pocket Dam in South East Queensland, Australia. The geochemistry of potential sources were compared to the geochemistry of sediment cores (n=12) sampled in the reservoir. The geochemical approach selected elements for modelling that provided expected, observed and statistical discrimination between sediment sources. Two statistical approaches selected elements for modelling with the Kruskal-Wallis H-test and Discriminatory Function Analysis (DFA). In particular, two different significance levels (0.05 & 0.35) for the DFA were included to investigate the importance of element selection on modelling results. A distribution model determined the relative contributions of different sources to sediment sampled in the Baroon Pocket Dam. Elemental discrimination was expected between one subcatchment (Obi Obi Creek) and the remaining subcatchments (Lexys, Falls and Bridge Creek). Six major elements were expected to provide discrimination. Of these six, only Fe2O3 and SiO2 provided expected, observed and statistical discrimination. Modelling results with this geological approach indicated 36% (+/- 9%) of sediment sampled in the reservoir cores were from mafic-derived sources and 64% (+/- 9%) were from felsic-derived sources. The geological and the first statistical approach (DFA0.05) differed by only 1% (σ 5%) for 5 out of 6 model groupings with only the Lexys Creek modelling results differing significantly (35%). The statistical model with expanded elemental selection (DFA0.35) differed from the geological model by an average of 30% for all 6 models. Elemental selection for sediment fingerprinting therefore has the potential to impact modeling results. Accordingly is important to incorporate both robust geological and statistical approaches when selecting elements for sediment fingerprinting. For the Baroon Pocket Dam, management should focus on reducing the supply of sediments derived from felsic sources in each of the subcatchments.

Prediction of beta-turns from amino acid sequences using the residue-coupled model.

PubMed

Guruprasad, K; Shukla, S

2003-04-01

We evaluated the prediction of beta-turns from amino acid sequences using the residue-coupled model with an enlarged representative protein data set selected from the Protein Data Bank. Our results show that the probability values derived from a data set comprising 425 protein chains yielded an overall beta-turn prediction accuracy 68.74%, compared with 94.7% reported earlier on a data set of 30 proteins using the same method. However, we noted that the overall beta-turn prediction accuracy using probability values derived from the 30-protein data set reduces to 40.74% when tested on the data set comprising 425 protein chains. In contrast, using probability values derived from the 425 data set used in this analysis, the overall beta-turn prediction accuracy yielded consistent results when tested on either the 30-protein data set (64.62%) used earlier or a more recent representative data set comprising 619 protein chains (64.66%) or on a jackknife data set comprising 476 representative protein chains (63.38%). We therefore recommend the use of probability values derived from the 425 representative protein chains data set reported here, which gives more realistic and consistent predictions of beta-turns from amino acid sequences.

Adipose-derived mesenchymal stem cells accelerate nerve regeneration and functional recovery in a rat model of recurrent laryngeal nerve injury.

PubMed

Li, Yun; Xu, Wen; Cheng, Li-Yu

2017-09-01

Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated whether adipose-derived stem cell transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 × 10 5 ) or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8 × 10 5 ) or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellular matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.

Development of Mobile Mapping System for 3D Road Asset Inventory.

PubMed

Sairam, Nivedita; Nagarajan, Sudhagar; Ornitz, Scott

2016-03-12

Asset Management is an important component of an infrastructure project. A significant cost is involved in maintaining and updating the asset information. Data collection is the most time-consuming task in the development of an asset management system. In order to reduce the time and cost involved in data collection, this paper proposes a low cost Mobile Mapping System using an equipped laser scanner and cameras. First, the feasibility of low cost sensors for 3D asset inventory is discussed by deriving appropriate sensor models. Then, through calibration procedures, respective alignments of the laser scanner, cameras, Inertial Measurement Unit and GPS (Global Positioning System) antenna are determined. The efficiency of this Mobile Mapping System is experimented by mounting it on a truck and golf cart. By using derived sensor models, geo-referenced images and 3D point clouds are derived. After validating the quality of the derived data, the paper provides a framework to extract road assets both automatically and manually using techniques implementing RANSAC plane fitting and edge extraction algorithms. Then the scope of such extraction techniques along with a sample GIS (Geographic Information System) database structure for unified 3D asset inventory are discussed.

Development of Mobile Mapping System for 3D Road Asset Inventory

PubMed Central

Sairam, Nivedita; Nagarajan, Sudhagar; Ornitz, Scott

2016-01-01

Asset Management is an important component of an infrastructure project. A significant cost is involved in maintaining and updating the asset information. Data collection is the most time-consuming task in the development of an asset management system. In order to reduce the time and cost involved in data collection, this paper proposes a low cost Mobile Mapping System using an equipped laser scanner and cameras. First, the feasibility of low cost sensors for 3D asset inventory is discussed by deriving appropriate sensor models. Then, through calibration procedures, respective alignments of the laser scanner, cameras, Inertial Measurement Unit and GPS (Global Positioning System) antenna are determined. The efficiency of this Mobile Mapping System is experimented by mounting it on a truck and golf cart. By using derived sensor models, geo-referenced images and 3D point clouds are derived. After validating the quality of the derived data, the paper provides a framework to extract road assets both automatically and manually using techniques implementing RANSAC plane fitting and edge extraction algorithms. Then the scope of such extraction techniques along with a sample GIS (Geographic Information System) database structure for unified 3D asset inventory are discussed. PMID:26985897

On the degrees of freedom of reduced-rank estimators in multivariate regression

PubMed Central

Mukherjee, A.; Chen, K.; Wang, N.; Zhu, J.

2015-01-01

Summary We study the effective degrees of freedom of a general class of reduced-rank estimators for multivariate regression in the framework of Stein's unbiased risk estimation. A finite-sample exact unbiased estimator is derived that admits a closed-form expression in terms of the thresholded singular values of the least-squares solution and hence is readily computable. The results continue to hold in the high-dimensional setting where both the predictor and the response dimensions may be larger than the sample size. The derived analytical form facilitates the investigation of theoretical properties and provides new insights into the empirical behaviour of the degrees of freedom. In particular, we examine the differences and connections between the proposed estimator and a commonly-used naive estimator. The use of the proposed estimator leads to efficient and accurate prediction risk estimation and model selection, as demonstrated by simulation studies and a data example. PMID:26702155

Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases

PubMed Central

Li, Haifeng; Ding, Fei; Xiao, Lingyun; Shi, Ruona; Wang, Hongyu; Han, Wenjing

2017-01-01

Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities. PMID:28753972

Mathematical prediction of core body temperature from environment, activity, and clothing: The heat strain decision aid (HSDA).

PubMed

Potter, Adam W; Blanchard, Laurie A; Friedl, Karl E; Cadarette, Bruce S; Hoyt, Reed W

2017-02-01

Physiological models provide useful summaries of complex interrelated regulatory functions. These can often be reduced to simple input requirements and simple predictions for pragmatic applications. This paper demonstrates this modeling efficiency by tracing the development of one such simple model, the Heat Strain Decision Aid (HSDA), originally developed to address Army needs. The HSDA, which derives from the Givoni-Goldman equilibrium body core temperature prediction model, uses 16 inputs from four elements: individual characteristics, physical activity, clothing biophysics, and environmental conditions. These inputs are used to mathematically predict core temperature (T c ) rise over time and can estimate water turnover from sweat loss. Based on a history of military applications such as derivation of training and mission planning tools, we conclude that the HSDA model is a robust integration of physiological rules that can guide a variety of useful predictions. The HSDA model is limited to generalized predictions of thermal strain and does not provide individualized predictions that could be obtained from physiological sensor data-driven predictive models. This fully transparent physiological model should be improved and extended with new findings and new challenging scenarios. Published by Elsevier Ltd.

Spherically symmetric Einstein-aether perfect fluid models

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

Coley, Alan A.; Latta, Joey; Leon, Genly

We investigate spherically symmetric cosmological models in Einstein-aether theory with a tilted (non-comoving) perfect fluid source. We use a 1+3 frame formalism and adopt the comoving aether gauge to derive the evolution equations, which form a well-posed system of first order partial differential equations in two variables. We then introduce normalized variables. The formalism is particularly well-suited for numerical computations and the study of the qualitative properties of the models, which are also solutions of Horava gravity. We study the local stability of the equilibrium points of the resulting dynamical system corresponding to physically realistic inhomogeneous cosmological models and astrophysicalmore » objects with values for the parameters which are consistent with current constraints. In particular, we consider dust models in (β−) normalized variables and derive a reduced (closed) evolution system and we obtain the general evolution equations for the spatially homogeneous Kantowski-Sachs models using appropriate bounded normalized variables. We then analyse these models, with special emphasis on the future asymptotic behaviour for different values of the parameters. Finally, we investigate static models for a mixture of a (necessarily non-tilted) perfect fluid with a barotropic equations of state and a scalar field.« less

Fundamental Travel Demand Model Example

NASA Technical Reports Server (NTRS)

Hanssen, Joel

2010-01-01

Instances of transportation models are abundant and detailed "how to" instruction is available in the form of transportation software help documentation. The purpose of this paper is to look at the fundamental inputs required to build a transportation model by developing an example passenger travel demand model. The example model reduces the scale to a manageable size for the purpose of illustrating the data collection and analysis required before the first step of the model begins. This aspect of the model development would not reasonably be discussed in software help documentation (it is assumed the model developer comes prepared). Recommendations are derived from the example passenger travel demand model to suggest future work regarding the data collection and analysis required for a freight travel demand model.

Incorporating biologically based models into assessments of risk from chemical contaminants

NASA Technical Reports Server (NTRS)

Bull, R. J.; Conolly, R. B.; De Marini, D. M.; MacPhail, R. C.; Ohanian, E. V.; Swenberg, J. A.

1993-01-01

The general approach to assessment of risk from chemical contaminants in drinking water involves three steps: hazard identification, exposure assessment, and dose-response assessment. Traditionally, the risks to humans associated with different levels of a chemical have been derived from the toxic responses observed in animals. It is becoming increasingly clear, however, that further information is needed if risks to humans are to be assessed accurately. Biologically based models help clarify the dose-response relationship and reduce uncertainty.

Automotive Control Systems: For Engine, Driveline, and Vehicle

NASA Astrophysics Data System (ADS)

Kiencke, Uwe; Nielsen, Lars

Advances in automotive control systems continue to enhance safety and comfort and to reduce fuel consumption and emissions. Reflecting the trend to optimization through integrative approaches for engine, driveline, and vehicle control, this valuable book enables control engineers to understand engine and vehicle models necessary for controller design, and also introduces mechanical engineers to vehicle-specific signal processing and automatic control. The emphasis on measurement, comparisons between performance and modeling, and realistic examples derive from the authors' unique industrial experience

Mitochondrion-Derived Reactive Oxygen Species Lead to Enhanced Amyloid Beta Formation

PubMed Central

Schütt, Tanja; Kurz, Christopher; Eckert, Schamim H.; Schiller, Carola; Occhipinti, Angelo; Mai, Sören; Jendrach, Marina; Eckert, Gunter P.; Kruse, Shane E.; Palmiter, Richard D.; Brandt, Ulrich; Dröse, Stephan; Wittig, Ilka; Willem, Michael; Haass, Christian; Reichert, Andreas S.; Müller, Walter E.

2012-01-01

Abstract Aims: Intracellular amyloid beta (Aβ) oligomers and extracellular Aβ plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Aβ production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species (ROS) are sufficient to increase Aβ generation and thereby initiate a vicious cycle further impairing mitochondrial function. Results: Complex I and III dysfunction was induced in a cell model using the respiratory inhibitors rotenone and antimycin, resulting in mitochondrial dysfunction and enhanced ROS levels. Both treatments lead to elevated levels of Aβ. Presence of an antioxidant rescued mitochondrial function and reduced formation of Aβ, demonstrating that the observed effects depended on ROS. Conversely, cells overproducing Aβ showed impairment of mitochondrial function such as comprised mitochondrial respiration, strongly altered morphology, and reduced intracellular mobility of mitochondria. Again, the capability of these cells to generate Aβ was partly reduced by an antioxidant, indicating that Aβ formation was also ROS dependent. Moreover, mice with a genetic defect in complex I, or AD mice treated with a complex I inhibitor, showed enhanced Aβ levels in vivo. Innovation: We show for the first time that mitochondrion-derived ROS are sufficient to trigger Aβ production in vitro and in vivo. Conclusion: Several lines of evidence show that mitochondrion-derived ROS result in enhanced amyloidogenic amyloid precursor protein processing, and that Aβ itself leads to mitochondrial dysfunction and increased ROS levels. We propose that starting from mitochondrial dysfunction a vicious cycle is triggered that contributes to the pathogenesis of sporadic AD. Antioxid. Redox Signal. 16, 1421–1433. PMID:22229260

Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor Exacerbates Neuropathology in a Mouse Model of Alzheimer's Disease.

PubMed

Braun, David J; Kalinin, Sergey; Feinstein, Douglas L

2017-01-01

Damage occurring to noradrenergic neurons in the locus coeruleus (LC) contributes to the evolution of neuroinflammation and neurodegeneration in a variety of conditions and diseases. One cause of LC damage may be loss of neurotrophic support from LC target regions. We tested this hypothesis by conditional unilateral knockout of brain-derived neurotrophic factor (BDNF) in adult mice. To evaluate the consequences of BDNF loss in the context of neurodegeneration, the mice harbored familial mutations for human amyloid precursor protein and presenilin-1. In these mice, BDNF depletion reduced tyrosine hydroxylase staining, a marker of noradrenergic neurons, in the rostral LC. BDNF depletion also reduced noradrenergic innervation in the hippocampus, the frontal cortex, and molecular layer of the cerebellum, assessed by staining for dopamine beta hydroxylase. BDNF depletion led to an increase in cortical amyloid plaque numbers and size but was without effect on plaque numbers in the striatum, a site with minimal innervation from the LC. Interestingly, cortical Iba1 staining for microglia was reduced by BDNF depletion and was correlated with reduced dopamine beta hydroxylase staining. These data demonstrate that reduction of BDNF levels in an LC target region can cause retrograde damage to LC neurons, leading to exacerbation of neuropathology in distinct LC target areas. Methods to reduce BDNF loss or supplement BDNF levels may be of value to reduce neurodegenerative processes normally limited by LC noradrenergic activities.

Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.

PubMed

Moisseiev, Elad; Anderson, Johnathon D; Oltjen, Sharon; Goswami, Mayank; Zawadzki, Robert J; Nolta, Jan A; Park, Susanna S

2017-10-01

Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline. Two weeks post-injection, fluorescein angiography (FA) and phase-variance optical coherence tomography angiography (pvOCTA) were used to assess retinal perfusion. Retinal thickness was determined by OCT. The extent of retinal neovascularization was quantitated histologically by counting vascular nuclei on the retinal surface. Among eyes with OIR, intravitreal exosome treatment partially preserved retinal vascular flow in vivo and reduced associated retinal thinning; retinal thickness on OCT was 111.1 ± 7.4µm with saline versus 132.1 ± 11.6µm with exosome, p < 0.001. Retinal neovascularization among OIR eyes was reduced with exosome treatment when compared to saline-treated eyes (7.75 ± 3.68 versus 2.68 ± 1.35 neovascular nuclei per section, p < 0.0001). No immunogenicity or ocular/systemic adverse effect was associated with intravitreal exosome treatment. Intravitreal administration of exosomes derived from hMSCs was well tolerated without immunosuppression and decreased the severity of retinal ischemia in this murine model. This appealing novel non-cellular therapeutic approach warrants further exploration.

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis.

PubMed

Delgado-Rosas, Francisco; Gómez, Raúl; Ferrero, Hortensia; Gaytan, Francisco; Garcia-Velasco, Juan; Simón, Carlos; Pellicer, Antonio

2011-11-01

Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50  μg/kg per day oral Cb2, or 50 or 200  μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.

Iron Sequestration in Microbiota Biofilms As A Novel Strategy for Treating Inflammatory Bowel Disease.

PubMed

Motta, Jean-Paul; Allain, Thibault; Green-Harrison, Luke E; Groves, Ryan A; Feener, Troy; Ramay, Hena; Beck, Paul L; Lewis, Ian A; Wallace, John L; Buret, Andre G

2018-06-08

Significant alterations of intestinal microbiota and anemia are hallmarks of inflammatory bowel disease (IBD). It is widely accepted that iron is a key nutrient for pathogenic bacteria, but little is known about its impact on microbiota associated with IBD. We used a model device to grow human mucosa-associated microbiota in its physiological anaerobic biofilm phenotype. Compared to microbiota from healthy donors, microbiota from IBD patients generate biofilms ex vivo that were larger in size and cell numbers, contained higher intracellular iron concentrations, and exhibited heightened virulence in a model of human intestinal epithelia in vitro and in the nematode Caenorhabditis elegans. We also describe an unexpected iron-scavenging property for an experimental hydrogen sulfide-releasing derivative of mesalamine. The findings demonstrate that this new drug reduces the virulence of IBD microbiota biofilms through a direct reduction of microbial iron intake and without affecting bacteria survival or species composition within the microbiota. Metabolomic analyses indicate that this drug reduces the intake of purine nucleosides (guanosine), increases the secretion of metabolite markers of purine catabolism (urate and hypoxanthine), and reduces the secretion of uracil (a pyrimidine nucleobase) in complex multispecies human biofilms. These findings demonstrate a new pathogenic mechanism for dysbiotic microbiota in IBD and characterize a novel mode of action for a class of mesalamine derivatives. Together, these observations pave the way towards a new therapeutic strategy for treatment of patients with IBD.

Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy

PubMed Central

Fung, Man-Lung; Liong, Emily C.; Chang, Raymond Chuen Chung; Ching, Yick-Pang; Tipoe, George L.

2013-01-01

Our previous study demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) ameliorated hepatic injury in a nonalcoholic fatty liver disease (NAFLD) rat model. Our present study aimed to investigate the mechanism of SAMC on NAFLD-induced hepatic apoptosis and autophagy. Adult female rats were fed with a high-fat diet for 8 weeks to develop NAFLD with or without intraperitoneal injection of 200 mg/kg SAMC for three times per week. During NAFLD development, increased apoptotic cells and caspase-3 activation were observed in the liver. Increased apoptosis was modulated through both intrinsic and extrinsic apoptotic pathways. NAFLD treatment also enhanced the expression of key autophagic markers in the liver with reduced activity of LKB1/AMPK and PI3K/Akt pathways. Increased expression of proapoptotic regulator p53 and decreased activity of antiautophagic regulator mTOR were also observed. Administration of SAMC reduced the number of apoptotic cells through downregulation of both intrinsic and extrinsic apoptotic mechanisms. SAMC also counteracted the effects of NAFLD on LKB1/AMPK and PI3K/Akt pathways. Treatment with SAMC further enhanced hepatic autophagy by regulating autophagic markers and mTOR activity. In conclusion, administration of SAMC during NAFLD development in rats protects the liver from chronic injury by reducing apoptosis and enhancing autophagy. PMID:23861709

Inhibition of mitochondrial fragmentation diminishes Huntington’s disease–associated neurodegeneration

PubMed Central

Guo, Xing; Disatnik, Marie-Helene; Monbureau, Marie; Shamloo, Mehrdad; Mochly-Rosen, Daria; Qi, Xin

2013-01-01

Huntington’s disease (HD) is the result of expression of a mutated Huntingtin protein (mtHtt), and is associated with a variety of cellular dysfunctions including excessive mitochondrial fission. Here, we tested whether inhibition of excessive mitochondrial fission prevents mtHtt-induced pathology. We developed a selective inhibitor (P110-TAT) of the mitochondrial fission protein dynamin-related protein 1 (DRP1). We found that P110-TAT inhibited mtHtt-induced excessive mitochondrial fragmentation, improved mitochondrial function, and increased cell viability in HD cell culture models. P110-TAT treatment of fibroblasts from patients with HD and patients with HD with iPS cell–derived neurons reduced mitochondrial fragmentation and corrected mitochondrial dysfunction. P110-TAT treatment also reduced the extent of neurite shortening and cell death in iPS cell–derived neurons in patients with HD. Moreover, treatment of HD transgenic mice with P110-TAT reduced mitochondrial dysfunction, motor deficits, neuropathology, and mortality. We found that p53, a stress gene involved in HD pathogenesis, binds to DRP1 and mediates DRP1-induced mitochondrial and neuronal damage. Furthermore, P110-TAT treatment suppressed mtHtt-induced association of p53 with mitochondria in multiple HD models. These data indicate that inhibition of DRP1-dependent excessive mitochondrial fission with a P110-TAT–like inhibitor may prevent or slow the progression of HD. PMID:24231356

Low-order modelling of shallow water equations for sensitivity analysis using proper orthogonal decomposition

NASA Astrophysics Data System (ADS)

Zokagoa, Jean-Marie; Soulaïmani, Azzeddine

2012-06-01

This article presents a reduced-order model (ROM) of the shallow water equations (SWEs) for use in sensitivity analyses and Monte-Carlo type applications. Since, in the real world, some of the physical parameters and initial conditions embedded in free-surface flow problems are difficult to calibrate accurately in practice, the results from numerical hydraulic models are almost always corrupted with uncertainties. The main objective of this work is to derive a ROM that ensures appreciable accuracy and a considerable acceleration in the calculations so that it can be used as a surrogate model for stochastic and sensitivity analyses in real free-surface flow problems. The ROM is derived using the proper orthogonal decomposition (POD) method coupled with Galerkin projections of the SWEs, which are discretised through a finite-volume method. The main difficulty of deriving an efficient ROM is the treatment of the nonlinearities involved in SWEs. Suitable approximations that provide rapid online computations of the nonlinear terms are proposed. The proposed ROM is applied to the simulation of hypothetical flood flows in the Bordeaux breakwater, a portion of the 'Rivière des Prairies' located near Laval (a suburb of Montreal, Quebec). A series of sensitivity analyses are performed by varying the Manning roughness coefficient and the inflow discharge. The results are satisfactorily compared to those obtained by the full-order finite volume model.

Fibroblasts derived from long-lived insulin receptor substrate 1 null mice are not resistant to multiple forms of stress

PubMed Central

Page, Melissa M; Sinclair, Amy; Robb, Ellen L; Stuart, Jeffrey A; Withers, Dominic J; Selman, Colin

2014-01-01

Reduced signalling through the insulin/insulin-like growth factor-1 signalling (IIS) pathway is a highly conserved lifespan determinant in model organisms. The precise mechanism underlying the effects of the IIS on lifespan and health is currently unclear, although cellular stress resistance may be important. We have previously demonstrated that mice globally lacking insulin receptor substrate 1 (Irs1−/−) are long-lived and enjoy a greater period of their life free from age-related pathology compared with wild-type (WT) controls. In this study, we show that primary dermal fibroblasts and primary myoblasts derived from Irs1−/− mice are no more resistant to a range of oxidant and nonoxidant chemical stressors than cells derived from WT mice. PMID:25059507

LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington’s Disease

PubMed Central

Chopra, Vanita; Quinti, Luisa; Khanna, Prarthana; Paganetti, Paolo; Kuhn, Rainer; Young, Anne B.; Kazantsev, Aleksey G.; Hersch, Steven

2016-01-01

Background: Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington’s disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. Objective: In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. Method: The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. Results: We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. Conclusions: Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates. PMID:27983565

Tracer Flux Balance at an Urban Canyon Intersection

NASA Astrophysics Data System (ADS)

Carpentieri, Matteo; Robins, Alan G.

2010-05-01

Despite their importance for pollutant dispersion in urban areas, the special features of dispersion at street intersections are rarely taken into account by operational air quality models. Several previous studies have demonstrated the complex flow patterns that occur at street intersections, even with simple geometry. This study presents results from wind-tunnel experiments on a reduced scale model of a complex but realistic urban intersection, located in central London. Tracer concentration measurements were used to derive three-dimensional maps of the concentration field within the intersection. In combination with a previous study (Carpentieri et al., Boundary-Layer Meteorol 133:277-296, 2009) where the velocity field was measured in the same model, a methodology for the calculation of the mean tracer flux balance at the intersection was developed and applied. The calculation highlighted several limitations of current state-of-the-art canyon dispersion models, arising mainly from the complex geometry of the intersection. Despite its limitations, the proposed methodology could be further developed in order to derive, assess and implement street intersection dispersion models for complex urban areas.

LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington's Disease.

PubMed

Chopra, Vanita; Quinti, Luisa; Khanna, Prarthana; Paganetti, Paolo; Kuhn, Rainer; Young, Anne B; Kazantsev, Aleksey G; Hersch, Steven

2016-12-15

Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington's disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates.

Improving parallel I/O autotuning with performance modeling

DOE PAGES

Behzad, Babak; Byna, Surendra; Wild, Stefan M.; ...

2014-01-01

Various layers of the parallel I/O subsystem offer tunable parameters for improving I/O performance on large-scale computers. However, searching through a large parameter space is challenging. We are working towards an autotuning framework for determining the parallel I/O parameters that can achieve good I/O performance for different data write patterns. In this paper, we characterize parallel I/O and discuss the development of predictive models for use in effectively reducing the parameter space. Furthermore, applying our technique on tuning an I/O kernel derived from a large-scale simulation code shows that the search time can be reduced from 12 hours to 2more » hours, while achieving 54X I/O performance speedup.« less

A novel taspine derivative, HMQ1611, inhibits breast cancer cell growth via estrogen receptor α and EGF receptor signaling pathways.

PubMed

Zhan, Yingzhuan; Zhang, Yanmin; Liu, Cuicui; Zhang, Jie; Smith, Wanli W; Wang, Nan; Chen, Yinnan; Zheng, Lei; He, Langchong

2012-06-01

Breast cancer is a common cancer with a leading cause of cancer mortality in women. Currently, the chemotherapy for breast cancer is underdeveloped. Here, we report a novel taspine derivative, HMQ1611, which has anticancer effects using in vitro and in vivo breast cancer models. HMQ1611 reduced cancer cell proliferation in four human breast cancer cell lines including MDA-MB-231, SK-BR-3, ZR-75-30, and MCF-7. HMQ1611 more potently reduced growth of estrogen receptor α (ERα)-positive breast cancer cells (ZR-75-30 and MCF-7) than ERα-negative cells (MDA-MB-231 and SK-BR-3). Moreover, HMQ1611 arrested breast cancer cell cycle at S-phase. In vivo tumor xenograft model, treatment of HMQ1611 significantly reduced tumor size and weight compared with vehicles. We also found that HMQ1611 reduced ERα expression and inhibited membrane ERα-mediated mitogen-activated protein kinase (MAPK) signaling following the stimulation of cells with estrogen. Knockdown of ERα by siRNA transfection in ZR-75-30 cells attenuated HMQ1611 effects. In contrast, overexpression of ERα in MDA-MB-231 cells enhanced HMQ1611 effects, suggesting that ERα pathway mediated HMQ1611's inhibition of breast cancer cell growth in ERα-positive breast cancer. HMQ1611 also reduced phosphorylation of EGF receptor (EGFR) and its downstream signaling players extracellular signal-regulated kinase (ERK)1/2 and AKT activation both in ZR-75-30 and MDA-MB-231 cells. These results showed that the novel compound HMQ1611 had anticancer effects, and partially via ERα and/or EGFR signaling pathways, suggesting that HMQ1611 may be a potential novel candidate for human breast cancer intervention. ©2012 AACR.

A social systems model of hospital utilization.

PubMed Central

Anderson, J G

1976-01-01

A social systems model for the health services system serving the state of New Mexico is presented. Utilization of short-term general hospitals is viewed as a function of sociodemographic characteristics of the population and of the supply of health manpower and facilities available to that population. The model includes a network specifying the causal relationships hypothesized as existing among a set of social, demographic, and economic variables known to be related to the supply of health manpower and facilities and to their utilization. Inclusion of feedback into the model as well as lagged values of physician supply variables permits examination of the dynamic behavior of the social system over time. A method for deriving the reduced form of the structural model is presented along with the reduced-form equations. These equations provide valuable information for policy decisions regarding the likely consequences of changes in the structure of the population and in the supply of health manpower and facilities. The structural and reduced-form equations have been used to predict the consequences for one New Mexico county of state and federal policies that would affect the organization and delivery of health services. PMID:1017949

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

UTP and Temporal Logic Model Checking

NASA Astrophysics Data System (ADS)

Anderson, Hugh; Ciobanu, Gabriel; Freitas, Leo

In this paper we give an additional perspective to the formal verification of programs through temporal logic model checking, which uses Hoare and He Unifying Theories of Programming (UTP). Our perspective emphasizes the use of UTP designs, an alphabetised relational calculus expressed as a pre/post condition pair of relations, to verify state or temporal assertions about programs. The temporal model checking relation is derived from a satisfaction relation between the model and its properties. The contribution of this paper is that it shows a UTP perspective to temporal logic model checking. The approach includes the notion of efficiency found in traditional model checkers, which reduced a state explosion problem through the use of efficient data structures

Modeling and Simulation of Shuttle Launch and Range Operations

NASA Technical Reports Server (NTRS)

Bardina, Jorge; Thirumalainambi, Rajkumar

2004-01-01

The simulation and modeling test bed is based on a mockup of a space flight operations control suitable to experiment physical, procedural, software, hardware and psychological aspects of space flight operations. The test bed consists of a weather expert system to advise on the effect of weather to the launch operations. It also simulates toxic gas dispersion model, impact of human health risk, debris dispersion model in 3D visualization. Since all modeling and simulation is based on the internet, it could reduce the cost of operations of launch and range safety by conducting extensive research before a particular launch. Each model has an independent decision making module to derive the best decision for launch.

Cur l 3, a major allergen of Curvularia lunata-derived short synthetic peptides, shows promise for successful immunotherapy.

PubMed

Sharma, Vidhu; Singh, Bhanu Pratap; Arora, Naveen

2011-12-01

Allergens with reduced IgE binding and intact T cell reactivity are required for safety and efficacy of immunotherapy (IT). Curvularia lunata is an important fungus for respiratory allergic disorders having cross-reactive and specific allergens. Previously, we have identified major allergens-namely, Cur l 1 (31 kD, serine protease), Cur l 2 (48 kD, enolase), and Cur l 3 (12 kD, cytochrome c)-from this fungus. Furthermore, Cur l 3 epitope-peptide, P6, showed immunogenicity and higher IgE binding, where cysteine and histidine were observed to be vital for IgE binding. Thus, this peptide and three derivatives with reduced IgE binding were selected for analysis in mice. In the present study, the effect of IT was assessed with Cur l 3, P6, its derivatives (P6.1-6.3), and P10 in a mouse model of allergy. IT with P6.2 and P10 reduced IgE and IgG1 levels significantly (P < 0.05), with increase in IgG2a levels as compared to other antigens. There was a significant reduction of IL-4 level associated with increased IFN-γ after IT. Airway inflammation was reduced significantly in terms of eosinophil counts in lung tissue and bronchoalveolar lavage fluid. IT with P6 and P6.2 induced significantly higher IL-10 secretion than baseline after 40 days of treatment. Generally, the effect of IT was more pronounced after 40 days than after 10 days of treatment. In summary, the modified peptide, P6.2, with reduced IgE binding, but intact immunogenicity, showed promise for successful IT.

Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study.

PubMed

Holvoet, Paul; Rull, Anna; García-Heredia, Anabel; López-Sanromà, Sílvia; Geeraert, Benjamine; Joven, Jorge; Camps, Jordi

2015-03-01

There is a close interaction between Type 2 Diabetes, obesity and liver disease. We have studied the effects of the two most abundant Stevia-derived steviol glycosides, stevioside and rebaudioside A, and their aglycol derivative steviol on liver steatosis and the hepatic effects of lipotoxicity using a mouse model of obesity and insulin resistance. We treated ob/ob and LDLR-double deficient mice with stevioside (10 mg⋅kg(-1)⋅day-1 p.o., n = 8), rebaudioside A (12 mg⋅kg(-1)⋅day-1 p.o., n = 8), or steviol (5 mg⋅kg(-1)⋅day(-1) p.o., n = 8). We determined their effects on liver steatosis and on the metabolic effects of lipotoxicity by histological analysis, and by combined gene-expression and metabolomic analyses. All compounds attenuated hepatic steatosis. This could be explained by improved glucose metabolism, fat catabolism, bile acid metabolism, and lipid storage and transport. We identified PPARs as important regulators and observed differences in effects on insulin resistance, inflammation and oxidative stress between Stevia-derived compounds. We conclude that Stevia-derived compounds reduce hepatic steatosis to a similar extent, despite differences in effects on glucose and lipid metabolism, and inflammation and oxidative stress. Thus our data show that liver toxicity can be reduced through several pathophysiological changes. Further identification of active metabolites and underlying mechanisms are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Unseren, M.A.

The report reviews a method for modeling and controlling two serial link manipulators which mutually lift and transport a rigid body object in a three dimensional workspace. A new vector variable is introduced which parameterizes the internal contact force controlled degrees of freedom. A technique for dynamically distributing the payload between the manipulators is suggested which yields a family of solutions for the contact forces and torques the manipulators impart to the object. A set of rigid body kinematic constraints which restricts the values of the joint velocities of both manipulators is derived. A rigid body dynamical model for themore » closed chain system is first developed in the joint space. The model is obtained by generalizing the previous methods for deriving the model. The joint velocity and acceleration variables in the model are expressed in terms of independent pseudovariables. The pseudospace model is transformed to obtain reduced order equations of motion and a separate set of equations governing the internal components of the contact forces and torques. A theoretic control architecture is suggested which explicitly decouples the two sets of equations comprising the model. The controller enables the designer to develop independent, non-interacting control laws for the position control and internal force control of the system.« less

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

Unseren, M.A.

The paper reviews a method for modeling and controlling two serial link manipulators which mutually lift and transport a rigid body object in a three dimensional workspace. A new vector variable is introduced which parameterizes the internal contact force controlled degrees of freedom. A technique for dynamically distributing the payload between the manipulators is suggested which yields a family of solutions for the contact forces and torques the manipulators impart to the object. A set of rigid body kinematic constraints which restrict the values of the joint velocities of both manipulators is derived. A rigid body dynamical model for themore » closed chain system is first developed in the joint space. The model is obtained by generalizing the previous methods for deriving the model. The joint velocity and acceleration variables in the model are expressed in terms of independent pseudovariables. The pseudospace model is transformed to obtain reduced order equations of motion and a separate set of equations governing the internal components of the contact forces and torques. A theoretic control architecture is suggested which explicitly decouples the two sets of equations comprising the model. The controller enables the designer to develop independent, non-interacting control laws for the position control and internal force control of the system.« less

Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase

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

Smith, Dayle MA; Xiong, Yijia; Straatsma, TP

2012-05-09

Classical molecular force-field parameters describing the structure and motion of metal clusters in [NiFe] hydrogenase enzymes can be used to compare the dynamics and thermodynamics of [NiFe] under different oxidation, protonation, and ligation circumstances. Using density functional theory (DFT) calculations of small model clusters representative of the active site and the proximal, medial, and distal Fe/S metal centers and their attached protein side chains, we have calculated classical force-field parameters for [NiFe] in reduced and oxidized states, including internal coordinates, force constants, and atom-centered charges. Derived force constants revealed that cysteinate ligands bound to the metal ions are more flexiblemore » in the Ni-B active site, which has a bridging hydroxide ligand, than in the Ni-C active site, which has a bridging hydride. Ten nanosecond all-atom, explicit-solvent MD simulations of [NiFe] hydrogenase in oxidized and reduced catalytic states established the stability of the derived force-field parameters in terms of C{alpha} and metal cluster fluctuations. Average active site structures from the protein MD simulations are consistent with [NiFe] structures from the Protein Data Bank, suggesting that the derived force-field parameters are transferrable to other hydrogenases beyond the structure used for testing. A comparison of experimental H{sub 2}-production rates demonstrated a relationship between cysteinate side chain rotation and activity, justifying the use of a fully dynamic model of [NiFe] metal cluster motion.« less

Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.

PubMed

Kemp, Kevin; Dey, Rimi; Cook, Amelia; Scolding, Neil; Wilkins, Alastair

2017-08-01

Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich's ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich's ataxia.

Derivation of Boundary Manikins: A Principal Component Analysis

NASA Technical Reports Server (NTRS)

Young, Karen; Margerum, Sarah; Barr, Abbe; Ferrer, Mike A.; Rajulu, Sudhakar

2008-01-01

When designing any human-system interface, it is critical to provide realistic anthropometry to properly represent how a person fits within a given space. This study aimed to identify a minimum number of boundary manikins or representative models of subjects anthropometry from a target population, which would realistically represent the population. The boundary manikin anthropometry was derived using, Principal Component Analysis (PCA). PCA is a statistical approach to reduce a multi-dimensional dataset using eigenvectors and eigenvalues. The measurements used in the PCA were identified as those measurements critical for suit and cockpit design. The PCA yielded a total of 26 manikins per gender, as well as their anthropometry from the target population. Reduction techniques were implemented to reduce this number further with a final result of 20 female and 22 male subjects. The anthropometry of the boundary manikins was then be used to create 3D digital models (to be discussed in subsequent papers) intended for use by designers to test components of their space suit design, to verify that the requirements specified in the Human Systems Integration Requirements (HSIR) document are met. The end-goal is to allow for designers to generate suits which accommodate the diverse anthropometry of the user population.

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.

Pauci ex tanto numero: reducing redundancy in multi-model ensembles

NASA Astrophysics Data System (ADS)

Solazzo, E.; Riccio, A.; Kioutsioukis, I.; Galmarini, S.

2013-02-01

We explicitly address the fundamental issue of member diversity in multi-model ensembles. To date no attempts in this direction are documented within the air quality (AQ) community, although 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 biases among models will determine a biased ensemble, making therefore essential the errors of the ensemble members to be independent so that bias can cancel out. 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.

The Analytic Information Warehouse (AIW): a Platform for Analytics using Electronic Health Record Data

PubMed Central

Post, Andrew R.; Kurc, Tahsin; Cholleti, Sharath; Gao, Jingjing; Lin, Xia; Bornstein, William; Cantrell, Dedra; Levine, David; Hohmann, Sam; Saltz, Joel H.

2013-01-01

Objective To create an analytics platform for specifying and detecting clinical phenotypes and other derived variables in electronic health record (EHR) data for quality improvement investigations. Materials and Methods We have developed an architecture for an Analytic Information Warehouse (AIW). It supports transforming data represented in different physical schemas into a common data model, specifying derived variables in terms of the common model to enable their reuse, computing derived variables while enforcing invariants and ensuring correctness and consistency of data transformations, long-term curation of derived data, and export of derived data into standard analysis tools. It includes software that implements these features and a computing environment that enables secure high-performance access to and processing of large datasets extracted from EHRs. Results We have implemented and deployed the architecture in production locally. The software is available as open source. We have used it as part of hospital operations in a project to reduce rates of hospital readmission within 30 days. The project examined the association of over 100 derived variables representing disease and co-morbidity phenotypes with readmissions in five years of data from our institution’s clinical data warehouse and the UHC Clinical Database (CDB). The CDB contains administrative data from over 200 hospitals that are in academic medical centers or affiliated with such centers. Discussion and Conclusion A widely available platform for managing and detecting phenotypes in EHR data could accelerate the use of such data in quality improvement and comparative effectiveness studies. PMID:23402960

An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells.

PubMed

Canfield, Scott G; Stebbins, Matthew J; Morales, Bethsymarie Soto; Asai, Shusaku W; Vatine, Gad D; Svendsen, Clive N; Palecek, Sean P; Shusta, Eric V

2017-03-01

The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human-induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor-like EZ-spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC-derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co-cultured with human iPSC-derived BMECs, the iPSC-derived neurons and astrocytes significantly elevated trans-endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p-glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans. Read the Editorial Highlight for this article on page 843. © 2016 International Society for Neurochemistry.

Phenomapping of rangelands in South Africa using time series of RapidEye data

NASA Astrophysics Data System (ADS)

Parplies, André; Dubovyk, Olena; Tewes, Andreas; Mund, Jan-Peter; Schellberg, Jürgen

2016-12-01

Phenomapping is an approach which allows the derivation of spatial patterns of vegetation phenology and rangeland productivity based on time series of vegetation indices. In our study, we propose a new spatial mapping approach which combines phenometrics derived from high resolution (HR) satellite time series with spatial logistic regression modeling to discriminate land management systems in rangelands. From the RapidEye time series for selected rangelands in South Africa, we calculated bi-weekly noise reduced Normalized Difference Vegetation Index (NDVI) images. For the growing season of 2011⿿2012, we further derived principal phenology metrics such as start, end and length of growing season and related phenological variables such as amplitude, left derivative and small integral of the NDVI curve. We then mapped these phenometrics across two different tenure systems, communal and commercial, at the very detailed spatial resolution of 5 m. The result of a binary logistic regression (BLR) has shown that the amplitude and the left derivative of the NDVI curve were statistically significant. These indicators are useful to discriminate commercial from communal rangeland systems. We conclude that phenomapping combined with spatial modeling is a powerful tool that allows efficient aggregation of phenology and productivity metrics for spatially explicit analysis of the relationships of crop phenology with site conditions and management. This approach has particular potential for disaggregated and patchy environments such as in farming systems in semi-arid South Africa, where phenology varies considerably among and within years. Further, we see a strong perspective for phenomapping to support spatially explicit modelling of vegetation.

Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions.

PubMed

Salmon, Adam B; Dorigatti, Jonathan; Huber, Hillary F; Li, Cun; Nathanielsz, Peter W

2018-05-25

Compelling data exist for programming of chronic later-life diseases and longevity by perinatal developmental programming challenges. Understanding mechanisms by which life course health trajectory and longevity are set is fundamental to understanding aging. Appropriate approaches are needed to determine programming effects on cellular function. We have developed a baboon model in which control mothers eat ad libitum while a second group eat 70% of the global diet fed controls, leading to male and female offspring intrauterine growth restriction (IUGR). We have shown that IUGR suffer from acceleration of several age-related physiological declines. Here, we report on a skin-derived fibroblast model with potential relevance for mechanistic studies on how IUGR impacts aging. Fibroblasts were cultured from the skin biopsies taken from adult baboons from control and IUGR cohorts. IUGR-derived fibroblasts grew in culture less well than controls and those derived from male, but not female, IUGR baboons had a significant reduction in maximum respiration rate compared to control-derived fibroblasts. We also show that relative levels of several mitochondrial protein subunits, including NDUFB8 and cytochrome c oxidase subunit IV, were reduced in IUGR-derived fibroblasts even after serial passaging in culture. The lower levels of electron transport system components provide potential mechanisms for accelerated life course aging in the setting of programmed IUGR. This observation fits with the greater sensitivity of males compared with females to many, but not all, outcomes in response to programming challenges. These approaches will be powerful in the determination of programming-aging interactions.

Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis

PubMed Central

Cosenza, Stella; Toupet, Karine; Maumus, Marie; Luz-Crawford, Patricia; Blanc-Brude, Olivier; Jorgensen, Christian; Noël, Danièle

2018-01-01

Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models. Results: Exos and MPs from MSCs inhibited T lymphocyte proliferation in a dose-dependent manner and decreased the percentage of CD4+ and CD8+ T cell subsets. Interestingly, Exos increased Treg cell populations while parental MSCs did not. Conversely, plasmablast differentiation was reduced to a similar extent by MSCs, Exos or MPs. IFN-γ priming of MSCs before vesicles isolation did not influence the immunomodulatory function of isolated Exos or MPs. In DTH, we observed a dose-dependent anti-inflammatory effect of MPs and Exos, while in the CIA model, Exos efficiently decreased clinical signs of inflammation. The beneficial effect of Exos was associated with fewer plasmablasts and more Breg-like cells in lymph nodes. Conclusions: Both MSCs-derived MPs and Exos exerted an anti-inflammatory role on T and B lymphocytes independently of MSCs priming. However, Exos were more efficient in suppressing inflammation in vivo. Our work is the first demonstration of the therapeutic potential of MSCs-derived EVs in inflammatory arthritis. PMID:29507629

Modelling Simple Experimental Platform for In Vitro Study of Drug Elution from Drug Eluting Stents (DES)

NASA Astrophysics Data System (ADS)

Kalachev, L. V.

2016-06-01

We present a simple model of experimental setup for in vitro study of drug release from drug eluting stents and drug propagation in artificial tissue samples representing blood vessels. The model is further reduced using the assumption on vastly different characteristic diffusion times in the stent coating and in the artificial tissue. The model is used to derive a relationship between the times at which the measurements have to be taken for two experimental platforms, with corresponding artificial tissue samples made of different materials with different drug diffusion coefficients, to properly compare the drug release characteristics of drug eluting stents.

One-dimensional nonlinear elastodynamic models and their local conservation laws with applications to biological membranes.

PubMed

Cheviakov, A F; Ganghoffer, J-F

2016-05-01

The framework of incompressible nonlinear hyperelasticity and viscoelasticity is applied to the derivation of one-dimensional models of nonlinear wave propagation in fiber-reinforced elastic solids. Equivalence transformations are used to simplify the resulting wave equations and to reduce the number of parameters. Local conservation laws and global conserved quantities of the models are systematically computed and discussed, along with other related mathematical properties. Sample numerical solutions are presented. The models considered in the paper are appropriate for the mathematical description of certain aspects of the behavior of biological membranes and similar structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reducing mTOR augments parietal epithelial cell density in a model of acute podocyte depletion and in aged kidneys

PubMed Central

McNicholas, Bairbre A.; Eng, Diana G.; Lichtnekert, Julia; Rabinowitz, Peter S.; Pippin, Jeffrey W.

2016-01-01

Parietal epithelial cell (PEC) response to glomerular injury may underlie a common pathway driving fibrogenesis following podocyte loss that typifies several glomerular disorders. Although the mammalian target of rapamycin (mTOR) pathway is important in cell homeostasis, little is known of the biological role or impact of reducing mTOR activity on PEC response following podocyte depletion, nor in the aging kidney. The purpose of these studies was to determine the impact on PECs of reducing mTOR activity following abrupt experimental depletion in podocyte number, as well as in a model of chronic podocyte loss and sclerosis associated with aging. Podocyte depletion was induced by an anti-podocyte antibody and rapamycin started at day 5 until death at day 14. Reducing mTOR did not lead to a greater reduction in podocyte density, despite greater glomerulosclerosis. However, mTOR inhibition lead to an increase in PEC density and PEC-derived crescent formation. Additionally, markers of epithelial-to-mesenchymal transition (platelet-derived growth factor receptor-β, α-smooth muscle actin, Notch-3) and PEC activation (CD44, collagen IV) were further increased by mTOR reduction. Aged mice treated with rapamycin for 1, 2, and 10 wk before death at 26.5 mo (≈75-yr-old human age) had increased the number of glomeruli with a crescentic appearance. mTOR inhibition at either a high or low level lead to changes in PEC phenotype, indicating PEC morphology is sensitive to changes mediated by global mTOR inhibition. PMID:27440779

An application of a hydraulic model simulator in flood risk assessment under changing climatic conditions

NASA Astrophysics Data System (ADS)

Doroszkiewicz, J. M.; Romanowicz, R. J.

2016-12-01

The standard procedure of climate change impact assessment on future hydrological extremes consists of a chain of consecutive actions, starting from the choice of GCM driven by an assumed CO2 scenario, through downscaling of climatic forcing to a catchment scale, estimation of hydrological extreme indices using hydrological modelling tools and subsequent derivation of flood risk maps with the help of a hydraulic model. Among many possible sources of uncertainty, the main are the uncertainties related to future climate scenarios, climate models, downscaling techniques and hydrological and hydraulic models. Unfortunately, we cannot directly assess the impact of these different sources of uncertainties on flood risk in future due to lack of observations of future climate realizations. The aim of this study is an assessment of a relative impact of different sources of uncertainty on the uncertainty of flood risk maps. Due to the complexity of the processes involved, an assessment of total uncertainty of maps of inundation probability might be very computer time consuming. As a way forward we present an application of a hydraulic model simulator based on a nonlinear transfer function model for the chosen locations along the river reach. The transfer function model parameters are estimated based on the simulations of the hydraulic model at each of the model cross-sections. The study shows that the application of a simulator substantially reduces the computer requirements related to the derivation of flood risk maps under future climatic conditions. Biala Tarnowska catchment, situated in southern Poland is used as a case study. Future discharges at the input to a hydraulic model are obtained using the HBV model and climate projections obtained from the EUROCORDEX project. The study describes a cascade of uncertainty related to different stages of the process of derivation of flood risk maps under changing climate conditions. In this context it takes into account the uncertainty of future climate projections, an uncertainty of flow routing model, the propagation of that uncertainty through the hydraulic model, and finally, the uncertainty related to the derivation of flood risk maps.

Deriving habitat models for northern long-eared bats from historical detection data: A case study using the Fernow Experimental Forest

USGS Publications Warehouse

Ford, W. Mark; Silvis, Alexander; Rodrigue, Jane L.; Kniowski, Andrew B.; Johnson, Joshua B.

2016-01-01

The listing of the northern long-eared bat (Myotis septentrionalis) as federally threatened under the Endangered Species Act following severe population declines from white-nose syndrome presents considerable challenges to natural resource managers. Because the northern long-eared bat is a forest habitat generalist, development of effective conservation measures will depend on appropriate understanding of its habitat relationships at individual locations. However, severely reduced population sizes make gathering data for such models difficult. As a result, historical data may be essential in development of habitat models. To date, there has been little evaluation of how effective historical bat presence data, such as data derived from mist-net captures, acoustic detection, and day-roost locations, may be in developing habitat models, nor is it clear how models created using different data sources may differ. We explored this issue by creating presence probability models for the northern long-eared bat on the Fernow Experimental Forest in the central Appalachian Mountains of West Virginia using a historical, presence-only data set. Each presence data type produced outputs that were dissimilar but that still corresponded with known traits of the northern long-eared bat or are easily explained in the context of the particular data collection protocol. However, our results also highlight potential limitations of individual data types. For example, models from mist-net capture data only showed high probability of presence along the dendritic network of riparian areas, an obvious artifact of sampling methodology. Development of ecological niche and presence models for northern long-eared bat populations could be highly valuable for resource managers going forward with this species. We caution, however, that efforts to create such models should consider the substantial limitations of models derived from historical data, and address model assumptions.

Testing a new Free Core Nutation empirical model

NASA Astrophysics Data System (ADS)

Belda, Santiago; Ferrándiz, José M.; Heinkelmann, Robert; Nilsson, Tobias; Schuh, Harald

2016-03-01

The Free Core Nutation (FCN) is a free mode of the Earth's rotation caused by the different material characteristics of the Earth's core and mantle. This causes the rotational axes of those layers to slightly diverge from each other, resulting in a wobble of the Earth's rotation axis comparable to nutations. In this paper we focus on estimating empirical FCN models using the observed nutations derived from the VLBI sessions between 1993 and 2013. Assuming a fixed value for the oscillation period, the time-variable amplitudes and phases are estimated by means of multiple sliding window analyses. The effects of using different a priori Earth Rotation Parameters (ERP) in the derivation of models are also addressed. The optimal choice of the fundamental parameters of the model, namely the window width and step-size of its shift, is searched by performing a thorough experimental analysis using real data. The former analyses lead to the derivation of a model with a temporal resolution higher than the one used in the models currently available, with a sliding window reduced to 400 days and a day-by-day shift. It is shown that this new model increases the accuracy of the modeling of the observed Earth's rotation. Besides, empirical models determined from USNO Finals as a priori ERP present a slightly lower Weighted Root Mean Square (WRMS) of residuals than IERS 08 C04 along the whole period of VLBI observations, according to our computations. The model is also validated through comparisons with other recognized models. The level of agreement among them is satisfactory. Let us remark that our estimates give rise to the lowest residuals and seem to reproduce the FCN signal in more detail.

Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies.

PubMed

Lee, Edmund C; Fitzgerald, Michael; Bannerman, Bret; Donelan, Jill; Bano, Kristen; Terkelsen, Jennifer; Bradley, Daniel P; Subakan, Ozlem; Silva, Matthew D; Liu, Ray; Pickard, Michael; Li, Zhi; Tayber, Olga; Li, Ping; Hales, Paul; Carsillo, Mary; Neppalli, Vishala T; Berger, Allison J; Kupperman, Erik; Manfredi, Mark; Bolen, Joseph B; Van Ness, Brian; Janz, Siegfried

2011-12-01

The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM). Both cell line-derived OCI-Ly10 and primary human lymphoma-derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMyc(Cα)/Bcl-X(L) GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc-disseminated model of iMyc(Cα)/Bcl-X(L) was used to determine antitumor activity and effects on osteolytic bone disease. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. ©2011 AACR.

Jacobian projection reduced-order models for dynamic systems with contact nonlinearities

NASA Astrophysics Data System (ADS)

Gastaldi, Chiara; Zucca, Stefano; Epureanu, Bogdan I.

2018-02-01

In structural dynamics, the prediction of the response of systems with localized nonlinearities, such as friction dampers, is of particular interest. This task becomes especially cumbersome when high-resolution finite element models are used. While state-of-the-art techniques such as Craig-Bampton component mode synthesis are employed to generate reduced order models, the interface (nonlinear) degrees of freedom must still be solved in-full. For this reason, a new generation of specialized techniques capable of reducing linear and nonlinear degrees of freedom alike is emerging. This paper proposes a new technique that exploits spatial correlations in the dynamics to compute a reduction basis. The basis is composed of a set of vectors obtained using the Jacobian of partial derivatives of the contact forces with respect to nodal displacements. These basis vectors correspond to specifically chosen boundary conditions at the contacts over one cycle of vibration. The technique is shown to be effective in the reduction of several models studied using multiple harmonics with a coupled static solution. In addition, this paper addresses another challenge common to all reduction techniques: it presents and validates a novel a posteriori error estimate capable of evaluating the quality of the reduced-order solution without involving a comparison with the full-order solution.

Plant-based foods containing cell wall polysaccharides rich in specific active monosaccharides protect against myocardial injury in rat myocardial infarction models.

PubMed

Lim, Sun Ha; Kim, Yaesil; Yun, Ki Na; Kim, Jin Young; Jang, Jung-Hee; Han, Mee-Jung; Lee, Jongwon

2016-12-08

Many cohort studies have shown that consumption of diets containing a higher composition of foods derived from plants reduces mortality from coronary heart disease (CHD). Here, we examined the active components of a plant-based diet and the underlying mechanisms that reduce the risk of CHD using three rat models and a quantitative proteomics approach. In a short-term myocardial infarction (MI) model, intake of wheat extract (WE), the representative cardioprotectant identified by screening approximately 4,000 samples, reduced myocardial injury by inhibiting apoptosis, enhancing ATP production, and maintaining protein homeostasis. In long-term post-MI models, this myocardial protection resulted in ameliorating adverse left-ventricular remodelling, which is a predictor of heart failure. Among the wheat components, arabinose and xylose were identified as active components responsible for the observed efficacy of WE, which was administered via ingestion and tail-vein injections. Finally, the food components of plant-based diets that contained cell wall polysaccharides rich in arabinose, xylose, and possibly fucose were found to confer protection against myocardial injury. These results show for the first time that specific monosaccharides found in the cell wall polysaccharides in plant-based diets can act as active ingredients that reduce CHD by inhibiting postocclusion steps, including MI and heart failure.

Symplectic modeling of beam loading in electromagnetic cavities

DOE PAGES

Abell, Dan T.; Cook, Nathan M.; Webb, Stephen D.

2017-05-22

Simulating beam loading in radio frequency accelerating structures is critical for understanding higher-order mode effects on beam dynamics, such as beam break-up instability in energy recovery linacs. Full wave simulations of beam loading in radio frequency structures are computationally expensive, and while reduced models can ignore essential physics, it can be difficult to generalize. Here, we present a self-consistent algorithm derived from the least-action principle which can model an arbitrary number of cavity eigenmodes and with a generic beam distribution. It has been implemented in our new Open Library for Investigating Vacuum Electronics (OLIVE).

Surface corrections for peridynamic models in elasticity and fracture

NASA Astrophysics Data System (ADS)

Le, Q. V.; Bobaru, F.

2018-04-01

Peridynamic models are derived by assuming that a material point is located in the bulk. Near a surface or boundary, material points do not have a full non-local neighborhood. This leads to effective material properties near the surface of a peridynamic model to be slightly different from those in the bulk. A number of methods/algorithms have been proposed recently for correcting this peridynamic surface effect. In this study, we investigate the efficacy and computational cost of peridynamic surface correction methods for elasticity and fracture. We provide practical suggestions for reducing the peridynamic surface effect.

Properties of Vector Preisach Models

NASA Technical Reports Server (NTRS)

Kahler, Gary R.; Patel, Umesh D.; Torre, Edward Della

2004-01-01

This paper discusses rotational anisotropy and rotational accommodation of magnetic particle tape. These effects have a performance impact during the reading and writing of the recording process. We introduce the reduced vector model as the basis for the computations. Rotational magnetization models must accurately compute the anisotropic characteristics of ellipsoidally magnetizable media. An ellipticity factor is derived for these media that computes the two-dimensional magnetization trajectory for all applied fields. An orientation correction must be applied to the computed rotational magnetization. For isotropic materials, an orientation correction has been developed and presented. For anisotropic materials, an orientation correction is introduced.

General slip regime permeability model for gas flow through porous media

NASA Astrophysics Data System (ADS)

Zhou, Bo; Jiang, Peixue; Xu, Ruina; Ouyang, Xiaolong

2016-07-01

A theoretical effective gas permeability model was developed for rarefied gas flow in porous media, which holds over the entire slip regime with the permeability derived as a function of the Knudsen number. This general slip regime model (GSR model) is derived from the pore-scale Navier-Stokes equations subject to the first-order wall slip boundary condition using the volume-averaging method. The local closure problem for the volume-averaged equations is studied analytically and numerically using a periodic sphere array geometry. The GSR model includes a rational fraction function of the Knudsen number which leads to a limit effective permeability as the Knudsen number increases. The mechanism for this behavior is the viscous fluid inner friction caused by converging-diverging flow channels in porous media. A linearization of the GSR model leads to the Klinkenberg equation for slightly rarefied gas flows. Finite element simulations show that the Klinkenberg model overestimates the effective permeability by as much as 33% when a flow approaches the transition regime. The GSR model reduces to the unified permeability model [F. Civan, "Effective correlation of apparent gas permeability in tight porous media," Transp. Porous Media 82, 375 (2010)] for the flow in the slip regime and clarifies the physical significance of the empirical parameter b in the unified model.

A transfer function type of simplified electrochemical model with modified boundary conditions and Padé approximation for Li-ion battery: Part 1. lithium concentration estimation

NASA Astrophysics Data System (ADS)

Yuan, Shifei; Jiang, Lei; Yin, Chengliang; Wu, Hongjie; Zhang, Xi

2017-06-01

To guarantee the safety, high efficiency and long lifetime for lithium-ion battery, an advanced battery management system requires a physics-meaningful yet computationally efficient battery model. The pseudo-two dimensional (P2D) electrochemical model can provide physical information about the lithium concentration and potential distributions across the cell dimension. However, the extensive computation burden caused by the temporal and spatial discretization limits its real-time application. In this research, we propose a new simplified electrochemical model (SEM) by modifying the boundary conditions for electrolyte diffusion equations, which significantly facilitates the analytical solving process. Then to obtain a reduced order transfer function, the Padé approximation method is adopted to simplify the derived transcendental impedance solution. The proposed model with the reduced order transfer function can be briefly computable and preserve physical meanings through the presence of parameters such as the solid/electrolyte diffusion coefficients (Ds&De) and particle radius. The simulation illustrates that the proposed simplified model maintains high accuracy for electrolyte phase concentration (Ce) predictions, saying 0.8% and 0.24% modeling error respectively, when compared to the rigorous model under 1C-rate pulse charge/discharge and urban dynamometer driving schedule (UDDS) profiles. Meanwhile, this simplified model yields significantly reduced computational burden, which benefits its real-time application.

A modular method for evaluating the performance of picture archiving and communication systems.

PubMed

Sanders, W H; Kant, L A; Kudrimoti, A

1993-08-01

Modeling can be used to predict the performance of picture archiving and communication system (PACS) configurations under various load conditions at an early design stage. This is important because choices made early in the design of a system can have a significant impact on the performance of the resulting implementation. Because PACS consist of many types of components, it is important to do such evaluations in a modular manner, so that alternative configurations and designs can be easily investigated. Stochastic activity networks (SANs) and reduced base model construction methods can aid in doing this. SANs are a model type particularly suited to the evaluation of systems in which several activities may be in progress concurrently, and each activity may affect the others through the results of its completion. Together with SANs, reduced base model construction methods provide a means to build highly modular models, in which models of particular components can be easily reused. In this article, we investigate the use of SANs and reduced base model construction techniques in evaluating PACS. Construction and solution of the models is done using UltraSAN, a graphic-oriented software tool for model specification, analysis, and simulation. The method is illustrated via the evaluation of a realistically sized PACS for a typical United States hospital of 300 to 400 beds, and the derivation of system response times and component utilizations.

An approach to the analysis of performance of quasi-optimum digital phase-locked loops.

NASA Technical Reports Server (NTRS)

Polk, D. R.; Gupta, S. C.

1973-01-01

An approach to the analysis of performance of quasi-optimum digital phase-locked loops (DPLL's) is presented. An expression for the characteristic function of the prior error in the state estimate is derived, and from this expression an infinite dimensional equation for the prior error variance is obtained. The prior error-variance equation is a function of the communication system model and the DPLL gain and is independent of the method used to derive the DPLL gain. Two approximations are discussed for reducing the prior error-variance equation to finite dimension. The effectiveness of one approximation in analyzing DPLL performance is studied.

Wavelet and Multiresolution Analysis for Finite Element Networking Paradigms

NASA Technical Reports Server (NTRS)

Kurdila, Andrew J.; Sharpley, Robert C.

1999-01-01

This paper presents a final report on Wavelet and Multiresolution Analysis for Finite Element Networking Paradigms. The focus of this research is to derive and implement: 1) Wavelet based methodologies for the compression, transmission, decoding, and visualization of three dimensional finite element geometry and simulation data in a network environment; 2) methodologies for interactive algorithm monitoring and tracking in computational mechanics; and 3) Methodologies for interactive algorithm steering for the acceleration of large scale finite element simulations. Also included in this report are appendices describing the derivation of wavelet based Particle Image Velocity algorithms and reduced order input-output models for nonlinear systems by utilizing wavelet approximations.

Collision properties of overtaking supersolitons with small amplitudes

NASA Astrophysics Data System (ADS)

Olivier, C. P.; Verheest, F.; Hereman, W. A.

2018-03-01

The collision properties of overtaking small-amplitude supersolitons are investigated for the fluid model of a plasma consisting of cold ions and two-temperature Boltzmann electrons. A reductive perturbation analysis is performed for compositional parameters near the supercritical composition. A generalized Korteweg-de Vries equation with a quartic nonlinearity is derived, referred to as the modified Gardner equation. Criteria for the existence of small-amplitude supersolitons are derived. The modified Gardner equation is shown to be not completely integrable, implying that supersoliton collisions are inelastic, as confirmed by numerical simulations. These simulations also show that supersolitons may reduce to regular solitons as a result of overtaking collisions.

Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection

NASA Astrophysics Data System (ADS)

Chen, Zhuo; Zhang, Yaxin; Wang, Dong; Li, Linsen; Zhou, Shanyong; Huang, Joy H.; Chen, Jincan; Hu, Ping; Huang, Mingdong

2016-01-01

Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-Lys). Compared with its anionic ZnPc counterpart, ZnPc-Lys showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-Lys was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.

Aerodynamic Design on Unstructured Grids for Turbulent Flows

NASA Technical Reports Server (NTRS)

Anderson, W. Kyle; Bonhaus, Daryl L.

1997-01-01

An aerodynamic design algorithm for turbulent flows using unstructured grids is described. The current approach uses adjoint (costate) variables for obtaining derivatives of the cost function. The solution of the adjoint equations is obtained using an implicit formulation in which the turbulence model is fully coupled with the flow equations when solving for the costate variables. The accuracy of the derivatives is demonstrated by comparison with finite-difference gradients and a few example computations are shown. In addition, a user interface is described which significantly reduces the time required for setting up the design problems. Recommendations on directions of further research into the Navier Stokes design process are made.

An improved push-pull voltage fed converter using a tapped output-filter inductor

NASA Technical Reports Server (NTRS)

Wester, G. W.

1983-01-01

A new concept of using a tapped output-filter inductor and an auxiliary commutating diode to reduce the likelihood of transformer core saturation in a push-pull, voltage-fed converter is presented. The linearized circuit model and transfer functions are derived with a hybrid approach using both state-space and circuit averaging. Operation of the new converter - including parasitic effects - is discussed, and a design equation for inductor tap ratio is established. It is predicted and experimentally confirmed that the new converter has more symmetrical transformer core operation, and the potential exits for lower transistor turnon current and reduced transistor voltage stress. These benefits reduce switching loss and enhance transistor reliability.

[Estimation of optimum normalized difference spectral index for nitrogen accumulation in wheat leaf based on reduced precise sampling method].

PubMed

Yao, Xia; Liu, Xiao-jun; Wang, Wei; Tian, Yong-chao; Cao, Wei-xing; Zhu, Yan

2010-12-01

Four independent field experiments with 6 wheat varieties and 5 nitrogen application levels were conducted, and time-course measurements were taken on the canopy hyperspectral reflectance and leaf N accumulation per unit soil area (LNA, g N x m(-2)). By adopting reduced precise sampling method, all possible normalized difference spectral indices [NDSI(i,j)] within the spectral range of 350-2500 nm were constructed, and the relationships of LNA to the NDSI(i,j) were quantified, aimed to explore the new sensitive spectral bands and key index from precise analysis of ground-based hyperspectral information, and to develop prediction models for wheat LNA. The results showed that the sensitive spectral bands for LNA were located in visible light and near infrared regions, especially at 860 nm and 720 nm for wheat LNA. The monitoring model based on the NDSI(860,720) was formulated as LNA = 26.34 x [NDSI(860,720)](1.887), with R2 = 0.900 and SE = 1.327. The fitness test of the derived equations with independent datasets showed that for wheat LNA, the model gave the estimation accuracy of 0.823 and the RMSE of 0.991 g N x m(-2), indicating a good fitness between the measured and estimated LNA. The present normalized hyperspectral parameter of NDSI(860,720) and its derived regression model could be reliably used for the estimation of winter wheat LNA.

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

Effects of SKF-83566 and haloperidol on performance on progressive ratio schedules maintained by sucrose and corn oil reinforcement: quantitative analysis using a new model derived from the Mathematical Principles of Reinforcement (MPR).

PubMed

Olarte-Sánchez, C M; Valencia-Torres, L; Cassaday, H J; Bradshaw, C M; Szabadi, E

2013-12-01

Mathematical models can assist the interpretation of the effects of interventions on schedule-controlled behaviour and help to differentiate between processes that may be confounded in traditional performance measures such as response rate and the breakpoint in progressive ratio (PR) schedules. The effects of a D1-like dopamine receptor antagonist, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide (SKF-83566), and a D2-like receptor antagonist, haloperidol, on rats' performance on PR schedules maintained by sucrose and corn oil reinforcers were assessed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement. Separate groups of rats were trained under a PR schedule using sucrose or corn oil reinforcers. SKF-83566 (0.015 and 0.03 mg kg(-1)) and haloperidol (0.05 and 0.1 mg kg(-1)) were administered intraperitoneally (five administrations of each treatment). Running and overall response rates in successive ratios were analysed using the new model, and estimates of the model's parameters were compared between treatments. Haloperidol reduced a (the parameter expressing incentive value) in the case of both reinforcers, but did not affect the parameters related to response time and post-reinforcement pausing. SKF-83566 reduced a and k (the parameter expressing sensitivity of post-reinforcement pausing to the prior inter-reinforcement interval) in the case of sucrose, but did not affect any of the parameters in the case of corn oil. The results are consistent with the hypothesis that blockade of both D1-like and D2-like receptors reduces the incentive value of sucrose, whereas the incentive value of corn oil is more sensitive to blockade of D2-like than D1-like receptors.

F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy.

PubMed

Le Grand, Bruno; Letienne, Robert; Dupont-Passelaigue, Elisabeth; Lantoine-Adam, Frédérique; Longo, Frédéric; David-Dufilho, Monique; Michael, Georghia; Nishida, Kunihiro; Catheline, Daniel; Legrand, Philippe; Hatem, Stéphane; Nattel, Stanley

2014-07-01

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 ± 111 s in the vehicle group to 79 ± 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 ± 7.4 %, n = 9 vs 17.6 ± 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.

Solving constrained inverse problems for waveform tomography with Salvus

NASA Astrophysics Data System (ADS)

Boehm, C.; Afanasiev, M.; van Driel, M.; Krischer, L.; May, D.; Rietmann, M.; Fichtner, A.

2016-12-01

Finding a good balance between flexibility and performance is often difficult within domain-specific software projects. To achieve this balance, we introduce Salvus: an open-source high-order finite element package built upon PETSc and Eigen, that focuses on large-scale full-waveform modeling and inversion. One of the key features of Salvus is its modular design, based on C++ mixins, that separates the physical equations from the numerical discretization and the mathematical optimization. In this presentation we focus on solving inverse problems with Salvus and discuss (i) dealing with inexact derivatives resulting, e.g., from lossy wavefield compression, (ii) imposing additional constraints on the model parameters, e.g., from effective medium theory, and (iii) integration with a workflow management tool. We present a feasible-point trust-region method for PDE-constrained inverse problems that can handle inexactly computed derivatives. The level of accuracy in the approximate derivatives is controlled by localized error estimates to ensure global convergence of the method. Additional constraints on the model parameters are typically cheap to compute without the need for further simulations. Hence, including them in the trust-region subproblem introduces only a small computational overhead, but ensures feasibility of the model in every iteration. We show examples with homogenization constraints derived from effective medium theory (i.e. all fine-scale updates must upscale to a physically meaningful long-wavelength model). Salvus has a built-in workflow management framework to automate the inversion with interfaces to user-defined misfit functionals and data structures. This significantly reduces the amount of manual user interaction and enhances reproducibility which we demonstrate for several applications from the laboratory to global scale.

Combining frozen-density embedding with the conductor-like screening model using Lagrangian techniques for response properties.

PubMed

Schieschke, Nils; Di Remigio, Roberto; Frediani, Luca; Heuser, Johannes; Höfener, Sebastian

2017-07-15

We present the explicit derivation of an approach to the multiscale description of molecules in complex environments that combines frozen-density embedding (FDE) with continuum solvation models, in particular the conductor-like screening model (COSMO). FDE provides an explicit atomistic description of molecule-environment interactions at reduced computational cost, while the outer continuum layer accounts for the effect of long-range isotropic electrostatic interactions. Our treatment is based on a variational Lagrangian framework, enabling rigorous derivations of ground- and excited-state response properties. As an example of the flexibility of the theoretical framework, we derive and discuss FDE + COSMO analytical molecular gradients for excited states within the Tamm-Dancoff approximation (TDA) and for ground states within second-order Møller-Plesset perturbation theory (MP2) and a second-order approximate coupled cluster with singles and doubles (CC2). It is shown how this method can be used to describe vertical electronic excitation (VEE) energies and Stokes shifts for uracil in water and carbostyril in dimethyl sulfoxide (DMSO), respectively. In addition, VEEs for some simplified protein models are computed, illustrating the performance of this method when applied to larger systems. The interaction terms between the FDE subsystem densities and the continuum can influence excitation energies up to 0.3 eV and, thus, cannot be neglected for general applications. We find that the net influence of the continuum in presence of the first FDE shell on the excitation energy amounts to about 0.05 eV for the cases investigated. The present work is an important step toward rigorously derived ab initio multilayer and multiscale modeling approaches. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Quantum coherence of planar spin models with Dzyaloshinsky-Moriya interaction

NASA Astrophysics Data System (ADS)

Radhakrishnan, Chandrashekar; Ermakov, Igor; Byrnes, Tim

2017-07-01

The quantum coherence of one-dimensional planar spin models with Dzyaloshinsky-Moriya interaction is investigated. The anisotropic XY model, the isotropic XX model, and the transverse field model are studied in the large N limit using two qubit reduced density matrices and two point correlation functions. From our investigations we find that the coherence as measured using Jensen-Shannon divergence can be used to detect quantum phase transitions and quantum critical points. The derivative of coherence shows nonanalytic behavior at critical points, leading to the conclusion that these transitions are of second order. Further, we show that the presence of Dzyaloshinsky-Moriya coupling suppresses the phase transition due to residual ferromagnetism, which is caused by spin canting.

Dimensional reduction of the Standard Model coupled to a new singlet scalar field

NASA Astrophysics Data System (ADS)

Brauner, Tomáš; Tenkanen, Tuomas V. I.; Tranberg, Anders; Vuorinen, Aleksi; Weir, David J.

2017-03-01

We derive an effective dimensionally reduced theory for the Standard Model augmented by a real singlet scalar. We treat the singlet as a superheavy field and integrate it out, leaving an effective theory involving only the Higgs and SU(2) L × U(1) Y gauge fields, identical to the one studied previously for the Standard Model. This opens up the possibility of efficiently computing the order and strength of the electroweak phase transition, numerically and nonperturbatively, in this extension of the Standard Model. Understanding the phase diagram is crucial for models of electroweak baryogenesis and for studying the production of gravitational waves at thermal phase transitions.

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

PubMed

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

2014-01-01

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

Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress.

PubMed

de Souza, Veruska Cintia Alexandrino; Pereira, Thiago Almeida; Teixeira, Valéria Wanderley; Carvalho, Helotonio; de Castro, Maria Carolina Accioly Brelaz; D'assunção, Carolline Guimarães; de Barros, Andréia Ferreira; Carvalho, Camila Lima; de Lorena, Virgínia Maria Barros; Costa, Vláudia Maria Assis; Teixeira, Álvaro Aguiar Coelho; Figueiredo, Regina Celia Bressan Queiroz; de Oliveira, Sheilla Andrade

2017-07-28

To evaluate the therapeutic effects of bone marrow-derived CD11b + CD14 + monocytes in a murine model of chronic liver damage. Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay. CD11b + CD14 + monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b + CD14 + monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin. Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Lagrange thermodynamic potential and intrinsic variables for He-3 He-4 dilute solutions

NASA Technical Reports Server (NTRS)

Jackson, H. W.

1983-01-01

For a two-fluid model of dilute solutions of He-3 in liquid He-4, a thermodynamic potential is constructed that provides a Lagrangian for deriving equations of motion by a variational procedure. This Lagrangian is defined for uniform velocity fields as a (negative) Legendre transform of total internal energy, and its primary independent variables, together with their thermodynamic conjugates, are identified. Here, similarities between relations in classical physics and quantum statistical mechanics serve as a guide for developing an alternate expression for this function that reveals its character as the difference between apparent kinetic energy and intrinsic internal energy. When the He-3 concentration in the mixtures tends to zero, this expression reduces to Zilsel's formula for the Lagrangian for pure liquid He-4. An investigation of properties of the intrinsic internal energy leads to the introduction of intrinsic chemical potentials along with other intrinsic variables for the mixtures. Explicit formulas for these variables are derived for a noninteracting elementary excitation model of the fluid. Using these formulas and others also derived from quantum statistical mechanics, another equivalent expression for the Lagrangian is generated.

A derivative of the brain metabolite lanthionine ketimine improves cognition and diminishes pathology in the 3 × Tg-AD mouse model of Alzheimer disease.

PubMed

Hensley, Kenneth; Gabbita, S Prasad; Venkova, Kalina; Hristov, Alexandar; Johnson, Ming F; Eslami, Pirooz; Harris-White, Marni E

2013-10-01

Lanthionine ketimine ([LK] 3,4-dihydro-2H-1,4-thiazine-3,5-dicarboxylic acid) is the archetype for a family of naturally occurring brain sulfur amino acid metabolites, the physiologic function of which is unknown. Lanthionine ketimine and its synthetic derivatives have recently demonstrated neurotrophic, neuroprotective, and antineuroinflammatory properties in vitro through a proposed mechanism involving the microtubule-associated protein collapsin response mediator protein 2. Therefore, studies were undertaken to test the effects of a bioavailable LK ester in the 3 × Tg-AD mouse model of Alzheimer disease. Lanthionine ketimine ester treatment substantially diminished cognitive decline and brain amyloid-β (Aβ) peptide deposition and phospho-Tau accumulation in 3 × Tg-AD mice and also reduced the density of Iba1-positive microglia. Furthermore, LK ester treatment altered collapsin response mediator protein 2 phosphorylation. These findings suggest that LK may not be a metabolic waste but rather a purposeful neurochemical, the synthetic derivatives of which constitute a new class of experimental therapeutics for Alzheimer disease and related entities.

Rapid discrimination of pork in Halal and non-Halal Chinese ham sausages by Fourier transform infrared (FTIR) spectroscopy and chemometrics.

PubMed

Xu, L; Cai, C B; Cui, H F; Ye, Z H; Yu, X P

2012-12-01

Rapid discrimination of pork in Halal and non-Halal Chinese ham sausages was developed by Fourier transform infrared (FTIR) spectrometry combined with chemometrics. Transmittance spectra ranging from 400 to 4000 cm⁻¹ of 73 Halal and 78 non-Halal Chinese ham sausages were measured. Sample preparation involved finely grinding of samples and formation of KBr disks (under 10 MPa for 5 min). The influence of data preprocessing methods including smoothing, taking derivatives and standard normal variate (SNV) on partial least squares discriminant analysis (PLSDA) and least squares support vector machine (LS-SVM) was investigated. The results indicate removal of spectral background and baseline plays an important role in discrimination. Taking derivatives, SNV can improve classification accuracy and reduce the complexity of PLSDA. Possibly due to the loss of detailed high-frequency spectral information, smoothing degrades the model performance. For the best models, the sensitivity and specificity was 0.913 and 0.929 for PLSDA with SNV spectra, 0.957 and 0.929 for LS-SVM with second derivative spectra, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors.

PubMed

de Oliveira Lopes, Raquel; Romeiro, Nelilma Correia; de Lima, Cleverton Kleiton F; Louback da Silva, Leandro; de Miranda, Ana Luisa Palhares; Nascimento, Paulo Gustavo B D; Cunha, Fernando Q; Barreiro, Eliezer J; Lima, Lídia Moreira

2012-08-01

p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-α production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Latitudinal distributions of particulate carbon export across the North Western Atlantic Ocean

NASA Astrophysics Data System (ADS)

Puigcorbé, Viena; Roca-Martí, Montserrat; Masqué, Pere; Benitez-Nelson, Claudia; Rutgers van der Loeff, Michiel; Bracher, Astrid; Moreau, Sebastien

2017-11-01

234Th-derived carbon export fluxes were measured in the Atlantic Ocean under the GEOTRACES framework to evaluate basin-scale export variability. Here, we present the results from the northern half of the GA02 transect, spanning from the equator to 64°N. As a result of limited site-specific C/234Th ratio measurements, we further combined our data with previous work to develop a basin wide C/234Th ratio depth curve. While the magnitude of organic carbon fluxes varied depending on the C/234Th ratio used, latitudinal trends were similar, with sizeable and variable organic carbon export fluxes occurring at high latitudes and low to negligible fluxes occurring in oligotrophic waters. Our results agree with previous studies, except at the boundaries between domains, where fluxes were relatively enhanced. Three different models were used to obtain satellite-derived net primary production (NPP). In general, NPP estimates had similar trends along the transect, but there were significant differences in the absolute magnitude depending on the model used. Nevertheless, organic carbon export efficiencies were generally < 25%, with the exception of a few stations located in the transition area between the riverine and the oligotrophic domains and between the oligotrophic and the temperate domains. Satellite-derived organic carbon export models from Dunne et al. (2005) (D05), Laws et al. (2011) (L11) and Henson et al. (2011) (H11) were also compared to our 234Th-derived carbon exports fluxes. D05 and L11 provided estimates closest to values obtained with the 234Th approach (within a 3-fold difference), but with no clear trends. The H11 model, on the other hand, consistently provided lower export estimates. The large increase in export data in the Atlantic Ocean derived from the GEOTRACES Program, combined with satellite observations and modeling efforts continue to improve the estimates of carbon export in this ocean basin and therefore reduce uncertainty in the global carbon budget. However, our results also suggest that tuning export models and including biological parameters at a regional scale is necessary for improving satellite-modeling efforts and providing export estimates that are more representative of in situ observations.

Constitutive law for seismicity rate based on rate and state friction: Dieterich 1994 revisited.

NASA Astrophysics Data System (ADS)

Heimisson, E. R.; Segall, P.

2017-12-01

Dieterich [1994] derived a constitutive law for seismicity rate based on rate and state friction, which has been applied widely to aftershocks, earthquake triggering, and induced seismicity in various geological settings. Here, this influential work is revisited, and re-derived in a more straightforward manner. By virtue of this new derivation the model is generalized to include changes in effective normal stress associated with background seismicity. Furthermore, the general case when seismicity rate is not constant under constant stressing rate is formulated. The new derivation provides directly practical integral expressions for the cumulative number of events and rate of seismicity for arbitrary stressing history. Arguably, the most prominent limitation of Dieterich's 1994 theory is the assumption that seismic sources do not interact. Here we derive a constitutive relationship that considers source interactions between sub-volumes of the crust, where the stress in each sub-volume is assumed constant. Interactions are considered both under constant stressing rate conditions and for arbitrary stressing history. This theory can be used to model seismicity rate due to stress changes or to estimate stress changes using observed seismicity from triggered earthquake swarms where earthquake interactions and magnitudes are take into account. We identify special conditions under which influence of interactions cancel and the predictions reduces to those of Dieterich 1994. This remarkable result may explain the apparent success of the model when applied to observations of triggered seismicity. This approach has application to understanding and modeling induced and triggered seismicity, and the quantitative interpretation of geodetic and seismic data. It enables simultaneous modeling of geodetic and seismic data in a self-consistent framework. To date physics-based modeling of seismicity with or without geodetic data has been found to give insight into various processes related to aftershocks, VT and injection-induced seismicity. However, the role of various processes such as earthquake interactions and magnitudes and effective normal stress has been unclear. The new theory presented resolves some of the pertinent issues raised in the literature with application of the Dieterich 1994 model.

Uncertainty vs. Information (Invited)

NASA Astrophysics Data System (ADS)

Nearing, Grey

2017-04-01

Information theory is the branch of logic that describes how rational epistemic states evolve in the presence of empirical data (Knuth, 2005), and any logic of science is incomplete without such a theory. Developing a formal philosophy of science that recognizes this fact results in essentially trivial solutions to several longstanding problems are generally considered intractable, including: • Alleviating the need for any likelihood function or error model. • Derivation of purely logical falsification criteria for hypothesis testing. • Specification of a general quantitative method for process-level model diagnostics. More generally, I make the following arguments: 1. Model evaluation should not proceed by quantifying and/or reducing error or uncertainty, and instead should be approached as a problem of ensuring that our models contain as much information as our experimental data. I propose that the latter is the only question a scientist actually has the ability to ask. 2. Instead of building geophysical models as solutions to differential equations that represent conservation laws, we should build models as maximum entropy distributions constrained by conservation symmetries. This will allow us to derive predictive probabilities directly from first principles. Knuth, K. H. (2005) 'Lattice duality: The origin of probability and entropy', Neurocomputing, 67, pp. 245-274.

Derivation of rigorous conditions for high cell-type diversity by algebraic approach.

PubMed

Yoshida, Hiroshi; Anai, Hirokazu; Horimoto, Katsuhisa

2007-01-01

The development of a multicellular organism is a dynamic process. Starting with one or a few cells, the organism develops into different types of cells with distinct functions. We have constructed a simple model by considering the cell number increase and the cell-type order conservation, and have assessed conditions for cell-type diversity. This model is based on a stochastic Lindenmayer system with cell-to-cell interactions for three types of cells. In the present model, we have successfully derived complex but rigorous algebraic relations between the proliferation and transition rates for cell-type diversity by using a symbolic method: quantifier elimination (QE). Surprisingly, three modes for the proliferation and transition rates have emerged for large ratios of the initial cells to the developed cells. The three modes have revealed that the equality between the development rates for the highest cell-type diversity is reduced during the development process of multicellular organisms. Furthermore, we have found that the highest cell-type diversity originates from order conservation.

Prediction of pressure and flow transients in a gaseous bipropellant reaction control rocket engine

NASA Technical Reports Server (NTRS)

Markowsky, J. J.; Mcmanus, H. N., Jr.

1974-01-01

An analytic model is developed to predict pressure and flow transients in a gaseous hydrogen-oxygen reaction control rocket engine feed system. The one-dimensional equations of momentum and continuity are reduced by the method of characteristics from partial derivatives to a set of total derivatives which describe the state properties along the feedline. System components, e.g., valves, manifolds, and injectors are represented by pseudo steady-state relations at discrete junctions in the system. Solutions were effected by a FORTRAN IV program on an IBM 360/65. The results indicate the relative effect of manifold volume, combustion lag time, feedline pressure fluctuations, propellant temperature, and feedline length on the chamber pressure transient. The analytical combustion model is verified by good correlation between predicted and observed chamber pressure transients. The developed model enables a rocket designer to vary the design parameters analytically to obtain stable combustion for a particular mode of operation which is prescribed by mission objectives.

Simplified paraboloid phase model-based phase tracker for demodulation of a single complex fringe.

PubMed

He, A; Deepan, B; Quan, C

2017-09-01

A regularized phase tracker (RPT) is an effective method for demodulation of single closed-fringe patterns. However, lengthy calculation time, specially designed scanning strategy, and sign-ambiguity problems caused by noise and saddle points reduce its effectiveness, especially for demodulating large and complex fringe patterns. In this paper, a simplified paraboloid phase model-based regularized phase tracker (SPRPT) is proposed. In SPRPT, first and second phase derivatives are pre-determined by the density-direction-combined method and discrete higher-order demodulation algorithm, respectively. Hence, cost function is effectively simplified to reduce the computation time significantly. Moreover, pre-determined phase derivatives improve the robustness of the demodulation of closed, complex fringe patterns. Thus, no specifically designed scanning strategy is needed; nevertheless, it is robust against the sign-ambiguity problem. The paraboloid phase model also assures better accuracy and robustness against noise. Both the simulated and experimental fringe patterns (obtained using electronic speckle pattern interferometry) are used to validate the proposed method, and a comparison of the proposed method with existing RPT methods is carried out. The simulation results show that the proposed method has achieved the highest accuracy with less computational time. The experimental result proves the robustness and the accuracy of the proposed method for demodulation of noisy fringe patterns and its feasibility for static and dynamic applications.

Pseudospectral reverse time migration based on wavefield decomposition

NASA Astrophysics Data System (ADS)

Du, Zengli; Liu, Jianjun; Xu, Feng; Li, Yongzhang

2017-05-01

The accuracy of seismic numerical simulations and the effectiveness of imaging conditions are important in reverse time migration studies. Using the pseudospectral method, the precision of the calculated spatial derivative of the seismic wavefield can be improved, increasing the vertical resolution of images. Low-frequency background noise, generated by the zero-lag cross-correlation of mismatched forward-propagated and backward-propagated wavefields at the impedance interfaces, can be eliminated effectively by using the imaging condition based on the wavefield decomposition technique. The computation complexity can be reduced when imaging is performed in the frequency domain. Since the Fourier transformation in the z-axis may be derived directly as one of the intermediate results of the spatial derivative calculation, the computation load of the wavefield decomposition can be reduced, improving the computation efficiency of imaging. Comparison of the results for a pulse response in a constant-velocity medium indicates that, compared with the finite difference method, the peak frequency of the Ricker wavelet can be increased by 10-15 Hz for avoiding spatial numerical dispersion, when the second-order spatial derivative of the seismic wavefield is obtained using the pseudospectral method. The results for the SEG/EAGE and Sigsbee2b models show that the signal-to-noise ratio of the profile and the imaging quality of the boundaries of the salt dome migrated using the pseudospectral method are better than those obtained using the finite difference method.

wFReDoW: A Cloud-Based Web Environment to Handle Molecular Docking Simulations of a Fully Flexible Receptor Model

PubMed Central

De Paris, Renata; Frantz, Fábio A.; Norberto de Souza, Osmar; Ruiz, Duncan D. A.

2013-01-01

Molecular docking simulations of fully flexible protein receptor (FFR) models are coming of age. In our studies, an FFR model is represented by a series of different conformations derived from a molecular dynamic simulation trajectory of the receptor. For each conformation in the FFR model, a docking simulation is executed and analyzed. An important challenge is to perform virtual screening of millions of ligands using an FFR model in a sequential mode since it can become computationally very demanding. In this paper, we propose a cloud-based web environment, called web Flexible Receptor Docking Workflow (wFReDoW), which reduces the CPU time in the molecular docking simulations of FFR models to small molecules. It is based on the new workflow data pattern called self-adaptive multiple instances (P-SaMIs) and on a middleware built on Amazon EC2 instances. P-SaMI reduces the number of molecular docking simulations while the middleware speeds up the docking experiments using a High Performance Computing (HPC) environment on the cloud. The experimental results show a reduction in the total elapsed time of docking experiments and the quality of the new reduced receptor models produced by discarding the nonpromising conformations from an FFR model ruled by the P-SaMI data pattern. PMID:23691504

Genetic improvement in mastitis resistance: comparison of selection criteria from cross-sectional and random regression sire models for somatic cell score.

PubMed

Odegård, J; Klemetsdal, G; Heringstad, B

2005-04-01

Several selection criteria for reducing incidence of mastitis were developed from a random regression sire model for test-day somatic cell score (SCS). For comparison, sire transmitting abilities were also predicted based on a cross-sectional model for lactation mean SCS. Only first-crop daughters were used in genetic evaluation of SCS, and the different selection criteria were compared based on their correlation with incidence of clinical mastitis in second-crop daughters (measured as mean daughter deviations). Selection criteria were predicted based on both complete and reduced first-crop daughter groups (261 or 65 daughters per sire, respectively). For complete daughter groups, predicted transmitting abilities at around 30 d in milk showed the best predictive ability for incidence of clinical mastitis, closely followed by average predicted transmitting abilities over the entire lactation. Both of these criteria were derived from the random regression model. These selection criteria improved accuracy of selection by approximately 2% relative to a cross-sectional model. However, for reduced daughter groups, the cross-sectional model yielded increased predictive ability compared with the selection criteria based on the random regression model. This result may be explained by the cross-sectional model being more robust, i.e., less sensitive to precision of (co)variance components estimates and effects of data structure.

The laboratory domestication of Caenorhabditis elegans.

PubMed

Sterken, Mark G; Snoek, L Basten; Kammenga, Jan E; Andersen, Erik C

2015-05-01

Model organisms are of great importance to our understanding of basic biology and to making advances in biomedical research. However, the influence of laboratory cultivation on these organisms is underappreciated, and especially how that environment can affect research outcomes. Recent experiments led to insights into how the widely used laboratory reference strain of the nematode Caenorhabditis elegans compares with natural strains. Here we describe potential selective pressures that led to the fixation of laboratory-derived alleles for the genes npr-1, glb-5, and nath-10. These alleles influence a large number of traits, resulting in behaviors that affect experimental interpretations. Furthermore, strong phenotypic effects caused by these laboratory-derived alleles hinder the discovery of natural alleles. We highlight strategies to reduce the influence of laboratory-derived alleles and to harness the full power of C. elegans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficient automatic OCR word validation using word partial format derivation and language model

NASA Astrophysics Data System (ADS)

Chen, Siyuan; Misra, Dharitri; Thoma, George R.

2010-01-01

In this paper we present an OCR validation module, implemented for the System for Preservation of Electronic Resources (SPER) developed at the U.S. National Library of Medicine.1 The module detects and corrects suspicious words in the OCR output of scanned textual documents through a procedure of deriving partial formats for each suspicious word, retrieving candidate words by partial-match search from lexicons, and comparing the joint probabilities of N-gram and OCR edit transformation corresponding to the candidates. The partial format derivation, based on OCR error analysis, efficiently and accurately generates candidate words from lexicons represented by ternary search trees. In our test case comprising a historic medico-legal document collection, this OCR validation module yielded the correct words with 87% accuracy and reduced the overall OCR word errors by around 60%.

Pricing and hedging derivative securities with neural networks: Bayesian regularization, early stopping, and bagging.

PubMed

Gençay, R; Qi, M

2001-01-01

We study the effectiveness of cross validation, Bayesian regularization, early stopping, and bagging to mitigate overfitting and improving generalization for pricing and hedging derivative securities with daily S&P 500 index daily call options from January 1988 to December 1993. Our results indicate that Bayesian regularization can generate significantly smaller pricing and delta-hedging errors than the baseline neural-network (NN) model and the Black-Scholes model for some years. While early stopping does not affect the pricing errors, it significantly reduces the hedging error (HE) in four of the six years we investigated. Although computationally most demanding, bagging seems to provide the most accurate pricing and delta hedging. Furthermore, the standard deviation of the MSPE of bagging is far less than that of the baseline model in all six years, and the standard deviation of the average HE of bagging is far less than that of the baseline model in five out of six years. We conclude that they be used at least in cases when no appropriate hints are available.

Reduced and simplified chemical kinetics for air dissociation using Computational Singular Perturbation

NASA Technical Reports Server (NTRS)

Goussis, D. A.; Lam, S. H.; Gnoffo, P. A.

1990-01-01

The Computational Singular Perturbation CSP methods is employed (1) in the modeling of a homogeneous isothermal reacting system and (2) in the numerical simulation of the chemical reactions in a hypersonic flowfield. Reduced and simplified mechanisms are constructed. The solutions obtained on the basis of these approximate mechanisms are shown to be in very good agreement with the exact solution based on the full mechanism. Physically meaningful approximations are derived. It is demonstrated that the deduction of these approximations from CSP is independent of the complexity of the problem and requires no intuition or experience in chemical kinetics.

Cost/benefit trade-offs for reducing the energy consumption of commercial air transportation (RECAT)

NASA Technical Reports Server (NTRS)

Gobetz, F. W.; Dubin, A. P.

1976-01-01

A study has been performed to evaluate the opportunities for reducing the energy requirements of the U.S. domestic air passenger transport system through improved operational techniques, modified in-service aircraft, derivatives of current production models, or new aircraft using either current or advanced technology. Each of the fuel-conserving alternatives has been investigated individually to test its potential for fuel conservation relative to a hypothetical baseline case in which current, in-production aircraft types are assumed to operate, without modification and with current operational techniques, into the future out to the year 2000.

Reduced order modeling of fluid/structure interaction.

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

Barone, Matthew Franklin; Kalashnikova, Irina; Segalman, Daniel Joseph

2009-11-01

This report describes work performed from October 2007 through September 2009 under the Sandia Laboratory Directed Research and Development project titled 'Reduced Order Modeling of Fluid/Structure Interaction.' This project addresses fundamental aspects of techniques for construction of predictive Reduced Order Models (ROMs). A ROM is defined as a model, derived from a sequence of high-fidelity simulations, that preserves the essential physics and predictive capability of the original simulations but at a much lower computational cost. Techniques are developed for construction of provably stable linear Galerkin projection ROMs for compressible fluid flow, including a method for enforcing boundary conditions that preservesmore » numerical stability. A convergence proof and error estimates are given for this class of ROM, and the method is demonstrated on a series of model problems. A reduced order method, based on the method of quadratic components, for solving the von Karman nonlinear plate equations is developed and tested. This method is applied to the problem of nonlinear limit cycle oscillations encountered when the plate interacts with an adjacent supersonic flow. A stability-preserving method for coupling the linear fluid ROM with the structural dynamics model for the elastic plate is constructed and tested. Methods for constructing efficient ROMs for nonlinear fluid equations are developed and tested on a one-dimensional convection-diffusion-reaction equation. These methods are combined with a symmetrization approach to construct a ROM technique for application to the compressible Navier-Stokes equations.« less

Incorporating Land-Use Mapping Uncertainty in Remote Sensing Based Calibration of Land-Use Change Models

NASA Astrophysics Data System (ADS)

Cockx, K.; Van de Voorde, T.; Canters, F.; Poelmans, L.; Uljee, I.; Engelen, G.; de Jong, K.; Karssenberg, D.; van der Kwast, J.

2013-05-01

Building urban growth models typically involves a process of historic calibration based on historic time series of land-use maps, usually obtained from satellite imagery. Both the remote sensing data analysis to infer land use and the subsequent modelling of land-use change are subject to uncertainties, which may have an impact on the accuracy of future land-use predictions. Our research aims to quantify and reduce these uncertainties by means of a particle filter data assimilation approach that incorporates uncertainty in land-use mapping and land-use model parameter assessment into the calibration process. This paper focuses on part of this work, more in particular the modelling of uncertainties associated with the impervious surface cover estimation and urban land-use classification adopted in the land-use mapping approach. Both stages are submitted to a Monte Carlo simulation to assess their relative contribution to and their combined impact on the uncertainty in the derived land-use maps. The approach was applied on the central part of the Flanders region (Belgium), using a time-series of Landsat/SPOT-HRV data covering the years 1987, 1996, 2005 and 2012. Although the most likely land-use map obtained from the simulation is very similar to the original classification, it is shown that the errors related to the impervious surface sub-pixel fraction estimation have a strong impact on the land-use map's uncertainty. Hence, incorporating uncertainty in the land-use change model calibration through particle filter data assimilation is proposed to address the uncertainty observed in the derived land-use maps and to reduce uncertainty in future land-use predictions.

Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.

PubMed

Miller, Martin L; Molinelli, Evan J; Nair, Jayasree S; Sheikh, Tahir; Samy, Rita; Jing, Xiaohong; He, Qin; Korkut, Anil; Crago, Aimee M; Singer, Samuel; Schwartz, Gary K; Sander, Chris

2013-09-24

Dedifferentiated liposarcoma (DDLS) is a rare but aggressive cancer with high recurrence and low response rates to targeted therapies. Increasing treatment efficacy may require combinations of targeted agents that counteract the effects of multiple abnormalities. To identify a possible multicomponent therapy, we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets. We measured the phosphorylation of multiple proteins and cell viability in response to systematic drug combinations and derived computational models of the signaling network. These models predict that the observed synergy in reducing cell viability with CDK4 and IGF1R inhibitors depends on the activity of the AKT pathway. Experiments confirmed that combined inhibition of CDK4 and IGF1R cooperatively suppresses the activation of proteins within the AKT pathway. Consistent with these findings, synergistic reductions in cell viability were also found when combining CDK4 inhibition with inhibition of either AKT or epidermal growth factor receptor (EGFR), another receptor similar to IGF1R that activates AKT. Thus, network models derived from context-specific proteomic measurements of systematically perturbed cancer cells may reveal cancer-specific signaling mechanisms and aid in the design of effective combination therapies.

Drug Synergy Screen and Network Modeling in Dedifferentiated Liposarcoma Identifies CDK4 and IGF1R as Synergistic Drug Targets

PubMed Central

Miller, Martin L.; Molinelli, Evan J.; Nair, Jayasree S.; Sheikh, Tahir; Samy, Rita; Jing, Xiaohong; He, Qin; Korkut, Anil; Crago, Aimee M.; Singer, Samuel; Schwartz, Gary K.; Sander, Chris

2014-01-01

Dedifferentiated liposarcoma (DDLS) is a rare but aggressive cancer with high recurrence and low response rates to targeted therapies. Increasing treatment efficacy may require combinations of targeted agents that counteract the effects of multiple abnormalities. To identify a possible multicomponent therapy, we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets. We measured the phosphorylation of multiple proteins and cell viability in response to systematic drug combinations and derived computational models of the signaling network. These models predict that the observed synergy in reducing cell viability with CDK4 and IGF1R inhibitors depend on activity of the AKT pathway. Experiments confirmed that combined inhibition of CDK4 and IGF1R cooperatively suppresses the activation of proteins within the AKT pathway. Consistent with these findings, synergistic reductions in cell viability were also found when combining CDK4 inhibition with inhibition of either AKT or epidermal growth factor receptor (EGFR), another receptor similar to IGF1R that activates AKT. Thus, network models derived from context-specific proteomic measurements of systematically perturbed cancer cells may reveal cancer-specific signaling mechanisms and aid in the design of effective combination therapies. PMID:24065146

Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

PubMed

Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

2016-05-01

Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.

Oxalobacter formigenes–Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial Cells

PubMed Central

Arvans, Donna; Jung, Yong-Chul; Antonopoulos, Dionysios; Koval, Jason; Granja, Ignacio; Bashir, Mohamed; Karrar, Eltayeb; Roy-Chowdhury, Jayanta; Musch, Mark; Asplin, John; Chang, Eugene

2017-01-01

Hyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O. formigenes culture conditioned medium (CM) on apical 14C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium, O. formigenes CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from Lactobacillus acidophilus did not. Treating the O. formigenes CM with heat or pepsin completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the O. formigenes–derived factors have molecular masses of 10–30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of O. formigenes CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that O. formigenes–derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with O. formigenes CM reflects the in vivo retention of biologic activity and the therapeutic potential of these factors. PMID:27738124

A Reduced Model for the Magnetorotational Instability

NASA Astrophysics Data System (ADS)

Jamroz, Ben; Julien, Keith; Knobloch, Edgar

2008-11-01

The magnetorotational instability is investigated within the shearing box approximation in the large Elsasser number regime. In this regime, which is of fundamental importance to astrophysical accretion disk theory, shear is the dominant source of energy, but the instability itself requires the presence of a weaker vertical magnetic field. Dissipative effects are weaker still. However, they are sufficiently large to permit a nonlinear feedback mechanism whereby the turbulent stresses generated by the MRI act on and modify the local background shear in the angular velocity profile. To date this response has been omitted in shearing box simulations and is captured by a reduced pde model derived here from the global MHD fluid equations using multiscale asymptotic perturbation theory. Results from numerical simulations of the reduced pde model indicate a linear phase of exponential growth followed by a nonlinear adjustment to algebraic growth and decay in the fluctuating quantities. Remarkably, the velocity and magnetic field correlations associated with these algebraic growth and decay laws conspire to achieve saturation of the angular momentum transport. The inclusion of subdominant ohmic dissipation arrests the algebraic growth of the fluctuations on a longer, dissipative time scale.

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.

On the effect of the degeneracy among dark energy parameters

NASA Astrophysics Data System (ADS)

Gong, Yungui; Gao, Qing

2014-01-01

The dynamics of scalar fields as dark energy is well approximated by some general relations between the equation of state parameter and the fractional energy density . Based on the approximation, for slowly rolling scalar fields, we derived the analytical expressions of which reduce to the popular Chevallier-Polarski-Linder parametrization with an explicit degeneracy relation between and . The models approximate the dynamics of scalar fields well and help eliminate the degeneracies among , , and . With the explicit degeneracy relations, we test their effects on the constraints of the cosmological parameters. We find that: (1) The analytical relations between and for the two models are consistent with observational data. (2) The degeneracies have little effect on . (3) The error of was reduced about 30 % with the degeneracy relations.

Electromagnetic Launch Vehicle Fairing and Acoustic Blanket Model of Received Power Using FEKO

NASA Technical Reports Server (NTRS)

Trout, Dawn H.; Stanley, James E.; Wahid, Parveen F.

2011-01-01

Evaluating the impact of radio frequency transmission in vehicle fairings is important to electromagnetically sensitive spacecraft. This study employs the multilevel fast multipole method (MLFMM) from a commercial electromagnetic tool, FEKO, to model the fairing electromagnetic environment in the presence of an internal transmitter with improved accuracy over industry applied techniques. This fairing model includes material properties representative of acoustic blanketing commonly used in vehicles. Equivalent surface material models within FEKO were successfully applied to simulate the test case. Finally, a simplified model is presented using Nicholson Ross Weir derived blanket material properties. These properties are implemented with the coated metal option to reduce the model to one layer within the accuracy of the original three layer simulation.

Factors related to reducing free sugar intake among white ethnic adults in the UK: a qualitative study.

PubMed

Rawahi, Said Harith Al; Asimakopoulou, Koula; Newton, Jonathon Timothy

2018-01-01

To determine the barriers and enablers to behavioural change to reduce free sugar intake related to dental caries in a sample of UK adults who identify their ethnicity as White. Qualitative study comprising semi-structured interviews of 27 participants. Interviews were recorded, transcribed and analysed using thematic analysis methods. The Capability-Opportunity-Motivation-Behaviour model (COM-B) and the Theoretical Domains Framework (TDF) were used to guide the derivation of themes. Data saturation occurred at 27 interviews. The COM-B Model and TDF domains captured various factors that may influence the consumption of free sugar. TDF elements which are reflected in the study are: Knowledge; Psychological skills; Memory, attention, and decision processes; Behavioural regulation; Physical skills; Social influence; Environmental context and resources; Social and professional role and identity; Beliefs about capabilities; Beliefs about consequence; Intentions and goals reinforcement; and Emotions. COM-B Model elements which are reflected in the study are: psychological capabilities, physical capabilities, social opportunities, physical opportunities, reflective motivation, and automatic motivation. The COM-B model and TDF framework provided a comprehensive account of the barriers and facilitators of reducing sugar intake among white ethnic groups.

Influence of isoprene chemical mechanism on modelled changes in tropospheric ozone due to climate and land use over the 21st century

NASA Astrophysics Data System (ADS)

Squire, O. J.; Archibald, A. T.; Griffiths, P. T.; Jenkin, M. E.; Smith, D.; Pyle, J. A.

2015-05-01

Isoprene is a~precursor to tropospheric ozone, a key pollutant and greenhouse gas. Anthropogenic activity over the coming century is likely to cause large changes in atmospheric CO2 levels, climate and land use, all of which will alter the global vegetation distribution leading to changes in isoprene emissions. Previous studies have used global chemistry-climate models to assess how possible changes in climate and land use could affect isoprene emissions and hence tropospheric ozone. The chemistry of isoprene oxidation, which can alter the concentration of ozone, is highly complex, therefore it must be parameterised in these models. In this work, we compare the effect of four different reduced isoprene chemical mechanisms, all currently used in Earth system models, on tropospheric ozone. Using a box model we compare ozone in these reduced schemes to that in a more explicit scheme (the Master Chemical Mechanism) over a range of NOx and isoprene emissions, through the use of O3 isopleths. We find that there is some variability, especially at high isoprene emissions, caused by differences in isoprene-derived NOx reservoir species. A global model is then used to examine how the different reduced schemes respond to potential future changes in climate, isoprene emissions, anthropogenic emissions and land use change. We find that, particularly in isoprene-rich regions, the response of the schemes varies considerably. The wide-ranging response is due to differences in the model descriptions of the peroxy radical chemistry, particularly their relative rates of reaction towards NO, leading to ozone formation, or HO2, leading to termination. Also important is the yield of isoprene nitrates and peroxyacyl nitrate precursors from isoprene oxidation. Those schemes that produce less of these NOx reservoir species, tend to produce more ozone locally and less away from the source region. We also note changes in other key oxidants such as NO3 and OH (due to the inclusion of additional isoprene-derived HOx recycling pathways). These have implications for secondary organic aerosol formation, as does the inclusion of an epoxide formation pathway in one of the mechanisms. By combining the emissions and O3 data from all of the global model integrations, we are able to construct isopleth plots comparable to those from the box model analysis. We find that the global and box model isopleths show good qualitative agreement, suggesting that comparing chemical mechanisms with a box model in this framework is a useful tool for assessing mechanistic performance in complex global models. We conclude that as the choice of reduced isoprene mechanism may alter both the magnitude and sign of the ozone response, how isoprene chemistry is parameterised in perturbation experiments such as these is a crucially important consideration. More measurements and laboratory studies are needed to validate these reduced mechanisms especially under high-volatile-organic-compound, low-NOx conditions.

Carotenoids in Adipose Tissue Biology and Obesity.

PubMed

Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

2016-01-01

Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition.

On Flexible Tubes Conveying Fluid: Geometric Nonlinear Theory, Stability and Dynamics

NASA Astrophysics Data System (ADS)

Gay-Balmaz, François; Putkaradze, Vakhtang

2015-08-01

We derive a fully three-dimensional, geometrically exact theory for flexible tubes conveying fluid. The theory also incorporates the change of the cross section available to the fluid motion during the dynamics. Our approach is based on the symmetry-reduced, exact geometric description for elastic rods, coupled with the fluid transport and subject to the volume conservation constraint for the fluid. We first derive the equations of motion directly, by using an Euler-Poincaré variational principle. We then justify this derivation with a more general theory elucidating the interesting mathematical concepts appearing in this problem, such as partial left (elastic) and right (fluid) invariance of the system, with the added holonomic constraint (volume). We analyze the fully nonlinear behavior of the model when the axis of the tube remains straight. We then proceed to the linear stability analysis and show that our theory introduces important corrections to previously derived results, both in the consistency at all wavelength and in the effects arising from the dynamical change of the cross section. Finally, we derive and analyze several analytical, fully nonlinear solutions of traveling wave type in two dimensions.

A Bayesian model averaging method for the derivation of reservoir operating rules

NASA Astrophysics Data System (ADS)

Zhang, Jingwen; Liu, Pan; Wang, Hao; Lei, Xiaohui; Zhou, Yanlai

2015-09-01

Because the intrinsic dynamics among optimal decision making, inflow processes and reservoir characteristics are complex, functional forms of reservoir operating rules are always determined subjectively. As a result, the uncertainty of selecting form and/or model involved in reservoir operating rules must be analyzed and evaluated. In this study, we analyze the uncertainty of reservoir operating rules using the Bayesian model averaging (BMA) model. Three popular operating rules, namely piecewise linear regression, surface fitting and a least-squares support vector machine, are established based on the optimal deterministic reservoir operation. These individual models provide three-member decisions for the BMA combination, enabling the 90% release interval to be estimated by the Markov Chain Monte Carlo simulation. A case study of China's the Baise reservoir shows that: (1) the optimal deterministic reservoir operation, superior to any reservoir operating rules, is used as the samples to derive the rules; (2) the least-squares support vector machine model is more effective than both piecewise linear regression and surface fitting; (3) BMA outperforms any individual model of operating rules based on the optimal trajectories. It is revealed that the proposed model can reduce the uncertainty of operating rules, which is of great potential benefit in evaluating the confidence interval of decisions.

Probing RNA tertiary structure: interhelical crosslinking of the hammerhead ribozyme.

PubMed Central

Sigurdsson, S T; Tuschl, T; Eckstein, F

1995-01-01

Distinct structural models for the hammerhead ribozyme derived from single-crystal X-ray diffraction and fluorescence resonance energy transfer (FRET) measurements have been compared. Both models predict the same overall geometry, a wishbone shape with helices II and III nearly colinear and helix I positioned close to helix II. However, the relative orientations of helices I and II are different. To establish whether one of the models represents a kinetically active structure, a new crosslinking procedure was developed in which helices I and II of hammerhead ribozymes were disulfide-crosslinked via the 2' positions of specific sugar residues. Crosslinking residues on helices I and II that are close according to the X-ray structure did not appreciably reduce the catalytic efficiency. In contrast, crosslinking residues closely situated according to the FRET model dramatically reduced the cleavage rate by at least three orders of magnitude. These correlations between catalytic efficiencies and spatial proximities are consistent with the X-ray structure. PMID:7489517

The uncertainty of crop yield projections is reduced by improved temperature response functions.

PubMed

Wang, Enli; Martre, Pierre; Zhao, Zhigan; Ewert, Frank; Maiorano, Andrea; Rötter, Reimund P; Kimball, Bruce A; Ottman, Michael J; Wall, Gerard W; White, Jeffrey W; Reynolds, Matthew P; Alderman, Phillip D; Aggarwal, Pramod K; Anothai, Jakarat; Basso, Bruno; Biernath, Christian; Cammarano, Davide; Challinor, Andrew J; De Sanctis, Giacomo; Doltra, Jordi; Fereres, Elias; Garcia-Vila, Margarita; Gayler, Sebastian; Hoogenboom, Gerrit; Hunt, Leslie A; Izaurralde, Roberto C; Jabloun, Mohamed; Jones, Curtis D; Kersebaum, Kurt C; Koehler, Ann-Kristin; Liu, Leilei; Müller, Christoph; Naresh Kumar, Soora; Nendel, Claas; O'Leary, Garry; Olesen, Jørgen E; Palosuo, Taru; Priesack, Eckart; Eyshi Rezaei, Ehsan; Ripoche, Dominique; Ruane, Alex C; Semenov, Mikhail A; Shcherbak, Iurii; Stöckle, Claudio; Stratonovitch, Pierre; Streck, Thilo; Supit, Iwan; Tao, Fulu; Thorburn, Peter; Waha, Katharina; Wallach, Daniel; Wang, Zhimin; Wolf, Joost; Zhu, Yan; Asseng, Senthold

2017-07-17

Increasing the accuracy of crop productivity estimates is a key element in planning adaptation strategies to ensure global food security under climate change. Process-based crop models are effective means to project climate impact on crop yield, but have large uncertainty in yield simulations. Here, we show that variations in the mathematical functions currently used to simulate temperature responses of physiological processes in 29 wheat models account for >50% of uncertainty in simulated grain yields for mean growing season temperatures from 14 °C to 33 °C. We derived a set of new temperature response functions that when substituted in four wheat models reduced the error in grain yield simulations across seven global sites with different temperature regimes by 19% to 50% (42% average). We anticipate the improved temperature responses to be a key step to improve modelling of crops under rising temperature and climate change, leading to higher skill of crop yield projections.

The Uncertainty of Crop Yield Projections Is Reduced by Improved Temperature Response Functions

NASA Technical Reports Server (NTRS)

Wang, Enli; Martre, Pierre; Zhao, Zhigan; Ewert, Frank; Maiorano, Andrea; Rotter, Reimund P.; Kimball, Bruce A.; Ottman, Michael J.; White, Jeffrey W.; Reynolds, Matthew P.;

Strong Langmuir Turbulence and Four-Wave Mixing

NASA Astrophysics Data System (ADS)

Glanz, James

1991-02-01

The staircase expansion is a new mathematical technique for deriving reduced, nonlinear-PDE descriptions from the plasma-moment equations. Such descriptions incorporate only the most significant linear and nonlinear terms of more complex systems. The technique is used to derive a set of Dawson-Zakharov or "master" equations, which unify and generalize previous work and show the limitations of models commonly used to describe nonlinear plasma waves. Fundamentally new wave-evolution equations are derived that admit of exact nonlinear solutions (solitary waves). Analytic calculations illustrate the competition between well-known effects of self-focusing, which require coupling to ion motion, and pure-electron nonlinearities, which are shown to be especially important in curved geometries. Also presented is an N -moment hydrodynamic model derived from the Vlasov equation. In this connection, the staircase expansion is shown to remain useful for all values of N >= 3. The relevance of the present work to nonlocally truncated hierarchies, which more accurately model dissipation, is briefly discussed. Finally, the general formalism is applied to the problem of electromagnetic emission from counterpropagating Langmuir pumps. It is found that previous treatments have neglected order-unity effects that increase the emission significantly. Detailed numerical results are presented to support these conclusions. The staircase expansion--so called because of its appearance when written out--should be effective whenever the largest contribution to the nonlinear wave remains "close" to some given frequency. Thus the technique should have application to studies of wake-field acceleration schemes and anomalous damping of plasma waves.

Conditional Depletion of Hippocampal Brain-Derived Neurotrophic Factor Exacerbates Neuropathology in a Mouse Model of Alzheimer’s Disease

PubMed Central

Braun, David J.; Kalinin, Sergey

2017-01-01

Damage occurring to noradrenergic neurons in the locus coeruleus (LC) contributes to the evolution of neuroinflammation and neurodegeneration in a variety of conditions and diseases. One cause of LC damage may be loss of neurotrophic support from LC target regions. We tested this hypothesis by conditional unilateral knockout of brain-derived neurotrophic factor (BDNF) in adult mice. To evaluate the consequences of BDNF loss in the context of neurodegeneration, the mice harbored familial mutations for human amyloid precursor protein and presenilin-1. In these mice, BDNF depletion reduced tyrosine hydroxylase staining, a marker of noradrenergic neurons, in the rostral LC. BDNF depletion also reduced noradrenergic innervation in the hippocampus, the frontal cortex, and molecular layer of the cerebellum, assessed by staining for dopamine beta hydroxylase. BDNF depletion led to an increase in cortical amyloid plaque numbers and size but was without effect on plaque numbers in the striatum, a site with minimal innervation from the LC. Interestingly, cortical Iba1 staining for microglia was reduced by BDNF depletion and was correlated with reduced dopamine beta hydroxylase staining. These data demonstrate that reduction of BDNF levels in an LC target region can cause retrograde damage to LC neurons, leading to exacerbation of neuropathology in distinct LC target areas. Methods to reduce BDNF loss or supplement BDNF levels may be of value to reduce neurodegenerative processes normally limited by LC noradrenergic activities. PMID:28266222

Wave propagation in strongly dispersive superthermal dusty plasma

NASA Astrophysics Data System (ADS)

El-Labany, S. K.; El-Shewy, E. K.; Abd El-Razek, H. N.; El-Rahman, A. A.

2017-04-01

The attributes of acoustic envelope waves in a collisionless dust ion unmagnetized plasmas model composed of cold ions, superthermal electrons and positive-negative dust grains have been studied. Using the derivative expansion technique in a strong dispersive medium, the system model is reduced to a nonlinearly form of Schrodinger equation (NLSE). Rational solution of NLSE in unstable region is responsible for the creation of large shape waves; namely rogue waves. The subjection of instability regions upon electron superthermality (via κ), carrier wave number and dusty grains charge is discussed.

Effect of thermal noise on vesicles and capsules in shear flow.

PubMed

Abreu, David; Seifert, Udo

2012-07-01

We add thermal noise consistently to reduced models of undeformable vesicles and capsules in shear flow and derive analytically the corresponding stochastic equations of motion. We calculate the steady-state probability distribution function and construct the corresponding phase diagrams for the different dynamical regimes. For fluid vesicles, we predict that at small shear rates thermal fluctuations induce a tumbling motion for any viscosity contrast. For elastic capsules, due to thermal mixing, an intermittent regime appears in regions where deterministic models predict only pure tank treading or tumbling.

A history of presatellite investigations of the earth's radiation budget

NASA Technical Reports Server (NTRS)

Hunt, G. E.; Kandel, R.; Mecherikunnel, A. T.

1986-01-01

The history of radiation budget studies from the early twentieth century to the advent of the space age is reviewed. By the beginning of the 1960's, accurate radiative models had been developed capable of estimating the global and zonally averaged components of the radiation budget, though great uncertainty in the derived parameters existed due to inaccuracy of the data describing the physical parameters used in the model, associated with clouds, the solar radiation, and the gaseous atmospheric absorbers. Over the century, the planetary albedo estimates had reduced from 89 to 30 percent.

Recombinant methioninase effectively targets a Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model

PubMed Central

Murakami, Takashi; Li, Shukuan; Han, Qinghong; Tan, Yuying; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Hwang, Ho Kyoung; Miyake, Kentaro; Singh, Arun S.; Nelson, Scott D.; Dry, Sarah M.; Li, Yunfeng; Hiroshima, Yukihiko; Lwin, Thinzar M.; DeLong, Jonathan C.; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C.; Hoffman, Robert M.

2017-01-01

Methionine dependence is due to the overuse of methionine for aberrant transmethylation reactions in cancer. Methionine dependence may be the only general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino-γ-mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant methioninase, or rMETase, has been tested in mouse models of human cancer cell lines. Ewing's sarcoma is recalcitrant disease even though development of multimodal therapy has improved patients'outcome. Here we report efficacy of rMETase against Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model. Eight Ewing's sarcoma PDOX mice were randomized into untreated control group (n = 4) and rMETase treatment group (n = 4). rMETase (100 units) was injected intraperitoneally (i.p.) every 24 hours for 14 consecutive days. All mice were sacrificed on day-15, 24 hours after the last rMETase administration. rMETase effectively reduced tumor growth compared to untreated control. The methionine level both of plasma and supernatants derived from sonicated tumors was lower in the rMETase group. Body weight did not significantly differ at any time points between the 2 groups. The present study is the first demonstrating rMETase efficacy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as Ewing's sarcoma. PMID:28404944

Recombinant methioninase effectively targets a Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model.

PubMed

Murakami, Takashi; Li, Shukuan; Han, Qinghong; Tan, Yuying; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Hwang, Ho Kyoung; Miyake, Kentaro; Singh, Arun S; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; Hiroshima, Yukihiko; Lwin, Thinzar M; DeLong, Jonathan C; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

2017-05-30

Methionine dependence is due to the overuse of methionine for aberrant transmethylation reactions in cancer. Methionine dependence may be the only general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino-γ-mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant methioninase, or rMETase, has been tested in mouse models of human cancer cell lines. Ewing's sarcoma is recalcitrant disease even though development of multimodal therapy has improved patients'outcome. Here we report efficacy of rMETase against Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model. Eight Ewing's sarcoma PDOX mice were randomized into untreated control group (n = 4) and rMETase treatment group (n = 4). rMETase (100 units) was injected intraperitoneally (i.p.) every 24 hours for 14 consecutive days. All mice were sacrificed on day-15, 24 hours after the last rMETase administration. rMETase effectively reduced tumor growth compared to untreated control. The methionine level both of plasma and supernatants derived from sonicated tumors was lower in the rMETase group. Body weight did not significantly differ at any time points between the 2 groups. The present study is the first demonstrating rMETase efficacy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as Ewing's sarcoma.

Olaratumab Exerts Antitumor Activity in Preclinical Models of Pediatric Bone and Soft Tissue Tumors through Inhibition of Platelet-Derived Growth Factor Receptor α.

PubMed

Lowery, Caitlin D; Blosser, Wayne; Dowless, Michele; Knoche, Shelby; Stephens, Jennifer; Li, Huiling; Surguladze, David; Loizos, Nick; Luffer-Atlas, Debra; Oakley, Gerard J; Guo, Qianxu; Iyer, Seema; Rubin, Brian P; Stancato, Louis

2018-02-15

Purpose: Platelet-derived growth factor receptor α (PDGFRα) is implicated in several adult and pediatric malignancies, where activated signaling in tumor cells and/or cells within the microenvironment drive tumorigenesis and disease progression. Olaratumab (LY3012207/IMC-3G3) is a human mAb that exclusively binds to PDGFRα and recently received accelerated FDA approval and conditional EMA approval for treatment of advanced adult sarcoma patients in combination with doxorubicin. In this study, we investigated olaratumab in preclinical models of pediatric bone and soft tissue tumors. Experimental Design: PDGFRα expression was evaluated by qPCR and Western blot analysis. Olaratumab was investigated in in vitro cell proliferation and invasion assays using pediatric osteosarcoma and rhabdoid tumor cell lines. In vivo activity of olaratumab was assessed in preclinical mouse models of pediatric osteosarcoma and malignant rhabdoid tumor. Results: In vitro olaratumab treatment of osteosarcoma and rhabdoid tumor cell lines reduced proliferation and inhibited invasion driven by individual platelet-derived growth factors (PDGFs) or serum. Furthermore, olaratumab delayed primary tumor growth in mouse models of pediatric osteosarcoma and malignant rhabdoid tumor, and this activity was enhanced by combination with either doxorubicin or cisplatin. Conclusions: Overall, these data indicate that olaratumab, alone and in combination with standard of care, blocks the growth of some preclinical PDGFRα-expressing pediatric bone and soft tissue tumor models. Clin Cancer Res; 24(4); 847-57. ©2017 AACR . ©2017 American Association for Cancer Research.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue

NASA Astrophysics Data System (ADS)

Jezernik, Sašo; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Deep-Sea-Derived Butyrolactone I Suppresses Ovalbumin-Induced Anaphylaxis by Regulating Mast Cell Function in a Murine Model.

PubMed

Liu, Qing-Mei; Xie, Chun-Lan; Gao, Yuan-Yuan; Liu, Bo; Lin, Wei-Xiang; Liu, Hong; Cao, Min-Jie; Su, Wen-Jin; Yang, Xian-Wen; Liu, Guang-Ming

2018-06-06

Deep-sea-derived butyrolactone I (BTL-I), which was identified as a type of butanolide, was isolated from Aspergillus sp. Ovalbumin (OVA)-induced BALB/c anaphylaxis was established to explore the antifood allergic activity of BTL-I. As a result, BTL-I was able to alleviate OVA-induced allergy symptoms, reduce the levels of histamine and mouse mast cell proteinases, inhibit OVA-specific IgE, and decrease the population of mast cells in the spleen and mesenteric lymph nodes. BTL-I also significantly suppressed mast-dependent passive cutaneous anaphylaxis. Additionally, the maturation of bone marrow-derived mast cells (BMMCs) declined as BTL-I caused down-regulation of c-KIT receptors. Furthermore, molecular docking analyses revealed that BTL-I interacted with the inhibitory receptor, FcγRIIB. In conclusion, the reduction of mast cell function by deep-sea-derived BTL-I as well as its interactions with the inhibitory receptor, FcγRIIB, may contribute to BTL-I-related protection against food anaphylaxis.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

PubMed

Jezernik, Saso; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Overexpression of MicA induces production of OmpC-enriched outer membrane vesicles that protect against Salmonella challenge.

PubMed

Choi, Hyun-Il; Kim, Moonjeong; Jeon, Jinseong; Han, Jin Kwan; Kim, Kwang-Sun

2017-08-26

Outer membrane vesicles (OMVs) derived from bacteria are promising candidates for subunit vaccines. Stresses that modulate the composition of outer membrane proteins (OMPs) are important for OMV synthesis. Small RNAs (sRNAs) expressed in response to stress regulate OMPs, although the mechanism underlying sRNA-mediated OMV biogenesis and its utility for developing vaccine platforms remains to be elucidated. Here, we characterized the role of a sRNA, MicA, which regulates OmpA, a major OMP involved in both production of OMVs and reactive immunity against Salmonella challenge. A Salmonella strain overexpressing MicA generated more OMVs than a control strain. In addition, OmpC was the major component of MicA-derived OMV proteins. MicA-derived OMVs induced Th1- and Th17-type immune responses in vitro and reduced Salmonella-mediated lethality in a mouse model. Thus, OmpA-regulatory sRNA-derived OMVs may facilitate production of Salmonella-protective vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Anterior Cruciate Ligament-Derived Stem Cells Transduced With BMP2 Accelerate Graft-Bone Integration After ACL Reconstruction.

PubMed

Kawakami, Yohei; Takayama, Koji; Matsumoto, Tomoyuki; Tang, Ying; Wang, Bing; Mifune, Yutaka; Cummins, James H; Warth, Ryan J; Kuroda, Ryosuke; Kurosaka, Masahiro; Fu, Freddie H; Huard, Johnny

2017-03-01

Strong graft-bone integration is a prerequisite for successful graft remodeling after reconstruction of the anterior cruciate ligament (ACL) using soft tissue grafts. Novel strategies to accelerate soft tissue graft-bone integration are needed to reduce the need for bone-tendon-bone graft harvest, reduce patient convalescence, facilitate rehabilitation, and reduce total recovery time after ACL reconstruction. The application of ACL-derived stem cells with enhanced expression of bone morphogenetic protein 2 (BMP2) onto soft tissue grafts in the form of cell sheets will both accelerate and improve the quality of graft-bone integration after ACL reconstruction in a rat model. Controlled laboratory study. ACL-derived CD34+ cells were isolated from remnant human ACL tissues, virally transduced to express BMP2, and embedded within cell sheets. In a rat model of ACL injury, bilateral single-bundle ACL reconstructions were performed, in which cell sheets were wrapped around tendon autografts before reconstruction. Four groups containing a total of 48 rats (96 knees) were established (n = 12 rats; 24 knees per group): CD34+BMP2 (100%), CD34+BMP2 (25%), CD34+ (untransduced), and a control group containing no cells. Six rats from each group were euthanized 2 and 4 weeks after surgery, and each graft was harvested for immunohistochemical and histological analyses. The remaining 6 rats in each group were euthanized at 4 and 8 weeks to evaluate in situ tensile load to failure in each femur-graft-tibia complex. In vitro, BMP2 transduction promoted the osteogenic differentiation of ACL-derived CD34+ cells while retaining their intrinsic multipotent capabilities. Osteoblast densities were greatest in the BMP2 (100%) and BMP2 (25%) groups. Bone tunnels in the CD34+BMP2 (100%) and CD34+BMP2 (25%) groups had the smallest cross-sectional areas according to micro-computed tomography analyses. Graft-bone integration occurred most rapidly in the CD34+BMP2 (25%) group. Tensile load to failure was significantly greater in the groups containing stem cells at 4 and 8 weeks after surgery. Tensile strength was greatest in the CD34+BMP2 (100%) group at 4 weeks, and in the CD34+BMP2 (25%) group at 8 weeks. ACL-derived CD34+ cells transduced with BMP2 accelerated graft-bone integration after ACL reconstruction using soft tissue autografts in a rat model, as evidenced by improved histological appearance and graft-bone interface biology along with tensile load to failure at each time point up to 8 weeks after surgery. A primary disadvantage of using soft tissue grafts for ACL reconstruction is the prolonged time required for bony ingrowth, which delays the initiation of midsubstance graft remodeling. The lack of consistent correlation between the appearance of a "healed" ACL on postoperative magnetic resonance imaging and readiness to return to sport results in athletes being released to sport before the graft is ready to handle high-intensity loading. Therefore, it is desirable to identify strategies that accelerate graft-bone integration, which would reduce the time to biologic fixation, improve the reliability of biologic fixation, allow for accelerated rehabilitation, and potentially reduce the incidence of early graft pullout and late midsubstance failure.

Evapotranspiration estimation using a parameter-parsimonious energy partition model over Amazon basin

NASA Astrophysics Data System (ADS)

Xu, D.; Agee, E.; Wang, J.; Ivanov, V. Y.

2017-12-01

The increased frequency and severity of droughts in the Amazon region have emphasized the potential vulnerability of the rainforests to heat and drought-induced stresses, highlighting the need to reduce the uncertainty in estimates of regional evapotranspiration (ET) and quantify resilience of the forest. Ground-based observations for estimating ET are resource intensive, making methods based on remotely sensed observations an attractive alternative. Several methodologies have been developed to estimate ET from satellite data, but challenges remained in model parameterization and satellite limited coverage reducing their utility for monitoring biodiverse regions. In this work, we apply a novel surface energy partition method (Maximum Entropy Production; MEP) based on Bayesian probability theory and nonequilibrium thermodynamics to derive ET time series using satellite data for Amazon basin. For a large, sparsely monitored region such as the Amazon, this approach has the advantage methods of only using single level measurements of net radiation, temperature, and specific humidity data. Furthermore, it is not sensitive to the uncertainty of the input data and model parameters. In this first application of MEP theory for a tropical forest biome, we assess its performance at various spatiotemporal scales against a diverse field data sets. Specifically, the objective of this work is to test this method using eddy flux data for several locations across the Amazonia at sub-daily, monthly, and annual scales and compare the new estimates with those using traditional methods. Analyses of the derived ET time series will contribute to reducing the current knowledge gap surrounding the much debated response of the Amazon Basin region to droughts and offer a template for monitoring the long-term changes in global hydrologic cycle due to anthropogenic and natural causes.

Nutritional and greenhouse gas impacts of removing animals from US agriculture.

PubMed

White, Robin R; Hall, Mary Beth

2017-11-28

As a major contributor to agricultural greenhouse gas (GHG) emissions, it has been suggested that reducing animal agriculture or consumption of animal-derived foods may reduce GHGs and enhance food security. Because the total removal of animals provides the extreme boundary to potential mitigation options and requires the fewest assumptions to model, the yearly nutritional and GHG impacts of eliminating animals from US agriculture were quantified. Animal-derived foods currently provide energy (24% of total), protein (48%), essential fatty acids (23-100%), and essential amino acids (34-67%) available for human consumption in the United States. The US livestock industry employs 1.6 × 10 6 people and accounts for $31.8 billion in exports. Livestock recycle more than 43.2 × 10 9 kg of human-inedible food and fiber processing byproducts, converting them into human-edible food, pet food, industrial products, and 4 × 10 9 kg of N fertilizer. Although modeled plants-only agriculture produced 23% more food, it met fewer of the US population's requirements for essential nutrients. When nutritional adequacy was evaluated by using least-cost diets produced from foods available, more nutrient deficiencies, a greater excess of energy, and a need to consume a greater amount of food solids were encountered in plants-only diets. In the simulated system with no animals, estimated agricultural GHG decreased (28%), but did not fully counterbalance the animal contribution of GHG (49% in this model). This assessment suggests that removing animals from US agriculture would reduce agricultural GHG emissions, but would also create a food supply incapable of supporting the US population's nutritional requirements. Copyright © 2017 the Author(s). Published by PNAS.

Nutritional and greenhouse gas impacts of removing animals from US agriculture

PubMed Central

White, Robin R.; Hall, Mary Beth

2017-01-01

As a major contributor to agricultural greenhouse gas (GHG) emissions, it has been suggested that reducing animal agriculture or consumption of animal-derived foods may reduce GHGs and enhance food security. Because the total removal of animals provides the extreme boundary to potential mitigation options and requires the fewest assumptions to model, the yearly nutritional and GHG impacts of eliminating animals from US agriculture were quantified. Animal-derived foods currently provide energy (24% of total), protein (48%), essential fatty acids (23–100%), and essential amino acids (34–67%) available for human consumption in the United States. The US livestock industry employs 1.6 × 106 people and accounts for $31.8 billion in exports. Livestock recycle more than 43.2 × 109 kg of human-inedible food and fiber processing byproducts, converting them into human-edible food, pet food, industrial products, and 4 × 109 kg of N fertilizer. Although modeled plants-only agriculture produced 23% more food, it met fewer of the US population’s requirements for essential nutrients. When nutritional adequacy was evaluated by using least-cost diets produced from foods available, more nutrient deficiencies, a greater excess of energy, and a need to consume a greater amount of food solids were encountered in plants-only diets. In the simulated system with no animals, estimated agricultural GHG decreased (28%), but did not fully counterbalance the animal contribution of GHG (49% in this model). This assessment suggests that removing animals from US agriculture would reduce agricultural GHG emissions, but would also create a food supply incapable of supporting the US population’s nutritional requirements. PMID:29133422

Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis

PubMed Central

Fiorucci, S; Orlandi, S; Mencarelli, A; Caliendo, G; Santagada, V; Distrutti, E; Santucci, L; Cirino, G; Wallace, J L

2007-01-01

Background and Purpose: Mesalamine is the first-line therapy for colitis, but it lacks potency and is only effective for mild-to-moderate forms of this disease. Hydrogen sulphide has been shown to be a potent, endogenous anti-inflammatory substance, modulating leukocyte-endothelial adhesion and leukocyte migration. The purpose of this study was to determine if an H2S-releasing derivative of mesalamine (ATB-429) would exhibit increased potency and effectiveness in a mouse model of colitis. Experimental Approach: Colitis was induced in mice with trinitrobenzene sulphonic acid and the effects of ATB-429 and mesalamine were compared in several treatment regimens. The severity of colitis was determined using several indices, including a disease activity score (comprised of scores for diarrhea, weight loss and fecal blood), colonic myeloperoxidase activity and macroscopic/microscopic scoring of tissue injury. Key Results: Irrespective of the treatment regiment, ATB-429 was more effective than mesalamine in reducing the severity of colitis. ATB-429 was particularly effective in reducing granulocyte infiltration into the colonic tissue (by ∼70%), as well as reducing the expression of mRNA for several key proinflammatory cytokines/chemokines (e.g., TNFα, IFNγ). Treatment with ADT-OH, the H2S-releasing moiety of ATB-429, did not affect severity of colitis. Conclusions and Implications: ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H2S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease. PMID:17339831

Transition between inverse and direct energy cascades in multiscale optical turbulence

DOE PAGES

Malkin, V. M.; Fisch, N. J.

2018-03-06

Transition between inverse and direct energy cascades in multiscale optical turbulence. Multiscale turbulence naturally develops and plays an important role in many fluid, gas, and plasma phenomena. Statistical models of multiscale turbulence usually employ Kolmogorov hypotheses of spectral locality of interactions (meaning that interactions primarily occur between pulsations of comparable scales) and scale-invariance of turbulent pulsations. However, optical turbulence described by the nonlinear Schrodinger equation exhibits breaking of both the Kolmogorov locality and scale-invariance. A weaker form of spectral locality that holds for multi-scale optical turbulence enables a derivation of simplified evolution equations that reduce the problem to a singlemore » scale modeling. We present the derivation of these equations for Kerr media with random inhomogeneities. Then, we find the analytical solution that exhibits a transition between inverse and direct energy cascades in optical turbulence.« less

Microscopic Interpretation and Generalization of the Bloch-Torrey Equation for Diffusion Magnetic Resonance

PubMed Central

Seroussi, Inbar; Grebenkov, Denis S.; Pasternak, Ofer; Sochen, Nir

2017-01-01

In order to bridge microscopic molecular motion with macroscopic diffusion MR signal in complex structures, we propose a general stochastic model for molecular motion in a magnetic field. The Fokker-Planck equation of this model governs the probability density function describing the diffusion-magnetization propagator. From the propagator we derive a generalized version of the Bloch-Torrey equation and the relation to the random phase approach. This derivation does not require assumptions such as a spatially constant diffusion coefficient, or ad-hoc selection of a propagator. In particular, the boundary conditions that implicitly incorporate the microstructure into the diffusion MR signal can now be included explicitly through a spatially varying diffusion coefficient. While our generalization is reduced to the conventional Bloch-Torrey equation for piecewise constant diffusion coefficients, it also predicts scenarios in which an additional term to the equation is required to fully describe the MR signal. PMID:28242566

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

Proportional integral derivative, modeling and ways of stabilization for the spark plasma sintering process

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

Manière, Charles; Lee, Geuntak; Olevsky, Eugene A.

The stability of the proportional–integral–derivative (PID) control of temperature in the spark plasma sintering (SPS) process is investigated. The PID regulations of this process are tested for different SPS tooling dimensions, physical parameters conditions, and areas of temperature control. It is shown that the PID regulation quality strongly depends on the heating time lag between the area of heat generation and the area of the temperature control. Tooling temperature rate maps are studied to reveal potential areas for highly efficient PID control. The convergence of the model and experiment indicates that even with non-optimal initial PID coefficients, it is possiblemore » to reduce the temperature regulation inaccuracy to less than 4 K by positioning the temperature control location in highly responsive areas revealed by the finite-element calculations of the temperature spatial distribution.« less

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

PubMed

Annibali, Daniela; Whitfield, Jonathan R; Favuzzi, Emilia; Jauset, Toni; Serrano, Erika; Cuartas, Isabel; Redondo-Campos, Sara; Folch, Gerard; Gonzàlez-Juncà, Alba; Sodir, Nicole M; Massó-Vallés, Daniel; Beaulieu, Marie-Eve; Swigart, Lamorna B; Mc Gee, Margaret M; Somma, Maria Patrizia; Nasi, Sergio; Seoane, Joan; Evan, Gerard I; Soucek, Laura

2014-08-18

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.

Proportional integral derivative, modeling and ways of stabilization for the spark plasma sintering process

DOE PAGES

Manière, Charles; Lee, Geuntak; Olevsky, Eugene A.

2017-04-21

The stability of the proportional–integral–derivative (PID) control of temperature in the spark plasma sintering (SPS) process is investigated. The PID regulations of this process are tested for different SPS tooling dimensions, physical parameters conditions, and areas of temperature control. It is shown that the PID regulation quality strongly depends on the heating time lag between the area of heat generation and the area of the temperature control. Tooling temperature rate maps are studied to reveal potential areas for highly efficient PID control. The convergence of the model and experiment indicates that even with non-optimal initial PID coefficients, it is possiblemore » to reduce the temperature regulation inaccuracy to less than 4 K by positioning the temperature control location in highly responsive areas revealed by the finite-element calculations of the temperature spatial distribution.« less

Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis.

PubMed

Veronesi, F; Giavaresi, G; Maglio, M; Scotto d'Abusco, A; Politi, L; Scandurra, R; Olivotto, E; Grigolo, B; Borzì, R M; Fini, M

2017-04-01

Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by joint structure changes and inflammation, both mediated by the IκB kinase (IKK) signalosome complex. The ability of N-acetyl phenylalanine derivative (NAPA) to increase cartilage matrix components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity, has been observed in vitro. The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM). 26 mice were divided into three groups: (1) DMM surgery without treatment; (2) DMM surgery treated after 2 weeks with one intra-articular injection of NAPA (2.5 mM) and (3) no DMM surgery. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and microhardness of subchondral bone (SB) tests. The injection of NAPA significantly improved cartilage thickness (CT) and reduced Chambers and Mankin modified scores and fibrillation index (FI), with weaker MMP13, ADAMTS5, MMP10 and IKKα staining. The microhardness measurements did not shown statistically significant differences between the different groups. NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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.

Revealing determinants of two-phase dynamics of P53 network under gamma irradiation based on a reduced 2D relaxation oscillator model.

PubMed

Demirkıran, Gökhan; Kalaycı Demir, Güleser; Güzeliş, Cüneyt

2018-02-01

This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator. This oscillator provides a mechanism that leads diverse modes underpinning cell fate, each corresponding to a cell state. To investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on the characteristics of oscillations, they introduce also a delay differential equation version of the 2D oscillator. They observe that the suppression of p53 inhibitors decreases the amplitudes of p53 oscillation, though the suppression increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible targets for cancer therapies considering their impact on the oscillator, supported by biological findings. They model some mutations as critical changes of the phase space characteristics. Possible cancer therapeutic strategies are then proposed for preventing these mutations' effects using the phase space approach.

Estimation of Satellite-Based SO42- and NH4+ Composition of Ambient Fine Particulate Matter Over China Using Chemical Transport Model

NASA Astrophysics Data System (ADS)

Si, Y.; Li, S.; Chen, L.; Yu, C.; Zhu, W.

2018-04-01

Epidemiologic and health impact studies have examined the chemical composition of ambient PM2.5 in China but have been constrained by the paucity of long-term ground measurements. Using the GEOS-Chem chemical transport model and satellite-derived PM2.5 data, sulfate and ammonium levels were estimated over China from 2004 to 2014. A comparison of the satellite-estimated dataset with model simulations based on ground measurements obtained from the literature indicated our results are more accurate. Using satellite-derived PM2.5 data with a spatial resolution of 0.1° × 0.1°, we further presented finer satellite-estimated sulfate and ammonium concentrations in anthropogenic polluted regions, including the NCP (the North China Plain), the SCB (the Sichuan Basin) and the PRD (the Pearl River Delta). Linear regression results obtained on a national scale yielded an r value of 0.62, NMB of -35.9 %, NME of 48.2 %, ARB_50 % of 53.68 % for sulfate and an r value of 0.63, slope of 0.67, and intercept of 5.14 for ammonium. In typical regions, the satellite-derived dataset was significantly robust. Based on the satellite-derived dataset, the spatial-temporal variation of 11-year annual average satellite-derived SO42- and NH4+ concentrations and time series of monthly average concentrations were also investigated. On a national scale, both exhibited a downward trend each year between 2004 and 2014 (SO42-: -0.61 %; NH4+: -0.21 %), large values were mainly concentrated in the NCP and SCB. For regions captured at a finer resolution, the inter-annual variation trends presented a positive trend over the periods 2004-2007 and 2008-2011, followed by a negative trend over the period 2012-2014, and sulfate concentrations varied appreciably. Moreover, the seasonal distributions of the 11-year satellite-derived dataset over China were presented. The distribution of both sulfate and ammonium concentrations exhibited seasonal characteristics, with the seasonal concentrations ranking as follows: winter > summer > autumn > spring. High concentrations of these species were concentrated in the NCP and SCB, originating from coal-fired power plants and agricultural activities, respectively. Efforts to reduce sulfur dioxide (SO2) emissions have yielded remarkable results since the government has adopted stricter control measures in recent years. Moreover, ammonia emissions should be controlled while reducing the concentration of sulfur, nitrogen and particulate matter. This study provides an assessment of the population's exposure to certain chemical components.

Matrix metalloproteinase inhibition reduces contraction by dupuytren fibroblasts.

PubMed

Townley, William A; Cambrey, Alison D; Khaw, Peng T; Grobbelaar, Adriaan O

2008-11-01

Dupuytren's disease is a common fibroproliferative condition of the hand characterized by fibrotic lesions (nodules and cords), leading to disability through progressive digital contracture. Although the etiology of the disease is poorly understood, recent evidence suggests that abnormal matrix metalloproteinase (MMP) activity may play a role in cell-mediated collagen contraction and tissue scarring. The aim of this study was to investigate the efficacy of ilomastat, a broad-spectrum MMP inhibitor, in an in vitro model of Dupuytren fibroblast-mediated contraction. Nodule-derived and cord-derived fibroblasts were isolated from Dupuytren patients; carpal ligament-derived fibroblasts acted as control. Stress-release fibroblast-populated collagen lattices (FPCLs) were used as a model of contraction. FPCLs were allowed to develop mechanical stress (48 hours) during treatment with ilomastat (0-100 micromol/L), released, and allowed to contract over a 48-hour period. Contraction was estimated by measuring lattice area compared with untreated cells or treatment with a control peptide. MMP-1, MMP-2, and MT1-MMP levels were assessed by zymography, Western blotting, and enzyme-linked immunosorbent assay. Nodule-derived fibroblasts contracted lattices (69% +/- 2) to a greater extent than did cord-derived (55% +/- 3) or carpal ligament-derived (55% +/- 1) fibroblasts. Exposure to ilomastat led to significant inhibition of lattice contraction by all fibroblasts, although a reduction in lattice contraction by nodule-derived fibroblasts was most prominent (84% +/- 8). In addition, treatment with ilomastat led to a concomitant suppression of MMP-1 and MMP-2 activity, whereas MT1-MMP activity was found to be upregulated. Our results demonstrate that inhibition of MMP activity results in a reduction in extracellular matrix contraction by Dupuytren fibroblasts and suggest that MMP activity may be a critical target in preventing recurrent contracture caused by this disease.

Assessing statistical differences between parameters estimates in Partial Least Squares path modeling.

PubMed

Rodríguez-Entrena, Macario; Schuberth, Florian; Gelhard, Carsten

2018-01-01

Structural equation modeling using partial least squares (PLS-SEM) has become a main-stream modeling approach in various disciplines. Nevertheless, prior literature still lacks a practical guidance on how to properly test for differences between parameter estimates. Whereas existing techniques such as parametric and non-parametric approaches in PLS multi-group analysis solely allow to assess differences between parameters that are estimated for different subpopulations, the study at hand introduces a technique that allows to also assess whether two parameter estimates that are derived from the same sample are statistically different. To illustrate this advancement to PLS-SEM, we particularly refer to a reduced version of the well-established technology acceptance model.

Distributed Web-Based Expert System for Launch Operations

NASA Technical Reports Server (NTRS)

Bardina, Jorge E.; Thirumalainambi, Rajkumar

2005-01-01

The simulation and modeling of launch operations is based on a representation of the organization of the operations suitable to experiment of the physical, procedural, software, hardware and psychological aspects of space flight operations. The virtual test bed consists of a weather expert system to advice on the effect of weather to the launch operations. It also simulates toxic gas dispersion model, and the risk impact on human health. Since all modeling and simulation is based on the internet, it could reduce the cost of operations of launch and range safety by conducting extensive research before a particular launch. Each model has an independent decision making module to derive the best decision for launch.

Identification of molecular descriptors for design of novel Isoalloxazine derivatives as potential Acetylcholinesterase inhibitors against Alzheimer's disease.

PubMed

Gurung, Arun Bahadur; Aguan, Kripamoy; Mitra, Sivaprasad; Bhattacharjee, Atanu

2017-06-01

In Alzheimer's disease (AD), the level of Acetylcholine (ACh) neurotransmitter is reduced. Since Acetylcholinesterase (AChE) cleaves ACh, inhibitors of AChE are very much sought after for AD treatment. The side effects of current inhibitors necessitate development of newer AChE inhibitors. Isoalloxazine derivatives have proved to be promising (AChE) inhibitors. However, their structure-activity relationship studies have not been reported till date. In the present work, various quantitative structure-activity relationship (QSAR) building methods such as multiple linear regression (MLR), partial least squares ,and principal component regression were employed to derive 3D-QSAR models using steric and electrostatic field descriptors. Statistically significant model was obtained using MLR coupled with stepwise selection method having r 2  = .9405, cross validated r 2 (q 2 ) = .6683, and a high predictability (pred_r 2  = .6206 and standard error, pred_r 2 se = .2491). Steric and electrostatic contribution plot revealed three electrostatic fields E_496, E_386 and E_577 and one steric field S_60 contributing towards biological activity. A ligand-based 3D-pharmacophore model was generated consisting of eight pharmacophore features. Isoalloxazine derivatives were docked against human AChE, which revealed critical residues implicated in hydrogen bonds as well as hydrophobic interactions. The binding modes of docked complexes (AChE_IA1 and AChE_IA14) were validated by molecular dynamics simulation which showed their stable trajectories in terms of root mean square deviation and molecular mechanics/Poisson-Boltzmann surface area binding free energy analysis revealed key residues contributing significantly to overall binding energy. The present study may be useful in the design of more potent Isoalloxazine derivatives as AChE inhibitors.

Model reduction of dynamical systems by proper orthogonal decomposition: Error bounds and comparison of methods using snapshots from the solution and the time derivatives [Proper orthogonal decomposition model reduction of dynamical systems: error bounds and comparison of methods using snapshots from the solution and the time derivatives

DOE PAGES

Kostova-Vassilevska, Tanya; Oxberry, Geoffrey M.

2017-09-17

In this study, we consider two proper orthogonal decomposition (POD) methods for dimension reduction of dynamical systems. The first method (M1) uses only time snapshots of the solution, while the second method (M2) augments the snapshot set with time-derivative snapshots. The goal of the paper is to analyze and compare the approximation errors resulting from the two methods by using error bounds. We derive several new bounds of the error from POD model reduction by each of the two methods. The new error bounds involve a multiplicative factor depending on the time steps between the snapshots. For method M1 themore » factor depends on the second power of the time step, while for method 2 the dependence is on the fourth power of the time step, suggesting that method M2 can be more accurate for small between-snapshot intervals. However, three other factors also affect the size of the error bounds. These include (i) the norm of the second (for M1) and fourth derivatives (M2); (ii) the first neglected singular value and (iii) the spectral properties of the projection of the system’s Jacobian in the reduced space. Because of the interplay of these factors neither method is more accurate than the other in all cases. Finally, we present numerical examples demonstrating that when the number of collected snapshots is small and the first neglected singular value has a value of zero, method M2 results in a better approximation.« less

Model reduction of dynamical systems by proper orthogonal decomposition: Error bounds and comparison of methods using snapshots from the solution and the time derivatives [Proper orthogonal decomposition model reduction of dynamical systems: error bounds and comparison of methods using snapshots from the solution and the time derivatives

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

Kostova-Vassilevska, Tanya; Oxberry, Geoffrey M.

In this study, we consider two proper orthogonal decomposition (POD) methods for dimension reduction of dynamical systems. The first method (M1) uses only time snapshots of the solution, while the second method (M2) augments the snapshot set with time-derivative snapshots. The goal of the paper is to analyze and compare the approximation errors resulting from the two methods by using error bounds. We derive several new bounds of the error from POD model reduction by each of the two methods. The new error bounds involve a multiplicative factor depending on the time steps between the snapshots. For method M1 themore » factor depends on the second power of the time step, while for method 2 the dependence is on the fourth power of the time step, suggesting that method M2 can be more accurate for small between-snapshot intervals. However, three other factors also affect the size of the error bounds. These include (i) the norm of the second (for M1) and fourth derivatives (M2); (ii) the first neglected singular value and (iii) the spectral properties of the projection of the system’s Jacobian in the reduced space. Because of the interplay of these factors neither method is more accurate than the other in all cases. Finally, we present numerical examples demonstrating that when the number of collected snapshots is small and the first neglected singular value has a value of zero, method M2 results in a better approximation.« less

Ischemic lesion volume determination on diffusion weighted images vs. apparent diffusion coefficient maps.

PubMed

Bråtane, Bernt Tore; Bastan, Birgul; Fisher, Marc; Bouley, James; Henninger, Nils

2009-07-07

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride (TTC)-derived infarct volumes. TTC-derived infarct volumes were not significantly different from the ADC and DWI-derived lesion volumes at the last imaging time points except for significantly smaller DWI lesions in the pMCAO model (p=0.02). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived lesions on ADC maps than DWI (p<0.05). Following reperfusion, lesion volumes on the ADC maps significantly reduced but no change was observed on DWI. Visually determined lesion volumes on ADC maps and DWI by both investigators correlated significantly with threshold-derived lesion volumes on ADC maps with the former method demonstrating a stronger correlation. There was also a better interrater agreement for ADC map analysis than for DWI analysis. Ischemic lesion determination by ADC was more accurate in final infarct prediction, rater independent, and provided exclusive information on ischemic lesion reversibility.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

A model for filtered backprojection reconstruction artifacts due to time-varying attenuation values in perfusion C-arm CT.

PubMed

Fieselmann, Andreas; Dennerlein, Frank; Deuerling-Zheng, Yu; Boese, Jan; Fahrig, Rebecca; Hornegger, Joachim

2011-06-21

Filtered backprojection is the basis for many CT reconstruction tasks. It assumes constant attenuation values of the object during the acquisition of the projection data. Reconstruction artifacts can arise if this assumption is violated. For example, contrast flow in perfusion imaging with C-arm CT systems, which have acquisition times of several seconds per C-arm rotation, can cause this violation. In this paper, we derived and validated a novel spatio-temporal model to describe these kinds of artifacts. The model separates the temporal dynamics due to contrast flow from the scan and reconstruction parameters. We introduced derivative-weighted point spread functions to describe the spatial spread of the artifacts. The model allows prediction of reconstruction artifacts for given temporal dynamics of the attenuation values. Furthermore, it can be used to systematically investigate the influence of different reconstruction parameters on the artifacts. We have shown that with optimized redundancy weighting function parameters the spatial spread of the artifacts around a typical arterial vessel can be reduced by about 70%. Finally, an inversion of our model could be used as the basis for novel dynamic reconstruction algorithms that further minimize these artifacts.

Virtual Institute of Microbial Stress and Survival: Deduction of Stress Response Pathways in Metal and Radionuclide Reducing Microorganisms

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

None

2004-04-17

The projects application goals are to: (1) To understand bacterial stress-response to the unique stressors in metal/radionuclide contamination sites; (2) To turn this understanding into a quantitative, data-driven model for exploring policies for natural and biostimulatory bioremediation; (3) To implement proposed policies in the field and compare results to model predictions; and (4) Close the experimental/computation cycle by using discrepancies between models and predictions to drive new measurements and construction of new models. The projects science goals are to: (1) Compare physiological and molecular response of three target microorganisms to environmental perturbation; (2) Deduce the underlying regulatory pathways that controlmore » these responses through analysis of phenotype, functional genomic, and molecular interaction data; (3) Use differences in the cellular responses among the target organisms to understand niche specific adaptations of the stress and metal reduction pathways; (4) From this analysis derive an understanding of the mechanisms of pathway evolution in the environment; and (5) Ultimately, derive dynamical models for the control of these pathways to predict how natural stimulation can optimize growth and metal reduction efficiency at field sites.« less

Mathematical modeling of wastewater-derived biodegradable dissolved organic nitrogen.

PubMed

Simsek, Halis

2016-11-01

Wastewater-derived dissolved organic nitrogen (DON) typically constitutes the majority of total dissolved nitrogen (TDN) discharged to surface waters from advanced wastewater treatment plants (WWTPs). When considering the stringent regulations on nitrogen discharge limits in sensitive receiving waters, DON becomes problematic and needs to be reduced. Biodegradable DON (BDON) is a portion of DON that is biologically degradable by bacteria when the optimum environmental conditions are met. BDON in a two-stage trickling filter WWTP was estimated using artificial intelligence techniques, such as adaptive neuro-fuzzy inference systems, multilayer perceptron, radial basis neural networks (RBNN), and generalized regression neural networks. Nitrite, nitrate, ammonium, TDN, and DON data were used as input neurons. Wastewater samples were collected from four different locations in the plant. Model performances were evaluated using root mean square error, mean absolute error, mean bias error, and coefficient of determination statistics. Modeling results showed that the R(2) values were higher than 0.85 in all four models for all wastewater samples, except only R(2) in the final effluent sample for RBNN modeling was low (0.52). Overall, it was found that all four computing techniques could be employed successfully to predict BDON.

Computational Planning in Facial Surgery.

PubMed

Zachow, Stefan

2015-10-01

This article reflects the research of the last two decades in computational planning for cranio-maxillofacial surgery. Model-guided and computer-assisted surgery planning has tremendously developed due to ever increasing computational capabilities. Simulators for education, planning, and training of surgery are often compared with flight simulators, where maneuvers are also trained to reduce a possible risk of failure. Meanwhile, digital patient models can be derived from medical image data with astonishing accuracy and thus can serve for model surgery to derive a surgical template model that represents the envisaged result. Computerized surgical planning approaches, however, are often still explorative, meaning that a surgeon tries to find a therapeutic concept based on his or her expertise using computational tools that are mimicking real procedures. Future perspectives of an improved computerized planning may be that surgical objectives will be generated algorithmically by employing mathematical modeling, simulation, and optimization techniques. Planning systems thus act as intelligent decision support systems. However, surgeons can still use the existing tools to vary the proposed approach, but they mainly focus on how to transfer objectives into reality. Such a development may result in a paradigm shift for future surgery planning. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[An ADAA model and its analysis method for agronomic traits based on the double-cross mating design].

PubMed

Xu, Z C; Zhu, J

2000-01-01

According to the double-cross mating design and using principles of Cockerham's general genetic model, a genetic model with additive, dominance and epistatic effects (ADAA model) was proposed for the analysis of agronomic traits. Components of genetic effects were derived for different generations. Monte Carlo simulation was conducted for analyzing the ADAA model and its reduced AD model by using different generations. It was indicated that genetic variance components could be estimated without bias by MINQUE(1) method and genetic effects could be predicted effectively by AUP method; at least three generations (including parent, F1 of single cross and F1 of double-cross) were necessary for analyzing the ADAA model and only two generations (including parent and F1 of double-cross) were enough for the reduced AD model. When epistatic effects were taken into account, a new approach for predicting the heterosis of agronomic traits of double-crosses was given on the basis of unbiased prediction of genotypic merits of parents and their crosses. In addition, genotype x environment interaction effects and interaction heterosis due to G x E interaction were discussed briefly.

The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

PubMed

Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

2013-01-01

Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

The TFPI-2 Derived Peptide EDC34 Improves Outcome of Gram-Negative Sepsis

PubMed Central

Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E.; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

2013-01-01

Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections. PMID:24339780

Modeling hippocampal neurogenesis using human pluripotent stem cells.

PubMed

Yu, Diana Xuan; Di Giorgio, Francesco Paolo; Yao, Jun; Marchetto, Maria Carolina; Brennand, Kristen; Wright, Rebecca; Mei, Arianna; McHenry, Lauren; Lisuk, David; Grasmick, Jaeson Michael; Silberman, Pedro; Silberman, Giovanna; Jappelli, Roberto; Gage, Fred H

2014-03-11

The availability of human pluripotent stem cells (hPSCs) offers the opportunity to generate lineage-specific cells to investigate mechanisms of human diseases specific to brain regions. Here, we report a differentiation paradigm for hPSCs that enriches for hippocampal dentate gyrus (DG) granule neurons. This differentiation paradigm recapitulates the expression patterns of key developmental genes during hippocampal neurogenesis, exhibits characteristics of neuronal network maturation, and produces PROX1+ neurons that functionally integrate into the DG. Because hippocampal neurogenesis has been implicated in schizophrenia (SCZD), we applied our protocol to SCZD patient-derived human induced pluripotent stem cells (hiPSCs). We found deficits in the generation of DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of spontaneous neurotransmitter release. Our approach offers important insights into the neurodevelopmental aspects of SCZD and may be a promising tool for drug screening and personalized medicine.

Effect of Porcine Chondrocyte-Derived Extracellular Membrane (CDECM) on Postoperative Wound Healing in an Experimental Rabbit Model of Glaucoma Filtration Surgery.

PubMed

Kim, Jung Lim; Lee, Hye Sook; Lee, Yoonjin; Kang, Mi Seon; Lee, Sang Joon; Yang, Jae Wook

2017-06-01

We investigated whether a chondrocyte-derived extracellular membrane (CDECM) could reduce postoperative scar formation in an experimental rabbit model of glaucoma filtration surgery. Thirty-six male New Zealand white rabbits underwent experimental glaucoma filtration surgeries on the right eye and were randomly divided into the following two treatment groups: the CDECM group was treated with subconjunctival injections of 0.1ml CDECM (25 mg/ml; n = 18 eyes), and the operation (OP) group was treated with subconjunctival injections of 0.1 ml balanced salt solution (n = 18 eyes). The left eyes were used as controls (n = 36 eyes). The effects of the CDECM on the experimental rabbit model were investigated using histopathological, immunochemical analyses and Western blotting analyses of the inflammation, fibrosis and angiogenesis. On the 14th postoperative day, the eyes of the CDECM group displayed reduced vascularity and fibrosis compared with the OP group. The vascular endothelial growth factor (VEGF), CD31 and TNFβ immunostaining were also reduced in the CDECM group. The level of TNFα mRNA was increased in the OP group. On the 28th postoperative day, the eyes of the CDECM group also exhibited reduced vascularity and less inflammation and fibrosis than those of the OP group. The expressions of VEGF, CD31, macrophage, TNFβ and NF-κB p65 were also decreased in the CDECM group. The levels of TNFα mRNA significantly differ, and the level of matrix metallopeptidase 9 (MMP9) was increased in the OP group. To determine the specific upstream pathway that was associated with NF-κB activation due to glaucoma filtration surgery, we measured Akt, PKCs and MAPKs signaling. The phosphorylation of p38 MAPK was increased in the OP group, whereas this expression was decreased by CDECM treatment. CDECM seems to suppress angiogenesis, inflammation and fibrosis, which were related to wound healing in the experimental rabbit model of glaucoma filtration surgery. This effect, resulting from the inhibition of NF-κB expression, may be the blocking of the p38 MAPK signaling pathway.

Certified dual-corrected radiation patterns of phased antenna arrays by offline–online order reduction of finite-element models

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

Sommer, A., E-mail: a.sommer@lte.uni-saarland.de; Farle, O., E-mail: o.farle@lte.uni-saarland.de; Dyczij-Edlinger, R., E-mail: edlinger@lte.uni-saarland.de

2015-10-15

This paper presents a fast numerical method for computing certified far-field patterns of phased antenna arrays over broad frequency bands as well as wide ranges of steering and look angles. The proposed scheme combines finite-element analysis, dual-corrected model-order reduction, and empirical interpolation. To assure the reliability of the results, improved a posteriori error bounds for the radiated power and directive gain are derived. Both the reduced-order model and the error-bounds algorithm feature offline–online decomposition. A real-world example is provided to demonstrate the efficiency and accuracy of the suggested approach.

Discrete-time model reduction in limited frequency ranges

NASA Technical Reports Server (NTRS)

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

1991-01-01

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

Large space structure model reduction and control system design based upon actuator and sensor influence functions

NASA Technical Reports Server (NTRS)

Yam, Y.; Lang, J. H.; Johnson, T. L.; Shih, S.; Staelin, D. H.

1983-01-01

A model reduction procedure based on aggregation with respect to sensor and actuator influences rather than modes is presented for large systems of coupled second-order differential equations. Perturbation expressions which can predict the effects of spillover on both the aggregated and residual states are derived. These expressions lead to the development of control system design constraints which are sufficient to guarantee, to within the validity of the perturbations, that the residual states are not destabilized by control systems designed from the reduced model. A numerical example is provided to illustrate the application of the aggregation and control system design method.

Alternative to Ritt's pseudodivision for finding the input-output equations of multi-output models.

PubMed

Meshkat, Nicolette; Anderson, Chris; DiStefano, Joseph J

2012-09-01

Differential algebra approaches to structural identifiability analysis of a dynamic system model in many instances heavily depend upon Ritt's pseudodivision at an early step in analysis. The pseudodivision algorithm is used to find the characteristic set, of which a subset, the input-output equations, is used for identifiability analysis. A simpler algorithm is proposed for this step, using Gröbner Bases, along with a proof of the method that includes a reduced upper bound on derivative requirements. Efficacy of the new algorithm is illustrated with several biosystem model examples. Copyright © 2012 Elsevier Inc. All rights reserved.

Applications of system identification methods to the prediction of helicopter stability, control and handling characteristics

NASA Technical Reports Server (NTRS)

Padfield, G. D.; Duval, R. K.

1982-01-01

A set of results on rotorcraft system identification is described. Flight measurements collected on an experimental Puma helicopter are reviewed and some notable characteristics highlighted. Following a brief review of previous work in rotorcraft system identification, the results of state estimation and model structure estimation processes applied to the Puma data are presented. The results, which were obtained using NASA developed software, are compared with theoretical predictions of roll, yaw and pitching moment derivatives for a 6 degree of freedom model structure. Anomalies are reported. The theoretical methods used are described. A framework for reduced order modelling is outlined.

Development of an accelerometer-based multivariate model to predict free-living energy expenditure in a large military cohort.

PubMed

Horner, Fleur; Bilzon, James L; Rayson, Mark; Blacker, Sam; Richmond, Victoria; Carter, James; Wright, Anthony; Nevill, Alan

2013-01-01

This study developed a multivariate model to predict free-living energy expenditure (EE) in independent military cohorts. Two hundred and eighty-eight individuals (20.6 ± 3.9 years, 67.9 ± 12.0 kg, 1.71 ± 0.10 m) from 10 cohorts wore accelerometers during observation periods of 7 or 10 days. Accelerometer counts (PAC) were recorded at 1-minute epochs. Total energy expenditure (TEE) and physical activity energy expenditure (PAEE) were derived using the doubly labelled water technique. Data were reduced to n = 155 based on wear-time. Associations between PAC and EE were assessed using allometric modelling. Models were derived using multiple log-linear regression analysis and gender differences assessed using analysis of covariance. In all models PAC, height and body mass were related to TEE (P < 0.01). For models predicting TEE (r (2) = 0.65, SE = 462 kcal · d(-1) (13.0%)), PAC explained 4% of the variance. For models predicting PAEE (r (2) = 0.41, SE = 490 kcal · d(-1) (32.0%)), PAC accounted for 6% of the variance. Accelerometry increases the accuracy of EE estimation in military populations. However, the unique nature of military life means accurate prediction of individual free-living EE is highly dependent on anthropometric measurements.

Probabilistic models for reactive behaviour in heterogeneous condensed phase media

NASA Astrophysics Data System (ADS)

Baer, M. R.; Gartling, D. K.; DesJardin, P. E.

2012-02-01

This work presents statistically-based models to describe reactive behaviour in heterogeneous energetic materials. Mesoscale effects are incorporated in continuum-level reactive flow descriptions using probability density functions (pdfs) that are associated with thermodynamic and mechanical states. A generalised approach is presented that includes multimaterial behaviour by treating the volume fraction as a random kinematic variable. Model simplifications are then sought to reduce the complexity of the description without compromising the statistical approach. Reactive behaviour is first considered for non-deformable media having a random temperature field as an initial state. A pdf transport relationship is derived and an approximate moment approach is incorporated in finite element analysis to model an example application whereby a heated fragment impacts a reactive heterogeneous material which leads to a delayed cook-off event. Modelling is then extended to include deformation effects associated with shock loading of a heterogeneous medium whereby random variables of strain, strain-rate and temperature are considered. A demonstrative mesoscale simulation of a non-ideal explosive is discussed that illustrates the joint statistical nature of the strain and temperature fields during shock loading to motivate the probabilistic approach. This modelling is derived in a Lagrangian framework that can be incorporated in continuum-level shock physics analysis. Future work will consider particle-based methods for a numerical implementation of this modelling approach.

Experimental and Modeling Studies of the Combustion Characteristics of Conventional and Alternative Jet Fuels. Final Report

NASA Technical Reports Server (NTRS)

Meeks, Ellen; Naik, Chitral V.; Puduppakkam, Karthik V.; Modak, Abhijit; Egolfopoulos, Fokion N.; Tsotsis, Theo; Westbrook, Charles K.

2011-01-01

The objectives of this project have been to develop a comprehensive set of fundamental data regarding the combustion behavior of jet fuels and appropriately associated model fuels. Based on the fundamental study results, an auxiliary objective was to identify differentiating characteristics of molecular fuel components that can be used to explain different fuel behavior and that may ultimately be used in the planning and design of optimal fuel-production processes. The fuels studied in this project were Fischer-Tropsch (F-T) fuels and biomass-derived jet fuels that meet certain specifications of currently used jet propulsion applications. Prior to this project, there were no systematic experimental flame data available for such fuels. One of the key goals has been to generate such data, and to use this data in developing and verifying effective kinetic models. The models have then been reduced through automated means to enable multidimensional simulation of the combustion characteristics of such fuels in real combustors. Such reliable kinetic models, validated against fundamental data derived from laminar flames using idealized flow models, are key to the development and design of optimal combustors and fuels. The models provide direct information about the relative contribution of different molecular constituents to the fuel performance and can be used to assess both combustion and emissions characteristics.

Characterisation of J(O1D) at Cape Grim 2000-2005

NASA Astrophysics Data System (ADS)

Wilson, S. R.

2014-07-01

Estimates of the rate of production of excited oxygen atoms due to the photolysis of ozone J(O1D) have been derived from radiation measurements carried out at Cape Grim, Tasmania (40.6° S, 144.7° E). These estimates agree well with measurements made during SOAPEX-II and with model estimates of clear sky photolysis rates. Observations spanning 2000-2005 have been used to quantify the impact of season, cloud and ozone column amount. The annual cycle of J(O1D) has been investigated via monthly means. These means show an inter-annual variation (monthly standard deviation) of 9%, but in midsummer and midwinter this reduces to 3-4%. Factors dependent upon solar zenith angle and satellite derived total ozone column explain 87% of the observed signal variation of the individual measurements. The impact of total column ozone, expressed as a Radiation Amplification Factor (RAF), is found to be ~1.45, in agreement with model estimates. This ozone dependence explains 20% of the variation observed at medium solar zenith angles (30-50°). The impact of clouds results in a median reduction of 14% in J(O1D) for the same solar zenith angle range. At all solar zenith angles less than 50° approximately 10% of measurements show enhanced J(O1D) due to cloud scattering and this fraction climbs to 25% at higher solar angles. Including estimates of cloudiness derived from Long Wave Radiation measurements resulted in a statistically significant fit to observations but the quality of the fit did not increase significantly as measured by the reduced R2.

Back-stepping active disturbance rejection control design for integrated missile guidance and control system via reduced-order ESO.

PubMed

Xingling, Shao; Honglun, Wang

2015-07-01

This paper proposes a novel composite integrated guidance and control (IGC) law for missile intercepting against unknown maneuvering target with multiple uncertainties and control constraint. First, by using back-stepping technique, the proposed IGC law design is separated into guidance loop and control loop. The unknown target maneuvers and variations of aerodynamics parameters in guidance and control loop are viewed as uncertainties, which are estimated and compensated by designed model-assisted reduced-order extended state observer (ESO). Second, based on the principle of active disturbance rejection control (ADRC), enhanced feedback linearization (FL) based control law is implemented for the IGC model using the estimates generated by reduced-order ESO. In addition, performance analysis and comparisons between ESO and reduced-order ESO are examined. Nonlinear tracking differentiator is employed to construct the derivative of virtual control command in the control loop. Third, the closed-loop stability for the considered system is established. Finally, the effectiveness of the proposed IGC law in enhanced interception performance such as smooth interception course, improved robustness against multiple uncertainties as well as reduced control consumption during initial phase are demonstrated through simulations. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Personalized drug discovery: HCA approach optimized for rare diseases at Tel Aviv University.

PubMed

Solmesky, Leonardo J; Weil, Miguel

2014-03-01

The Cell screening facility for personalized medicine (CSFPM) at Tel Aviv University in Israel is devoted to screening small molecules libraries for finding new drugs for rare diseases using human cell based models. The main strategy of the facility is based on smartly reducing the size of the compounds collection in similarity clusters and at the same time keeping high diversity of pharmacophores. This strategy allows parallel screening of several patient derived - cells in a personalized screening approach. The tested compounds are repositioned drugs derived from collections of phase III and FDA approved small molecules. In addition, the facility carries screenings using other chemical libraries and toxicological characterizations of nanomaterials.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction.

PubMed

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-08-15

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

PubMed Central

Liu, Jing; Wang, Xiaofeng; Liu, Ying; Yang, Na; Xu, Jing; Ren, Xiaotun

2013-01-01

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. PMID:25206528

[Mutations of APOC3 gene, metabolism of triglycerides and reduction of ischemic cardiovascular events].

PubMed

Pirillo, Angela; Catapano, Alberico Luigi

2015-05-01

A direct relationship between high plasma triglyceride (TG) levels and increased risk of cardiovascular disease has been shown in several studies. TG are present in the blood associated with different lipoprotein classes, including hepatically-derived very low density lipoproteins (VLDL) and intestinally-derived chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG, releasing free fatty acids that accumulate in peripheral tissues and remnant lipoproteins, that are then cleared by the liver. LPL activity is finely modulated by several cofactors, including apolipoprotein C-III (apoC-III) which acts as a LPL inhibitor. The key role of apoCIII has been established in several studies: animal models lacking APOC3 gene exhibit reduced plasma TG levels, whereas the overexpression of APOC3 gene led to increased TG levels. In humans, several mutations in APOC3 gene have been identified, leading to lower apoC-III levels and associated with reduced plasma TG levels. Recently, these mutations were found to be associated with a reduced risk for cardiovascular ischemia and coronary heart disease, thus confirming the negative role of apoC-III in TG metabolism and suggesting apoC-III as possible therapeutic target for the management of hypertriglyceridemia.

The strategic use of noise in pragmatic reasoning.

PubMed

Bergen, Leon; Goodman, Noah D

2015-04-01

We combine two recent probabilistic approaches to natural language understanding, exploring the formal pragmatics of communication on a noisy channel. We first extend a model of rational communication between a speaker and listener, to allow for the possibility that messages are corrupted by noise. In this model, common knowledge of a noisy channel leads to the use and correct understanding of sentence fragments. A further extension of the model, which allows the speaker to intentionally reduce the noise rate on a word, is used to model prosodic emphasis. We show that the model derives several well-known changes in meaning associated with prosodic emphasis. Our results show that nominal amounts of actual noise can be leveraged for communicative purposes. Copyright © 2015 Cognitive Science Society, Inc.

Nonlinear model predictive control of a wave energy converter based on differential flatness parameterisation

NASA Astrophysics Data System (ADS)

Li, Guang

2017-01-01

This paper presents a fast constrained optimization approach, which is tailored for nonlinear model predictive control of wave energy converters (WEC). The advantage of this approach relies on its exploitation of the differential flatness of the WEC model. This can reduce the dimension of the resulting nonlinear programming problem (NLP) derived from the continuous constrained optimal control of WEC using pseudospectral method. The alleviation of computational burden using this approach helps to promote an economic implementation of nonlinear model predictive control strategy for WEC control problems. The method is applicable to nonlinear WEC models, nonconvex objective functions and nonlinear constraints, which are commonly encountered in WEC control problems. Numerical simulations demonstrate the efficacy of this approach.

Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis.

PubMed

Qin, Chenjie; Zhang, Huilu; Zhao, Linghao; Zeng, Min; Huang, Weijian; Fu, Gongbo; Zhou, Weiping; Wang, Hongyang; Yan, Hexin

2017-11-29

Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine (DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium (DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine, the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota.

Reduced-Rank Array Modes of the California Current Observing System

NASA Astrophysics Data System (ADS)

Moore, Andrew M.; Arango, Hernan G.; Edwards, Christopher A.

2018-01-01

The information content of the ocean observing array spanning the U.S. west coast is explored using the reduced-rank array modes (RAMs) derived from a four-dimensional variational (4D-Var) data assimilation system covering a period of three decades. RAMs are an extension of the original formulation of array modes introduced by Bennett (1985) but in the reduced model state-space explored by the 4D-Var system, and reveal the extent to which this space is activated by the observations. The projection of the RAMs onto the empirical orthogonal functions (EOFs) of the 4D-Var background error correlation matrix provides a quantitative measure of the effectiveness of the measurements in observing the circulation. It is found that much of the space spanned by the background error covariance is unconstrained by the present ocean observing system. The RAM spectrum is also used to introduce a new criterion to prevent 4D-Var from overfitting the model to the observations.

Optimal Control of Malaria Transmission using Insecticide Treated Nets and Spraying

NASA Astrophysics Data System (ADS)

Athina, D.; Bakhtiar, T.; Jaharuddin

2017-03-01

In this paper, we consider a model of the transmission of malaria which was developed by Silva and Torres equipped with two control variables, namely the use of insecticide treated nets (ITN) to reduce the number of human beings infected and spraying to reduce the number of mosquitoes. Pontryagin maximum principle was applied to derive the differential equation system as optimality conditions which must be satisfied by optimal control variables. The Mangasarian sufficiency theorem shows that Pontryagin maximum principle is necessary as well as sufficient conditions for optimization problem. The 4th-order Runge Kutta method was then performed to solve the differential equations system. The numerical results show that both controls given at once can reduce the number of infected individuals as well as the number of mosquitoes which reduce the impact of malaria transmission.

Spike-train spectra and network response functions for non-linear integrate-and-fire neurons.

PubMed

Richardson, Magnus J E

2008-11-01

Reduced models have long been used as a tool for the analysis of the complex activity taking place in neurons and their coupled networks. Recent advances in experimental and theoretical techniques have further demonstrated the usefulness of this approach. Despite the often gross simplification of the underlying biophysical properties, reduced models can still present significant difficulties in their analysis, with the majority of exact and perturbative results available only for the leaky integrate-and-fire model. Here an elementary numerical scheme is demonstrated which can be used to calculate a number of biologically important properties of the general class of non-linear integrate-and-fire models. Exact results for the first-passage-time density and spike-train spectrum are derived, as well as the linear response properties and emergent states of recurrent networks. Given that the exponential integrate-fire model has recently been shown to agree closely with the experimentally measured response of pyramidal cells, the methodology presented here promises to provide a convenient tool to facilitate the analysis of cortical-network dynamics.

Simulation of branched serial first-order decay of atrazine and metabolites in adapted and nonadapted soils

USGS Publications Warehouse

Webb, R.M.; Sandstrom, M.W.; Krutz, L.J.; Shaner, D.L.

2011-01-01

In the present study a branched serial first-order decay (BSFOD) model is presented and used to derive transformation rates describing the decay of a common herbicide, atrazine, and its metabolites observed in unsaturated soils adapted to previous atrazine applications and in soils with no history of atrazine applications. Calibration of BSFOD models for soils throughout the country can reduce the uncertainty, relative to that of traditional models, in predicting the fate and transport of pesticides and their metabolites and thus support improved agricultural management schemes for reducing threats to the environment. Results from application of the BSFOD model to better understand the degradation of atrazine supports two previously reported conclusions: atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine) and its primary metabolites are less persistent in adapted soils than in nonadapted soils; and hydroxyatrazine was the dominant primary metabolite in most of the soils tested. In addition, a method to simulate BSFOD in a one-dimensional solute-transport unsaturated zone model is also presented. ?? 2011 SETAC.

Simulation of branched serial first-order decay of atrazine and metabolites in adapted and nonadapted soils

USGS Publications Warehouse

Webb, Richard M.; Sandstrom, Mark W.; Jason L. Krutz,; Dale L. Shaner,

2011-01-01

In the present study a branched serial first-order decay (BSFOD) model is presented and used to derive transformation rates describing the decay of a common herbicide, atrazine, and its metabolites observed in unsaturated soils adapted to previous atrazine applications and in soils with no history of atrazine applications. Calibration of BSFOD models for soils throughout the country can reduce the uncertainty, relative to that of traditional models, in predicting the fate and transport of pesticides and their metabolites and thus support improved agricultural management schemes for reducing threats to the environment. Results from application of the BSFOD model to better understand the degradation of atrazine supports two previously reported conclusions: atrazine (6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine) and its primary metabolites are less persistent in adapted soils than in nonadapted soils; and hydroxyatrazine was the dominant primary metabolite in most of the soils tested. In addition, a method to simulate BSFOD in a one-dimensional solute-transport unsaturated zone model is also presented.

Reducing a cortical network to a Potts model yields storage capacity estimates

NASA Astrophysics Data System (ADS)

Naim, Michelangelo; Boboeva, Vezha; Kang, Chol Jun; Treves, Alessandro

2018-04-01

An autoassociative network of Potts units, coupled via tensor connections, has been proposed and analysed as an effective model of an extensive cortical network with distinct short- and long-range synaptic connections, but it has not been clarified in what sense it can be regarded as an effective model. We draw here the correspondence between the two, which indicates the need to introduce a local feedback term in the reduced model, i.e. in the Potts network. An effective model allows the study of phase transitions. As an example, we study the storage capacity of the Potts network with this additional term, the local feedback w, which contributes to drive the activity of the network towards one of the stored patterns. The storage capacity calculation, performed using replica tools, is limited to fully connected networks, for which a Hamiltonian can be defined. To extend the results to the case of intermediate partial connectivity, we also derive the self-consistent signal-to-noise analysis for the Potts network; and finally we discuss the implications for semantic memory in humans.

Handling of subpixel structures in the application of satellite derived irradiance data for solar energy system analysis - a review

NASA Astrophysics Data System (ADS)

Beyer, Hans Georg

2016-04-01

With the increasing availability of satellite derived irradiance information, this type of data set is more and more in use for the design and operation of solar energy systems, most notably PV- and CSP-systems. By this, the need for data measured on-site is reduced. However, due to basic limitations of the satellite-derived data, several requirements put by the intended application cannot be coped with this data type directly. Traw satellite information has to be enhanced in both space and time resolution by additional information to be fully applicable for all aspects of the modelling od solar energy systems. To cope with this problem, several individual and collaborative projects had been performed in the recent years or are ongoing. Approaches are on one hand based on pasting synthesized high-resolution data into the low-resolution original sets. Pre-requite is an appropriate model, validated against real world data. For the case of irradiance data, these models can be extracted either directly from ground measured data sets or from data referring to the cloud situation as gained from the images of sky cameras or from monte -carlo initialized physical models. The current models refer to the spatial structure of the cloud fields. Dynamics are imposed by moving the cloud structures according to a large scale cloud motion vector, either extracted from the dynamics interfered from consecutive satellite images or taken from a meso-scale meteorological model. Dynamic irradiance information is then derived from the cloud field structure and the cloud motion vector. This contribution, which is linked to subtask A - Solar Resource Applications for High Penetration of Solar Technologies - of IEA SHC task 46, will present the different approaches and discuss examples in view of validation, need for auxiliary information and respective general applicability.

Derivation and validation of a two-biomarker panel for diagnosis of ARDS in patients with severe traumatic injuries

PubMed Central

Ware, Lorraine B; Zhao, Zhiguo; Koyama, Tatsuki; Brown, Ryan M; Semler, Matthew W; Janz, David R; May, Addison K; Fremont, Richard D; Matthay, Michael A; Cohen, Mitchell J; Calfee, Carolyn S

2017-01-01

Background Acute respiratory distress syndrome (ARDS) is common after severe traumatic injuries but is underdiagnosed and undertreated. We hypothesized that a panel of plasma biomarkers could be used to diagnose ARDS in severe trauma. To test this hypothesis, we derived and validated a biomarker panel in three independent cohorts and compared the diagnostic performance to clinician recognition of ARDS. Methods Eleven plasma biomarkers of inflammation, lung epithelial and endothelial injury were measured in a derivation cohort of 439 severe trauma patients. ARDS status was analyzed by two-investigator consensus, and cases were required to meet Berlin criteria on intensive care unit (ICU) day 1. Controls were subjects without ARDS during the first 4 days of study enrollment. A multivariable logistic regression model was used to generate probabilities for ARDS. A reduced model with the top two performing markers was then tested in two independent validation cohorts. To assess clinical diagnosis of ARDS, medical records in the derivation cohort were systematically searched for documentation of ARDS diagnosis made by a clinical provider. Results Among 11 biomarkers, the combination of the endothelial injury marker angiopoietin-2 (Ang-2) and the lung epithelial injury marker receptor for advanced glycation endproducts (RAGE) provided good discrimination for ARDS in the derivation cohort (area under the curve (AUC)=0.74 (95% CI 0.67 to 0.80). In the validation cohorts, the AUCs for this model were 0.70 (0.61 to 0.77) and 0.78 (0.71 to 0.84). In contrast, provider assessment demonstrated poor diagnostic accuracy for ARDS, with AUC of 0.55 (0.51 to 0.60). Discussion A two-biomarker panel consisting of Ang-2 and RAGE performed well across multiple patient cohorts and outperformed clinical providers for diagnosing ARDS in severe trauma. Clinical application of this model could improve both diagnosis and treatment of ARDS in patients with severe trauma. Level of evidence Diagnostic study, level II. PMID:29766112

Derivation and validation of a two-biomarker panel for diagnosis of ARDS in patients with severe traumatic injuries.

PubMed

Ware, Lorraine B; Zhao, Zhiguo; Koyama, Tatsuki; Brown, Ryan M; Semler, Matthew W; Janz, David R; May, Addison K; Fremont, Richard D; Matthay, Michael A; Cohen, Mitchell J; Calfee, Carolyn S

2017-01-01

Acute respiratory distress syndrome (ARDS) is common after severe traumatic injuries but is underdiagnosed and undertreated. We hypothesized that a panel of plasma biomarkers could be used to diagnose ARDS in severe trauma. To test this hypothesis, we derived and validated a biomarker panel in three independent cohorts and compared the diagnostic performance to clinician recognition of ARDS. Eleven plasma biomarkers of inflammation, lung epithelial and endothelial injury were measured in a derivation cohort of 439 severe trauma patients. ARDS status was analyzed by two-investigator consensus, and cases were required to meet Berlin criteria on intensive care unit (ICU) day 1. Controls were subjects without ARDS during the first 4 days of study enrollment. A multivariable logistic regression model was used to generate probabilities for ARDS. A reduced model with the top two performing markers was then tested in two independent validation cohorts. To assess clinical diagnosis of ARDS, medical records in the derivation cohort were systematically searched for documentation of ARDS diagnosis made by a clinical provider. Among 11 biomarkers, the combination of the endothelial injury marker angiopoietin-2 (Ang-2) and the lung epithelial injury marker receptor for advanced glycation endproducts (RAGE) provided good discrimination for ARDS in the derivation cohort (area under the curve (AUC)=0.74 (95% CI 0.67 to 0.80). In the validation cohorts, the AUCs for this model were 0.70 (0.61 to 0.77) and 0.78 (0.71 to 0.84). In contrast, provider assessment demonstrated poor diagnostic accuracy for ARDS, with AUC of 0.55 (0.51 to 0.60). A two-biomarker panel consisting of Ang-2 and RAGE performed well across multiple patient cohorts and outperformed clinical providers for diagnosing ARDS in severe trauma. Clinical application of this model could improve both diagnosis and treatment of ARDS in patients with severe trauma. Diagnostic study, level II.

RNA Futile Cycling in Model Persisters Derived from MazF Accumulation (Open Access)

DTIC Science & Technology

2015-11-17

they remained highly metabolically active . We further uncovered a futile cycle driven by continued transcription and MazF-mediated transcript degradation...presence of antibiotics (7), although exceptions have been noted for prod- rugs that require activation (8). Rather, they are rare phenotypic variants...arise from slowly grow- ing or nongrowing bacteria with reduced metabolic activity , where antibiotic targets are inactive and resilient to antibiotic

A hierarchy for modeling high speed propulsion systems

NASA Technical Reports Server (NTRS)

Hartley, Tom T.; Deabreu, Alex

1991-01-01

General research efforts on reduced order propulsion models for control systems design are overviewed. Methods for modeling high speed propulsion systems are discussed including internal flow propulsion systems that do not contain rotating machinery such as inlets, ramjets, and scramjets. The discussion is separated into four sections: (1) computational fluid dynamics model for the entire nonlinear system or high order nonlinear models; (2) high order linearized model derived from fundamental physics; (3) low order linear models obtained from other high order models; and (4) low order nonlinear models. Included are special considerations on any relevant control system designs. The methods discussed are for the quasi-one dimensional Euler equations of gasdynamic flow. The essential nonlinear features represented are large amplitude nonlinear waves, moving normal shocks, hammershocks, subsonic combustion via heat addition, temperature dependent gases, detonation, and thermal choking.

Integration of airborne LiDAR data and voxel-based ray tracing to determine high-resolution solar radiation dynamics at the forest floor: implications for improving stand-scale distributed snowmelt models

NASA Astrophysics Data System (ADS)

Musselman, K. N.; Molotch, N. P.; Margulis, S. A.

2012-12-01

Forest architecture dictates sub-canopy solar irradiance and the resulting patterns can vary seasonally and over short spatial distances. These radiation dynamics are thought to have significant implications on snowmelt processes, regional hydrology, and remote sensing signatures. The variability calls into question many assumptions inherent in traditional canopy models (e.g. Beer's Law) when applied at high resolution (i.e. 1 m). We present a method of estimating solar canopy transmissivity using airborne LiDAR data. The canopy structure is represented in 3-D voxel space (i.e. a cubic discretization of a 3-D domain analogous to a pixel representation of a 2-D space). The solar direct beam canopy transmissivity (DBT) is estimated with a ray-tracing algorithm and the diffuse component is estimated from LiDAR-derived effective LAI. Results from one year at five-minute temporal and 1 m spatial resolutions are presented from Sequoia National Park. Compared to estimates from 28 hemispherical photos, the ray-tracing model estimated daily mean DBT with a 10% average error, while the errors from a Beer's-type DBT estimate exceeded 20%. Compared to the ray-tracing estimates, the Beer's-type transmissivity method was unable to resolve complex spatial patterns resulting from canopy gaps, individual tree canopies and boles, and steep variable terrain. The snowmelt model SNOWPACK was applied at locations of ultrasonic snow depth sensors. Two scenarios were tested; 1) a nominal case where canopy model parameters were obtained from hemispherical photographs, and 2) an explicit scenario where the model was modified to accept LiDAR-derived time-variant DBT. The bulk canopy treatment was generally unable to simulate the sub-canopy snowmelt dynamics observed at the depth sensor locations. The explicit treatment reduced error in the snow disappearance date by one week and both positive and negative melt-season SWE biases were reduced. The results highlight the utility of LiDAR canopy measurements and physically based snowmelt models to simulate spatially distributed stand- and slope-scale snowmelt dynamics at resolutions necessary to capture the inherent underlying variability.iDAR-derived solar direct beam canopy transmissivity computed as the daily average for March 1st and May 1st.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

PubMed

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-12-14

To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

PubMed Central

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-01-01

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. RESULTS We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. PMID:29290652

Second-order singular pertubative theory for gravitational lenses

NASA Astrophysics Data System (ADS)

Alard, C.

2018-03-01

The extension of the singular perturbative approach to the second order is presented in this paper. The general expansion to the second order is derived. The second-order expansion is considered as a small correction to the first-order expansion. Using this approach, it is demonstrated that in practice the second-order expansion is reducible to a first order expansion via a re-definition of the first-order pertubative fields. Even if in usual applications the second-order correction is small the reducibility of the second-order expansion to the first-order expansion indicates a potential degeneracy issue. In general, this degeneracy is hard to break. A useful and simple second-order approximation is the thin source approximation, which offers a direct estimation of the correction. The practical application of the corrections derived in this paper is illustrated by using an elliptical NFW lens model. The second-order pertubative expansion provides a noticeable improvement, even for the simplest case of thin source approximation. To conclude, it is clear that for accurate modelization of gravitational lenses using the perturbative method the second-order perturbative expansion should be considered. In particular, an evaluation of the degeneracy due to the second-order term should be performed, for which the thin source approximation is particularly useful.

Ligand reorganization and activation energies in nonadiabatic electron transfer reactions

NASA Astrophysics Data System (ADS)

Zhu, Jianjun; Wang, Jianji; Stell, George

2006-10-01

The activation energy and ligand reorganization energy for nonadiabatic electron transfer reactions in chemical and biological systems are investigated in this paper. The free energy surfaces and the activation energy are derived exactly in the general case in which the ligand vibration frequencies are not equal. The activation energy is derived by free energy minimization at the transition state. Our formulation leads to the Marcus-Hush [J. Chem. Phys. 24, 979 (1956); 98, 7170 (1994); 28, 962 (1958)] results in the equal-frequency limit and also generalizes the Marcus-Sumi [J. Chem. Phys. 84, 4894 (1986)] model in the context of studying the solvent dynamic effect on electron transfer reactions. It is found that when the ligand vibration frequencies are different, the activation energy derived from the Marcus-Hush formula deviates by 5%-10% from the exact value. If the reduced reorganization energy approximation is introduced in the Marcus-Hush formula, the result is almost exact.

Closed-form Capacity Expressions for the α-μ Fading Channel with SC Diversity under Different Adaptive Transmission Strategies

NASA Astrophysics Data System (ADS)

Mohamed, Refaat; Ismail, Mahmoud H.; Newagy, Fatma; Mourad, Heba M.

2013-03-01

Stemming from the fact that the α-μ fading distribution is one of the very general fading models used in the literature to describe the small scale fading phenomenon, in this paper, closed-form expressions for the Shannon capacity of the α-μ fading channel operating under four main adaptive transmission strategies are derived assuming integer values for μ. These expressions are derived for the case of no diversity as well as for selection combining diversity with independent and identically distributed branches. The obtained expressions reduce to those previously derived in the literature for the Weibull as well as the Rayleigh fading cases, which are both special cases of the α-μ channel. Numerical results are presented for the capacity under the four adaptive transmission strategies and the effect of the fading parameter as well as the number of diversity branches is studied.

Breather management in the derivative nonlinear Schrödinger equation with variable coefficients

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

Zhong, Wei-Ping, E-mail: zhongwp6@126.com; Texas A&M University at Qatar, P.O. Box 23874 Doha; Belić, Milivoj

2015-04-15

We investigate breather solutions of the generalized derivative nonlinear Schrödinger (DNLS) equation with variable coefficients, which is used in the description of femtosecond optical pulses in inhomogeneous media. The solutions are constructed by means of the similarity transformation, which reduces a particular form of the generalized DNLS equation into the standard one, with constant coefficients. Examples of bright and dark breathers of different orders, that ride on finite backgrounds and may be related to rogue waves, are presented. - Highlights: • Exact solutions of a generalized derivative NLS equation are obtained. • The solutions are produced by means of amore » transformation to the usual integrable equation. • The validity of the solutions is verified by comparing them to numerical counterparts. • Stability of the solutions is checked by means of direct simulations. • The model applies to the propagation of ultrashort pulses in optical media.« less

Characterizing the efficacy of cancer therapeutics in patient-derived xenograft models of metastatic breast cancer.

PubMed

Turner, Tia H; Alzubi, Mohammad A; Sohal, Sahib S; Olex, Amy L; Dozmorov, Mikhail G; Harrell, J Chuck

2018-03-12

Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro. Four of the effective drugs-carboplatin, cyclophosphamide, bortezomib, and dacarbazine-were tested in vivo for their efficacy in treating mammary tumors, and metastases generated by intracardiac injection of tumor cells. RNA sequencing showed that global gene expression of PDX cells grown in the mammary gland was similar to those tested in culture. In vitro, carboplatin was cytotoxic to WHIM30 but not WHIM2, whereas bortezomib, dacarbazine, and cyclophosphamide were cytotoxic to both lines. Yet, these drugs were ineffective in treating both primary and metastatic WHIM2 tumors in vivo. Carboplatin and cyclophosphamide were effective in treating WHIM30 mammary tumors and reducing metastatic burden in the brain, liver, and lungs. WHIM2 and WHIM30 metastases showed distinct patterns of cytokeratin and vimentin expression, regardless of treatment, suggesting that different tumor cell subpopulations may preferentially seed in different organs. This study highlights the utility of PDX models for studying the efficacy of therapeutics in reducing metastatic burden in specific organs. The differential treatment responses between two PDX models of the same intrinsic subtype, in both the primary and metastatic setting, recapitulates the challenges faced in treating cancer patients and highlights the need for combination therapies and predictive biomarkers.

Predicting sugar consumption: Application of an integrated dual-process, dual-phase model.

PubMed

Hagger, Martin S; Trost, Nadine; Keech, Jacob J; Chan, Derwin K C; Hamilton, Kyra

2017-09-01

Excess consumption of added dietary sugars is related to multiple metabolic problems and adverse health conditions. Identifying the modifiable social cognitive and motivational constructs that predict sugar consumption is important to inform behavioral interventions aimed at reducing sugar intake. We tested the efficacy of an integrated dual-process, dual-phase model derived from multiple theories to predict sugar consumption. Using a prospective design, university students (N = 90) completed initial measures of the reflective (autonomous and controlled motivation, intentions, attitudes, subjective norm, perceived behavioral control), impulsive (implicit attitudes), volitional (action and coping planning), and behavioral (past sugar consumption) components of the proposed model. Self-reported sugar consumption was measured two weeks later. A structural equation model revealed that intentions, implicit attitudes, and, indirectly, autonomous motivation to reduce sugar consumption had small, significant effects on sugar consumption. Attitudes, subjective norm, and, indirectly, autonomous motivation to reduce sugar consumption predicted intentions. There were no effects of the planning constructs. Model effects were independent of the effects of past sugar consumption. The model identified the relative contribution of reflective and impulsive components in predicting sugar consumption. Given the prominent role of the impulsive component, interventions that assist individuals in managing cues-to-action and behavioral monitoring are likely to be effective in regulating sugar consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunotherapy Added to Antibiotic Treatment Reduces Relapse of Disease in a Mouse Model of Tuberculosis.

PubMed

Mourik, Bas C; Leenen, Pieter J M; de Knegt, Gerjo J; Huizinga, Ruth; van der Eerden, Bram C J; Wang, Jinshan; Krois, Charles R; Napoli, Joseph L; Bakker-Woudenberg, Irma A J M; de Steenwinkel, Jurriaan E M

2017-02-01

Immune-modulating drugs that target myeloid-derived suppressor cells or stimulate natural killer T cells have been shown to reduce mycobacterial loads in tuberculosis (TB). We aimed to determine if a combination of these drugs as adjunct immunotherapy to conventional antibiotic treatment could also increase therapeutic efficacy against TB. In our model of pulmonary TB in mice, we applied treatment with isoniazid, rifampicin, and pyrazinamide for 13 weeks alone or combined with immunotherapy consisting of all-trans retinoic acid, 1,25(OH) 2 -vitamin D3, and α-galactosylceramide. Outcome parameters were mycobacterial load during treatment (therapeutic activity) and 13 weeks after termination of treatment (therapeutic efficacy). Moreover, cellular changes were analyzed using flow cytometry and cytokine expression was assessed at the mRNA and protein levels. Addition of immunotherapy was associated with lower mycobacterial loads after 5 weeks of treatment and significantly reduced relapse of disease after a shortened 13-week treatment course compared with antibiotic treatment alone. This was accompanied by reduced accumulation of immature myeloid cells in the lungs at the end of treatment and increased TNF-α protein levels throughout the treatment period. We demonstrate, in a mouse model of pulmonary TB, that immunotherapy consisting of three clinically approved drugs can improve the therapeutic efficacy of standard antibiotic treatment.

Insights on pumping well interpretation from flow dimension analysis: The learnings of a multi-context field database

NASA Astrophysics Data System (ADS)

Ferroud, Anouck; Chesnaux, Romain; Rafini, Silvain

2018-01-01

The flow dimension parameter n, derived from the Generalized Radial Flow model, is a valuable tool to investigate the actual flow regimes that really occur during a pumping test rather than suppose them to be radial, as postulated by the Theis-derived models. A numerical approach has shown that, when the flow dimension is not radial, using the derivative analysis rather than the conventional Theis and Cooper-Jacob methods helps to estimate much more accurately the hydraulic conductivity of the aquifer. Although n has been analysed in numerous studies including field-based studies, there is a striking lack of knowledge about its occurrence in nature and how it may be related to the hydrogeological setting. This study provides an overview of the occurrence of n in natural aquifers located in various geological contexts including crystalline rock, carbonate rock and granular aquifers. A comprehensive database is compiled from governmental and industrial sources, based on 69 constant-rate pumping tests. By means of a sequential analysis approach, we systematically performed a flow dimension analysis in which straight segments on drawdown-log derivative time series are interpreted as successive, specific and independent flow regimes. To reduce the uncertainties inherent in the identification of n sequences, we used the proprietary SIREN code to execute a dual simultaneous fit on both the drawdown and the drawdown-log derivative signals. Using the stated database, we investigate the frequency with which the radial and non-radial flow regimes occur in fractured rock and granular aquifers, and also provide outcomes that indicate the lack of applicability of Theis-derived models in representing nature. The results also emphasize the complexity of hydraulic signatures observed in nature by pointing out n sequential signals and non-integer n values that are frequently observed in the database.

Image charge models for accurate construction of the electrostatic self-energy of 3D layered nanostructure devices.

PubMed

Barker, John R; Martinez, Antonio

2018-04-04

Efficient analytical image charge models are derived for the full spatial variation of the electrostatic self-energy of electrons in semiconductor nanostructures that arises from dielectric mismatch using semi-classical analysis. The methodology provides a fast, compact and physically transparent computation for advanced device modeling. The underlying semi-classical model for the self-energy has been established and validated during recent years and depends on a slight modification of the macroscopic static dielectric constants for individual homogeneous dielectric regions. The model has been validated for point charges as close as one interatomic spacing to a sharp interface. A brief introduction to image charge methodology is followed by a discussion and demonstration of the traditional failure of the methodology to derive the electrostatic potential at arbitrary distances from a source charge. However, the self-energy involves the local limit of the difference between the electrostatic Green functions for the full dielectric heterostructure and the homogeneous equivalent. It is shown that high convergence may be achieved for the image charge method for this local limit. A simple re-normalisation technique is introduced to reduce the number of image terms to a minimum. A number of progressively complex 3D models are evaluated analytically and compared with high precision numerical computations. Accuracies of 1% are demonstrated. Introducing a simple technique for modeling the transition of the self-energy between disparate dielectric structures we generate an analytical model that describes the self-energy as a function of position within the source, drain and gated channel of a silicon wrap round gate field effect transistor on a scale of a few nanometers cross-section. At such scales the self-energies become large (typically up to ~100 meV) close to the interfaces as well as along the channel. The screening of a gated structure is shown to reduce the self-energy relative to un-gated nanowires.

Image charge models for accurate construction of the electrostatic self-energy of 3D layered nanostructure devices

NASA Astrophysics Data System (ADS)

Barker, John R.; Martinez, Antonio

2018-04-01

Efficient analytical image charge models are derived for the full spatial variation of the electrostatic self-energy of electrons in semiconductor nanostructures that arises from dielectric mismatch using semi-classical analysis. The methodology provides a fast, compact and physically transparent computation for advanced device modeling. The underlying semi-classical model for the self-energy has been established and validated during recent years and depends on a slight modification of the macroscopic static dielectric constants for individual homogeneous dielectric regions. The model has been validated for point charges as close as one interatomic spacing to a sharp interface. A brief introduction to image charge methodology is followed by a discussion and demonstration of the traditional failure of the methodology to derive the electrostatic potential at arbitrary distances from a source charge. However, the self-energy involves the local limit of the difference between the electrostatic Green functions for the full dielectric heterostructure and the homogeneous equivalent. It is shown that high convergence may be achieved for the image charge method for this local limit. A simple re-normalisation technique is introduced to reduce the number of image terms to a minimum. A number of progressively complex 3D models are evaluated analytically and compared with high precision numerical computations. Accuracies of 1% are demonstrated. Introducing a simple technique for modeling the transition of the self-energy between disparate dielectric structures we generate an analytical model that describes the self-energy as a function of position within the source, drain and gated channel of a silicon wrap round gate field effect transistor on a scale of a few nanometers cross-section. At such scales the self-energies become large (typically up to ~100 meV) close to the interfaces as well as along the channel. The screening of a gated structure is shown to reduce the self-energy relative to un-gated nanowires.

In Silico and in Vitro Modeling of Hepatocyte Drug Transport Processes: Importance of ABCC2 Expression Levels in the Disposition of CarboxydichloroflurosceinS⃞

PubMed Central

Howe, Katharine; Gibson, G. Gordon; Coleman, Tanya; Plant, Nick

2009-01-01

The impact of transport proteins in the disposition of chemicals is becoming increasingly evident. Alteration in disposition can cause altered pharmacokinetic and pharmacodynamic parameters, potentially leading to reduced efficacy or overt toxicity. We have developed a quantitative in silico model, based upon literature and experimentally derived data, to model the disposition of carboxydichlorofluroscein (CDF), a substrate for the SLCO1A/B and ABCC subfamilies of transporters. Kinetic parameters generated by the in silico model closely match both literature and experimentally derived kinetic values, allowing this model to be used for the examination of transporter action in primary rat hepatocytes. In particular, we show that the in silico model is suited to the rapid, accurate determination of Ki values, using 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571) as a prototypical pan-ABCC inhibitor. In vitro-derived data are often used to predict in vivo response, and we have examined how differences in protein expression levels between these systems may affect chemical disposition. We show that ABCC2 and ABCC3 are overexpressed in sandwich culture hepatocytes by 3.5- and 2.3-fold, respectively, at the protein level. Correction for this in markedly different disposition of CDF, with the area under the concentration versus time curve and Cmax of intracellular CDF increasing by 365 and 160%, respectively. Finally, using kinetic simulations we show that ABCC2 represents a fragile node within this pathway, with alterations in ABCC2 having the most prominent effects on both the Km and Vmax through the pathway. This is the first demonstration of the utility of modeling approaches to estimate the impact of drug transport processes on chemical disposition. PMID:19022944

An improved car-following model from the perspective of driver’s forecast behavior

NASA Astrophysics Data System (ADS)

Liu, Da-Wei; Shi, Zhong-Ke; Ai, Wen-Huan

In this paper, a new car-following model considering effect of the driver’s forecast behavior is proposed based on the full velocity difference model (FVDM). Using the new model, we investigate the starting process of the vehicle motion under a traffic signal and find that the delay time of vehicle motion is reduced. Then the stability condition of the new model is derived and the modified Korteweg-de Vries (mKdV) equation is constructed to describe the traffic behavior near the critical point. Numerical simulation is compatible with the analysis of theory such as density wave, hysteresis loop, which shows that the new model is reasonable. The results show that considering the effect of driver’s forecast behavior can help to enhance the stability of traffic flow.

Physically based model for extracting dual permeability parameters using non-Newtonian fluids

NASA Astrophysics Data System (ADS)

Abou Najm, M. R.; Basset, C.; Stewart, R. D.; Hauswirth, S.

2017-12-01

Dual permeability models are effective for the assessment of flow and transport in structured soils with two dominant structures. The major challenge to those models remains in the ability to determine appropriate and unique parameters through affordable, simple, and non-destructive methods. This study investigates the use of water and a non-Newtonian fluid in saturated flow experiments to derive physically-based parameters required for improved flow predictions using dual permeability models. We assess the ability of these two fluids to accurately estimate the representative pore sizes in dual-domain soils, by determining the effective pore sizes of macropores and micropores. We developed two sub-models that solve for the effective macropore size assuming either cylindrical (e.g., biological pores) or planar (e.g., shrinkage cracks and fissures) pore geometries, with the micropores assumed to be represented by a single effective radius. Furthermore, the model solves for the percent contribution to flow (wi) corresponding to the representative macro and micro pores. A user-friendly solver was developed to numerically solve the system of equations, given that relevant non-Newtonian viscosity models lack forms conducive to analytical integration. The proposed dual-permeability model is a unique attempt to derive physically based parameters capable of measuring dual hydraulic conductivities, and therefore may be useful in reducing parameter uncertainty and improving hydrologic model predictions.

Simulator for beam-based LHC collimator alignment

NASA Astrophysics Data System (ADS)

Valentino, Gianluca; Aßmann, Ralph; Redaelli, Stefano; Sammut, Nicholas

2014-02-01

In the CERN Large Hadron Collider, collimators need to be set up to form a multistage hierarchy to ensure efficient multiturn cleaning of halo particles. Automatic algorithms were introduced during the first run to reduce the beam time required for beam-based setup, improve the alignment accuracy, and reduce the risk of human errors. Simulating the alignment procedure would allow for off-line tests of alignment policies and algorithms. A simulator was developed based on a diffusion beam model to generate the characteristic beam loss signal spike and decay produced when a collimator jaw touches the beam, which is observed in a beam loss monitor (BLM). Empirical models derived from the available measurement data are used to simulate the steady-state beam loss and crosstalk between multiple BLMs. The simulator design is presented, together with simulation results and comparison to measurement data.

A combining rule calculation of the ground-state van der Waals potentials of the magnesium rare-gas complexes

NASA Astrophysics Data System (ADS)

Saidi, Samah; Alharzali, Nissrin; Berriche, Hamid

2017-04-01

The potential energy curves and spectroscopic constants of the ground-state of the Mg-Rg (Rg = He, Ne, Ar, Kr, and Xe) van der Waals complexes are generated by the Tang-Toennies potential model and a set of derived combining rules. The parameters of the model are calculated from the potentials of the homonuclear magnesium and rare-gas dimers. The predicted spectroscopic constants are comparable to other available theoretical and experimental results, except in the case of Mg-He, we note that there are large differences between various determinations. Moreover, in order to reveal relative differences between species more obviously we calculated the reduced potential of these five systems. The curves are clumped closely together, but at intermediate range the Mg-He reduced potential is clearly very different from the others.

Large Hysteresis effect in Synchronization of Nanocontact Vortex Oscillators by Microwave Fields

PubMed Central

Perna, S.; Lopez-Diaz, L.; d’Aquino, M.; Serpico, C.

2016-01-01

Current-induced vortex oscillations in an extended thin-film with point-contact geometry are considered. The synchronization of these oscillations with a microwave external magnetic field is investigated by a reduced order model that takes into account the dynamical effects associated with the significant deformation of the vortex structure produced by the current, which cannot be taken care of by using the standard rigid vortex theory. The complete phase diagram of the vortex oscillation dynamics is derived and it is shown that strong hysteretic behavior occurs in the synchronization with the external field. The complex nonlinear nature of the synchronization manifests itself also through the appearance of asymmetry in the locking frequency bands for moderate microwave field amplitudes. Predictions from the reduced order model are confirmed by full micromagnetic simulations. PMID:27538476

Advanced Noise Abatement Procedures for a Supersonic Business Jet

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.; Jones, Scott M.; Seidel, Jonathan A.; Huff, Dennis L.

2017-01-01

Supersonic civil aircraft present a unique noise certification challenge. High specific thrust required for supersonic cruise results in high engine exhaust velocity and high levels of jet noise during takeoff. Aerodynamics of thin, low-aspect-ratio wings equipped with relatively simple flap systems deepen the challenge. Advanced noise abatement procedures have been proposed for supersonic aircraft. These procedures promise to reduce airport noise, but they may require departures from normal reference procedures defined in noise regulations. The subject of this report is a takeoff performance and noise assessment of a notional supersonic business jet. Analytical models of an airframe and a supersonic engine derived from a contemporary subsonic turbofan core are developed. These models are used to predict takeoff trajectories and noise. Results indicate advanced noise abatement takeoff procedures are helpful in reducing noise along lateral sidelines.

Modeling the Rock Glacier Cycle

NASA Astrophysics Data System (ADS)

Anderson, R. S.; Anderson, L. S.

2016-12-01

Rock glaciers are common in many mountain ranges in which the ELA lies above the peaks. They represent some of the most identifiable components of today's cryosphere in these settings. Their oversteepened snouts pose often-overlooked hazards to travel in alpine terrain. Rock glaciers are supported by avalanches and by rockfall from steep headwalls. The winter's avalanche cone must be sufficiently thick not to melt entirely in the summer. The spatial distribution of rock glaciers reflects this dependence on avalanche sources; they are most common on lee sides of ridges where wind-blown snow augments the avalanche source. In the absence of rockfall, this would support a short, cirque glacier. Depending on the relationship between rockfall and avalanche patterns, "talus-derived" and "glacier-derived" rock glaciers are possible. Talus-derived: If the spatial distribution of rock delivery is similar to the avalanche pattern, the rock-ice mixture will travel an englacial path that is downward through the short accumulation zone before turning upward in the ablation zone. Advected debris is then delivered to the base of a growing surface debris layer that reduces the ice melt rate. The physics is identical to the debris-covered glacier case. Glacier-derived: If on the other hand rockfall from the headwall rolls beyond the avalanche cone, it is added directly to the ablation zone of the glacier. The avalanche accumulation zone then supports a pure ice core to the rock glacier. We have developed numerical models designed to capture the full range of glacier to debris-covered glacier to rock glacier behavior. The hundreds of meter lengths, tens of meters thicknesses, and meter per year speeds of rock glaciers are well described by the models. The model can capture both "talus-derived" and "glacier-derived" rock glaciers. We explore the dependence of glacier behavior on climate histories. As climate warms, a pure ice debris-covered glacier can transform to a much shorter rock glacier, leaving in its wake a thinning ice-cored moraine. Rock glaciers have much longer response times to climate change than their pure ice cousins.

Mitochondriotropic and Cardioprotective Effects of Triphenylphosphonium-Conjugated Derivatives of the Diterpenoid Isosteviol

PubMed Central

Strobykina, Irina; Semenov, Victor V.; Semenova, Marina; Martelli, Alma; Citi, Valentina; Breschi, Maria C.; Kataev, Vladimir E.; Calderone, Vincenzo

2017-01-01

Mitochondria play a crucial role in the cell fate; in particular, reducing the accumulation of calcium in the mitochondrial matrix offers cardioprotection. This affect is achieved by a mild depolarization of the mitochondrial membrane potential, which prevents the assembly and opening of the mitochondrial permeability transition pore. For this reason, mitochondria are an attractive target for pharmacological interventions that prevent ischaemia/reperfusion injury. Isosteviol is a diterpenoid created from the acid hydrolysis of Stevia rebaudiana Bertoni (fam. Asteraceae) glycosides that has shown protective effects against ischaemia/reperfusion injury, which are likely mediated through the activation of mitochondrial adenosine tri-phosphate (ATP)-sensitive potassium (mitoKATP) channels. Some triphenylphosphonium (triPP)-conjugated derivatives of isosteviol have been developed, and to evaluate the possible pharmacological benefits that result from these synthetic modifications, in this study, the mitochondriotropic properties of isosteviol and several triPP-conjugates were investigated in rat cardiac mitochondria and in the rat heart cell line H9c2. This study’s main findings highlight the ability of isosteviol to depolarize the mitochondrial membrane potential and reduce calcium uptake by the mitochondria, which are typical functions of mitochondrial potassium channel openings. Moreover, triPP-conjugated derivatives showed a similar behavior to isosteviol but at lower concentrations, indicative of their improved uptake into the mitochondrial matrix. Finally, the cardioprotective property of a selected triPP-conjugated derivative was demonstrated in an in vivo model of acute myocardial infarct. PMID:28954424

Principal Dynamic Mode Analysis of the Hodgkin–Huxley Equations

PubMed Central

Eikenberry, Steffen E.; Marmarelis, Vasilis Z.

2015-01-01

We develop an autoregressive model framework based on the concept of Principal Dynamic Modes (PDMs) for the process of action potential (AP) generation in the excitable neuronal membrane described by the Hodgkin–Huxley (H–H) equations. The model's exogenous input is injected current, and whenever the membrane potential output exceeds a specified threshold, it is fed back as a second input. The PDMs are estimated from the previously developed Nonlinear Autoregressive Volterra (NARV) model, and represent an efficient functional basis for Volterra kernel expansion. The PDM-based model admits a modular representation, consisting of the forward and feedback PDM bases as linear filterbanks for the exogenous and autoregressive inputs, respectively, whose outputs are then fed to a static nonlinearity composed of polynomials operating on the PDM outputs and cross-terms of pair-products of PDM outputs. A two-step procedure for model reduction is performed: first, influential subsets of the forward and feedback PDM bases are identified and selected as the reduced PDM bases. Second, the terms of the static nonlinearity are pruned. The first step reduces model complexity from a total of 65 coefficients to 27, while the second further reduces the model coefficients to only eight. It is demonstrated that the performance cost of model reduction in terms of out-of-sample prediction accuracy is minimal. Unlike the full model, the eight coefficient pruned model can be easily visualized to reveal the essential system components, and thus the data-derived PDM model can yield insight into the underlying system structure and function. PMID:25630480

Model-based assessment of a Northwestern Tropical Pacific moored array to monitor intraseasonal variability

NASA Astrophysics Data System (ADS)

Liu, Danian; Zhu, Jiang; Shu, Yeqiang; Wang, Dongxiao; Wang, Weiqiang; Cai, Shuqun

2018-06-01

The Northwestern Tropical Pacific Ocean (NWTPO) moorings observing system, including 15 moorings, was established in 2013 to provide velocity profile data. Observing system simulation experiments (OSSEs) were carried out to assess the ability of the observation system to monitor intraseasonal variability in a pilot study, where ideal "mooring-observed" velocity was assimilated using Ensemble Optimal Interpolation (EnOI) based on the Regional Oceanic Modeling System (ROMS). Because errors between the control and "nature" runs have a mesoscale structure, a random ensemble derived from 20-90-day bandpass-filtered nine-year model outputs is proved to be more appropriate for the NWTPO mooring array assimilation than a random ensemble derived from a 30-day running mean. The simulation of the intraseasonal currents in the North Equatorial Current (NEC), North Equatorial Countercurrent (NECC), and Equatorial Undercurrent (EUC) areas can be improved by assimilating velocity profiles using a 20-90-day bandpass-filtered ensemble. The root mean square errors (RMSEs) of the intraseasonal zonal (U) and meridional velocity (V) above 500 m depth within the study area (between 0°N-18°N and 122°E-147°E) were reduced by 15.4% and 16.9%, respectively. Improvements in the downstream area of the NEC moorings transect were optimum where the RMSEs of the intraseasonal velocities above 500 m were reduced by more than 30%. Assimilating velocity profiles can have a positive impact on the simulation and forecast of thermohaline structure and sea level anomalies in the ocean.

Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration

PubMed Central

Carnicella, Sebastien; He, Dao-Yao; Yowell, Quinn V.; Glick, Stanley D.; Ron, Dorit

2013-01-01

Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action. PMID:21040239

A new weighted mean temperature model in China

NASA Astrophysics Data System (ADS)

Liu, Jinghong; Yao, Yibin; Sang, Jizhang

2018-01-01

The Global Positioning System (GPS) has been applied in meteorology to monitor the change of Precipitable Water Vapor (PWV) in atmosphere, transformed from Zenith Wet Delay (ZWD). A key factor in converting the ZWD into the PWV is the weighted mean temperature (Tm), which has a direct impact on the accuracy of the transformation. A number of Bevis-type models, like Tm -Ts and Tm -Ts,Ps type models, have been developed by statistics approaches, and are not able to clearly depict the relationship between Tm and the surface temperature, Ts . A new model for Tm , called weighted mean temperature norm model (abbreviated as norm model), is derived as a function of Ts , the lapse rate of temperature, δ, the tropopause height, htrop , and the radiosonde station height, hs . It is found that Tm is better related to Ts through an intermediate temperature. The small effects of lapse rate can be ignored and the tropopause height be obtained from an empirical model. Then the norm model is reduced to a simplified form, which causes fewer loss of accuracy and needs two inputs, Ts and hs . In site-specific fittings, the norm model performs much better, with RMS values reduced averagely by 0.45 K and the Mean of Absolute Differences (MAD) values by 0.2 K. The norm model is also found more appropriate than the linear models to fit Tm in a large area, not only with the RMS value reduced from 4.3 K to 3.80 K, correlation coefficient R2 increased from 0.84 to 0.88, and MAD decreased from 3.24 K to 2.90 K, but also with the distribution of simplified model values to be more reasonable. The RMS and MAD values of the differences between reference and computed PWVs are reduced by on average 16.3% and 14.27%, respectively, when using the new norm models instead of the linear model.

An Evaluation Technique for an F/A-18 Aircraft Loads Model Using F/A-18 Systems Research Aircraft Flight Data

NASA Technical Reports Server (NTRS)

Olney, Candida D.; Hillebrandt, Heather; Reichenbach, Eric Y.

2000-01-01

A limited evaluation of the F/A-18 baseline loads model was performed on the Systems Research Aircraft at NASA Dryden Flight Research Center (Edwards, California). Boeing developed the F/A-18 loads model using a linear aeroelastic analysis in conjunction with a flight simulator to determine loads at discrete locations on the aircraft. This experiment was designed so that analysis of doublets could be used to establish aircraft aerodynamic and loads response at 20 flight conditions. Instrumentation on the right outboard leading edge flap, left aileron, and left stabilator measured the hinge moment so that comparisons could be made between in-flight-measured hinge moments and loads model-predicted values at these locations. Comparisons showed that the difference between the loads model-predicted and in-flight-measured hinge moments was up to 130 percent of the flight limit load. A stepwise regression technique was used to determine new loads derivatives. These derivatives were placed in the loads model, which reduced the error to within 10 percent of the flight limit load. This paper discusses the flight test methodology, a process for determining loads coefficients, and the direct comparisons of predicted and measured hinge moments and loads coefficients.

Formulation of an experimental substructure model using a Craig-Bampton based transmission simulator

NASA Astrophysics Data System (ADS)

Kammer, Daniel C.; Allen, Mathew S.; Mayes, Randy L.

2015-12-01

Experimental-analytical substructuring is attractive when there is motivation to replace one or more system subcomponents with an experimental model. This experimentally derived substructure can then be coupled to finite element models of the rest of the structure to predict the system response. The transmission simulator method couples a fixture to the component of interest during a vibration test in order to improve the experimental model for the component. The transmission simulator is then subtracted from the tested system to produce the experimental component. The method reduces ill-conditioning by imposing a least squares fit of constraints between substructure modal coordinates to connect substructures, instead of directly connecting physical interface degrees of freedom. This paper presents an alternative means of deriving the experimental substructure model, in which a Craig-Bampton representation of the transmission simulator is created and subtracted from the experimental measurements. The corresponding modal basis of the transmission simulator is described by the fixed-interface modes, rather than free modes that were used in the original approach. These modes do a better job of representing the shape of the transmission simulator as it responds within the experimental system, leading to more accurate results using fewer modes. The new approach is demonstrated using a simple finite element model based example with a redundant interface.

Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy.

PubMed

Angell-Petersen, Even; Hirschberg, Henry; Madsen, Steen J

2007-01-01

Light and heat distributions are measured in a rat glioma model used in photodynamic therapy. A fiber delivering 632-nm light is fixed in the brain of anesthetized BDIX rats. Fluence rates are measured using calibrated isotropic probes that are positioned stereotactically. Mathematical models are then used to derive tissue optical properties, enabling calculation of fluence rate distributions for general tumor and light application geometries. The fluence rates in tumor-free brains agree well with the models based on diffusion theory and Monte Carlo simulation. In both cases, the best fit is found for absorption and reduced scattering coefficients of 0.57 and 28 cm(-1), respectively. In brains with implanted BT(4)C tumors, a discrepancy between diffusion and Monte Carlo-derived two-layer models is noted. Both models suggest that tumor tissue has higher absorption and less scattering than normal brain. Temperatures are measured by inserting thermocouples directly into tumor-free brains. A model based on diffusion theory and the bioheat equation is found to be in good agreement with the experimental data and predict a thermal penetration depth of 0.60 cm in normal rat brain. The predicted parameters can be used to estimate the fluences, fluence rates, and temperatures achieved during photodynamic therapy.

Computational Benefits Using an Advanced Concatenation Scheme Based on Reduced Order Models for RF Structures

NASA Astrophysics Data System (ADS)

Heller, Johann; Flisgen, Thomas; van Rienen, Ursula

The computation of electromagnetic fields and parameters derived thereof for lossless radio frequency (RF) structures filled with isotropic media is an important task for the design and operation of particle accelerators. Unfortunately, these computations are often highly demanding with regard to computational effort. The entire computational demand of the problem can be reduced using decomposition schemes in order to solve the field problems on standard workstations. This paper presents one of the first detailed comparisons between the recently proposed state-space concatenation approach (SSC) and a direct computation for an accelerator cavity with coupler-elements that break the rotational symmetry.

Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

PubMed

Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

2017-11-05

Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis.

PubMed

Han, Ying; Yue, Lanzhu; Wei, Max; Ren, Xiubao; Shao, Zonghong; Zhang, Ling; Levine, Ross L; Epling-Burnette, Pearlie K

2017-01-01

Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo. TGFβ production by malignant megakaryocytes plays a definitive role promoting myelofibrosis in MPNs. However, TGFβ was equally expressed by MSCs derived from MPLWT and MPLW515L expressing mice and the addition of neutralizing anti-TGFβ antibody only partially reduced collagen secretion in vitro. Interestingly, profibrotic MSCs displayed increased levels of pSmad3 and pSTAT3 suggesting that inflammatory mediators cooperating with the TGFβ-receptor signaling may maintain the aberrant phenotype ex vivo. FGFb is a known suppressor of TGFβ signaling. Reduced collagen deposition by FGFb-treated MSCs derived from MPLW515L mice suggests that the activating pathway is vulnerable to this suppressive mediator. Therefore, our findings have implications for the future investigation of therapies to reverse fibrosis in MPNs.

Mesenchymal Cell Reprogramming in Experimental MPLW515L Mouse Model of Myelofibrosis

PubMed Central

Wei, Max; Ren, Xiubao; Shao, Zonghong; Zhang, Ling; Levine, Ross L.; Epling-Burnette, Pearlie K.

2017-01-01

Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo. TGFβ production by malignant megakaryocytes plays a definitive role promoting myelofibrosis in MPNs. However, TGFβ was equally expressed by MSCs derived from MPLWT and MPLW515L expressing mice and the addition of neutralizing anti-TGFβ antibody only partially reduced collagen secretion in vitro. Interestingly, profibrotic MSCs displayed increased levels of pSmad3 and pSTAT3 suggesting that inflammatory mediators cooperating with the TGFβ-receptor signaling may maintain the aberrant phenotype ex vivo. FGFb is a known suppressor of TGFβ signaling. Reduced collagen deposition by FGFb-treated MSCs derived from MPLW515L mice suggests that the activating pathway is vulnerable to this suppressive mediator. Therefore, our findings have implications for the future investigation of therapies to reverse fibrosis in MPNs. PMID:28135282

Effect of glycation derived from α-dicarbonyl compounds on the in vitro digestibility of β-casein and β-lactoglobulin: A model study with glyoxal, methylglyoxal and butanedione.

PubMed

Zhao, Di; Le, Thao T; Larsen, Lotte Bach; Li, Lin; Qin, Dan; Su, Guoying; Li, Bing

2017-12-01

α-Dicarbonyl compounds, which are widely found in common consumed food, are one of the precursors of advanced glycation end products (AGEs). In this study, the effect of glycation derived from glyoxal (GO), methylglyoxal (MGO) or butanedione (BU) on the in vitro digestibility of β-casein (β-CN) and β-lactoglobulin (β-Lg) was investigated. Glycation from α-dicarbonyl compounds reduced the in vitro digestibility of studied proteins in both gastric and intestinal stage. In addition, glycation substantially altered the peptides released through gastric and gastrointestinal digestion, as detected by liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-MS/MS). Crosslinked glycation structures derived from BU considerably reduced the sensitivity of glycated β-Lg towards digestive proteases, albeit to a lesser degree in glycated β-CN due to its intrinsic unordered structure. By contrast, non-crosslinked AGEs that formed adjacent to enzymatic cleavage sites did not block the enzymatic reaction in several cases, as evidenced by the corresponding digested peptides modified with glycation structures. These findings expand our understanding of the nutritional influence of α-dicarbonyl compounds and health impact of relevant dietary AGEs. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Fibrin-Derived Peptide Bβ15-42 (FX06) Ameliorates Vascular Leakage and Improves Survival and Neurocognitive Recovery: Implications From Two Animal Models of Cardiopulmonary Resuscitation.

PubMed

Bergt, Stefan; Gruenewald, Matthias; Beltschany, Claudia; Grub, Andrea; Neumann, Tobias; Albrecht, Martin; Vollmar, Brigitte; Zacharowski, Kai; Roesner, Jan P; Meybohm, Patrick

2016-10-01

The fibrin-derived peptide Bβ15-42 (FX06) has been proven to attenuate ischemia/reperfusion injury. We tested the hypothesis that Bβ15-42 improves survival rate and neurocognitive recovery after cardiopulmonary resuscitation. Pig and mouse model of cardiopulmonary resuscitation. Two university hospitals. Pigs and mice. Pigs (n = 16) were subjected to 8-minute cardiac arrest. Successful resuscitated pigs (n = 12) were randomized either to 3 mg/kg Bβ15-42 followed by a continuous infusion of 1 mg/kg/hr for 5 hours (pFX06; n = 6) or the control group (pCONTROL; n = 6). Cardiac damage, function, and hemodynamics were recorded up to 8 hours. Mice (n = 52) were subjected to 4-minute cardiac arrest followed by cardiopulmonary resuscitation, and randomized either to two boli of 2.4 mg/kg Bβ15-42 (mFX06; n = 26) or the control group (mCONTROL; n = 26). Fourteen-day survival rate, neurocognitive function, and endothelial integrity (additional experiment with n = 26 mice) were evaluated. Bβ15-42 reduced cumulative fluid intake (3,500 [2,600-4,200] vs 6,800 [5,700-7,400] mL; p = 0.004) within 8 hours in pigs. In mice, Bβ15-42 improved 14-day survival rate (mFX06 vs mCONTROL; 11/26 vs 6/26; p < 0.05) and fastened neurocognitive recovery in the Water-Maze test (15/26 vs 9/26 mice with competence to perform test; p < 0.05). Bβ15-42-treated mice showed a significant higher length of intact pulmonary endothelium and reduced pulmonary leukocyte infiltration. This study confirms the new concept of an important role of fibrin derivatives in global ischemia/reperfusion injury, which can be attenuated by the fibrin-derived peptide Bβ15-42.

Effect of human milk as a treatment for dry eye syndrome in a mouse model

PubMed Central

Diego, Jose L.; Bidikov, Luke; Pedler, Michelle G.; Kennedy, Jeffrey B.; Quiroz-Mercado, Hugo; Gregory, Darren G.; Petrash, J. Mark

2016-01-01

Purpose Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies’ efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. Methods The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. Results Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 μm in the control mice to 21.29±3.2 μm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 μm) or fat-reduced milk (36.1±1.58 μm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 μm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 μm and 27.99±2.75 μm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 μm for ethyl acetate, 21.59±5.87 μm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to increase in eyes treated with nopal-derived materials. Conclusions Whole and fat-reduced human milk showed promising effects in the prevention of BAK-induced loss of corneal epithelial thickness and epithelial damage in this mouse model. Further studies are required to determine whether human milk may be safely used to treat dry eye in patients. PMID:27667918

Effect of human milk as a treatment for dry eye syndrome in a mouse model.

PubMed

Diego, Jose L; Bidikov, Luke; Pedler, Michelle G; Kennedy, Jeffrey B; Quiroz-Mercado, Hugo; Gregory, Darren G; Petrash, J Mark; McCourt, Emily A

Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 μm in the control mice to 21.29±3.2 μm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 μm) or fat-reduced milk (36.1±1.58 μm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 μm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 μm and 27.99±2.75 μm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 μm for ethyl acetate, 21.59±5.87 μm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to increase in eyes treated with nopal-derived materials. Whole and fat-reduced human milk showed promising effects in the prevention of BAK-induced loss of corneal epithelial thickness and epithelial damage in this mouse model. Further studies are required to determine whether human milk may be safely used to treat dry eye in patients.

The uncertainty cascade in flood risk assessment under changing climatic conditions - the Biala Tarnowska case study

NASA Astrophysics Data System (ADS)

Doroszkiewicz, Joanna; Romanowicz, Renata

2016-04-01

Uncertainty in the results of the hydraulic model is not only associated with the limitations of that model and the shortcomings of data. An important factor that has a major impact on the uncertainty of the flood risk assessment in a changing climate conditions is associated with the uncertainty of future climate scenarios (IPCC WG I, 2013). Future climate projections provided by global climate models are used to generate future runoff required as an input to hydraulic models applied in the derivation of flood risk maps. Biala Tarnowska catchment, situated in southern Poland is used as a case study. Future discharges at the input to a hydraulic model are obtained using the HBV model and climate projections obtained from the EUROCORDEX project. The study describes a cascade of uncertainty related to different stages of the process of derivation of flood risk maps under changing climate conditions. In this context it takes into account the uncertainty of future climate projections, an uncertainty of flow routing model, the propagation of that uncertainty through the hydraulic model, and finally, the uncertainty related to the derivation of flood risk maps. One of the aims of this study is an assessment of a relative impact of different sources of uncertainty on the uncertainty of flood risk maps. Due to the complexity of the process, an assessment of total uncertainty of maps of inundation probability might be very computer time consuming. As a way forward we present an application of a hydraulic model simulator based on a nonlinear transfer function model for the chosen locations along the river reach. The transfer function model parameters are estimated based on the simulations of the hydraulic model at each of the model cross-section. The study shows that the application of the simulator substantially reduces the computer requirements related to the derivation of flood risk maps under future climatic conditions. Acknowledgements: This work was supported by the project CHIHE (Climate Change Impact on Hydrological Extremes), carried out in the Institute of Geophysics Polish Academy of Sciences, funded by Norway Grants (contract No. Pol-Nor/196243/80/2013). The hydro-meteorological observations were provided by the Institute of Meteorology and Water Management (IMGW), Poland.

The Impairment of Macrophage-to-Feces Reverse Cholesterol Transport during Inflammation Does Not Depend on Serum Amyloid A

PubMed Central

de Beer, Maria C.; Wroblewski, Joanne M.; Noffsinger, Victoria P.; Meyer, Jason M.; van der Westhuyzen, Deneys R.

2013-01-01

Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with 3H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. 3H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of 3H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36% (P < 0.05) and 80% (P < 0.001), respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived 3H-cholesterol in bile, and fecal excretion was reduced by only 45% (P < 0.05). Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment. PMID:23431457

The Impairment of Macrophage-to-Feces Reverse Cholesterol Transport during Inflammation Does Not Depend on Serum Amyloid A.

PubMed

de Beer, Maria C; Wroblewski, Joanne M; Noffsinger, Victoria P; Ji, Ailing; Meyer, Jason M; van der Westhuyzen, Deneys R; de Beer, Frederick C; Webb, Nancy R

2013-01-01

Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with (3)H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. (3)H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of (3)H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36% (P < 0.05) and 80% (P < 0.001), respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived (3)H-cholesterol in bile, and fecal excretion was reduced by only 45% (P < 0.05). Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment.

MAG-EPA resolves lung inflammation in an allergic model of asthma.

PubMed

Morin, C; Fortin, S; Cantin, A M; Rousseau, É

2013-09-01

Asthma is a chronic disease characterized by airways hyperresponsiveness, inflammation and airways remodelling involving reversible bronchial obstruction. Omega-3 fatty acids and their derivatives are known to reduce inflammation in several tissues including lung. The effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA), a newly synthesized EPA derivative, were determined on the resolution of lung inflammation and airway hyperresponsiveness in an in vivo model of allergic asthma. Ovalbumin (OVA)-sensitized guinea-pigs were treated or not with MAG-EPA administered per os. Isometric tension measurements, histological analyses, homogenate preparation for Western blot experiments or total RNA extraction for RT-PCR were performed to assess the effect of MAG-EPA treatments. Mechanical tension measurements revealed that oral MAG-EPA treatments reduced methacholine (MCh)-induced bronchial hyperresponsiveness in OVA-sensitized guinea-pigs. Moreover, MAG-EPA treatments also decreased Ca(2+) hypersensitivity of bronchial smooth muscle. Histological analyses and leucocyte counts in bronchoalveolar lavages revealed that oral MAG-EPA treatments led to less inflammatory cell recruitment in the lung of OVA-sensitized guinea-pigs when compared with lungs from control animals. Results also revealed a reduction in mucin production and MUC5AC expression level in OVA-sensitized animals treated with MAG-EPA. Following MAG-EPA treatments, the transcript levels of pro-inflammatory markers such as IL-5, eotaxin, IL-13 and IL-4 were markedly reduced. Moreover, per os MAG-EPA administrations reduced COX2 over-expression in OVA-sensitized animals. We demonstrate that MAG-EPA reduces airway hyperresponsiveness and lung inflammation in OVA-sensitized animals, a finding consistent with a decrease in IL-4, IL-5, IL-13, COX-2 and MUC5AC expression levels in the lung. The present data suggest that MAG-EPA represents a new potential therapeutic strategy for resolving inflammation in allergic asthma. © 2013 John Wiley & Sons Ltd.

Assessing the Utility of Uav-Borne Hyperspectral Image and Photogrammetry Derived 3d Data for Wetland Species Distribution Quick Mapping

NASA Astrophysics Data System (ADS)

Li, Q. S.; Wong, F. K. K.; Fung, T.

2017-08-01

Lightweight unmanned aerial vehicle (UAV) loaded with novel sensors offers a low cost and minimum risk solution for data acquisition in complex environment. This study assessed the performance of UAV-based hyperspectral image and digital surface model (DSM) derived from photogrammetric point clouds for 13 species classification in wetland area of Hong Kong. Multiple feature reduction methods and different classifiers were compared. The best result was obtained when transformed components from minimum noise fraction (MNF) and DSM were combined in support vector machine (SVM) classifier. Wavelength regions at chlorophyll absorption green peak, red, red edge and Oxygen absorption at near infrared were identified for better species discrimination. In addition, input of DSM data reduces overestimation of low plant species and misclassification due to the shadow effect and inter-species morphological variation. This study establishes a framework for quick survey and update on wetland environment using UAV system. The findings indicate that the utility of UAV-borne hyperspectral and derived tree height information provides a solid foundation for further researches such as biological invasion monitoring and bio-parameters modelling in wetland.

Observers Exploit Stochastic Models of Sensory Change to Help Judge the Passage of Time

PubMed Central

Ahrens, Misha B.; Sahani, Maneesh

2011-01-01

Summary Sensory stimulation can systematically bias the perceived passage of time [1–5], but why and how this happens is mysterious. In this report, we provide evidence that such biases may ultimately derive from an innate and adaptive use of stochastically evolving dynamic stimuli to help refine estimates derived from internal timekeeping mechanisms [6–15]. A simplified statistical model based on probabilistic expectations of stimulus change derived from the second-order temporal statistics of the natural environment [16, 17] makes three predictions. First, random noise-like stimuli whose statistics violate natural expectations should induce timing bias. Second, a previously unexplored obverse of this effect is that similar noise stimuli with natural statistics should reduce the variability of timing estimates. Finally, this reduction in variability should scale with the interval being timed, so as to preserve the overall Weber law of interval timing. All three predictions are borne out experimentally. Thus, in the context of our novel theoretical framework, these results suggest that observers routinely rely on sensory input to augment their sense of the passage of time, through a process of Bayesian inference based on expectations of change in the natural environment. PMID:21256018

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

PubMed Central

Kuempel, Eileen D.; Sweeney, Lisa M.; Morris, John B.; Jarabek, Annie M.

2015-01-01

The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. PMID:26551218

Simple Analytic Expressions for the Magnetic Field of a Circular Current Loop

NASA Technical Reports Server (NTRS)

Simpson, James C.; Lane, John E.; Immer, Christopher D.; Youngquist, Robert C.

2001-01-01

Analytic expressions for the magnetic induction (magnetic flux density, B) of a simple planar circular current loop have been published in Cartesian and cylindrical coordinates [1,2], and are also known implicitly in spherical coordinates [3]. In this paper, we present explicit analytic expressions for B and its spatial derivatives in Cartesian, cylindrical, and spherical coordinates for a filamentary current loop. These results were obtained with extensive use of Mathematica "TM" and are exact throughout all space outside of the conductor. The field expressions reduce to the well-known limiting cases and satisfy V · B = 0 and V x B = 0 outside the conductor. These results are general and applicable to any model using filamentary circular current loops. Solenoids of arbitrary size may be easily modeled by approximating the total magnetic induction as the sum of those for the individual loops. The inclusion of the spatial derivatives expands their utility to magnetohydrodynamics where the derivatives are required. The equations can be coded into any high-level programming language. It is necessary to numerically evaluate complete elliptic integrals of the first and second kind, but this capability is now available with most programming packages.

Hydrogeologic controls on the groundwater interactions with an acidic lake in karst terrain, Lake Barco, Florida

USGS Publications Warehouse

Lee, T.M.

1996-01-01

Transient groundwater interactions and lake stage were simulated for Lake Barco, an acidic seepage lake in the mantled karst of north central Florida. Karst subsidence features affected groundwater flow patterns in the basin and groundwater fluxes to and from the lake. Subsidence features peripheral to the lake intercepted potential groundwater inflow and increased leakage from the shallow perimeter of the lake bed. Simulated groundwater fluxes were checked against net groundwater flow derived from a detailed lake hydrologic budget with short-term lake evaporation computed by the energy budget method. Discrepancies between modeled and budget-derived net groundwater flows indicated that the model underestimated groundwater inflow, possibly contributed to by transient water table mounding near the lake. Recharge from rainfall reduced lake leakage by 10 to 15 times more than it increased groundwater inflow. As a result of the karst setting, the contributing groundwater basin to the lake was 2.4 ha for simulated average rainfall conditions, compared to the topographically derived drainage basin area of 81 ha. Short groundwater inflow path lines and rapid travel times limit the contribution of acid-neutralizing solutes from the basin, making Lake Barco susceptible to increased acidification by acid rain.

Improving Global Mass Flux Solutions from Gravity Recovery and Climate Experiment (GRACE) Through Forward Modeling and Continuous Time Correlation

NASA Technical Reports Server (NTRS)

Sabaka, T. J.; Rowlands, D. D.; Luthcke, S. B.; Boy, J.-P.

2010-01-01

We describe Earth's mass flux from April 2003 through November 2008 by deriving a time series of mas cons on a global 2deg x 2deg equal-area grid at 10 day intervals. We estimate the mass flux directly from K band range rate (KBRR) data provided by the Gravity Recovery and Climate Experiment (GRACE) mission. Using regularized least squares, we take into account the underlying process dynamics through continuous space and time-correlated constraints. In addition, we place the mascon approach in the context of other filtering techniques, showing its equivalence to anisotropic, nonsymmetric filtering, least squares collocation, and Kalman smoothing. We produce mascon time series from KBRR data that have and have not been corrected (forward modeled) for hydrological processes and fmd that the former produce superior results in oceanic areas by minimizing signal leakage from strong sources on land. By exploiting the structure of the spatiotemporal constraints, we are able to use a much more efficient (in storage and computation) inversion algorithm based upon the conjugate gradient method. This allows us to apply continuous rather than piecewise continuous time-correlated constraints, which we show via global maps and comparisons with ocean-bottom pressure gauges, to produce time series with reduced random variance and full systematic signal. Finally, we present a preferred global model, a hybrid whose oceanic portions are derived using forward modeling of hydrology but whose land portions are not, and thus represent a pure GRACE-derived signal.

Generation of stable PDX derived cell lines using conditional reprogramming.

PubMed

Borodovsky, Alexandra; McQuiston, Travis J; Stetson, Daniel; Ahmed, Ambar; Whitston, David; Zhang, Jingwen; Grondine, Michael; Lawson, Deborah; Challberg, Sharon S; Zinda, Michael; Pollok, Brian A; Dougherty, Brian A; D'Cruz, Celina M

2017-12-06

Efforts to develop effective cancer therapeutics have been hindered by a lack of clinically predictive preclinical models which recapitulate this complex disease. Patient derived xenograft (PDX) models have emerged as valuable tools for translational research but have several practical limitations including lack of sustained growth in vitro. In this study, we utilized Conditional Reprogramming (CR) cell technology- a novel cell culture system facilitating the generation of stable cultures from patient biopsies- to establish PDX-derived cell lines which maintain the characteristics of the parental PDX tumor. Human lung and ovarian PDX tumors were successfully propagated using CR technology to create stable explant cell lines (CR-PDX). These CR-PDX cell lines maintained parental driver mutations and allele frequency without clonal drift. Purified CR-PDX cell lines were amenable to high throughput chemosensitivity screening and in vitro genetic knockdown studies. Additionally, re-implanted CR-PDX cells proliferated to form tumors that retained the growth kinetics, histology, and drug responses of the parental PDX tumor. CR technology can be used to generate and expand stable cell lines from PDX tumors without compromising fundamental biological properties of the model. It offers the ability to expand PDX cells in vitro for subsequent 2D screening assays as well as for use in vivo to reduce variability, animal usage and study costs. The methods and data detailed here provide a platform to generate physiologically relevant and predictive preclinical models to enhance drug discovery efforts.

Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies

PubMed Central

Lee, Edmund C.; Fitzgerald, Michael; Bannerman, Bret; Donelan, Jill; Bano, Kristen; Terkelsen, Jennifer; Bradley, Daniel P.; Subakan, Ozlem; Silva, Matthew D.; Liu, Ray; Pickard, Michael; Li, Zhi; Tayber, Olga; Li, Ping; Hales, Paul; Carsillo, Mary; Neppalli, Vishala T.; Berger, Allison J.; Kupperman, Erik; Manfredi, Mark; Bolen, Joseph B.; Van Ness, Brian; Janz, Siegfried

2012-01-01

Purpose The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM). Experimental Design Both cell line–derived OCI-Ly10 and primary human lymphoma–derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMycCα/Bcl-XL GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc–disseminated model of iMycCα/ Bcl-XL was used to determine antitumor activity and effects on osteolytic bone disease. Results MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMycCα/Bcl-XL GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. Conclusions Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. PMID:21903769

Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury

PubMed Central

Pannu, Neesh; Hemmelgarn, Brenda R.; Austin, Peter C.; Tan, Zhi; McArthur, Eric; Manns, Braden J.; Tonelli, Marcello; Wald, Ron; Quinn, Robert R.; Ravani, Pietro; Garg, Amit X.

2017-01-01

Importance Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. Objective To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Design, Setting, and Participants Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Exposures Demographic, laboratory, and comorbidity variables measured prior to discharge. Main Outcomes and Measures Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. Results The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). Conclusions and Relevance A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research. PMID:29136443

Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

PubMed

James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

2017-11-14

Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Demographic, laboratory, and comorbidity variables measured prior to discharge. Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research.

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.

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion.

PubMed

Mackins, Christina J; Kano, Seiichiro; Seyedi, Nahid; Schäfer, Ulrich; Reid, Alicia C; Machida, Takuji; Silver, Randi B; Levi, Roberto

2006-04-01

Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell-deficient mice than in control hearts. Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

A new mean estimator using auxiliary variables for randomized response models

NASA Astrophysics Data System (ADS)

Ozgul, Nilgun; Cingi, Hulya

2013-10-01

Randomized response models are commonly used in surveys dealing with sensitive questions such as abortion, alcoholism, sexual orientation, drug taking, annual income, tax evasion to ensure interviewee anonymity and reduce nonrespondents rates and biased responses. Starting from the pioneering work of Warner [7], many versions of RRM have been developed that can deal with quantitative responses. In this study, new mean estimator is suggested for RRM including quantitative responses. The mean square error is derived and a simulation study is performed to show the efficiency of the proposed estimator to other existing estimators in RRM.