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Sample records for mdcnev model formulation

  1. HIGH-LEVEL WASTE GLASS FORMULATION MODEL SENSITIVITY STUDY 2009 GLASS FORMULATION MODEL VERSUS 1996 GLASS FORMULATION MODEL

    SciTech Connect

    BELSHER JD; MEINERT FL

    2009-12-07

    This document presents the differences between two HLW glass formulation models (GFM): The 1996 GFM and 2009 GFM. A glass formulation model is a collection of glass property correlations and associated limits, as well as model validity and solubility constraints; it uses the pretreated HLW feed composition to predict the amount and composition of glass forming additives necessary to produce acceptable HLW glass. The 2009 GFM presented in this report was constructed as a nonlinear optimization calculation based on updated glass property data and solubility limits described in PNNL-18501 (2009). Key mission drivers such as the total mass of HLW glass and waste oxide loading are compared between the two glass formulation models. In addition, a sensitivity study was performed within the 2009 GFM to determine the effect of relaxing various constraints on the predicted mass of the HLW glass.

  2. Rheology of Model Dough Formulation

    NASA Astrophysics Data System (ADS)

    Desai, Kiran; Lele, Smita; Lele, Ashish

    2008-07-01

    Dough is generally considered a viscoelastic material, and its elasticity is attributed to the hydrated gluten matrix. Since starch is a major constituent of flour (˜70 wt% on dry basis) we may expect it to contribute to dough rheology in a non-trivial manner. Considering dough to belong to the generic class of soft solid materials, we use the Strain-Rate Frequency Superposition (SRFS) technique to study rheology of various model dough compositions in which the starch/gluten ratio is systematically varied from 100/0 to 0/100. We find that for compositions containing 0-25% gluten the SRFS superposition principle works well, while for compositions containing greater than 25% gluten the quality of SRFS mastercurves deteriorates gradually. Thus we propose that starch particles contribute substantially to the rheology of dough containing up to 25% gluten.

  3. A Formulation of the Interactive Evaluation Model

    PubMed Central

    Walsh, Peter J.; Awad-Edwards, Roger; Engelhardt, K. G.; Perkash, Inder

    1985-01-01

    The development of highly technical devices for specialized users requires continual feedback from potential users to the project team designing the device to assure that a useful product will result. This necessity for user input is the basis for the Interactive Evaluation Model which has been applied to complex computer assisted robotic aids for individuals with disabilities and has wide application to the development of a variety of technical devices. We present a preliminary mathematical formulation of the Interactive Evaluation Model which maximizes the rate of growth toward success, at a constant cost rate, of the efforts of a team having the diverse expertises needed to produce a complex technical product. Close interaction is simulated by a growth rate which is a multiplicative product involving the number of participants within a given class of necessary expertise and evaluation is included by demanding that users form one of the necessary classes. In the multipliers, the number of class participants is raised to a power termed the class weight exponent. In the simplest case, the optimum participant number varies as the ratio of the class weight exponent to the average class cost. An illustrative example, based on our experience with medical care assistive aids, shows the dramatic cost reduction possible with users on the team.

  4. Model Formulation for Physics Problem Solving. Draft.

    ERIC Educational Resources Information Center

    Novak, Gordon S., Jr.

    The major task in solving a physics problem is to construct an appropriate model of the problem in terms of physical principles. The functions performed by such a model, the information which needs to be represented, and the knowledge used in selecting and instantiating an appropriate model are discussed. An example of a model for a mechanics…

  5. Computer formulations of aircraft models for simulation studies

    NASA Technical Reports Server (NTRS)

    Howard, J. C.

    1979-01-01

    Recent developments in formula manipulation compilers and the design of several symbol manipulation languages, enable computers to be used for symbolic mathematical computation. A computer system and language that can be used to perform symbolic manipulations in an interactive mode are used to formulate a mathematical model of an aeronautical system. The example demonstrates that once the procedure is established, the formulation and modification of models for simulation studies can be reduced to a series of routine computer operations.

  6. Discontinuous Galerkin flood model formulation: Luxury or necessity?

    NASA Astrophysics Data System (ADS)

    Kesserwani, Georges; Wang, Yueling

    2014-08-01

    The finite volume Godunov-type flood model formulation is the most comprehensive amongst those currently employed for flood risk modeling. The local Discontinuous Galerkin method constitutes a more complex, rigorous, and extended local Godunov-type formulation. However, the practical merit associated with such an increase in the level of complexity of the formulation is yet to be decided. This work makes the case for a second-order Runge-Kutta Discontinuous Galerkin (RKDG2) formulation and contrasts it with the equivalently accurate finite volume (MUSCL) formulation, both of which solve the Shallow Water Equations (SWE) in two space dimensions. The numerical complexity of both formulations are presented and their capabilities are explored for wide-ranging diagnostic and real-scale tests, incorporating all challenging features relevant to flood inundation modeling. Our findings reveal that the extra complexity associated with the RKDG2 model pays off by providing higher-quality solution behavior on very coarse meshes and improved velocity predictions. The practical implication of this is that improved accuracy for flood modeling simulations will result when terrain data are limited or of a low resolution.

  7. Modeling of autocatalytic hydrolysis of adefovir dipivoxil in solid formulations.

    PubMed

    Dong, Ying; Zhang, Yan; Xiang, Bingren; Deng, Haishan; Wu, Jingfang

    2011-04-01

    The stability and hydrolysis kinetics of a phosphate prodrug, adefovir dipivoxil, in solid formulations were studied. The stability relationship between five solid formulations was explored. An autocatalytic mechanism for hydrolysis could be proposed according to the kinetic behavior which fits the Prout-Tompkins model well. For the classical kinetic models could hardly describe and predict the hydrolysis kinetics of adefovir dipivoxil in solid formulations accurately when the temperature is high, a feedforward multilayer perceptron (MLP) neural network was constructed to model the hydrolysis kinetics. The build-in approaches in Weka, such as lazy classifiers and rule-based learners (IBk, KStar, DecisionTable and M5Rules), were used to verify the performance of MLP. The predictability of the models was evaluated by 10-fold cross-validation and an external test set. It reveals that MLP should be of general applicability proposing an alternative efficient way to model and predict autocatalytic hydrolysis kinetics for phosphate prodrugs.

  8. Physiologically Based Absorption Modeling for Amorphous Solid Dispersion Formulations.

    PubMed

    Mitra, Amitava; Zhu, Wei; Kesisoglou, Filippos

    2016-09-06

    Amorphous solid dispersion (ASD) formulations are routinely used to enable the delivery of poorly soluble compounds. This type of formulations can enhance bioavailability due to higher kinetic solubility of the drug substance and increased dissolution rate of the formulation, by the virtue of the fact that the drug molecule exists in the formulation in a high energy amorphous state. In this article we report the application of physiologically based absorption models to mechanistically understand the clinical pharmacokinetics of solid dispersion formulations. Three case studies are shown here to cover a wide range of ASD bioperformance in human and modeling to retrospectively understand their in vivo behavior. Case study 1 is an example of fairly linear PK observed with dose escalation and the use of amorphous solubility to predict bioperformance. Case study 2 demonstrates the development of a model that was able to accurately predict the decrease in fraction absorbed (%Fa) with dose escalation thus demonstrating that such model can be used to predict the clinical bioperformance in the scenario where saturation of absorption is observed. Finally, case study 3 shows the development of an absorption model with the intent to describe the observed incomplete and low absorption in clinic with dose escalation. These case studies highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of ASD performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  9. AERMOD: MODEL FORMULATION AND EVALUATION RESULTS

    EPA Science Inventory

    AERMOD is an advanced plume model that incorporates updated treatments of the boundary layer theory, understanding of turbulence and dispersion, and includes handling of terrain interactions. This paper presents an overview of AERMOD's features relative to ISCST3.

    AERM...

  10. AERMOD: MODEL FORMULATION AND EVALUATION RESULTS

    EPA Science Inventory

    AERMOD is an advanced plume model that incorporates updated treatments of the boundary layer theory, understanding of turbulence and dispersion, and includes handling of terrain interactions. This paper presents an overview of AERMOD's features relative to ISCST3.

    AERM...

  11. Wavelet formulation of the polarizable continuum model.

    PubMed

    Weijo, Ville; Randrianarivony, Maharavo; Harbrecht, Helmut; Frediani, Luca

    2010-05-01

    The first implementation of a wavelet discretization of the Integral Equation Formalism (IEF) for the Polarizable Continuum Model (PCM) is presented here. The method is based on the application of a general purpose wavelet solver on the cavity boundary to solve the integral equations of the IEF-PCM problem. Wavelet methods provide attractive properties for the solution of the electrostatic problem at the cavity boundary: the system matrix is highly sparse and iterative solution schemes can be applied efficiently; the accuracy of the solver can be increased systematically and arbitrarily; for a given system, discretization error accuracy is achieved at a computational expense that scales linearly with the number of unknowns. The scaling of the computational time with the number of atoms N is formally quadratic but a N(1.5) scaling has been observed in practice. The current bottleneck is the evaluation of the potential integrals at the cavity boundary which scales linearly with the system size. To reduce this overhead, interpolation of the potential integrals on the cavity surface has been successfully used.

  12. Stable and flux-conserved meshfree formulation to model shocks

    NASA Astrophysics Data System (ADS)

    Roth, Michael J.; Chen, Jiun-Shyan; Slawson, Thomas R.; Danielson, Kent T.

    2016-05-01

    Accurate shock modeling requires that two critical issues be addressed: (1) correct representation of the essential shock physics, and (2) control of Gibbs phenomenon oscillation at the discontinuity. In this work a stable (oscillation limiting) and flux-conserved formulation under the reproducing kernel particle method is developed for shock modeling. A smoothed flux divergence is constructed under the framework of stabilized conforming nodal integration, which is locally-enriched with a Riemann solution to satisfy the entropy production constraints. This Riemann-enriched flux divergence is embedded into the reproducing kernel formulation through a velocity correction that also provides oscillation control at the shock. The correction is constrained to the shock region by an automatic shock detection algorithm that is constructed using the intrinsic spectral decomposition feature of the reproducing kernel approximation. Several numerical examples are provided to verify accuracy of the proposed formulation.

  13. On the formulation of a crystal plasticity model.

    SciTech Connect

    Marin, Esteban B.

    2006-08-01

    This report presents the formulation of a crystal elasto-viscoplastic model and the corresponding integration scheme. The model is suitable to represent the isothermal, anisotropic, large deformation of polycrystalline metals. The formulation is an extension of a rigid viscoplastic model to account for elasticity effects, and incorporates a number of changes with respect to a previous formulation [Marin & Dawson, 1998]. This extension is formally derived using the well-known multiplicative decomposition of the deformation gradient into an elastic and plastic components, where the elastic part is additionally decomposed into the elastic stretch V{sup e} and the proper orthogonal R{sup e} tensors. The constitutive equations are written in the intermediate, stress-free configuration obtained by unloading the deformed crystal through the elastic stretch V{sup e-}. The model is framed in a thermodynamic setting, and developed initially for large elastic strains. The crystal equations are then specialized to the case of small elastic strains, an assumption typically valid for metals. The developed integration scheme is implicit and proceeds by separating the spherical and deviatoric crystal responses. An ''approximate'' algorithmic material moduli is also derived for applications in implicit numerical codes. The model equations and their integration procedure have been implemented in both a material point simulator and a commercial finite element code. Both implementations are validated by solving a number of examples involving aggregates of either face centered cubic (FCC) or hexagonal close-packed (HCP) crystals subjected to different loading paths.

  14. Oil ganglion dynamics during immiscible displacement: model formulation

    SciTech Connect

    Payatakes, A.C.; Ng, K.M.; Flumerfelt, R.W.

    1980-05-01

    A model is formulated in order to study the transient behavior of oil ganglion populations during immiscible displacement in oil recovery processes. The model is composed of 3 components: a suitable model for granular porous media; a stochastic simulation method capable of predicting the expected fate (mobilization, breakup, stranding) of solitary oil ganglia moving through granular porous media; and 2 coupled ganglion population balance equations, one applying to moving ganglia and the other to stranded ones. The porous medium model consists of a regular network of randomly sized unit cells of the constricted tube type. 32 references.

  15. A binary model of textile composites; 1: Formulation

    SciTech Connect

    Cox, B.N.; Carter, W.C. ); Fleck, N.A. . Engineering Dept.)

    1994-10-01

    This paper presents a finite element model of polymer composites with three-dimensional (3D) reinforcement. The model performs Monte Carlo simulations of failure under monotonic and fatigue loading. The formulation of the model is guided by extensive prior experimental observations of 3D woven composites. Special emphasis is placed on realistic representation of the pattern of reinforcing tows, random irregularity in two positioning, randomness of the strengths of constituent elements, and the mechanics of stress redistribution around sites of local failure. The constitutive properties of model elements (or their distributions) are based on micromechanical models of observed failure events. Material properties that are appropriate analyzed by the model are contrasted with those amenable to much simpler models. Some illustrative model simulations are presented. Prescriptions for the calibration of the model for design and reliability applications and details of its performance in simulating the elastic and damaged regimes of 3D woven composites will appear in subsequent papers.

  16. Space-time formulation for finite element modeling of superconductors

    SciTech Connect

    Ashworth, Stephen P; Grilli, Francesco; Sirois, Frederic; Laforest, Marc

    2008-01-01

    In this paper we present a new model for computing the current density and field distributions in superconductors by means of a periodic space-time formulation for finite elements (FE). By considering a space dimension as time, we can use a static model to solve a time dependent problem. This allows overcoming one of the major problems of FE modeling of superconductors: the length of simulations, even for relatively simple cases. We present our first results and compare them to those obtained with a 'standard' time-dependent method and with analytical solutions.

  17. The Pantex Process model: Formulations of the evaluation planning module

    SciTech Connect

    JONES,DEAN A.; LAWTON,CRAIG R.; LIST,GEORGE FISHER; TURNQUIST,MARK ALAN

    1999-12-01

    This paper describes formulations of the Evaluation Planning Module that have been developed since its inception. This module is one of the core algorithms in the Pantex Process Model, a computerized model to support production planning in a complex manufacturing system at the Pantex Plant, a US Department of Energy facility. Pantex is responsible for three major DOE programs -- nuclear weapons disposal, stockpile evaluation, and stockpile maintenance -- using shared facilities, technicians, and equipment. The model reflects the interactions of scheduling constraints, material flow constraints, and the availability of required technicians and facilities.

  18. EMPIRICAL MODEL FOR FORMULATION OF CRYSTAL-TOLERANT HLW GLASSES

    SciTech Connect

    Matyas, Josef; Huckleberry, Adam R.; Rodriguez, Carmen P.; Vienna, John D.; Kruger, Albert A.

    2012-11-07

    Historically, high-level waste (HLW) glasses have been formulated with a low liquidus temperature (TL), or temperature at which the equilibrium fraction of spinel crystals in the melt is below 1 vol % (T0.01), nominally below 1050°C. These constraints cannot prevent the accumulation of large spinel crystals in considerably cooler regions (~ 850°C) of the glass discharge riser during melter idling and significantly limit the waste loading, which is reflected in a high volume of waste glass, and would result in high capital, production, and disposal costs. A developed empirical model predicts crystal accumulation in the riser of the melter as a function of concentration of spinel-forming components in glass, and thereby provides guidance in formulating crystal-tolerant glasses that would allow high waste loadings by keeping the spinel crystals small and therefore suspended in the glass.

  19. Lumped mass formulations for modeling flexible body systems

    NASA Technical Reports Server (NTRS)

    Rampalli, Rajiv

    1989-01-01

    The efforts of Mechanical Dynamics, Inc. in obtaining a general formulation for flexible bodies in a multibody setting are discussed. The efforts being supported by MDI, both in house and externally are summarized. The feasibility of using lumped mass approaches to modeling flexibility in a multibody dynamics context is examined. The kinematics and kinetics for a simple system consisting of two rigid bodies connected together by an elastic beam are developed in detail. Accuracy, efficiency and ease of use using this approach are some of the issues that are then looked at. The formulation is then generalized to a superelement containing several nodes and connecting several bodies. Superelement kinematics and kinetics equations are developed. The feasibility and effectiveness of the method is illustrated by the use of some examples illustrating phenomena common in the context of spacecraft motions.

  20. EMPIRICAL MODEL FOR FORMULATION OF CRYSTAL-TOLERANT HLW GLASSES

    SciTech Connect

    KRUGER AA; MATYAS J; HUCKLEBERRY AR; VIENNA JD; RODRIGUEZ CA

    2012-03-07

    Historically, high-level waste (HLW) glasses have been formulated with a low liquideus temperature (T{sub L}), or temperature at which the equilibrium fraction of spinel crystals in the melt is below 1 vol % (T{sub 0.01}), nominally below 1050 C. These constraints cannot prevent the accumulation of large spinel crystals in considerably cooler regions ({approx} 850 C) of the glass discharge riser during melter idling and significantly limit the waste loading, which is reflected in a high volume of waste glass, and would result in high capital, production, and disposal costs. A developed empirical model predicts crystal accumulation in the riser of the melter as a function of concentration of spinel-forming components in glass, and thereby provides guidance in formulating crystal-tolerant glasses that would allow high waste loadings by keeping the spinel crystals small and therefore suspended in the glass.

  1. Moisture desorption rates from TATB formulations: experiments and kinetic models.

    PubMed

    Glascoe, Elizabeth A; Dinh, Long N; Small, Ward; Overturf, George E

    2012-06-07

    The rate of water desorption from PBX-9502, a formulation containing 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), is measured using temperature-programmed desorption and modeled using conventional kinetic modeling methods. The results of these studies show two stages of moisture release. At lower temperatures, the release is likely assisted by thermal expansion of the TATB and melting of the Kel-F binder. At higher temperatures, a considerable amount of water is released and is attributed to sublimation of the TATB, which exposes new surfaces for water desorption.

  2. Retrostructural model to predict biomass formulations for barrier performance.

    PubMed

    Zhu Ryberg, Y Z; Edlund, U; Albertsson, A-C

    2012-08-13

    Barrier performance and retrostructural modeling of the macromolecular components demonstrate new design principles for film formulations based on renewable wood hydrolysates. Hardwood hydrolysates, which contain a fair share of lignin coexisting with poly- and oligosaccharides, offer excellent oxygen-barrier performance. A Hansen solubility parameter (HSP) model has been developed to convert the complex hydrolysate structural compositions into relevant matrix oxygen-permeability data allowing a systematic prediction of how the biomass should be formulated to generate an efficient barrier. HSP modeling suggests that the molecular packing ability plays a key role in the barrier performance. The actual size and distribution of free volume holes in the matrices were quantified in the subnanometer scale with Positron annihilation lifetime spectroscopy (PALS) verifying the affinity-driven assembly of macromolecular segments in a densely packed morphology and regulating the diffusion of small permeants through the matrix. The model is general and can be adapted to determine the macromolecular affinities of any hydrolysate biomass based on chemical composition.

  3. Modeling downstream fining in sand-bed rivers. I: Formulation

    USGS Publications Warehouse

    Wright, S.; Parker, G.

    2005-01-01

    In this paper a numerical modeling formulation is presented for simulation of the development of the longitudinal profile and bed sediment distribution in sand-bed rivers. The objective of the model application, which is presented in the companion paper (Wright and Parker, 2005), is to study the development of two characteristics of large, low-slope, sand-bed rivers: (1) a downstream decrease in bed slope (i.e. concave upward longitudinal profile) and (2) a downstream decrease in characteristic bed sediment diameter (e.g. the median bed surface size D50). Three mechanisms that lead to an upward concave profile and downstream fining are included in the modeling formulation: (1) a delta prograding into standing water at the downstream boundary, (2) sea-level rise, and (3) tectonic subsidence. In the companion paper (Wright and Parker, 2005) the model is applied to simulate the development of the longitudinal profile and downstream fining in sand-bed rivers flowing into the ocean during the past 5000 years of relatively slow sea-level rise. ?? 2005 International Association of Hydraulic Engineering and Research.

  4. On matrix model formulations of noncommutative Yang-Mills theories

    SciTech Connect

    Azeyanagi, Tatsuo; Hirata, Tomoyoshi; Hanada, Masanori

    2008-11-15

    We study the stability of noncommutative spaces in matrix models and discuss the continuum limit which leads to the noncommutative Yang-Mills theories. It turns out that most noncommutative spaces in bosonic models are unstable. This indicates perturbative instability of fuzzy R{sup D} pointed out by Van Raamsdonk and Armoni et al. persists to nonperturbative level in these cases. In this sense, these bosonic noncommutative Yang-Mills theories are not well-defined, or at least their matrix model formulations studied in this paper do not work. We also show that noncommutative backgrounds are stable in a supersymmetric matrix model deformed by a cubic Myers term, though the deformation itself breaks supersymmetry.

  5. Variational formulation of Budyko-Sellers climate models

    NASA Technical Reports Server (NTRS)

    North, G. R.; Howard, L.; Pollard, D.; Wielicki, B.

    1979-01-01

    A class of simple climate models including those of the Budyko-Sellers type are formulated from a variational principle. A functional is constructed for the zonally averaged mean annual temperature field such that extrema of the functional occur when the climate satisfies the usual energy-balance equation. Local minima of the functional correspond to stable solutions while saddle points correspond to unstable solutions. The technique can be used to construct approximate solutions from trial functions and to carry out finite-amplitude stability analyses. A spectral example is given in explicit detail.

  6. A general formulation for a mathematical PEM fuel cell model

    NASA Astrophysics Data System (ADS)

    Baschuk, J. J.; Li, Xianguo

    A general formulation for a comprehensive fuel cell model, based on the conservation principle is presented. The model formulation includes the electro-chemical reactions, proton migration, and the mass transport of the gaseous reactants and liquid water. Additionally, the model formulation can be applied to all regions of the PEM fuel cell: the bipolar plates, gas flow channels, electrode backing, catalyst, and polymer electrolyte layers. The model considers the PEM fuel cell to be composed of three phases: reactant gas, liquid water, and solid. These three phases can co-exist within the gas flow channels, electrode backing, catalyst, and polymer electrolyte layers. The conservation of mass, momentum, species, and energy are applied to each phase, with the technique of volume averaging being used to incorporate the interactions between the phases as interfacial source terms. In order to avoid problems arising from phase discontinuities, the gas and liquid phases are considered as a mixture. The momentum interactions between the fluid and solid phases are modeled by the Darcy-Forchheimer term. The electro-oxidation of H and CO, the reduction of O, and the heterogeneous oxidation of H and CO are considered in the catalyst layers. Due to the small pore size of the polymer electrolyte layer, the generalized Stefan-Maxwell equations, with the polymer considered as a diffusing species, are used to describe species transport. One consequence of considering the gas and liquid phases as a mixture is that expressions for the velocity of the individual phases relative to the mixture must be developed. In the gas flow channels, the flow is assumed homogeneous, while the Darcy and Schlögl equations are used to describe liquid water transport in the electrode backing and polymer electrolyte layers. Thus, two sets of equations, one for the mixture and another for the solid phase, can be developed to describe the processes occurring within a PEM fuel cell. These equations are in

  7. A multilayer biochemical dry deposition model. 1. Model formulation

    NASA Astrophysics Data System (ADS)

    Wu, Yihua; Brashers, Bart; Finkelstein, Peter L.; Pleim, Jonathan E.

    2003-01-01

    A multilayer biochemical dry deposition model has been developed based on the NOAA Multilayer Model (MLM; [1998]) to study gaseous exchanges between the soil, plants, and the atmosphere. Most of the parameterizations and submodels have been updated or replaced. The numerical integration was improved, and an aerodynamic resistance based on Monin-Obukhov theory was added. An appropriate parameterization for the leaf boundary layer resistance was chosen. A biochemical stomatal resistance model was chosen based on comparisons of four different existing stomatal resistance schemes. It describes photosynthesis and respiration and their coupling with stomatal resistance for sunlit and shaded leaves separately. Various aspects of the photosynthetic process in both C3 and C4 plants are considered in the model. To drive the photosynthesis model, the canopy radiation scheme has been updated. Leaf area index measurements are adjusted to account for stem area index. A normalized soil water stress factor was applied to potential photosynthesis to account for plant response to both drought and water-logging stresses. A new cuticle resistance model was derived based on membrane passive transport theory and Fick's first law. It accounts for the effects of diffusivity and solubility of specific gases in the cuticle membrane, as well as the thickness of the cuticle membrane. The model is designed for use in the nationwide dry deposition networks, for example, the Clean Air Status And Trends Network (CASTNet), and mesoscale models, for example, the Community Multiscale Air Quality model (CMAQ) and even the Weather Research and Forecasting model (WRF).

  8. Affine group formulation of the Standard Model coupled to gravity

    SciTech Connect

    Chou, Ching-Yi; Ita, Eyo; Soo, Chopin

    2014-04-15

    In this work we apply the affine group formalism for four dimensional gravity of Lorentzian signature, which is based on Klauder’s affine algebraic program, to the formulation of the Hamiltonian constraint of the interaction of matter and all forces, including gravity with non-vanishing cosmological constant Λ, as an affine Lie algebra. We use the hermitian action of fermions coupled to gravitation and Yang–Mills theory to find the density weight one fermionic super-Hamiltonian constraint. This term, combined with the Yang–Mills and Higgs energy densities, are composed with York’s integrated time functional. The result, when combined with the imaginary part of the Chern–Simons functional Q, forms the affine commutation relation with the volume element V(x). Affine algebraic quantization of gravitation and matter on equal footing implies a fundamental uncertainty relation which is predicated upon a non-vanishing cosmological constant. -- Highlights: •Wheeler–DeWitt equation (WDW) quantized as affine algebra, realizing Klauder’s program. •WDW formulated for interaction of matter and all forces, including gravity, as affine algebra. •WDW features Hermitian generators in spite of fermionic content: Standard Model addressed. •Constructed a family of physical states for the full, coupled theory via affine coherent states. •Fundamental uncertainty relation, predicated on non-vanishing cosmological constant.

  9. Formulation of a k - ω based DDES model

    NASA Astrophysics Data System (ADS)

    Rudra Reddy, Karthik; Durbin, Paul

    2013-11-01

    DES models fall under the category of Hybrid RANS/LES models, and they employ RANS to resolve near-wall boundary layers in the flow domain and LES away from the surface. The idea of DES is applicable to any RANS model, and various versions of the method reflect this. A general DDES formulation was put forth (Spalart et al., 2006) suitable for use with any RANS model, and later adapted for use with the k - ω SST model (Gritskevich et al., 2012). The current work develops a variant based on the k - ω model. In this version, length scales enter directly in the subgrid eddy-viscosity, rather than being used in the dissipation term of the k-equation; indeed, one can approach it as replacing length-scale clipping, in standard DDES, with velocity scale clipping. The length scales were modified in order to account for the log-layer mismatch, a well-known issue with DDES. Simulation results from channel flow and flow over a backward-facing step are presented.

  10. A MULTILAYER BIOCHEMICAL DRY DEPOSITION MODEL 1. MODEL FORMULATION

    EPA Science Inventory

    A multilayer biochemical dry deposition model has been developed based on the NOAA Multilayer Model (MLM) to study gaseous exchanges between the soil, plants, and the atmosphere. Most of the parameterizations and submodels have been updated or replaced. The numerical integration ...

  11. A MULTILAYER BIOCHEMICAL DRY DEPOSITION MODEL 1. MODEL FORMULATION

    EPA Science Inventory

    A multilayer biochemical dry deposition model has been developed based on the NOAA Multilayer Model (MLM) to study gaseous exchanges between the soil, plants, and the atmosphere. Most of the parameterizations and submodels have been updated or replaced. The numerical integration ...

  12. Differential geometry based solvation model I: Eulerian formulation.

    PubMed

    Chen, Zhan; Baker, Nathan A; Wei, G W

    2010-11-01

    This paper presents a differential geometry based model for the analysis and computation of the equilibrium property of solvation. Differential geometry theory of surfaces is utilized to define and construct smooth interfaces with good stability and differentiability for use in characterizing the solvent-solute boundaries and in generating continuous dielectric functions across the computational domain. A total free energy functional is constructed to couple polar and nonpolar contributions to the salvation process. Geometric measure theory is employed to rigorously convert a Lagrangian formulation of the surface energy into an Eulerian formulation so as to bring all energy terms into an equal footing. By minimizing the total free energy functional, we derive coupled generalized Poisson-Boltzmann equation (GPBE) and generalized geometric flow equation (GGFE) for the electrostatic potential and the construction of realistic solvent-solute boundaries, respectively. By solving the coupled GPBE and GGFE, we obtain the electrostatic potential, the solvent-solute boundary profile, and the smooth dielectric function, and thereby improve the accuracy and stability of implicit solvation calculations. We also design efficient second order numerical schemes for the solution of the GPBE and GGFE. Matrix resulted from the discretization of the GPBE is accelerated with appropriate preconditioners. An alternative direct implicit (ADI) scheme is designed to improve the stability of solving the GGFE. Two iterative approaches are designed to solve the coupled system of nonlinear partial differential equations. Extensive numerical experiments are designed to validate the present theoretical model, test computational methods, and optimize numerical algorithms. Example solvation analysis of both small compounds and proteins are carried out to further demonstrate the accuracy, stability, efficiency and robustness of the present new model and numerical approaches. Comparison is given to

  13. Differential geometry based solvation model I: Eulerian formulation

    PubMed Central

    Chen, Zhan; Baker, Nathan A.; Wei, G. W.

    2010-01-01

    This paper presents a differential geometry based model for the analysis and computation of the equilibrium property of solvation. Differential geometry theory of surfaces is utilized to define and construct smooth interfaces with good stability and differentiability for use in characterizing the solvent-solute boundaries and in generating continuous dielectric functions across the computational domain. A total free energy functional is constructed to couple polar and nonpolar contributions to the salvation process. Geometric measure theory is employed to rigorously convert a Lagrangian formulation of the surface energy into an Eulerian formulation so as to bring all energy terms into an equal footing. By minimizing the total free energy functional, we derive coupled generalized Poisson-Boltzmann equation (GPBE) and generalized geometric flow equation (GGFE) for the electrostatic potential and the construction of realistic solvent-solute boundaries, respectively. By solving the coupled GPBE and GGFE, we obtain the electrostatic potential, the solvent-solute boundary profile, and the smooth dielectric function, and thereby improve the accuracy and stability of implicit solvation calculations. We also design efficient second order numerical schemes for the solution of the GPBE and GGFE. Matrix resulted from the discretization of the GPBE is accelerated with appropriate preconditioners. An alternative direct implicit (ADI) scheme is designed to improve the stability of solving the GGFE. Two iterative approaches are designed to solve the coupled system of nonlinear partial differential equations. Extensive numerical experiments are designed to validate the present theoretical model, test computational methods, and optimize numerical algorithms. Example solvation analysis of both small compounds and proteins are carried out to further demonstrate the accuracy, stability, efficiency and robustness of the present new model and numerical approaches. Comparison is given to

  14. Radiolysis Model Formulation for Integration with the Mixed Potential Model

    SciTech Connect

    Buck, Edgar C.; Wittman, Richard S.

    2014-07-10

    The U.S. Department of Energy Office of Nuclear Energy (DOE-NE), Office of Fuel Cycle Technology has established the Used Fuel Disposition Campaign (UFDC) to conduct the research and development activities related to storage, transportation, and disposal of used nuclear fuel (UNF) and high-level radioactive waste. Within the UFDC, the components for a general system model of the degradation and subsequent transport of UNF is being developed to analyze the performance of disposal options [Sassani et al., 2012]. Two model components of the near-field part of the problem are the ANL Mixed Potential Model and the PNNL Radiolysis Model. This report is in response to the desire to integrate the two models as outlined in [Buck, E.C, J.L. Jerden, W.L. Ebert, R.S. Wittman, (2013) “Coupling the Mixed Potential and Radiolysis Models for Used Fuel Degradation,” FCRD-UFD-2013-000290, M3FT-PN0806058

  15. Biomechanical behaviour of ankle ligaments: constitutive formulation and numerical modelling.

    PubMed

    Forestiero, A; Carniel, E L; Natali, A N

    2014-01-01

    This study was aimed at the definition of a constitutive formulation of ankle ligaments and of a procedure for the constitutive parameters evaluation, for the biomechanical analysis by means of numerical models. To interpret the typical features of ligaments mechanical response, as anisotropic configuration, geometric non-linearity, non-linear elasticity and time-dependent behaviour, a specific fibre-reinforced visco-hyperelastic model is provided. The identification of constitutive parameters is performed by a stochastic-deterministic procedure that minimises the discrepancy between experimental and computational results. A preliminary evaluation of parameters is performed by analytical models in order to define reference values. Afterwards, solid models are developed to consider the complex histo-morphometric configuration of samples as a basis for the definition of numerical models. The results obtained are adopted for upgrading parameter values by comparison with specific mechanical tests. Assuming the new parameters set, the final numerical results are compared with the overall set of experimental data, to assess the reliability and efficacy of the analysis developed for the interpretation of the mechanical response of ankle ligaments.

  16. A Bayesian state-space formulation of dynamic occupancy models.

    PubMed

    Royle, J Andrew; Kéry, Marc

    2007-07-01

    Species occurrence and its dynamic components, extinction and colonization probabilities, are focal quantities in biogeography and metapopulation biology, and for species conservation assessments. It has been increasingly appreciated that these parameters must be estimated separately from detection probability to avoid the biases induced by non-detection error. Hence, there is now considerable theoretical and practical interest in dynamic occupancy models that contain explicit representations of metapopulation dynamics such as extinction, colonization, and turnover as well as growth rates. We describe a hierarchical parameterization of these models that is analogous to the state-space formulation of models in time series, where the model is represented by two components, one for the partially observable occupancy process and another for the observations conditional on that process. This parameterization naturally allows estimation of all parameters of the conventional approach to occupancy models, but in addition, yields great flexibility and extensibility, e.g., to modeling heterogeneity or latent structure in model parameters. We also highlight the important distinction between population and finite sample inference; the latter yields much more precise estimates for the particular sample at hand. Finite sample estimates can easily be obtained using the state-space representation of the model but are difficult to obtain under the conventional approach of likelihood-based estimation. We use R and WinBUGS to apply the model to two examples. In a standard analysis for the European Crossbill in a large Swiss monitoring program, we fit a model with year-specific parameters. Estimates of the dynamic parameters varied greatly among years, highlighting the irruptive population dynamics of that species. In the second example, we analyze route occupancy of Cerulean Warblers in the North American Breeding Bird Survey (BBS) using a model allowing for site

  17. A Bayesian state-space formulation of dynamic occupancy models

    USGS Publications Warehouse

    Royle, J. Andrew; Kery, M.

    2007-01-01

    Species occurrence and its dynamic components, extinction and colonization probabilities, are focal quantities in biogeography and metapopulation biology, and for species conservation assessments. It has been increasingly appreciated that these parameters must be estimated separately from detection probability to avoid the biases induced by nondetection error. Hence, there is now considerable theoretical and practical interest in dynamic occupancy models that contain explicit representations of metapopulation dynamics such as extinction, colonization, and turnover as well as growth rates. We describe a hierarchical parameterization of these models that is analogous to the state-space formulation of models in time series, where the model is represented by two components, one for the partially observable occupancy process and another for the observations conditional on that process. This parameterization naturally allows estimation of all parameters of the conventional approach to occupancy models, but in addition, yields great flexibility and extensibility, e.g., to modeling heterogeneity or latent structure in model parameters. We also highlight the important distinction between population and finite sample inference; the latter yields much more precise estimates for the particular sample at hand. Finite sample estimates can easily be obtained using the state-space representation of the model but are difficult to obtain under the conventional approach of likelihood-based estimation. We use R and Win BUGS to apply the model to two examples. In a standard analysis for the European Crossbill in a large Swiss monitoring program, we fit a model with year-specific parameters. Estimates of the dynamic parameters varied greatly among years, highlighting the irruptive population dynamics of that species. In the second example, we analyze route occupancy of Cerulean Warblers in the North American Breeding Bird Survey (BBS) using a model allowing for site

  18. Differential geometry based solvation model. III. Quantum formulation.

    PubMed

    Chen, Zhan; Wei, Guo-Wei

    2011-11-21

    to many other classic and quantum models. By using experimental data, we show that the present quantum formulation of our differential geometry based multiscale solvation model improves the prediction of our earlier models, and outperforms some explicit solvation model.

  19. The integrated Earth System Model Version 1: formulation and functionality

    SciTech Connect

    Collins, William D.; Craig, Anthony P.; Truesdale, John E.; Di Vittorio, Alan; Jones, Andrew D.; Bond-Lamberty, Benjamin; Calvin, Katherine V.; Edmonds, James A.; Kim, Son H.; Thomson, Allison M.; Patel, Pralit L.; Zhou, Yuyu; Mao, Jiafu; Shi, Xiaoying; Thornton, Peter E.; Chini, Louise M.; Hurtt, George C.

    2015-07-23

    The integrated Earth System Model (iESM) has been developed as a new tool for pro- jecting the joint human/climate system. The iESM is based upon coupling an Integrated Assessment Model (IAM) and an Earth System Model (ESM) into a common modeling in- frastructure. IAMs are the primary tool for describing the human–Earth system, including the sources of global greenhouse gases (GHGs) and short-lived species, land use and land cover change, and other resource-related drivers of anthropogenic climate change. ESMs are the primary scientific tools for examining the physical, chemical, and biogeochemical impacts of human-induced changes to the climate system. The iESM project integrates the economic and human dimension modeling of an IAM and a fully coupled ESM within a sin- gle simulation system while maintaining the separability of each model if needed. Both IAM and ESM codes are developed and used by large communities and have been extensively applied in recent national and international climate assessments. By introducing heretofore- omitted feedbacks between natural and societal drivers, we can improve scientific under- standing of the human–Earth system dynamics. Potential applications include studies of the interactions and feedbacks leading to the timing, scale, and geographic distribution of emissions trajectories and other human influences, corresponding climate effects, and the subsequent impacts of a changing climate on human and natural systems. This paper de- scribes the formulation, requirements, implementation, testing, and resulting functionality of the first version of the iESM released to the global climate community.

  20. The integrated Earth system model version 1: formulation and functionality

    NASA Astrophysics Data System (ADS)

    Collins, W. D.; Craig, A. P.; Truesdale, J. E.; Di Vittorio, A. V.; Jones, A. D.; Bond-Lamberty, B.; Calvin, K. V.; Edmonds, J. A.; Kim, S. H.; Thomson, A. M.; Patel, P.; Zhou, Y.; Mao, J.; Shi, X.; Thornton, P. E.; Chini, L. P.; Hurtt, G. C.

    2015-07-01

    The integrated Earth system model (iESM) has been developed as a new tool for projecting the joint human/climate system. The iESM is based upon coupling an integrated assessment model (IAM) and an Earth system model (ESM) into a common modeling infrastructure. IAMs are the primary tool for describing the human-Earth system, including the sources of global greenhouse gases (GHGs) and short-lived species (SLS), land use and land cover change (LULCC), and other resource-related drivers of anthropogenic climate change. ESMs are the primary scientific tools for examining the physical, chemical, and biogeochemical impacts of human-induced changes to the climate system. The iESM project integrates the economic and human-dimension modeling of an IAM and a fully coupled ESM within a single simulation system while maintaining the separability of each model if needed. Both IAM and ESM codes are developed and used by large communities and have been extensively applied in recent national and international climate assessments. By introducing heretofore-omitted feedbacks between natural and societal drivers, we can improve scientific understanding of the human-Earth system dynamics. Potential applications include studies of the interactions and feedbacks leading to the timing, scale, and geographic distribution of emissions trajectories and other human influences, corresponding climate effects, and the subsequent impacts of a changing climate on human and natural systems. This paper describes the formulation, requirements, implementation, testing, and resulting functionality of the first version of the iESM released to the global climate community.

  1. The integrated Earth system model version 1: formulation and functionality

    DOE PAGES

    Collins, W. D.; Craig, A. P.; Truesdale, J. E.; ...

    2015-07-23

    The integrated Earth system model (iESM) has been developed as a new tool for projecting the joint human/climate system. The iESM is based upon coupling an integrated assessment model (IAM) and an Earth system model (ESM) into a common modeling infrastructure. IAMs are the primary tool for describing the human–Earth system, including the sources of global greenhouse gases (GHGs) and short-lived species (SLS), land use and land cover change (LULCC), and other resource-related drivers of anthropogenic climate change. ESMs are the primary scientific tools for examining the physical, chemical, and biogeochemical impacts of human-induced changes to the climate system. Themore » iESM project integrates the economic and human-dimension modeling of an IAM and a fully coupled ESM within a single simulation system while maintaining the separability of each model if needed. Both IAM and ESM codes are developed and used by large communities and have been extensively applied in recent national and international climate assessments. By introducing heretofore-omitted feedbacks between natural and societal drivers, we can improve scientific understanding of the human–Earth system dynamics. Potential applications include studies of the interactions and feedbacks leading to the timing, scale, and geographic distribution of emissions trajectories and other human influences, corresponding climate effects, and the subsequent impacts of a changing climate on human and natural systems. This paper describes the formulation, requirements, implementation, testing, and resulting functionality of the first version of the iESM released to the global climate community.« less

  2. Analytical formulation of a discrete chiral elastic metamaterial model

    NASA Astrophysics Data System (ADS)

    Liu, X. N.; Huang, G. L.; Hu, G. K.

    2012-04-01

    By embedding appropriately designed chiral local resonators in a host elastic media, a chiral metamaterial with simultaneously negative effective density and bulk modulus can be achieved. In this work, an two dimentional (2D) ideal discrete model for the chiral elastic metamaterial is proposed. The discrete dynamic equation is derived and then homogenized to give the continuous description of the metamaterial. The homogenization procedure is validated by the agreement of the dispersion curve of the discrete and homogenized formulations. The form of homogenized governing equations of the metamaterial cannot be classified as a traditional Cauchy elastic theory. This result conforms the conscience that the Cauchy elasticity cannot reflect the chirality, which is usually captured by higher order theory such as the non-centrosymmetric micropolar elasticity. However when reduced to a (2D) problem, the existing chiral micropolar theory becomes non-chiral. Based on reinterpretation of isotropic tensors in a 2D case, we propose a continuum theory to model the chiral effect for 2D isotropic chiral solids. This 2D chiral micropolar theory constitutes a hopeful macroscopic framework for the theory development of chiral metamaterials.

  3. Microscopic formulation of the interacting boson model for rotational nuclei

    SciTech Connect

    Nomura, Kosuke; Shimizu, Noritaka; Otsuka, Takaharu; Guo, Lu

    2011-04-15

    We propose a novel formulation of the interacting boson model (IBM) for rotational nuclei with axially symmetric, strong deformation. The intrinsic structure represented by the potential-energy surface (PES) of a given multinucleon system has a certain similarity to that of the corresponding multiboson system. Based on this feature, one can derive an appropriate boson Hamiltonian, as already reported. This prescription, however, has a major difficulty in the rotational spectra of strongly deformed nuclei: the bosonic moment of inertia is significantly smaller than the corresponding nucleonic one. We present that this difficulty originates in the difference between the rotational response of a nucleon system and that of the corresponding boson system, and could arise even if the PESs of the two systems were identical. We further suggest that the problem can be solved by implementing the L{center_dot}L term into the IBM Hamiltonian, with the coupling constant derived from the cranking approach of Skyrme mean-field models. The validity of the method is confirmed for rare-earth and actinoid nuclei, as their experimental rotational yrast bands are reproduced nicely.

  4. Potts-model formulation of the random resistor network

    NASA Astrophysics Data System (ADS)

    Harris, A. B.; Lubensky, T. C.

    1987-05-01

    The randomly diluted resistor network is formulated in terms of an n-replicated s-state Potts model with a spin-spin coupling constant J in the limit when first n, then s, and finally 1/J go to zero. This limit is discussed and to leading order in 1/J the generalized susceptibility is shown to reproduce the results of the accompanying paper where the resistor network is treated using the xy model. This Potts Hamiltonian is converted into a field theory by the usual Hubbard-Stratonovich transformation and thereby a renormalization-group treatment is developed to obtain the corrections to the critical exponents to first order in ɛ=6-d, where d is the spatial dimensionality. The recursion relations are shown to be the same as for the xy model. Their detailed analysis (given in the accompanying paper) gives the resistance crossover exponent as φ1=1+ɛ/42, and determines the critical exponent, t for the conductivity of the randomly diluted resistor network at concentrations, p, just above the percolation threshold: t=(d-2)ν+φ1, where ν is the critical exponent for the correlation length at the percolation threshold. These results correct previously accepted results giving φ=1 to all orders in ɛ. The new result for φ1 removes the paradox associated with the numerical result that t>1 for d=2, and also shows that the Alexander-Orbach conjecture, while numerically quite accurate, is not exact, since it disagrees with the ɛ expansion.

  5. Bayesian Estimation of Graded Response Multilevel Models Using Gibbs Sampling: Formulation and Illustration

    ERIC Educational Resources Information Center

    Natesan, Prathiba; Limbers, Christine; Varni, James W.

    2010-01-01

    The present study presents the formulation of graded response models in the multilevel framework (as nonlinear mixed models) and demonstrates their use in estimating item parameters and investigating the group-level effects for specific covariates using Bayesian estimation. The graded response multilevel model (GRMM) combines the formulation of…

  6. Differential geometry based solvation model II: Lagrangian formulation.

    PubMed

    Chen, Zhan; Baker, Nathan A; Wei, G W

    2011-12-01

    Solvation is an elementary process in nature and is of paramount importance to more sophisticated chemical, biological and biomolecular processes. The understanding of solvation is an essential prerequisite for the quantitative description and analysis of biomolecular systems. This work presents a Lagrangian formulation of our differential geometry based solvation models. The Lagrangian representation of biomolecular surfaces has a few utilities/advantages. First, it provides an essential basis for biomolecular visualization, surface electrostatic potential map and visual perception of biomolecules. Additionally, it is consistent with the conventional setting of implicit solvent theories and thus, many existing theoretical algorithms and computational software packages can be directly employed. Finally, the Lagrangian representation does not need to resort to artificially enlarged van der Waals radii as often required by the Eulerian representation in solvation analysis. The main goal of the present work is to analyze the connection, similarity and difference between the Eulerian and Lagrangian formalisms of the solvation model. Such analysis is important to the understanding of the differential geometry based solvation model. The present model extends the scaled particle theory of nonpolar solvation model with a solvent-solute interaction potential. The nonpolar solvation model is completed with a Poisson-Boltzmann (PB) theory based polar solvation model. The differential geometry theory of surfaces is employed to provide a natural description of solvent-solute interfaces. The optimization of the total free energy functional, which encompasses the polar and nonpolar contributions, leads to coupled potential driven geometric flow and PB equations. Due to the development of singularities and nonsmooth manifolds in the Lagrangian representation, the resulting potential-driven geometric flow equation is embedded into the Eulerian representation for the purpose of

  7. Differential geometry based solvation model II: Lagrangian formulation

    PubMed Central

    Chen, Zhan; Baker, Nathan A.; Wei, G. W.

    2010-01-01

    Solvation is an elementary process in nature and is of paramount importance to more sophisticated chemical, biological and biomolecular processes. The understanding of solvation is an essential prerequisite for the quantitative description and analysis of biomolecular systems. This work presents a Lagrangian formulation of our differential geometry based solvation model. The Lagrangian representation of biomolecular surfaces has a few utilities/advantages. First, it provides an essential basis for biomolecular visualization, surface electrostatic potential map and visual perception of biomolecules. Additionally, it is consistent with the conventional setting of implicit solvent theories and thus, many existing theoretical algorithms and computational software packages can be directly employed. Finally, the Lagrangian representation does not need to resort to artificially enlarged van der Waals radii as often required by the Eulerian representation in solvation analysis. The main goal of the present work is to analyze the connection, similarity and difference between the Eulerian and Lagrangian formalisms of the solvation model. Such analysis is important to the understanding of the differential geometry based solvation model. The present model extends the scaled particle theory (SPT) of nonpolar solvation model with a solvent-solute interaction potential. The nonpolar solvation model is completed with a Poisson-Boltzmann (PB) theory based polar solvation model. The differential geometry theory of surfaces is employed to provide a natural description of solvent-solute interfaces. The minimization of the total free energy functional, which encompasses the polar and nonpolar contributions, leads to coupled potential driven geometric flow and Poisson-Boltzmann equations. Due to the development of singularities and nonsmooth manifolds in the Lagrangian representation, the resulting potential-driven geometric flow equation is embedded into the Eulerian representation for

  8. Modeling individual effects in the Cormack-Jolly-Seber Model: A state-space formulation

    USGS Publications Warehouse

    Royle, J. Andrew

    2008-01-01

    In population and evolutionary biology, there exists considerable interest in individual heterogeneity in parameters of demographic models for open populations. However, flexible and practical solutions to the development of such models have proven to be elusive. In this article, I provide a state-space formulation of open population capture-recapture models with individual effects. The state-space formulation provides a generic and flexible framework for modeling and inference in models with individual effects, and it yields a practical means of estimation in these complex problems via contemporary methods of Markov chain Monte Carlo. A straightforward implementation can be achieved in the software package WinBUGS. I provide an analysis of a simple model with constant parameter detection and survival probability parameters. A second example is based on data from a 7-year study of European dippers, in which a model with year and individual effects is fitted.

  9. Higher Order Modeling In the BEM/FEM Hybrid Formulation

    NASA Technical Reports Server (NTRS)

    Fink, Patrick W.; Wilton, Don R.

    2000-01-01

    Hybrid formulations using low order curl-conforming bases to represent the total electric field within a finite element region and low order divergence-conforming bases to represent equivalent electric and magnetic currents on the boundary are well known. However, higher-order divergence and curl-conforming bases have been shown to provide significant benefits in convergence rates and accuracy when employed in strictly integral equation and strictly finite element formulations. In this paper, a hybrid electric field formulation employing higher order bases is presented. The paper addresses benefits and issues associated with using higher order divergence-and curl-conforming bases in the hybrid finite element/boundary element electric field formulation. The method of singularity subtraction may be used to compute the self terms of the boundary integral when the bases are of low order. But this method becomes laborious and requires great care when the divergence conforming bases are of higher order. In order to handle these singularities simply and accurately, a generalized Gaussian quadrature method is employed in which the expansion functions account for the singularity. In preliminary tests of the higher order hybrid formulation, the equivalent electric current induced by scattering of a plane wave from a square dielectric cylinder is examined. Accurate results are obtained using only a two-triangle mesh when the current basis is of order 4 or 5. Additional results are presented comparing the error obtained using higher order bases to that obtained using lower order bases when the number of unknowns is approximately equal. Also, convergence rates obtained with higher order bases are compared to those obtained with lower order bases for selected sample problems.

  10. Schwinger Boson Formulation and Solution of the Crow-Kimura and Eigen Models of Quasispecies Theory

    NASA Astrophysics Data System (ADS)

    Park, Jeong-Man; Deem, Michael W.

    2006-11-01

    We express the Crow-Kimura and Eigen models of quasispecies theory in a functional integral representation. We formulate the spin coherent state functional integrals using the Schwinger Boson method. In this formulation, we are able to deduce the long-time behavior of these models for arbitrary replication and degradation functions. We discuss the phase transitions that occur in these models as a function of mutation rate. We derive for these models the leading order corrections to the infinite genome length limit.

  11. Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks.

    PubMed

    Saa, Pedro A; Nielsen, Lars K

    2017-09-12

    Kinetic models are critical to predict the dynamic behaviour of metabolic networks. Mechanistic kinetic models for large networks remain uncommon due to the difficulty of fitting their parameters. Recent modelling frameworks promise new ways to overcome this obstacle while retaining predictive capabilities. In this review, we present an overview of the relevant mathematical frameworks for kinetic formulation, construction and analysis. Starting with kinetic formalisms, we next review statistical methods for parameter inference, as well as recent computational frameworks applied to the construction and analysis of kinetic models. Finally, we discuss opportunities and limitations hindering the development of larger kinetic reconstructions. Copyright © 2017. Published by Elsevier Inc.

  12. AERMOD: A DISPERSION MODEL FOR INDUSTRIAL SOURCE APPLICATIONS PART I: GENERAL MODEL FORMULATION AND BOUNDARY LAYER CHARACTERIZATION

    EPA Science Inventory

    The formulations of the AMS/EPA Regulatory Model Improvement Committee's applied air dispersion model (AERMOD) as related to the characterization of the planetary boundary layer are described. This is the first in a series of three articles. Part II describes the formulation of...

  13. AERMOD: A DISPERSION MODEL FOR INDUSTRIAL SOURCE APPLICATIONS PART I: GENERAL MODEL FORMULATION AND BOUNDARY LAYER CHARACTERIZATION

    EPA Science Inventory

    The formulations of the AMS/EPA Regulatory Model Improvement Committee's applied air dispersion model (AERMOD) as related to the characterization of the planetary boundary layer are described. This is the first in a series of three articles. Part II describes the formulation of...

  14. An optimisation model for regional integrated solid waste management I. Model formulation.

    PubMed

    Najm, M Abou; El-Fadel, M; Ayoub, G; El-Taha, M; Al-Awar, F

    2002-02-01

    Increased environmental concerns and the emphasis on material and energy recovery are gradually changing the orientation of MSW management and planning. In this context, the application of optimisation techniques have been introduced to design the least cost solid waste management systems, considering the variety of management processes. This study presents a model that was developed and applied to serve as a solid waste decision support system for MSW management taking into account both socio-economic and environmental considerations. The model accounts for solid waste generation rates, composition, collection, treatment, disposal as well as potential environmental impacts of various MSW management techniques. The model follows a linear programming formulation with the framework of dynamic optimisation. The model can serve as a tool to evaluate various MSW management alternatives and obtain the optimal combination of technologies for the handling, treatment and disposal of MSW in an economic and environmentally sustainable way. The sensitivity of various waste management policies will be also addressed. The work is presented in a series of two papers: (I) model formulation, and (II) model application and sensitivity analysis.

  15. Problem Formulation for Optimal Array Modeling and Planning

    NASA Technical Reports Server (NTRS)

    Cheung, Kar-Ming; Lee, Charles H.; Ho, Jeannie

    2006-01-01

    In this paper we describe an optimal modeling and planning framework for the future large array of DSN antennas. This framework takes into account the array link performance models, reliability models, constrain models, and objective functions, and determines the optimal sub-array clusters configuration that will support the maximum number of concurrent missions based on mission link properties, antenna element reliabilities, mission requests, and array operation constraints. ..

  16. A Corrected Formulation of the Multilayer Model (MLM) for Inferring Gaseous Dry Deposition to Vegetated Surfaces

    NASA Technical Reports Server (NTRS)

    Saylor, Rick D.; Wolfe, Glenn M.; Meyers, Tilden P.; Hicks, Bruce B.

    2014-01-01

    The Multilayer Model (MLM) has been used for many years to infer dry deposition fluxes from measured trace species concentrations and standard meteorological measurements for national networks in the U.S., including the U.S. Environmental Protection Agency's Clean Air Status and Trends Network (CASTNet). MLM utilizes a resistance analogy to calculate deposition velocities appropriate for whole vegetative canopies, while employing a multilayer integration to account for vertically varying meteorology, canopy morphology and radiative transfer within the canopy. However, the MLM formulation, as it was originally presented and as it has been subsequently employed, contains a non-physical representation related to the leaf-level quasi-laminar boundary layer resistance that affects the calculation of the total canopy resistance. In this note, the non-physical representation of the canopy resistance as originally formulated in MLM is discussed and a revised, physically consistent, formulation is suggested as a replacement. The revised canopy resistance formulation reduces estimates of HNO3 deposition velocities by as much as 38% during mid-day as compared to values generated by the original formulation. Inferred deposition velocities for SO2 and O3 are not significantly altered by the change in formulation (less than 3%). Inferred deposition loadings of oxidized and total nitrogen from CASTNet data may be reduced by 10-20% and 5-10%, respectively, for the Eastern U. S. when employing the revised formulation of MLM as compared to the original formulation.

  17. A corrected formulation of the Multilayer Model (MLM) for inferring gaseous dry deposition to vegetated surfaces

    NASA Astrophysics Data System (ADS)

    Saylor, Rick D.; Wolfe, Glenn M.; Meyers, Tilden P.; Hicks, Bruce B.

    2014-08-01

    The Multilayer Model (MLM) has been used for many years to infer dry deposition fluxes from measured trace species concentrations and standard meteorological measurements for national networks in the U.S., including the U.S. Environmental Protection Agency's Clean Air Status and Trends Network (CASTNet). MLM utilizes a resistance analogy to calculate deposition velocities appropriate for whole vegetative canopies, while employing a multilayer integration to account for vertically varying meteorology, canopy morphology and radiative transfer within the canopy. However, the MLM formulation, as it was originally presented and as it has been subsequently employed, contains a non-physical representation related to the leaf-level quasi-laminar boundary layer resistance that affects the calculation of the total canopy resistance. In this note, the non-physical representation of the canopy resistance as originally formulated in MLM is discussed and a revised, physically consistent, formulation is suggested as a replacement. The revised canopy resistance formulation reduces estimates of HNO3 deposition velocities by as much as 38% during mid-day as compared to values generated by the original formulation. Inferred deposition velocities for SO2 and O3 are not significantly altered by the change in formulation (<3%). Inferred deposition loadings of oxidized and total nitrogen from CASTNet data may be reduced by 10-20% and 5-10%, respectively, for the Eastern U. S. when employing the revised formulation of MLM as compared to the original formulation.

  18. Modeling of polymer networks for application to solid propellant formulating

    NASA Technical Reports Server (NTRS)

    Marsh, H. E.

    1979-01-01

    Methods for predicting the network structural characteristics formed by the curing of pourable elastomers were presented; as well as the logic which was applied in the development of mathematical models. A universal approach for modeling was developed and verified by comparison with other methods in application to a complex system. Several applications of network models to practical problems are described.

  19. An Empirical Model for Formulating Operational Missions for Community Colleges.

    ERIC Educational Resources Information Center

    Richardson, Richard C., Jr.; Doucette, Donald S.

    A research project was conducted to develop and implement a model for community college missions. The new model would depart from existing models, which utilize a hierarchy of decreasing levels of generality beginning with institutional missions and culminating in objectives. In contrast, this research defined institutional mission in terms of…

  20. Automated model formulation for time-varying flexible structures

    NASA Technical Reports Server (NTRS)

    Glass, B. J.; Hanagud, S.

    1989-01-01

    Presented here is an identification technique that uses the sensor information to choose a new model out of a finite set of discrete model space, in order to follow the observed changes to the given time varying flexible structure. Boundary condition sets or other information on model variations are used to organize the set of possible models laterally into a search tree with levels of abstraction used to order the models vertically within branches. An object-oriented programming approach is used to represent the model set in the search tree. A modified A (asterisk) best first search algorithm finds the model where the model response best matches the current observations. Several extensions to this methodology are discussed. Methods of possible integration of rules with the current search algorithm are considered to give weight to interpreted trends that may be found in a series of observations. This capability might lead, for instance, to identifying a model that incorporates a progressive damage rather than with incorrect paramenters such as added mass. Another new direction is to consider the use of noisy time domain sensor feedback rather than frequency domain information in the search algorithm to improve the real-time capability of the developed procedure.

  1. Automated model formulation for time-varying flexible structures

    NASA Technical Reports Server (NTRS)

    Glass, B. J.; Hanagud, S.

    1989-01-01

    Presented here is an identification technique that uses the sensor information to choose a new model out of a finite set of discrete model space, in order to follow the observed changes to the given time varying flexible structure. Boundary condition sets or other information on model variations are used to organize the set of possible models laterally into a search tree with levels of abstraction used to order the models vertically within branches. An object-oriented programming approach is used to represent the model set in the search tree. A modified A (asterisk) best first search algorithm finds the model where the model response best matches the current observations. Several extensions to this methodology are discussed. Methods of possible integration of rules with the current search algorithm are considered to give weight to interpreted trends that may be found in a series of observations. This capability might lead, for instance, to identifying a model that incorporates a progressive damage rather than with incorrect paramenters such as added mass. Another new direction is to consider the use of noisy time domain sensor feedback rather than frequency domain information in the search algorithm to improve the real-time capability of the developed procedure.

  2. Practical Formulations of the Latent Growth Item Response Model

    ERIC Educational Resources Information Center

    McGuire, Leah Walker

    2010-01-01

    Growth modeling using longitudinal data seems to be a promising direction for improving the methodology associated with the accountability movement. Longitudinal modeling requires that the measurements of ability are comparable over time and on the same scale. One way to create the vertical scale is through concurrent estimation with…

  3. Practical Formulations of the Latent Growth Item Response Model

    ERIC Educational Resources Information Center

    McGuire, Leah Walker

    2010-01-01

    Growth modeling using longitudinal data seems to be a promising direction for improving the methodology associated with the accountability movement. Longitudinal modeling requires that the measurements of ability are comparable over time and on the same scale. One way to create the vertical scale is through concurrent estimation with…

  4. Application of mathematical modeling for the development and optimization formulation with bioactive copper complex.

    PubMed

    Savic, Ivana M; Nikolic, Katarina; Nikolic, Goran; Savic, Ivan; Agbaba, Danica; Cakic, Milorad

    2013-07-01

    New formulation for treatment a copper deficiency in human organism was developed and optimized by application of mathematical modeling. This formulation contained copper (II) complex with polysaccharide pullulan, as active substance. The binder concentration [polyvinyl pyrrolidone (PVP %)], the disintegrant concentration (corn starch %) and the resistance to crushing (hardness) were taken as independent variables. In vitro measured drug release characteristics of the tablets at pH 1.20 and 7.56 were studied as response variables. Initially, the created full factorial 2(3) model showed that the resistance to crushing has the most significant effect on copper (II) complex release from the formulation. Optimal tablet formulation F2, with lower Hardness (50 N), lower Starch (20.0%) and higher PVP (2.7%) concentrations, is selected using the partial least squares (PLS) regression modeling. The selected formulation F2 has expressed the best drug release profile at both pH (98.66% pH = 1.20; 93.35% pH = 7.56), and the lowest variation of tablets weight. The presented theoretical approach and created PLS model can be readily applied in future copper complexes studies and formulation design.

  5. Isotope-based Fluvial Organic Carbon (ISOFLOC) Model: Model formulation, sensitivity, and evaluation

    NASA Astrophysics Data System (ADS)

    Ford, William I.; Fox, James F.

    2015-06-01

    Watershed-scale carbon budgets remain poorly understood, in part due to inadequate simulation tools to assess in-stream carbon fate and transport. A new numerical model termed ISOtope-based FLuvial Organic Carbon (ISOFLOC) is formulated to simulate the fluvial organic carbon budget in watersheds where hydrologic, sediment transport, and biogeochemical processes are coupled to control benthic and transported carbon composition and flux. One ISOFLOC innovation is the formulation of new stable carbon isotope model subroutines that include isotope fractionation processes in order to estimate carbon isotope source, fate, and transport. A second innovation is the coupling of transfers between carbon pools, including algal particulate organic carbon, fine particulate and dissolved organic carbon, and particulate and dissolved inorganic carbon, to simulate the carbon cycle in a comprehensive manner beyond that of existing watershed water quality models. ISOFLOC was tested and verified in a low-gradient, agriculturally impacted stream. Results of a global sensitivity analysis suggested the isotope response variable had unique sensitivity to the coupled interaction between fluvial shear resistance of algal biomass and the concentration of dissolved inorganic carbon. Model calibration and validation suggested good agreement at event, seasonal, and annual timescales. Multiobjective uncertainty analysis suggested inclusion of the carbon stable isotope routine reduced uncertainty by 80% for algal particulate organic carbon flux estimates.

  6. Formulations of transport in catchment-scale conceptual models

    NASA Astrophysics Data System (ADS)

    De Vos, Lotte; Hrachowitz, Markus

    2017-04-01

    Standard conceptual hydrological models can rarely accommodate stream tracer dynamics at the catchment scale. They rely on the generation of runoff through the propagation of a pressure wave and do not account for the actual advective movement of particles. Over the last years different model frameworks have been developed to account for this shortcoming. The difference between the frameworks lies in whether they are based on mixing coefficients or storage age selection functions. Both methods have shown their ability to capture the stream chemistry response. It is however not clear how these distinct approaches compare to each other and to reality. The object of this research is to provide clarification in this matter. To achieve this, the hydrological and stream water chemistry response for a set of contrasting research catchments is modelled, using both the mixing coefficient and the storage age selection approach. The results are analysed using the concept of transit times, where information on the fluxes and states in all model components is used to generate distributions that describe the age structure of water. By comparing the distributions generated by both methods and by evaluating the overall model performances, more insight is gained on how mixing occurs at the catchment scale. This contributes to the understanding of the integrated system dynamics of catchments, which is relevant for the development of good water quality models that accurately describe the integrated response of a hydrological system.

  7. An Inadequacy Formulation for an Uncertain Flamelet Model

    NASA Astrophysics Data System (ADS)

    Sondak, David; Oliver, Todd; Simmons, Chris; Moser, Robert

    2016-11-01

    We report progress on the development of an uncertain flamelet library for use in non-premixed turbulent combustion. A stochastic inadequacy operator is generalized from previous work and is now used to incorporate uncertainties in chemical reaction mechanisms in a flamelet model. The original form of the inadequacy operator was designed to enforce positivity of chemical species concentrations and conservation of species while representing inadequacies in reduced chemical mechanisms. As a first step towards generalization, we are exploring temperature dependent modifications to the inadequacy operator. The temperature dependence helps ensure that the operator is inactive in the absence of chemical reactions and becomes active only after ignition. A Bayesian inverse problem is used to calibrate the stochastic operator on a hydrogen-oxygen zero-dimensional reactor and to infer model parameters, and their uncertainties, from data obtained via a detailed chemical mechanism. The inferred model parameters are then propagated through a laminar, non-premixed, counterflow hydrogen-oxygen flame. Temperature and species profiles at various scalar dissipation rates are compared to those predicted from a five-reaction reduced model and the detailed model.

  8. Mathematical Formulation Requirements and Specifications for the Process Models

    SciTech Connect

    Steefel, C.; Moulton, D.; Pau, G.; Lipnikov, K.; Meza, J.; Lichtner, P.; Wolery, T.; Bacon, D.; Spycher, N.; Bell, J.; Moridis, G.; Yabusaki, S.; Sonnenthal, E.; Zyvoloski, G.; Andre, B.; Zheng, L.; Davis, J.

    2010-11-01

    The Advanced Simulation Capability for Environmental Management (ASCEM) is intended to be a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The ASCEM program is aimed at addressing critical EM program needs to better understand and quantify flow and contaminant transport behavior in complex geological systems. It will also address the long-term performance of engineered components including cementitious materials in nuclear waste disposal facilities, in order to reduce uncertainties and risks associated with DOE EM's environmental cleanup and closure activities. Building upon national capabilities developed from decades of Research and Development in subsurface geosciences, computational and computer science, modeling and applied mathematics, and environmental remediation, the ASCEM initiative will develop an integrated, open-source, high-performance computer modeling system for multiphase, multicomponent, multiscale subsurface flow and contaminant transport. This integrated modeling system will incorporate capabilities for predicting releases from various waste forms, identifying exposure pathways and performing dose calculations, and conducting systematic uncertainty quantification. The ASCEM approach will be demonstrated on selected sites, and then applied to support the next generation of performance assessments of nuclear waste disposal and facility decommissioning across the EM complex. The Multi-Process High Performance Computing (HPC) Simulator is one of three thrust areas in ASCEM. The other two are the Platform and Integrated Toolsets (dubbed the Platform) and Site Applications. The primary objective of the HPC Simulator is to provide a flexible and extensible computational engine to simulate the coupled processes and flow scenarios described by the conceptual models developed using the ASCEM Platform. The graded and iterative approach to assessments naturally

  9. Regressive logistic models for familial diseases: a formulation assuming an underlying liability model.

    PubMed Central

    Demenais, F M

    1991-01-01

    Statistical models have been developed to delineate the major-gene and non-major-gene factors accounting for the familial aggregation of complex diseases. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affection is defined by a threshold on the liability scale. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype, phenotypes of antecedents and other covariates. An equivalence between these two approaches cannot be derived analytically. I propose a formulation of the regressive logistic models on the supposition of an underlying liability model of disease. Relatives are assumed to have correlated liabilities to the disease; affected persons have liabilities exceeding an estimable threshold. Under the assumption that the correlation structure of the relatives' liabilities follows a regressive model, the regression coefficients on antecedents are expressed in terms of the relevant familial correlations. A parsimonious parameterization is a consequence of the assumed liability model, and a one-to-one correspondence with the parameters of the mixed model can be established. The logits, derived under the class A regressive model and under the class D regressive model, can be extended to include a large variety of patterns of family dependence, as well as gene-environment interactions. PMID:1897524

  10. Precision diet formulation to improve performance and profitability across various climates: Modeling the implications of increasing the formulation frequency of dairy cattle diets.

    PubMed

    White, Robin R; Capper, Judith L

    2014-03-01

    The objective of this study was to use a precision nutrition model to simulate the relationship between diet formulation frequency and dairy cattle performance across various climates. Agricultural Modeling and Training Systems (AMTS) CattlePro diet-balancing software (Cornell Research Foundation, Ithaca, NY) was used to compare 3 diet formulation frequencies (weekly, monthly, or seasonal) and 3 levels of climate variability (hot, cold, or variable). Predicted daily milk yield (MY), metabolizable energy (ME) balance, and dry matter intake (DMI) were recorded for each frequency-variability combination. Economic analysis was conducted to calculate the predicted revenue over feed and labor costs. Diet formulation frequency affected ME balance and MY but did not affect DMI. Climate variability affected ME balance and DMI but not MY. The interaction between climate variability and formulation frequency did not affect ME balance, MY, or DMI. Formulating diets more frequently increased MY, DMI, and ME balance. Economic analysis showed that formulating diets weekly rather than seasonally could improve returns over variable costs by $25,000 per year for a moderate-sized (300-cow) operation. To achieve this increase in returns, an entire feeding system margin of error of <1% was required. Formulating monthly, rather than seasonally, may be a more feasible alternative as this requires a margin of error of only 2.5% for the entire feeding system. Feeding systems with a low margin of error must be developed to better take advantage of the benefits of precision nutrition.

  11. Formulating the Brogden Classification Framework as a Discrete Choice Model

    DTIC Science & Technology

    2012-11-01

    that satisfy the job quota constraints using an MMNL parameter estimation algorithm. Biogeme ( Bierle , 2003) model files for carrying out the...demand. Cambridge, MA: MIT Press. Bierle , M. (2003). An introduction to BIOGEME (Version 1.3) http://roso.epfl.ch/biogeme. Brogden, H. E. (1954). A

  12. Formulation and Testing of a Novel River Nitrification Model

    EPA Science Inventory

    The nitrification process in many riverwater quality models has been approximated by a simple first order dependency on the water column ammonia concentration, while the benthic contribution has routinely been neglected. In this study a mathematical framework was developed for se...

  13. Industrial processing of complex fluids: Formulation and modeling

    SciTech Connect

    Scovel, J.C.; Bleasdale, S.; Forest, G.M.; Bechtel, S.

    1997-08-01

    The production of many important commercial materials involves the evolution of a complex fluid through a cooling phase into a hardened product. Textile fibers, high-strength fibers(KEVLAR, VECTRAN), plastics, chopped-fiber compounds, and fiber optical cable are such materials. Industry desires to replace experiments with on-line, real time models of these processes. Solutions to the problems are not just a matter of technology transfer, but require a fundamental description and simulation of the processes. Goals of the project are to develop models that can be used to optimize macroscopic properties of the solid product, to identify sources of undesirable defects, and to seek boundary-temperature and flow-and-material controls to optimize desired properties.

  14. Sublethal toxicant effects with dynamic energy budget theory: model formulation.

    PubMed

    Muller, Erik B; Nisbet, Roger M; Berkley, Heather A

    2010-01-01

    We develop and test a general modeling framework to describe the sublethal effects of pollutants by adding toxicity modules to an established dynamic energy budget (DEB) model. The DEB model describes the rates of energy acquisition and expenditure by individual organisms; the toxicity modules describe how toxicants affect these rates by changing the value of one or more DEB parameters, notably the parameters quantifying the rates of feeding and maintenance. We investigate four toxicity modules that assume: (1) effects on feeding only; (2) effects on maintenance only; (3) effects on feeding and maintenance with similar values for the toxicity parameters; and (4) effects on feeding and maintenance with different values for the toxicity parameters. We test the toxicity modules by fitting each to published data on feeding, respiration, growth and reproduction. Among the pollutants tested are metals (mercury and copper) and various organic compounds (chlorophenols, toluene, polycyclic aromatic hydrocarbons, tetradifon and pyridine); organisms include mussels, oysters, earthworms, water fleas and zebrafish. In most cases, the data sets could be adequately described with any of the toxicity modules, and no single module gave superior fits to all data sets. We therefore propose that for many applications, it is reasonable to use the most general and parameter sparse module, i.e. module 3 that assumes similar effects on feeding and maintenance, as a default. For one example (water fleas), we use parameter estimates to calculate the impact of food availability and toxicant levels on the long term population growth rate.

  15. Modeling surface tension using a ghost fluid technique within a volume of fluid formulation

    SciTech Connect

    Francois, M. M.; Kothe, D. B.; Cummins, S. J.

    2004-01-01

    Ghost fluid methods (GFM) are a viable approach for imposing sharp boundary conditions on interfaces that are arbitrarily embedded within the computational mesh. All GFM to date are formulated with an interface distance function that resides within a level-set (LS) framework. Recently we proposed a technique for reconstructing distance functions from volume fractions. This technique enables the exploitation of GFM within a volume of fluid formulation for modeling an interfacial phenomenon like surface tension. Combining GFM with a volume of fluid (VOF) formulation is attractive because of the VOF method's superior mass conservation and because of the ability of GFM to maintain sharp jump conditions. The continuum surface tension force (CSF) method, however, has the propensity to produce smooth jump. In the following, the combined VOF-GFM and more classical VOF-CSF formulations are compared and contrasted. Static and dynamic numerical results are used to illustrate our findings and support our claims.

  16. Effects of Model Formulation on Estimates of Health in Individual Right Whales (Eubalaena glacialis).

    PubMed

    Schick, Robert S; Kraus, Scott D; Rolland, Rosalind M; Knowlton, Amy R; Hamilton, Philip K; Pettis, Heather M; Thomas, Len; Harwood, John; Clark, James S

    2016-01-01

    Right whales are vulnerable to many sources of anthropogenic disturbance including ship strikes, entanglement with fishing gear, and anthropogenic noise. The effect of these factors on individual health is unclear. A statistical model using photographic evidence of health was recently built to infer the true or hidden health of individual right whales. However, two important prior assumptions about the role of missing data and unexplained variance on the estimates were not previously assessed. Here we tested these factors by varying prior assumptions and model formulation. We found sensitivity to each assumption and used the output to make guidelines on future model formulation.

  17. Predictive formulation of the Nambu-Jona-Lasinio model

    SciTech Connect

    Battistel, O. A.; Dallabona, G.; Krein, G.

    2008-03-15

    A novel strategy to handle divergences typical of perturbative calculations is implemented for the Nambu-Jona-Lasinio model and its phenomenological consequences investigated. The central idea of the method is to avoid the critical step involved in the regularization process, namely, the explicit evaluation of divergent integrals. This goal is achieved by assuming a regularization distribution in an implicit way and making use, in intermediary steps, only of very general properties of such regularization. The finite parts are separated from the divergent ones and integrated free from effects of the regularization. The divergent parts are organized in terms of standard objects, which are independent of the (arbitrary) momenta running in internal lines of loop graphs. Through the analysis of symmetry relations, a set of properties for the divergent objects are identified, which we denominate consistency relations, reducing the number of divergent objects to only a few. The calculational strategy eliminates unphysical dependencies of the arbitrary choices for the routing of internal momenta, leading to ambiguity-free, and symmetry-preserving physical amplitudes. We show that the imposition of scale properties for the basic divergent objects leads to a critical condition for the constituent quark mass such that the remaining arbitrariness is removed. The model becomes predictive in the sense that its phenomenological consequences do not depend on possible choices made in intermediary steps. Numerical results are obtained for physical quantities at the one-loop level for the pion and sigma masses and pion-quark and sigma-quark coupling constants.

  18. Variational formulation of macroparticle models for electromagnetic plasma simulations

    DOE PAGES

    Stamm, Alexander B.; Shadwick, Bradley A.; Evstatiev, Evstati G.

    2014-06-01

    A variational method is used to derive a self-consistent macroparticle model for relativistic electromagnetic kinetic plasma simulations. Extending earlier work, discretization of the electromagnetic Low Lagrangian is performed via a reduction of the phase-space distribution function onto a collection of finite-sized macroparticles of arbitrary shape and discretization of field quantities onto a spatial grid. This approach may be used with lab frame coordinates or moving window coordinates; the latter can greatly improve computational efficiency for studying some types of laser-plasma interactions. The primary advantage of the variational approach is the preservation of Lagrangian symmetries, which in our case leads tomore » energy conservation and thus avoids difficulties with grid heating. In addition, this approach decouples particle size from grid spacing and relaxes restrictions on particle shape, leading to low numerical noise. The variational approach also guarantees consistent approximations in the equations of motion and is amenable to higher order methods in both space and time. We restrict our attention to the 1.5-D case (one coordinate and two momenta). Lastly, simulations are performed with the new models and demonstrate energy conservation and low noise.« less

  19. Variational formulation of macroparticle models for electromagnetic plasma simulations

    SciTech Connect

    Stamm, Alexander B.; Shadwick, Bradley A.; Evstatiev, Evstati G.

    2014-06-01

    A variational method is used to derive a self-consistent macroparticle model for relativistic electromagnetic kinetic plasma simulations. Extending earlier work, discretization of the electromagnetic Low Lagrangian is performed via a reduction of the phase-space distribution function onto a collection of finite-sized macroparticles of arbitrary shape and discretization of field quantities onto a spatial grid. This approach may be used with lab frame coordinates or moving window coordinates; the latter can greatly improve computational efficiency for studying some types of laser-plasma interactions. The primary advantage of the variational approach is the preservation of Lagrangian symmetries, which in our case leads to energy conservation and thus avoids difficulties with grid heating. In addition, this approach decouples particle size from grid spacing and relaxes restrictions on particle shape, leading to low numerical noise. The variational approach also guarantees consistent approximations in the equations of motion and is amenable to higher order methods in both space and time. We restrict our attention to the 1.5-D case (one coordinate and two momenta). Lastly, simulations are performed with the new models and demonstrate energy conservation and low noise.

  20. Formulation of consumables management models. Volume 1: Mission planning

    NASA Technical Reports Server (NTRS)

    Torian, J. G.; Zamora, M. A.

    1978-01-01

    Development of an STS (Space Transportation System) interactive computer program MPP (Mission Planning Processor) working model was conducted. A summary of the computer program development and those supporting tasks conducted is presented. Development of the MPP Computer Program is discussed. This development was supported by several parallel tasks. These tasks either directly supported the program development, or provided information for future application and/or modification to the program in relation to the flight planning and flight operations of the STS and advanced spacecraft. The supporting tasks also included development of a Space Station MPP to demonstrate the applicability of the analytical methods developed under this RTOP to more advanced spacecraft than the STS.

  1. Individual-based model formulation for cutthroat trout, Little Jones Creek, California

    Treesearch

    Steven F. Railsback; Bret C. Harvey

    2001-01-01

    This report contains the detailed formulation of an individual-based model (IBM) of cutthroat trout developed for three study sites on Little Jones Creek, Del Norte County, in northwestern California. The model was designed to support research on relations between habitat and fish population dynamics, the importance of small tributaries to trout populations, and the...

  2. [Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations].

    PubMed

    Liu, Ying; Yi, Tao; Di, Huan; Xiao, Lu; He, Ji-Kui

    2011-08-01

    A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.

  3. Formulating a stand-growth model for mathematical programming problems in Appalachian forests

    Treesearch

    Gary W. Miller; Jay Sullivan

    1993-01-01

    Some growth and yield simulators applicable to central hardwood forests can be formulated for use in mathematical programming models that are designed to optimize multi-stand, multi-resource management problems. Once in the required format, growth equations serve as model constraints, defining the dynamics of stand development brought about by harvesting decisions. In...

  4. Free radical scavenging property and diuretic effect of triglize, a polyherbal formulation in experimental models

    PubMed Central

    Parasuraman, S; Kumar, EP; Kumar, Anil; Emerson, SF

    2010-01-01

    Objective: To determine the in vitro free radical scavenging property and in vivo diuretic effect of Triglize™ , a marketed polyherbal formulation in experimental models. Materials and Methods: The aqueous extract of polyherbal formulation (PHF) triglize was used for the experiment. The free radical scavenging property and antioxidant effect of PHF were studied by LPS-induced free radicals in rat macrophages cells and DPPH (2, 2-Diphenyl-1-Picrylhydrazyl) methods, respectively. The diuretic effect of a PHF was studied with Lipschitz model using male Wistar rats. Results: PHF significantly inhibited lipopolysaccharide -induced free radicals in rat macrophages and it showed moderate antioxidant potential in DPPH model. Polyherbal formulation at 50, 200 and 400 mg/ kg significantly increased potassium excretion in urine at 0-5 h and 5-24 h. The diuretic effect of PHF was as similar as furosemide. Conclusion: The PHF has significant diuretic effect and free radical scavenging properties. PMID:21808589

  5. One-dimensional discrete formulation of a hygrolock model for wood hygromechanics

    NASA Astrophysics Data System (ADS)

    Colmars, J.; Dubois, F.; Gril, J.

    2014-02-01

    A new 1D discrete formulation of hygrolock models is proposed for modeling wood time-dependent behavior. This discrete formulation is compared to an integral formulation presented in a previously published paper. Simulations with various humidity cycles are performed under constant stress (creep) or constant strain (relaxation) using first a hygrolock spring and then a generalized Kelvin-Voigt model with a time-spectral distribution of hygrolocks springs. The discrete formulation presented here, based on an original idea of a mixed series/parallel rheological model, is shown to be very practical for implementation in scientific numerical codes. In order to compensate a lack of complete data-set on wood material, a generic time- and moisture-dependent material is proposed to compare the various models: this dataset could be re-used in other studies. Finally, the relevance of hygrolock models for wood time-dependent behavior is discussed. It appears that hygrolock models suit well to the upper part of the wood hygroscopic domain, whereas further hypothesis should be tested for the dry domain. A judicious choice in moisture activation of material parameters, combined with the blocking effect of hygrolock, agrees with recent experimental results on simplifying the description of the so-called ++ effect.

  6. Finite strain formulation of viscoelastic damage model for simulation of fabric reinforced polymers under dynamic loading

    NASA Astrophysics Data System (ADS)

    Treutenaere, S.; Lauro, F.; Bennani, B.; Matsumoto, T.; Mottola, E.

    2015-09-01

    The use of fabric reinforced polymers in the automotive industry is growing significantly. The high specific stiffness and strength, the ease of shaping as well as the great impact performance of these materials widely encourage their diffusion. The present model increases the predictability of explicit finite element analysis and push the boundaries of the ongoing phenomenological model. Carbon fibre composites made up various preforms were tested by applying different mechanical load up to dynamic loading. This experimental campaign highlighted the physical mechanisms affecting the initial mechanical properties, namely intra- and interlaminar matrix damage, viscoelasticty and fibre failure. The intralaminar behaviour model is based on the explicit formulation of the matrix damage model developed by the ONERA as the given damage formulation correlates with the experimental observation. Coupling with a Maxwell-Wiechert model, the viscoelasticity is included without losing the direct explicit formulation. Additionally, the model is formulated under a total Lagrangian scheme in order to maintain consistency for finite strain. Thus, the material frame-indifference as well as anisotropy are ensured. This allows reorientation of fibres to be taken into account particularly for in-plane shear loading. Moreover, fall within the framework of the total Lagrangian scheme greatly makes the parameter identification easier, as based on the initial configuration. This intralaminar model thus relies upon a physical description of the behaviour of fabric composites and the numerical simulations show a good correlation with the experimental results.

  7. A local formulation of lattice Wess-Zumino model with exact U(1)R symmetry

    NASA Astrophysics Data System (ADS)

    Kikukawa, Yoshio; Suzuki, Hiroshi

    2005-02-01

    A lattice Wess-Zumino model is formulated on the basis of Ginsparg-Wilson fermions. In perturbation theory, our formulation is equivalent to the formulation by Fujikawa and Ishibashi and by Fujikawa. Our formulation is, however, free from a singular nature of the latter formulation due to an additional auxiliary chiral supermultiplet on a lattice. The model posssesses an exact U(1)R symmetry as a supersymmetric counterpart of the Lüscher lattice chiral U(1) symmetry. A restration of the supersymmetric Ward-Takahashi identity in the continuum limit is analyzed in renormalized perturbation theory. In the one-loop level, a supersymmetric continuum limit is ensured by suitably adjusting a coefficient of a single local term tilde F*tilde F. The non-renormalization theorem holds to this order of perturbation theory. In higher orders, on the other hand, coefficents of local terms with dimension <= 4 that are consistent with the U(1)R symmetry have to be adjusted for a supersymmetric continuum limit. The origin of this complexicity in higher-order loops is clarified on the basis of the Reisz power counting theorem. Therefore, from a view point of supersymmetry, the present formulation is not quite better than a lattice Wess-Zumino model formulated by using Wilson fermions, although a number of coefficients which require adjustment is much less due to the exact U(1)R symmetry. We also comment on an exact non-linear fermionic symmetry which corresponds to the one studied by Bonini and Feo; an existence of this exact symmetry itself does not imply a restoration of supersymmetry in the continuum limit without any adjustment of parameters.

  8. Modeling the effect of formulation on the properties of extruded corn flour-based foamed plastic

    NASA Astrophysics Data System (ADS)

    Julson, James Lawrence

    The effects of formulation on resiliency, unit density and thermal conductivity of an extruded corn flour-based foamed plastic were studied. A central composite design was used to establish the levels of corn flour, water, sodium bicarbonate, soy protein and polystyrene used to develop the individual models. Three separate multiple regression models were developed to predict resiliency, unit density and thermal conductivity as functions of formulation ingredient levels. The models were used to isolate the formulations that produced the minimum unit density, maximum resiliency and minimum thermal conductivity. These optimal formulations were extruded using a commercial scale extruder. The results produced extrudates those resiliency, unit density and thermal conductivity were 89.9%, 0.041 g/cmsp3 and 0.045 W/(m{*}C), respectively. The unit density and thermal conductivity were within the range of commercial rigid cellular polystyrene. The resiliency was 5% less than commercial polystyrene loose-fill. A foamed sheet product was also successfully extruded using, the formulations developed. A computer based data acquisition and control system, used with the thermal probe, was developed to measure thermal conductivity of the extrudates. Errors due to short test times and differences in thermal mass of the probe and sample were determined. A multiple regression equation was developed to allow convenient calculation of those values required to assess the error associated with short test times and differences in thermal mass. A method to calculate the error was developed and used to correct the measured thermal conductivity values.

  9. Model sustainability in DSS design and scenario formulation: what are the right scenarios?

    PubMed

    Schreider SYu; Mostovaia, A D

    2001-09-01

    A concept of the integrated approach in designing multidisciplinary decision support systems (DSS) based on agricultural scenarios for sustainable catchment management is discussed. A principle of holism underlying the integrated approach to DSS design is formulated. For a model to be viable and sustainable, it should be based on scenarios that are plausible and highly typical from the point of view of those 'doing' agriculture. Problems concerning principles of scenario formulation within the integrated approach are considered. A notion of 'prototype' scenarios based on 'joint venture' of modellers and stakeholders is proposed.

  10. Variational formulation of a quantitative phase-field model for nonisothermal solidification in a multicomponent alloy

    NASA Astrophysics Data System (ADS)

    Ohno, Munekazu; Takaki, Tomohiro; Shibuta, Yasushi

    2017-09-01

    A variational formulation of a quantitative phase-field model is presented for nonisothermal solidification in a multicomponent alloy with two-sided asymmetric diffusion. The essential ingredient of this formulation is that the diffusion fluxes for conserved variables in both the liquid and solid are separately derived from functional derivatives of the total entropy and then these fluxes are related to each other on the basis of the local equilibrium conditions. In the present formulation, the cross-coupling terms between the phase-field and conserved variables naturally arise in the phase-field equation and diffusion equations, one of which corresponds to the antitrapping current, the phenomenological correction term in early nonvariational models. In addition, this formulation results in diffusivities of tensor form inside the interface. Asymptotic analysis demonstrates that this model can exactly reproduce the free-boundary problem in the thin-interface limit. The present model is widely applicable because approximations and simplifications are not formally introduced into the bulk's free energy densities and because off-diagonal elements of the diffusivity matrix are explicitly taken into account. Furthermore, we propose a nonvariational form of the present model to achieve high numerical performance. A numerical test of the nonvariational model is carried out for nonisothermal solidification in a binary alloy. It shows fast convergence of the results with decreasing interface thickness.

  11. Application of co-grinding to formulate a model pMDI suspension.

    PubMed

    Williams, R O; Repka, M A; Barron, M K

    1999-09-01

    The objective of this study was to investigate the effect of co-grinding the model drug, triamcinolone acetonide (TAA), with a polymeric surfactant on the in vitro performance of a model pMDI suspension system. The physicochemical properties of TAA after co-grinding with the surfactant, Pluronic F77, were determined by laser light diffraction, helium pycnometry and equilibrium solubility measurements. TAA-surfactant interaction was investigated by differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). The suspension characteristics of pMDI formulations prepared with co-ground TAA and surfactant were investigated by determining their in situ sedimentation, rheological profiles and vapor pressure. The performance characteristics of the pMDI formulations were determined by cascade impaction and dose delivery through-the-valve (DDV) measurements. It was found that the presence of Pluronic F77 decreased the solubility of TAA in the propellant medium. Co-grinding TAA particles with Pluronic F77 influenced the particle size distribution, sedimentation and flocculation characteristics of the pMDI suspension formulation. The addition of Pluronic F77 decreased the viscosity of the pMDI formulation. Formulating the suspension pMDI system with co-ground TAA and Pluronic F77 decreased the mass median aerodynamic diameter (MMAD) of the emitted aerosol and increased the percent respirable fraction (%RF). The co-ground TAA and Pluronic F77 pMDI suspension formulation exhibited greater physical stability which was due to the influence of the co-grinding technique on the physicochemical properties of the TAA particle surface and the propellant dispersion medium. The changes induced by co-grinding with Pluronic F77 improved the performance characteristics of a pMDI suspension formulation by stabilizing the suspension and influencing the flocculation characteristics. Co-grinding is a process which may be useful when developing new pMDI systems containing

  12. Model-based optimal design of experiments - semidefinite and nonlinear programming formulations

    PubMed Central

    Duarte, Belmiro P.M.; Wong, Weng Kee; Oliveira, Nuno M.C.

    2015-01-01

    We use mathematical programming tools, such as Semidefinite Programming (SDP) and Nonlinear Programming (NLP)-based formulations to find optimal designs for models used in chemistry and chemical engineering. In particular, we employ local design-based setups in linear models and a Bayesian setup in nonlinear models to find optimal designs. In the latter case, Gaussian Quadrature Formulas (GQFs) are used to evaluate the optimality criterion averaged over the prior distribution for the model parameters. Mathematical programming techniques are then applied to solve the optimization problems. Because such methods require the design space be discretized, we also evaluate the impact of the discretization scheme on the generated design. We demonstrate the techniques for finding D–, A– and E–optimal designs using design problems in biochemical engineering and show the method can also be directly applied to tackle additional issues, such as heteroscedasticity in the model. Our results show that the NLP formulation produces highly efficient D–optimal designs but is computationally less efficient than that required for the SDP formulation. The efficiencies of the generated designs from the two methods are generally very close and so we recommend the SDP formulation in practice. PMID:26949279

  13. Model-based optimal design of experiments - semidefinite and nonlinear programming formulations.

    PubMed

    Duarte, Belmiro P M; Wong, Weng Kee; Oliveira, Nuno M C

    2016-02-15

    We use mathematical programming tools, such as Semidefinite Programming (SDP) and Nonlinear Programming (NLP)-based formulations to find optimal designs for models used in chemistry and chemical engineering. In particular, we employ local design-based setups in linear models and a Bayesian setup in nonlinear models to find optimal designs. In the latter case, Gaussian Quadrature Formulas (GQFs) are used to evaluate the optimality criterion averaged over the prior distribution for the model parameters. Mathematical programming techniques are then applied to solve the optimization problems. Because such methods require the design space be discretized, we also evaluate the impact of the discretization scheme on the generated design. We demonstrate the techniques for finding D-, A- and E-optimal designs using design problems in biochemical engineering and show the method can also be directly applied to tackle additional issues, such as heteroscedasticity in the model. Our results show that the NLP formulation produces highly efficient D-optimal designs but is computationally less efficient than that required for the SDP formulation. The efficiencies of the generated designs from the two methods are generally very close and so we recommend the SDP formulation in practice.

  14. Evaluation of soy-based surface active copolymers as surfactant ingredients in model shampoo formulations.

    PubMed

    Popadyuk, A; Kalita, H; Chisholm, B J; Voronov, A

    2014-12-01

    A new non-toxic soybean oil-based polymeric surfactant (SBPS) for personal-care products was developed and extensively characterized, including an evaluation of the polymeric surfactant performance in model shampoo formulations. To experimentally assure applicability of the soy-based macromolecules in shampoos, either in combination with common anionic surfactants (in this study, sodium lauryl sulfate, SLS) or as a single surface-active ingredient, the testing of SBPS physicochemical properties, performance and visual assessment of SBPS-based model shampoos was carried out. The results obtained, including foaming and cleaning ability of model formulations, were compared to those with only SLS as a surfactant as well as to SLS-free shampoos. Overall, the results show that the presence of SBPS improves cleaning, foaming, and conditioning of model formulations. SBPS-based formulations meet major requirements of multifunctional shampoos - mild detergency, foaming, good conditioning, and aesthetic appeal, which are comparable to commercially available shampoos. In addition, examination of SBPS/SLS mixtures in model shampoos showed that the presence of the SBPS enables the concentration of SLS to be significantly reduced without sacrificing shampoo performance. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  15. Integrating gene set analysis and nonlinear predictive modeling of disease phenotypes using a Bayesian multitask formulation.

    PubMed

    Gönen, Mehmet

    2016-12-13

    Identifying molecular signatures of disease phenotypes is studied using two mainstream approaches: (i) Predictive modeling methods such as linear classification and regression algorithms are used to find signatures predictive of phenotypes from genomic data, which may not be robust due to limited sample size or highly correlated nature of genomic data. (ii) Gene set analysis methods are used to find gene sets on which phenotypes are linearly dependent by bringing prior biological knowledge into the analysis, which may not capture more complex nonlinear dependencies. Thus, formulating an integrated model of gene set analysis and nonlinear predictive modeling is of great practical importance. In this study, we propose a Bayesian binary classification framework to integrate gene set analysis and nonlinear predictive modeling. We then generalize this formulation to multitask learning setting to model multiple related datasets conjointly. Our main novelty is the probabilistic nonlinear formulation that enables us to robustly capture nonlinear dependencies between genomic data and phenotype even with small sample sizes. We demonstrate the performance of our algorithms using repeated random subsampling validation experiments on two cancer and two tuberculosis datasets by predicting important disease phenotypes from genome-wide gene expression data. We are able to obtain comparable or even better predictive performance than a baseline Bayesian nonlinear algorithm and to identify sparse sets of relevant genes and gene sets on all datasets. We also show that our multitask learning formulation enables us to further improve the generalization performance and to better understand biological processes behind disease phenotypes.

  16. A General Pressure Gradient Formulation for Ocean Models - Part II: Energy, Momentum, and Bottom Torque Consistency

    NASA Technical Reports Server (NTRS)

    Song, Y.; Wright, D.

    1998-01-01

    A formulation of the pressure gradient force for use in models with topography-following coordinates is proposed and diagnostically analyzed by Song. We investigate numerical consistency with respect to global energy conservation, depth-integrated momentum changes, and the represent of the bottom pressure torque.

  17. A General Pressure Gradient Formulation for Ocean Models - Part II: Energy, Momentum, and Bottom Torque Consistency

    NASA Technical Reports Server (NTRS)

    Song, Y.; Wright, D.

    1998-01-01

    A formulation of the pressure gradient force for use in models with topography-following coordinates is proposed and diagnostically analyzed by Song. We investigate numerical consistency with respect to global energy conservation, depth-integrated momentum changes, and the represent of the bottom pressure torque.

  18. Archimedes: a new model for simulating health care systems--the mathematical formulation.

    PubMed

    Schlessinger, Leonard; Eddy, David M

    2002-02-01

    This paper designs an object-oriented, continuous-time, full simulation model for addressing a wide range of clinical, procedural, administrative, and financial decisions in health care at a high level of biological, clinical, and administrative detail. The full model has two main parts, which with some simplification can be designated "physiology models" and "models of care processes." The models of care processes, although highly detailed, are mathematically straightforward. However, the mathematics that describes human biology, diseases, and the effects of interventions are more difficult. This paper describes the mathematical formulation and methods for deriving equations, for a variety of different sources of data. Although Archimedes was originally designed for health care applications, the formulation, and equations are general and can be applied to many natural systems.

  19. Improved Formulations for Air-Surface Exchanges Related to National Security Needs: Dry Deposition Models

    SciTech Connect

    Droppo, James G.

    2006-07-01

    The Department of Homeland Security and others rely on results from atmospheric dispersion models for threat evaluation, event management, and post-event analyses. The ability to simulate dry deposition rates is a crucial part of our emergency preparedness capabilities. Deposited materials pose potential hazards from radioactive shine, inhalation, and ingestion pathways. A reliable characterization of these potential exposures is critical for management and mitigation of these hazards. A review of the current status of dry deposition formulations used in these atmospheric dispersion models was conducted. The formulations for dry deposition of particulate materials from am event such as a radiological attack involving a Radiological Detonation Device (RDD) is considered. The results of this effort are applicable to current emergency preparedness capabilities such as are deployed in the Interagency Modeling and Atmospheric Assessment Center (IMAAC), other similar national/regional emergency response systems, and standalone emergency response models. The review concludes that dry deposition formulations need to consider the full range of particle sizes including: 1) the accumulation mode range (0.1 to 1 micron diameter) and its minimum in deposition velocity, 2) smaller particles (less than .01 micron diameter) deposited mainly by molecular diffusion, 3) 10 to 50 micron diameter particles deposited mainly by impaction and gravitational settling, and 4) larger particles (greater than 100 micron diameter) deposited mainly by gravitational settling. The effects of the local turbulence intensity, particle characteristics, and surface element properties must also be addressed in the formulations. Specific areas for improvements in the dry deposition formulations are 1) capability of simulating near-field dry deposition patterns, 2) capability of addressing the full range of potential particle properties, 3) incorporation of particle surface retention/rebound processes, and

  20. Compositional Models of Glass/Melt Properties and their Use for Glass Formulation

    DOE PAGES

    Vienna, John D.; USA, Richland Washington

    2014-12-18

    Nuclear waste glasses must simultaneously meet a number of criteria related to their processability, product quality, and cost factors. The properties that must be controlled in glass formulation and waste vitrification plant operation tend to vary smoothly with composition allowing for glass property-composition models to be developed and used. Models have been fit to the key glass properties. The properties are transformed so that simple functions of composition (e.g., linear, polynomial, or component ratios) can be used as model forms. The model forms are fit to experimental data designed statistically to efficiently cover the composition space of interest. Examples ofmore » these models are found in literature. The glass property-composition models, their uncertainty definitions, property constraints, and optimality criteria are combined to formulate optimal glass compositions, control composition in vitrification plants, and to qualify waste glasses for disposal. An overview of current glass property-composition modeling techniques is summarized in this paper along with an example of how those models are applied to glass formulation and product qualification at the planned Hanford high-level waste vitrification plant.« less

  1. Compositional Models of Glass/Melt Properties and their Use for Glass Formulation

    SciTech Connect

    Vienna, John D.; USA, Richland Washington

    2014-12-18

    Nuclear waste glasses must simultaneously meet a number of criteria related to their processability, product quality, and cost factors. The properties that must be controlled in glass formulation and waste vitrification plant operation tend to vary smoothly with composition allowing for glass property-composition models to be developed and used. Models have been fit to the key glass properties. The properties are transformed so that simple functions of composition (e.g., linear, polynomial, or component ratios) can be used as model forms. The model forms are fit to experimental data designed statistically to efficiently cover the composition space of interest. Examples of these models are found in literature. The glass property-composition models, their uncertainty definitions, property constraints, and optimality criteria are combined to formulate optimal glass compositions, control composition in vitrification plants, and to qualify waste glasses for disposal. An overview of current glass property-composition modeling techniques is summarized in this paper along with an example of how those models are applied to glass formulation and product qualification at the planned Hanford high-level waste vitrification plant.

  2. Aphrodisiac activity of polyherbal formulation in experimental models on male rats

    PubMed Central

    Sahoo, Himanshu Bhusan; Nandy, Subhangkar; Senapati, Aswini Kumar; Sarangi, Sarada Prasad; Sahoo, Saroj Kumar

    2014-01-01

    Objective: To investigate the aphrodisiac potential of polyherbal formulations prepared from different parts of Tribulus terrestris, Curculigo orchioides, Allium tuberosum, Cucurbita pepo, Elephant creeper, Mucuna pruriens, and Terminalia catappa in Albino rats in specified ratio as suspension. Materials and Methods: The different concentrations of prepared polyherbal formulations i.e. 150, 300, and 600 mg/kg and sildenafil citrate as standard (5 mg/kg) and vehicle (control) were administered orally to rats (n = 6 animals per group) for 3 weeks. Mating behavior parameters in male rats was monitored in first week and third week week of treatment pairing with receptive females. After termination of drug treatment, the mating performance, hormonal analysis, sperm count, and testes-body weight ratio were also evaluated. Results: The polyherbal formulation showed a significant increase in mating behavior as well as mating performance, serum hormonal levels, sperm count, and testes-body weight ratio with dose-dependent relationship as compared to vehicle control. But the dose of 600 mg/kg of polyherbal formulation assumes closer resemblance of above parameters with the standard used. Conclusion: The results of the study strongly suggest that the polyherbal formulations have a good aphrodisiac activity on rats in the above experimental models, which may be an alternative weapon for various sexual dysfunctions in future. PMID:24761115

  3. [Evaluation of Gastric Mucosal Injury Model Animals of Rebamipide Formulation--Study of Therapeutic Equivalence].

    PubMed

    Abe, Noriaki; Funato, Hiroki; Hirata, Ayumu; Nakai, Megumi; Iizuka, Michiro; Shiraishi, Hisashi; Jobu, Kohei; Yagi, Yusuke; Kadota, Aki; Ogi, Kyoko; Yokota, Junko; Miyamura, Mitsuhiko

    2016-01-01

    The introduction of generic drugs is promoted from the perspective of medical economics. In this context, we need to understand not only the bioequivalence of generic drugs specified in "the Guidelines for Bioequivalence Studies of Generic Products", but also formulation properties to consider their effect on pharmacological therapy. We evaluated the pharmaceutical characteristics of rebamipide formulations, a brand-name drug and two generic drugs, and their clinical functionality by using rat models of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Pharmaceutical evaluation showed significant differences in hardness. The inter-lot variation was small in all rebamipide formulations. In the clinical functionality study, biochemistry test values 7 d after the administration of rebamipide showed no differences among formulations. Higher levels of mucosal fluid secretion and antioxidative enzymes were observed in the groups administered rebamipide than in the control group. The levels of lipid peroxide were lower in the groups administered rebamipide than the control group. Multivariate analysis showed slight divergence between the brand-name and generic drugs. In future, it will be necessary to select generic drugs after careful consideration of bioequivalence, clinical functionality, and therapeutic equivalence by reviewing scientific evidence such as indication and formulation design, not to mention stable provision.

  4. Assessing the Problem Formulation in an Integrated Assessment Model: Implications for Climate Policy Decision-Support

    NASA Astrophysics Data System (ADS)

    Garner, G. G.; Reed, P. M.; Keller, K.

    2014-12-01

    Integrated assessment models (IAMs) are often used with the intent to aid in climate change decisionmaking. Numerous studies have analyzed the effects of parametric and/or structural uncertainties in IAMs, but uncertainties regarding the problem formulation are often overlooked. Here we use the Dynamic Integrated model of Climate and the Economy (DICE) to analyze the effects of uncertainty surrounding the problem formulation. The standard DICE model adopts a single objective to maximize a weighted sum of utilities of per-capita consumption. Decisionmakers, however, may be concerned with a broader range of values and preferences that are not captured by this a priori definition of utility. We reformulate the problem by introducing three additional objectives that represent values such as (i) reliably limiting global average warming to two degrees Celsius and minimizing both (ii) the costs of abatement and (iii) the damages due to climate change. We derive a set of Pareto-optimal solutions over which decisionmakers can trade-off and assess performance criteria a posteriori. We illustrate the potential for myopia in the traditional problem formulation and discuss the capability of this multiobjective formulation to provide decision support.

  5. Thermodynamic Model Formulations for Inhomogeneous Solids with Application to Non-isothermal Phase Field Modelling

    NASA Astrophysics Data System (ADS)

    Gladkov, Svyatoslav; Kochmann, Julian; Reese, Stefanie; Hütter, Markus; Svendsen, Bob

    2016-04-01

    The purpose of the current work is the comparison of thermodynamic model formulations for chemically and structurally inhomogeneous solids at finite deformation based on "standard" non-equilibrium thermodynamics [SNET: e. g. S. de Groot and P. Mazur, Non-equilibrium Thermodynamics, North Holland, 1962] and the general equation for non-equilibrium reversible-irreversible coupling (GENERIC) [H. C. Öttinger, Beyond Equilibrium Thermodynamics, Wiley Interscience, 2005]. In the process, non-isothermal generalizations of standard isothermal conservative [e. g. J. W. Cahn and J. E. Hilliard, Free energy of a non-uniform system. I. Interfacial energy. J. Chem. Phys. 28 (1958), 258-267] and non-conservative [e. g. S. M. Allen and J. W. Cahn, A macroscopic theory for antiphase boundary motion and its application to antiphase domain coarsening. Acta Metall. 27 (1979), 1085-1095; A. G. Khachaturyan, Theory of Structural Transformations in Solids, Wiley, New York, 1983] diffuse interface or "phase-field" models [e. g. P. C. Hohenberg and B. I. Halperin, Theory of dynamic critical phenomena, Rev. Modern Phys. 49 (1977), 435-479; N. Provatas and K. Elder, Phase Field Methods in Material Science and Engineering, Wiley-VCH, 2010.] for solids are obtained. The current treatment is consistent with, and includes, previous works [e. g. O. Penrose and P. C. Fife, Thermodynamically consistent models of phase-field type for the kinetics of phase transitions, Phys. D 43 (1990), 44-62; O. Penrose and P. C. Fife, On the relation between the standard phase-field model and a "thermodynamically consistent" phase-field model. Phys. D 69 (1993), 107-113] on non-isothermal systems as a special case. In the context of no-flux boundary conditions, the SNET- and GENERIC-based approaches are shown to be completely consistent with each other and result in equivalent temperature evolution relations.

  6. Comparison and Tensorial Formulation of Inelastic Constitutive Models of Salt Rock Behaviour and Efficient Numerical Implementatio

    NASA Astrophysics Data System (ADS)

    Nagel, T.; Böttcher, N.; Görke, U. J.; Kolditz, O.

    2014-12-01

    The design process of geotechnical installations includes the application of numerical simulation tools for safety assessment, dimensioning and long term effectiveness estimations. Underground salt caverns can be used for the storage of natural gas, hydrogen, oil, waste or compressed air. For their design one has to take into account fluctuating internal pressures due to different levels of filling, the stresses imposed by the surrounding rock mass, irregular geometries and possibly heterogeneous material properties [3] in order to estimate long term cavern convergence as well as locally critical wall stresses. Constitutive models applied to rock salt are usually viscoplastic in nature and most often based on a Burgers-type rheological model extended by non-linear viscosity functions and/or plastic friction elements. Besides plastic dilatation, healing and damage are sometimes accounted for as well [2]. The scales of the geotechnical system to be simulated and the laboratory tests from which material parameters are determined are vastly different. The most common material testing modalities to determine material parameters in geoengineering are the uniaxial and the triaxial compression tests. Some constitutive formulations in widespread use are formulated based on equivalent rather than tensorial quantities valid under these specific test conditions and are subsequently applied to heterogeneous underground systems and complex 3D load cases. We show here that this procedure is inappropriate and can lead to erroneous results. We further propose alternative formulations of the constitutive models in question that restore their validity under arbitrary loading conditions. For an efficient numerical simulation, the discussed constitutive models are integrated locally with a Newton-Raphson algorithm that directly provides the algorithmically consistent tangent matrix for the global Newton iteration of the displacement based finite element formulation. Finally, the finite

  7. A mesostructurally-based anisotropic continuum model for biological soft tissues--decoupled invariant formulation.

    PubMed

    Limbert, Georges

    2011-11-01

    Characterising and modelling the mechanical behaviour of biological soft tissues is an essential step in the development of predictive computational models to assist research for a wide range of applications in medicine, biology, tissue engineering, pharmaceutics, consumer goods, cosmetics, transport or military. It is therefore critical to develop constitutive models that can capture particular rheological mechanisms operating at specific length scales so that these models are adapted for their intended applications. Here, a novel mesoscopically-based decoupled invariant-based continuum constitutive framework for transversely isotropic and orthotropic biological soft tissues is developed. A notable feature of the formulation is the full decoupling of shear interactions. The constitutive model is based on a combination of the framework proposed by Lu and Zhang [Lu, J., Zhang, L., 2005. Physically motivated invariant formulation for transversely isotropic hyperelasticity. International Journal of Solids and Structures 42, 6015-6031] and the entropic mechanics of tropocollagen molecules and collagen assemblies. One of the key aspects of the formulation is to use physically-based nanoscopic quantities that could be extracted from experiments and/or atomistic/molecular dynamics simulations to inform the macroscopic constitutive behaviour. This effectively couples the material properties at different levels of the multi-scale hierarchical structure of collagenous tissues. The orthotropic hyperelastic model was shown to reproduce very well the experimental multi-axial properties of rabbit skin. A new insight into the shear response of a skin sample subjected to a simulated indentation test was obtained using numerical direct sensitivity analyses.

  8. In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications.

    PubMed

    Dwivedi, Vibha; Anandan, E M; Mony, Rajesh S; Muraleedharan, T S; Valiathan, M S; Mutsuddi, Mousumi; Lakhotia, Subhash C

    2012-01-01

    Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their "active" components as is done in most current studies. We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of different Ayurvedic

  9. In Vivo Effects Of Traditional Ayurvedic Formulations in Drosophila melanogaster Model Relate with Therapeutic Applications

    PubMed Central

    Dwivedi, Vibha; Anandan, E. M.; Mony, Rajesh S.; Muraleedharan, T. S.; Valiathan, M. S.; Mutsuddi, Mousumi; Lakhotia, Subhash C.

    2012-01-01

    Background Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their “active” components as is done in most current studies. Methods We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. Results A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. Conclusions The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular

  10. On the formulation, parameter identification and numerical integration of the EMMI model :plasticity and isotropic damage.

    SciTech Connect

    Bammann, Douglas J.; Johnson, G. C. (University of California, Berkeley, CA); Marin, Esteban B.; Regueiro, Richard A.

    2006-01-01

    In this report we present the formulation of the physically-based Evolving Microstructural Model of Inelasticity (EMMI) . The specific version of the model treated here describes the plasticity and isotropic damage of metals as being currently applied to model the ductile failure process in structural components of the W80 program . The formulation of the EMMI constitutive equations is framed in the context of the large deformation kinematics of solids and the thermodynamics of internal state variables . This formulation is focused first on developing the plasticity equations in both the relaxed (unloaded) and current configurations. The equations in the current configuration, expressed in non-dimensional form, are used to devise the identification procedure for the plasticity parameters. The model is then extended to include a porosity-based isotropic damage state variable to describe the progressive deterioration of the strength and mechanical properties of metals induced by deformation . The numerical treatment of these coupled plasticity-damage constitutive equations is explained in detail. A number of examples are solved to validate the numerical implementation of the model.

  11. A new pressure formulation for gas-compressibility dampening in bubble dynamics models.

    PubMed

    Gadi Man, Yezaz Ahmed; Trujillo, Francisco J

    2016-09-01

    We formulated a pressure equation for bubbles performing nonlinear radial oscillations under ultrasonic high pressure amplitudes. The proposed equation corrects the gas pressure at the gas-liquid interface on inertial bubbles. This pressure formulation, expressed in terms of gas-Mach number, accounts for dampening due to gas compressibility during the violent collapse of cavitation bubbles and during subsequent rebounds. We refer to this as inhomogeneous pressure, where the gas pressure at the gas-liquid interface can differ to the pressure at the centre of the bubble, in contrast to homogenous pressure formulations that consider that pressure inside the bubble is spatially uniform from the wall to the centre. The pressure correction was applied to two bubble dynamic models: the incompressible Rayleigh-Plesset equation and the compressible Keller and Miksis equation. This improved the predictions of the nonlinear radial motion of the bubble vs time obtained with both models. Those simulations were also compared with other bubble dynamics models that account for liquid and gas compressibility effects. It was found that our corrected models are in closer agreement with experimental data than alternative models. It was concluded that the Rayleigh-Plesset family of equations improve accuracy by using our proposed pressure correction.

  12. Formulation of human-structure interaction system models for vertical vibration

    NASA Astrophysics Data System (ADS)

    Caprani, Colin C.; Ahmadi, Ehsan

    2016-09-01

    In this paper, human-structure interaction system models for vibration in the vertical direction are considered. This work assembles various moving load models from the literature and proposes extension of the single pedestrian to a crowd of pedestrians for the FE formulation for crowd-structure interaction systems. The walking pedestrian vertical force is represented as a general time-dependent force, and the pedestrian is in turn modelled as moving force, moving mass, and moving spring-mass-damper. The arbitrary beam structure is modelled using either a formulation in modal coordinates or finite elements. In each case, the human-structure interaction (HSI) system is first formulated for a single walking pedestrian and then extended to consider a crowd of pedestrians. Finally, example applications for single pedestrian and crowd loading scenarios are examined. It is shown how the models can be used to quantify the interaction between the crowd and bridge structure. This work should find use for the evaluation of existing and new footbridges.

  13. Modelling formulations using gene expression programming--a comparative analysis with artificial neural networks.

    PubMed

    Colbourn, E A; Roskilly, S J; Rowe, R C; York, P

    2011-10-09

    This study has investigated the utility and potential advantages of gene expression programming (GEP)--a new development in evolutionary computing for modelling data and automatically generating equations that describe the cause-and-effect relationships in a system--to four types of pharmaceutical formulation and compared the models with those generated by neural networks, a technique now widely used in the formulation development. Both methods were capable of discovering subtle and non-linear relationships within the data, with no requirement from the user to specify the functional forms that should be used. Although the neural networks rapidly developed models with higher values for the ANOVA R(2) these were black box and provided little insight into the key relationships. However, GEP, although significantly slower at developing models, generated relatively simple equations describing the relationships that could be interpreted directly. The results indicate that GEP can be considered an effective and efficient modelling technique for formulation data. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    NASA Astrophysics Data System (ADS)

    Coradeschi, Francesco; de Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2)L⊗SU(2)R in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  15. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    SciTech Connect

    Coradeschi, Francesco; De Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2){sub L} x SU(2){sub R} in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  16. Continuum Level Formulation and Implementation of a Multi-scale Model for Vanadium

    SciTech Connect

    Lawrence Livermore National Laboratory

    2009-08-17

    A multi-scale approach is used to construct a continuum strength model for vanadium. The model is formulated assuming plastic deformation by dislocation motion and strain hardening due to dislocation interactions. Dislocation density is adopted as the state variable in the model. Information from molecular statics, molecular dynamics and dislocation dynamics simulations is combined to create kinetic relations for dislocation motion, strain hardening relations and evolution equations for the dislocation density. Implicit time integration of the constitutive equations is described in the context of implementation in a finite element code. Results are provided illustrating the strain, strain rate, temperature and pressure dependence of the constitutive model.

  17. A direct comparison of a depth-dependent Radiation stress formulation and a Vortex force formulation within a three-dimensional coastal ocean model

    NASA Astrophysics Data System (ADS)

    Moghimi, Saeed; Klingbeil, Knut; Gräwe, Ulf; Burchard, Hans

    2013-10-01

    In this study a model system consisting of the three-dimensional General Estuarine Transport Model (GETM) and the third generation wind wave model SWAN was developed. Both models were coupled in two-way mode. The effects of waves were included into the ocean model by implementing the depth-dependent Radiation stress formulation (RS) of Mellor (2011a) and the Vortex force formulation (VF) presented by Bennis et al. (2011). Thus, the developed model system offers a direct comparison of these two formulations. The enhancement of the vertical eddy viscosity due to the energy transfer by white capping and breaking waves was taken into account by means of injecting turbulent kinetic energy at the surface. Wave-current interaction inside the bottom boundary layer was considered as well. The implementation of both wave-averaged formulations was validated against three flume experiments. One of these experiments with long period surface waves (swell), had not been evaluated before. The validation showed the capability of the model system to reproduce the three-dimensional interaction of waves and currents. For the flume test cases the wave-induced water level changes (wave set-up and set-down) and the corresponding depth-integrated wave-averaged velocities were similar for RS and VF. Both formulations produced comparable velocity profiles for short period waves. However, for large period waves, VF overestimated the wave set-down near the main breaking points and RS showed artificial offshore-directed transport at the surface where wave shoaling was taking place. Finally the validated model system was applied to a realistic barred beach scenario. For RS and VF the resulting velocity profiles were similar after being significantly improved by a roller evolution method. Both wave-averaged formulations generally provided similar results, but some shortcomings were revealed. Although VF partly showed significant deviations from the measurements, its results were still physically

  18. Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

    PubMed

    Polster, Christopher S; Wu, Sy-Juen; Gueorguieva, Ivelina; Sperry, David C

    2015-04-06

    An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A pharmacokinetic study in humans demonstrated the enhanced performance of the solid dispersion formulation relative to the HSWG formulation. The Cmax and AUC of the solid dispersion was 2.6 and 1.9 times greater, respectively, compared to the HSWG formulation. In the ASD, the solid dispersion formulation performance was characterized by three main phases: (1) rapid release in the stomach, creating a supersaturated concentration of drug, (2) precipitation in the stomach, and (3) rapid redissolution of the precipitate in the duodenum to concentration levels that are supersaturated relative to crystalline drug. A series of complementary experiments were employed to describe this performance behavior mechanistically. Imaging experiments with a pH indicating dye showed that local pH gradients from meglumine in the solid dispersion formulation were responsible for creating a high initial supersaturation concentration in the stomach. Upon dissipation of meglumine, the drug precipitated in the stomach as an amorphous solid. Because the precipitated drug is in an amorphous form, it can then rapidly redissolve as it transits to the more neutral environment of the duodenum. This unexpected sequence of physical state changes gives a mechanistic explanation for the enhanced in vivo performance of the solid dispersion formulation relative to the HSWG formulation.

  19. Models for evaluation of relative immunogenic potential of protein particles in biopharmaceutical protein formulations.

    PubMed

    Johnson, Richard; Jiskoot, Wim

    2012-10-01

    An immune response to a therapeutic protein that compromises the biopharmaceutical activity or cross-reacts with an endogenous protein is a serious clinical event. The role of protein aggregates and particles in biopharmaceutical formulations in mediating this immune response has gained considerable attention over the recent past. Model systems that could consistently and reliably predict the relative immunogenicity of biopharmaceutical protein formulations would be extremely valuable. Several approaches have been developed in an attempt to provide this insight, including in silico algorithms, in vitro tests utilizing human leukocytes and in vivo animal models. This commentary provides an update of these various approaches as well as the author's perspectives on the pros and cons of these different methods. Copyright © 2012 Wiley Periodicals, Inc.

  20. Formulation of probabilistic models of protein structure in atomic detail using the reference ratio method.

    PubMed

    Valentin, Jan B; Andreetta, Christian; Boomsma, Wouter; Bottaro, Sandro; Ferkinghoff-Borg, Jesper; Frellsen, Jes; Mardia, Kanti V; Tian, Pengfei; Hamelryck, Thomas

    2014-02-01

    We propose a method to formulate probabilistic models of protein structure in atomic detail, for a given amino acid sequence, based on Bayesian principles, while retaining a close link to physics. We start from two previously developed probabilistic models of protein structure on a local length scale, which concern the dihedral angles in main chain and side chains, respectively. Conceptually, this constitutes a probabilistic and continuous alternative to the use of discrete fragment and rotamer libraries. The local model is combined with a nonlocal model that involves a small number of energy terms according to a physical force field, and some information on the overall secondary structure content. In this initial study we focus on the formulation of the joint model and the evaluation of the use of an energy vector as a descriptor of a protein's nonlocal structure; hence, we derive the parameters of the nonlocal model from the native structure without loss of generality. The local and nonlocal models are combined using the reference ratio method, which is a well-justified probabilistic construction. For evaluation, we use the resulting joint models to predict the structure of four proteins. The results indicate that the proposed method and the probabilistic models show considerable promise for probabilistic protein structure prediction and related applications. Copyright © 2013 Wiley Periodicals, Inc.

  1. Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations

    PubMed Central

    Gesquiere, Ina; Darwich, Adam S; Van der Schueren, Bart; de Hoon, Jan; Lannoo, Matthias; Matthys, Christophe; Rostami, Amin; Foulon, Veerle; Augustijns, Patrick

    2015-01-01

    Aims The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB. Methods A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6–8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB. Results After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC0–24 h) was shown, although a tendency towards an increased oral exposure could be observed as the AUC0–24 h was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled-release formulation, respectively. This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity. Conclusions The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation. PMID:25917170

  2. Formulation of consumables management models: Mission planning processor payload interface definition

    NASA Technical Reports Server (NTRS)

    Torian, J. G.

    1977-01-01

    Consumables models required for the mission planning and scheduling function are formulated. The relation of the models to prelaunch, onboard, ground support, and postmission functions for the space transportation systems is established. Analytical models consisting of an orbiter planning processor with consumables data base is developed. A method of recognizing potential constraint violations in both the planning and flight operations functions, and a flight data file storage/retrieval of information over an extended period which interfaces with a flight operations processor for monitoring of the actual flights is presented.

  3. The interplay between transpiration and Runoff formulations in land surface schemes used with atmospheric models

    USGS Publications Warehouse

    Koster, R.D.; Milly, P.C.D.

    1997-01-01

    The Project for Intercomparison of Land-surface Parameterization Schemes (PILPS) has shown that different land surface models (LSMs) driven by the same meteorological forcing can produce markedly different surface energy and water budgets, even when certain critical aspects of the LSMs (vegetation cover, albedo, turbulent drag coefficient, and snowcover) are carefully controlled. To help explain these differences, the authors devised a monthly water balance model that successfully reproduces the annual and seasonal water balances of the different PILPS schemes. Analysis of this model leads to the identification of two quantities that characterize an LSM's formulation of soil water balance dynamics: 1) the efficiency of the soil's evaporation sink integrated over the active soil moisture range, and 2) the fraction of this range over which runoff is generated. Regardless of the LSM's complexity, the combination of these two derived parameters with rates of interception loss, potential evaporation, and precipitation provides a reasonable estimate for the LSM's simulated annual water balance. The two derived parameters shed light on how evaporation and runoff formulations interact in an LSM, and the analysis as a whole underscores the need for compatibility in these formulations.

  4. The Interplay Between Transpiration and Runoff Formulations in Land Surface Schemes Used with Atmospheric Models

    NASA Technical Reports Server (NTRS)

    Koster, Rindal D.; Milly, P. C. D.

    1997-01-01

    The Project for Intercomparison of Land-surface Parameterization Schemes (PILPS) has shown that different land surface models (LSMS) driven by the same meteorological forcing can produce markedly different surface energy and water budgets, even when certain critical aspects of the LSMs (vegetation cover, albedo, turbulent drag coefficient, and snow cover) are carefully controlled. To help explain these differences, the authors devised a monthly water balance model that successfully reproduces the annual and seasonal water balances of the different PILPS schemes. Analysis of this model leads to the identification of two quantities that characterize an LSM's formulation of soil water balance dynamics: (1) the efficiency of the soil's evaporation sink integrated over the active soil moisture range, and (2) the fraction of this range over which runoff is generated. Regardless of the LSM's complexity, the combination of these two derived parameters with rates of interception loss, potential evaporation, and precipitation provides a reasonable estimate for the LSM's simulated annual water balance. The two derived parameters shed light on how evaporation and runoff formulations interact in an LSM, and the analysis as a whole underscores the need for compatibility in these formulations.

  5. Ignition and Growth Modeling of Shock Initiation of Different Particle Size Formulations of PBXC03 Explosive

    NASA Astrophysics Data System (ADS)

    Hussain, Tariq; Liu, Yan; Huang, Fenglei; Duan, Zhuoping

    2016-01-01

    The change in shock sensitivity of explosives having various explosive grain sizes is discussed. Along with other parameters, explosive grain size is one of the key parameters controlling the macroscopic behavior of shocked pressed explosives. Ignition and growth reactive flow modeling is performed for the shock initiation experiments carried out by using the in situ manganin piezoresistive pressure gauge technique to investigate the influences of the octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) particle size on the shock initiation and the subsequent detonation growth process for the three explosive formulations of pressed PBXC03 (87% HMX, 7% 1,3,5-trichloro-2,4,6-trinitrobenzene (TATB), 6% Viton by weight). All of the formulation studied had the same density but different explosive grain sizes. A set of ignition and growth parameters was obtained for all three formulations. Only the coefficient G1 of the first growth term in the reaction rate equation was varied with the grain size; all other parameters were kept the same for all formulations. It was found that G1 decreases almost linearly with HMX particle size for PBXC03. However, the equation of state (EOS) for solid explosive had to be adjusted to fit the experimental data. Both experimental and numerical simulation results show that the shock sensitivity of PBXC03 decreases with increasing HMX particle size for the sustained pressure pulses (around 4 GPa) as obtained in the experiment. This result is in accordance with the results reported elsewhere in literature. For future work, a better approach may be to find standard solid Grüneisen EOS and product Jones-Wilkins-Lee (JWL) EOS for each formulation for the best fit to the experimental data.

  6. System-approach methods for modeling and testing similarity of in vitro dissolutions of drug dosage formulations.

    PubMed

    Dedík, Ladislav; Durisová, Mária

    2002-07-01

    System-approach based modeling methods are used to model dynamic systems describing in vitro dissolutions of drug dosage formulations. Employing the models of these systems, model-dependent criteria are proposed for testing similarity between in vitro dissolutions of different drug dosage formulations. The criteria proposed are exemplified and compared with the criterion called the similarity factor f(2), commonly used in the field of biomedicine. Advantages of the criteria proposed over this factor are presented.

  7. A Novel Model Predictive Control Formulation for Hybrid Systems With Application to Adaptive Behavioral Interventions

    PubMed Central

    Nandola, Naresh N.; Rivera, Daniel E.

    2010-01-01

    This paper presents a novel model predictive control (MPC) formulation for linear hybrid systems. The algorithm relies on a multiple-degree-of-freedom formulation that enables the user to adjust the speed of setpoint tracking, measured disturbance rejection and unmeasured disturbance rejection independently in the closed-loop system. Consequently, controller tuning is more flexible and intuitive than relying on move suppression weights as traditionally used in MPC schemes. The formulation is motivated by the need to achieve robust performance in using the algorithm in emerging applications, for instance, as a decision policy for adaptive, time-varying interventions used in behavioral health. The proposed algorithm is demonstrated on a hypothetical adaptive intervention problem inspired by the Fast Track program, a real-life preventive intervention for improving parental function and reducing conduct disorder in at-risk children. Simulation results in the presence of simultaneous disturbances and significant plant-model mismatch are presented. These demonstrate that a hybrid MPC-based approach for this class of interventions can be tuned for desired performance under demanding conditions that resemble participant variability that is experienced in practice when applying an adaptive intervention to a population. PMID:20830213

  8. Biomechanical behaviour of heel pad tissue: experimental testing, constitutive formulation, and numerical modelling.

    PubMed

    Natali, A N; Fontanella, C G; Carniel, E L; Young, Miller

    2011-05-01

    This paper deals with the constitutive formulation of heel pad tissue and presents a procedure for identifying constitutive parameters using experimental data, with the aim of developing a computational approach for investigating the actual biomechanical response. The preliminary definition of constitutive parameters was developed using a visco-hyperelastic formulation, considering experimental data from in vitro compression tests on specimens of fat pad tissue and data from in vivo tests to identify the actual trend of tissue stiffness. The discrepancy between model results and experimental data was evaluated on the basis of a specific cost function, adopting a stochastic/deterministic procedure. The parameter evaluation was upgraded by considering experimental tests performed on the fat pad tissues of a cadaveric foot using in situ indentation tests at 0.01 and 350 mm/s strain rates. The constitutive formulation was implemented in a numerical model. The comparison of data from in situ tests and numerical results led to an optimal domain of parameters based on an admissible discrepancy criterion. Numerical results evaluated for different sets of parameters inside the domain are reported and compared with experimental data for a reliability evaluation of the proposed procedure.

  9. Early Formulation Model-centric Engineering on NASA's Europa Mission Concept Study

    NASA Technical Reports Server (NTRS)

    Bayer, Todd; Chung, Seung; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Chris; Gontijo, Ivair; Lewis, Kari; Moshir, Mehrdad; Rasmussen, Robert; hide

    2012-01-01

    The proposed Jupiter Europa Orbiter and Jupiter Ganymede Orbiter missions were formulated using current state-of-the-art MBSE facilities: - JPL's TeamX, Rapid Mission Architecting - ESA's Concurrent Design Facility - APL's ACE Concurrent Engineering Facility. When JEO became an official "pre-project" in Sep 2010, we had already developed a strong partnership with JPL's Integrated Model Centric Engineering (IMCE) initiative; decided to apply Architecting and SysML-based MBSE from the beginning, begun laying these foundations to support work in Phase A. Release of Planetary Science Decadal Survey and FY12 President's Budget in March 2011 changed the landscape. JEO reverted to being a pre-phase A study. A conscious choice was made to continue application of MBSE on the Europa Study, refocused for early formulation. This presentation describes the approach, results, and lessons.

  10. Early Formulation Model-centric Engineering on NASA's Europa Mission Concept Study

    NASA Technical Reports Server (NTRS)

    Bayer, Todd; Chung, Seung; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Chris; Gontijo, Ivair; Lewis, Kari; Moshir, Mehrdad; Rasmussen, Robert; Wagner, David

    2012-01-01

    The proposed Jupiter Europa Orbiter and Jupiter Ganymede Orbiter missions were formulated using current state-of-the-art MBSE facilities: - JPL's TeamX, Rapid Mission Architecting - ESA's Concurrent Design Facility - APL's ACE Concurrent Engineering Facility. When JEO became an official "pre-project" in Sep 2010, we had already developed a strong partnership with JPL's Integrated Model Centric Engineering (IMCE) initiative; decided to apply Architecting and SysML-based MBSE from the beginning, begun laying these foundations to support work in Phase A. Release of Planetary Science Decadal Survey and FY12 President's Budget in March 2011 changed the landscape. JEO reverted to being a pre-phase A study. A conscious choice was made to continue application of MBSE on the Europa Study, refocused for early formulation. This presentation describes the approach, results, and lessons.

  11. Abelian embedding formulation of the Stueckelberg model and its power-counting renormalizable extension

    NASA Astrophysics Data System (ADS)

    Quadri, Andrea

    2006-03-01

    We elucidate the geometry of the polynomial formulation of the non-Abelian Stueckelberg mechanism. We show that a natural off-shell nilpotent Becchi-Rouet-Stora-Tyutin (BRST) differential exists allowing to implement the constraint on the σ field by means of BRST techniques. This is achieved by extending the ghost sector by an additional U(1) factor (Abelian embedding). An important consequence is that a further BRST-invariant but not gauge-invariant mass term can be written for the non-Abelian gauge fields. As all versions of the Stueckelberg theory, also the Abelian embedding formulation yields a nonpower-counting renormalizable theory in D=4. We then derive its natural power-counting renormalizable extension and show that the physical spectrum contains a physical massive scalar particle. Physical unitarity is also established. This model implements the spontaneous symmetry breaking in the Abelian embedding formalism.

  12. The parameterization of the planetary boundary layer in the UCLA general circulation model - Formulation and results

    NASA Technical Reports Server (NTRS)

    Suarez, M. J.; Arakawa, A.; Randall, D. A.

    1983-01-01

    A planetary boundary layer (PBL) parameterization for general circulation models (GCMs) is presented. It uses a mixed-layer approach in which the PBL is assumed to be capped by discontinuities in the mean vertical profiles. Both clear and cloud-topped boundary layers are parameterized. Particular emphasis is placed on the formulation of the coupling between the PBL and both the free atmosphere and cumulus convection. For this purpose a modified sigma-coordinate is introduced in which the PBL top and the lower boundary are both coordinate surfaces. The use of a bulk PBL formulation with this coordinate is extensively discussed. Results are presented from a July simulation produced by the UCLA GCM. PBL-related variables are shown, to illustrate the various regimes the parameterization is capable of simulating.

  13. The parameterization of the planetary boundary layer in the UCLA general circulation model - Formulation and results

    NASA Technical Reports Server (NTRS)

    Suarez, M. J.; Arakawa, A.; Randall, D. A.

    1983-01-01

    A planetary boundary layer (PBL) parameterization for general circulation models (GCMs) is presented. It uses a mixed-layer approach in which the PBL is assumed to be capped by discontinuities in the mean vertical profiles. Both clear and cloud-topped boundary layers are parameterized. Particular emphasis is placed on the formulation of the coupling between the PBL and both the free atmosphere and cumulus convection. For this purpose a modified sigma-coordinate is introduced in which the PBL top and the lower boundary are both coordinate surfaces. The use of a bulk PBL formulation with this coordinate is extensively discussed. Results are presented from a July simulation produced by the UCLA GCM. PBL-related variables are shown, to illustrate the various regimes the parameterization is capable of simulating.

  14. Early Formulation Model-centric Engineering on Nasa's Europa Mission Concept Study

    NASA Technical Reports Server (NTRS)

    Bayer, Todd; Chung, Seung; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Chris; Gontijo, I.; Lewis, Kari; Moshir, Mehrdad; Rasmussen, Robert; hide

    2012-01-01

    By leveraging the existing Model-Based Systems Engineering (MBSE) infrastructure at JPL and adding a modest investment, the Europa Mission Concept Study made striking advances in mission concept capture and analysis. This effort has reaffirmed the importance of architecting and successfully harnessed the synergistic relationship of system modeling to mission architecting. It clearly demonstrated that MBSE can provide greater agility than traditional systems engineering methods. This paper will describe the successful application of MBSE in the dynamic environment of early mission formulation, the significant results produced and lessons learned in the process.

  15. Early Formulation Model-centric Engineering on Nasa's Europa Mission Concept Study

    NASA Technical Reports Server (NTRS)

    Bayer, Todd; Chung, Seung; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Chris; Gontijo, I.; Lewis, Kari; Moshir, Mehrdad; Rasmussen, Robert; Wagner, David

    2012-01-01

    By leveraging the existing Model-Based Systems Engineering (MBSE) infrastructure at JPL and adding a modest investment, the Europa Mission Concept Study made striking advances in mission concept capture and analysis. This effort has reaffirmed the importance of architecting and successfully harnessed the synergistic relationship of system modeling to mission architecting. It clearly demonstrated that MBSE can provide greater agility than traditional systems engineering methods. This paper will describe the successful application of MBSE in the dynamic environment of early mission formulation, the significant results produced and lessons learned in the process.

  16. HSCT Assessment Calculations with the AER 2-D Model: Sensitivities to Transport Formulation, PSC Formulation, Interannual Temperature Variation. Appendix C

    NASA Technical Reports Server (NTRS)

    Weisenstein, Debra K.; Ko, Malcolm K. W.; Scott, Courtney J.; Shia, Run-Lie; Jackman, Charles; Fleming, Eric; Considine, David; Kinnison, Douglas; Connell, Peter; Rotman, Douglas

    1998-01-01

    The summary are: (1) Some chemical differences in background atmosphere are surprisingly large (NOY). (2) Differences in model transport explain a majority of the intertnodel differences in the absence of PSCs. (3) With PSCS, large differences exist in predicted O3 depletion between models with the same transport. (4) AER/LLNL model calculates more O3 depletion in NH than LLNL. (5) AER/GSFC model cannot match calculated O3 depletion of GSFC model in SH. and (6) Results sensitive to interannual temperature variations (at least in NH).

  17. An energetic formulation of a one-dimensional model of superelastic SMA

    NASA Astrophysics Data System (ADS)

    Pham, Kim

    2014-03-01

    This paper presents an energetic framework for the study of the macroscopic evolution of shape memory alloys (SMA) with softening behavior. It is written for a class of standard rate-independent materials with an internal variable derived from the Drucker-Ilyushin work property. This one-dimensional model is defined by three material functions of the internal variable and one material parameter. The quasi-static evolution is formulated for a one-dimensional bar under traction and is based on two physical principles: a stability criterion which consists in selecting the local minima of the total energy and an energy balance condition which requires the absolute continuity of the total energy. The stability criterion aims to overcome the non-uniqueness issue associated with the intrinsic softening character of SMA while the energy balance condition accounts for evolutions even with possible time discontinuities. While being consistent with the classical Kuhn-Tucker formulation of the phase transformations, such energetic formulation proved to be more suitable than this latter for the study of stress-softening SMA. Both homogeneous and non-homogenous solutions are investigated with respect to this variational evolution problem. Specifically, we show the instability of the homogeneous states for softening materials and construct, in this latter case, a non-homogeneous stable evolution that follows a transformation stress line which corresponds to the Maxwell line of the softening intrinsic behavior.

  18. Cohesive surface model for fracture based on a two-scale formulation: computational implementation aspects

    NASA Astrophysics Data System (ADS)

    Toro, S.; Sánchez, P. J.; Podestá, J. M.; Blanco, P. J.; Huespe, A. E.; Feijóo, R. A.

    2016-10-01

    The paper describes the computational aspects and numerical implementation of a two-scale cohesive surface methodology developed for analyzing fracture in heterogeneous materials with complex micro-structures. This approach can be categorized as a semi-concurrent model using the representative volume element concept. A variational multi-scale formulation of the methodology has been previously presented by the authors. Subsequently, the formulation has been generalized and improved in two aspects: (i) cohesive surfaces have been introduced at both scales of analysis, they are modeled with a strong discontinuity kinematics (new equations describing the insertion of the macro-scale strains, into the micro-scale and the posterior homogenization procedure have been considered); (ii) the computational procedure and numerical implementation have been adapted for this formulation. The first point has been presented elsewhere, and it is summarized here. Instead, the main objective of this paper is to address a rather detailed presentation of the second point. Finite element techniques for modeling cohesive surfaces at both scales of analysis (FE^2 approach) are described: (i) finite elements with embedded strong discontinuities are used for the macro-scale simulation, and (ii) continuum-type finite elements with high aspect ratios, mimicking cohesive surfaces, are adopted for simulating the failure mechanisms at the micro-scale. The methodology is validated through numerical simulation of a quasi-brittle concrete fracture problem. The proposed multi-scale model is capable of unveiling the mechanisms that lead from the material degradation phenomenon at the meso-structural level to the activation and propagation of cohesive surfaces at the structural scale.

  19. A finite element formulation for modeling dynamic wetting on flexible substrates and in deformable porous media.

    SciTech Connect

    Schunk, Peter Randall; Cairncross, Richard A.; Madasu, S.

    2004-03-01

    This report summarizes research advances pursued with award funding issued by the DOE to Drexel University through the Presidential Early Career Award (PECASE) program. Professor Rich Cairncross was the recipient of this award in 1997. With it he pursued two related research topics under Sandia's guidance that address the outstanding issue of fluid-structural interactions of liquids with deformable solid materials, focusing mainly on the ubiquitous dynamic wetting problem. The project focus in the first four years was aimed at deriving a predictive numerical modeling approach for the motion of the dynamic contact line on a deformable substrate. A formulation of physical model equations was derived in the context of the Galerkin finite element method in an arbitrary Lagrangian/Eulerian (ALE) frame of reference. The formulation was successfully integrated in Sandia's Goma finite element code and tested on several technologically important thin-film coating problems. The model equations, the finite-element implementation, and results from several applications are given in this report. In the last year of the five-year project the same physical concepts were extended towards the problem of capillary imbibition in deformable porous media. A synopsis of this preliminary modeling and experimental effort is also discussed.

  20. A constrained multinomial Probit route choice model in the metro network: Formulation, estimation and application.

    PubMed

    Zhang, Yongsheng; Yao, Enjian; Wei, Heng; Zheng, Kangning

    2017-01-01

    Considering that metro network expansion brings us with more alternative routes, it is attractive to integrate the impacts of routes set and the interdependency among alternative routes on route choice probability into route choice modeling. Therefore, the formulation, estimation and application of a constrained multinomial probit (CMNP) route choice model in the metro network are carried out in this paper. The utility function is formulated as three components: the compensatory component is a function of influencing factors; the non-compensatory component measures the impacts of routes set on utility; following a multivariate normal distribution, the covariance of error component is structured into three parts, representing the correlation among routes, the transfer variance of route, and the unobserved variance respectively. Considering multidimensional integrals of the multivariate normal probability density function, the CMNP model is rewritten as Hierarchical Bayes formula and M-H sampling algorithm based Monte Carlo Markov Chain approach is constructed to estimate all parameters. Based on Guangzhou Metro data, reliable estimation results are gained. Furthermore, the proposed CMNP model also shows a good forecasting performance for the route choice probabilities calculation and a good application performance for transfer flow volume prediction.

  1. The perspective awareness model - Eliciting multiple perspectives to formulate high quality decisions

    SciTech Connect

    Boucher, Laurel

    2013-07-01

    A great deal of attention is given to the importance of communication in environmental remediation and radioactive waste management. However, very little attention is given to eliciting multiple perspectives so as to formulate high quality decisions. Plans that are based on a limited number of perspectives tend to be narrowly focused whereas those that are based on a wide variety of perspectives tend to be comprehensive, higher quality, and more apt to be put into application. In addition, existing methods of dialogue have built-in limitations in that they typically draw from the predominant thinking patterns which focus in some areas but ignore others. This can result in clarity but a lack of comprehensiveness. This paper presents a Perspective Awareness Model which helps groups such as partnering teams, interagency teams, steering committees, and working groups elicit a wide net of perspectives and viewpoints. The paper begins by describing five factors that makes cooperation among such groups challenging. Next, a Perspective Awareness Model that makes it possible to manage these five factors is presented. The two primary components of this model --- the eight 'Thinking Directions' and the 'Shared Documentation' --- are described in detail. Several examples are given to illustrate how the Perspective Awareness Model can be used to elicit multiple perspectives to formulate high quality decisions in the area of environmental remediation and radioactive waste management. (authors)

  2. A constrained multinomial Probit route choice model in the metro network: Formulation, estimation and application

    PubMed Central

    Zhang, Yongsheng; Wei, Heng; Zheng, Kangning

    2017-01-01

    Considering that metro network expansion brings us with more alternative routes, it is attractive to integrate the impacts of routes set and the interdependency among alternative routes on route choice probability into route choice modeling. Therefore, the formulation, estimation and application of a constrained multinomial probit (CMNP) route choice model in the metro network are carried out in this paper. The utility function is formulated as three components: the compensatory component is a function of influencing factors; the non-compensatory component measures the impacts of routes set on utility; following a multivariate normal distribution, the covariance of error component is structured into three parts, representing the correlation among routes, the transfer variance of route, and the unobserved variance respectively. Considering multidimensional integrals of the multivariate normal probability density function, the CMNP model is rewritten as Hierarchical Bayes formula and M-H sampling algorithm based Monte Carlo Markov Chain approach is constructed to estimate all parameters. Based on Guangzhou Metro data, reliable estimation results are gained. Furthermore, the proposed CMNP model also shows a good forecasting performance for the route choice probabilities calculation and a good application performance for transfer flow volume prediction. PMID:28591188

  3. A density-scaled continuum surface force model within a balanced force formulation

    NASA Astrophysics Data System (ADS)

    Yokoi, Kensuke

    2014-12-01

    We propose a numerical framework which can simulate free surface flows with complex moving interfaces like droplet splashing as minimizing spurious currents. The numerical framework is based on the CLSVOF (coupled level set and volume-of-fluid) method, the THINC/WLIC (tangent of hyperbola for interface capturing/weighted line interface calculation) scheme, multi-moment methods (CIP-CSL and VSIAM3) and density-scaled CSF (continuum surface force) model within a balanced force formulation. In this paper, we propose a level set based algorithm of the density-scaled balanced CSF model and show that the density-scaled balanced CSF model can reduce spurious currents more than the standard balanced CSF model without using the density-scaling when the exact curvature is not given. We also show that the numerical framework can well capture the physics of droplet splashing.

  4. An indirect latent informational conformity social influence choice model: Formulation and case study

    DOE PAGES

    Maness, Michael; Cirillo, Cinzia

    2016-11-01

    The current state-of-the-art in social influence models of travel behavior is conformity models with direct benefit social influence effects. Indirect effects have seen limited development, but this paper presents a latent class discrete choice model of an indirect informational conformity hypothesis. Moreover, class membership depends on the proportion of group members who adopt a behavior. Membership into the more informed class causes changes in the preferences of those individuals thus making adoption more attractive. Equilibrium properties are derived for this model showing the possibility of multiple equilibria but under different conditions than the direct-benefit formulations. Social influence elasticity is derivedmore » for both models types. The informational conformity model can represent non-linear elasticity behavior unlike the direct-benefit formulation. Additionally, a two-stage control function is developed to obtain consistent parameter estimates in the presence of an endogenous class membership model covariate that is correlated with choice model unobservables. A case study to study social influence in bicycle ownership in the United States is presented. Our results showed that more informed households had a greater chance of owning a bike due to preference changes with less sensitivity to smaller home footprints and limited incomes. The behavioral hypothesis of positive preference change due to information transfer was confirmed. Observed ownership share closely matched predicted local-level equilibrium in some metropolitan areas but was unable to achieve expected prediction rate within confidence intervals. Finally, the elasticity of social influence was found to range locally from about 0.5% to 1.0%.« less

  5. An indirect latent informational conformity social influence choice model: Formulation and case study

    SciTech Connect

    Maness, Michael; Cirillo, Cinzia

    2016-11-01

    The current state-of-the-art in social influence models of travel behavior is conformity models with direct benefit social influence effects. Indirect effects have seen limited development, but this paper presents a latent class discrete choice model of an indirect informational conformity hypothesis. Moreover, class membership depends on the proportion of group members who adopt a behavior. Membership into the more informed class causes changes in the preferences of those individuals thus making adoption more attractive. Equilibrium properties are derived for this model showing the possibility of multiple equilibria but under different conditions than the direct-benefit formulations. Social influence elasticity is derived for both models types. The informational conformity model can represent non-linear elasticity behavior unlike the direct-benefit formulation. Additionally, a two-stage control function is developed to obtain consistent parameter estimates in the presence of an endogenous class membership model covariate that is correlated with choice model unobservables. A case study to study social influence in bicycle ownership in the United States is presented. Our results showed that more informed households had a greater chance of owning a bike due to preference changes with less sensitivity to smaller home footprints and limited incomes. The behavioral hypothesis of positive preference change due to information transfer was confirmed. Observed ownership share closely matched predicted local-level equilibrium in some metropolitan areas but was unable to achieve expected prediction rate within confidence intervals. Finally, the elasticity of social influence was found to range locally from about 0.5% to 1.0%.

  6. Large eddy simulation models for incompressible magnetohydrodynamics derived from the variational multiscale formulation

    SciTech Connect

    Sondak, David; Oberai, Assad A.

    2012-10-15

    Novel large eddy simulation (LES) models are developed for incompressible magnetohydrodynamics (MHD). These models include the application of the variational multiscale formulation of LES to the equations of incompressible MHD. Additionally, a new residual-based eddy viscosity model is introduced for MHD. A mixed LES model that combines the strengths of both of these models is also derived. The new models result in a consistent numerical method that is relatively simple to implement. The need for a dynamic procedure in determining model coefficients is no longer required. The new LES models are tested on a decaying Taylor-Green vortex generalized to MHD and benchmarked against classical LES turbulence models. The LES simulations are run in a periodic box of size [-{pi}, {pi}]{sup 3} with 32 modes in each direction and are compared to a direct numerical simulation (DNS) with 512 modes in each direction. The new models are able to account for the essential MHD physics which is demonstrated via comparisons of energy spectra. We also compare the performance of our models to a DNS simulation by Pouquet et al.['The dynamics of unforced turbulence at high Reynolds number for Taylor-Green vortices generalized to MHD,' Geophys. Astrophys. Fluid Dyn. 104, 115-134 (2010)], for which the ratio of DNS modes to LES modes is 262:144.

  7. Development of a Novel Simplified PBPK Absorption Model to Explain the Higher Relative Bioavailability of the OROS® Formulation of Oxybutynin.

    PubMed

    Olivares-Morales, Andrés; Ghosh, Avijit; Aarons, Leon; Rostami-Hodjegan, Amin

    2016-11-01

    A new minimal Segmented Transit and Absorption model (mSAT) model has been recently proposed and combined with intrinsic intestinal effective permeability (P eff,int ) to predict the regional gastrointestinal (GI) absorption (f abs ) of several drugs. Herein, this model was extended and applied for the prediction of oral bioavailability and pharmacokinetics of oxybutynin and its enantiomers to provide a mechanistic explanation of the higher relative bioavailability observed for oxybutynin's modified-release OROS® formulation compared to its immediate-release (IR) counterpart. The expansion of the model involved the incorporation of mechanistic equations for the prediction of release, transit, dissolution, permeation and first-pass metabolism. The predicted pharmacokinetics of oxybutynin enantiomers after oral administration for both the IR and OROS® formulations were in close agreement with the observed data. The predicted absolute bioavailability for the IR formulation was within 5% of the observed value, and the model adequately predicted the higher relative bioavailability observed for the OROS® formulation vs. the IR counterpart. From the model predictions, it can be noticed that the higher bioavailability observed for the OROS® formulation was mainly attributable to differences in the intestinal availability (F G ) rather than due to a higher colonic f abs , thus confirming previous hypotheses. The predicted f abs was almost 70% lower for the OROS® formulation compared to the IR formulation, whereas the F G was almost eightfold higher than in the IR formulation. These results provide further support to the hypothesis of an increased F G as the main factor responsible for the higher bioavailability of oxybutynin's OROS® formulation vs. the IR.

  8. A BEM formulation applied in the mechanical material modelling of viscoelastic cracked structures

    NASA Astrophysics Data System (ADS)

    Oliveira, Hugo Luiz; Leonel, Edson Denner

    2016-12-01

    The present study aims at performing a mechanical analysis of 2D viscoelastic cracked structural materials using the Boundary Element Method (BEM). The mesh dimensionality reduction provided by the BEM and its accuracy in representing high gradient fields make this numerical method robust to solve fracture mechanics problems. Viscoelastic models address phenomena that provide changes on the mechanical material properties along time. Well-established viscoelastic models such as Maxwell, Kelvin-Voigt and Boltzmann are used in this study. The numerical viscoelastic scheme, which is based on algebraic BEM equations, utilizes the Euler method for time derivative evaluation. Therefore, the unknown variables at the structural boundary and its variations along time are determined through an ordinary linear system of equations. Moreover, time-dependent boundary conditions may be considered, which represent loading phases. The dual BEM formulation is adopted for modelling the mechanical structural behaviour of cracks bodies. Three examples are considered to illustrate the robustness of the adopted formulation. The results achieved by the BEM are in good agreement with reported data and numerical stability is observed.

  9. A BEM formulation applied in the mechanical material modelling of viscoelastic cracked structures

    NASA Astrophysics Data System (ADS)

    Oliveira, Hugo Luiz; Leonel, Edson Denner

    2017-03-01

    The present study aims at performing a mechanical analysis of 2D viscoelastic cracked structural materials using the Boundary Element Method (BEM). The mesh dimensionality reduction provided by the BEM and its accuracy in representing high gradient fields make this numerical method robust to solve fracture mechanics problems. Viscoelastic models address phenomena that provide changes on the mechanical material properties along time. Well-established viscoelastic models such as Maxwell, Kelvin-Voigt and Boltzmann are used in this study. The numerical viscoelastic scheme, which is based on algebraic BEM equations, utilizes the Euler method for time derivative evaluation. Therefore, the unknown variables at the structural boundary and its variations along time are determined through an ordinary linear system of equations. Moreover, time-dependent boundary conditions may be considered, which represent loading phases. The dual BEM formulation is adopted for modelling the mechanical structural behaviour of cracks bodies. Three examples are considered to illustrate the robustness of the adopted formulation. The results achieved by the BEM are in good agreement with reported data and numerical stability is observed.

  10. Simultaneous geologic scenario identification and flow model calibration with group-sparsity formulations

    NASA Astrophysics Data System (ADS)

    Golmohammadi, Azarang; Jafarpour, Behnam

    2016-06-01

    Adopting representative geologic connectivity scenarios is critical for reliable modeling and prediction of flow and transport processes in subsurface environments. Geologic scenarios are often developed by integrating several sources of information, including knowledge of the depositional environment, qualitative and quantitative data such as outcrop and well logs, and process-based geologic modeling. In general, flow and transport response data are usually not included in constructing geologic scenarios for a basin. Instead, these data are typically matched using a given prior geologic scenario as constraint. Since data limitations, modeling assumptions and subjective interpretations can lead to significant uncertainty in the adopted geologic scenarios, flow and transport data may also be useful for constraining the uncertainty in proposed geologic scenarios. Constraining geologic scenarios with flow-related data opens an interesting and challenging research area, which goes beyond the traditional model calibration formulations where the geologic scenario is assumed given. In this paper, a novel concept, known as group-sparsity regularization, is proposed as an effective formulation to constrain the uncertainty in the prior geologic scenario during subsurface flow model calibration. Given a collection of model realizations from several plausible geologic scenarios, the proposed method first applies the truncated singular value decomposition (TSVD) to compactly represent the models from each geologic scenario. The TSVD basis for representing each scenario forms a distinct group. The proposed approach searches over these groups (i.e., geologic scenarios) to eliminate inconsistent groups that are not supported by the observed flow/pressure data. The group-sparsity regularization minimizes a l1/l2mixed norm, where the l2-norm quantifies the contribution of each group and operates on the coefficients within the groups while the l1-norm, having a selection property, is

  11. Modeling and analysis of power processing systems: Feasibility investigation and formulation of a methodology

    NASA Technical Reports Server (NTRS)

    Biess, J. J.; Yu, Y.; Middlebrook, R. D.; Schoenfeld, A. D.

    1974-01-01

    A review is given of future power processing systems planned for the next 20 years, and the state-of-the-art of power processing design modeling and analysis techniques used to optimize power processing systems. A methodology of modeling and analysis of power processing equipment and systems has been formulated to fulfill future tradeoff studies and optimization requirements. Computer techniques were applied to simulate power processor performance and to optimize the design of power processing equipment. A program plan to systematically develop and apply the tools for power processing systems modeling and analysis is presented so that meaningful results can be obtained each year to aid the power processing system engineer and power processing equipment circuit designers in their conceptual and detail design and analysis tasks.

  12. Functional testing of topical skin formulations using an optimised ex vivo skin organ culture model.

    PubMed

    Sidgwick, G P; McGeorge, D; Bayat, A

    2016-07-01

    A number of equivalent-skin models are available for investigation of the ex vivo effect of topical application of drugs and cosmaceuticals onto skin, however many have their drawbacks. With the March 2013 ban on animal models for cosmetic testing of products or ingredients for sale in the EU, their utility for testing toxicity and effect on skin becomes more relevant. The aim of this study was to demonstrate proof of principle that altered expression of key gene and protein markers could be quantified in an optimised whole tissue biopsy culture model. Topical formulations containing green tea catechins (GTC) were investigated in a skin biopsy culture model (n = 11). Punch biopsies were harvested at 3, 7 and 10 days, and analysed using qRT-PCR, histology and HPLC to determine gene and protein expression, and transdermal delivery of compounds of interest. Reduced gene expression of α-SMA, fibronectin, mast cell tryptase, mast cell chymase, TGF-β1, CTGF and PAI-1 was observed after 7 and 10 days compared with treated controls (p < 0.05). Histological analysis indicated a reduction in mast cell tryptase and chymase positive cell numbers in treated biopsies compared with untreated controls at day 7 and day 10 (p < 0.05). Determination of transdermal uptake indicated that GTCs were detected in the biopsies. This model could be adapted to study a range of different topical formulations in both normal and diseased skin, negating the requirement for animal models in this context, prior to study in a clinical trial environment.

  13. A new LP formulation of the admission control problem modelled as an MDP under average reward criterion

    NASA Astrophysics Data System (ADS)

    Pietrabissa, Antonio

    2011-12-01

    The admission control problem can be modelled as a Markov decision process (MDP) under the average cost criterion and formulated as a linear programming (LP) problem. The LP formulation is attractive in the present and future communication networks, which support an increasing number of classes of service, since it can be used to explicitly control class-level requirements, such as class blocking probabilities. On the other hand, the LP formulation suffers from scalability problems as the number C of classes increases. This article proposes a new LP formulation, which, even if it does not introduce any approximation, is much more scalable: the problem size reduction with respect to the standard LP formulation is O((C + 1)2/2 C ). Theoretical and numerical simulation results prove the effectiveness of the proposed approach.

  14. A priori testing of subgrid-scale models for the velocity-pressure and vorticity-velocity formulations

    NASA Technical Reports Server (NTRS)

    Winckelmans, G. S.; Lund, T. S.; Carati, D.; Wray, A. A.

    1996-01-01

    Subgrid-scale models for Large Eddy Simulation (LES) in both the velocity-pressure and the vorticity-velocity formulations were evaluated and compared in a priori tests using spectral Direct Numerical Simulation (DNS) databases of isotropic turbulence: 128(exp 3) DNS of forced turbulence (Re(sub(lambda))=95.8) filtered, using the sharp cutoff filter, to both 32(exp 3) and 16(exp 3) synthetic LES fields; 512(exp 3) DNS of decaying turbulence (Re(sub(Lambda))=63.5) filtered to both 64(exp 3) and 32(exp 3) LES fields. Gaussian and top-hat filters were also used with the 128(exp 3) database. Different LES models were evaluated for each formulation: eddy-viscosity models, hyper eddy-viscosity models, mixed models, and scale-similarity models. Correlations between exact versus modeled subgrid-scale quantities were measured at three levels: tensor (traceless), vector (solenoidal 'force'), and scalar (dissipation) levels, and for both cases of uniform and variable coefficient(s). Different choices for the 1/T scaling appearing in the eddy-viscosity were also evaluated. It was found that the models for the vorticity-velocity formulation produce higher correlations with the filtered DNS data than their counterpart in the velocity-pressure formulation. It was also found that the hyper eddy-viscosity model performs better than the eddy viscosity model, in both formulations.

  15. An Improved Formulation of Hybrid Model Predictive Control With Application to Production-Inventory Systems

    PubMed Central

    Nandola, Naresh N.; Rivera, Daniel E.

    2013-01-01

    We consider an improved model predictive control (MPC) formulation for linear hybrid systems described by mixed logical dynamical (MLD) models. The algorithm relies on a multiple-degree-of-freedom parametrization that enables the user to adjust the speed of setpoint tracking, measured disturbance rejection and unmeasured disturbance rejection independently in the closed-loop system. Consequently, controller tuning is more flexible and intuitive than relying on objective function weights (such as move suppression) traditionally used in MPC schemes. The controller formulation is motivated by the needs of non-traditional control applications that are suitably described by hybrid production-inventory systems. Two applications are considered in this paper: adaptive, time-varying interventions in behavioral health, and inventory management in supply chains under conditions of limited capacity. In the adaptive intervention application, a hypothetical intervention inspired by the Fast Track program, a real-life preventive intervention for reducing conduct disorder in at-risk children, is examined. In the inventory management application, the ability of the algorithm to judiciously alter production capacity under conditions of varying demand is presented. These case studies demonstrate that MPC for hybrid systems can be tuned for desired performance under demanding conditions involving noise and uncertainty. PMID:24348004

  16. Glass Property Models, Constraints, and Formulation Approaches for Vitrification of High-Level Nuclear Wastes at the US Hanford Site

    SciTech Connect

    Kim, Dong-Sang

    2015-03-02

    The legacy nuclear wastes stored in underground tanks at the US Department of Energy’s Hanford site is planned to be separated into high-level waste and low-activity waste fractions and vitrified separately. Formulating optimized glass compositions that maximize the waste loading in glass is critical for successful and economical treatment and immobilization of nuclear wastes. Glass property-composition models have been developed and applied to formulate glass compositions for various objectives for the past several decades. The property models with associated uncertainties and combined with composition and property constraints have been used to develop preliminary glass formulation algorithms designed for vitrification process control and waste form qualification at the planned waste vitrification plant. This paper provides an overview of current status of glass property-composition models, constraints applicable to Hanford waste vitrification, and glass formulation approaches that have been developed for vitrification of hazardous and highly radioactive wastes stored at the Hanford site.

  17. The Ocean-Land-Atmosphere Model (OLAM): A Formulation for High Resolution Weather and Climate Simulation

    NASA Astrophysics Data System (ADS)

    Walko, R. L.; Avissar, R.

    2008-12-01

    As Atmospheric General Circulation Models (AGCMs) continue to exploit the almost unbelievable growth rate of computing resources, they are rapidly moving toward resolving nonhydrostatic mesoscale and microscale circulations, convective clouds, steep topography, and small-scale variations in land cover, soil moisture, and land-water boundaries. Many AGCMs were not originally designed for the finer scales and therefore require significant modification. For example, many models assume hydrostatic balance, represent moist convection only by means of subgrid-scale parameterization, and use a numerical formulation that would be subject to significant error with large topographic slope. A separate class of high resolution models, developed and improved since the 1970s and designed for limited area rather than global coverage, has achieved considerable sophistication in the detailed treatment of cloud dynamics and microphysics, atmosphere- surface interaction, and land surface processes. These models offer valuable techniques for high resolution global modeling. The Ocean-Land-Atmosphere Model (OLAM) was developed at Duke University to investigate a wide range of phenomena important to weather, climate, and the ecosystem, from global to local scales. Its formulation combines advanced techniques in both global and high resolution limited-area modeling, and introduces additional features. OLAM's dynamic core uses an unstructured global geodesic grid that permits local mesh refinement to unlimited degree. Model coordinate levels are horizontal, thus avoiding the transformation terms and numerical errors introduced by terrain-following coordinates, and topography is represented by shaved grid cells. Dynamic equations are fully compressible, finite-volume conservative, and use an explicit time-split differencing method that facilitates efficient parallelization. Physical parameterizations are largely adapted from leading high resolution models, including in particular the

  18. Novel Formulation of Adaptive MPC as EKF Using ANN Model: Multiproduct Semibatch Polymerization Reactor Case Study.

    PubMed

    Kamesh, Reddi; Rani, Kalipatnapu Yamuna

    2016-10-13

    In this paper, a novel formulation for nonlinear model predictive control (MPC) has been proposed incorporating the extended Kalman filter (EKF) control concept using a purely data-driven artificial neural network (ANN) model based on measurements for supervisory control. The proposed scheme consists of two modules focusing on online parameter estimation based on past measurements and control estimation over control horizon based on minimizing the deviation of model output predictions from set points along the prediction horizon. An industrial case study for temperature control of a multiproduct semibatch polymerization reactor posed as a challenge problem has been considered as a test bed to apply the proposed ANN-EKFMPC strategy at supervisory level as a cascade control configuration along with proportional integral controller [ANN-EKFMPC with PI (ANN-EKFMPC-PI)]. The proposed approach is formulated incorporating all aspects of MPC including move suppression factor for control effort minimization and constraint-handling capability including terminal constraints. The nominal stability analysis and offset-free tracking capabilities of the proposed controller are proved. Its performance is evaluated by comparison with a standard MPC-based cascade control approach using the same adaptive ANN model. The ANN-EKFMPC-PI control configuration has shown better controller performance in terms of temperature tracking, smoother input profiles, as well as constraint-handling ability compared with the ANN-MPC with PI approach for two products in summer and winter. The proposed scheme is found to be versatile although it is based on a purely data-driven model with online parameter estimation.

  19. Modeling turbulent flow over fractal trees using renormalized numerical simulation: Alternate formulations and numerical experiments

    NASA Astrophysics Data System (ADS)

    Graham, Jason; Meneveau, Charles

    2012-12-01

    Simulating turbulent flows over objects characterized by hierarchies of length-scales poses special challenges associated with the cost of resolving small-scale elements. If these are treated as subgrid-scale elements, their effects on the resolved scales must be captured realistically. Most importantly, the associated drag forces must be parameterized. Prior work [S. Chester, C. Meneveau, and M. B. Parlange, "Modeling turbulent flow over fractal trees with renormalized numerical simulation," J. Comput. Phys. 225, 427-448 (2007), 10.1016/j.jcp.2006.12.009] proposed a technique called renormalized numerical simulation (RNS), which is applicable to objects that display scale-invariant geometric (fractal) properties. The idea of RNS is similar to that of the dynamic model used in large eddy simulation to determine model parameters for the subgrid-stress tensor model in the bulk of the flow. In RNS, drag forces from the resolved elements that are obtained during the simulation are re-scaled appropriately by determining drag coefficients that are then applied to specify the drag forces associated with the subgrid-scale elements. The technique has already been applied to model turbulent flow over a canopy of fractal trees [S. Chester, C. Meneveau, and M. B. Parlange, "Modeling turbulent flow over fractal trees with renormalized numerical simulation," J. Comput. Phys. 225, 427-448 (2007), 10.1016/j.jcp.2006.12.009], using a particular set of assumptions in evaluating the drag coefficient. In the current work we introduce a generalized framework for describing and implementing the RNS methodology. Furthermore, we describe various other possible practical implementations of RNS that differ on important, technical aspects related to (1) time averaging, (2) spatial localization, and (3) numerical representation of the drag forces. As part of this study, several RNS formulations are presented and compared. The various models are first implemented and compared in simulations of

  20. Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development-Industry Case Studies.

    PubMed

    Kesisoglou, Filippos; Chung, John; van Asperen, Judith; Heimbach, Tycho

    2016-09-01

    In recent years, there has been a significant increase in use of physiologically based pharmacokinetic models in drug development and regulatory applications. Although most of the published examples have focused on aspects such as first-in-human (FIH) dose predictions or drug-drug interactions, several publications have highlighted the application of these models in the biopharmaceutics field and their use to inform formulation development. In this report, we present 5 case studies of use of such models in this biopharmaceutics/formulation space across different pharmaceutical companies. The case studies cover different aspects of biopharmaceutics or formulation questions including (1) prediction of absorption prior to FIH studies; (2) optimization of formulation and dissolution method post-FIH data; (3) early exploration of a modified-release formulation; (4) addressing bridging questions for late-stage formulation changes; and (5) prediction of pharmacokinetics in the fed state for a Biopharmaceutics Classification System class I drug with fasted state data. The discussion of the case studies focuses on how such models can facilitate decisions and biopharmaceutic understanding of drug candidates and the opportunities for increased use and acceptance of such models in drug development and regulatory interactions.

  1. Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model.

    PubMed

    Ibrahim, Fady; Gershkovich, Pavel; Sivak, Olena; Wasan, Ellen K; Wasan, Kishor M

    2012-08-15

    The purpose of this study was to investigate the intraluminal processing of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Amphotericin B (AmB) was formulated in three lipid-based formulations consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various lipid loads (0.25, 0.5, 1 and 2 g) were digested using the lipolysis model to assess AmB distribution among the lipolysis phases. The duration of lipolysis was comparable among the three formulations except for 2 g load of iCo-009 which had a significantly longer lipolysis than iCo-010 and iCo-011. The lipid components of iCo-009 experienced lower extent of lipolysis as compared to other formulations. Amphotericin B concentration in the aqueous phases was the highest with iCo-010 which also had the lowest sediment recovery. Amphotericin B levels in the undigested lipid layers were comparable between iCo-009 and iCo-010 and were higher than with iCo-011. Given the observation that iCo-010 had the highest aqueous micellar solubilization and the lowest sediment recovery of AmB among the tested formulations, these results could potentially be used to interpret and predict the in vivo performance of AmB- SEDDS formulations in future studies. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  2. Formulation of cidofovir improves the anti-papillomaviral activity of topical treatments in the CRPV/rabbit model

    PubMed Central

    Christensen, Neil D.; Cladel, Nancy M.; Hu, Jiafen; Balogh, Karla K.

    2014-01-01

    Current topical treatments for papillomas use ablative, cytotoxic and immunomodulating strategies and reagents. However, the effectiveness of topical treatments using different formulations has not been examined in preclinical models or clinical trials. The purpose of this study was to determine whether formulation of the small molecule acyclic nucleoside, cidofovir (CDV), could lead to improved therapeutic endpoints following topical treatment of papillomas using the cottontail rabbit papillomavirus (CRPV)/rabbit model. Different formulations with a set dose of 1% cidofovir were tested to establish comparative data. The results demonstrated that anti-papilloma treatments with topical CDV were greatly enhanced when formulated versus unformulated. Best results were obtained with CDV formulated in cremophor, then in carbomer 940, and then in DMSO. Further studies indicated that effective formulations led to complete cures of papillomas at dilutions less than 0.3% CDV. These studies together with previous observations demonstrated that unformulated CDV under the same treatment regime required doses of 2% to achieve cures demonstrating that much less compound can be used when properly formulated. PMID:24946003

  3. Reversible Discrete Event Formulation and Optimistic Parallel Execution of Vehicular Traffic Models

    SciTech Connect

    Yoginath, Srikanth B; Perumalla, Kalyan S

    2009-01-01

    Vehicular traffic simulations are useful in applications such as emergency planning and traffic management. High speed of traffic simulations translates to speed of response and level of resilience in those applications. Discrete event formulation of traffic flow at the level of individual vehicles affords both the flexibility of simulating complex scenarios of vehicular flow behavior as well as rapid simulation time advances. However, efficient parallel/distributed execution of the models becomes challenging due to synchronization overheads. Here, a parallel traffic simulation approach is presented that is aimed at reducing the time for simulating emergency vehicular traffic scenarios. Our approach resolves the challenges that arise in parallel execution of microscopic, vehicular-level models of traffic. We apply a reverse computation-based optimistic execution approach to address the parallel synchronization problem. This is achieved by formulating a reversible version of a discrete event model of vehicular traffic, and by utilizing this reversible model in an optimistic execution setting. Three unique aspects of this effort are: (1) exploration of optimistic simulation applied to vehicular traffic simulation (2) addressing reverse computation challenges specific to optimistic vehicular traffic simulation (3) achieving absolute (as opposed to self-relative) speedup with a sequential speed close to that of a fast, de facto standard sequential simulator for emergency traffic. The design and development of the parallel simulation system is presented, along with a performance study that demonstrates excellent sequential performance as well as parallel performance. The benefits of optimistic execution are demonstrated, including a speed up of nearly 20 on 32 processors observed on a vehicular network of over 65,000 intersections and over 13 million vehicles.

  4. 3D Higher Order Modeling in the BEM/FEM Hybrid Formulation

    NASA Technical Reports Server (NTRS)

    Fink, P. W.; Wilton, D. R.

    2000-01-01

    Higher order divergence- and curl-conforming bases have been shown to provide significant benefits, in both convergence rate and accuracy, in the 2D hybrid finite element/boundary element formulation (P. Fink and D. Wilton, National Radio Science Meeting, Boulder, CO, Jan. 2000). A critical issue in achieving the potential for accuracy of the approach is the accurate evaluation of all matrix elements. These involve products of high order polynomials and, in some instances, singular Green's functions. In the 2D formulation, the use of a generalized Gaussian quadrature method was found to greatly facilitate the computation and to improve the accuracy of the boundary integral equation self-terms. In this paper, a 3D, hybrid electric field formulation employing higher order bases and higher order elements is presented. The improvements in convergence rate and accuracy, compared to those resulting from lower order modeling, are established. Techniques developed to facilitate the computation of the boundary integral self-terms are also shown to improve the accuracy of these terms. Finally, simple preconditioning techniques are used in conjunction with iterative solution procedures to solve the resulting linear system efficiently. In order to handle the boundary integral singularities in the 3D formulation, the parent element- either a triangle or rectangle-is subdivided into a set of sub-triangles with a common vertex at the singularity. The contribution to the integral from each of the sub-triangles is computed using the Duffy transformation to remove the singularity. This method is shown to greatly facilitate t'pe self-term computation when the bases are of higher order. In addition, the sub-triangles can be further divided to achieve near arbitrary accuracy in the self-term computation. An efficient method for subdividing the parent element is presented. The accuracy obtained using higher order bases is compared to that obtained using lower order bases when the number

  5. Forward Modeling and validation of a new formulation to compute self-potential signals associated with ground water flow

    NASA Astrophysics Data System (ADS)

    Bolève, A.; Revil, A.; Janod, F.; Mattiuzzo, J. L.; Jardani, A.

    2007-10-01

    The classical formulation of the coupled hydroelectrical flow in porous media is based on a linear formulation of two coupled constitutive equations for the electrical current density and the seepage velocity of the water phase and obeying Onsager's reciprocity. This formulation shows that the streaming current density is controlled by the gradient of the fluid pressure of the water phase and a streaming current coupling coefficient that depends on the so-called zeta potential. Recently a new formulation has been introduced in which the streaming current density is directly connected to the seepage velocity of the water phase and to the excess of electrical charge per unit pore volume in the porous material. The advantages of this formulation are numerous. First this new formulation is more intuitive not only in terms of establishing a constitutive equation for the generalized Ohm's law but also in specifying boundary conditions for the influence of the flow field upon the streaming potential. With the new formulation, the streaming potential coupling coefficient shows a decrease of its magnitude with permeability in agreement with published results. The new formulation has been extended in the inertial laminar flow regime and to unsaturated conditions with applications to the vadose zone. This formulation is suitable to model self-potential signals in the field. We investigate infiltration of water from an agricultural ditch, vertical infiltration of water into a sinkhole, and preferential horizontal flow of ground water in a paleochannel. For the three cases reported in the present study, a good match is obtained between finite element simulations performed and field observations. Thus, this formulation could be useful for the inverse mapping of the geometry of groundwater flow from self-potential field measurements.

  6. Carbon deposition model for oxygen-hydrocarbon combustion. Task 6: Data analysis and formulation of an empirical model

    NASA Technical Reports Server (NTRS)

    Makel, Darby B.; Rosenberg, Sanders D.

    1990-01-01

    The formation and deposition of carbon (soot) was studied in the Carbon Deposition Model for Oxygen-Hydrocarbon Combustion Program. An empirical, 1-D model for predicting soot formation and deposition in LO2/hydrocarbon gas generators/preburners was derived. The experimental data required to anchor the model were identified and a test program to obtain the data was defined. In support of the model development, cold flow mixing experiments using a high injection density injector were performed. The purpose of this investigation was to advance the state-of-the-art in LO2/hydrocarbon gas generator design by developing a reliable engineering model of gas generator operation. The model was formulated to account for the influences of fluid dynamics, chemical kinetics, and gas generator hardware design on soot formation and deposition.

  7. Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

    PubMed

    Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

    2015-08-01

    In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR).

  8. Suicide risk assessment and suicide risk formulation: essential components of the therapeutic risk management model.

    PubMed

    Silverman, Morton M

    2014-09-01

    Suicide and other suicidal behaviors are often associated with psychiatric disorders and dysfunctions. Therefore, psychiatrists have significant opportunities to identify at-risk individuals and offer treatment to reduce that risk. Although a suicide risk assessment is a core competency requirement, many clinical psychiatrists lack the requisite training and skills to appropriately assess for suicide risk. Moreover, the standard of care requires psychiatrists to foresee the possibility that a patient might engage in suicidal behavior, hence to conduct a suicide risk formulation sufficient to guide triage and treatment planning. Based on data collected via a suicide risk assessment, a suicide risk formulation is a process whereby the psychiatrist forms a judgment about a patient's foreseeable risk of suicidal behavior in order to inform triage decisions, safety and treatment planning, and interventions to reduce risk. This paper addresses the components of this process in the context of the model for therapeutic risk management of the suicidal patient developed at the Veterans Integrated Service Network (VISN) 19 Mental Illness Research, Education and Clinical Center by Wortzel et al.

  9. A robust anisotropic hyperelastic formulation for the modelling of soft tissue.

    PubMed

    Nolan, D R; Gower, A L; Destrade, M; Ogden, R W; McGarry, J P

    2014-11-01

    The Holzapfel-Gasser-Ogden (HGO) model for anisotropic hyperelastic behaviour of collagen fibre reinforced materials was initially developed to describe the elastic properties of arterial tissue, but is now used extensively for modelling a variety of soft biological tissues. Such materials can be regarded as incompressible, and when the incompressibility condition is adopted the strain energy Ψ of the HGO model is a function of one isotropic and two anisotropic deformation invariants. A compressible form (HGO-C model) is widely used in finite element simulations whereby the isotropic part of Ψ is decoupled into volumetric and isochoric parts and the anisotropic part of Ψ is expressed in terms of isochoric invariants. Here, by using three simple deformations (pure dilatation, pure shear and uniaxial stretch), we demonstrate that the compressible HGO-C formulation does not correctly model compressible anisotropic material behaviour, because the anisotropic component of the model is insensitive to volumetric deformation due to the use of isochoric anisotropic invariants. In order to correctly model compressible anisotropic behaviour we present a modified anisotropic (MA) model, whereby the full anisotropic invariants are used, so that a volumetric anisotropic contribution is represented. The MA model correctly predicts an anisotropic response to hydrostatic tensile loading, whereby a sphere deforms into an ellipsoid. It also computes the correct anisotropic stress state for pure shear and uniaxial deformations. To look at more practical applications, we developed a finite element user-defined material subroutine for the simulation of stent deployment in a slightly compressible artery. Significantly higher stress triaxiality and arterial compliance are computed when the full anisotropic invariants are used (MA model) instead of the isochoric form (HGO-C model).

  10. A multibody motorcycle model with rigid-ring tyres: formulation and validation

    NASA Astrophysics Data System (ADS)

    Leonelli, Luca; Mancinelli, Nicolò

    2015-06-01

    The aim of this paper is the development and validation of a three-dimensional multibody motorcycle model including a rigid-ring tyre model, taking into account both the slopes and elevation of the road surface. In order to achieve accurate assessment of ride and handling performances of a road racing motorcycle, a tyre model capable of reproducing the dynamic response to actual road excitation is required. While a number of vehicle models with such feature are available for car application, the extension to the motorcycle modelling has not been addressed yet. To do so, a novel parametrisation for the general motorcycle kinematics is proposed, using a mixed reference point and relative coordinates approach. The resulting description, developed in terms of dependent coordinates, makes it possible to include the rigid-ring kinematics as well as road elevation and slopes, without affecting computational efficiency. The equations of motion for the whole multibody system are derived symbolically and the constraint equations arising from the dependent coordinate formulation are handled using the position and velocity vector projection technique. The resulting system of equations is integrated in time domain using a standard ordinary differential equation (ODE) algorithm. Finally, the model is validated with respect to experimentally measured data in both time and frequency domains.

  11. Effects of annealing on enthalpy relaxation in lyophilized disaccharide formulations: mathematical modeling of DSC curves.

    PubMed

    Luthra, Suman A; Hodge, Ian M; Pikal, Michael J

    2008-08-01

    The overall objective of these studies was to investigate, by experimental studies and theoretical analysis, the optimum annealing conditions to obtain maximum structural relaxation in lyophilized glasses of pharmaceutical significance. The model formulations used in this work were aspartame: sucrose and aspartame: trehalose (1:10 w/w) freeze-dried glasses. In this article, structural relaxation in amorphous systems was described in terms of the change in the fictive temperature (T(f)) and was measured using the enthalpy relaxation endotherm in a differential scanning calorimeter (DSC). The theoretical analysis was performed using the Tool-Narayanaswamy-Moynihan (TNM) model. The effect of different annealing conditions (temperature and time) on fictive temperature obtained from the theoretical analysis was calculated and compared with the experimental results. The model reproduced the experimental data very well for samples that were quench cooled from the liquid. However, the model fits were poor for lyophilized samples, indicating an inability to incorporate the complex thermal history of freeze-drying in the TNM model. The optimum aging conditions were determined from both DSC and approximated best-fit parameters of the TNM model, and it was found that annealing when done at a temperature about 15-25 degrees C below T(g) resulted in maximum structural relaxation.

  12. The formulation and implementation of a stochastic model that explores HIV infection. (Volumes I and II). [HIV (human immunodeficiency virus)

    SciTech Connect

    Salsburg, M.A.

    1992-01-01

    This thesis presents the research, formulation, implementation and results of a stochastic model that projects HIV prevalence and crude demographic statistics. The background research includes demographic and epidemiological modeling issues. Published models and results are presented and discussed. The formulation of this model included demographic considerations. To model couple formations, a formulation of age-dependent couple formation was developed. Using the couple formation formulation, a two-sex model was developed to project population births. The epidemiological model addressed population types that were classified by HIV risk group, HIV state and age for both non-married populations and coupled populations. Males and females were partitioned into three risk groups each. The effects of heterogeneity caused by the behavior of diverse risk groups is discussed. Six states of HIV were modeled: susceptible (non-infected), initial infection, dormancy, AIDS Related Complex (ARC), full-blown AIDS and death due to AIDS. Male and female ages were considered in simulations that used age aggregation and in simulations that accounted for yearly ages. The projection of the spread of HIV was modeled on a monthly time scale. The projection of demographic statistics were modeled on a yearly time scale. The underlying stochastic model, with nonlinear different equations, are presented. Simulation models were run to consider the sensitivity of various parameters. The model results are shown, with a discussion of parameters used in previously published HIV model projections. The structure of the software developed to implement the model is presented. A cross-reference is provided to indicate software parameters that correspond with the formal model parameters. Another cross-reference provides the name of the APL function used to implement the calculations in the model formulation. The APL source code listing is included in the Appendix.

  13. Recovering thermodynamic consistency of the antitrapping model: A variational phase-field formulation for alloy solidification

    NASA Astrophysics Data System (ADS)

    Fang, Angbo; Mi, Yongli

    2013-01-01

    The phenomenological antitrapping phase-field model has attained much success in describing alloy solidification. The heuristically introduced antitrapping current enables removing artificial effects due to the use of large interfacial width. Nevertheless, such a model is not thermodynamically consistent and has not been fitted into a variational framework. Here we present two approaches to develop a variational phase-field model to describe patten formation in alloys. Following the principles of linear irreversible thermodynamics we build in the cross-coupling between the phase transition rate and solute diffusion current. Our formulation not only naturally incorporates the antitrapping current but also predicts the conjugated mesoscopic solute drag effect. A more general form of the antitrapping current is obtained by thin-interface analysis. Benchmark simulations on isothermal dendrite growth are carried out to show the capability of our model to quantitatively characterize the interface evolution and solute profile even with a large interface width used. Importantly, our theory also provides general insights on how to obtain the genuine dynamic coupling between nonconserved and conserved order parameters. This leads to a thermodynamically consistent generalization of the celebrated model C proposed by Hohenberg and Halperin [Rev. Mod. Phys.0034-686110.1103/RevModPhys.49.435 49, 435 (1977)].

  14. An Improved Experimental Model of Hemorrhoids in Rats: Evaluation of Antihemorrhoidal Activity of an Herbal Formulation

    PubMed Central

    Azeemuddin, Mohammed; Viswanatha, Gollapalle Lakshminarayanashastry; Thippeswamy, Agadi HireMath; Baig, Mirza Rizwan; Kavya, Kethaganahalli Jayaramaiah; Patki, Pralhad Sadashiv; Shyam, Ramakrishnan

    2014-01-01

    Objective. To improve the existing experimental model of croton oil-induced hemorrhoids in rats by using Evans Blue (EB) dye extravasation technique. Further, an herbal formulation (Pilex) was evaluated for its antihemorrhoidal activity in this model. Methods. Two sets of experiments were carried out: first to improve the experimental model and to validate the same using Pilex and second to evaluate the effect of Pilex on cytoarchitecture of rectoanal tissue in croton oil-induced hemorrhoids. In both sets, hemorrhoids were induced to all the animals, except normal controls, by applying croton oil via rectoanal region and the effect of Pilex ointment (PO), Pilex granules (PG), and combination of PG and PO was evaluated. In the first set, extravasation of EB dye, TNF-α, IL-6, and rectoanal coefficient (RAC) was determined. In the second set, severity of score, RAC, and histopathology were evaluated. Results. The elevated levels of TNF-α, IL-6, and extravasations of EB dye were decreased with the Pilex treatment. The cytoarchitecture of rectoanal portion of the animals treated with Pilex was near to normal. Conclusion. The improved experimental model of hemorrhoid is useful in quantifying the inflammatory exudates and extent of inflammation. In this improved experimental model Pilex showed antihemorrhoidal activity, which further validates its clinical usage. PMID:25006493

  15. Non Linear Programming (NLP) formulation for quantitative modeling of protein signal transduction pathways.

    PubMed

    Mitsos, Alexander; Melas, Ioannis N; Morris, Melody K; Saez-Rodriguez, Julio; Lauffenburger, Douglas A; Alexopoulos, Leonidas G

    2012-01-01

    Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms.

  16. Non Linear Programming (NLP) Formulation for Quantitative Modeling of Protein Signal Transduction Pathways

    PubMed Central

    Morris, Melody K.; Saez-Rodriguez, Julio; Lauffenburger, Douglas A.; Alexopoulos, Leonidas G.

    2012-01-01

    Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms. PMID:23226239

  17. Surface energy and interparticle forces correlations in model pMDI formulations.

    PubMed

    Traini, Daniela; Rogueda, Philippe; Young, Paul; Price, Robert

    2005-05-01

    To compare experimental measurements of particle cohesion and adhesion forces in a model propellant with theoretical measurements of the interfacial free energy of particulate interactions; with the aim of characterizing suspension stability of pressurized metered dose inhalers (pMDIs). Interparticulate forces of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H,3H perfluoropentane. The surface thermodynamic properties were determined by contact angle (CA) and inverse gas chromatography (IGC). Experimental data were compared with theoretical work of adhesion/cohesion using a surface component approach (SCA), taking into account both dispersive and polar contributions of the surface free energy. Results indicated that the measured forces of interaction between particles in model propellant could not be accounted for by theoretical treatment of the dispersive surface free energies via CA and IGC. A correlation between theoretical work of adhesion/cohesion and AFM measurements was observed upon the introduction of the polar interfacial interactions within the SCA model. It is suggested that the polar contributions of the surface free energy measurements of particles may play a crucial role in particle interaction within propellant-based systems. Together with the application of a SCA model, this approach may be capable of predicting suspension stability of pMDI formulations.

  18. An improved experimental model of hemorrhoids in rats: evaluation of antihemorrhoidal activity of an herbal formulation.

    PubMed

    Azeemuddin, Mohammed; Viswanatha, Gollapalle Lakshminarayanashastry; Rafiq, Mohamed; Thippeswamy, Agadi HireMath; Baig, Mirza Rizwan; Kavya, Kethaganahalli Jayaramaiah; Patki, Pralhad Sadashiv; Shyam, Ramakrishnan

    2014-01-01

    Objective. To improve the existing experimental model of croton oil-induced hemorrhoids in rats by using Evans Blue (EB) dye extravasation technique. Further, an herbal formulation (Pilex) was evaluated for its antihemorrhoidal activity in this model. Methods. Two sets of experiments were carried out: first to improve the experimental model and to validate the same using Pilex and second to evaluate the effect of Pilex on cytoarchitecture of rectoanal tissue in croton oil-induced hemorrhoids. In both sets, hemorrhoids were induced to all the animals, except normal controls, by applying croton oil via rectoanal region and the effect of Pilex ointment (PO), Pilex granules (PG), and combination of PG and PO was evaluated. In the first set, extravasation of EB dye, TNF- α , IL-6, and rectoanal coefficient (RAC) was determined. In the second set, severity of score, RAC, and histopathology were evaluated. Results. The elevated levels of TNF- α , IL-6, and extravasations of EB dye were decreased with the Pilex treatment. The cytoarchitecture of rectoanal portion of the animals treated with Pilex was near to normal. Conclusion. The improved experimental model of hemorrhoid is useful in quantifying the inflammatory exudates and extent of inflammation. In this improved experimental model Pilex showed antihemorrhoidal activity, which further validates its clinical usage.

  19. Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.

    PubMed

    Chen, W; Desai, D; Good, D; Crison, J; Timmins, P; Paruchuri, S; Wang, J; Ha, K

    2016-08-01

    A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.

  20. Biopharmaceutical modeling of drug supersaturation during lipid-based formulation digestion considering an absorption sink.

    PubMed

    Stillhart, Cordula; Imanidis, Georgios; Griffin, Brendan T; Kuentz, Martin

    2014-12-01

    In vitro lipolysis is widely utilized for predicting in vivo performance of oral lipid-based formulations (LBFs). However, evaluation of LBFs in the absence of an absorption sink may have limited in vivo relevance. This study aimed at employing biopharmaceutical modeling to simulate LBF digestion and drug supersaturation in a continuous absorptive environment. Three fenofibrate-loaded LBFs were characterized in vitro (dispersion and lipolysis) and drug precipitation was monitored using in-line Raman spectroscopy. In vitro data were combined with pharmacokinetic data derived from an in vivo study in pigs to simulate intestinal LBF transit. This biopharmaceutical model allowed calculation of lipolysis-triggered drug supersaturation while drug and lipolysis products are absorbed from the intestine. The biopharmaceutical model predicted that, in a continuous absorption environment, fenofibrate supersaturation was considerably lower compared to in vitro lipolysis (non-sink). Hence, the extensive drug precipitation observed in vitro was predicted to be unlikely in vivo. The absorption of lipolysis products increased drug supersaturation, but drug precipitation was unlikely for highly permeable drugs. Biopharmaceutical modeling is a valuable approach for predicting LBFs performance in vivo. In the absence of in vitro tools simulating absorptive conditions, modeling strategies should be further considered.

  1. Formulation and computational aspects of plasticity and damage models with application to quasi-brittle materials

    SciTech Connect

    Chen, Z.; Schreyer, H.L.

    1995-09-01

    The response of underground structures and transportation facilities under various external loadings and environments is critical for human safety as well as environmental protection. Since quasi-brittle materials such as concrete and rock are commonly used for underground construction, the constitutive modeling of these engineering materials, including post-limit behaviors, is one of the most important aspects in safety assessment. From experimental, theoretical, and computational points of view, this report considers the constitutive modeling of quasi-brittle materials in general and concentrates on concrete in particular. Based on the internal variable theory of thermodynamics, the general formulations of plasticity and damage models are given to simulate two distinct modes of microstructural changes, inelastic flow and degradation of material strength and stiffness, that identify the phenomenological nonlinear behaviors of quasi-brittle materials. The computational aspects of plasticity and damage models are explored with respect to their effects on structural analyses. Specific constitutive models are then developed in a systematic manner according to the degree of completeness. A comprehensive literature survey is made to provide the up-to-date information on prediction of structural failures, which can serve as a reference for future research.

  2. Mixed direct-iterative methods for boundary integral formulations of dielectric solvation models.

    PubMed

    Corcelli, S A; Kress, J D; Pratt, L R; Tawa, G J

    1996-01-01

    This paper describes a mixed direct-iterative method for boundary integral formulations of dielectric solvation models. We give an example for which a direct solution at thermal accuracy is nontrivial and for which Gauss-Seidel iteration diverges in rare but reproducible cases. This difficulty is analyzed by obtaining the eigenvalues and the spectral radius of the iteration matrix. This establishes that the nonconvergence is due to inaccuracies of the asymptotic approximations for the matrix elements for accidentally close boundary element pairs on different spheres. This difficulty is cured by checking for boundary element pairs closer than the typical spatial extent of the boundary elements and for those pairs performing an 'in-line' Monte Carlo integration to evaluate the required matrix elements. This difficulty are not expected and have not been observed when only a direct solution is sought. Finally, we give an example application of these methods to deprotonation of monosilicic acid in water.

  3. Behavior of the gypsy moth life system model and development of synoptic model formulations

    Treesearch

    J. J. Colbert; Xu Rumei

    1991-01-01

    Aims of the research: The gypsy moth life system model (GMLSM) is a complex model which incorporates numerous components (both biotic and abiotic) and ecological processes. It is a detailed simulation model which has much biological reality. However, it has not yet been tested with life system data. For such complex models, evaluation and testing cannot be adequately...

  4. Effects of Orange Juice Formulation on Prebiotic Functionality Using an In Vitro Colonic Model System

    PubMed Central

    Costabile, Adele; Walton, Gemma E.; Tzortzis, George; Vulevic, Jelena; Charalampopoulos, Dimitris; Gibson, Glenn R.

    2015-01-01

    A three-stage continuous fermentative colonic model system was used to monitor in vitro the effect of different orange juice formulations on prebiotic activity. Three different juices with and without Bimuno, a GOS mixture containing galactooligosaccharides (B-GOS) were assessed in terms of their ability to induce a bifidogenic microbiota. The recipe development was based on incorporating 2.75g B-GOS into a 250 ml serving of juice (65°Brix of concentrate juice). Alongside the production of B-GOS juice, a control juice – orange juice without any additional Bimuno and a positive control juice, containing all the components of Bimuno (glucose, galactose and lactose) in the same relative proportions with the exception of B-GOS were developed. Ion Exchange Chromotography analysis was used to test the maintenance of bimuno components after the production process. Data showed that sterilisation had no significant effect on concentration of B-GOS and simple sugars. The three juice formulations were digested under conditions resembling the gastric and small intestinal environments. Main bacterial groups of the faecal microbiota were evaluated throughout the colonic model study using 16S rRNA-based fluorescence in situ hybridization (FISH). Potential effects of supplementation of the juices on microbial metabolism were studied measuring short chain fatty acids (SCFAs) using gas chromatography. Furthermore, B-GOS juices showed positive modulations of the microbiota composition and metabolic activity. In particular, numbers of faecal bifidobacteria and lactobacilli were significantly higher when B-GOS juice was fermented compared to controls. Furthermore, fermentation of B-GOS juice resulted in an increase in Roseburia subcluster and concomitantly increased butyrate production, which is of potential benefit to the host. In conclusion, this study has shown B-GOS within orange juice can have a beneficial effect on the fecal microbiota. PMID:25807417

  5. Effects of orange juice formulation on prebiotic functionality using an in vitro colonic model system.

    PubMed

    Costabile, Adele; Walton, Gemma E; Tzortzis, George; Vulevic, Jelena; Charalampopoulos, Dimitris; Gibson, Glenn R

    2015-01-01

    A three-stage continuous fermentative colonic model system was used to monitor in vitro the effect of different orange juice formulations on prebiotic activity. Three different juices with and without Bimuno, a GOS mixture containing galactooligosaccharides (B-GOS) were assessed in terms of their ability to induce a bifidogenic microbiota. The recipe development was based on incorporating 2.75g B-GOS into a 250 ml serving of juice (65°Brix of concentrate juice). Alongside the production of B-GOS juice, a control juice--orange juice without any additional Bimuno and a positive control juice, containing all the components of Bimuno (glucose, galactose and lactose) in the same relative proportions with the exception of B-GOS were developed. Ion Exchange Chromotography analysis was used to test the maintenance of bimuno components after the production process. Data showed that sterilisation had no significant effect on concentration of B-GOS and simple sugars. The three juice formulations were digested under conditions resembling the gastric and small intestinal environments. Main bacterial groups of the faecal microbiota were evaluated throughout the colonic model study using 16S rRNA-based fluorescence in situ hybridization (FISH). Potential effects of supplementation of the juices on microbial metabolism were studied measuring short chain fatty acids (SCFAs) using gas chromatography. Furthermore, B-GOS juices showed positive modulations of the microbiota composition and metabolic activity. In particular, numbers of faecal bifidobacteria and lactobacilli were significantly higher when B-GOS juice was fermented compared to controls. Furthermore, fermentation of B-GOS juice resulted in an increase in Roseburia subcluster and concomitantly increased butyrate production, which is of potential benefit to the host. In conclusion, this study has shown B-GOS within orange juice can have a beneficial effect on the fecal microbiota.

  6. Evaluation of novel lipid based formulation of β-Artemether and Lumefantrine in murine malaria model.

    PubMed

    Patil, Sushant; Suryavanshi, Shital; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2013-10-15

    The present investigation aims at formulating lipid based drug delivery system of β-Artemether and Lumefantrine and comparative pharmacological evaluation with innovator formulation. Commercial modified oil and indigenous natural fatty acids comprised the oily phase in developing lipidic formulation of β-Artemether and Lumefantrine. The developed system was characterized for mean globule size, stability by freeze thaw cycles, and birefringence. Developed formulation and innovator formulation were compared for their in vivo anti-malarial activity at different dose levels in male Swiss mice, infected with lethal ANKA strain of Plasmodium berghei. The percent parasitemia, activity against time and animal survival period were examined. On fourth day of antimalarial studies, at normal and ½ dose levels, formulations revealed zero percent parasitemia while control showed 33.92±6.00% parasitemia. At 1/10 dose level, developed and innovator formulations revealed zero percent parasitemia upto 11th day, however, three mice from innovator formulation demonstrated recrudescence after 12th day. Both the formulations at normal dose and ½ dose levels showed 100% activity and survival whereas at 1/10 dose level, innovator formulation showed, 62.5% survival. The developed lipidic system of β-Artemether and Lumefantrine exhibited excellent antimalarial activity with 100% survival.

  7. A formulation of multidimensional growth models for the assessment and forecast of technology attributes

    NASA Astrophysics Data System (ADS)

    Danner, Travis W.

    Developing technology systems requires all manner of investment---engineering talent, prototypes, test facilities, and more. Even for simple design problems the investment can be substantial; for complex technology systems, the development costs can be staggering. The profitability of a corporation in a technology-driven industry is crucially dependent on maximizing the effectiveness of research and development investment. Decision-makers charged with allocation of this investment are forced to choose between the further evolution of existing technologies and the pursuit of revolutionary technologies. At risk on the one hand is excessive investment in an evolutionary technology which has only limited availability for further improvement. On the other hand, the pursuit of a revolutionary technology may mean abandoning momentum and the potential for substantial evolutionary improvement resulting from the years of accumulated knowledge. The informed answer to this question, evolutionary or revolutionary, requires knowledge of the expected rate of improvement and the potential a technology offers for further improvement. This research is dedicated to formulating the assessment and forecasting tools necessary to acquire this knowledge. The same physical laws and principles that enable the development and improvement of specific technologies also limit the ultimate capability of those technologies. Researchers have long used this concept as the foundation for modeling technological advancement through extrapolation by analogy to biological growth models. These models are employed to depict technology development as it asymptotically approaches limits established by the fundamental principles on which the technological approach is based. This has proven an effective and accurate approach to modeling and forecasting simple single-attribute technologies. With increased system complexity and the introduction of multiple system objectives, however, the usefulness of this

  8. Development of self-lubricating coatings via cold spray process: Feedstock formulation and deformation modeling

    NASA Astrophysics Data System (ADS)

    Aggarwal, Gaurav

    Because of their low density, high specific strength and high stiffness, titanium alloys are one of the prime candidates for structural application often requiring specific tribological properties. However, their relatively high friction coefficients and low wear resistance are limiting their application over a wider temperature range. Various coatings deposited with technologies like high velocity oxy flame (HVOF), detonation gun (DGun), electron beam physical vapor deposition (EB-PVD), etc., can improve wear performance and decrease corrosion damage. These technologies require high processing temperatures precluding the integration of thermally vulnerable lubricants. This research looks at a relatively new coating process called Cold Spray for self-lubricating coatings on Ti-6Al-4V alloys. Cold Spray can produce coatings without significant heating of the sprayed powder or substrate. The particles are in solid state as they hit the substrate, and the formation of coatings occurs mainly due to the kinetic energy of the particles. Therefore, the impact velocity plays an important role. Below a critical value, the particles can cause densification and abrasion of the substrate. The focus of this study is to design composite coatings for the cold spray process and determination of the critical velocity through finite element modeling. Different powders and feedstock formulation techniques are discussed in order to find an optimum formulation for self-lubricating coatings. A composite powder (Ni coated hBN) was found to be the best candidate for the feedstock. The deformation of composite particles upon impact on the substrate was modeled and compared to the experiments. A number of approaches involving different modeling platforms, particle-substrate geometries, and material models have been tried. This work presents the results of ANSYS (version 10.0) analysis using an axisymmetric model of the particle impact. Stress and strain distributions in the particle

  9. Formulating physical processes in a full-range model of soil water retention

    NASA Astrophysics Data System (ADS)

    Nimmo, J. R.

    2016-12-01

    Currently-used water retention models vary in how much their formulas correspond to controlling physical processes such as capillarity, adsorption, and air-trapping. In model development, realistic correspondence to physical processes has often been a lower priority than ease of use and compatibility with other models. For example, the wettest range is normally represented simplistically, as by a straight line of zero slope, or by default using the same formulation as for the middle range. The new model presented here recognizes dominant processes within three segments of the range from oven-dryness to saturation. The adsorption-dominated dry range is represented by a logarithmic relation used in earlier models. The middle range of capillary advance/retreat and Haines jumps is represented by a new adaptation of the lognormal distribution function. In the wet range, the expansion of trapped air in response to matric pressure change is important because (1) it displaces water, and (2) it triggers additional volume-adjusting processes such as the collapse of liquid bridges between air pockets. For this range, the model incorporates the Boyles' law inverse-proportionality of trapped air volume and pressure, amplified by an empirical factor to account for the additional processes. With their basis in processes, the model's parameters have a strong physical interpretation, and in many cases can be assigned values from knowledge of fundamental relationships or individual measurements. An advantage of the physically-plausible treatment of the wet range is that it avoids such problems as the blowing-up of derivatives on approach to saturation, enhancing the model's utility for important but challenging wet-range phenomena such as domain exchange between preferential flow paths and soil matrix. Further development might be able to accommodate hysteresis by a systematic adjustment of the relation between the wet and middle ranges.

  10. A New Thermal Lattice Boltzmann Formulation for Modeling Thermal Transport in Complex Heterogeneous Media

    NASA Astrophysics Data System (ADS)

    Karani, H.; Huber, C.

    2014-12-01

    Modeling heat transfer in porous media has numerous industrial and biological applications. Natural porous structures which can be found in many geological and biological systems are complex and generally heterogeneous over a wide range of length scales. The ability of multicomponent media to transfer heat at the continuum scale depends directly on the transport of heat through interfaces between the different constituents. Therefore constraining heat and also mass balance at a macroscopic level depends on the development of quantitative models that account for the processes occurring at smaller scales. Consequently, one needs to deal with several temporal and spatial scales which makes modeling of transport phenomena a complicated task. In the present study, we first investigate thermal transport in natural heterogeneous structures at the discrete scale. We introduce a new and simple lattice Boltzmann formulation which handles conjugate thermal boundary conditions at interfaces between two phases/components. Verification of the present interface treatment on benchmark problems confirms the accuracy and simplicity of the proposed approach. The model's implementation is independent of the interface geometry and provides a powerful method to model thermal transport in heterogeneous media with random microstructures. Because we are ultimately interested in developing macroscale (homogenized) conservation laws for heterogeneous media, we introduce a macroscopic thermal model based on variable-order (VO) time and space derivatives. The proposed thermal model maps the heterogeneities in temporal and spatial scales into the order of the fractional derivative, which allows us to steer away from a classical diffusion equation for complex heterogeneous media. We then verify the VO thermal model for benchmark problems and discuss the possible links between values of VO derivatives in the new conservation equation and microstructure through spatial correlation functions.

  11. New formulation feed method in tariff model of solar PV in Indonesia

    NASA Astrophysics Data System (ADS)

    Djamal, Muchlishah Hadi; Setiawan, Eko Adhi; Setiawan, Aiman

    2017-03-01

    Geographically, Indonesia has 18 latitudes that correlated strongly with the potential of solar radiation for the implementation of solar photovoltaic (PV) technologies. This is becoming the basis assumption to develop a proportional model of Feed In Tariff (FIT), consequently the FIT will be vary, according to the various of latitudes in Indonesia. This paper proposed a new formulation of solar PV FIT based on the potential of solar radiation and some independent variables such as latitude, longitude, Levelized Cost of Electricity (LCOE), and also socio-economic. The Principal Component Regression (PCR) method is used to analyzed the correlation of six independent variables C1-C6 then three models of FIT are presented. Model FIT-2 is chosen because it has a small residual value and has higher financial benefit compared to the other models. This study reveals the value of variable FIT associated with solar energy potential in each region, can reduce the total FIT to be paid by the state around 80 billion rupiahs in 10 years of 1 MW photovoltaic operation at each 34 provinces in Indonesia.

  12. A model for wet aggregation of ash particles in volcanic plumes and clouds: 1. Theoretical formulation

    NASA Astrophysics Data System (ADS)

    Costa, Antonio; Folch, Arnau; Macedonio, Giovanni

    2010-09-01

    We develop a model to describe ash aggregates in a volcanic plume. The model is based on a solution of the classical Smoluchowski equation, obtained by introducing a similarity variable and a fractal relationship for the number of primary particles in an aggregate. The considered collision frequency function accounts for different mechanisms of aggregation, such as Brownian motion, ambient fluid shear, and differential sedimentation. Although model formulation is general, here only sticking efficiency related to the presence of water is considered. However, the different binding effect of liquid water and ice is discerned. The proposed approach represents a first compromise between the full description of the aggregation process and the need to decrease the computational time necessary for solving the full Smoluchowski equation. We also perform a parametric study on the main model parameters and estimate coagulation kernels and timescales of the aggregation process under simplified conditions of interest in volcanology. Further analyses and applications to real eruptions are presented in the companion paper by Folch et al.

  13. Stochastic modelling of landfill leachate and biogas production incorporating waste heterogeneity. Model formulation and uncertainty analysis

    SciTech Connect

    Zacharof, A.I.; Butler, A.P

    2004-07-01

    A mathematical model simulating the hydrological and biochemical processes occurring in landfilled waste is presented and demonstrated. The model combines biochemical and hydrological models into an integrated representation of the landfill environment. Waste decomposition is modelled using traditional biochemical waste decomposition pathways combined with a simplified methodology for representing the rate of decomposition. Water flow through the waste is represented using a statistical velocity model capable of representing the effects of waste heterogeneity on leachate flow through the waste. Given the limitations in data capture from landfill sites, significant emphasis is placed on improving parameter identification and reducing parameter requirements. A sensitivity analysis is performed, highlighting the model's response to changes in input variables. A model test run is also presented, demonstrating the model capabilities. A parameter perturbation model sensitivity analysis was also performed. This has been able to show that although the model is sensitive to certain key parameters, its overall intuitive response provides a good basis for making reasonable predictions of the future state of the landfill system. Finally, due to the high uncertainty associated with landfill data, a tool for handling input data uncertainty is incorporated in the model's structure. It is concluded that the model can be used as a reasonable tool for modelling landfill processes and that further work should be undertaken to assess the model's performance.

  14. Using the Landlab toolkit to evaluate and compare alternative geomorphic and hydrologic model formulations

    NASA Astrophysics Data System (ADS)

    Tucker, G. E.; Adams, J. M.; Doty, S. G.; Gasparini, N. M.; Hill, M. C.; Hobley, D. E. J.; Hutton, E.; Istanbulluoglu, E.; Nudurupati, S. S.

    2016-12-01

    Developing a better understanding of catchment hydrology and geomorphology ideally involves quantitative hypothesis testing. Often one seeks to identify the simplest mathematical and/or computational model that accounts for the essential dynamics in the system of interest. Development of alternative hypotheses involves testing and comparing alternative formulations, but the process of comparison and evaluation is made challenging by the rigid nature of many computational models, which are often built around a single assumed set of equations. Here we review a software framework for two-dimensional computational modeling that facilitates the creation, testing, and comparison of surface-dynamics models. Landlab is essentially a Python-language software library. Its gridding module allows for easy generation of a structured (raster, hex) or unstructured (Voronoi-Delaunay) mesh, with the capability to attach data arrays to particular types of element. Landlab includes functions that implement common numerical operations, such as gradient calculation and summation of fluxes within grid cells. Landlab also includes a collection of process components, which are encapsulated pieces of software that implement a numerical calculation of a particular process. Examples include downslope flow routing over topography, shallow-water hydrodynamics, stream erosion, and sediment transport on hillslopes. Individual components share a common grid and data arrays, and they can be coupled through the use of a simple Python script. We illustrate Landlab's capabilities with a case study of Holocene landscape development in the northeastern US, in which we seek to identify a collection of model components that can account for the formation of a series of incised canyons that have that developed since the Laurentide ice sheet last retreated. We compare sets of model ingredients related to (1) catchment hydrologic response, (2) hillslope evolution, and (3) stream channel and gully incision

  15. Simulation of reactive nanolaminates using reduced models: III. Ingredients for a general multidimensional formulation

    SciTech Connect

    Salloum, Maher; Knio, Omar M.

    2010-06-15

    A transient multidimensional reduced model is constructed for the simulation of reaction fronts in Ni/Al multilayers. The formulation is based on the generalization of earlier methodologies developed for quasi-1D axial and normal propagation, specifically by adapting the reduced formalism for atomic mixing and heat release. This approach enables us to focus on resolving the thermal front structure, whose evolution is governed by thermal diffusion and heat release. A mixed integration scheme is used for this purpose, combining an extended-stability, Runge-Kutta-Chebychev (RKC) integration of the diffusion term with exact treatment of the chemical source term. Thus, a detailed description of atomic mixing within individual layers is avoided, which enables transient modeling of the reduced equations of motion in multiple dimensions. Two-dimensional simulations are first conducted of front propagation in composites combining two bilayer periods. Results are compared with the experimental measurements of Knepper et al., which reveal that the reaction velocity can depend significantly on layering frequency. The comparison indicates that, using a concentration-dependent conductivity model, the transient 2D computations can reasonably reproduce the experimental behavior. Additional tests are performed based on 3D computations of surface initiated reactions. Comparison of computed predictions with laser ignition measurements indicates that the computations provide reasonable estimates of ignition thresholds. A detailed discussion is finally provided of potential generalizations and associated hurdles. (author)

  16. Formulation of solid dispersion of rebamipide evaluated in a rat model for improved bioavailability and efficacy.

    PubMed

    Tung, Nguyen-Thach; Park, Chun-Woong; Oh, Tack-oon; Kim, Ju-Young; Ha, Jung-Myung; Rhee, Yun-Seok; Park, Eun-Seok

    2011-12-01

    Rebamipide, a novel anti-ulcer agent, is listed in biopharmaceutics classification class IV because of its low aqueous solubility and permeability. Consequently, the bioavailability of rebamipide is under 10% in humans. The aim of this study was to increase the solubility and determine the effect of solubility enhancement on the bioavailability and efficacy of rebamipide (RBM). After taking into account the physiochemical properties of RBM (solubility, melting point, dosage etc.), solid dispersion was chosen as the solubility enhancement method. A rebamipide solid dispersion system containing the drug, l-lysine, PVP-VA 64 and poloxamer 407 was obtained from a spray-drying method. Solubility enhancement of RBM from the solid dispersion was determined by a dissolution test in 900 ml at pH 1.2. The bioavailability and efficacy of RBM solid dispersion were evaluated in a rat model. The aqueous solubility of RBM was improved 62.17 times by solid dispersion. The oral bioavailability of the drug was also increased 1.74-fold from solid dispersion compared with the reference product in a rat model. With regard to the anti-ulcer effect, the percentage inhibition of the solid dispersion was 2.71 times higher than that of the reference product in the ulcer-induced rat model. A solid dispersion of rebamipide was successfully formulated using the spray-drying method. Bioavailability and efficacy of rebamipide were increased significantly by solubility enhancement of the drug. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  17. A methodology for formulating a minimal uncertainty model for robust control system design and analysis

    NASA Technical Reports Server (NTRS)

    Belcastro, Christine M.; Chang, B.-C.; Fischl, Robert

    1989-01-01

    In the design and analysis of robust control systems for uncertain plants, the technique of formulating what is termed an M-delta model has become widely accepted and applied in the robust control literature. The M represents the transfer function matrix M(s) of the nominal system, and delta represents an uncertainty matrix acting on M(s). The uncertainty can arise from various sources, such as structured uncertainty from parameter variations or multiple unstructured uncertainties from unmodeled dynamics and other neglected phenomena. In general, delta is a block diagonal matrix, and for real parameter variations the diagonal elements are real. As stated in the literature, this structure can always be formed for any linear interconnection of inputs, outputs, transfer functions, parameter variations, and perturbations. However, very little of the literature addresses methods for obtaining this structure, and none of this literature addresses a general methodology for obtaining a minimal M-delta model for a wide class of uncertainty. Since have a delta matrix of minimum order would improve the efficiency of structured singular value (or multivariable stability margin) computations, a method of obtaining a minimal M-delta model would be useful. A generalized method of obtaining a minimal M-delta structure for systems with real parameter variations is given.

  18. A Method for Formulizing Disaster Evacuation Demand Curves Based on SI Model

    PubMed Central

    Song, Yulei; Yan, Xuedong

    2016-01-01

    The prediction of evacuation demand curves is a crucial step in the disaster evacuation plan making, which directly affects the performance of the disaster evacuation. In this paper, we discuss the factors influencing individual evacuation decision making (whether and when to leave) and summarize them into four kinds: individual characteristics, social influence, geographic location, and warning degree. In the view of social contagion of decision making, a method based on Susceptible-Infective (SI) model is proposed to formulize the disaster evacuation demand curves to address both social influence and other factors’ effects. The disaster event of the “Tianjin Explosions” is used as a case study to illustrate the modeling results influenced by the four factors and perform the sensitivity analyses of the key parameters of the model. Some interesting phenomena are found and discussed, which is meaningful for authorities to make specific evacuation plans. For example, due to the lower social influence in isolated communities, extra actions might be taken to accelerate evacuation process in those communities. PMID:27735875

  19. Levels of Question Formulation in Negotiation of Information Need during the Online Presearch Interview: A Proposed Model.

    ERIC Educational Resources Information Center

    Markey, Karen

    1981-01-01

    Assesses the adequacy of Robert S. Taylor's model of question formulation in the context of online presearch interviews, and presents an altered model which introduces the bearers of needs and makes distinctions about those needs as isolated or negotiated events in the interviews. Thirty-three references are listed. (FM)

  20. Sustainable conjunctive water management in irrigated agriculture: Model formulation and application to the Yaqui Valley, Mexico

    NASA Astrophysics Data System (ADS)

    Schoups, Gerrit; Addams, C. Lee; Minjares, José Luis; Gorelick, Steven M.

    2006-10-01

    This paper investigates strategies to alleviate the effects of droughts on the profitability and sustainability of irrigated agriculture. These strategies include conjunctive management of surface water and groundwater resources, and engineered improvements such as lining of irrigation canals and addition of regional pumping well capacity. A spatially distributed simulation-optimization model was developed for an irrigated system consisting of multiple surface water reservoirs and an alluvial aquifer. The simulation model consists of an agronomic component and simulators describing the hydrologic system. The physical models account for storage and flow through the reservoirs, routing through the irrigation canals, and regional groundwater flow. The agronomic model describes crop productivity as a function of irrigation quantity and salinity, and determines agricultural profit. A profit maximization problem was formulated and solved using large-scale constrained gradient-based optimization. The model was applied to a real-world conjunctive surface water/groundwater management problem in the Yaqui Valley, an irrigated agricultural region in Sonora, Mexico. The model reproduces recorded reductions in agricultural production during a historical drought. These reductions were caused by a decline in surface water availability and limited installed pumping capacity. Results indicate that the impact of the historical 8-year drought could have been significantly reduced without affecting profit in wet years by better managing surface water and groundwater resources. Namely, groundwater could have been more heavily relied upon and surface water allocation capped at a sustainable level as an operating rule. Lining the irrigation canals would have resulted in water savings of 30% of historical reservoir releases during wet years, which could have been used in subsequent drier years to increase agricultural production. The benefits of a greater reliance on groundwater pumping

  1. Formulation of non-reflecting boundary conditions in numerical models of the atmosphere

    NASA Astrophysics Data System (ADS)

    Kar, Sajal Kumar

    To eliminate/minimize spurious reflections of small-scale gravity-inertia waves at the material-surface upper boundary of a numerical model of the atmosphere, an energy-absorbing sponge layer is formulated. The sponge layer is designed for forced internal gravity-inertia waves in a resting isothermal atmosphere on an f-plane. The sponge layer is introduced immediately below the material-surface upper boundary. The sponge terms appear as linear damping of the vorticity, divergence, and temperature perturbations inside the sponge layer. The damping coefficient (L) is same for all sponge terms. For small-scale gravity-inertia waves that are most effective in propagating vertical wave energy upwards, two approximate forms of L, namely L(sub 1) and L(sub 2) are derived, neither of which explicitly depend on the sign of frequency and equivalent depth, and as such either can be readily implemented into a time-dependent model. The sponge layer with the coefficient L(sub 1) is designed for a spectral model. The sponge layer with the coefficient L(sub 2), on the other hand, is designed for a finite-difference. The sponge layers in linear time-dependent models were implemented and tested. A lateral sponge layer is designed for linear one-dimensional shallow-water gravity waves. The damping terms inside the sponge layer can selectively damp the characteristic variable advected back (or reflected) into the model domain from the lateral boundary. The lateral sponge layer was implemented in a linear time-dependent model.

  2. In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation.

    PubMed

    McCarthy, Carol A; Faisal, Waleed; O'Shea, Joseph P; Murphy, Colm; Ahern, Robert J; Ryan, Katie B; Griffin, Brendan T; Crean, Abina M

    2017-03-28

    Drug release from mesoporous silica systems has been widely investigated in vitro using USP Type II (paddle) dissolution apparatus. However, it is not clear if the observed enhanced in vitro dissolution can forecast drug bioavailability in vivo. In this study, the ability of different in vitro dissolution models to predict in vivo oral bioavailability in a pig model was examined. The fenofibrate-loaded mesoporous silica formulation was compared directly to a commercial reference product, Lipantil Supra®. Three in vitro dissolution methods were considered; USP Type II (paddle) apparatus, USP Type IV (flow-through cell) apparatus and a USP IV Transfer model (incorporating a SGF to FaSSIF-V2 media transfer). In silico modelling, using a physiologically based pharmacokinetic modelling and simulation software package (Gastroplus™), to generate in vitro/in vivo relationships, was also investigated. The study demonstrates that the in vitro dissolution performance of a mesoporous silica formulation varies depending on the dissolution apparatus utilised and experimental design. The findings show that the USP IV transfer model was the best predictor of in vivo bioavailability. The USP Type II (paddle) apparatus was not effective at forecasting in vivo behaviour. This observation is likely due to hydrodynamic differences between the two apparatus and the ability of the transfer model to better simulate gastrointestinal transit. The transfer model is advantageous in forecasting in vivo behaviour for formulations which promote drug supersaturation and as a result are prone to precipitation to a more energetically favourable, less soluble form. The USP IV transfer model could prove useful in future mesoporous silica formulation development. In silico modelling has the potential to assist in this process. However, further investigation is required to overcome the limitations of the model for solubility enhancing formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Formulation of consumables management models: Test plan for the mission planning processor working model

    NASA Technical Reports Server (NTRS)

    Connelly, L. C.

    1977-01-01

    The test plan and test procedures to be used in the verification and validation of the software being implemented in the mission planning processor working model program are documented. The mission planning processor is a user oriented tool for consumables management and is part of the total consumables subsystem management concept. An overview of the working model is presented. Execution of the test plan will comprehensively exercise the working model software. An overview of the test plan, including a testing schedule, is presented along with the test plan for the unit, module, and system levels. The criteria used to validate the working model results for each consumables subsystem is discussed.

  4. Formulation of consumables management models. Development approach for the mission planning processor working model

    NASA Technical Reports Server (NTRS)

    Connelly, L. C.

    1977-01-01

    The mission planning processor is a user oriented tool for consumables management and is part of the total consumables subsystem management concept. The approach to be used in developing a working model of the mission planning processor is documented. The approach includes top-down design, structured programming techniques, and application of NASA approved software development standards. This development approach: (1) promotes cost effective software development, (2) enhances the quality and reliability of the working model, (3) encourages the sharing of the working model through a standard approach, and (4) promotes portability of the working model to other computer systems.

  5. Sparse geologic dictionaries for subsurface flow model calibration: Part I. Inversion formulation

    NASA Astrophysics Data System (ADS)

    Khaninezhad, Mohammadreza Mohammad; Jafarpour, Behnam; Li, Lianlin

    2012-04-01

    Inference of heterogeneous rock properties from low-resolution dynamic flow measurements often leads to underdetermined nonlinear inverse problems that can have many non-unique solutions. The problem is usually regularized by reducing the number of unknown parameters and/or incorporating direct or indirect prior information. In subsurface flow modeling, structural connectivity in hydraulic properties plays a critical role in determining local and global flow and displacement processes. When reliable prior information about the structural connectivity of a formation is available it can be used to discourage implausible inversion solutions. In this two-part paper, we introduce a geologically-inspired conceptual framework, geologic dictionaries, for reconstructing complex subsurface physical properties from the flow data. We evaluate the performance of our method under both reliable and highly uncertain prior knowledge and measurements. In Part I, we present inversion with sparse geologic dictionaries, learned from prior models, for estimation of complex heterogeneous subsurface hydraulic properties. We show how learning methods can be adapted to build, from a prior training library, specialized sparse geologic dictionaries that contain relevant structural elements (words) for constructing the solution of subsurface flow inverse problems. The key property of the constructed geologic dictionaries that we invoke during flow data integration is its "sparsity"; that is, we require that only a small subset of geologic dictionary elements be sufficient for accurately approximating any prior model realizations in the training library, and hence the model calibration solution. Using the sparsity property of the geologic dictionary, we formulate and solve the nonlinear model calibration as a feature estimation problem. To construct a solution, we adopt an iteratively reweighted least-squares (IRLS) algorithm to identify the important dictionary elements by minimizing a

  6. Statistical multifragmentation model with discretized energy and the generalized Fermi breakup: Formulation of the model

    NASA Astrophysics Data System (ADS)

    Souza, S. R.; Carlson, B. V.; Donangelo, R.; Lynch, W. G.; Tsang, M. B.

    2013-07-01

    The generalized Fermi breakup model, recently demonstrated to be formally equivalent to the statistical multifragmentation model, if the contribution of excited states is included in the state densities of the former, is implemented. Because this treatment requires application of the statistical multifragmentation model repeatedly on hot fragments until they have decayed to their ground states, it becomes extremely computationally demanding, making its application to the systems of interest extremely difficult. Based on exact recursion formulas previously developed by Chase and Mekjian to calculate statistical weights very efficiently, we present an implementation which is efficient enough to allow it to be applied to large systems at high excitation energies. Comparison with the gemini++ sequential decay code and the Weisskopf-Ewing evaporation model shows that the predictions obtained with our treatment are fairly similar to those obtained with these more traditional models.

  7. An Extended Damage Plasticity Model for Shotcrete: Formulation and Comparison with Other Shotcrete Models

    PubMed Central

    Neuner, Matthias; Gamnitzer, Peter; Hofstetter, Günter

    2017-01-01

    The aims of the present paper are (i) to briefly review single-field and multi-field shotcrete models proposed in the literature; (ii) to propose the extension of a damage-plasticity model for concrete to shotcrete; and (iii) to evaluate the capabilities of the proposed extended damage-plasticity model for shotcrete by comparing the predicted response with experimental data for shotcrete and with the response predicted by shotcrete models, available in the literature. The results of the evaluation will be used for recommendations concerning the application and further improvements of the investigated shotcrete models and they will serve as a basis for the design of a new lab test program, complementing the existing ones. PMID:28772445

  8. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

    PubMed Central

    Chavez, Brittany K.; Agarabi, Cyrus D.; Read, Erik K.; Boyne II, Michael T.; Khan, Mansoor A.; Brorson, Kurt A.

    2016-01-01

    Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24 full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Thus, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules. PMID:27042659

  9. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations.

    PubMed

    Chavez, Brittany K; Agarabi, Cyrus D; Read, Erik K; Boyne, Michael T; Khan, Mansoor A; Brorson, Kurt A

    2016-01-01

    Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 2(4) full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Thus, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.

  10. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

    SciTech Connect

    Chavez, Brittany K.; Agarabi, Cyrus D.; Read, Erik K.; Boyne II, Michael T.; Khan, Mansoor A.; Brorson, Kurt A.

    2016-01-01

    Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 24full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Therefore, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.

  11. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

    DOE PAGES

    Chavez, Brittany K.; Agarabi, Cyrus D.; Read, Erik K.; ...

    2016-01-01

    Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potentialmore » storage buffer due to significant visible precipitate formation. An additional 24full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Therefore, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.« less

  12. A Regional Scale Coupled Atmosphere-Ecosystem Model: Formulation and Results

    NASA Astrophysics Data System (ADS)

    Medvigy, D.; Moorcroft, P. R.; Albani, M.; Avissar, R.; Walko, R. L.

    2004-12-01

    The formulation of self-consistent and computationally efficient atmosphere-ecosystem models requires the bridging of a wide range of spatial and temporal scales. Disturbance events such wind-throw, fire and land-use change give rise to significant sub-grid scale heterogeneity in ecosystem structure and function at a variety scales ranging down to the the size of an individual canopy tree, far below the resolution of both climate and numerical weather prediction models. Moreover, over decadal timescales, the spatial distribution of this heterogeneity is dynamic due to the successional dynamics that follow disturbance events within ecosystems. To address this problem, we have developed the Ecosystem Demography Land Surface Model (ED-LSM), an integrated biosphere model that incorporates plant community dynamics, soil carbon and nitrogen biogeochemistry and land surface biophysics. The fast timescale fluxes of carbon, water and energy between the ecosystem and the atmosphere are captured using the leaf photosynthesis and soil decomposition modules of Ecosystem Demography (ED) model coupled to a multi-leaf layer, multi-soil layer implementation of the LEAF-2 biophysical scheme. Long term changes in the biophsyical, ecological and biogeochemical structure of the ecosystem are captured using the ED model's system of size- and age-structured partial differential equations that track the changes in the vertical and horizontal heterogeneity of above and below ground ecosystem structure that result from ecosystem responses to the atmosphere that play out over years, decades and centuries. The model can be run both off-line and coupled to the Regional Atmospheric Modeling System (RAMS), which simulates both atmospheric dynamics and tracer transport of carbon dioxide. We have carried out coupled simulations of the model in temperate, tropical and boreal regions. Comparison of our results with observations from eddy-flux towers and meteorological stations highlights the models

  13. a New, Regional-Scale Coupled Atmosphere-Ecosystem Model: Formulation and Results

    NASA Astrophysics Data System (ADS)

    Moorcroft, P. R.; Medvigy, D. M.; Avissar, R.; Walko, R. L.

    2004-05-01

    The formulation of self-consistent and computationally efficient atmosphere-ecosystem models requires the bridging of a wide range of spatial and temporal scales. Disturbance events such wind-throw, fire and land-use change give rise to significant sub-grid scale heterogeneity in ecosystem structure and function at a variety scales ranging down to the the size of an individual canopy tree, far below the resolution of both climate and numerical weather prediction models. Moreover, over decadal timescales, the spatial distribution of this heterogeneity is dynamic due to the successional dynamics that follow disturbance events within ecosystems. To address this problem, we have developed the Ecosystem Demography Land Surface Model (ED-LSM), an integrated biosphere model that incorporates plant community dynamics, soil carbon and nitrogen biogeochemistry and land surface biophysics. The fast timescale fluxes of carbon, water and energy between the ecosystem and the atmosphere are captured using the leaf photosynthesis and soil decomposition modules of the Ecosystem Demography (ED) model coupled to a multi-leaf layer, multi-soil layer implementation of the LEAF-2 biophysical scheme. Long term changes in the biophysical, ecological and biogeochemical structure of the ecosystem are captured using the ED model's system of size- and age-structured partial differential equations that track the changes in the vertical and horizontal heterogeneity of above and below ground ecosystem structure that result from ecosystem responses to the atmosphere that play out over years, decades and centuries. The model can be run both off-line and coupled to the Regional Atmospheric Modeling System (RAMS), which simulates both atmospheric dynamics and tracer transport of carbon dioxide. We have carried out coupled simulations of the model in temperate, tropical and boreal regions. Comparison of our results with observations from eddy-flux towers and meteorological stations highlights the

  14. A proteoliposome formulation derived from Bordetella pertussis induces protection in two murine challenge models.

    PubMed

    Fernández, Sonsire; Fajardo, Esther M; Mandiarote, Aleida; Año, Gemma; Padrón, Maria A; Acosta, Michel; Cabrera, Rubén A; Riverón, Luis A; Álvarez, Maydelis; Blaín, Kirenia; Fariñas, Mildrey; Cardoso, Daniel; García, Luis G; Campa, Concepción; Pérez, José L

    2013-01-01

    Whooping cough remains a health problem despite high vaccination coverage. It has been recommended that development of new strategies provide long-lasting immunity. The aim of this work was to evaluate the potential of proteoliposomes (PL) extracted from Bordetella pertussis as a vaccine candidate against whooping cough. The size of the B. pertussis PL was estimated to be 96.7 ± 50.9 nm by Scanning Correlation Spectroscopy and the polydispersity index was 0.268. Western blots using monoclonal antibodies revealed the presence of pertussis toxin, pertactin, and fimbriae 3. The Limulus Amebocyte Lisate (LAL) assay showed endotoxin levels lower than those reported for whole cell pertussis licensed vaccines, while the Pyrogen Test indicated 75 ng/mL/Kg. The PL showed high protection capacity in mouse challenge models. There was 89.7% survival in the intracerebral challenge and total reduction of the number of CFU in the intranasal challenge. No significant differences (p > 0.05) were observed between mice immunized with B. pertussis PL and the Cuban DTwP vaccine, whichever challenge model used. These results encouraged us to continue the development of the B. pertussis PL as a component of a new combined vaccine formulated with tetanus and diphtheria toxoids or as a booster dose for adolescents and adults.

  15. On modelling large deformations of heterogeneous biological tissues using a mixed finite element formulation.

    PubMed

    Wu, Tim; Hung, Alice P-L; Hunter, Peter; Mithraratne, Kumar

    2015-01-01

    This study addresses the issue of modelling material heterogeneity of incompressible bodies. It is seen that when using a mixed (displacement-pressure) finite element formulation, the basis functions used for pressure field may not be able to capture the nonlinearity of material parameters, resulting in pseudo-residual stresses. This problem can be resolved by modifying the constitutive relation using Flory's decomposition of the deformation gradient. A two-parameter Mooney-Rivlin constitutive relation is used to demonstrate the methodology. It is shown that for incompressible materials, the modification does not alter the mechanical behaviour described by the original constitutive model. In fact, the modified constitutive equation shows a better predictability when compared against analytical solutions. Two strategies of describing the material variation (i.e. linear and step change) are explained, and their solutions are evaluated for an ideal two-material interfacing problem. When compared with the standard tied coupling approach, the step change method exhibited a much better agreement because of its ability to capture abrupt changes of the material properties. The modified equation in conjunction with integration point-based material heterogeneity is then used to simulate the deformations of heterogeneous biological structures to illustrate its applications.

  16. A corrected formulation for marginal inference derived from two-part mixed models for longitudinal semi-continuous data.

    PubMed

    Tom, Brian Dm; Su, Li; Farewell, Vernon T

    2016-10-01

    For semi-continuous data which are a mixture of true zeros and continuously distributed positive values, the use of two-part mixed models provides a convenient modelling framework. However, deriving population-averaged (marginal) effects from such models is not always straightforward. Su et al. presented a model that provided convenient estimation of marginal effects for the logistic component of the two-part model but the specification of marginal effects for the continuous part of the model presented in that paper was based on an incorrect formulation. We present a corrected formulation and additionally explore the use of the two-part model for inferences on the overall marginal mean, which may be of more practical relevance in our application and more generally. © The Author(s) 2013.

  17. A corrected formulation for marginal inference derived from two-part mixed models for longitudinal semi-continuous data

    PubMed Central

    Su, Li; Farewell, Vernon T

    2013-01-01

    For semi-continuous data which are a mixture of true zeros and continuously distributed positive values, the use of two-part mixed models provides a convenient modelling framework. However, deriving population-averaged (marginal) effects from such models is not always straightforward. Su et al. presented a model that provided convenient estimation of marginal effects for the logistic component of the two-part model but the specification of marginal effects for the continuous part of the model presented in that paper was based on an incorrect formulation. We present a corrected formulation and additionally explore the use of the two-part model for inferences on the overall marginal mean, which may be of more practical relevance in our application and more generally. PMID:24201470

  18. GFDL's CM2 global coupled climate models. Part I: Formulation and simulation characteristics

    USGS Publications Warehouse

    Delworth, T.L.; Broccoli, A.J.; Rosati, A.; Stouffer, R.J.; Balaji, V.; Beesley, J.A.; Cooke, W.F.; Dixon, K.W.; Dunne, J.; Dunne, K.A.; Durachta, J.W.; Findell, K.L.; Ginoux, P.; Gnanadesikan, A.; Gordon, C.T.; Griffies, S.M.; Gudgel, R.; Harrison, M.J.; Held, I.M.; Hemler, R.S.; Horowitz, L.W.; Klein, S.A.; Knutson, T.R.; Kushner, P.J.; Langenhorst, A.R.; Lee, H.-C.; Lin, S.-J.; Lu, J.; Malyshev, S.L.; Milly, P.C.D.; Ramaswamy, V.; Russell, J.; Schwarzkopf, M.D.; Shevliakova, E.; Sirutis, J.J.; Spelman, M.J.; Stern, W.F.; Winton, M.; Wittenberg, A.T.; Wyman, B.; Zeng, F.; Zhang, R.

    2006-01-01

    The formulation and simulation characteristics of two new global coupled climate models developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) are described. The models were designed to simulate atmospheric and oceanic climate and variability from the diurnal time scale through multicentury climate change, given our computational constraints. In particular, an important goal was to use the same model for both experimental seasonal to interannual forecasting and the study of multicentury global climate change, and this goal has been achieved. Tw o versions of the coupled model are described, called CM2.0 and CM2.1. The versions differ primarily in the dynamical core used in the atmospheric component, along with the cloud tuning and some details of the land and ocean components. For both coupled models, the resolution of the land and atmospheric components is 2?? latitude ?? 2.5?? longitude; the atmospheric model has 24 vertical levels. The ocean resolution is 1?? in latitude and longitude, with meridional resolution equatorward of 30?? becoming progressively finer, such that the meridional resolution is 1/3?? at the equator. There are 50 vertical levels in the ocean, with 22 evenly spaced levels within the top 220 m. The ocean component has poles over North America and Eurasia to avoid polar filtering. Neither coupled model employs flux adjustments. The co ntrol simulations have stable, realistic climates when integrated over multiple centuries. Both models have simulations of ENSO that are substantially improved relative to previous GFDL coupled models. The CM2.0 model has been further evaluated as an ENSO forecast model and has good skill (CM2.1 has not been evaluated as an ENSO forecast model). Generally reduced temperature and salinity biases exist in CM2.1 relative to CM2.0. These reductions are associated with 1) improved simulations of surface wind stress in CM2.1 and associated changes in oceanic gyre circulations; 2) changes in cloud tuning and

  19. A New Model for Chemical Evolution of the Galactic Halo: Formulation and Applications

    NASA Astrophysics Data System (ADS)

    Tsujimoto, Takuji; Shigeyama, Toshikazu; Yoshii, Yuzuru

    A model for Galactic chemical evolution, driven by supernova-induced star formation, is formulated and used to examine the nature of the Galactic halo at early epochs. In this model, new stars are formed following each supernova event, thus their abundance pattern is determined by the combination of heavy elements ejected from the supernova itself and those elements which are already present in the interstellar gas swept up by the supernova remnant. The end result is a prediction of large scatter in the abundance ratios among low-metallicity stars, reflecting a different nucleosynthesis yield for each Type II supernova (SN II) with a different progenitor mass. Formation of new stars is terminated when supernova remnants sweep up too little gas to form shells. We show from calculations based on the above scenario that (i) the observed [Fe/H] distribution for the Galactic halo field stars can be reproduced without effectively decreasing the heavy-element yields from SNe II by some manipulation required by previous models (e.g., via mass lass from the early Galaxy, or later mixing with "pristine" hydrogen clouds), (ii) the large observed scatter in the abundante ratio [Eu/Fe] for the most metal-poor stars can also be reproduced, and (iii) the frequency distribution of stars in the [Eu/Fe]-[Fe/H] plane can be predicted. Our model suggests that the probability of identifying essentially metal-free stars (Population III) in the local halo is around one in 103-4, provided that star formation in the halo is confined to individual gas clouds with mass of 10 ^{6-7} M_⊙ and that the initial mass function of metal-free stars is not significantly different from the Salpeter mass function.

  20. Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model.

    PubMed

    Kaderli, Sema; Viguier, Eric; Watrelot-Virieux, Dorothée; Roger, Thierry; Gurny, Robert; Scapozza, Leonardo; Möller, Michael; Boulocher, Caroline; Jordan, Olivier

    2015-10-01

    Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra-articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation. ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used. In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by μCT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA-reacetylated chitosan hydrogel surprisingly led to increased subchondral bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies toward more effective

  1. An inverse problem formulation for parameter estimation of a reaction-diffusion model of low grade gliomas

    PubMed Central

    Gholami, Amir; Mang, Andreas; Biros, George

    2015-01-01

    We present a numerical scheme for solving a parameter estimation problem for a model of low-grade glioma growth. Our goal is to estimate the spatial distribution of tumor concentration, as well as the magnitude of anisotropic tumor diffusion. We use a constrained optimization formulation with a reaction-diffusion model that results in a system of nonlinear partial differential equations (PDEs). In our formulation, we estimate the parameters using partially observed, noisy tumor concentration data at two different time instances, along with white matter fiber directions derived from diffusion tensor imaging (DTI). The optimization problem is solved with a Gauss-Newton reduced space algorithm. We present the formulation and outline the numerical algorithms for solving the resulting equations. We test the method using synthetic dataset and compute the reconstruction error for different noise levels and detection thresholds for monofocal and multifocal test cases. PMID:25963601

  2. Aeroelastic modeling of rotor blades with spanwise variable elastic axis offset: Classic issues revisited and new formulations

    NASA Technical Reports Server (NTRS)

    Bielawa, Richard L.

    1988-01-01

    In response to a systematic methodology assessment program directed to the aeroelastic stability of hingeless helicopter rotor blades, improved basic aeroelastic reformulations and new formulations relating to structural sweep were achieved. Correlational results are presented showing the substantially improved performance of the G400 aeroelastic analysis incorporating these new formulations. The formulations pertain partly to sundry solutions to classic problem areas, relating to dynamic inflow with vortex-ring state operation and basic blade kinematics, but mostly to improved physical modeling of elastic axis offset (structural sweep) in the presence of nonlinear structural twist. Specific issues addressed are an alternate modeling of the delta EI torsional excitation due to compound bending using a force integration approach, and the detailed kinematic representation of an elastically deflected point mass of a beam with both structural sweep and nonlinear twist.

  3. Kernel Density Reconstruction for Lagrangian Photochemical Modelling. Part 1: Model Formulation and Preliminary Tests

    SciTech Connect

    Monforti, F; Vitali, L; Bellasio, R; Bianconi, R

    2006-02-21

    In this paper a new approach to photochemical modeling is investigated and a lagrangian particle model named Photochemical Lagrangian Particle Model (PLPM) is described. Lagrangian particle models are a consolidated tool to deal with the dispersion of pollutants in the atmosphere. Good results have been obtained dealing with inert pollutants. In recent years, a number of pioneering works have shown as Lagrangian models can be of great interest when dealing with photochemistry, provided that special care is given in the reconstruction of chemicals concentration in the atmosphere. Density reconstruction can be performed through the so called ''box counting'' method: an Eulerian grid for chemistry is introduced and density is computed counting particles in each box. In this way one of the main advantages of the Lagrangian approach, the grid independence, is lost. Photochemical reactions are treated in PLPM by means of the complex chemical mechanism SAPRC90 and four density reconstruction methods have been developed, based on the kernel density estimator approach, in order to obtain grid-free accurate concentrations. These methods are all fully grid-free but they differ each other in considering local or global features of the particles distribution, in treating the Cartesian directions separately or together and in being based on receptors or particles positions in space.

  4. Development of an extended-release formulation of capecitabine making use of in vitro-in vivo correlation modelling.

    PubMed

    Meulenaar, Jelte; Keizer, Ron J; Beijnen, Jos H; Schellens, Jan H M; Huitema, Alwin D R; Nuijen, Bastiaan

    2014-02-01

    An oral extended-release (ER) formulation of capecitabine was developed for twice daily dosing, theoretically providing a continuous exposure to capecitabine, thus avoiding the undesirable in-between dosing gap inherent to the dosing schedule of the marketed capecitabine immediate-release formulation (Xeloda(®)). The target 12-hour in vivo release profile was correlated to an in vitro dissolution profile using an in vitro-in vivo correlation model based on the pharmacokinetic (PK) and dissolution characteristics of Xeloda(®). Making use of the slow dissolution characteristics of amorphous capecitabine as reported previously and screening of a panel of ER excipients, an ER formulation was designed. Kollidon(®) SR induced the most prominent ER. Moreover, it was shown that tablets prepared from CoSD capecitabine and Kollidon(®) SR have an additional threefold delay in dissolution compared with tablets prepared from the same but only physically mixed components. Therefore, a prototype tablet formulation composed of co-spray-dried capecitabine and Kollidon(®) SR (98/2%, w/w) mixed with colloidal silicon dioxide (0.5%, w/w) and magnesium stearate (2.5%, w/w) was defined. This prototype shows similar dissolution characteristics as the modelled dissolution profile. Currently, the in vivo PK of our designed ER capecitabine formulations is investigated in a clinical study. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. An evaluation of models of bare soil evaporation formulated with different land surface boundary conditions and assumptions

    NASA Astrophysics Data System (ADS)

    Smits, Kathleen M.; Ngo, Viet V.; Cihan, Abdullah; Sakaki, Toshihiro; Illangasekare, Tissa H.

    2012-12-01

    Bare soil evaporation is a key process for water exchange between the land and the atmosphere and an important component of the water balance. However, there is no agreement on the best modeling methodology to determine evaporation under different atmospheric boundary conditions. Also, there is a lack of directly measured soil evaporation data for model validation to compare these methods to establish the validity of their mathematical formulations. Thus, a need exists to systematically compare evaporation estimates using existing methods to experimental observations. The goal of this work is to test different conceptual and mathematical formulations that are used to estimate evaporation from bare soils to critically investigate various formulations and surface boundary conditions. Such a comparison required the development of a numerical model that has the ability to incorporate these boundary conditions. For this model, we modified a previously developed theory that allows nonequilibrium liquid/gas phase change with gas phase vapor diffusion to better account for dry soil conditions. Precision data under well-controlled transient heat and wind boundary conditions were generated, and results from numerical simulations were compared with experimental data. Results demonstrate that the approaches based on different boundary conditions varied in their ability to capture different stages of evaporation. All approaches have benefits and limitations, and no one approach can be deemed most appropriate for every scenario. Comparisons of different formulations of the surface boundary condition validate the need for further research on heat and vapor transport processes in soil for better modeling accuracy.

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

    PubMed

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

    2017-09-08

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

  7. Application of physiologically based pharmacokinetic modeling in the prediction of pharmacokinetics of bicyclol controlled-release formulation in human.

    PubMed

    Wang, Baolian; Liu, Zhihao; Li, Dan; Yang, Shuang; Hu, Jinping; Chen, Hui; Sheng, Li; Li, Yan

    2015-09-18

    Physiologically based pharmacokinetic (PBPK) modeling can assist in formulation development. Bicyclol is a novel anti-hepatitis drug. A bilayer osmotic pump table of bicyclol is being developed. PBPK models for bicyclol immediate-release (IR) and controlled-release (CR) tablets in beagle dog, as well as PBPK model for IR tablets in human were constructed. These models incorporated physicochemical properties and in vitro preclinical data. Parameter sensitivity analysis was performed for the effects of solubility and dissolution on pharmacokinetic (PK) parameters. Models were refined by comparing simulated results to experimental measurements. Furthermore, the clinical PK for bicyclol CR tablets was predicted using the in vivo dissolution profile by deconvolution of the mean PK profile of CR tablets in dogs. In summary, the present study described a strategy employing PBPK models to evaluate the effects of formulation factors on PK profiles and predict the performance of bicyclol CR tablets in human. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Electromagnetic modeling of REBCO high field coils by the H-formulation

    NASA Astrophysics Data System (ADS)

    Xia, Jing; Bai, Hongyu; Lu, Jun; Gavrilin, Andrew V.; Zhou, Youhe; Weijers, Hubertus W.

    2015-12-01

    In this paper, we employ the anisotropic bulk approximation to successfully implement the electromagnetic modeling of superconducting coils wound with rare-earth-barium-copper-oxide (REBCO) tapes based on the H-formulation, in which the field-dependent critical current density and highly nonlinear E-J characteristic are considered. The total number of turns in the stacks of REBCO pancake coils is up to several thousand. We validate the anisotropic bulk model by comparing the ac loss of a small four-pancake coil between the bulk model and the original model which takes the actual thickness of the superconducting layer into account. Then, the anisotropic bulk model is used to investigate the self-field problem of the REBCO prototype coils of the National High Magnetic Field Laboratory 32 {{T}} all-superconducting magnet. The field and current density distributions are obtained, and an obvious shielding effect is observed at the top and bottom of the coils. The ac losses in the first and second cycles are calculated. The former is crucial to the design of the cooling system and the latter relates to the routine consumption of the liquid helium. It is found that the ac loss in the first cycle is 2.6 times as large as that in the second cycle. We also study the ac loss dependences on some key parameters (the critical current, n-value and ramp rate of the applied current). It is found that both in the first and second cycles, the ac loss increases with decreasing critical current. Moreover, the influence of the n-value on the ac loss is negligible. In addition, the ac loss decreases logarithmically with increasing ramp rate. However, the average power loss increases linearly with increasing ramp rate. We also compare some analytical estimates with the simulation result for the ac loss of the dual prototype coils. It is found that the results of Bean’s slab model are closer to the simulation result. The presented model is a useful tool to help us understand

  9. Variational formulation and stability analysis of a three dimensional superelastic model for shape memory alloys

    NASA Astrophysics Data System (ADS)

    Alessi, Roberto; Pham, Kim

    2016-02-01

    This paper presents a variational framework for the three-dimensional macroscopic modelling of superelastic shape memory alloys in an isothermal setting. Phase transformation is accounted through a unique second order tensorial internal variable, acting as the transformation strain. Postulating the total strain energy density as the sum of a free energy and a dissipated energy, the model depends on two material scalar functions of the norm of the transformation strain and a material scalar constant. Appropriate calibration of these material functions allows to render a wide range of constitutive behaviours including stress-softening and stress-hardening. The quasi-static evolution problem of a domain is formulated in terms of two physical principles based on the total energy of the system: a stability criterion, which selects the local minima of the total energy, and an energy balance condition, which ensures the consistency of the evolution of the total energy with respect to the external loadings. The local phase transformation laws in terms of Kuhn-Tucker relations are deduced from the first-order stability condition and the energy balance condition. The response of the model is illustrated with a numerical traction-torsion test performed on a thin-walled cylinder. Evolutions of homogeneous states are given for proportional and non-proportional loadings. Influence of the stress-hardening/softening properties on the evolution of the transformation domain is emphasized. Finally, in view of an identification process, the issue of stability of homogeneous states in a multi-dimensional setting is answered based on the study of second-order derivative of the total energy. Explicit necessary and sufficient conditions of stability are provided.

  10. Eulerian formulation of the interacting particle representation model of homogeneous turbulence

    NASA Astrophysics Data System (ADS)

    Campos, Alejandro; Duraisamy, Karthik; Iaccarino, Gianluca

    2016-10-01

    The Interacting Particle Representation Model (IPRM) of homogeneous turbulence incorporates information about the morphology of turbulent structures within the confines of a one-point model. In the original formulation [Kassinos and Reynolds, Center for Turbulence Research: Annual Research Briefs, 31-51 (1996)], the IPRM was developed in a Lagrangian setting by evolving second moments of velocity conditional on a given gradient vector. In the present work, the IPRM is reformulated in an Eulerian framework, and evolution equations are developed for the marginal probability density functions (PDFs). Eulerian methods avoid the issues associated with statistical estimators used by Lagrangian approaches, such as slow convergence. A specific emphasis of this work is to use the IPRM to examine the long time evolution of homogeneous turbulence. We first describe the derivation of the marginal PDF in spherical coordinates, which reduces the number of independent variables and the cost associated with Eulerian simulations of PDF models. Next, a numerical method based on radial basis functions over a spherical domain is adapted to the IPRM. Finally, results obtained with the new Eulerian solution method are thoroughly analyzed. The sensitivity of the Eulerian simulations to parameters of the numerical scheme, such as the size of the time step and the shape parameter of the radial basis functions, is examined. A comparison between Eulerian and Lagrangian simulations is performed to discern the capabilities of each of the methods. Finally, a linear stability analysis based on the eigenvalues of the discrete differential operators is carried out for both the new Eulerian solution method and the original Lagrangian approach.

  11. A Poisson equation formulation for pressure calculations in penalty finite element models for viscous incompressible flows

    NASA Technical Reports Server (NTRS)

    Sohn, J. L.; Heinrich, J. C.

    1990-01-01

    The calculation of pressures when the penalty-function approximation is used in finite-element solutions of laminar incompressible flows is addressed. A Poisson equation for the pressure is formulated that involves third derivatives of the velocity field. The second derivatives appearing in the weak formulation of the Poisson equation are calculated from the C0 velocity approximation using a least-squares method. The present scheme is shown to be efficient, free of spurious oscillations, and accurate. Examples of applications are given and compared with results obtained using mixed formulations.

  12. Liposomal butamben gel formulations: toxicity assays and topical anesthesia in an animal model.

    PubMed

    Cereda, Cintia Maria Saia; Guilherme, Viviane Aparecida; Alkschbirs, Melissa Inger; de Brito Junior, Rui Barbosa; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Araujo, Daniele Ribeiro; de Paula, Eneida

    2017-03-01

    The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect and local toxicity of the local anesthetic butamben (BTB) encapsulated in conventional or elastic liposomes incorporated in gel formulations. The results showed that both gel formulations of liposomal BTB reduced the cytotoxicity (p < 0.001; one-way ANOVA/Tukey's test) and increased the topical analgesic effect (p < 0.05; one-way ANOVA/Tukey's test) of butamben, compared to plain BTB gel. The gel formulations presented good rheological properties, and stability assays detected no differences in physicochemical stability up to 30 d after preparation. Moreover, histological assessment revealed no morphological changes in rat skin after application of any of the gel formulations tested.

  13. Fitting-determined formulation of effective medium approximation for 3D trench structures in model-based infrared reflectrometry.

    PubMed

    Zhang, Chuanwei; Liu, Shiyuan; Shi, Tielin; Tang, Zirong

    2011-02-01

    The success of the model-based infrared reflectrometry (MBIR) technique relies heavily on accurate modeling and fast calculation of the infrared metrology process, which continues to be a challenge, especially for three-dimensional (3D) trench structures. In this paper, we present a simplified formulation for effective medium approximation (EMA), determined by a fitting-based method for the modeling of 3D trench structures. Intensive investigations have been performed with an emphasis on the generality of the fitting-determined (FD)-EMA formulation in terms of trench depth, trench pitch, and incidence angle so that its application is not limited to a particular configuration. Simulations conducted on a taper trench structure have further verified the proposed FD-EMA and demonstrated that the MBIR metrology with the FD-EMA-based model achieves an accuracy one order higher than that of the conventional zeroth-order EMA-based model.

  14. Application of a mixing-ratios based formulation to model mixing-driven dissolution experiments

    NASA Astrophysics Data System (ADS)

    Guadagnini, Alberto; Sanchez-Vila, Xavier; Saaltink, Maarten W.; Bussini, Michele; Berkowitz, Brian

    2009-05-01

    We address the question of how one can combine theoretical and numerical modeling approaches with limited measurements from laboratory flow cell experiments to realistically quantify salient features of complex mixing-driven multicomponent reactive transport problems in porous media. Flow cells are commonly used to examine processes affecting reactive transport through porous media, under controlled conditions. An advantage of flow cells is their suitability for relatively fast and reliable experiments, although measuring spatial distributions of a state variable within the cell is often difficult. In general, fluid is sampled only at the flow cell outlet, and concentration measurements are usually interpreted in terms of integrated reaction rates. In reactive transport problems, however, the spatial distribution of the reaction rates within the cell might be more important than the bulk integrated value. Recent advances in theoretical and numerical modeling of complex reactive transport problems [De Simoni M, Carrera J, Sanchez-Vila X, Guadagnini A. A procedure for the solution of multicomponent reactive transport problems. Water Resour Res 2005;41:W11410. doi: 10.1029/2005WR004056, De Simoni M, Sanchez-Vila X, Carrera J, Saaltink MW. A mixing ratios-based formulation for multicomponent reactive transport. Water Resour Res 2007;43:W07419. doi: 10.1029/2006WR005256] result in a methodology conducive to a simple exact expression for the space-time distribution of reaction rates in the presence of homogeneous or heterogeneous reactions in chemical equilibrium. The key points of the methodology are that a general reactive transport problem, involving a relatively high number of chemical species, can be formulated in terms of a set of decoupled partial differential equations, and the amount of reactants evolving into products depends on the rate at which solutions mix. The main objective of the current study is to show how this methodology can be used in conjunction

  15. Role of vertex corrections in the matrix formulation of the random phase approximation for the multiorbital Hubbard model

    SciTech Connect

    Altmeyer, Michaela; Guterding, Daniel; Hirschfeld, P. J.; Maier, Thomas A.; Valentí, Roser; Scalapino, Douglas J.

    2016-12-21

    In the framework of a multiorbital Hubbard model description of superconductivity, a matrix formulation of the superconducting pairing interaction that has been widely used is designed to treat spin, charge, and orbital fluctuations within a random phase approximation (RPA). In terms of Feynman diagrams, this takes into account particle-hole ladder and bubble contributions as expected. It turns out, however, that this matrix formulation also generates additional terms which have the diagrammatic structure of vertex corrections. As a result we examine these terms and discuss the relationship between the matrix-RPA superconducting pairing interaction and the Feynman diagrams that it sums.

  16. Role of vertex corrections in the matrix formulation of the random phase approximation for the multiorbital Hubbard model

    NASA Astrophysics Data System (ADS)

    Altmeyer, Michaela; Guterding, Daniel; Hirschfeld, P. J.; Maier, Thomas A.; Valentí, Roser; Scalapino, Douglas J.

    2016-12-01

    In the framework of a multiorbital Hubbard model description of superconductivity, a matrix formulation of the superconducting pairing interaction that has been widely used is designed to treat spin, charge, and orbital fluctuations within a random phase approximation (RPA). In terms of Feynman diagrams, this takes into account particle-hole ladder and bubble contributions as expected. It turns out, however, that this matrix formulation also generates additional terms which have the diagrammatic structure of vertex corrections. Here we examine these terms and discuss the relationship between the matrix-RPA superconducting pairing interaction and the Feynman diagrams that it sums.

  17. An efficient 3D finite element method model based on the T-A formulation for superconducting coated conductors

    NASA Astrophysics Data System (ADS)

    Zhang, Huiming; Zhang, Min; Yuan, Weijia

    2017-02-01

    An efficient three dimensional (3D) finite element method numerical model is proposed for superconducting coated conductors. The model is based on the T-A formulation and can be used to tackle 3D computational challenges for superconductors with high aspect ratios. By assuming a sheet approximation for the conductors, the model can speed up the computational process. The model has been validated by established analytical solutions. Two examples with complex geometries, which can hardly be simulated by the 2D model, are given. The model could be used to characterise and design large-scale applications using superconducting coated conductors, such as high field magnets and other electrical devices.

  18. Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate.

    PubMed

    Kesisoglou, Filippos; Xia, Binfeng; Agrawal, Nancy G B

    2015-11-01

    In vitro-in vivo correlations (IVIVC) are predictive mathematical models describing the relationship between dissolution and plasma concentration for a given drug compound. The traditional deconvolution/convolution-based approach is the most common methodology to establish a level A IVIVC that provides point to point relationship between the in vitro dissolution and the in vivo input rate. The increasing application of absorption physiologically based pharmacokinetic model (PBPK) has provided an alternative IVIVC approach. The current work established and compared two IVIVC models, via the traditional deconvolution/convolution method and via absorption PBPK modeling, for two types of modified release (MR) formulations (matrix and multi-particulate tablets) of MK-0941, a BCS III drug development candidate. Three batches with distinct release rates were studied for each formulation technology. A two-stage linear regression model was used for the deconvolution/convolution approach while optimization of the absorption scaling factors (a model parameter that relates permeability and input rate) in Gastroplus(TM) Advanced Compartmental Absorption and Transit model was used for the absorption PBPK approach. For both types of IVIVC models established, and for either the matrix or the multiparticulate formulations, the average absolute prediction errors for AUC and C max were below 10% and 15%, respectively. Both the traditional deconvolution/convolution-based and the absorption/PBPK-based level A IVIVC model adequately described the compound pharmacokinetics to guide future formulation development. This case study highlights the potential utility of absorption PBPK model to complement the traditional IVIVC approaches for MR products.

  19. Use of minipig skin biopsy model as an innovative tool to design topical formulation to achieve desired pharmacokinetics in humans.

    PubMed

    Mitra, Amitava; Leyes, Aquiles; Manser, Kimberly; Roadcap, Brad; Mestre, Christine; Tatosian, Daniel; Jin, Lan; Uemura, Naoto

    2015-05-01

    In vitro cadaver skin permeation studies are often conducted to characterize the permeation profile of compounds for dermal delivery. However, its utility could be limited in the case of topical products because of lack of reliable prediction of in vivo skin kinetics. In this paper, the use of in vivo skin biopsy data to guide topical formulation development is described. A formulation was developed by compounding MK-0873, a phosphodiesterase 4 (PDE4) inhibitor, into a commercially available cream base. The cream was characterized by skin pharmacokinetic studies in minipigs, which demonstrated that MK-0873 concentrations in the epidermis and dermis were substantially higher than the IC80 for human whole blood PDE4 inhibition of ∼200 nM, suggesting that cream should provide sufficient skin exposure to assess clinical efficacy. In toxicological studies, after 1 month repeat application in minipigs minor dermal irritation and minimal systemic exposure were observed. Based on these preclinical data, the cream formulation was chosen for single rising dose clinical studies, where plasma levels of MK-0873 were mostly below the LOQ, whereas skin biopsy concentrations ranged from 6.5 to 25.1 μM. These data suggested that minipig skin biopsy model can be a valuable tool to assess performance of topical formulations and guide formulation development. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Reduced-order kinetic plasma models using principal component analysis: Model formulation and manifold sensitivity

    NASA Astrophysics Data System (ADS)

    Bellemans, Aurélie; Magin, Thierry; Coussement, Axel; Parente, Alessandro

    2017-07-01

    Plasma flows involve hundreds of species and thousands of reactions at different time scales, resulting in a very large set of governing equations to solve. Simulating large reacting systems in nonequilibrium plasma mixtures remains a challenge with the currently available computational resources. Principal component analysis (PCA) offers a general and rather simple and automated method to reduce large kinetic mechanisms by principal variable selection. This work shows how to adapt and apply the PCA-scores technique, which has its origin in the combustion field, to a collisional-radiative model. We have successfully applied this technique to argon plasmas, reducing the set of governing equations by more than 90%, leading to an important speed-up of the calculation and a reduction of computational cost.

  1. Expressions of dissipated powers and stored energies in poroelastic media modeled by {u,U} and {u,P} formulations.

    PubMed

    Dazel, Olivier; Sgard, Franck; Becot, François-Xavier; Atalla, Noureddine

    2008-04-01

    This paper is devoted to the rigorous obtention of the energy balance in porous materials. The wave propagation in the porous media is described by Biot-Allard's {u,U} and {u,P} formulations. The paper derives the expressions for stored kinetic and strain energies together with dissipated energies. It is shown that, in the case of mixed formulations, these expressions do not correspond to the real and imaginary parts of the variational formulations. A quantitative convergence analysis of finite element scheme is then undertaken with the help of these indicators. It is shown that the order of convergence of these indicators for linear finite-element is one and that they are then well fitted to check the validity of finite-element models.

  2. A mixed finite element formulation for a non-linear, transversely isotropic material model for the cardiac tissue.

    PubMed

    Thorvaldsen, Tom; Osnes, Harald; Sundnes, Joakim

    2005-12-01

    In this paper we present a mixed finite element method for modeling the passive properties of the myocardium. The passive properties are described by a non-linear, transversely isotropic, hyperelastic material model, and the myocardium is assumed to be almost incompressible. Single-field, pure displacement-based formulations are known to cause numerical difficulties when applied to incompressible or slightly compressible material cases. This paper presents an alternative approach in the form of a mixed formulation, where a separately interpolated pressure field is introduced as a primary unknown in addition to the displacement field. Moreover, a constraint term is included in the formulation to enforce (almost) incompressibility. Numerical results presented in the paper demonstrate the difficulties related to employing a pure displacement-based method, applying a set of physically relevant material parameter values for the cardiac tissue. The same problems are not experienced for the proposed mixed method. We show that the mixed formulation provides reasonable numerical results for compressible as well as nearly incompressible cases, also in situations of large fiber stretches. There is good agreement between the numerical results and the underlying analytical models.

  3. Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer.

    PubMed

    Liang, Su; Bian, Xiaomei; Liang, Dong; Sivils, Jeffrey C; Neckers, Leonard M; Cox, Marc B; Xie, Huan

    2016-01-01

    MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water (0.28 µg/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls.

  4. Phase field modeling of brittle fracture for enhanced assumed strain shells at large deformations: formulation and finite element implementation

    NASA Astrophysics Data System (ADS)

    Reinoso, J.; Paggi, M.; Linder, C.

    2017-02-01

    Fracture of technological thin-walled components can notably limit the performance of their corresponding engineering systems. With the aim of achieving reliable fracture predictions of thin structures, this work presents a new phase field model of brittle fracture for large deformation analysis of shells relying on a mixed enhanced assumed strain (EAS) formulation. The kinematic description of the shell body is constructed according to the solid shell concept. This enables the use of fully three-dimensional constitutive models for the material. The proposed phase field formulation integrates the use of the (EAS) method to alleviate locking pathologies, especially Poisson thickness and volumetric locking. This technique is further combined with the assumed natural strain method to efficiently derive a locking-free solid shell element. On the computational side, a fully coupled monolithic framework is consistently formulated. Specific details regarding the corresponding finite element formulation and the main aspects associated with its implementation in the general purpose packages FEAP and ABAQUS are addressed. Finally, the applicability of the current strategy is demonstrated through several numerical examples involving different loading conditions, and including linear and nonlinear hyperelastic constitutive models.

  5. Phase field modeling of brittle fracture for enhanced assumed strain shells at large deformations: formulation and finite element implementation

    NASA Astrophysics Data System (ADS)

    Reinoso, J.; Paggi, M.; Linder, C.

    2017-06-01

    Fracture of technological thin-walled components can notably limit the performance of their corresponding engineering systems. With the aim of achieving reliable fracture predictions of thin structures, this work presents a new phase field model of brittle fracture for large deformation analysis of shells relying on a mixed enhanced assumed strain (EAS) formulation. The kinematic description of the shell body is constructed according to the solid shell concept. This enables the use of fully three-dimensional constitutive models for the material. The proposed phase field formulation integrates the use of the (EAS) method to alleviate locking pathologies, especially Poisson thickness and volumetric locking. This technique is further combined with the assumed natural strain method to efficiently derive a locking-free solid shell element. On the computational side, a fully coupled monolithic framework is consistently formulated. Specific details regarding the corresponding finite element formulation and the main aspects associated with its implementation in the general purpose packages FEAP and ABAQUS are addressed. Finally, the applicability of the current strategy is demonstrated through several numerical examples involving different loading conditions, and including linear and nonlinear hyperelastic constitutive models.

  6. Formulation of detailed consumables management models for the development (preoperational) period of advanced space transportation system: Executive summary

    NASA Technical Reports Server (NTRS)

    Torian, J. G.

    1976-01-01

    Formulation of models required for the mission planning and scheduling function and establishment of the relation of those models to prelaunch, onboard, ground support, and postmission functions for the development phase of space transportation systems (STS) was conducted. The preoperational space shuttle is used as the design baseline for the subject model formulations. Analytical models were developed which consist of a mission planning processor with appropriate consumables data base and a method of recognizing potential constraint violations in both the planning and flight operations functions. A flight data file for storage/retrieval of information over an extended period which interfaces with a flight operations processor for monitoring of the actual flights was examined.

  7. Updated Lagrangian finite element formulations of various biological soft tissue non-linear material models: a comprehensive procedure and review.

    PubMed

    Townsend, Molly T; Sarigul-Klijn, Nesrin

    2016-01-01

    Simplified material models are commonly used in computational simulation of biological soft tissue as an approximation of the complicated material response and to minimize computational resources. However, the simulation of complex loadings, such as long-duration tissue swelling, necessitates complex models that are not easy to formulate. This paper strives to offer the updated Lagrangian formulation comprehensive procedure of various non-linear material models for the application of finite element analysis of biological soft tissues including a definition of the Cauchy stress and the spatial tangential stiffness. The relationships between water content, osmotic pressure, ionic concentration and the pore pressure stress of the tissue are discussed with the merits of these models and their applications.

  8. The Role of Physiologically Based Oral Absorption Modelling in Formulation Development Under a Quality by Design Paradigm.

    PubMed

    Kesisoglou, Filippos

    2016-12-11

    Within the last decade, Quality by Design (QbD) has been getting increased attention in its implementation in the development of pharmaceutical drug products. Understanding of the impact of formulation composition and process on clinical performance is a centerpiece of QbD. Physiologically based pharmacokinetic modeling incorporating biorelevant dissolution and a systems parameter approach to gastrointestinal absorption has been gaining increased traction in the pharmaceutical industry as an important tool to guide early formulation development. Extension of the models to support QbD appears the next logical step. This commentary discusses the current status of use of these models in the pharmaceutical industry and the opportunities these models can offer in ensuring drug product quality moving forward, including the development of clinically relevant specifications.

  9. Formulation and study some inverse problems in modeling of hydrophysical fields in water areas with "liquid" boundaries

    NASA Astrophysics Data System (ADS)

    Agoshkov, Valery

    2017-04-01

    There are different approaches for modeling boundary conditions describing hydrophysical fields in water areas with "liquid" boundaries. Variational data assimilation may also be considered as one of such approaches. Development of computer equipment, together with an increase in the quantity and quality of data from the satellites and other monitoring tools proves that the development of this particular approach is perspective. The range of connected the problems is wide - different recording forms of boundary conditions, observational data assimilation procedures and used models of hydrodynamics are possible. In this work some inverse problems and corresponding variational data assimilation ones, connected with mathematical modeling of hydrophysical fields in water areas (seas and oceans) with "liquid" ("open") boundaries, are formulated and studied. Note that the surface of water area (which can also be considered as a "liquid" boundary) is not included in the set of "liquid" boundaries, in this case "liquid" boundaries are borders between the areas "water-water". In the work, mathematical model of hydrothermodynamics in the water areas with "liquid" ("open") part of the boundary, a generalized statement of the problem and the splitting method for time approximation are formulated. Also the problem of variational data assimilation and iterative algorithm for solving inverse problems mentioned above are formulated. The work is based on [1]. The work was partly supported by the Russian Science Foundation (project 14-11-00609, the general formulation of the inverse problems) and by the Russian Foundation for Basic Research (project 16-01-00548, the formulation of the problem and its study). [1] V.I. Agoshkov, Methods for solving inverse problems and variational data assimilation problems of observations in the problems of the large-scale dynamics of the oceans and seas, Institute of Numerical Mathematics, RAS, Moscow, 2016 (in Russian).

  10. Effects of direct spiking of silicone oil into a model pMDI formulation.

    PubMed

    Fallon, John K; Peyron, Isabelle D; Hickey, Anthony J

    2013-05-01

    Silicone oil is used as a valve lubricant in pressurized metered dose inhalers (pMDIs). Its possible impact on drug delivery, through such effects as particle aggregation, has recently been discussed. To examine the effects of a range of directly spiked silicone oil amounts on pMDI performance. pMDI canisters containing a corticosteroid medicinal compound, HFA134a and accurately measured amounts of silicone oil (0, 200, 400 and 550 µg) were prepared. Samples were characterized for actuation weight, aerodynamic size (by Andersen cascade impaction, ACI), charge (by electrical low-pressure impaction, ELPI) and product appearance by visual imaging. Actuation weights were unaffected by silicone oil. A small increase in aerodynamic size was observed in the presence of silicone oil as a shift from stage 5 to impactor throat. No significant change in medicinal compound recovery was seen (t-tests, p > 0.05). Fine particle fraction as a percentage of dose delivered (FPF) was unchanged, as was particle size distribution derived from charge measurements, with the addition of silicone oil (t-tests, p > 0.05). Canister opening did not indicate container interaction but that sedimentation occurred in the presence of silicone oil. Decanted suspensions containing silicone oil were more transparent. Possible interactions inside and outside the pMDI canister are described. As demonstrated previously with an alternative experimental design the study showed that silicone oil has little effect on product performance, when added to a model pMDI formulation at levels that could potentially be observed as a leachable from the metering valve.

  11. In silico modelling of drug–polymer interactions for pharmaceutical formulations

    PubMed Central

    Ahmad, Samina; Johnston, Blair F.; Mackay, Simon P.; Schatzlein, Andreas G.; Gellert, Paul; Sengupta, Durba; Uchegbu, Ijeoma F.

    2010-01-01

    Selecting polymers for drug encapsulation in pharmaceutical formulations is usually made after extensive trial and error experiments. To speed up excipient choice procedures, we have explored coarse-grained computer simulations (dissipative particle dynamics (DPD) and coarse-grained molecular dynamics using the MARTINI force field) of polymer–drug interactions to study the encapsulation of prednisolone (log p = 1.6), paracetamol (log p = 0.3) and isoniazid (log p = −1.1) in poly(l-lactic acid) (PLA) controlled release microspheres, as well as the encapsulation of propofol (log p = 4.1) in bioavailability enhancing quaternary ammonium palmitoyl glycol chitosan (GCPQ) micelles. Simulations have been compared with experimental data. DPD simulations, in good correlation with experimental data, correctly revealed that hydrophobic drugs (prednisolone and paracetamol) could be encapsulated within PLA microspheres and predicted the experimentally observed paracetamol encapsulation levels (5–8% of the initial drug level) in 50 mg ml−1 PLA microspheres, but only when initial paracetamol levels exceeded 5 mg ml−1. However, the mesoscale technique was unable to model the hydrophilic drug (isoniazid) encapsulation (4–9% of the initial drug level) which was observed in experiments. Molecular dynamics simulations using the MARTINI force field indicated that the self-assembly of GCPQ is rapid, with propofol residing at the interface between micellar hydrophobic and hydrophilic groups, and that there is a heterogeneous distribution of propofol within the GCPQ micelle population. GCPQ–propofol experiments also revealed a population of relatively empty and drug-filled GCPQ particles. PMID:20519214

  12. Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease.

    PubMed

    Ismail, Manal Fouad; Elmeshad, Aliaa Nabil; Salem, Neveen Abdel-Hameed

    2013-01-01

    To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl(3))-induced Alzheimer's model. Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl(3) (50 mg/kg/day). The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl(3), with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na(+)/K(+)-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl(3)-treated animals; however, RLs succeeded in normalization of AChE and Na(+)/K(+) ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl(3)-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl(3)-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain. RLs could be a potential drug-delivery system for ameliorating Alzheimer's disease.

  13. Parameterization of gaseous dry deposition in atmospheric chemistry models: Sensitivity to aerodynamic resistance formulations under statically stable conditions

    NASA Astrophysics Data System (ADS)

    Toyota, Kenjiro; Dastoor, Ashu P.; Ryzhkov, Andrei

    2016-12-01

    Turbulence controls the vertical transfer of momentum, heat and trace constituents in the atmospheric boundary layer. In the lowest 10% of this layer lies the surface boundary layer (SBL) where the vertical fluxes of transferred quantities have been successfully parameterized using the Monin-Obukhov similarity theory in weather forecast, climate and atmospheric chemistry models. However, there is a large degree of empiricism in the stability-correction parameterizations used to formulate eddy diffusivity and aerodynamic resistance particularly under strongly stable ambient conditions. Although the influence of uncertainties in stability-correction parameterizations on eddy diffusivity is actively studied in boundary-layer meteorological modeling, its impact on dry deposition in atmospheric chemistry modeling is not well characterized. In this study, we address this gap by providing the mathematical basis for the relationship between the formulations of vertical surface flux used in meteorological and atmospheric chemistry modeling communities, and by examining the sensitivity of the modeled dry deposition velocities in statically stable SBL to the choice of stability-correction parameterizations used in three operational and/or research environmental models (GEM/GEM-MACH, ECMWF IFS and CMAQ-MM5). Aerodynamic resistances (ra) calculated by the three sets of parameterizations are notably different from each other and are also different from those calculated by a "z-less" scaling formulation under strongly stable conditions (the bulk Richardson number > 0.2). Furthermore, we show that many atmospheric chemistry models calculate ra using formulations which are inconsistent with the derivation of micro-meteorological parameters. Finally, practical implications of the differences in stability-correction algorithms are discussed for the computations of dry deposition velocities of SO2, O3 and reactive bromine compounds for specific cases of stable SBL.

  14. Evaluation of antitussive activity of formulations with herbal extracts in sulphur dioxide (SO2) induced cough model in mice.

    PubMed

    Gupta, Y K; Katyal, Jatinder; Kumar, Gajendra; Mehla, Jogender; Katiyar, C K; Sharma, Naveen; Yadav, Satpal

    2009-01-01

    Cough is the most common symptom of respiratory diseases. When cough becomes serious, opioids are effective, but they have side effects like sedation, constipation, some addiction liability and also compromise the respiratory function. Therefore, there is need to have effective anti-tussive agent which do not have respiratory suppressant activity. The present study was carried out to evaluate anti-tussive activity of combination of herbal drugs as formulations in sulphur dioxide (SO2)-induced cough model in mice. Albino mice of either sex, weighing 25-30 g were divided into eight groups, (n = 6). Group 1 served as normal control, group 2 mice were given distilled water, group 3 was positive control and received codeine sulphate (10 mg/kg, p.o.) and group 4, 5, 6, 7 received coded 1 formulations 1, 2, 3 and 4 respectively at a dose of 0.3 ml/mice, orally, while group VIII was the vehicle control. Thirty minutes later, the mice were exposed to sulphur dioxide again for 45 sec. The mice were then placed in an observation chamber for counting of cough bouts, by two independent observers, for five minutes. All the formulations used showed significant antitussive activity in sulphur dioxide induced cough model. Thus, these formulations can prove to be useful for alleviating cough.

  15. Use of statistical modeling to predict the effect of formulation composition on conditioning shampoo performance.

    PubMed

    Lepilleur, Carole; Giovannitti-Jensen, Ann; Kyer, Carol

    2013-01-01

    Formulation composition has a dramatic influence on the performance of conditioning shampoos. The purpose of this study is to determine the factors affecting the performance of various cationic polymers in those systems. An experiment was conducted by varying the levels of three surfactants (sodium lauryl ether sulfate, sodium lauryl sulfate, and cocamidopropyl betaine) in formulations containing various cationic polymers such as cationic cassia derivatives of different cationic charge densities (1.9, 2.3, and 3.0 mEq/g), cationic guar (0.98 mEq/g), and cationic hydroxyethyl cellulose (1.03 mEq/g). The results show the formulation composition dramatically affects silicone and cationic polymer deposition. In particular, three parameters are of importance in determining deposition efficiency: ionic strength, surfactant (micelle) charge, and total amount of surfactant. The cationic polymer composition, molecular weight, and charge density are also important in determining which of the previous three parameters influence the performance most.

  16. Open-ended formulation of self-consistent field response theory with the polarizable continuum model for solvation.

    PubMed

    Di Remigio, Roberto; Beerepoot, Maarten T P; Cornaton, Yann; Ringholm, Magnus; Steindal, Arnfinn Hykkerud; Ruud, Kenneth; Frediani, Luca

    2016-12-21

    The study of high-order absorption properties of molecules is a field of growing importance. Quantum-chemical studies can help design chromophores with desirable characteristics. Given that most experiments are performed in solution, it is important to devise a cost-effective strategy to include solvation effects in quantum-chemical studies of these properties. We here present an open-ended formulation of self-consistent field (SCF) response theory for a molecular solute coupled to a polarizable continuum model (PCM) description of the solvent. Our formulation relies on the open-ended, density matrix-based quasienergy formulation of SCF response theory of Thorvaldsen, et al., [J. Chem. Phys., 2008, 129, 214108] and the variational formulation of the PCM, as presented by Lipparini et al., [J. Chem. Phys., 2010, 133, 014106]. Within the PCM approach to solvation, the mutual solute-solvent polarization is represented by means of an apparent surface charge (ASC) spread over the molecular cavity defining the solute-solvent boundary. In the variational formulation, the ASC is an independent, variational degree of freedom. This allows us to formulate response theory for molecular solutes in the fixed-cavity approximation up to arbitrary order and with arbitrary perturbation operators. For electric dipole perturbations, pole and residue analyses of the response functions naturally lead to the identification of excitation energies and transition moments. We document the implementation of this approach in the Dalton program package using a recently developed open-ended response code and the PCMSolver libraries and present results for one-, two-, three-, four- and five-photon absorption processes of three small molecules in solution.

  17. Sensitivity of secondary production and export flux to choice of trophic transfer formulation in marine ecosystem models

    NASA Astrophysics Data System (ADS)

    Anderson, Thomas R.; Hessen, Dag O.; Mitra, Aditee; Mayor, Daniel J.; Yool, Andrew

    2013-09-01

    The performance of four contemporary formulations describing trophic transfer, which have strongly contrasting assumptions as regards the way that consumer growth is calculated as a function of food C:N ratio and in the fate of non-limiting substrates, was compared in two settings: a simple steady-state ecosystem model and a 3D biogeochemical general circulation model. Considerable variation was seen in predictions for primary production, transfer to higher trophic levels and export to the ocean interior. The physiological basis of the various assumptions underpinning the chosen formulations is open to question. Assumptions include Liebig-style limitation of growth, strict homeostasis in zooplankton biomass, and whether excess C and N are released by voiding in faecal pellets or via respiration/excretion post-absorption by the gut. Deciding upon the most appropriate means of formulating trophic transfer is not straightforward because, despite advances in ecological stoichiometry, the physiological mechanisms underlying these phenomena remain incompletely understood. Nevertheless, worrying inconsistencies are evident in the way in which fundamental transfer processes are justified and parameterised in the current generation of marine ecosystem models, manifested in the resulting simulations of ocean biogeochemistry. Our work highlights the need for modellers to revisit and appraise the equations and parameter values used to describe trophic transfer in marine ecosystem models.

  18. The effect of formulation variables and breathing patterns on the site of nasal deposition in an anatomically correct model.

    PubMed

    Guo, Yang; Laube, Beth; Dalby, Richard

    2005-11-01

    This study was conducted to evaluate the effect of formulation variables and breathing patterns on aerosol distribution in the nasal cavity. Placebo nasal spray formulations containing 0.25% w/v Avicel CL611 (viscosity = 4 cP) and 2% w/v methylcellulose (MC; viscosity = 18.2 cP) were radiolabeled with (99m)Technicium. Following spraying into a silicone nose model, through which air was drawn at one of three constant rates (0, 10, and 20 L/min) or one of two breathing profiles (representing fast and slow inhalations), aerosol deposition in the model was quantified by gamma scintigraphy. Regional deposition was expressed as horizontal[inner, middle (h), outer] and vertical distribution [upper, middle (v), lower] in the nose model. Compared to 2% MC, Avicel CL611 significantly increased aerosol deposition in the middle (h) region of the nasal cavity under all breathing conditions, and in the inner region at 0 and 20 L/min and with a slow inhalation. The different breathing rates showed no effect on deposition of 2% MC. However, 10 L/min significantly increased the upper deposition of Avicel compared to 0 and 20 L/min. Nasal sprays with a low viscosity provided greater surface coverage of the nasal mucosa than higher viscosity formulations. Changes in breathing profiles did not affect aerosol deposition in this nose model.

  19. Behavioural and neurochemical evaluation of Perment an herbal formulation in chronic unpredictable mild stress induced depressive model.

    PubMed

    Ramanathan, M; Balaji, B; Justin, A

    2011-04-01

    Perment, a polyherbal Ayurvedic formulation that contains equal parts of Clitoria ternatea Linn., Withania somnifera Dun., Asparagus racemosus Linn., Bacopa monniera Linn., is used clinically as mood elevators. The aim of the present study was to explore the behavioural effects and to understand possible mode of action of Perment in stress induced depressive model. Chronic unpredictable mild stress (CUMS) was used to induce depression in rats. Open field exploratory behaviour, elevated plus maze, social interaction and behavioural despair tests were used to assess behaviour. Using standard protocols plasma noradrenaline, serotonin, corticosterone and brain/adrenal corticosterone levels were measured to support the behavioural effects of Perment. Exposure to CUMS for 21 days caused anxiety and depression in rats, as indicated by significant decrease in locomotor activity in the open field exploratory behaviour test and increased immobility period in the behavioural despair test. Perment predominantly exhibited antidepressant action than anxiolytic activity. Further Perment increased the plasma noradrenaline and serotonin levels in stressed rats. No significant alteration in the brain corticosterone level in stressed rats was observed with Perment treatment. However the adrenal corticosterone level is decreased with Perment. It can be concluded that the Perment formulation exhibited synergistic activity, has a significant antidepressant and anxiolytic activity, which may be mediated through adrenergic and serotonergic system activation. Currently the formulation is clinically used as anxiolytic but the present results suggest that the formulation can also be indicated in patients affected with depression.

  20. Uptake of phenothiazines by the harvested chylomicrons ex vivo model: influence of self-nanoemulsifying formulation design.

    PubMed

    Shahnaz, Gul; Hartl, Markus; Barthelmes, Jan; Leithner, Katharina; Sarti, Federica; Hintzen, Fabian; Rahmat, Deni; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

    2011-09-01

    The aim of this study was to examine the potential of self-nanoemulsifying drug delivery systems (SNEDDS) on the uptake of the lipophilic and poorly water soluble phenothiazines thioridazine and chlorpromazine with the isolated plasma derived chylomicron (CM) ex vivo model. The multi-component delivery systems were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation. The uptake of phenothiazines by isolated plasma derived chylomicrons was investigated with short chain triglyceride (SCT) SNEDDS, medium chain triglyceride (MCT) SNEDDS, and long chain triglyceride (LCT) SNEDDS. SNEDDS were also evaluated for their stabilities, dispersibilities, percentage transmittances and by particle size analyses. For thioridazine a 5.6-fold and for chlorpromazine a 3.7-fold higher CM uptake could be observed using a LCT-SNEDDS formulation compared to the drugs without formulation. In contrast, ex vivo uptake by isolated CM was not significantly increased by SNEDDS formulations based on MCT and SCT. Compared with isolated CM, the CM sizes were increased 2.5-fold in LCT-SNEDDS, whereas in MCT-SNEDDS or SCT-SNEDDS only a small, non-significant (P<0.05) increase in CM size was observed. These results show that distinct SNEDDS formulations containing phenothiazines are efficiently uptaken by plasma derived chylomicrons ex vivo.

  1. Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer’s disease

    PubMed Central

    Ismail, Manal Fouad; ElMeshad, Aliaa Nabil; Salem, Neveen Abdel-Hameed

    2013-01-01

    Background To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs) in comparison to rivastigmine solution (RS) was assessed in an aluminium chloride (AlCl3)-induced Alzheimer’s model. Methods Liposomes were prepared by lipid hydration (F1) and heating (F2) methods. Rats were treated with either RS or RLs (1 mg/kg/day) concomitantly with AlCl3 (50 mg/kg/day). Results The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm) than F2 (528.7 ± 15.5 nm), but both entrapped the same amount of the drug (92.1% ± 1.4%). After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethy-larginine levels. RS significantly attenuated acetylcholinesterase (AChE) activity, whereas Na+/K+-adenosine triphosphatase (ATPase) activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was evidenced by nearly preventing amyloid plaque formation, as shown in the histopathological examination of rat brain. Conclusion RLs could be a potential drug-delivery system for ameliorating Alzheimer’s disease. PMID:23378761

  2. A mixed-contact formulation for a dynamics simulation of flexible systems: An integration with model-reduction techniques

    NASA Astrophysics Data System (ADS)

    Starc, Blaž; Čepon, Gregor; Boltežar, Miha

    2017-04-01

    A new numerical procedure for efficient dynamics simulations of linear-elastic systems with unilateral contacts is proposed. The method is based on the event-driven integration of a contact problem with a combination of single- and set-valued force laws together with classical model-reduction techniques. According to the contact state, the developed event-driven integration enables the formulation of reduced system matrices. Moreover, to enable the transition among different reduced spaces the formulation of the initial conditions is also presented. The method has been developed separately for each of the four most popular model-reduction techniques (Craig-Bampton, MacNeal, Rubin and dual Craig-Bampton). The applicability of the newly presented method is demonstrated on a simple clamped-beam structure with a unilateral contact, which is excited with a harmonic force at the free end.

  3. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop

    PubMed Central

    Duan, J; Kesisoglou, F; Novakovic, J; Amidon, GL; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-01-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled “Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation.”1 The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole‐body framework.2 PMID:28571121

  4. Hypothesis Formulation, Model Interpretation, and Model Equivalence: Implications of a Mereological Causal Interpretation of Structural Equation Models

    ERIC Educational Resources Information Center

    Markus, Keith A.

    2008-01-01

    One can distinguish statistical models used in causal modeling from the causal interpretations that align them with substantive hypotheses. Causal modeling typically assumes an efficient causal interpretation of the statistical model. Causal modeling can also make use of mereological causal interpretations in which the state of the parts…

  5. A single MCR-ALS model for drug analysis in different formulations: Application on diazepam commercial preparations.

    PubMed

    De Luca, Michele; Ioele, Giuseppina; Spatari, Claudia; Ragno, Gaetano

    2017-02-05

    A multivariate curve resolution - alternating least squares (MCR-ALS) analysis was used to quantify diazepam (DZP) in thirty commercial liquid formulations. MCR calibration was run on the UV spectrophotometric data of the commercial DZP samples over the range 200-400nm, allowing the resolution of the drug signal and then the excipients contained in all the formulations. A single model MCR for the determination of the drug in all samples was then built through the adoption of the correlation constraint. This model was optimized by an appropriate selection of the most useful wavelength ranges and then validated on external samples. DZP concentrations in the pharmaceutical formulations were measured by HPLC-DAD analysis. The performance of the MCR model was compared with that from application of classical partial least squares regression (PLSR). The results, in terms of error of prediction, were very satisfactory, reaching a relative error below of 1.66% against 2.56%, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Effect of new polyherbal formulations DF1911, DF2112 and DF2813 on CFA induced inflammation in rat model.

    PubMed

    Nagarkar, Bhagyashri; Jagtap, Suresh

    2017-04-04

    Aim of the present study was to evaluate anti-inflammatory activity of newly developed polyherbal formulations DF1911, DF2112 and DF2813. These newly developed formulations are modifications of Dashamoola, a well known Ayurvedic formulation, along with addition of new plants. Complete Freund's adjuvant (CFA) induced inflammation in rat was used as an experimental model. Effects of the treatment in rats were monitored by physiological and biochemical parameters, histopathology and through gene expression studies. Diclofenac sodium showed maximum percentage inhibition (56.8 ± 3.5%) of paw edema followed by Dashamoola Kwatha (19.9 ± 1.8%). Among test formulations treated groups, DF1911 at 250 mg/kg bw (48.2 ± 5.4%, p < 0.001) and DF2112 at 250 mg/kg bw (49.9 ± 3.5%, p < 0.001) showed significant and maximum increase in percentage inhibition of paw edema as compared to Dashamoola Kwatha. Hematological alterations in CFA rats were normalized after treatment with test formulations. Results of serum markers and histopathological observations also supported the activity of formulations. Increased MDA levels in liver tissue of CFA injected animals significantly (p < 0.05) decreased by Diclofenac sodium and test formulation treated groups. DF1911, DF2112 and DF2813 showed down-regulation of IL1-β (~6.4-fold, ~5.2-fold and ~7.6-fold), IL-6 (~1.1-fold, ~1.6-fold and ~1.9-fold), TNF-α (~2.0-fold, ~4.6-fold and ~3.5-fold), and iNOS (~1.2-fold, ~1.8-fold and ~1.1-fold) in inflamed paw tissue compared to negative control group, respectively. The anti-inflammatory effects of DF1911 and DF2112 in rats were significantly higher than the Dashamoola Kwatha and are comparable to Diclofenac sodium.

  7. Pharmacokinetic modeling and simulation of gastrointestinal transit effects on plasma concentrations of drugs from mixed immediate-release and enteric-coated pellet formulations.

    PubMed

    Watanalumlerd, Prapoch; Christensen, J Mark; Ayres, James W

    2007-01-01

    Effects of gastrointestinal transit on plasma concentrations of drugs from mixed immediate-release and enteric-coated pellet formulation were simulated with models developed by including gastric emptying time and lag time of emptying. Models were evaluated by comparing simulated plasma concentrations of amphetamine from Monte Carlo simulations to available published data of a commercial mixed pellet formulation (Adderall XR). Results show that the plasma profile from the mixed pellet formulation does not mimic that from two immediate-release doses administered at different times. Instead, the plasma profile from the mixed pellets of amphetamine is similar to a typical sustained-release formulation. The pharmacokinetic models presented herein describe plasma concentrations of amphetamine from mixed pellet formulation quite well. The models and assumptions are general and can be applied to other drugs in similar mixed pellet dosage forms.

  8. Improvement in bone properties by using risedronate adsorbed hydroxyapatite novel nanoparticle based formulation in a rat model of osteoporosis.

    PubMed

    Sahana, H; Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, D Roy; Bhat, M R; Suresh, Sarasija; Rao, R Ramachandra; Mariappan, L

    2013-02-01

    A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500, 350 and 250 microg/kg intravenous single dose) and sodium risedronate (500 microg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 microg/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 microg/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.

  9. A Decentralized Approach to the Formulation of Hypotheses: A Hierarchical Structural Model for a Prion Self-Assembled System

    NASA Astrophysics Data System (ADS)

    Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin

    2016-07-01

    Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure.

  10. A Decentralized Approach to the Formulation of Hypotheses: A Hierarchical Structural Model for a Prion Self-Assembled System

    PubMed Central

    Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin

    2016-01-01

    Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure. PMID:27464832

  11. Application of RPMI 2650 as a cell model to evaluate solid formulations for intranasal delivery of drugs.

    PubMed

    Gonçalves, Vanessa S S; Matias, Ana A; Poejo, Joana; Serra, Ana T; Duarte, Catarina M M

    2016-12-30

    During the development of intranasal drug delivery systems for local/systemic effect or brain targeting, it is necessary to assess its cytotoxicity and drug transport through nasal epithelium. In order to avoid animal experiments or the use of excised tissues, in vitro cell models, such as RPMI 2650 cells, are being preferred during recent years. Nevertheless, the deposition of solid formulations into nasal cell layers with further transepithelial transport rate of drugs has been poorly studied or reported. Thus, the purpose of this work is to further investigate RPMI 2650 cell line as an effective alternative to animal tissues for solid drug-loaded formulations cytotoxicity and drug permeation studies in order to become an option as a tool for drug discovery. Furthermore, we wanted to determine the extent to which the administration of drugs in particulate forms would differ in relation to the permeability of the same compounds applied as solutions. RPMI 2650 cells were cultured in submersed or at air-liquid interface conditions and characterized regarding transepithelial electrical resistance (TEER) and production of mucus. Pure ketoprofen (used as model compound) and five formulations loaded with same drug, namely solid lipid particles (Gelucire 43/01™), structured lipid particles (Gelucire 43/01™:Glyceryl monooleate) and aerogel microparticles (Alginate, Alginate:Pectin, Alginate:Carrageenan), were evaluated with RPMI 2650 model in terms of cytotoxicity and permeability of drug (applied as solution, dispersion or powder+buffer). RPMI 2650 cells were capable to grow in monolayer and multilayer, showing the same permeability as excised human nasal mucosa for sodium fluorescein (paracellular marker), with analogous TEER values and production of mucus, as referred by other authors. None of the powders showed cytotoxicity when applied to RPMI 2650 cells. Regarding permeation of drug through cell layers, not only the form of application of powders but also their

  12. Comparison of neurofuzzy logic and neural networks in modelling experimental data of an immediate release tablet formulation.

    PubMed

    Shao, Qun; Rowe, Raymond C; York, Peter

    2006-08-01

    This study compares the performance of neurofuzzy logic and neural networks using two software packages (INForm and FormRules) in generating predictive models for a published database for an immediate release tablet formulation. Both approaches were successful in developing good predictive models for tablet tensile strength and drug dissolution profiles. While neural networks demonstrated a slightly superior capability in predicting unseen data, neurofuzzy logic had the added advantage of generating rule sets representing the cause-effect relationships contained in the experimental data.

  13. A half-analytical formulation for the impedance variation in axisymmetrical modelling of eddy current non destructive testing

    NASA Astrophysics Data System (ADS)

    Maouche, B.; Feliachi, M.; Khenfer, N.

    2006-01-01

    We present the calculation of the impedance variation using a half-analytical formulation based on coupled electromagnetic variables. Such a formulation concerns an axisymmetrical device constituted with a voltage supplied solenoïdal inductor and a conducting workpiece. In this field of modelling, authors have already developed a method [Maouche and Feliachi, J. Phys. III France 10, 1967 (1997)] that determines the current distribution inside inductor coil loops in the case of weak skin depth and a low number of these coil loops. In the proposed development, the number of loops is relatively large and the skin effect in these loops is negligible. This formulation uses a voltage excitation, which makes the source field depending on induced currents and permits to consider the real geometry of the inductor. The model is applied to study an eddy current non destructive testing (ECNDT) device. The variation of the system impedance is calculated in the case of an axisymmetrical device. The obtained modelling results are validated by comparison to measurements and finite element computations [Rémy, Ph.D. thesis, University of Compiègne, France, 1997; La et al., Rev. Prog. Quant. Non-Destructive Eval. 16A, 295 (1997)]. Once validated, the proposed model is applied to determine geometrical and physical characteristics of an ECNDT device. To assemble this interest, we visualise the evolution of the impedance variation according respectively to the air-gap, to the thickness of the workpiece and its electric conductivity. The model is implemented within a software tool (CECM: Coupling Electromagnetic Circuits Method) developed in Matlab environment.

  14. Volumetric formulation for a class of kinetic models with energy conservation.

    PubMed

    Sbragaglia, M; Sugiyama, K

    2010-10-01

    We analyze a volumetric formulation of lattice Boltzmann for compressible thermal fluid flows. The velocity set is chosen with the desired accuracy, based on the Gauss-Hermite quadrature procedure, and tested against controlled problems in bounded and unbounded fluids. The method allows the simulation of thermohydrodyamical problems without the need to preserve the exact space-filling nature of the velocity set, but still ensuring the exact conservation laws for density, momentum, and energy. Issues related to boundary condition problems and improvements based on grid refinement are also investigated.

  15. Influence of model complexity and problem formulation on the forces in the knee calculated using optimization methods

    PubMed Central

    2013-01-01

    Background Predictions of the forces transmitted by the redundant force-bearing structures in the knee are often performed using optimization methods considering only moment equipollence as a result of simplified knee modeling without ligament contributions. The current study aimed to investigate the influence of model complexity (with or without ligaments), problem formulation (moment equipollence with or without force equipollence) and optimization criteria on the prediction of the forces transmitted by the force-bearing structures in the knee. Methods Ten healthy young male adults walked in a gait laboratory while their kinematic and ground reaction forces were measured simultaneously. A validated 3D musculoskeletal model of the locomotor system with a knee model that included muscles, ligaments and articular surfaces was used to calculate the joint resultant forces and moments, and subsequently the forces transmitted in the considered force-bearing structures via optimization methods. Three problem formulations with eight optimization criteria were evaluated. Results Among the three problem formulations, simultaneous consideration of moment and force equipollence for the knee model with ligaments and articular contacts predicted contact forces (first peak: 3.3-3.5 BW; second peak: 3.2-4.2 BW; swing: 0.3 BW) that were closest to previously reported theoretical values (2.0-4.0 BW) and in vivo data telemetered from older adults with total knee replacements (about 2.8 BW during stance; 0.5 BW during swing). Simultaneous consideration of moment and force equipollence also predicted more physiological ligament forces (< 1.0 BW), which appeared to be independent of the objective functions used. Without considering force equipollence, the calculated contact forces varied from 1.0 to 4.5 BW and were as large as 2.5 BW during swing phase; the calculated ACL forces ranged from 1 BW to 3.7 BW, and those of the PCL from 3 BW to 7 BW. Conclusions Model complexity and problem

  16. Analysis and calculation of macrosegregation in a casting ingot. MPS solidification model. Volume 1: Formulation and analysis

    NASA Technical Reports Server (NTRS)

    Maples, A. L.; Poirier, D. R.

    1980-01-01

    The physical and numerical formulation of a model for the horizontal solidification of a binary alloy is described. It can be applied in an ingot. The major purpose of the model is to calculate macrosegregation in a casting ingot which results from flow of interdendritic liquid during solidification. The flow, driven by solidification contractions and by gravity acting on density gradients in the interdendritic liquid, was modeled as flow through a porous medium. The symbols used are defined. The physical formulation of the problem leading to a set of equations which can be used to obtain: (1) the pressure field; (2) the velocity field: (3) mass flow and (4) solute flow in the solid plus liquid zone during solidification is presented. With these established, the model calculates macrosegregation after solidification is complete. The numerical techniques used to obtain solution on a computational grid are presented. Results, evaluation of the results, and recommendations for future development of the model are given. The macrosegregation and flow field predictions for tin-lead, aluminum-copper, and tin-bismuth alloys are included as well as comparisons of some of the predictions with published predictions or with empirical data.

  17. The precision of DCE-MRI using the tissue homogeneity model with continuous formulation of the perfusion parameters.

    PubMed

    Bartoš, Michal; Jiřík, Radovan; Kratochvíla, Jiří; Standara, Michal; Starčuk, Zenon; Taxt, Torfinn

    2014-06-01

    The present trend in dynamic contrast-enhanced MRI is to increase the number of estimated perfusion parameters using complex pharmacokinetic models. However, less attention is given to the precision analysis of the parameter estimates. In this paper, the distributed capillary adiabatic tissue homogeneity pharmacokinetic model is extended by the bolus arrival time formulated as a free continuous parameter. With the continuous formulation of all perfusion parameters, it is possible to use standard gradient-based optimization algorithms in the approximation of the tissue concentration time sequences. This new six-parameter model is investigated by comparing Monte-Carlo simulations with theoretically derived covariance matrices. The covariance-matrix approach is extended from the usual analysis of the primary perfusion parameters of the pharmacokinetic model to the analysis of the perfusion parameters derived from the primary ones. The results indicate that the precision of the estimated perfusion parameters can be described by the covariance matrix for signal-to-noise ratio higher than~20dB. The application of the new analysis model on a real DCE-MRI data set is also presented. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Parallelized 3D CSEM modeling using edge-based finite element with total field formulation and unstructured mesh

    NASA Astrophysics Data System (ADS)

    Cai, Hongzhu; Hu, Xiangyun; Li, Jianhui; Endo, Masashi; Xiong, Bin

    2017-02-01

    We solve the 3D controlled-source electromagnetic (CSEM) problem using the edge-based finite element method. The modeling domain is discretized using unstructured tetrahedral mesh. We adopt the total field formulation for the quasi-static variant of Maxwell's equation and the computation cost to calculate the primary field can be saved. We adopt a new boundary condition which approximate the total field on the boundary by the primary field corresponding to the layered earth approximation of the complicated conductivity model. The primary field on the modeling boundary is calculated using fast Hankel transform. By using this new type of boundary condition, the computation cost can be reduced significantly and the modeling accuracy can be improved. We consider that the conductivity can be anisotropic. We solve the finite element system of equations using a parallelized multifrontal solver which works efficiently for multiple source and large scale electromagnetic modeling.

  19. Therapeutic evaluation of grain based functional food formulation in a geriatric animal model.

    PubMed

    Teradal, Deepa; Joshi, Neena; Aladakatti, Ravindranath H

    2017-08-01

    This study investigates the effect of wholesome grain based functional food formulation, on clinical and biochemical parameters in 24-30 months old Wistar albino geriatric rats, corresponding to human age 60-75 years. Animals were randomly divided into five, groups. Experimental diets were compared to the basal rat diet (Group I). Four food, formulation were-wheat based (Group II), finger millet based (Group III), wheat based, diet + fenugreek seed powder (Group IV), finger millet based diet + fenugreek powder, (Group V). These five types of diets were fed to the experimental rats for 6 weeks. Hematological and biochemical parameters were evaluated. The results showed that, feed intake was influenced by the type of feed. Diets supplemented with, fenugreek (Group IV) caused a significant increase in serum hemoglobin. The total serum protein values were significantly highest in Group III. Total serum albumin was found to be lower in Group I and highest in Group II. The concentration of BUN was highest in Group I and the lowest in control diet. Serum cholesterol and glucose were significantly reduced in Group IV. Several hematological and serum mineral values were influenced by the type of diet. The type of diet did not influence the organs weight. A moderate hypoglycemic and hypercholesterolemic effect was observed in composite mix fed rats. This study clearly justifies the recommendation to use wholesome grain based functional foods for geriatric population.

  20. Semisolid formulations containing cetirizine: human skin permeation and topical antihistaminic evaluation in a rabbit model.

    PubMed

    Ciurlizza, Claudia; Fernández, Francisco; Calpena, Ana Cristina; Lázaro, Raquel; Parra, Alexander; Clares, Beatriz

    2014-10-01

    Cetirizine dihydrochloride (CTZ) is a second-generation histamine H1 antagonist, effective for the treatment of a wide range of allergic diseases. It has been utilized for managing the symptoms of chronic urticaria and atopic skin conditions. Thus, two novel semisolid formulations, nanoemulsion (NE) and hydrogel (HG) were developed to study their potential utility as vehicles including cetirizine (CTZ) and evaluate the potential use as topical H1-antihistamines agents. The physicochemical and stability properties of both vehicles were tested. Drug release kinetics and human skin permeation studies were performed using Franz cells. The antihistaminic activity was assayed in New Zealand rabbits and compared with two commercial first generation antihistamines. Both formulations were stable and provided a sustained drug release. Amounts of CTZ remaining in the skin were higher for HG, showing the maximum biological effect at 30 min, similar to topical first generation H1-antihistamines commercially available. These results suggest that CTZ-HG could be a promising system for the treatment of topical allergy bringing rapid antihistaminic relief.

  1. Development of population pharmacokinetic models and optimal sampling times for ibuprofen tablet and suspension formulations in children with cystic fibrosis.

    PubMed

    Beringer, Paul; Aminimanizani, Amir; Synold, Timothy; Scott, Christy

    2002-04-01

    High-dose ibuprofen therapy has demonstrated to slow deterioration in pulmonary function in children with cystic fibrosis with mild lung disease. Therapeutic drug monitoring has been recommended to maintain peak concentrations within the range of 50 to 100 mg/L to ensure efficacy. Current methods for dosage individualization are based on dose proportionality using visual inspection of the peak concentration; however, because of interpatient variability in the absorption of the various formulations this method may result in incorrect assessments of the peak concentration achieved. Maximum a posteriori Bayesian analysis (MAP-B) has proven to be a useful and precise method of individualizing the dose of aminoglycosides but requires a description of the structural model. In this study we performed parametric population modeling analysis on plasma concentrations of ibuprofen after single doses of 20 to 30-mg/kg tablet or suspension in children with cystic fibrosis. Patients evaluated in this study were part of a single dose pharmacokinetic study that has been published previously. A one-compartment model with first order absorption and a lag time best described the data. The pharmacokinetic parameters differed significantly depending on the formulation administered. D-optimal sampling times for the suspension and tablet formulations are 0, 0.25 to 0.5, 1, and 3 to 4 hours and 0, 0.25 to 0.5, 1 to 1.5, and 5 hours respectively. Use of MAP-B analysis performed with the 4 d-optimal sampling strategy resulted in accurate and precise estimates of the pharmacokinetic parameters when compared with maximum likelihood analysis using the complete plasma concentrations data set. Further studies are needed to evaluate the performance of these models and the impact on patient outcomes.

  2. Viscoelastic-damage interface model formulation with friction to simulate the delamination growth in mode II shear

    NASA Astrophysics Data System (ADS)

    Goodarzi, Mohammad Saeed; Hosseini-Toudeshky, Hossein

    2017-02-01

    In this paper a formulation of a viscoelastic-damage interface model with friction in mode-II is presented. The cohesive constitutive law contains elastic and damage regimes. It has been assumed that the shear stress in the elastic regime follows the viscoelastic properties of the matrix material. The three element Voigt model has been used for the formulation of relaxation modulus of the material. Damage evolution proceeds according to the bilinear cohesive constitutive law combined with friction stress consideration. Combination of damage and friction is based on the presumption that the damaged area, related to an integration point, can be dismembered into the un-cracked area with the cohesive damage and cracked area with friction. Samples of a one element model have been presented to see the effect of parameters on the cohesive constitutive law. A comparison between the predicted results with available results of end-notched flexure specimens in the literature is also presented to verify the model. Transverse crack tension specimens are also simulated for different applied displacement velocities.

  3. Development and validation of a new LBM-MRT hybrid model with enthalpy formulation for melting with natural convection

    NASA Astrophysics Data System (ADS)

    Miranda Fuentes, Johann; Kuznik, Frédéric; Johannes, Kévyn; Virgone, Joseph

    2014-01-01

    This article presents a new model to simulate melting with natural convection of a phase change material. For the phase change problem, the enthalpy formulation is used. Energy equation is solved by a finite difference method, whereas the fluid flow is solved by the multiple relaxation time (MRT) lattice Boltzmann method. The model is first verified and validated using the data from the literature. Then, the model is applied to a tall brick filled with a fatty acid eutectic mixture and the results are presented. The main results are (1) the spatial convergence rate is of second order, (2) the new model is validated against data from the literature and (3) the natural convection plays an important role in the melting process of the fatty acid mixture considered in our work.

  4. Pharmacokinetic/pharmacodynamic model of the testosterone effects of triptorelin administered in sustained release formulations in patients with prostate cancer.

    PubMed

    Romero, Elba; Vélez de Mendizabal, Nieves; Cendrós, Josep-María; Peraire, Concepción; Bascompta, Emma; Obach, Rosendo; Trocóniz, Iñaki F

    2012-09-01

    The objectives of the current work were to develop a predictive population pharmacokinetic (PK)/pharmacodynamic (PD) model for the testosterone (TST) effects of triptorelin (TRP) administered in sustained-release (SR) formulations to patients with prostate cancer and determine the minimal required triptorelin serum concentration (C(TRP_min)) to keep the testosterone levels of the patients below or equal to the level of castration (TST ≤ 0.5 ng/ml). A total of eight healthy male volunteers and 74 patients with prostate cancer received one or two doses of triptorelin injected subcutaneously or intramuscularly. Five different triptorelin formulations were tested. Pharmacokinetic (serum concentration of triptorelin) and pharmacodynamic (TST levels in serum) data were analyzed by using the population approach with NONMEM software (http://www.iconplc.com/technology/products/nonmem/). The PK/PD model was constructed by assembling the agonist nature of triptorelin with the competitive reversible receptor binding interaction with the endogenous agonist, a process responsible for the initial and transient TST flare-up, and triggering down-regulation mechanisms described as a decrease in receptor synthesis. The typical population values of K(D), the receptor equilibrium dissociation constant of triptorelin, and C(TRP_min) to keep 95% of the patients castrated were 0.931 and 0.0609 ng/ml, respectively. The semimechanistic nature of the model renders the predictions of the effect of triptorelin on TST possible regardless the type of SR formulation administered, while exploring different designs during the development of new delivery systems.

  5. Comparison of signal to noise ratios from spatial and frequency domain formulations of nonprewhitening model observers in digital mammography

    SciTech Connect

    Sisini, Francesco; Zanca, Federica; Marshall, Nicholas W.; Taibi, Angelo; Cardarelli, Paolo; Bosmans, Hilde

    2012-09-15

    Purpose: Image quality indices based upon model observers are promising alternatives to laborious human readings of contrast-detail images. This is especially appealing in digital mammography as limiting values for contrast thresholds determine, according to some international protocols, the acceptability of these systems in the radiological practice. The objective of the present study was to compare the signal to noise ratios (SNR) obtained with two nonprewhitening matched filter model observer approaches, one in the spatial domain and the other in the frequency domain, and with both of them worked out for disks as present in the CDMAM phantom. Methods: The analysis was performed using images acquired with the Siemens Novation and Inspiration digital mammography systems. The spatial domain formulation uses a series of high dose CDMAM images as the signal and a routine exposure of two flood images to calculate the covariance matrix. The frequency domain approach uses the mathematical description of a disk and modulation transfer function (MTF) and noise power spectrum (NPS) calculated from images. Results: For both systems most of the SNR values calculated in the frequency domain were in very good agreement with the SNR values calculated in the spatial domain. Both the formulations in the frequency domain and in the spatial domain show a linear relationship between SNR and the diameter of the CDMAM discs. Conclusions: The results suggest that both formulations of the model observer lead to very similar figures of merit. This is a step forward in the adoption of figures of merit based on NPS and MTF for the acceptance testing of mammography systems.

  6. Use of the pentagastrin dog model to explore the food effects on formulations in early drug development.

    PubMed

    Zane, P; Guo, Z; MacGerorge, D; Vicat, P; Ollier, C

    2014-06-16

    The ability to extrapolate dosage performance from in vitro to in vivo situations has an important role in early drug development. In parallel, the Beagle dog has come to represent a useful animal model for extrapolation to humans especially when drugs formulated for humans are to be tested. In this article, the pentagastrin-induced Beagle dog model was validated internally to show that in the colony the dogs were generally responsive to known doses of pentagastrin that produces effects similar to gastrin in the stomach, i.e., increasing gastric acid production and lowering gastric pH. The effect was observed with a short time course, maximum pH lowering was observed between 0.5 and 1h with return to baseline at 2-4h. The dog stomach pH is a better representative of the human fasted stomach with this pretreatment. The ultimate goal was to use these animals in a food effect studies to predict the behavior of formulations in humans. The results for 4 compounds were provided in the dog and a clear relationship between the effect of food in the dog and the effect of food in humans was observed. While the directionality (positive or negative) of the effect could be adequately predicted, the extent of the effect could not be predicted for all the tested formulations of the 4 compounds. The data will be used to generate a database of known compounds from which a correlation can be drawn to make future predictions using the pentagastrin dog model. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. A formulation to compute mass-consistent models of hydrodynamic flows

    NASA Astrophysics Data System (ADS)

    Núñez, M. A.; Sánchez-Sánchez, J. E.

    2012-04-01

    Standard interpolation methods of measured data of an incompressible fluid yield a non-solenoidal field v 0. A formulation to estimate a solenoidal field from v 0, is proposed. Variational calculus reduces the problem to the solution of an elliptic equation for a Lagrange multiplier. Examples illustrate how boundary conditions improve the mass-balance of velocity fields obtained in meteorology with similar approaches. The elliptic equation is separable in meteorological problems over a complex orography. This allows the use of fast-Poisson solvers. It is shown how the flow-rate can be used to define a low-pass filter which improves the results given by the Fast Fourier Algorithm.

  8. Simulating groundwater flow and runoff for the Oro Moraine aquifer system. Part I. Model formulation and conceptual analysis

    NASA Astrophysics Data System (ADS)

    Beckers, J.; Frind, E. O.

    2000-04-01

    A steady-state groundwater model that incorporates the vadose zone in an approximate fashion is developed to account for situations where recharge may be significantly affected by heterogeneity above the water table. The model is intended for basin-scale applications where the exact representation of the unsaturated zone is no longer feasible. The pseudo-unsaturated model is compared to a variably saturated model making use of an idealized cross-section approximating the complex Oro Moraine aquifer system. Differences in predicted flow regimes between the two models arise from the coarser mesh used in the pseudo-unsaturated simulations, but are minimal below the water table. The pseudo-unsaturated model yields an accurate overall system water mass balance although a loss in spatial resolution of predicted fluxes may occur. Such accuracy losses are offset by drastically lower computer memory requirements. The flow simulations further show that near-surface heterogeneity has a profound impact on the sustainable capacity of a groundwater system and the location of sensitive recharge areas. The pseudo-unsaturated model is then coupled to a high-conductivity layer atop the model domain to simulate rainfall runoff. An important advantage of this model formulation is that precipitation and evapotranspiration measurements can be directly used as model input, while groundwater infiltration is part of the flow solution. Runoff and baseflow contributions to long-term streamflow generation are also calculated and can be compared to data from gauging stations during model calibration.

  9. A General Pressure Gradient Formulation for Ocean Models, Part 1: Scheme Design and Diagnostic Analysis, Part II: Energy, Momentum, and Bottom Torque Consistency

    NASA Technical Reports Server (NTRS)

    Song, Y. T.

    1998-01-01

    A Jacobian formulation of the pressure gradient force for use in models with topography following coordinates is proposed. It can be used in conjunction with any vertical coordinate system and is easily implemented.

  10. A General Pressure Gradient Formulation for Ocean Models, Part 1: Scheme Design and Diagnostic Analysis, Part II: Energy, Momentum, and Bottom Torque Consistency

    NASA Technical Reports Server (NTRS)

    Song, Y. T.

    1998-01-01

    A Jacobian formulation of the pressure gradient force for use in models with topography following coordinates is proposed. It can be used in conjunction with any vertical coordinate system and is easily implemented.

  11. Utility of PBPK Absorption Modeling to Guide Modified Release Formulation Development of Gaboxadol, a Highly Soluble Compound With Region-Dependent Absorption.

    PubMed

    Kesisoglou, Filippos; Balakrishnan, Anand; Manser, Kimberly

    2016-02-01

    Given the complexity of controlled release (CR) formulations, selecting the right preclinical tools is important to enable decision making on the in vivo performance of these formulations during development. In recent years, with the advancements of absorption/physiologically based pharmacokinetic (PBPK) modeling, such computational approaches play an increasing role in guiding formulation development. Development of PBPK models for CR formulations requires additional information compared with immediate release (IR) products. Perhaps the most important aspect is the need to simulate absorption in the lower intestine. Relatively few publications have investigated the use of PBPK models for compounds with region-dependent absorption. In this manuscript, we use gaboxadol as a model compound with region-dependent absorption. We first explored gaboxadol regional absorption in dogs to develop a PBPK model for absorption in the large intestine. Two matrix-based CR formulations were subsequently developed and tested in minipigs and demonstrated distinctly different pharmacokinetic profiles from the IR formulation. A minipig absorption PBPK model successfully predicted the observed plasma concentration data, with the predictions based on the in vitro dissolution being within the observed experimental variability. Finally, we demonstrate the development of an in vitro-in vivo correlation for the preclinical data using the same PBPK model.

  12. Effect of Trasina, an ayurvedic herbal formulation, on experimental models of Alzheimer's disease and central cholinergic markers in rats.

    PubMed

    Bhattacharya, S K; Kumar, A

    1997-01-01

    Trasina is a herbal formulation of some Indian medicinal plants classified in Ayurveda, the classic Indian system of medicine, as Medhyarasayanas or drugs reputed to improve memory and intellect. Earlier experimental and clinical investigations have indicated that the formulation has a memory-facilitating action. In this investigation, the effect of Trasina, after subchronic administration for 21 days, was assessed on two rodent models simulating some biochemical features known to be associated with Alzheimer's disease (AD). The models, in rats, included intracerebroventricularly (i.c.v.) administered colchicine (15 micrograms/rat) and lesioning of nucleus basalis magnocellularis (nbm) by ibotenic acid (10 micrograms/rat). Retention of an active avoidance response was used as the memory parameter. In addition, the effect of Trasina was evaluated on i.c.v. colchicine-induced depletion of acetylcholine (ACh) concentrations, reduction in choline acetyltransferase (ChAT) activity, and decrease in muscarinic cholinergic receptor (MCR) binding in rat brain frontal cortex and hippocampus. The behavioral and biochemical investigations were done 7, 14, and 21 days after colchicine or ibotenic acid lesioning. Trasina (200 and 500 mg/kg) was administered orally (p.o.) once daily for 21 days, the first drug administration being given just prior to lesioning. Colchicine and ibotenic acid induced marked retention deficit of active avoidance learning that was attenuated in a dose-dependent manner by Trasina after 14 and 21 days of treatment. Frontal cortical and hippocampal ACh concentrations, ChAT activity and MCR binding was significantly reduced after colchicine treatment. Trasina (200 and 500 mg/kg) reversed these deficits after 14 and 21 days of treatment. The findings indicate that the herbal formulation exerts a significant nootropic effect after subchronic treatment that may be due to reversal of perturbed cholinergic function.

  13. Predicting Cortisol Exposure from Paediatric Hydrocortisone Formulation Using a Semi-Mechanistic Pharmacokinetic Model Established in Healthy Adults.

    PubMed

    Melin, Johanna; Parra-Guillen, Zinnia P; Hartung, Niklas; Huisinga, Wilhelm; Ross, Richard J; Whitaker, Martin J; Kloft, Charlotte

    2017-07-31

    Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort(®) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort(®) or 20 mg of Infacort(®)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline cort,15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing <20 kg. Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing <20 kg. EudraCT number: 2013-000260-28, 2013-000259-42.

  14. Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics.

    PubMed

    Rodrigues de Azevedo, Cristiana; von Stosch, Moritz; Costa, Mariana S; Ramos, A M; Cardoso, M Margarida; Danhier, Fabienne; Préat, Véronique; Oliveira, Rui

    2017-10-30

    A substantial drug release from poly(lactic-co-glycolic) acid (PLGA) micro- and nanoparticles can occur in the first hours of immersion, which is referred to as burst release. A strong burst release (when not intentional) is to be avoided as it decreases the efficacy of the treatment and could be dangerous to the host. In this work we analyze the total amount of drug released during burst and respective kinetics in relation to formulations characteristics, experimental conditions and drug molecular properties in 154 drug release experiments with 41 different drugs by partial least squares (PLS) and decision tree regression. The model created enables to quantify to which degree the physicochemical parameters control the burst release from PLGA particles. Our analysis shows that the amount of drug released during burst is mostly influenced by the formulation characteristics and the synthesis parameters, whereas the drug release kinetics is also influenced by the molecular properties of the drug. The variables that significantly influence the amount and kinetics of the burst release are discussed in detail and compared with findings from other researchers. The final regression models are shown to predict the release profile of a new drug, opening the possibility to be applied to systematically manipulate the burst release by means of designing an optimized drug delivery system. Copyright © 2017. Published by Elsevier B.V.

  15. An atomic finite element model for biodegradable polymers. Part 1. Formulation of the finite elements.

    PubMed

    Gleadall, Andrew; Pan, Jingzhe; Ding, Lifeng; Kruft, Marc-Anton; Curcó, David

    2015-11-01

    Molecular dynamics (MD) simulations are widely used to analyse materials at the atomic scale. However, MD has high computational demands, which may inhibit its use for simulations of structures involving large numbers of atoms such as amorphous polymer structures. An atomic-scale finite element method (AFEM) is presented in this study with significantly lower computational demands than MD. Due to the reduced computational demands, AFEM is suitable for the analysis of Young's modulus of amorphous polymer structures. This is of particular interest when studying the degradation of bioresorbable polymers, which is the topic of an accompanying paper. AFEM is derived from the inter-atomic potential energy functions of an MD force field. The nonlinear MD functions were adapted to enable static linear analysis. Finite element formulations were derived to represent interatomic potential energy functions between two, three and four atoms. Validation of the AFEM was conducted through its application to atomic structures for crystalline and amorphous poly(lactide). Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Twisted C⋆-algebra formulation of quantum cosmology with application to the Bianchi I model

    NASA Astrophysics Data System (ADS)

    Rosenbaum, Marcos; Vergara, J. David; Juárez, Román; Minzoni, A. A.

    2014-04-01

    A twisted C⋆-algebra of the extended (noncommutative) Heisenberg-Weyl group has been constructed which takes into account the uncertainty principle for coordinates in the Planck-length regime. This general construction is then used to generate an appropriate Hilbert space and observables for the noncommutative theory which, when applied to the Bianchi I cosmology, leads to a new set of equations that describe the quantum evolution of the Universe. We find that this formulation matches theories based on a reticular Heisenberg-Weyl algebra in the bouncing and expanding regions of a collapsing Bianchi universe. There is, however, an additional effect introduced by the dynamics generated by the noncommutativity. This is an oscillation in the spectrum of the volume operator of the Universe, within the bouncing region of the commutative theories. We show that this effect is generic and produced by the noncommutative momentum exchange between the degrees of freedom in the cosmology. We give asymptotic and numerical solutions which show the above mentioned effects of the noncommutativity.

  17. Aerodynamic and electrostatic properties of model dry powder aerosols: a comprehensive study of formulation factors.

    PubMed

    Telko, M J; Hickey, A J

    2014-12-01

    The impact of formulation variables on aerodynamic and electrostatic properties of dry powder aerosol particles is of great importance to the development of efficient and reproducible inhaler products. Systematic evaluation requires a well-designed series of experiments using appropriate methods. A factorial experimental design was employed. In broad terms, the conditions considered were two drugs, albuterol and budesonide, in combination with different excipients, drug concentrations, delivered doses, and metering system (capsule composition) and sampled under different flow conditions using standard entrainment tubes. Samples were collected in an electrical low-pressure impactor, to evaluate distribution of electrostatic properties, and an Andersen eight-stage nonviable cascade impactor, to estimate aerodynamic particle size distribution, concurrently. The deposition studies allowed calculation of approximate per particle charge levels for drug. The results showed very high particle charge levels, often in the 1,000-10,000 of elementary charges per particle range, orders of magnitude higher than charge levels predicted by the Boltzmann charge distribution. The charge levels are considerably higher than had previously been estimated (200e per particle).

  18. The application of remote sensing to the development and formulation of hydrologic planning models

    NASA Technical Reports Server (NTRS)

    Fowler, T. R.; Castruccio, P. A.; Loats, H. L., Jr.

    1977-01-01

    The development of a remote sensing model and its efficiency in determining parameters of hydrologic models are reviewed. Procedures for extracting hydrologic data from LANDSAT imagery, and the visual analysis of composite imagery are presented. A hydrologic planning model is developed and applied to determine seasonal variations in watershed conditions. The transfer of this technology to a user community and contract arrangements are discussed.

  19. The application of remote sensing to the development and formulation of hydrologic planning models

    NASA Technical Reports Server (NTRS)

    Castruccio, P. A.; Loats, H. L., Jr.; Fowler, T. R.

    1976-01-01

    A hydrologic planning model is developed based on remotely sensed inputs. Data from LANDSAT 1 are used to supply the model's quantitative parameters and coefficients. The use of LANDSAT data as information input to all categories of hydrologic models requiring quantitative surface parameters for their effects functioning is also investigated.

  20. Evaluation of a photosyntheses-based canopy resistance formulation in the Noah Land-surface model

    USDA-ARS?s Scientific Manuscript database

    Accurately representing complex land-surface processes balancing complexity and realism remains one challenge that the weather modelling community is facing nowadays. In this study, a photosynthesis-based Gas-exchange Evapotranspiration Model (GEM) is integrated into the Noah land-surface model repl...

  1. Determination of the quench velocity and rewetting temperature of hot surfaces: Formulation of a nonisothermal microscale hydrodynamic model.

    PubMed

    David, M B; Zvirin, Y; Zimmels, Y

    1999-06-01

    A nonisothermal microscale model of the three-phase, solid-liquid-gas, contact zone is formulated in the context of rewetting phenomena. The model incorporates hydrodynamics, heat transfer, interfacial phenomena, and intermolecular long range forces, in a two-dimensional proximal region of the order of 1000 A in width and 100 A in thickness. The model comprises scaled mass, momentum, and energy balances, and their corresponding scaled boundary conditions. The small contact angles which are characteristic of rewetting situations facilitate the use of the lubrication approximation, and the dynamics of the liquid and gas phases is decoupled by applying the one-sided simplification. The microscale hydrodynamic model reflects the strong effect of the solid-liquid interactions on the film profile, and the attendant flow and thermal fields. Thinner films having smaller contact angles involve stronger solid-liquid attraction forces, and consequently they exhibit higher rewetting temperatures and lower evaporation and vapor recoil effects. Thermocapillary and evaporation and conduction effects are expressed by appropriate dimensionless numbers. A set of such numbers is defined in the context of the differential equations of the microscale model. This model covers the hydrodynamic aspect of rewetting phenomena, which are also controlled by thermodynamic and macroscale constraints. This calls for interfacing and appropriate combination between the microscale hydrodynamic model, thermodynamics, and other macroscale rewetting models, for the determination of rewetting temperatures and quench velocities of liquids on hot solid surfaces. This is addressed elsewhere, in subsequent papers that follow this work.

  2. An upscaled two-equation model of transport in porous media through unsteady-state closure of volume averaged formulations

    NASA Astrophysics Data System (ADS)

    Chaynikov, S.; Porta, G.; Riva, M.; Guadagnini, A.

    2012-04-01

    We focus on a theoretical analysis of nonreactive solute transport in porous media through the volume averaging technique. Darcy-scale transport models based on continuum formulations typically include large scale dispersive processes which are embedded in a pore-scale advection diffusion equation through a Fickian analogy. This formulation has been extensively questioned in the literature due to its inability to depict observed solute breakthrough curves in diverse settings, ranging from the laboratory to the field scales. The heterogeneity of the pore-scale velocity field is one of the key sources of uncertainties giving rise to anomalous (non-Fickian) dispersion in macro-scale porous systems. Some of the models which are employed to interpret observed non-Fickian solute behavior make use of a continuum formulation of the porous system which assumes a two-region description and includes a bimodal velocity distribution. A first class of these models comprises the so-called ''mobile-immobile'' conceptualization, where convective and dispersive transport mechanisms are considered to dominate within a high velocity region (mobile zone), while convective effects are neglected in a low velocity region (immobile zone). The mass exchange between these two regions is assumed to be controlled by a diffusive process and is macroscopically described by a first-order kinetic. An extension of these ideas is the two equation ''mobile-mobile'' model, where both transport mechanisms are taken into account in each region and a first-order mass exchange between regions is employed. Here, we provide an analytical derivation of two region "mobile-mobile" meso-scale models through a rigorous upscaling of the pore-scale advection diffusion equation. Among the available upscaling methodologies, we employ the Volume Averaging technique. In this approach, the heterogeneous porous medium is supposed to be pseudo-periodic, and can be represented through a (spatially) periodic unit cell

  3. Microscopic formulation of the Zimm-Bragg model for the helix-coil transition.

    PubMed

    Badasyan, A V; Giacometti, A; Mamasakhlisov, Y Sh; Morozov, V F; Benight, A S

    2010-02-01

    A microscopic spin model is proposed for the phenomenological Zimm-Bragg model for the helix-coil transition in biopolymers. This model is shown to provide the same thermophysical properties of the original Zimm-Bragg model and it allows a very convenient framework to compute statistical quantities. Physical origins of this spin model are made transparent by an exact mapping into a one-dimensional Ising model with an external field. However, the dependence on temperature of the reduced external field turns out to differ from the standard one-dimensional Ising model and hence it gives rise to different thermophysical properties, despite the exact mapping connecting them. We discuss how this point has been frequently overlooked in the recent literature.

  4. Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations.

    PubMed

    Brvar, Nina; Mateović-Rojnik, Tatjana; Grabnar, Iztok

    2014-10-01

    This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics. Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers. Tramadol plasma concentration-time data were described by an inverse Gaussian function to model the complete input process linked to a two-compartment disposition model with first-order elimination. Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model. The final model estimated parameters with reasonable precision and was able to estimate the interindividual variability of all parameters except for the relative bioavailability of PR vs. IR formulation. Validity of the model was further tested using the nonparametric bootstrap approach. Finally, the model was applied to assess absorption kinetics of tramadol and predict steady-state pharmacokinetics following administration of both types of formulations. For both formulations, the final model yielded a stable estimate of the absorption time profiles. Steady-state simulation supports switching of patients from IR to PR formulation.

  5. Antibacterial Efficacy against an In Vivo Salmonella typhimurium Infection Model and Pharmacokinetics of a Liposomal Ciprofloxacin Formulation

    PubMed Central

    Webb, Murray S.; Boman, Nancy L.; Wiseman, David J.; Saxon, Dawn; Sutton, Kym; Wong, Kim F.; Logan, Patricia; Hope, Michael J.

    1998-01-01

    The fluoroquinolone antibiotic ciprofloxacin has been encapsulated into large unilamellar vesicles (LUV) at efficiencies approaching 100%. Drug accumulation proceeded in response to a transmembrane gradient of methylammonium sulfate and occurred concomitantly with the efflux of methylamine. A mechanism for the encapsulation process is described. LUV composed of dipalmitoylphosphatidylcholine-cholesterol (DPPC/chol), distearoylphosphatidylcholine-cholesterol (DSPC/chol), or sphingomyelin-cholesterol (SM/chol) increased the circulation lifetime of ciprofloxacin after intravenous (i.v.) administration by >15-fold. The retention of ciprofloxacin in liposomes in the circulation decreased in the sequence SM/chol > DSPC/chol > DPPC/chol. Increased circulation lifetimes were associated with enhanced delivery of the drug to the livers, spleens, kidneys, and lungs of mice. Encapsulation of ciprofloxacin also conferred significant increases in the longevity of the drug in the plasma after intraperitoneal administration and in the lungs after intratracheal administration in comparison to free ciprofloxacin. The efficacy of a single i.v. administration of an SM/chol formulation of ciprofloxacin was measured in a Salmonella typhimurium infection model. At 20 mg of ciprofloxacin per kg of body weight, the encapsulated formulation resulted in 103- to 104-fold fewer viable bacteria in the livers and spleens of infected mice than was observed for animals treated with free ciprofloxacin. These results show the utility of liposomal encapsulation of ciprofloxacin in improving the pharmacokinetics, biodistribution, and antibacterial efficacy of the antibiotic. In addition, these formulations are well suited for i.v., intraperitoneal, and intratracheal or aerosol administration. PMID:9449259

  6. Multicomponent reactive transport modeling in variably saturated porous media using a generalized formulation for kinetically controlled reactions

    NASA Astrophysics Data System (ADS)

    Mayer, K. Ulrich; Frind, Emil O.; Blowes, David W.

    2002-09-01

    A generalized formulation for kinetically controlled reactions has been developed and incorporated into a multicomponent reactive transport model to facilitate the investigation of a large variety of problems involving inorganic and organic chemicals in variably saturated media. The general kinetic formulation includes intra-aqueous and dissolution-precipitation reactions in addition to geochemical equilibrium expressions for hydrolysis, aqueous complexation, oxidation-reduction, ion exchange, surface complexation, and gas dissolution-exsolution reactions. The generalized approach allows consideration of fractional order terms with respect to any dissolved species in terms of species activities or in terms of total concentrations, which facilitates the incorporation of a variety of experimentally derived rate expressions. Monod and inhibition terms can be used to describe microbially mediated reactions or to limit the reaction progress of inorganic reactions. Dissolution-precipitation reactions can be described as surface-controlled or transport-controlled reactions. The formulation also facilitates the consideration of any number of parallel reaction pathways, and reactions can be treated as irreversible or reversible processes. Two groundwater contamination scenarios, both set in variably saturated media but with significantly different geochemical reaction networks, are investigated and demonstrate the advantage of the generalized approach. The first problem focuses on a hypothetical case study of the natural attenuation of organic contaminants undergoing dissolution, volatilization, and biodegradation in an unconfined aquifer overlaid by unsaturated sediments. The second problem addresses the generation of acid mine drainage in the unsaturated zone of a tailings impoundment at the Nickel Rim Mine Site near Sudbury, Ontario, and subsequent reactive transport in the saturated portion of the tailings.

  7. In vivo imaging of a new indocyanine green micelle formulation in an animal model of laser-induced choroidal neovascularization.

    PubMed

    Meyer, Johanna; Cunea, Alexander; Sonntag-Bensch, Dagmar; Welker, Pia; Licha, Kai; Holz, Frank G; Schmitz-Valckenberg, Steffen

    2014-09-04

    We investigated a novel formulation of indocyanine green (ICG/HS 15) in an animal model of laser-induced choroidal neovascularization (CNV). The ICG was formulated with the nonionic solubilizer and emulsifying agent Kolliphor HS 15 to create ICG/HS 15 to improve the chemical stability and fluorescence efficacy. In vivo imaging was performed in rats that had undergone laser photocoagulation. Retinal uptake and fluorescence intensity of ICG and ICG/HS 15 were compared following intravenous injection of 3 dosages (0.05, 0.1, and 0.15 mg/kg body weight) at 7, 14, and 21 days following laser treatment. Postmortem analysis included histology with frozen sections and flat mounts. Immediately following injection of ICG or ICG/HS 15, a strong fluorescence was visible in the retinal vasculature and at the site of laser lesions. Pixel intensity was higher for ICG/HS 15 compared to conventional ICG at 8 minutes after injection for all different injection days and dosages. Over time, a continuous decrease of the fluorescent signal was observed for up to 60 minutes to baseline level. Flow cytometry data showed an increased uptake of micellar dye of macrophages and endothelial cells. Histology revealed an accumulation of the micellar dye within the laser lesion. Micelle formulated ICG can be visualized in the retinal vasculature and laser-induced CNV in vivo and ex vivo. Micellar ICG/HS 15 showed in vivo stronger signal intensity when compared to ICG for all tested dosages. Following further investigations, ICG/HS 15 may be evaluated in patients with retinal and choroidal diseases for more refined diagnosis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  8. Evaluation of different fluoridated dentifrice formulations using an in situ erosion remineralization model.

    PubMed

    Barlow, A P; Sufi, F; Mason, S C

    2009-01-01

    The objective of these three clinical in situ studies was to investigate the relative performance of commercially available and experimental dentifrice formulations, having different fluoride sources and excipient ingredients, at remineralizing a bovine enamel surface previously softened by a dietary acid challenge. Each study utilized the same randomized, placebo-controlled, single-blind, crossover design. Subjects undertook single brushings of their natural teeth, with an in situ appliance in place, using different dentifrices in a randomly assigned order. Study A involved 58 subjects with the following dentifrices: Sensodyne Pronamel (1450 ppm F as NaF/5% KNO3); Blend-a-Med Classic (1450 ppm F as NaF); and a matched (Pronamel) placebo control (0 ppm F). Study B involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Crest Cavity Protection (1100 ppm F as NaF); Crest Pro-Health (0.454% SnF2 [1100 ppm F]/sodium hexametaphosphate); and a matched (Pronamel) placebo control (0 ppm F). Study C involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Sensodyne Pronamel Gentle Whitening (1150 ppm F as NaF/5% KNO3); Colgate Sensitive Multi Protection (1000 ppm F as NaMFP/5.53% potassium citrate/2% zinc citrate); and a matched (Pronamel) placebo control (0 ppm F). Subjects wore their palatal appliances holding eight bovine enamel blocks, previously exposed for 25 minutes to an in vitro erosive challenge with grapefruit juice, for the duration of the experiment. Five minutes after appliance insertion, subjects undertook a supervised, 90-second brush/rinse regimen with their assigned dentifrice. Surface microhardness (SMH) of the specimens was determined prior to the erosive challenge (baseline), after the in vitro erosive challenge, and were remeasured after four hours in situ remineralization following the tooth brushing event. Finally, SMH values were determined after a second in

  9. Parallelization of the integral equation formulation of the polarizable continuum model for higher-order response functions

    NASA Astrophysics Data System (ADS)

    Ferrighi, Lara; Frediani, Luca; Fossgaard, Eirik; Ruud, Kenneth

    2006-10-01

    We present a parallel implementation of the integral equation formalism of the polarizable continuum model for Hartree-Fock and density functional theory calculations of energies and linear, quadratic, and cubic response functions. The contributions to the free energy of the solute due to the polarizable continuum have been implemented using a master-slave approach with load balancing to ensure good scalability also on parallel machines with a slow interconnect. We demonstrate the good scaling behavior of the code through calculations of Hartree-Fock energies and linear, quadratic, and cubic response function for a modest-sized sample molecule. We also explore the behavior of the parallelization of the integral equation formulation of the polarizable continuum model code when used in conjunction with a recent scheme for the storage of two-electron integrals in the memory of the different slaves in order to achieve superlinear scaling in the parallel calculations.

  10. A linearized kinetic formulation including a second-order slip model for an impulsive start problem at arbitrary Knudsen numbers

    NASA Astrophysics Data System (ADS)

    Hadjiconstantinou, N. G.; Al-Mohssen, H. A.

    2005-06-01

    We investigate the time evolution of an impulsive start problem for arbitrary Knudsen numbers (Kn) using a linearized kinetic formulation. The early-time behaviour is described by a solution of the collisionless Boltzmann equation. The same solution can be used to describe the late-time behaviour for Kn ≫ 1. The late-time behaviour for Kn < 0.5 is captured by a newly proposed second-order slip model with no adjustable parameters. All theoretical results are verified by direct Monte Carlo solutions of the nonlinear Boltzmann equation. A measure of the timescale to steady state, normalized by the momentum diffusion timescale, shows that the timescale to steady state is significantly extended by ballistic transport, even at low Knudsen numbers where the latter is only important close to the system walls. This effect is captured for Kn < 0.5 by the slip model which predicts the equivalent effective domain size increase (slip length).

  11. Parallelization of the integral equation formulation of the polarizable continuum model for higher-order response functions.

    PubMed

    Ferrighi, Lara; Frediani, Luca; Fossgaard, Eirik; Ruud, Kenneth

    2006-10-21

    We present a parallel implementation of the integral equation formalism of the polarizable continuum model for Hartree-Fock and density functional theory calculations of energies and linear, quadratic, and cubic response functions. The contributions to the free energy of the solute due to the polarizable continuum have been implemented using a master-slave approach with load balancing to ensure good scalability also on parallel machines with a slow interconnect. We demonstrate the good scaling behavior of the code through calculations of Hartree-Fock energies and linear, quadratic, and cubic response function for a modest-sized sample molecule. We also explore the behavior of the parallelization of the integral equation formulation of the polarizable continuum model code when used in conjunction with a recent scheme for the storage of two-electron integrals in the memory of the different slaves in order to achieve superlinear scaling in the parallel calculations.

  12. Integration of fuzzy analytic hierarchy process and probabilistic dynamic programming in formulating an optimal fleet management model

    NASA Astrophysics Data System (ADS)

    Teoh, Lay Eng; Khoo, Hooi Ling

    2013-09-01

    This study deals with two major aspects of airlines, i.e. supply and demand management. The aspect of supply focuses on the mathematical formulation of an optimal fleet management model to maximize operational profit of the airlines while the aspect of demand focuses on the incorporation of mode choice modeling as parts of the developed model. The proposed methodology is outlined in two-stage, i.e. Fuzzy Analytic Hierarchy Process is first adopted to capture mode choice modeling in order to quantify the probability of probable phenomena (for aircraft acquisition/leasing decision). Then, an optimization model is developed as a probabilistic dynamic programming model to determine the optimal number and types of aircraft to be acquired and/or leased in order to meet stochastic demand during the planning horizon. The findings of an illustrative case study show that the proposed methodology is viable. The results demonstrate that the incorporation of mode choice modeling could affect the operational profit and fleet management decision of the airlines at varying degrees.

  13. Application of remote sensing to hydrology. [for the formulation of watershed behavior models

    NASA Technical Reports Server (NTRS)

    Ambaruch, R.; Simmons, J. W.

    1973-01-01

    Streamflow forecasting and hydrologic modelling are considered in a feasibility assessment of using the data produced by remote observation from space and/or aircraft to reduce the time and expense normally involved in achieving the ability to predict the hydrological behavior of an ungaged watershed. Existing watershed models are described, and both stochastic and parametric techniques are discussed towards the selection of a suitable simulation model. Technical progress and applications are reported and recommendations are made for additional research.

  14. Plan, formulate, and discuss a NASTRAN finite element model of the AH-64A helicopter airframe

    NASA Technical Reports Server (NTRS)

    Christ, Richard A.; Ferg, Douglas A.; Kilroy, Kevin A.; Toossi, Mostafa; Weisenburger, Richard K.

    1990-01-01

    A discussion of modeling plan objectives, followed by a description of the AH-64A aircraft including all general features, major components, and primary and structure definitions are presented. Following the aircraft description, a discussion of the modeling guidelines and model checkout procedure are provided. The NASTRAN finite element analysis is set up to be suitable to predict both static internal loads and vibrations. Finally, the results, schedule, and planned versus actual manhours for this work are presented.

  15. Comparison of the antifungal efficacy of terbinafine hydrochloride and ciclopirox olamine containing formulations against the dermatophyte Trichophyton rubrum in an infected nail plate model.

    PubMed

    Täuber, Anja; Müller-Goymann, Christel C

    2014-07-07

    Onychomycosis is a fungal infection mostly induced by dermatophytes such as Trichophyton rubrum. Due to slow nail growth, the treatment takes 3-9 months depending on the nail size and infected area. Hence, high efficacy of the active ingredient without systemic side effects is of major interest. To test the efficacy of an antifungal formulation, an appropriate in vitro model reflecting the in vivo situation as close as possible is required. In this study, a variety of antifungal formulations, i.e., commercial ones (Ciclopoli and Lamisil cream), those used in compounding pharmacies (Pentravan) as well as poloxamer 407-based systems, have been evaluated in an infected nail plate model. The active pharmaceutical ingredients (APIs) were ciclopirox olamine and terbinafine hydrochloride. The poloxamer 407-based formulations consisted of poloxamer 407, double distilled water, propylene glycol, isopropyl alcohol, medium chain triglycerides and either 1% ciclopirox olamine or 1% terbinafine hydrochloride as API, respectively. Former studies have shown high permeation rates of terbinafine hydrochloride from similar poloxamer 407-based formulations with dimethyl isosorbide instead of propylene glycol. The present contribution shows superior inhibition of T. rubrum growth from poloxamer 407-based formulations in comparison to the commercial Lamisil cream. Moreover, poloxamer 407-based formulations were equally effective as the nail lacquer Ciclopoli even though the poloxamer formulations contained only 1% of the drug instead of 8% in the marketed lacquer. Poloxamer 407-based systems containing ciclopirox olamine proved to be about as effective as similar terbinafine hydrochloride systems.

  16. Integrated surface/subsurface permafrost thermal hydrology: Model formulation and proof-of-concept simulations

    SciTech Connect

    Painter, Scott L.; Coon, Ethan T.; Atchley, Adam L.; Berndt, Markus; Garimella, Rao; Moulton, J. David; Svyatskiy, Daniil; Wilson, Cathy J.

    2016-08-11

    The need to understand potential climate impacts and feedbacks in Arctic regions has prompted recent interest in modeling of permafrost dynamics in a warming climate. A new fine-scale integrated surface/subsurface thermal hydrology modeling capability is described and demonstrated in proof-of-concept simulations. The new modeling capability combines a surface energy balance model with recently developed three-dimensional subsurface thermal hydrology models and new models for nonisothermal surface water flows and snow distribution in the microtopography. Surface water flows are modeled using the diffusion wave equation extended to include energy transport and phase change of ponded water. Variation of snow depth in the microtopography, physically the result of wind scour, is also modeled heuristically with a diffusion wave equation. The multiple surface and subsurface processes are implemented by leveraging highly parallel community software. Fully integrated thermal hydrology simulations on the tilted open book catchment, an important test case for integrated surface/subsurface flow modeling, are presented. Fine-scale 100-year projections of the integrated permafrost thermal hydrological system on an ice wedge polygon at Barrow Alaska in a warming climate are also presented. Finally, these simulations demonstrate the feasibility of microtopography-resolving, process-rich simulations as a tool to help understand possible future evolution of the carbon-rich Arctic tundra in a warming climate.

  17. A one-dimensional interactive soil-atmosphere model for testing formulations of surface hydrology

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Eagleson, Peter S.

    1990-01-01

    A model representing a soil-atmosphere column in a GCM is developed for off-line testing of GCM soil hydrology parameterizations. Repeating three representative GCM sensitivity experiments with this one-dimensional model demonstrates that, to first order, the model reproduces a GCM's sensitivity to imposed changes in parameterization and therefore captures the essential physics of the GCM. The experiments also show that by allowing feedback between the soil and atmosphere, the model improves on off-line tests that rely on prescribed precipitation, radiation, and other surface forcing.

  18. Integrated surface/subsurface permafrost thermal hydrology: Model formulation and proof-of-concept simulations

    SciTech Connect

    Painter, Scott L.; Coon, Ethan T.; Atchley, Adam L.; Berndt, Markus; Garimella, Rao; Moulton, J. David; Svyatskiy, Daniil; Wilson, Cathy J.

    2016-08-11

    The need to understand potential climate impacts and feedbacks in Arctic regions has prompted recent interest in modeling of permafrost dynamics in a warming climate. A new fine-scale integrated surface/subsurface thermal hydrology modeling capability is described and demonstrated in proof-of-concept simulations. The new modeling capability combines a surface energy balance model with recently developed three-dimensional subsurface thermal hydrology models and new models for nonisothermal surface water flows and snow distribution in the microtopography. Surface water flows are modeled using the diffusion wave equation extended to include energy transport and phase change of ponded water. Variation of snow depth in the microtopography, physically the result of wind scour, is also modeled heuristically with a diffusion wave equation. The multiple surface and subsurface processes are implemented by leveraging highly parallel community software. Fully integrated thermal hydrology simulations on the tilted open book catchment, an important test case for integrated surface/subsurface flow modeling, are presented. Fine-scale 100-year projections of the integrated permafrost thermal hydrological system on an ice wedge polygon at Barrow Alaska in a warming climate are also presented. Finally, these simulations demonstrate the feasibility of microtopography-resolving, process-rich simulations as a tool to help understand possible future evolution of the carbon-rich Arctic tundra in a warming climate.

  19. Integrated surface/subsurface permafrost thermal hydrology: Model formulation and proof-of-concept simulations

    NASA Astrophysics Data System (ADS)

    Painter, Scott L.; Coon, Ethan T.; Atchley, Adam L.; Berndt, Markus; Garimella, Rao; Moulton, J. David; Svyatskiy, Daniil; Wilson, Cathy J.

    2016-08-01

    The need to understand potential climate impacts and feedbacks in Arctic regions has prompted recent interest in modeling of permafrost dynamics in a warming climate. A new fine-scale integrated surface/subsurface thermal hydrology modeling capability is described and demonstrated in proof-of-concept simulations. The new modeling capability combines a surface energy balance model with recently developed three-dimensional subsurface thermal hydrology models and new models for nonisothermal surface water flows and snow distribution in the microtopography. Surface water flows are modeled using the diffusion wave equation extended to include energy transport and phase change of ponded water. Variation of snow depth in the microtopography, physically the result of wind scour, is modeled phenomenologically with a diffusion wave equation. The multiple surface and subsurface processes are implemented by leveraging highly parallel community software. Fully integrated thermal hydrology simulations on the tilted open book catchment, an important test case for integrated surface/subsurface flow modeling, are presented. Fine-scale 100 year projections of the integrated permafrost thermal hydrological system on an ice wedge polygon at Barrow Alaska in a warming climate are also presented. These simulations demonstrate the feasibility of microtopography-resolving, process-rich simulations as a tool to help understand possible future evolution of the carbon-rich Arctic tundra in a warming climate.

  20. Integrated surface/subsurface permafrost thermal hydrology: Model formulation and proof-of-concept simulations

    DOE PAGES

    Painter, Scott L.; Coon, Ethan T.; Atchley, Adam L.; ...

    2016-08-11

    The need to understand potential climate impacts and feedbacks in Arctic regions has prompted recent interest in modeling of permafrost dynamics in a warming climate. A new fine-scale integrated surface/subsurface thermal hydrology modeling capability is described and demonstrated in proof-of-concept simulations. The new modeling capability combines a surface energy balance model with recently developed three-dimensional subsurface thermal hydrology models and new models for nonisothermal surface water flows and snow distribution in the microtopography. Surface water flows are modeled using the diffusion wave equation extended to include energy transport and phase change of ponded water. Variation of snow depth in themore » microtopography, physically the result of wind scour, is also modeled heuristically with a diffusion wave equation. The multiple surface and subsurface processes are implemented by leveraging highly parallel community software. Fully integrated thermal hydrology simulations on the tilted open book catchment, an important test case for integrated surface/subsurface flow modeling, are presented. Fine-scale 100-year projections of the integrated permafrost thermal hydrological system on an ice wedge polygon at Barrow Alaska in a warming climate are also presented. Finally, these simulations demonstrate the feasibility of microtopography-resolving, process-rich simulations as a tool to help understand possible future evolution of the carbon-rich Arctic tundra in a warming climate.« less

  1. Spectroscopic-Based Chemometric Models for Quantifying Low Levels of Solid-State Transitions in Extended Release Theophylline Formulations.

    PubMed

    Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval A; Khan, Mansoor A

    2016-01-01

    Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q(2) were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products. Copyright © 2016. Published by Elsevier Inc.

  2. A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.

    PubMed

    Gharagozloo, P; Gutiérrez-Adán, A; Champroux, A; Noblanc, A; Kocer, A; Calle, A; Pérez-Cerezales, S; Pericuesta, E; Polhemus, A; Moazamian, A; Drevet, J R; Aitken, R J

    2016-02-01

    Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress? Oral administration of a novel antioxidant formulation significantly reduced sperm DNA damage in glutathione peroxidase 5 (GPX5), knockout mice and restored pregnancy rates to near-normal levels in mice subjected to scrotal heat stress. Animal and human studies have documented the adverse effect of sperm DNA damage on fertilization rates, embryo quality, miscarriage rates and the transfer of de novo mutations to offspring. Semen samples of infertile men are known to be deficient in several key antioxidants relative to their fertile counterparts. Antioxidants alone or in combination have demonstrated limited efficacy against sperm oxidative stress and DNA damage in numerous human clinical trials, however these studies have not been definitive and an optimum combination has remained elusive. The efficacy of the antioxidant formulation was evaluated in two well-established mouse models of oxidative stress, scrotal heating and Gpx5 knockout (KO) mice, (n = 12 per experimental group), by two independent laboratories. Mice were provided the antioxidant product in their drinking water for 2-8 weeks and compared with control groups for sperm DNA damage and pregnancy rates. In the Gpx5 KO model, oxidative DNA damage was monitored in spermatozoa by immunocytochemical detection of 8-hydroxy-2'-deoxyguanosine (8OHdG). In the scrotal heat stress model, male fertility was tested by partnering with three females for 5 days. The percentage of pregnant females, number of vaginal plugs, resorptions per litter, and litter size were recorded. Using immunocytochemical detection of 8OHdG as a biomarker of DNA oxidation, analysis of control mice revealed that around 30% of the sperm population was positively stained. This level increased to about 60% in transgenic mice deficient in the

  3. Formulating "Principles of Procedure" for the Foreign Language Classroom: A Framework for Process Model Language Curricula

    ERIC Educational Resources Information Center

    Villacañas de Castro, Luis S.

    2016-01-01

    This article aims to apply Stenhouse's process model of curriculum to foreign language (FL) education, a model which is characterized by enacting "principles of procedure" which are specific to the discipline which the school subject belongs to. Rather than to replace or dissolve current approaches to FL teaching and curriculum…

  4. The application of remote sensing to the development and formulation of hydrologic planning models

    NASA Technical Reports Server (NTRS)

    Castruccio, P. A.; Loats, H. L., Jr.; Fowler, T. R.; Frech, S. L.

    1975-01-01

    Regional hydrologic planning models built upon remote sensing capabilities and suited for ungaged watersheds are developed. The effectiveness of such models is determined along with which parameters impact most the minimization of errors associated with the prediction of peak flow events (floods). Emphasis is placed on peak flood prediction because of its significance to users for the purpose of planning, sizing, and designing waterworks.

  5. Formulating "Principles of Procedure" for the Foreign Language Classroom: A Framework for Process Model Language Curricula

    ERIC Educational Resources Information Center

    Villacañas de Castro, Luis S.

    2016-01-01

    This article aims to apply Stenhouse's process model of curriculum to foreign language (FL) education, a model which is characterized by enacting "principles of procedure" which are specific to the discipline which the school subject belongs to. Rather than to replace or dissolve current approaches to FL teaching and curriculum…

  6. Infected nail plate model made of human hair keratin for evaluating the efficacy of different topical antifungal formulations against Trichophyton rubrum in vitro.

    PubMed

    Lusiana; Reichl, Stephan; Müller-Goymann, Christel C

    2013-08-01

    A novel model of infected nail plate for testing the efficacy of topical antifungal formulations has been developed. This model utilized keratin film made of human hair keratin as a nail plate model. Subsequent to infection by Trichophyton rubrum, the common causative agent of onychomycosis, keratin films as infected nail plate models were treated with selected topical formulations, that is cream, gel, and nail lacquer. Bovine hoof was compared to keratin film. In contrast to the common antifungal susceptibility test, the antifungal drugs tested were applied as ready-to-use formulations because the vehicle may modify and control the drug action both in vitro and in vivo. Extrapolating the potency of an antifungal drug from an in vitro susceptibility test only would not be representative of the in vivo situation since these drugs are applied as ready-to-use formulations, for example as a nail lacquer. Although terbinafine has been acknowledged to be the most effective antifungal agent against T. rubrum, its antifungal efficacy was improved by its incorporation into an optimal formulation. Different gels proved superior to cream. Therefore, this study is able to discriminate between efficacies of different topical antifungal formulations based on their activities against T. rubrum. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Exploratory Randomized Clinical Trial of an Experimental Gel-to-Foam Fluoride Dentifrice Formulation Using an In Situ Caries Model.

    PubMed

    Barlow, Ashley; Butler, Andrew; Mason, Stephen; Zero, Domenick

    2015-01-01

    To evaluate the in situ caries performance and safety of two experimental fluoride dentifrice formulations (1450 ppm fluoride) with and without 2% isopentane as an excipient, in comparison to a positive control, currently marketed dentifrice (1450 ppm fluoride) and a negative control dentifrice (0 ppm fluoride). This was a single-center, examiner-blind, randomized, controlled, four-treatment cross-over study. During each treatment period, the subject wore a modified mandibular partial denture fitted with two gauze-covered, partially demineralized human enamel specimens, and brushed at home for one timed minute, twice daily, for two weeks. At the end of each treatment period, the enamel specimens were removed from the dentures for analysis. During the week between treatment periods, subjects returned to their usual dental hygiene practices for four to five days, received a dental prophylaxis, and used a study-designated non-fluoride dentifrice for two to three days before starting the next treatment. Treatment effect on enamel specimen remineralization was assessed by surface microhardness (SMH). Enamel fluoride uptake was assessed using microdrill enamel biopsy. All fluoride-containing dentifrices demonstrated significant, superior SMH recovery and levels of fluoride uptake compared to the negative control dentifrice. No significant differences were observed for either efficacy variable between the experimental dentifrice formulations and the positive control dentifrice. No significant difference was observed between the 2% isopentane dentifrice and the 0% isopentane dentifrice for SMH recovery. The addition of 2% isopentane did not positively or negatively affect fluoride efficacy in this model.

  8. Classical and Quantum Formulations of S1xS2 and S3 Gowdy Models Coupled with Matter

    NASA Astrophysics Data System (ADS)

    Gómez Vergel, Daniel

    2009-10-01

    We explore the features of gravity in its quantum regime in a mathematically rigorous way by carrying out the classical and quantum formulations of some two-Killing symmetry reductions of general relativity which admit an exact Fock/Schrödinger quantization. Concretely, we analyze in depth the linearly polarized 3-handle (S1xS2) and 3-sphere (S3) Gowdy cosmological models coupled to massless scalar fields. Within the classical formulation, this study requires a careful application of modern differential geometry techniques and the Dirac-Bergmann theory of constrained systems. Regarding the quantization process, we analyze the construction of both Fock and Schrödinger representations, the unitarity of the time evolution, and the existence of semiclassical states for these systems by making use of the algebraic formalism of quantum theory and the theory of unitary implementation of symplectic transformations. Several appendices give additional information on the results attained in the main body of the thesis, going deeply into the relevant mathematical aspects of the text.

  9. Multi-scale defect interactions in high-rate brittle material failure. Part I: Model formulation and application to ALON

    NASA Astrophysics Data System (ADS)

    Tonge, Andrew L.; Ramesh, K. T.

    2016-01-01

    Within this two part series we develop a new material model for ceramic protection materials to provide an interface between microstructural parameters and bulk continuum behavior to provide guidance for materials design activities. Part I of this series focuses on the model formulation that captures the strength variability and strain rate sensitivity of brittle materials and presents a statistical approach to assigning the local flaw distribution within a specimen. The material model incorporates a Mie-Grüneisen equation of state, micromechanics based damage growth, granular flow and dilatation of the highly damaged material, and pore compaction for the porosity introduced by granular flow. To provide initial qualitative validation and illustrate the usefulness of the model, we use the model to investigate Edge on Impact experiments (Strassburger, 2004) on Aluminum Oxynitride (AlON), and discuss the interactions of multiple mechanisms during such an impact event. Part II of this series is focused on additional qualitative validation and using the model to suggest material design directions for boron carbide.

  10. Quasispecies dynamics on a network of interacting genotypes and idiotypes: formulation of the model

    NASA Astrophysics Data System (ADS)

    Barbosa, Valmir C.; Donangelo, Raul; Souza, Sergio R.

    2015-01-01

    A quasispecies is the stationary state of a set of interrelated genotypes that evolve according to the usual principles of selection and mutation. Quasispecies studies have for the most part concentrated on the possibility of errors during genotype replication and their role in promoting either the survival or the demise of the quasispecies. In a previous work, we introduced a network model of quasispecies dynamics, based on a single probability parameter (p) and capable of addressing several plausibility issues of previous models. Here we extend that model by pairing its network with another one aimed at modeling the dynamics of the immune system when confronted with the quasispecies. The new network is based on the idiotypic-network model of immunity and, together with the previous one, constitutes a network model of interacting genotypes and idiotypes. The resulting model requires further parameters and as a consequence leads to a vast phase space. We have focused on a particular niche in which it is possible to observe the trade-offs involved in the quasispecies' survival or destruction. Within this niche, we give simulation results that highlight some key preconditions for quasispecies survival. These include a minimum initial abundance of genotypes relative to that of the idiotypes and a minimum value of p. The latter, in particular, is to be contrasted with the stand-alone quasispecies network of our previous work, in which arbitrarily low values of p constitute a guarantee of quasispecies survival.

  11. Comparability of Results from Pair and Classical Model Formulations for Different Sexually Transmitted Infections

    PubMed Central

    Ong, Jimmy Boon Som; Fu, Xiuju; Lee, Gary Kee Khoon; Chen, Mark I-Cheng

    2012-01-01

    The “classical model” for sexually transmitted infections treats partnerships as instantaneous events summarized by partner change rates, while individual-based and pair models explicitly account for time within partnerships and gaps between partnerships. We compared predictions from the classical and pair models over a range of partnership and gap combinations. While the former predicted similar or marginally higher prevalence at the shortest partnership lengths, the latter predicted self-sustaining transmission for gonorrhoea (GC) and Chlamydia (CT) over much broader partnership and gap combinations. Predictions on the critical level of condom use (Cc) required to prevent transmission also differed substantially when using the same parameters. When calibrated to give the same disease prevalence as the pair model by adjusting the infectious duration for GC and CT, and by adjusting transmission probabilities for HIV, the classical model then predicted much higher Cc values for GC and CT, while Cc predictions for HIV were fairly close. In conclusion, the two approaches give different predictions over potentially important combinations of partnership and gap lengths. Assuming that it is more correct to explicitly model partnerships and gaps, then pair or individual-based models may be needed for GC and CT since model calibration does not resolve the differences. PMID:22761828

  12. Mathematical Model Formulation And Validation Of Water And Solute Transport In Whole Hamster Pancreatic Islets

    PubMed Central

    Benson, Charles T.; Critser, John K.

    2014-01-01

    Optimization of cryopreservation protocols for cells and tissues requires accurate models of heat and mass transport. Model selection often depends on the configuration of the tissue. Here, a mathematical and conceptual model of water and solute transport for whole hamster pancreatic islets has been developed and experimentally validated incorporating fundamental biophysical data from previous studies on individual hamster islet cells while retaining whole-islet structural information. It describes coupled transport of water and solutes through the islet by three methods: intracellularly, intercellularly, and in combination. In particular we use domain decomposition techniques to couple a transmembrane flux model with an interstitial mass transfer model. The only significant undetermined variable is the cellular surface area which is in contact with the intercellularly transported solutes, Ais. The model was validated and Ais determined using a 3 × 3 factorial experimental design blocked for experimental day. Whole islet physical experiments were compared with model predictions at three temperatures, three perfusing solutions, and three islet size groups. A mean of 4.4 islets were compared at each of the 27 experimental conditions and found to correlate with a coefficient of determination of 0.87 ± 0.06 (mean ± S.D.). Only the treatment variable of perfusing solution was found to be significant (p < 0.05). We have devised a model that retains much of the intrinsic geometric configuration of the system, and thus fewer laboratory experiments are needed to determine model parameters and thus to develop new optimized cryopreservation protocols. Additionally, extensions to ovarian follicles and other concentric tissue structures may be made. PMID:24950195

  13. Mathematical model formulation and validation of water and solute transport in whole hamster pancreatic islets.

    PubMed

    Benson, James D; Benson, Charles T; Critser, John K

    2014-08-01

    Optimization of cryopreservation protocols for cells and tissues requires accurate models of heat and mass transport. Model selection often depends on the configuration of the tissue. Here, a mathematical and conceptual model of water and solute transport for whole hamster pancreatic islets has been developed and experimentally validated incorporating fundamental biophysical data from previous studies on individual hamster islet cells while retaining whole-islet structural information. It describes coupled transport of water and solutes through the islet by three methods: intracellularly, intercellularly, and in combination. In particular we use domain decomposition techniques to couple a transmembrane flux model with an interstitial mass transfer model. The only significant undetermined variable is the cellular surface area which is in contact with the intercellularly transported solutes, Ais. The model was validated and Ais determined using a 3×3 factorial experimental design blocked for experimental day. Whole islet physical experiments were compared with model predictions at three temperatures, three perfusing solutions, and three islet size groups. A mean of 4.4 islets were compared at each of the 27 experimental conditions and found to correlate with a coefficient of determination of 0.87±0.06 (mean ± SD). Only the treatment variable of perfusing solution was found to be significant (p<0.05). We have devised a model that retains much of the intrinsic geometric configuration of the system, and thus fewer laboratory experiments are needed to determine model parameters and thus to develop new optimized cryopreservation protocols. Additionally, extensions to ovarian follicles and other concentric tissue structures may be made. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Formulation and validation of high-order linearized models of helicopter flight mechanics

    NASA Technical Reports Server (NTRS)

    Kim, Frederick D.; Celi, Roberto; Tischler, Mark B.

    1990-01-01

    A high-order linearized model of helicopter flight dynamics is extracted from a nonlinear time domain simulation. The model has 29 states that describe the fuselage rigid body degrees of freedom, the flap and lag dynamics in a nonrotating coordinate system, the inflow dynamics, the delayed entry of the horizontal tail into the main rotor wake, and, approximately, the blade torsion dynamics. The nonlinear simulation is obtained by extensively modifying the GENHEL computer program. The results indicate that the agreement between the linearized and the nonlinear model is good for small perturbations, and deteriorates for large amplitude maneuvers.

  15. Guidance for the Development of Conceptual Models for a Problem Formulation Developed for Registration Review

    EPA Pesticide Factsheets

    Conceptual models for aquatic and terrestrial exposures. Graphic representation of predicted relationships between the ecological entities, both listed (threatened and endangered) and non-listed species, and the stressors to which they may be exposed.

  16. ATMOSPHERIC MERCURY SIMULATION USING THE CMAQ MODEL: FORMULATION DESCRIPTION AND ANALYSIS OF WET DEPOSITION RESULTS

    EPA Science Inventory

    The Community Multiscale Air Quality (CMAQ) modeling system has recently been adapted to simulate the emission, transport, transformation and deposition of atmospheric mercury in three distinct forms; elemental mercury gas, reactive gaseous mercury, and particulate mercury. Emis...

  17. Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

    PubMed

    Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

    2013-12-01

    Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

  18. Scalable Parallel Approximate Formulations of Multidimensional Spatial Auto-Regression Models for Spatial Data Mining

    DTIC Science & Technology

    2004-12-01

    classical data mining techniques, cannot be applied to geo-spatial data, because its assumption of independent identical distribution (IID) in learning...size of very large datasets. Recently, the Topographic Engineering Center initiated a project that uses spatial data mining and the SAR model...Multidimensional Spatial Auto-Regression Models For Spatial Data Mining 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  19. Conservative formulation of unsteady pipe-flow model for water in its liquid form

    NASA Astrophysics Data System (ADS)

    Supriyadi, Bambang; Gusti Ketut Puja, I.; Rusdi Sambada, F. A.; Mungkasi, Sudi

    2017-05-01

    We consider flows in a pipe system. The problem relating to the pipe system usually occurs in real life as well as in the laboratory, such as in the distillation process. This unsteady problem can be modeled into a hyperbolic system of partial differential equations. Our goal is to propose the use of a conservative finite-volume numerical method for solving the unsteady pipe-flow model. We obtain that the method is able to solve the pipe-flow problem successfully.

  20. A compositional simulator for modeling surfactant enhanced aquifer remediation, 1 formulation

    NASA Astrophysics Data System (ADS)

    Delshad, M.; Pope, G. A.; Sepehrnoori, K.

    1996-08-01

    We describe a three-dimensional, multicomponent, multiphase compositional finite-difference simulator for application to the analysis of contaminant transport and surfactant enhanced aquifer remediation (SEAR) of non aqueous- phase liquid (NAPL) pollutants. Mixtures of surfactant, water and NAPL can form many types of micellar and microemulsion phases with a complex and important dependence on many variables of which the dilute aqueous solution typically assumed in SEAR models is just one example. The phase behavior model is central to our approach and allows for the full range of the commonly observed micellar and microemulsion behavior pertinent to SEAR. The other surfactant related properties such as adsorption, interfacial tension, capillary pressure, capillary number and microemulsion viscosity are all dependent on an accurate phase behavior model. This has proven to be a highly successful approach for surfactant enhanced oil recovery modeling, so it was adapted to SEAR modeling. However, there are many significant differences between petroleum and environmental applications of surfactants, so many new features have been added to model contaminant transport and remediation and these are described and illustrated for the first time here.

  1. Equivalent Sensor Radiance Generation and Remote Sensing from Model Parameters. Part 1; Equivalent Sensor Radiance Formulation

    NASA Technical Reports Server (NTRS)

    Wind, Galina; DaSilva, Arlindo M.; Norris, Peter M.; Platnick, Steven E.

    2013-01-01

    In this paper we describe a general procedure for calculating equivalent sensor radiances from variables output from a global atmospheric forecast model. In order to take proper account of the discrepancies between model resolution and sensor footprint the algorithm takes explicit account of the model subgrid variability, in particular its description of the probably density function of total water (vapor and cloud condensate.) The equivalent sensor radiances are then substituted into an operational remote sensing algorithm processing chain to produce a variety of remote sensing products that would normally be produced from actual sensor output. This output can then be used for a wide variety of purposes such as model parameter verification, remote sensing algorithm validation, testing of new retrieval methods and future sensor studies. We show a specific implementation using the GEOS-5 model, the MODIS instrument and the MODIS Adaptive Processing System (MODAPS) Data Collection 5.1 operational remote sensing cloud algorithm processing chain (including the cloud mask, cloud top properties and cloud optical and microphysical properties products.) We focus on clouds and cloud/aerosol interactions, because they are very important to model development and improvement.

  2. Stability constraints for oceanic numerical models: implications for the formulation of space-time discretizations

    NASA Astrophysics Data System (ADS)

    Lemarie, Florian; Debreu, Laurent; Madec, Gurvan

    2015-04-01

    Except for vertical diffusion (and possibly the external mode and bottom drag), oceanic models usually rely on explicit time-stepping algorithms subject to Courant-Friedrichs-Lewy (CFL) stability criteria. Implicit methods could be unconditionally stable, but an algebraic system must be solved at each time step and other considerations such as accuracy and efficiency are less straightforward to achieve. Depending on the target application, the process limiting the maximum allowed time-step is generally different. In this study, we introduce offline diagnostics to predict stability limits associated with internal gravity waves, advection, diffusion, and rotation. This suite of diagnostics is applied to a set of global, regional and coastal numerical simulations with several horizontal/vertical resolutions and different numerical models. We show that, for resolutions finer that 1/2°, models with an eulerian vertical coordinate are generally constrained by vertical advection in a few hot spots and that numerics must be extremely robust to changes in Courant number. Based on those results, we review the stability and accuracy of existing numerical kernels in vogue in primitive equations oceanic models with a focus on advective processes and the dynamics of internal waves. We emphasize the additional value of studying the numerical kernel of oceanic models in the light of coupled space-time approaches instead of studying the time schemes independently from spatial discretizations. From this study, we suggest some guidelines for the development of temporal schemes in future generation multi-purpose oceanic models.

  3. Stability constraints for oceanic numerical models: implications for the formulation of time and space discretizations

    NASA Astrophysics Data System (ADS)

    Lemarié, F.; Debreu, L.; Madec, G.; Demange, J.; Molines, J. M.; Honnorat, M.

    2015-08-01

    Except for vertical diffusion (and possibly the external mode and bottom drag), oceanic models usually rely on explicit time-stepping algorithms subject to Courant-Friedrichs-Lewy (CFL) stability criteria. Implicit methods could be unconditionally stable, but an algebraic system must be solved at each time step and other considerations such as accuracy and efficiency are less straightforward to achieve. Depending on the target application, the process limiting the maximum allowed time-step is generally different. In this paper, we introduce offline diagnostics to predict stability limits associated with internal gravity waves, advection, diffusion, and rotation. This suite of diagnostics is applied to a set of global, regional and coastal numerical simulations with several horizontal/vertical resolutions and different numerical models. We show that, for resolutions finer that 1/2°, models with an Eulerian vertical coordinate are generally constrained by vertical advection in a few hot spots and that numerics must be extremely robust to changes in Courant number. Based on those results, we review the stability and accuracy of existing numerical kernels in vogue in primitive equations oceanic models with a focus on advective processes and the dynamics of internal waves. We emphasize the additional value of studying the numerical kernel of oceanic models in the light of coupled space-time approaches instead of studying the time schemes independently from spatial discretizations. From this study, we suggest some guidelines for the development of temporal schemes in future generation multi-purpose oceanic models.

  4. Implementation of a friction model in an Eulerian viscoplastic formulation for steady flow

    SciTech Connect

    Dawson, P.R.; Boyce, D.E.

    1996-04-01

    The goal of this project was to implement the routines necessary to use the friction model of Wilson and Korzekwa into the finite element analysis program {ital hickory}, in the case of an Eulerian reference frame. {ital hickory} is a deformation simulation code based on finite element modeling of viscoplastic deformation When using {ital hickory}, time-dependent problems are modeled from a Lagrangian reference frame; while steady-state problems are modeled from an Eulerian reference frame. The friction model had been implemented in earlier versions of {ital hickory}, for use with a Lagrangian reference frame. Additional modifications were required, however, to extend this capability to the case of an Eulerian reference frame. That is the subject of this report. The necessary modifications were related to the time integration of the friction state variables. The application of an Eulerian reference frame to study a steady-state flow requires that each specified boundary segment be a streamline of the flow. As such, an initial value for each state variable must be given at the first point of the streamline, and subsequent values must be determined by previous values by integration along the streamline. Additional routines were added to {ital hickory} to implement the streamline integration along the boundary. A plane strain rolling problem was used both to test the implementation and as a source of comparison among friction models.

  5. An accurate elasto-plastic frictional tangential force displacement model for granular-flow simulations: Displacement-driven formulation

    NASA Astrophysics Data System (ADS)

    Zhang, Xiang; Vu-Quoc, Loc

    2007-07-01

    We present in this paper the displacement-driven version of a tangential force-displacement (TFD) model that accounts for both elastic and plastic deformations together with interfacial friction occurring in collisions of spherical particles. This elasto-plastic frictional TFD model, with its force-driven version presented in [L. Vu-Quoc, L. Lesburg, X. Zhang. An accurate tangential force-displacement model for granular-flow simulations: contacting spheres with plastic deformation, force-driven formulation, Journal of Computational Physics 196(1) (2004) 298-326], is consistent with the elasto-plastic frictional normal force-displacement (NFD) model presented in [L. Vu-Quoc, X. Zhang. An elasto-plastic contact force-displacement model in the normal direction: displacement-driven version, Proceedings of the Royal Society of London, Series A 455 (1991) 4013-4044]. Both the NFD model and the present TFD model are based on the concept of additive decomposition of the radius of contact area into an elastic part and a plastic part. The effect of permanent indentation after impact is represented by a correction to the radius of curvature. The effect of material softening due to plastic flow is represented by a correction to the elastic moduli. The proposed TFD model is accurate, and is validated against nonlinear finite element analyses involving plastic flows in both the loading and unloading conditions. The proposed consistent displacement-driven, elasto-plastic NFD and TFD models are designed for implementation in computer codes using the discrete-element method (DEM) for granular-flow simulations. The model is shown to be accurate and is validated against nonlinear elasto-plastic finite-element analysis.

  6. Analysis of Dynamic Fracture Compliance Based on Poroelastic Theory. Part I: Model Formulation and Analytical Expressions

    NASA Astrophysics Data System (ADS)

    Wang, Ding; Qu, Shou-Li; Ding, Ping-Bo; Zhao, Qun

    2017-05-01

    The presence of bedding-parallel fractures at any scale in a rock will considerably add to its compliance and elastic anisotropy. Those properties will be more significantly affected when there is a relatively high degree of connectivity between the fractures and the corresponding interconnected pores. This contribution uses linear poroelasticity to reveal the characteristics of the full frequency-dependent compliance of an infinitely extended fracture model assuming the periodicity of the fractured structures. The fracture compliance tensor is complex-valued due to the wave-induced fluid flow between fractures and pores. The interaction between the adjacent fractures is considered under fluid mass conservation throughout the whole pore space. The quantitative effects of fracture (volume) density (the ratio between fracture thickness and spacing) and host rock porosity are analyzed by the diffusion equation for a relatively low-frequency band. The model in this paper is equivalent to the classical dry linear slip model when the bulk modulus of fluid in the fractures tends to zero. For the liquid-filled case, the model becomes the anisotropic Gassmann's model and sealed saturated linear slip model at the low-frequency and high-frequency limits, respectively. Using the dynamic compliance definition, we can effectively distinguish the saturating fluids in the fractures with the same order magnitude of bulk modulus (e.g., water and oil) using the compliance ratio method. Additionally, the modified dynamic model can be simplified as acceptable empirical formulas if the strain on the fractures induced by the incoming waves is small enough.

  7. Comparison of nonideal sorption formulations in modeling the transport of phthalate esters through packed soil columns

    NASA Astrophysics Data System (ADS)

    Maraqa, Munjed A.; Zhao, Xianda; Lee, Jae-ug; Allan, Fathi; Voice, Thomas C.

    2011-07-01

    Sorption of dimethyl phthalate (DMP), diethyl phthalate (DEP) and dipropyl phthalate (DPP) to two soil materials that vary in organic matter content was investigated using miscible displacement experiments under saturated flow conditions. Generated breakthrough curves (BTCs) were inversely simulated using linear, equilibrium sorption (LE), nonlinear, equilibrium sorption (NL), linear, first-order nonequilibrium sorption (LFO), linear, radial diffusion (LRD), and nonlinear, first-order nonequilibrium sorption (NFO) models. The Akaike information criterion was utilized to determine the preferred model. The LE model could not adequately describe phthalate ester (PE) BTCs in higher organic matter soil or for more hydrophobic PEs. The LFO and LRD models adequately described the BTCs but a slight improvement in curve-fitting was gained in some cases when the NFO model was used. However, none of the models could properly describe the desorptive tail of DPP for the high organic matter soil. Transport of DPP through this soil was adequately predicted when degradation or sorption hysteresis was considered. Using the optimized parameter values along with values reported by others it was shown that the organic carbon distribution coefficient ( Koc) of PEs correlates well with the octanol/water partition coefficient ( Kow). Also, a strong relationship was found between the first-order sorption rate coefficient normalized to injection pulse size and compound residence time. A similar trend of timescale dependence was found for the rate parameter in the radial diffusion model. Results also revealed that the fraction of instantaneous sorption sites is dependent on Kow and appears to decrease with the increase in the sorption rate parameter.

  8. Comparison of nonideal sorption formulations in modeling the transport of phthalate esters through packed soil columns.

    PubMed

    Maraqa, Munjed A; Zhao, Xianda; Lee, Jae-ug; Allan, Fathi; Voice, Thomas C

    2011-07-01

    Sorption of dimethyl phthalate (DMP), diethyl phthalate (DEP) and dipropyl phthalate (DPP) to two soil materials that vary in organic matter content was investigated using miscible displacement experiments under saturated flow conditions. Generated breakthrough curves (BTCs) were inversely simulated using linear, equilibrium sorption (LE), nonlinear, equilibrium sorption (NL), linear, first-order nonequilibrium sorption (LFO), linear, radial diffusion (LRD), and nonlinear, first-order nonequilibrium sorption (NFO) models. The Akaike information criterion was utilized to determine the preferred model. The LE model could not adequately describe phthalate ester (PE) BTCs in higher organic matter soil or for more hydrophobic PEs. The LFO and LRD models adequately described the BTCs but a slight improvement in curve-fitting was gained in some cases when the NFO model was used. However, none of the models could properly describe the desorptive tail of DPP for the high organic matter soil. Transport of DPP through this soil was adequately predicted when degradation or sorption hysteresis was considered. Using the optimized parameter values along with values reported by others it was shown that the organic carbon distribution coefficient (K(oc)) of PEs correlates well with the octanol/water partition coefficient (K(ow)). Also, a strong relationship was found between the first-order sorption rate coefficient normalized to injection pulse size and compound residence time. A similar trend of timescale dependence was found for the rate parameter in the radial diffusion model. Results also revealed that the fraction of instantaneous sorption sites is dependent on K(ow) and appears to decrease with the increase in the sorption rate parameter.

  9. Analysis of Dynamic Fracture Compliance Based on Poroelastic Theory. Part I: Model Formulation and Analytical Expressions

    NASA Astrophysics Data System (ADS)

    Wang, Ding; Qu, Shou-Li; Ding, Ping-Bo; Zhao, Qun

    2017-03-01

    The presence of bedding-parallel fractures at any scale in a rock will considerably add to its compliance and elastic anisotropy. Those properties will be more significantly affected when there is a relatively high degree of connectivity between the fractures and the corresponding interconnected pores. This contribution uses linear poroelasticity to reveal the characteristics of the full frequency-dependent compliance of an infinitely extended fracture model assuming the periodicity of the fractured structures. The fracture compliance tensor is complex-valued due to the wave-induced fluid flow between fractures and pores. The interaction between the adjacent fractures is considered under fluid mass conservation throughout the whole pore space. The quantitative effects of fracture (volume) density (the ratio between fracture thickness and spacing) and host rock porosity are analyzed by the diffusion equation for a relatively low-frequency band. The model in this paper is equivalent to the classical dry linear slip model when the bulk modulus of fluid in the fractures tends to zero. For the liquid-filled case, the model becomes the anisotropic Gassmann's model and sealed saturated linear slip model at the low-frequency and high-frequency limits, respectively. Using the dynamic compliance definition, we can effectively distinguish the saturating fluids in the fractures with the same order magnitude of bulk modulus (e.g., water and oil) using the compliance ratio method. Additionally, the modified dynamic model can be simplified as acceptable empirical formulas if the strain on the fractures induced by the incoming waves is small enough.

  10. Evaluation of the existing triple point path models with new experimental data: proposal of an original empirical formulation

    NASA Astrophysics Data System (ADS)

    Boutillier, J.; Ehrhardt, L.; De Mezzo, S.; Deck, C.; Magnan, P.; Naz, P.; Willinger, R.

    2017-08-01

    With the increasing use of improvised explosive devices (IEDs), the need for better mitigation, either for building integrity or for personal security, increases in importance. Before focusing on the interaction of the shock wave with a target and the potential associated damage, knowledge must be acquired regarding the nature of the blast threat, i.e., the pressure-time history. This requirement motivates gaining further insight into the triple point (TP) path, in order to know precisely which regime the target will encounter (simple reflection or Mach reflection). Within this context, the purpose of this study is to evaluate three existing TP path empirical models, which in turn are used in other empirical models for the determination of the pressure profile. These three TP models are the empirical function of Kinney, the Unified Facilities Criteria (UFC) curves, and the model of the Natural Resources Defense Council (NRDC). As discrepancies are observed between these models, new experimental data were obtained to test their reliability and a new promising formulation is proposed for scaled heights of burst ranging from 24.6-172.9 cm/kg^{1/3}.

  11. Invariant formulation for dispersed transverse isotropy in aortic heart valves: An efficient means for modeling fiber splay

    SciTech Connect

    Freed, Alan D.; Einstein, Daniel R.; Vesely, Ivan

    2005-11-01

    Most soft tissues possess an oriented architecture of collagen fiber bundles, conferring both anisotropy and nonlinearity to their elastic behavior. Transverse isotropy has often been assumed for a subset of these tissues that have a single macroscopically-identifiable preferred fiber direction. Micro-structural studies, however, suggest that, in some tissues, collagen fibers are approximately normally distributed about a mean preferred fiber direction. Structural constitutive equations that account for this dispersion of fibers have been shown to capture the mechanical complexity of these tissues quite well. Such descriptions, however, are computationally cumbersome for two-dimensional (2D) fiber distributions, let alone for fully three-dimensional (3D) fiber populations. In this paper, we develop a new constitutive law for such tissues, based on a novel invariant theory for dispersed transverse isotropy. The invariant theory is based on a novel closed-form ''splay invariant'' that can easily handle 3D fiber populations, and that only requires a single parameter in the 2D case. The model is polyconvex and fits biaxial data for aortic valve tissue as accurately as the standard structural model. Modification of the fiber stress-strain law requires no re-formulation of the constitutive tangent matrix, making the model flexible for different types of soft tissues. Most importantly, the model is computationally expedient in a finite-element analysis, demonstrated by modeling a bioprosthetic heart valve.

  12. Elastic-viscoplastic modeling of soft biological tissues using a mixed finite element formulation based on the relative deformation gradient.

    PubMed

    Weickenmeier, J; Jabareen, M

    2014-11-01

    The characteristic highly nonlinear, time-dependent, and often inelastic material response of soft biological tissues can be expressed in a set of elastic-viscoplastic constitutive equations. The specific elastic-viscoplastic model for soft tissues proposed by Rubin and Bodner (2002) is generalized with respect to the constitutive equations for the scalar quantity of the rate of inelasticity and the hardening parameter in order to represent a general framework for elastic-viscoplastic models. A strongly objective integration scheme and a new mixed finite element formulation were developed based on the introduction of the relative deformation gradient-the deformation mapping between the last converged and current configurations. The numerical implementation of both the generalized framework and the specific Rubin and Bodner model is presented. As an example of a challenging application of the new model equations, the mechanical response of facial skin tissue is characterized through an experimental campaign based on the suction method. The measurement data are used for the identification of a suitable set of model parameters that well represents the experimentally observed tissue behavior. Two different measurement protocols were defined to address specific tissue properties with respect to the instantaneous tissue response, inelasticity, and tissue recovery.

  13. Fine-tuning of DDES and IDDES formulations to the k-ω shear stress transport model

    NASA Astrophysics Data System (ADS)

    Gritskevich, M. S.; Garbaruk, A. V.; Menter, F. R.

    2013-06-01

    Modifications are proposed of two recently developed hybrid CFD (computational fluid dynamics) strategies, Delayed Detached Eddy Simulation (DDES), and DDES with Improved wall-modeling capability (IDDES). The modifications are aimed at fine-tuning of these approaches to the k-ω SST (shear stress transport) background RANS (Reynolds-averaged Navier-Stokes) model. The first one includes recalibrated empirical constants in the shielding function of the Spalart-Allmaras (SA) based DDES which are shown to be suboptimal (not providing a needed level of elimination of the Model Stress Depletion (MSD)) for the SST-based DDES model. For the SST-IDDES variant, in addition to that, a simplification of the original SA-based formulation is proposed, which does not cause any visible degradation of the model performance. Both modifications are extensively tested on a range of attached and separated flows (developed channel, backward-facing step, periodic hills, wall-mounted hump, and hydrofoil with trailing edge separation).

  14. On the selection of primary variables in numerical formulation for modeling multiphase flow in porous media

    NASA Astrophysics Data System (ADS)

    Wu, Yu-Shu; Forsyth, Peter A.

    2001-04-01

    Selecting the proper primary variables is a critical step in efficiently modeling the highly nonlinear problem of multiphase subsurface flow in a heterogeneous porous-fractured media. Current simulation and ground modeling techniques consist of (1) spatial discretization of mass and/or heat conservation equations using finite difference or finite element methods; (2) fully implicit time discretization; (3) solving the nonlinear, discrete algebraic equations using a Newton iterative scheme. Previous modeling efforts indicate that the choice of primary variables for a Newton iteration not only impacts computational performance of a numerical code, but may also determine the feasibility of a numerical modeling study in many field applications. This paper presents an analysis and general recommendations for selecting primary variables in simulating multiphase, subsurface flow for one-active phase (Richards' equation), two-phase (gas and liquid) and three-phase (gas, water and nonaqueous phase liquid or NAPL) conditions. In many cases, a dynamic variable switching or variable substitution scheme may have to be used in order to achieve optimal numerical performance and robustness. The selection of primary variables depends in general on the sensitivity of the system of equations to the variables selected at given phase and flow conditions. We will present a series of numerical tests and large-scale field simulation examples, including modeling one (active)-phase, two-phase and three-phase flow problems in multi-dimensional, porous-fractured subsurface systems.

  15. On the selection of primary variables in numerical formulation for modeling multiphase flow in porous media.

    PubMed

    Wu, Y S; Forsyth, P A

    2001-04-01

    Selecting the proper primary variables is a critical step in efficiently modeling the highly nonlinear problem of multiphase subsurface flow in a heterogeneous porous-fractured media. Current simulation and ground modeling techniques consist of (1) spatial discretization of mass and/or heat conservation equations using finite difference or finite element methods; (2) fully implicit time discretization; (3) solving the nonlinear, discrete algebraic equations using a Newton iterative scheme. Previous modeling efforts indicate that the choice of primary variables for a Newton iteration not only impacts computational performance of a numerical code, but may also determine the feasibility of a numerical modeling study in many field applications. This paper presents an analysis and general recommendations for selecting primary variables in simulating multiphase, subsurface flow for one-active phase (Richards' equation), two-phase (gas and liquid) and three-phase (gas, water and nonaqueous phase liquid or NAPL) conditions. In many cases, a dynamic variable switching or variable substitution scheme may have to be used in order to achieve optimal numerical performance and robustness. The selection of primary variables depends in general on the sensitivity of the system of equations to the variables selected at given phase and flow conditions. We will present a series of numerical tests and large-scale field simulation examples, including modeling one (active)-phase, two-phase and three-phase flow problems in multi-dimensional, porous-fractured subsurface systems.

  16. Formulation of an experimental substructure model using a Craig-Bampton based transmission simulator

    DOE PAGES

    Kammer, Daniel C.; Allen, Matthew S.; Mayes, Randall L.

    2015-09-26

    An 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. This method reduces ill-conditioning by imposing a least squares fit of constraints between substructure modal coordinatesmore » 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. Moreover, 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.« less

  17. Formulation of an experimental substructure model using a Craig-Bampton based transmission simulator

    SciTech Connect

    Kammer, Daniel C.; Allen, Matthew S.; Mayes, Randall L.

    2015-09-26

    An 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. This 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. Moreover, 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.

  18. A model for real-time quantitative rainfall forecasting using remote sensing. 1. Formulation

    NASA Astrophysics Data System (ADS)

    French, Mark N.; Krajewski, Witold F.

    1994-04-01

    A physically based rainfall forecasting model for real-time hydrologic applications is developed with emphasis on utilization of remote sensing observations. Temporal and spatial scales of interest are lead times of the order of hours and areas of the order of 10 km2. The dynamic model is derived from conservation of mass in a cloud column as defined by the continuity equations for air, liquid water, water vapor, and cloud water. Conservation of momentum is modeled using a semi-Lagrangian frame of reference. The model state is vertically integrated liquid water content in a column of the atmosphere. Additionally, laws of thermodynamics, adiabatic air parcel theory, and cloud microphysics are applied to derive a basic parameterization of the governing equations of model dynamics. The parameterization is in terms of hydrometeorologic observables including radar reflectivity, satellite-infrared brightness temperature, and ground-level air temperature, dew point temperature, and pressure. Implementation and application is described by French et al. (this issue) and involves incorporation of uncertainty analysis and a two-dimensional spatial domain, where the dynamics of the continuous space-time rainfall process are discretized onto a rectangular grid.

  19. 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.

  20. Biopsychosocial Formulation: Recognizing Educational Shortcomings

    ERIC Educational Resources Information Center

    McClain, Tina; O'Sullivan, Patricia S.; Clardy, James A.

    2004-01-01

    Objective: Since Engel introduced the biopsychosocial model, it has been extensively examined. The authors expect psychiatrists to formulate cases using the biopsychosocial model. However, resident psychiatrists' ability to generate formulations using this model has received little attention. Methods: The authors evaluated resident biopsychosocial…

  1. Biopsychosocial Formulation: Recognizing Educational Shortcomings

    ERIC Educational Resources Information Center

    McClain, Tina; O'Sullivan, Patricia S.; Clardy, James A.

    2004-01-01

    Objective: Since Engel introduced the biopsychosocial model, it has been extensively examined. The authors expect psychiatrists to formulate cases using the biopsychosocial model. However, resident psychiatrists' ability to generate formulations using this model has received little attention. Methods: The authors evaluated resident biopsychosocial…

  2. Formulation, Implementation and Validation of a Two-Fluid model in a Fuel Cell CFD Code

    SciTech Connect

    Jain, Kunal; Cole, J. Vernon; Kumar, Sanjiv; Gidwani, Ashok; Vaidya, N.

    2008-12-01

    Water management is one of the main challenges in PEM Fuel Cells. While water is essential for membrane electrical conductivity, excess liquid water leads to flooding of catalyst layers. Despite the fact that accurate prediction of two-phase transport is key for optimal water management, understanding of the two-phase transport in fuel cells is relatively poor. Wang et. al. have studied the two-phase transport in the channel and diffusion layer separately using a multiphase mixture model. The model fails to accurately predict saturation values for high humidity inlet streams. Nguyen et. al. developed a two-dimensional, two-phase, isothermal, isobaric, steady state model of the catalyst and gas diffusion layers. The model neglects any liquid in the channel. Djilali et. al. developed a three-dimensional two-phase multicomponent model. The model is an improvement over previous models, but neglects drag between the liquid and the gas phases in the channel. In this work, we present a comprehensive two-fluid model relevant to fuel cells. Models for two-phase transport through Channel, Gas Diffusion Layer (GDL) and Channel-GDL interface, are discussed. In the channel, the gas and liquid pressures are assumed to be same. The surface tension effects in the channel are incorporated using the continuum surface force (CSF) model. The force at the surface is expressed as a volumetric body force and added as a source to the momentum equation. In the GDL, the gas and liquid are assumed to be at different pressures. The difference in the pressures (capillary pressure) is calculated using an empirical correlations. At the Channel-GDL interface, the wall adhesion affects need to be taken into account. SIMPLE-type methods recast the continuity equation into a pressure-correction equation, the solution of which then provides corrections for velocities and pressures. However, in the two-fluid model, the presence of two phasic continuity equations gives more freedom and more

  3. The formulation and performance of a perturbative correction to the perfect quadruples model

    NASA Astrophysics Data System (ADS)

    Parkhill, John A.; Azar, Julian; Head-Gordon, Martin

    2011-04-01

    A recently published alternative hierarchy of coupled-cluster approximations is reformulated as a perturbative correction. A single variant, a model for the total electronic energy based on the perfect quadruples model, is explored in detail. The computational scaling of the method developed is the same as canonical second order Møller-Plesset perturbation theory (fifth order in the number of molecular orbitals), but its accuracy competes with the high-accuracy, high-cost standard CCSD(T), even when the latter is allowed to break spin-symmetry. The variation presented can be implemented without explicit calculation and storage of the most expensive energy contributions, thereby improving the range of systems which can be treated. The performance and scaling of the method are demonstrated with calculations on the water, fluorine, and oxirane molecules, and compared to the parent model.

  4. Mathematical modeling of cement paste microstructure by mosaic pattern Part I. Formulation

    SciTech Connect

    Xi, Y.; Tennis, P.D.; Jennings, H.M.

    1996-08-01

    This paper develops a mathematical model using mosaic patterns to characterize structural features of complex, multiphase and multidimensional microstructures, such as those for cement paste. A multiphase microstructure can be characterized by {ital m} independent parameters: the first {ital m}{minus}1 parameters are equivalent to the volume fractions of the phases, while the final parameter describes the grain size, and thus, the spatial arrangement of the microstructure. An evaluation procedure for the parameters is given; they can be evaluated based on a 2D image, and then the 3D microstructure can be simulated by the present model. The relationship among the model parameters and material parameters, such as water-to-cement ratio and particle size distribution, are also established. {copyright} {ital 1996 Materials Research Society.}

  5. A new in vitro lipid digestion - in vivo absorption model to evaluate the mechanisms of drug absorption from lipid-based formulations.

    PubMed

    Crum, Matthew F; Trevaskis, Natalie L; Williams, Hywel D; Pouton, Colin W; Porter, Christopher J H

    2016-04-01

    In vitro lipid digestion models are commonly used to screen lipid-based formulations (LBF), but in vitro-in vivo correlations are in some cases unsuccessful. Here we enhance the scope of the lipid digestion test by incorporating an absorption 'sink' into the experimental model. An in vitro model of lipid digestion was coupled directly to a single pass in situ intestinal perfusion experiment in an anaesthetised rat. The model allowed simultaneous real-time analysis of the digestion and absorption of LBFs of fenofibrate and was employed to evaluate the influence of formulation digestion, supersaturation and precipitation on drug absorption. Formulations containing higher quantities of co-solvent and surfactant resulted in higher supersaturation and more rapid drug precipitation in vitro when compared to those containing higher quantities of lipid. In contrast, when the same formulations were examined using the coupled in vitro lipid digestion - in vivo absorption model, drug flux into the mesenteric vein was similar regardless of in vitro formulation performance. For some drugs, simple in vitro lipid digestion models may underestimate the potential for absorption from LBFs. Consistent with recent in vivo studies, drug absorption for rapidly absorbed drugs such as fenofibrate may occur even when drug precipitation is apparent during in vitro digestion.

  6. GFDL's ESM2 global coupled climate-carbon Earth System Models. Part I: physical formulation and baseline simulation characteristics

    USGS Publications Warehouse

    Dunne, John P.; John, Jasmin G.; Adcroft, Alistair J.; Griffies, Stephen M.; Hallberg, Robert W.; Shevalikova, Elena; Stouffer, Ronald J.; Cooke, William; Dunne, Krista A.; Harrison, Matthew J.; Krasting, John P.; Malyshev, Sergey L.; Milly, P.C.D.; Phillipps, Peter J.; Sentman, Lori A.; Samuels, Bonita L.; Spelman, Michael J.; Winton, Michael; Wittenberg, Andrew T.; Zadeh, Niki

    2012-01-01

    We describe the physical climate formulation and simulation characteristics of two new global coupled carbon-climate Earth System Models, ESM2M and ESM2G. These models demonstrate similar climate fidelity as the Geophysical Fluid Dynamics Laboratory's previous CM2.1 climate model while incorporating explicit and consistent carbon dynamics. The two models differ exclusively in the physical ocean component; ESM2M uses Modular Ocean Model version 4.1 with vertical pressure layers while ESM2G uses Generalized Ocean Layer Dynamics with a bulk mixed layer and interior isopycnal layers. Differences in the ocean mean state include the thermocline depth being relatively deep in ESM2M and relatively shallow in ESM2G compared to observations. The crucial role of ocean dynamics on climate variability is highlighted in the El Niño-Southern Oscillation being overly strong in ESM2M and overly weak ESM2G relative to observations. Thus, while ESM2G might better represent climate changes relating to: total heat content variability given its lack of long term drift, gyre circulation and ventilation in the North Pacific, tropical Atlantic and Indian Oceans, and depth structure in the overturning and abyssal flows, ESM2M might better represent climate changes relating to: surface circulation given its superior surface temperature, salinity and height patterns, tropical Pacific circulation and variability, and Southern Ocean dynamics. Our overall assessment is that neither model is fundamentally superior to the other, and that both models achieve sufficient fidelity to allow meaningful climate and earth system modeling applications. This affords us the ability to assess the role of ocean configuration on earth system interactions in the context of two state-of-the-art coupled carbon-climate models.

  7. A lateral boundary formulation for multi-level prediction models. [numerical weather forecasting

    NASA Technical Reports Server (NTRS)

    Davies, H. C.

    1976-01-01

    A method is proposed for treating the lateral boundaries of a limited-area weather prediction model. The method involves the relaxation of the interior flow in the vicinity of the boundary to the external fully prescribed flow. Analytical and numerical results obtained with a linearized multilevel model confirm the effectiveness of this computationally effective method. The method is shown to give an adequate representation of outgoing gravity waves with and without an ambient shear flow and to allow the substantially undistorted transmission of geostrophically balanced flow out of the interior of the limited domain.

  8. Simulation of Oil Slick Transport in Great Lakes Connecting Channels. Volume 1. Theory and Model Formulation

    DTIC Science & Technology

    1986-03-01

    Under Rough Ice," Proceedings of the 1981 Oil Spill Conference, American Petroleum Institute , Washington, D.C.,3 pp. 203-208. DiPietro, N.D. and R.G. Cox...Models," Proceedings of the 1983 Oil Spill Conference, American Petroleum Institute , Washington, D.C., pp. 313-322. Huang, J.C. and Monastero, F.C...1982). "Review of the State-of-the-Art of Oil Spill Simulation Models," Final Report submitted to the American Petroleum Institute . Hunter, J.R., (1980

  9. A lateral boundary formulation for multi-level prediction models. [numerical weather forecasting

    NASA Technical Reports Server (NTRS)

    Davies, H. C.

    1976-01-01

    A method is proposed for treating the lateral boundaries of a limited-area weather prediction model. The method involves the relaxation of the interior flow in the vicinity of the boundary to the external fully prescribed flow. Analytical and numerical results obtained with a linearized multilevel model confirm the effectiveness of this computationally effective method. The method is shown to give an adequate representation of outgoing gravity waves with and without an ambient shear flow and to allow the substantially undistorted transmission of geostrophically balanced flow out of the interior of the limited domain.

  10. A cross-scale model for 3D baroclinic circulation in estuary plume shelf systems: I. Formulation and skill assessment

    NASA Astrophysics Data System (ADS)

    Zhang, Yinglong; Baptista, António M.; Myers, Edward P.

    2004-12-01

    Challenges posed by the Columbia River estuary-plume-shelf system have led to the development of ELCIRC, a model designed for the effective simulation of 3D baroclinic circulation across river-to-ocean scales. ELCIRC uses a finite-volume/finite-difference Eulerian-Lagrangian algorithm to solve the shallow water equations, written to realistically address a wide range of physical processes and of atmospheric, ocean and river forcings. The numerical algorithm is volume conservative, stable and computationally efficient, and it naturally incorporates wetting and drying of tidal flats. ELCIRC has been subject to systematic benchmarking, and applied to the description of the Columbia River circulation. This paper motivates and describes the formulation, presents and critically analyzes the results of selected benchmarks, and introduces ELCIRC as an open-source code available for community use and enhancement. A companion paper describes the application of ELCIRC to the Columbia River.

  11. Loss, Psychosis, and Chronic Suicidality in a Korean American Immigrant Man: Integration of Cultural Formulation Model and Multicultural Case Conceptualization

    PubMed Central

    Shea, Munyi; Yang, Lawrence H.; Leong, Frederick T. L.

    2011-01-01

    Culture shapes the nature, experience, and expression of psychopathology and help-seeking behavior across ethnically diverse groups. Although the study of psychopathology among Asian Americans has advanced, clinicians remain in need of culturally appropriate tools for the assessment and diagnosis of severe mental disorders including psychotic symptoms among Asian Americans. In this article, we present a brief overview of two culturally relevant conceptual tools: a) the Cultural Formulation Model, and b) the Multicultural Case Conceptualization approach. We use a case scenario to illustrate the integration of these two approaches in providing culturally responsive clinical conceptualization, assessment and treatment of a Korean American immigrant suffering from prominent psychiatric symptoms. We intend this discussion to engender further empirical work to advance our knowledge of the manifestation and experience of severe mental illness including psychotic disorders among Asian Americans, and contribute to culturally competent prevention and intervention of chronic and persistent mental illness within this group. PMID:21603157

  12. Preventive effects of different probiotic formulations on travelers' diarrhea model in wistar rats : preventive effects of probiotics on TD.

    PubMed

    Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

    2010-04-01

    A new animal model of travelers' diarrhea has been developed by infecting rats orally with a strain of enterotoxigenic Escherichia coli in order to assess the efficacy of three probiotic formulations for the prevention of travelers' diarrhea. Five groups of six rats were given daily (by oral gavage) either a placebo (negative and positive control groups), the suspension of bacterial probiotics called FF1, the yeast probiotic Saccharomyces boulardii, or a combination of both, called Protecflor(TM). After 14 days of treatment, all groups except the negative control one were infected by oral administration of E. coli. Body temperature, body weight, food and water consumption, stools consistency, behavior, and cytokines secretion were disturbed following E. coli infection. Probiotics-treated groups generally displayed less-pronounced symptoms, the combination of probiotics Protecflor(TM) being the most effective.

  13. Improved Efficiency of Marine EM Subsurface Modeling Using the Total-Field Scattered-Field FDTD Formulation

    NASA Astrophysics Data System (ADS)

    Dukeshire, Andrea

    To efficiently model the effect of the airwave in the controlled-source electromagnetics (CSEM) method has historically been a problem of major interest. The methods proposed in this thesis provide a new method of simulating CSEM interactions in the finite-difference time-domain (FDTD) by using the total-field scattered-field (TFSF) formulation. TFSF provides an inherent separation of the total and scattered fields, which allows the proposed method to decompose the CSEM domain into separate simulation runs. By simulating the problem in stages, the process of extracting the response of the scatterer is streamlined. If the increased efficiency options within the proposed method are utilized, the efficiency of single forward simulations can be improved. This method shows potential for computational cost savings, especially in typical CSEM data analysis and reconstruction situations where numerous iterations of various scatterers are required.

  14. Unsteady Aerodynamic Response of Oscillating Contra-Rotating Annular Cascades Part I: Description of Model and Mathematical Formulations

    NASA Astrophysics Data System (ADS)

    Namba, Masanobu; Nishino, Ryohei

    The purpose of this paper is to study the effect of neighboring blade rows on the unsteady aerodynamic response of oscillating cascade blades on the basis of a genuine three-dimensional model. To this end, mathematical formulations based on the lifting surface theory are developed for a pair of contra-rotating annular cascades of oscillating blades. The mechanism of frequency scattering of blade loadings and mode scattering of acoustic waves resulting from interaction between the blade rows in relative rotational motions is mathematically explained. Simultaneous integral equations for all frequency components of blade loadings are derived from the flow tangency condition on the blade surfaces of both blade rows. The validity of the computation codes is verified.

  15. Laminated Composite Shell Element Using Absolute Nodal Coordinate Formulation and Its Application to ANCF Tire Model

    DTIC Science & Technology

    2015-04-24

    Technical Paper 971100. [3] Gruber, P., Sharp, R. S. and Crocombe, A. D., 2012, "Normal and Shear Forces in the Contact Patch of a Braked Racing Tyre ...Part 2: Development of a Physical Tyre Model", Vehicle System Dynamics, vol. 50, pp. 339-356. [4] Sugiyama, H., Yamashita, H. and Jayakumar, P., 2014

  16. Formulating a Conceptual Model of Nontraditional Student Attrition and Persistence in Postsecondary Vocational Education Programs.

    ERIC Educational Resources Information Center

    Johnson, David R.

    Few studies have been conducted on nontraditional student attrition in postsecondary vocational educational programs. This lack of attention is due to methodological limitations, lack of priority on data collection in vocational education, and lack of perceived need for research. The conceptual model of student attrition in postsecondary…

  17. Application of TZERO calibrated modulated temperature differential scanning calorimetry to characterize model protein formulations.

    PubMed

    Badkar, Aniket; Yohannes, Paulos; Banga, Ajay

    2006-02-17

    The objective of this study was to evaluate the feasibility of using T(ZERO) modulated temperature differential scanning calorimetry (MDSC) as a novel technique to characterize protein solutions using lysozyme as a model protein and IgG as a model monoclonal antibody. MDSC involves the application of modulated heating program, along with the standard heating program that enables the separation of overlapping thermal transitions. Although characterization of unfolding transitions for protein solutions requires the application of high sensitive DSC, separation of overlapping transitions like aggregation and other exothermic events may be possible only by use of MDSC. A newer T(ZERO) calibrated MDSC model from TA instruments that has improved sensitivity than previous models was used. MDSC analysis showed total, reversing and non-reversing heat flow signals. Total heat flow signals showed a combination of melting endotherms and overlapping exothermic events. Under the operating conditions used, the melting endotherms were seen in reversing heat flow signal while the exothermic events were seen in non-reversing heat flow signal. This enabled the separation of overlapping thermal transitions, improved data analysis and decreased baseline noise. MDSC was used here for characterization of lysozyme solutions, but its feasibility for characterizing therapeutic protein solutions needs further assessment.

  18. The impact of a boundary layer height formulation on the GEOS-5 model climate

    NASA Astrophysics Data System (ADS)

    McGrath-Spangler, E. L.

    2016-04-01

    Planetary boundary layer (PBL) processes are important for the estimation of surface-atmosphere exchanges that impact global climate. One way of characterizing the strength of these processes is the PBL depth. In the Goddard Earth Observing System (GEOS-5) atmospheric general circulation model, the PBL depth is also used in calculating the turbulent length scale, which, in turn, is used in estimating the turbulence and vertical mixing within the model. Therefore, changing the PBL depth definition directly affects the model climate. This study evaluates the climatological model response of two long-term simulations using different PBL depth definitions. The first definition is based on a bulk Richardson number; the second uses a combination of the same bulk Richardson number definition over land plus a definition based on the turbulent eddy diffusion coefficient over water. The two simulations produce different spatiotemporal patterns of temperature, specific humidity, and wind speed related to the differences in turbulence. The largest differences, as expected, are present over water. Due to differences in atmospheric stability, the relationship between the two PBL depth estimates differ among the majority of the oceans and off the west coasts of continents, affecting the climatic response. Due to its optimization of the climatic response while maintaining a realistic diurnal cycle of PBL depth, the mixed PBL depth configuration is preferred.

  19. The application of remote sensing to the development and formulation of hydrologic planning models: Executive summary

    NASA Technical Reports Server (NTRS)

    Castruccio, P. A.; Loats, H. L., Jr.; Fowler, T. R.

    1977-01-01

    Methods for the reduction of remotely sensed data and its application in hydrologic land use assessment, surface water inventory, and soil property studies are presented. LANDSAT data is used to provide quantitative parameters and coefficients to construct watershed transfer functions for a hydrologic planning model aimed at estimating peak outflow from rainfall inputs.

  20. Evaluation of a Photosynthesis-Based Canopy Resistance Formulation in the Noah Land-Surface Model

    NASA Astrophysics Data System (ADS)

    Kumar, Anil; Chen, Fei; Niyogi, Dev; Alfieri, Joseph G.; Ek, Michael; Mitchell, Kenneth

    2011-02-01

    Accurately representing complex land-surface processes balancing complexity and realism remains one challenge that the weather modelling community is facing nowadays. In this study, a photosynthesis-based Gas-exchange Evapotranspiration Model (GEM) is integrated into the Noah land-surface model replacing the traditional Jarvis scheme for estimating the canopy resistance and transpiration. Using 18-month simulations from the High Resolution Land Data Assimilation System (HRLDAS), the impact of the photosynthesis-based approach on the simulated canopy resistance, surface heat fluxes, soil moisture, and soil temperature over different vegetation types is evaluated using data from the Atmospheric Radiation Measurement (ARM) site, Oklahoma Mesonet, 2002 International H2O Project (IHOP_2002), and three Ameriflux sites. Incorporation of GEM into Noah improves the surface energy fluxes as well as the associated diurnal cycle of soil moisture and soil temperature during both wet and dry periods. An analysis of midday, average canopy resistance shows similar day-to-day trends in the model fields as seen in observed patterns. Bias and standard deviation analyses for soil temperature and surface fluxes show that GEM responds somewhat better than the Jarvis scheme, mainly because the Jarvis approach relies on a parametrised minimum canopy resistance and meteorological variables such as air temperature and incident radiation. The analyses suggest that adding a photosynthesis-based transpiration scheme such as GEM improves the ability of the land-data assimilation system to simulate evaporation and transpiration under a range of soil and vegetation conditions.

  1. Formulation of Subgrid Variability and Boundary-Layer Cloud Cover in Large-Scale Models

    DTIC Science & Technology

    1999-02-28

    prescribed as described above. Additional model details are given in the appendix. 3. Advection and Radiation Forcing To make a fair comparison with...BATS land-surface scheme to study land- surface/atmosphere interactions. Dept de Termodinamica Universität de Valencia SPAIN Ernesto LOPEZ-BAEZA

  2. Construction of dissipative particle dynamics models for complex fluids via the Mori-Zwanzig formulation.

    PubMed

    Li, Zhen; Bian, Xin; Caswell, Bruce; Karniadakis, George Em

    2014-11-21

    We present a bottom-up coarse-graining procedure to construct mesoscopic force fields directly from microscopic dynamics. By grouping many bonded atoms in the molecular dynamics (MD) system into a single cluster, we compute both the conservative and non-conservative interactions between neighboring clusters. In particular, we perform MD simulations of polymer melts to provide microscopic trajectories for evaluating coarse-grained (CG) interactions. Subsequently, dissipative particle dynamics (DPD) is considered as the effective dynamics resulting from the Mori-Zwanzig (MZ) projection of the underlying atomistic dynamics. The forces between finite-size clusters have, in general, both radial and transverse components and hence we employ four different DPD models to account differently for such interactions. Quantitative comparisons between these DPD models indicate that the DPD models with MZ-guided force fields yield much better static and dynamics properties, which are consistent with the underlying MD system, compared to standard DPD with empirical formulae. When the rotational motion of the particle is properly taken into account, the entire velocity autocorrelation function of the MD system as well as the pair correlation function can be accurately reproduced by the MD-informed DPD model. Since this coarse-graining procedure is performed on an unconstrained MD system, our framework is general and can be used in other soft matter systems in which the clusters can be faithfully defined as CG particles.

  3. Formulation, General Features and Global Calibration of a Bioenergetically-Constrained Fishery Model

    PubMed Central

    Bianchi, Daniele; Galbraith, Eric D.

    2017-01-01

    Human exploitation of marine resources is profoundly altering marine ecosystems, while climate change is expected to further impact commercially-harvested fish and other species. Although the global fishery is a highly complex system with many unpredictable aspects, the bioenergetic limits on fish production and the response of fishing effort to profit are both relatively tractable, and are sure to play important roles. Here we describe a generalized, coupled biological-economic model of the global marine fishery that represents both of these aspects in a unified framework, the BiOeconomic mArine Trophic Size-spectrum (BOATS) model. BOATS predicts fish production according to size spectra as a function of net primary production and temperature, and dynamically determines harvest spectra from the biomass density and interactive, prognostic fishing effort. Within this framework, the equilibrium fish biomass is determined by the economic forcings of catchability, ex-vessel price and cost per unit effort, while the peak harvest depends on the ecosystem parameters. Comparison of a large ensemble of idealized simulations with observational databases, focusing on historical biomass and peak harvests, allows us to narrow the range of several uncertain ecosystem parameters, rule out most parameter combinations, and select an optimal ensemble of model variants. Compared to the prior distributions, model variants with lower values of the mortality rate, trophic efficiency, and allometric constant agree better with observations. For most acceptable parameter combinations, natural mortality rates are more strongly affected by temperature than growth rates, suggesting different sensitivities of these processes to climate change. These results highlight the utility of adopting large-scale, aggregated data constraints to reduce model parameter uncertainties and to better predict the response of fisheries to human behaviour and climate change. PMID:28103280

  4. Effect of roughness formulation on the performance of a coupled wave, hydrodynamic, and sediment transport model

    USGS Publications Warehouse

    Ganju, Neil K.; Sherwood, Christopher R.

    2010-01-01

    A variety of algorithms are available for parameterizing the hydrodynamic bottom roughness associated with grain size, saltation, bedforms, and wave–current interaction in coastal ocean models. These parameterizations give rise to spatially and temporally variable bottom-drag coefficients that ostensibly provide better representations of physical processes than uniform and constant coefficients. However, few studies have been performed to determine whether improved representation of these variable bottom roughness components translates into measurable improvements in model skill. We test the hypothesis that improved representation of variable bottom roughness improves performance with respect to near-bed circulation, bottom stresses, or turbulence dissipation. The inner shelf south of Martha’s Vineyard, Massachusetts, is the site of sorted grain-size features which exhibit sharp alongshore variations in grain size and ripple geometry over gentle bathymetric relief; this area provides a suitable testing ground for roughness parameterizations. We first establish the skill of a nested regional model for currents, waves, stresses, and turbulent quantities using a uniform and constant roughness; we then gauge model skill with various parameterization of roughness, which account for the influence of the wave-boundary layer, grain size, saltation, and rippled bedforms. We find that commonly used representations of ripple-induced roughness, when combined with a wave–current interaction routine, do not significantly improve skill for circulation, and significantly decrease skill with respect to stresses and turbulence dissipation. Ripple orientation with respect to dominant currents and ripple shape may be responsible for complicating a straightforward estimate of the roughness contribution from ripples. In addition, sediment-induced stratification may be responsible for lower stresses than predicted by the wave–current interaction model.

  5. Evaluation of -2 RANTES vaginal microbicide formulations in a nonhuman primate simian/human immunodeficiency virus (SHIV) challenge model.

    PubMed

    Kish-Catalone, Tina; Pal, Ranajit; Parrish, John; Rose, Nicholas; Hocker, Lindsey; Hudacik, Lauren; Reitz, Marvin; Gallo, Robert; Devico, Anthony

    2007-01-01

    A potential strategy to combat the worldwide AIDS epidemic is to develop a vaginal microbicide that prevents the sexual transmission of HIV-1. One approach for preventing vaginal HIV transmission is to block the viral coreceptor CCR5 with naturally occurring chemokine ligands. In this study, we used a cynomolgus macaque model to evaluate whether a variant of the CCR5 ligand RANTES (-2 RANTES), tested alone or in a nonphospholipid liposome carrier (Novasomes 7474), blocks vaginal challenge with a CCR5-tropic simian/human immunodeficiency virus (SHIV(162P3)). When tested in vitro, the synthetic chemokine potently inhibited SHIV(162P3) infection of cynomolgus macaque peripheral blood mononuclear cells (PBMC). Colposcopic examinations of treated animals and histological examination of cervicovaginal biopsies showed minimal signs of tissue inflammation following vaginal application of Novasomes 7474, -2 RANTES formulated in Novasomes 7474, or -2 RANTES alone. Following vaginal challenge with SHIV(162P3), complete protection was observed in four of six animals treated vaginally with -2 RANTES (0.13 mM) formulated in Novasomes 7474. However, the same proportion of animals was protected by treatment with Novasomes 7474 carrier alone. Two of five animals treated with 0.5 mM -2 RANTES in PBS were protected from infection. Further, all animals were infected when treated with lower chemokine concentrations. These findings indicate that natural CCR5 ligands may have limited efficacy in stringent nonhuman primate models for vaginal infection. In comparison, liposomal agents such as Novasomes 7474 provide comparatively robust protection against vaginal transmission.

  6. Napping-Ultra Flash Profile as a Tool for Category Identification and Subsequent Model System Formulation of Caramel Corn Products.

    PubMed

    Mayhew, Emily; Schmidt, Shelly; Lee, Soo-Yeun

    2016-07-01

    In a novel approach to formulation, the flash descriptive profiling technique Napping-Ultra Flash Profile (Napping-UFP) was used to characterize a wide range of commercial caramel corn products. The objectives were to identify product categories, develop model systems based on product categories, and correlate analytical parameters with sensory terms generated through the Napping-UFP exercise. In one 2 h session, 12 panelists participated in 4 Napping-UFP exercises, describing and grouping, on a 43×56 cm paper sheet, 12 commercial caramel corn samples by degree of similarity, globally and in terms of aroma-by-mouth, texture, and taste. The coordinates of each sample's placement on the paper sheet and descriptive terms generated by the panelists were used to conduct Multiple Factor Analysis (MFA) and hierarchical clustering of the samples. Strong trends in the clustering of samples across the 4 Napping-UFP exercises resulted in the determination of 3 overarching types of commercial caramel corn: "small-scale dark" (typified by burnt, rich caramel corn), "large-scale light" (typified by light and buttery caramel corn), and "large-scale dark" (typified by sweet and molasses-like caramel corn). Representative samples that best exemplified the properties of each category were used as guides in the formulation of 3 model systems that represent the spread of commercial caramel corn products. Analytical testing of the commercial products, including aw measurement, moisture content determination, and thermal characterization via differential scanning calorimetry, were conducted and results related to sensory descriptors using Spearman's correlation.

  7. Aquivalence revisited--new model formulation and application to assess environmental fate of ionic pharmaceuticals in Hamilton Harbour, Lake Ontario.

    PubMed

    Csiszar, Susan A; Gandhi, Nilima; Alexy, Radka; Benny, Donald T; Struger, John; Marvin, Chris; Diamond, Miriam L

    2011-07-01

    A model formulation based on "aquivalence", as defined in terms of activity is presented to estimate the multimedia fate of ionizing chemicals. The aquivalence approach is analogous to fugacity but aquivalence is applicable to neutral and ionizing compounds, and has been applied previously to speciating chemicals, notably metals. The new aquivalence-based mass-balance model treats ionizing organic compounds that exist as interconverting neutral and ionic species which are subject to fate processes at differing rates. The model is illustrated by application to four ionizing pharmaceuticals in Hamilton Harbour, Lake Ontario. At the system pH of 7.9-8.5, ibuprofen, gemfibrozil, and naproxen are expected to be almost entirely ionic and triclosan split between ionic and neutral forms. Measured seasonal surface water concentrations, which were 2-10 times lower in the late summer and fall than during spring, were used to solve for unknown values of chemical half-life in the water column due to degradation (photo- and bio-) of the ionizing and neutral forms and secondarily, ionic sorption coefficients of the ionizing forms. Model estimates of half-lives in the habour's water ranged from 11 to 77, 11 to 147 and 10 to 37 for ionic ibuprofen, gemfibrozil, and naproxen, respectively; and 4-22 days and 2-9 days for ionic and neutral triclosan, respectively, with the shortest half-lives in spring and the longest in summer.

  8. Population pharmacokinetic and pharmacodynamic modeling of different formulations of ONO-5334, cathepsin K inhibitor, in Caucasian and Japanese postmenopausal females.

    PubMed

    Hasegawa, Chihiro; Ohno, Tomoya; Umemura, Takeo; Honda, Naoki; Ohyama, Michiyo; Nagase, Shinichi; Small, Maria; Deacon, Steve; Ogawa, Mikio; Ieiri, Ichiro

    2014-01-01

    ONO-5334, a selective inhibitor of cathepsin K, is a potential new treatment for osteoporosis. The objectives of this study were to (1) develop population pharmacokinetic-pharmacodynamic (PK-PD) models for ONO-5334 using dose-ascending data from healthy postmenopausal females, (2) examine comparability of PK and/or PD profile between Caucasian and Japanese, and (3) compare PK-PD profile between immediate release tablet (IRT) and sustained release tablet (SRT). The population PK-PD models were developed for each formulation for post-dose levels of bone resorption markers (serum CTX and NTX). The data were provided from 4 phase 1 studies with total of 201 Caucasian and 94 Japanese subjects. Plasma concentrations of ONO-5334 and bone resorption markers were thoroughly evaluated in those studies. An indirect response model described relationships between bone resorption markers and plasma concentrations of ONO-5334. There was no significant difference in PK and pharmacodynamic potency (IC50 ) between Caucasian and Japanese. Based on the developed model, serum CTX and NTX after administration of ONO-5334 IRT or SRT were simulated, and the results showed that ONO-5334 SRT would provide comparable PD effect on bone resorption markers with lower dose relative to IRT.

  9. Utilizing physiologically based pharmacokinetic modeling to inform formulation and clinical development for a compound with pH-dependent solubility.

    PubMed

    Chung, John; Alvarez-Nunez, Fernando; Chow, Vincent; Daurio, Dominick; Davis, John; Dodds, Michael; Emery, Maurice; Litwiler, Kevin; Paccaly, Anne; Peng, Joanna; Rock, Brooke; Wienkers, Larry; Yang, Charles; Yu, Zhigang; Wahlstrom, Jan

    2015-04-01

    ARRY-403 is a glucokinase activator developed for the treatment of diabetes. Less than dose-proportional exposure was observed during single ascending dose studies with ARRY-403. A physiologically based pharmacokinetic (PBPK) model for ARRY-403 was developed through integration of in vitro physicochemical data with precipitation time estimations based on results from the single ascending dose studies; PBPK modeling indicated that the primary cause of the less than dose-proportional exposure was dose-limited absorption because of pH-dependent solubility. The impact of dose, particle size, and fasted or fed state on ARRY-403 exposure was examined through sensitivity analyses and used to refine the PBPK model. On the basis of the marked pH-dependent solubility of ARRY-403, the refined PBPK model was used to simulate the effects of acid-reducing agents (ARAs) on ARRY-403 exposure, as these agents are widely available and could be coadministered with ARRY-403. The simulations indicated that a clinical study with an ARA was warranted; in a clinical study, famotidine had a marked effect on ARRY-403 exposure. This approach, based on the "predict, learn, and confirm" paradigm, demonstrates the utility of integrating physicochemical properties, in vitro experiments, and clinical results using PBPK to inform formulation development and to guide clinical study design. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Phase field model of fluid-driven fracture in elastic media: Immersed-fracture formulation and validation with analytical solutions

    NASA Astrophysics Data System (ADS)

    Santillán, David; Juanes, Ruben; Cueto-Felgueroso, Luis

    2017-04-01

    Propagation of fluid-driven fractures plays an important role in natural and engineering processes, including transport of magma in the lithosphere, geologic sequestration of carbon dioxide, and oil and gas recovery from low-permeability formations, among many others. The simulation of fracture propagation poses a computational challenge as a result of the complex physics of fracture and the need to capture disparate length scales. Phase field models represent fractures as a diffuse interface and enjoy the advantage that fracture nucleation, propagation, branching, or twisting can be simulated without ad hoc computational strategies like remeshing or local enrichment of the solution space. Here we propose a new quasi-static phase field formulation for modeling fluid-driven fracturing in elastic media at small strains. The approach fully couples the fluid flow in the fracture (described via the Reynolds lubrication approximation) and the deformation of the surrounding medium. The flow is solved on a lower dimensionality mesh immersed in the elastic medium. This approach leads to accurate coupling of both physics. We assessed the performance of the model extensively by comparing results for the evolution of fracture length, aperture, and fracture fluid pressure against analytical solutions under different fracture propagation regimes. The excellent performance of the numerical model in all regimes builds confidence in the applicability of phase field approaches to simulate fluid-driven fracture.

  11. Moving Towards Integrated Policy Formulation and Evaluation: The Green Economy Model

    NASA Astrophysics Data System (ADS)

    Bassi, Andrea M.

    2015-12-01

    The mainstreaming of concepts related to the Green Economy, an action-oriented approach to reach sustainable development, has increased demands for integrated models that can shed light on the complex relations existing across social, economic and environmental indicators. A gap exists, whereby our thinking is rapidly evolving, but the tools available are still in the vast majority of cases sectorial, leading to planning processes taking place in silos. To avoid the emergence of side effects, and anticipate future threats and opportunities, a more systemic approach is needed. The Green Economy Model (GEM) was created taking into account four main capitals and their interconnections: physical capital, human capital, social capital and natural capital. The application of GEM in 10 countries has shown its capability to coherently represent reality and generate results that can more effectively inform decision making.

  12. Geometry Optimization in Polarizable QM/MM Models: The Induced Dipole Formulation.

    PubMed

    Caprasecca, Stefano; Jurinovich, Sandro; Viani, Lucas; Curutchet, Carles; Mennucci, Benedetta

    2014-04-08

    We present the mathematical derivation and the computational implementation of the analytical geometry derivatives for a polarizable QM/MM model (QM/MMPol). In the adopted QM/MMPol model, the focused part is treated at QM level of theory, while the remaining part (the environment) is described classically as a set of fixed charges and induced dipoles. The implementation is performed within the ONIOM procedure, resulting in a polarizable embedding scheme, which can be applied to solvated and embedded systems and combined with different polarizable force fields available in the literature. Two test cases characterized by strong hydrogen-bond and dipole-dipole interactions, respectively, are used to validate the method with respect to the nonpolarizable one. Finally, an application to geometry optimization of the chromophore of Rhodopsin is presented to investigate the impact of including mutual polarization between the QM and the classical parts in conjugated systems.

  13. Modelling Viscoelastic Behaviour of Polymer by A Mixed Velocity, Displacement Formulation - Numerical and Experimental Results

    SciTech Connect

    Pham, VT.; Silva, L.; Digonnet, H.; Combeaud, C.; Billon, N.; Coupez, T.

    2011-05-04

    The objective of this work is to model the viscoelastic behaviour of polymer from the solid state to the liquid state. With this objective, we perform experimental tensile tests and compare with simulation results. The chosen polymer is a PMMA whose behaviour depends on its temperature. The computation simulation is based on Navier-Stokes equations where we propose a mixed finite element method with an interpolation P1+/P1 using displacement (or velocity) and pressure as principal variables. The implemented technique uses a mesh composed of triangles (2D) or tetrahedra (3D). The goal of this approach is to model the viscoelastic behaviour of polymers through a fluid-structure coupling technique with a multiphase approach.

  14. A Riemann-Hilbert formulation for the finite temperature Hubbard model

    NASA Astrophysics Data System (ADS)

    Cavaglià, Andrea; Cornagliotto, Martina; Mattelliano, Massimo; Tateo, Roberto

    2015-06-01

    Inspired by recent results in the context of AdS/CFT integrability, we reconsider the Thermodynamic Bethe Ansatz equations describing the 1D fermionic Hubbard model at finite temperature. We prove that the infinite set of TBA equations are equivalent to a simple nonlinear Riemann-Hilbert problem for a finite number of unknown functions. The latter can be transformed into a set of three coupled nonlinear integral equations defined over a finite support, which can be easily solved numerically. We discuss the emergence of an exact Bethe Ansatz and the link between the TBA approach and the results by Jüttner, Klümper and Suzuki based on the Quantum Transfer Matrix method. We also comment on the analytic continuation mechanism leading to excited states and on the mirror equations describing the finite-size Hubbard model with twisted boundary conditions.

  15. Formulation of a generalized experimental model for a manually driven flywheel motor and its optimization.

    PubMed

    Modak, J P; Bapat, A R

    1994-04-01

    A manually driven brick-making machine has recently been developed without the benefit of any design data. The machine consists of three main units: a pedal-driven flywheel motor; the transmission between the flywheel shaft and the input shaft of the process machine; and the process unit, consisting of auger, cone and die. The machine was essentially developed on the basis of general mechanical design experience and intuition. In spite of this, it proved to be functional and economically viable. However, it was felt essential to develop it scientifically. This paper reports on the full development of the pedal-driven flywheel motor. As this is a human-machine system it is highly unlikely that a logic-based model can be established. Therefore an experimental method is adopted to evolve a generalized experimental model, which is further optimized to satisfy several objective functions.

  16. Final Report for Formulation of Moist Dynamics and Physics for Future Climate Models

    SciTech Connect

    Celal S. Konor

    2008-04-30

    In this project, one of our goals is to develop atmospheric models, in which innovative ideas on improving the quality of moisture predictions can be tested. Our other goal is to develop an explicit time integration scheme based on the multi-point differencing (MED) that does the same job as an implicit trapezoidal scheme but uses information only from limited number of grid points. Below we discuss the work performed at UCLA toward these goals during the funding period indicated above.

  17. Atmospheric mercury simulation using the CMAQ model: formulation description and analysis of wet deposition results

    NASA Astrophysics Data System (ADS)

    Bullock, O. Russell; Brehme, Katherine A.

    The community multiscale air quality (CMAQ) modeling system has been adapted to simulate the emission, transport, transformation and deposition of atmospheric mercury (Hg) in three distinct forms: elemental Hg gas, reactive gaseous Hg, and particulate Hg. Emissions of Hg are currently defined from information published in the Environmental Protection Agency's Mercury Study Report to Congress. The atmospheric transport of these three forms of Hg is simulated in the same manner as for all other substances simulated by the CMAQ model to date. Transformations of Hg are simulated with four new chemical reactions within the standard CMAQ gaseous chemistry framework and a highly modified cloud chemistry mechanism which includes a compound-specific speciation for oxidized forms of Hg, seven new aqueous-phase Hg reactions, six aqueous Hg chemical equilibria, and a two-way mechanism for the sorption of dissolved oxidized Hg to elemental carbon particles. The CMAQ Hg model simulates the partitioning of reactive gaseous Hg between air and cloud water based on the Henry's constant for mercuric chloride. Henry's equilibrium is assumed for elemental Hg also. Particulate Hg is assumed to be incorporated into the aqueous medium during cloud nucleation. Wet and dry deposition is simulated for each of the three forms of Hg. Wet deposition rate is calculated based on precipitation information from the CMAQ meteorological processor and the physicochemical Hg speciation in the cloud chemistry mechanism. Dry deposition rate is calculated based on dry deposition velocity and air concentration information for each of the three forms of Hg. The horizontal modeling domain covers the central and eastern United States and adjacent southern Canada. An analysis of simulated Hg wet deposition versus weekly observations is performed. The results are described for two evaluation periods: 4 April-2 May 1995, and 20 June-18 July 1995.

  18. Dynamic Rate Dependent Elastoplastic Damage Modeling of Concrete Subject to Blast Loading: Formulation and Computational Aspects

    DTIC Science & Technology

    1990-10-31

    continuum theory may be considered for damage mechanics; see, e.g., Bazant , Lin and Pijaudier-Cabot [1987], Eringen [1983], Eringen [1987], Eringen and...Edelen [1972], Pijaudier-Cabot and Bazant [19871, Xia et al. [1987]. The essence of nonlocal theory includes the characteristic length (1) and the...Eringen and Edelen [1972], Bazant et al. [1987], Xia et al. [1987]), or the viscous damage model presented in Section 3.4. The nonlocal damage

  19. Introduction of an interproximal mineralisation model to measure remineralisation caused by novel formulations containing calcium silicate, sodium phosphate salts and fluoride.

    PubMed

    Jones, Siân Bodfel; Davies, Maria; Chapman, Nicholas; Willson, Richard; Hornby, Kate; Joiner, Andrew; West, Nicola X

    2014-06-01

    To introduce a new interproximal mineralisation model and to investigate the effectiveness of novel toothpaste and dual phase gel formulations to remineralise acid softened enamel in a simulated interproximal environment. Specimens were positioned opposite each other with an approximately 100 μm space between enamel surfaces to simulate an interproximal environment. Target specimens were demineralised in 1% (w/v) citric acid, pH3.75. Specimens were daily immersed in artificial saliva (AS) for 1h, treated with formulations, re-immersed in AS for 6h, re-treated and re-immersed in AS for a further 1h. Study 1 evaluated prototype calcium silicate/phosphate fluoride toothpaste formulations. Study 2 evaluated novel calcium silicate/phosphate fluoride toothpaste and dual phase gel formulations. Both studies contained fluoridated and non-fluoridated controls. The surface microhardness of each target enamel block was measured following demineralisation and following days three, seven and fourteen for study one and after days one, three and seven for study two. This new mineralisation model was able to show increased remineralisation from calcium silicate/phosphate fluoride prototype formulations over fluoridated formulations alone, after three and seven days of treatment. Using this new model, the combined application of novel calcium silicate/phosphate fluoride toothpaste and novel calcium silicate/phosphate fluoride dual phase gel showed the greatest amount of remineralisation, which was significantly greater than sodium fluoride and non-fluoride controls. Employing a new interproximal mineralisation model successfully determined the remineralisation potential of novel calcium silicate/phosphate fluoride oral healthcare formulations. Modifying a mineralisation model to include specimens positioned in an interproximal environment allows us to better understand the remineralisation potential of oral healthcare products. It is important to minimise mineral loss at

  20. Analysis of Initial Cell Spreading Using Mechanistic Contact Formulations for a Deformable Cell Model

    PubMed Central

    Odenthal, Tim; Smeets, Bart; Van Liedekerke, Paul; Tijskens, Engelbert; Van Oosterwyck, Hans; Ramon, Herman

    2013-01-01

    Adhesion governs to a large extent the mechanical interaction between a cell and its microenvironment. As initial cell spreading is purely adhesion driven, understanding this phenomenon leads to profound insight in both cell adhesion and cell-substrate interaction. It has been found that across a wide variety of cell types, initial spreading behavior universally follows the same power laws. The simplest cell type providing this scaling of the radius of the spreading area with time are modified red blood cells (RBCs), whose elastic responses are well characterized. Using a mechanistic description of the contact interaction between a cell and its substrate in combination with a deformable RBC model, we are now able to investigate in detail the mechanisms behind this universal power law. The presented model suggests that the initial slope of the spreading curve with time results from a purely geometrical effect facilitated mainly by dissipation upon contact. Later on, the spreading rate decreases due to increasing tension and dissipation in the cell's cortex as the cell spreads more and more. To reproduce this observed initial spreading, no irreversible deformations are required. Since the model created in this effort is extensible to more complex cell types and can cope with arbitrarily shaped, smooth mechanical microenvironments of the cells, it can be useful for a wide range of investigations where forces at the cell boundary play a decisive role. PMID:24146605

  1. Nasal administration of an angiotensin antagonist in the rat model: effect of bioadhesive formulations on the distribution of drugs to the systemic and central nervous systems.

    PubMed

    Charlton, S T; Davis, S S; Illum, L

    2007-06-29

    The effect of bioadhesive formulations on the direct transport of an angiotensin antagonist drug ((14)C-GR138950) from the nasal cavity to the central nervous system was evaluated in a rat model. Three different bioadhesive polymer formulations (3% pectin LM-5, 1.0% pectin LM-12 and 0.5% chitosan G210) containing the drug were administered nasally to rats by inserting a dosing cannula 7mm into the nasal cavity after which the plasma and brain tissue levels were measured. It was found that the polymer formulations provided significantly higher plasma levels and significantly lower brain tissue levels of drug than a control, in the form of a simple drug solution. Changing the depth of insertion of the cannula from 7 to 15mm, in order to reach the olfactory region in the nasal cavity significantly decreased plasma levels and significantly increased brain tissue levels of drug for the two formulations studied (1.0% pectin LM-12 and a simple drug solution). There was no significant difference between the drug availability for the bioadhesive formulation and the control in the brain when the longer cannula was used for administration. It is suggested that the conventional rat model is not suitable for evaluation of the effects of bioadhesive formulations in nose-to-brain delivery.

  2. Numerical Modeling of Crystal of ZnSe by Physical Vapor Transport - Towards a more Comprehensive Formulations

    NASA Technical Reports Server (NTRS)

    Ramachandran, N.

    1999-01-01

    Crystal growth from the vapor phase has various advantages over melt growth. The main advantage is from a lower processing temperature which makes the process more amenable in instances where the melting temperature of the crystal is high. Other benefits stem from the inherent purification mechanism in the process due to differences in the vapor pressures of the native elements and impurities, and the enhanced interfacial morphological stability during the growth process. Further, the implementation of PVT growth in closed ampoules affords experimental simplicity with minimal needs for complex process control which makes it an ideal candidate for space investigations in systems where gravity tends to have undesirable effects on the growth process. Bulk growth of wide band gap II-VI semiconductors by physical vapor transport has been developed and refined over the past several years at NASA MSFC. Results from a modeling study of PVT crystal growth of ZnSe are reported in this paper. The PVT process is numerically investigated using both two-dimensional and fully three-dimensional formulation of the governing equations and associated boundary conditions. Both the incompressible Boussinesq approximation and the compressible model are tested to determine the influence of gravity on the process and to discern the differences between the two approaches. The influence of a residual gas is included in the models. The results show that both the incompressible and compressible approximations provide comparable results and the presence of a residual gas tends to measurably reduce the mass flux in the system. Detailed flow, thermal and concentration profiles will be provided in the final manuscript along with computed heat and mass transfer rates. Comparisons with the 1-D model will also be provided. The effect of gravity on the process from numerical computations shows subtle effects although experimental evidence from vertically and horizontally grown samples show dramatic

  3. Comparison between a Terramechanics Model and a Continuum Soil Model Implemented within the Absolute Nodal Coordinate Formulation

    DTIC Science & Technology

    2012-08-01

    an empirically derived constitutive model are two clear assumptions inherent in terramechanics based approaches. The (modified) Bekker soil models...an empirically derived constitutive model are two clear assumptions inherent in terramechanics based approaches. The (modified) Bekker soil models...relationships that could be used to predict at least qualitatively the response of soils under various conditions ( Bekker , 1969). Parametric models, which

  4. Atmospheric infrasound propagation modelling using the reflectivity method with a direct formulation of the wind effect

    NASA Astrophysics Data System (ADS)

    Maupin, Valerie; Näsholm, Sven Peter; Schweitzer, Johannes; Gibbons, Steven J.

    2016-04-01

    We recently advocated using the reflectivity method, also known as the wavenumber integration method or fast-field program, to model atmospheric infrasound propagation at regional distances. The advantage of the reflectivity method is its ability to model the full wavefield, including diffractive effects with head waves and shadow zone arrivals, in a broad frequency range but still at a relatively low computational cost. Attenuation can easily be included, giving the possibility to analyse relative amplitudes and frequency content of the different arrivals. It has clear advantages compared with ray theory in terms of predicting phases considering the particular frequent occurrence of shadow zone arrivals in infrasound observations. Its main limitation, at least in the traditional form of the method, lies in the fact that it can only handle range-independent models. We presented earlier some reflectivity method simulations of an observed accidental explosion in Norway. Wind intensity and direction are non-negligible parameters for infrasound propagation and these are appropriately taken into account in most infrasound ray-tracing codes. On the other hand, in the previous reflectivity simulations wind was taken into account only through the effective sound speed approximation where the horizontal projection of the wind field is added to the adiabatic sound speed profiles. This approximation is appropriate for dominantly horizontal propagation but can give incorrect arrival times and shadow zone locations for waves which have a significant portion of their propagation path at more vertical incidence, like thermospheric arrivals. We present here how we have modified the original reflectivity algorithm in order to take the wind into account in a more correct fashion, and how this improvement influences the synthetics.

  5. On the formulation of a minimal uncertainty model for robust control with structured uncertainty

    NASA Technical Reports Server (NTRS)

    Belcastro, Christine M.; Chang, B.-C.; Fischl, Robert

    1991-01-01

    In the design and analysis of robust control systems for uncertain plants, representing the system transfer matrix in the form of what has come to be termed an M-delta model has become widely accepted and applied in the robust control literature. The M represents a transfer function matrix M(s) of the nominal closed loop system, and the delta represents an uncertainty matrix acting on M(s). The nominal closed loop system M(s) results from closing the feedback control system, K(s), around a nominal plant interconnection structure P(s). The uncertainty can arise from various sources, such as structured uncertainty from parameter variations or multiple unsaturated uncertainties from unmodeled dynamics and other neglected phenomena. In general, delta is a block diagonal matrix, but for real parameter variations delta is a diagonal matrix of real elements. Conceptually, the M-delta structure can always be formed for any linear interconnection of inputs, outputs, transfer functions, parameter variations, and perturbations. However, very little of the currently available literature addresses computational methods for obtaining this structure, and none of this literature addresses a general methodology for obtaining a minimal M-delta model for a wide class of uncertainty, where the term minimal refers to the dimension of the delta matrix. Since having a minimally dimensioned delta matrix would improve the efficiency of structured singular value (or multivariable stability margin) computations, a method of obtaining a minimal M-delta would be useful. Hence, a method of obtaining the interconnection system P(s) is required. A generalized procedure for obtaining a minimal P-delta structure for systems with real parameter variations is presented. Using this model, the minimal M-delta model can then be easily obtained by closing the feedback loop. The procedure involves representing the system in a cascade-form state-space realization, determining the minimal uncertainty matrix

  6. Hydrology Model Formulation within the Training Range Environmental Evaluation and Characterization System (TREECS)

    DTIC Science & Technology

    2014-02-01

    pore water. Consequently, the ground must be free of any snowpack for rainfall impact to occur. The model calculates whether the daily mean air...EL TR-14-2 13 where, bmlt = melt factor (mm H2O/day-oC) snocov = fraction of area covered by snow (0 to 1.0) isnow T = snowpack ...é ù+ê ú = ê ú ê ú ê úë û 2 (14) The temperature of the snowpack can be estimated from ( )T T l T lsnow snow sno av snoi i = - + ´ - 1 1 (15

  7. Cubic spline function interpolation in atmosphere models for the software development laboratory: Formulation and data

    NASA Technical Reports Server (NTRS)

    Kirkpatrick, J. C.

    1976-01-01

    A tabulation of selected altitude-correlated values of pressure, density, speed of sound, and coefficient of viscosity for each of six models of the atmosphere is presented in block data format. Interpolation for the desired atmospheric parameters is performed by using cubic spline functions. The recursive relations necessary to compute the cubic spline function coefficients are derived and implemented in subroutine form. Three companion subprograms, which form the preprocessor and processor, are also presented. These subprograms, together with the data element, compose the spline fit atmosphere package. Detailed FLOWGM flow charts and FORTRAN listings of the atmosphere package are presented in the appendix.

  8. Multi-sensor Cloud Retrieval Simulator and Remote Sensing from Model Parameters . Pt. 1; Synthetic Sensor Radiance Formulation; [Synthetic Sensor Radiance Formulation

    NASA Technical Reports Server (NTRS)

    Wind, G.; DaSilva, A. M.; Norris, P. M.; Platnick, S.

    2013-01-01

    In this paper we describe a general procedure for calculating synthetic sensor radiances from variable output from a global atmospheric forecast model. In order to take proper account of the discrepancies between model resolution and sensor footprint, the algorithm takes explicit account of the model subgrid variability, in particular its description of the probability density function of total water (vapor and cloud condensate.) The simulated sensor radiances are then substituted into an operational remote sensing algorithm processing chain to produce a variety of remote sensing products that would normally be produced from actual sensor output. This output can then be used for a wide variety of purposes such as model parameter verification, remote sensing algorithm validation, testing of new retrieval methods and future sensor studies.We show a specific implementation using the GEOS-5 model, the MODIS instrument and the MODIS Adaptive Processing System (MODAPS) Data Collection 5.1 operational remote sensing cloud algorithm processing chain (including the cloud mask, cloud top properties and cloud optical and microphysical properties products). We focus on clouds because they are very important to model development and improvement.

  9. A novel protective formulation of Palmitoylethanolamide in experimental model of contrast agent induced nephropathy.

    PubMed

    Cordaro, M; Impellizzeri, D; Bruschetta, G; Siracusa, R; Crupi, R; Di Paola, R; Esposito, E; Cuzzocrea, S

    2016-01-05

    Contrast-induced nephropathy (CIN) is a complication in patients after administration of iodinated contrast media. Several risk factors contribute to the development and progression of CIN, including hypertension, diabetes, and dyslipidemia. Animal models of CIN by surgical intervention to reproduce its clinical and pathology has been developed, and thus, therapeutic methods tested. Palmitoylethanolamide (PEA) is a member of the fatty acid ethanolamine family with analgesic and anti-inflammatory effects. In this study, we analyzed streptozotocin-induced diabetes model and in an another set of experiment a surgical remotion of the kidney with the aim of evaluating effect of ultramicronized Palmitoylethanolamide (PEA-um(®)) on contrast induced renal disfunction and glomerular morphology alteration. In a first step of our study, we demonstrated that PEA-um(®) significantly reduced CIN-mediated glomerular dysfunction, modulates Na(+) and K(+) levels in plasma and decreased urine and plasma NGAL levels and α-GST urine levels. Moreover, in a second set of experiment we investigated how PEA-um(®) reduced creatinine and BUN plasma levels after nephrectomy, ameliorate renal and medullary blood flow and re-established renal parenchymal after CIN induction as well as after nephrectomy. Take together our results demonstrated that PEA-um(®) are able to preventing CIN in diabetic rats and alteration of biochemical parameters after nephrectomy.

  10. Environmental fate and transport of chemical signatures from buried landmines -- Screening model formulation and initial simulations

    SciTech Connect

    Phelan, J.M.; Webb, S.W.

    1997-06-01

    The fate and transport of chemical signature molecules that emanate from buried landmines is strongly influenced by physical chemical properties and by environmental conditions of the specific chemical compounds. Published data have been evaluated as the input parameters that are used in the simulation of the fate and transport processes. A one-dimensional model developed for screening agricultural pesticides was modified and used to simulate the appearance of a surface flux above a buried landmine, estimate the subsurface total concentration, and show the phase specific concentrations at the ground surface. The physical chemical properties of TNT cause a majority of the mass released to the soil system to be bound to the solid phase soil particles. The majority of the transport occurs in the liquid phase with diffusion and evaporation driven advection of soil water as the primary mechanisms for the flux to the ground surface. The simulations provided herein should only be used for initial conceptual designs of chemical pre-concentration subsystems or complete detection systems. The physical processes modeled required necessary simplifying assumptions to allow for analytical solutions. Emerging numerical simulation tools will soon be available that should provide more realistic estimates that can be used to predict the success of landmine chemical detection surveys based on knowledge of the chemical and soil properties, and environmental conditions where the mines are buried. Additional measurements of the chemical properties in soils are also needed before a fully predictive approach can be confidently applied.

  11. Using Historical Precipitation, Temperature, and Runoff Observations to Evaluate Evaporation Formulations in Land Surface Models

    NASA Technical Reports Server (NTRS)

    Koster, Randal D.; Mahanama, P. P.

    2012-01-01

    Key to translating soil moisture memory into subseasonal precipitation and air temperature forecast skill is a realistic treatment of evaporation in the forecast system used - in particular, a realistic treatment of how evaporation responds to variations in soil moisture. The inherent soil moisture-evaporation relationships used in today's land surface models (LSMs), however, arguably reflect little more than guesswork given the lack of evaporation and soil moisture data at the spatial scales represented by regional and global models. Here we present a new approach for evaluating this critical aspect of LSMs. Seasonally averaged precipitation is used as a proxy for seasonally-averaged soil moisture, and seasonally-averaged air temperature is used as a proxy for seasonally-averaged evaporation (e.g., more evaporative cooling leads to cooler temperatures) the relationship between historical precipitation and temperature measurements accordingly mimics in certain important ways nature's relationship between soil moisture and evaporation. Additional information on the relationship is gleaned from joint analysis of precipitation and streamflow measurements. An experimental framework that utilizes these ideas to guide the development of an improved soil moisture-evaporation relationship is described and demonstrated.

  12. CFD modeling of turbulent flows around the SSME main injector assembly using porosity formulation

    NASA Technical Reports Server (NTRS)

    Cheng, Gary C.; Chen, Y. S.; Ruf, Joseph H.

    1992-01-01

    Hot gas turbulent flow distribution around the main injector assembly of the Space Shuttle Main Engine (SSME) and liquid oxygen (LOX) flow distributions through the LOX posts have great effect on the combustion phenomenon inside the main combustion chamber. An advanced computational fluid dynamics (CFD) analysis will help to provide more accurate and efficient characterization of this type of flow field. In order to design a CFD model to be an effective engineering analysis tool with good computational turn-around time and still maintain good accuracy in describing the flow features, the concept of porosity is employed to describe the effects of blockage and drag force due to the presence of the LOX posts in the turbulent flow field around the main injector assembly of the SSME. A validated non-isotropic porosity model is developed and incorporated into an existing Navier-Stokes flow solver (FDNS). Volume and surface porosity parameters, which are based on the configurations of local LOX post clustering, are introduced into the governing equations.

  13. Formulation of an Integrated Model for Freshwater Resources Policy Evaluation in Jordan

    NASA Astrophysics Data System (ADS)

    Gorelick, S.; Yoon, J.; Gawel, E.; Klauer, B.; Klassert, C. J. A.; Sigel, K.; Tilmant, A.; Lachaut, T.; Avisse, N.; Harou, J. J.; Padula, S.; Mustafa, D.

    2014-12-01

    Jordan is one of the four water poorest countries in the world. It is a highly vulnerable arid region whose freshwater system is at a tipping point due to the confluence of severely limited water supplies, rapid population growth, refugee influxes, climate change and variability, internal and transboundary competition for shared freshwater resources, and institutional impediments. Our team is engaged in an interdisciplinary effort aimed at developing a new approach to evaluate policies that enhance sustainability of freshwater resource systems. Our work adopts a multi-agent modeling framework that incorporates institutional complexity to evaluate policy instruments for improving water security in Jordan. We are developing this model using a modular approach, integrating biophysical modules that simulate natural and engineered phenomena (e.g., groundwater-surface water flow, reservoir storage, network routing, salt balance, and crop yield) with human modules that represent behavior at multiple scales of decision making. The human modules adopt a multi-agent simulation approach, defining agents as autonomous decision-makers at the government, administrative, organizational, and user levels. Our goal is to construct a suite of policy intervention scenarios that will form the basis for analysis of freshwater sustainability. This work has benefitted from a strong working relationship with leaders of the water sector in Jordan. Our approach and the merit of the policy interventions should have significant transfer value to other water-stressed regions.

  14. Hamiltonian formulation of the spin-orbit model with time-varying non-conservative forces

    NASA Astrophysics Data System (ADS)

    Gkolias, Ioannis; Efthymiopoulos, Christos; Pucacco, Giuseppe; Celletti, Alessandra

    2017-10-01

    In a realistic scenario, the evolution of the rotational dynamics of a celestial or artificial body is subject to dissipative effects. Time-varying non-conservative forces can be due to, for example, a variation of the moments of inertia or to tidal interactions. In this work, we consider a simplified model describing the rotational dynamics, known as the spin-orbit problem, where we assume that the orbital motion is provided by a fixed Keplerian ellipse. We consider different examples in which a non-conservative force acts on the model and we propose an analytical method, which reduces the system to a Hamiltonian framework. In particular, we compute a time parametrisation in a series form, which allows us to transform the original system into a Hamiltonian one. We also provide applications of our method to study the rotational motion of a body with time-varying moments of inertia, e.g. an artificial satellite with flexible components, as well as subject to a tidal torque depending linearly on the velocity.

  15. A biphasic viscohyperelastic fibril-reinforced model for articular cartilage: formulation and comparison with experimental data.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2007-01-01

    Experiments in articular cartilage have shown highly nonlinear stress-strain curves under finite deformations, nonlinear tension-compression response as well as intrinsic viscous effects of the proteoglycan matrix and the collagen fibers. A biphasic viscohyperelastic fibril-reinforced model is proposed here, which is able to describe the intrinsic viscoelasticity of the fibrillar and nonfibrillar components of the solid phase, the nonlinear tension-compression response and the nonlinear stress-strain curves under tension and compression. A viscohyperelastic constitutive equation was used for the matrix and the fibers encompassing, respectively, a hyperelastic function used previously for the matrix and a hyperelastic law used before to represent biological connective tissues. This model, implemented in an updated Lagrangian finite element code, displayed good ability to follow experimental stress-strain equilibrium curves under tension and compression for human humeral cartilage. In addition, curve fitting of experimental reaction force and lateral displacement unconfined compression curves showed that the inclusion of viscous effects in the matrix allows the description of experimental data with material properties for the fibers consistent with experimental tensile tests, suggesting that intrinsic viscous effects in the matrix of articular cartilage plays an important role in the mechanical response of the tissue.

  16. CFD modeling of turbulent flows around the SSME main injector assembly using porosity formulation

    NASA Astrophysics Data System (ADS)

    Cheng, Gary C.; Chen, Y. S.; Ruf, Joseph H.

    1992-07-01

    Hot gas turbulent flow distribution around the main injector assembly of the Space Shuttle Main Engine (SSME) and liquid oxygen (LOX) flow distributions through the LOX posts have great effect on the combustion phenomenon inside the main combustion chamber. An advanced computational fluid dynamics (CFD) analysis will help to provide more accurate and efficient characterization of this type of flow field. In order to design a CFD model to be an effective engineering analysis tool with good computational turn-around time and still maintain good accuracy in describing the flow features, the concept of porosity is employed to describe the effects of blockage and drag force due to the presence of the LOX posts in the turbulent flow field around the main injector assembly of the SSME. A validated non-isotropic porosity model is developed and incorporated into an existing Navier-Stokes flow solver (FDNS). Volume and surface porosity parameters, which are based on the configurations of local LOX post clustering, are introduced into the governing equations.

  17. CFD modeling of turbulent flows around the SSME main injector assembly using porosity formulation

    NASA Technical Reports Server (NTRS)

    Cheng, Gary C.; Chen, Y. S.; Farmer, Richard C.

    1992-01-01

    Hot gas turbulent flow distribution around the main injector assembly of the Space Shuttle Main Engine (SSME) and LOX flow distribution through the LOX posts have a great effect on the combustion phenomena inside the main combustion chamber. In order to design a CFD model to be an effective engineering analysis tool with good computational turn-around time (especially for 3-D flow problems) and still maintain good accuracy in describing the flow features, the concept of porosity was employed to describe the effects of blockage and drag force due to the presence of the LOX posts in the turbulent flow field around the main injector assembly of the SSME. Two-dimensional numerical studies were conducted to identify the drag coefficients of the flows, both through tube banks and round the shielded posts, over a wide range of Reynolds numbers. Empirical, analytical expressions of the drag coefficients as a function of local flow Reynolds number were then deduced. The porosity model was applied to the turbulent flow around the main injector assembly of the SSME, and analyses were performed. The 3-D CFD analysis was divided into three parts: LOX dome, hot gas injector assembly, and hydrogen cavity. The numerical results indicate that the mixture ratio at the downstream of injector face was close to stoichiometric around baffle elements.

  18. Effect of gasoline formulation on the formation of photosmog: a box model study.

    PubMed

    Geiger, Herald; Becker, Karl H; Wiesen, Peter

    2003-04-01

    Based on exhaust gas analyses from the combustion of five different types of gasoline in a passenger car operated on a chassis dynamometer, box model simulations of the irradiation of exhaust/NOx/air mixtures using an established chemical mechanism for a standardized photosmog scenario were performed. The fuel matrix used covered wide fractional ranges for paraffinic, olefinic, and aromatic hydrocarbons. Two fuels also contained methyl tertiary butyl ether (MTBE). The different O3 profiles calculated for each run were compared and interpreted. The O3 levels obtained were strongly influenced by the exhaust gas concentrations of aromatic and olefinic hydrocarbons. The higher exhaust content of these compounds caused higher O3 production in the smog system investigated. The conclusion of the present study is that the composition of gasoline cannot be taken directly for the estimation of the emissions' O3 creation potential from its combustion. Variation of the dilution in the different calculations showed evidence for an additional influence of transport effects. Accordingly, further detailed exhaust gas analyses followed by more complex modeling studies are necessary for a proper characterization of the relationship between fuel blend and gasoline combustion products.

  19. Moisture Outgassing Rates from TATB-Formulations: Experiments and Kinetic Model Development

    SciTech Connect

    Glascoe, E A; Dinh, L N; Small IV, W

    2009-07-29

    diffusion through pressed parts, or the effects of wet vs. dry machining, or the influence of the synthesis methods in the amount of water present. There are a few different models that have been developed to predict the rate of water release from LX-17 or PBX-9502. These models are, to some extent, limited by the limitations of the experiments. Because all these experiments looked at water release over a relatively short period of time and left the samples relatively undamaged, they serve as a lower bound. In this work, we perform experiments and develop models that can serve as an upper bound on the rate and amount of water that can be released. Our experimental approach is to use temperature programmed desorption (TPD) and monitor the rate and amount of water release as a function of temperature. We analyzed our experimental data using two different kinetic analysis methods (isoconversional analysis and nth-order Arrhenius kinetic fits) and used the results to make predictions. The suitability of these kinetic analysis methods as well as the applicability of these experiments to long term aging (e.g. years) issues are discussed. Using the kinetics from our experiments, we predict the water release at temperature and timescales relevant to the existing literature. Based on our analysis and comparison with older data, the kinetic model(s) developed in this work serve as a relatively accurate (i.e. order of magnitude) method for predicting the water release under a variety of thermal histories.

  20. Computational Models of the Gastrointestinal Environment. 2. Phase Behavior and Drug Solubilization Capacity of a Type I Lipid-Based Drug Formulation after Digestion.

    PubMed

    Birru, Woldeamanuel A; Warren, Dallas B; Han, Sifei; Benameur, Hassan; Porter, Christopher J H; Pouton, Colin W; Chalmers, David K

    2017-03-06

    Lipid-based drug formulations can greatly enhance the bioavailability of poorly water-soluble drugs. Following the oral administration of formulations containing tri- or diglycerides, the digestive processes occurring within the gastrointestinal (GI) tract hydrolyze the glycerides to mixtures of free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior of drugs within the resulting colloidal mixtures is currently not well characterized. This work presents matched in vitro experimental and molecular dynamics (MD) theoretical models of the GI microenvironment containing a digested triglyceride-based (Type I) drug formulation. Both the experimental and theoretical models consist of molecular species representing bile (glycodeoxycholic acid), digested triglyceride (1:2 glyceryl-1-monooleate and oleic acid), and water. We have characterized the phase behavior of the physical system using nephelometry, dynamic light scattering, and polarizing light microscopy and compared these measurements to phase behavior observed in multiple MD simulations. Using this model microenvironment, we have investigated the dissolution of the poorly water-soluble drug danazol experimentally using LC-MS and theoretically by MD simulation. The results show how the formulation lipids alter the environment of the GI tract and improve the solubility of danazol. The MD simulations successfully reproduce the experimental results showing the utility of MD in modeling the fate of drugs after digestion of lipid-based formulations within the intestinal lumen.

  1. rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand white rabbit posterolateral fusion model.

    PubMed

    Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N

    2007-05-15

    The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

  2. Vector Schwinger Model with a Photon Mass Term:. Gauge-Invariant Reformulation, Operator Solutions and Hamiltonian and Path Integral Formulations

    NASA Astrophysics Data System (ADS)

    Kulshreshtha, Usha

    We consider the vector Schwinger model (VSM) describing two-dimensional electrodynamics with massless fermions, where the left-handed and right-handed fermions are coupled to the electromagnetic field with equal couplings, with a mass term for the U(1) gauge field and then study its operator solutions and the Hamiltonian and path integral formulations. We emphasize here that although the VSM has been studied in the literature rather widely but only without a photon mass term (which was a consequence of demanding the regularization for the VSM to be gauge-invariant (GI)). The VSM with a photon mass term is seen to be a gauge-noninvariant (GNI) theory. Using the standard Stueckelberg formalism we then construct a GI theory corresponding to the proposed GNI model. From this reformulated GI theory, we further recover the physical contents of the proposed GNI theory under a very special gauge choice. The theory proposed and studied here presents a new class of models in the two-dimensional quantum electrodynamics with massless fermions but with a photon mass term.

  3. Population pharmacokinetic modeling and simulation to guide dose selection for RBP-7000, a new sustained-release formulation of risperidone.

    PubMed

    Laffont, Celine M; Gomeni, Roberto; Zheng, Bo; Heidbreder, Christian; Fudala, Paul J; Nasser, Azmi F

    2015-01-01

    RBP-7000 is a long-acting formulation of risperidone designed for once-monthly subcutaneous injection for the treatment of schizophrenia. The objective was to estimate clinically effective doses of RBP-7000 based on model simulations and on the comparison with other long-acting injectable antipsychotics. A population pharmacokinetic model of RBP-7000 was developed in 90 clinically stable schizophrenic patients having received single/repeated doses of 60, 90, or 120 mg. Model simulations were conducted to compare active moiety plasma exposure after repeated RBP-7000 administrations to the published data of long-acting risperidone injection (Risperdal® Consta®) at 25 and 50 mg, and of paliperidone palmitate (Invega® Sustenna®) at 50 and 100 mg equivalent paliperidone. Predictions of dopamine D2 receptor occupancy were derived from the simulated active moiety concentrations. Simulations showed similar active moiety plasma exposure at steady-state for 90 mg of RBP-7000 and 25 mg of long-acting risperidone. In comparison to risperidone, RBP-7000 reached effective concentrations immediately after the first administration. RBP-7000 at the doses of 60 and 90 mg provided similar active moiety plasma concentrations at steady-state compared to 50 and 100 mg equivalent paliperidone, respectively. These findings provide guidance for dose selection in Phase III clinical trials and suggest potential benefits for RBP-7000 over competitors.

  4. Semi-Implicit Formulations of the Navier-Stokes Equations: Application to Nonhydrostatic Atmospheric Modeling

    DTIC Science & Technology

    2009-01-01

    αρ̂+ βρ̂b)− 1 G0 ( αΘ̂ + βΘ̂b ))] (3.34) Semi-Implicit Nonhydrostatic Atmospheric Models 11 where P 2C = PC2C with C2C = ( 1 0 0 1c2C ) (3.35) and c2...analysis for SE2NC is identical since c2NC = c1. 4.3.3. SE2C. For SE2C, instabilities can occur if and only if c2C ≡ 1 + (αλ)2 g G0 dG0 dz = 0. Since G0...Θ0 ρ0 = θ0 then we see that c2C can never be zero because it is the same expression as for SE1 and SE2NC. 4.3.4. SE3. For SE3 we need to show that

  5. A gauged finite-element potential formulation for accurate inductive and galvanic modelling of 3-D electromagnetic problems

    NASA Astrophysics Data System (ADS)

    Ansari, S. M.; Farquharson, C. G.; MacLachlan, S. P.

    2017-07-01

    In this paper, a new finite-element solution to the potential formulation of the geophysical electromagnetic (EM) problem that explicitly implements the Coulomb gauge, and that accurately computes the potentials and hence inductive and galvanic components, is proposed. The modelling scheme is based on using unstructured tetrahedral meshes for domain subdivision, which enables both realistic Earth models of complex geometries to be considered and efficient spatially variable refinement of the mesh to be done. For the finite-element discretization edge and nodal elements are used for approximating the vector and scalar potentials respectively. The issue of non-unique, incorrect potentials from the numerical solution of the usual incomplete-gauged potential system is demonstrated for a benchmark model from the literature that uses an electric-type EM source, through investigating the interface continuity conditions for both the normal and tangential components of the potential vectors, and by showing inconsistent results obtained from iterative and direct linear equation solvers. By explicitly introducing the Coulomb gauge condition as an extra equation, and by augmenting the Helmholtz equation with the gradient of a Lagrange multiplier, an explicitly gauged system for the potential formulation is formed. The solution to the discretized form of this system is validated for the above-mentioned example and for another classic example that uses a magnetic EM source. In order to stabilize the iterative solution of the gauged system, a block diagonal pre-conditioning scheme that is based upon the Schur complement of the potential system is used. For all examples, both the iterative and direct solvers produce the same responses for the potentials, demonstrating the uniqueness of the numerical solution for the potentials and fixing the problems with the interface conditions between cells observed for the incomplete-gauged system. These solutions of the gauged system also

  6. Nonlocal continuum-based modeling of a nanoplate subjected to a moving nanoparticle. Part I: Theoretical formulations

    NASA Astrophysics Data System (ADS)

    Kiani, Keivan

    2011-10-01

    The potential applications of nanoplates in energy storage, chemical and biological sensors, solar cells, field emission, and transporting of nanocars have been attracted the attentions of the nanotechnology community to them during recent years. Herein, the later application of nanoplates from nonlocal elastodynamic point of view is of interest. To this end, dynamic response of a nanoplate subjected to a moving nanoparticle is examined within the context of nonlocal continuum theory of Eringen. The fully simply supported nanoplate is modeled based on the nonlocal Kirchhoff, Mindlin, and higher-order plate theories. The non-dimensional equations of motion of the nonlocal plate models are established. The effects of moving nanoparticle's weight and existing friction between the surfaces of the moving nanoparticle and nanoplate on the in-plane and out-of-plane vibrations of the nanoplate are incorporated into the formulations of the proposed models. The eigen function expansion and the Laplace transform methods are employed for discretization of the governing equations in the spatial and the time domains, respectively. The analytical expressions of the dynamic deformation field associated with each nonlocal plate theory are obtained when the moving nanoparticle traverses the nanoplate on an arbitrary straight path (an opened path) as well as an ellipse path (a closed path). The dynamic in-plane forces and moments of each nonlocal plate model are also derived. Furthermore, the critical velocity and the critical angular velocity of the moving nanoparticle for the proposed models are expressed analytically for the aforementioned paths. Part II of this work consists in a comprehensive parametric study where the effects of influential parameters on dynamic response of the proposed nonlocal plate models are scrutinized in some detail.

  7. Computational approaches and metrics required for formulating biologically realistic nanomaterial pharmacokinetic models

    NASA Astrophysics Data System (ADS)

    Riviere, Jim E.; Scoglio, Caterina; Sahneh, Faryad D.; Monteiro-Riviere, Nancy A.

    2013-01-01

    The field of nanomaterial pharmacokinetics is in its infancy, with major advances largely restricted by a lack of biologically relevant metrics, fundamental differences between particles and small molecules of organic chemicals and drugs relative to biological processes involved in disposition, a scarcity of sufficiently rich and characterized in vivo data and a lack of computational approaches to integrating nanomaterial properties to biological endpoints. A central concept that links nanomaterial properties to biological disposition, in addition to their colloidal properties, is the tendency to form a biocorona which modulates biological interactions including cellular uptake and biodistribution. Pharmacokinetic models must take this crucial process into consideration to accurately predict in vivo disposition, especially when extrapolating from laboratory animals to humans since allometric principles may not be applicable. The dynamics of corona formation, which modulates biological interactions including cellular uptake and biodistribution, is thereby a crucial process involved in the rate and extent of biodisposition. The challenge will be to develop a quantitative metric that characterizes a nanoparticle's surface adsorption forces that are important for predicting biocorona dynamics. These types of integrative quantitative approaches discussed in this paper for the dynamics of corona formation must be developed before realistic engineered nanomaterial risk assessment can be accomplished.

  8. Controlled comparison of two fluorometholone formulations in the antigen challenge model of allergic conjunctivitis.

    PubMed

    Harper, D G; Chen, C E; Friedlaender, M H

    1995-10-01

    We compared the safety and efficacy of MethaSite, a gel-forming suspension (0.1% fluorometholone), to a commercially available 0.1% fluorometholone ointment, FML S.O.P., using an antigen challenge model. Subjects with known allergic histories were exposed to increasing concentrations of cat dander, ragweed, or grass at visits 1 and 2. Allergic responses of conjunctival injection, chemosis, and subjective itching were quantified on a scale from zero to 3; the sum of these ratings constituted the total allergic score. At visit 3, 105 subjects with total scores of > or = 5 received a drop of MethaSite in one eye and a 0.5 inch ribbon of FML ointment in the other eye. Three and 6 hours postdose, the eyes were challenged with the antigen concentration that provoked significant allergic response at visit 2. We determined safety by evaluating changes in visual acuity, intraocular pressure, and biomicroscopy that occurred between visits 1 and 3. Eyes treated with MethaSite and FML responded similarly to the antigen challenges. Both groups demonstrated suppression of allergic response 3 and 6 hours postdose through equivalent and significant reductions in total allergy scores and individual ratings of injection, chemosis, and itching. In this population, MethaSite was equivalent to FML ointment in safety and efficacy.

  9. Formulation of predictive models for use in first principles design of non-centrosymmetric perovskite oxides

    NASA Astrophysics Data System (ADS)

    Young, Joshua; Rondinelli, James

    2014-03-01

    Because many useful electronic properties such as ferroelectricity arise solely due to the lack of inversion in a material's crystal structure, predictive microscopic models describing how to deterministically remove this symmetry operation can allow for the rapid identification and design of new polar compounds. By understanding how structural distortions influence the connectivity between oxygen polyhedra in solid state oxides, we elucidate a series of geometric design rules necessary to develop polar materials. We then apply these criteria to the family of ABO3 perovskite oxides by systematically investigating how distortions of the corner-connected BO6 polyhedral network influence the A-site environments, resulting in a detailed description of the octahedral rotation patterns and A- and B-site cation ordering arrangements capable of producing centrosymmetric, polar, and enantiomorphic structures. Using this as a guide, we then show how such a method allows for the targeted design of new non-centrosymmetric oxides. We conclude by using these rules in combination with density functional theory calculations to predict a series of rhombohedral (A,A')B2O6 perovskites displaying electric polarizations in their ground state.

  10. A new class of ensemble conserving algorithms for approximate quantum dynamics: Theoretical formulation and model problems

    SciTech Connect

    Smith, Kyle K. G.; Poulsen, Jens Aage Nyman, Gunnar; Rossky, Peter J.

    2015-06-28

    We develop two classes of quasi-classical dynamics that are shown to conserve the initial quantum ensemble when used in combination with the Feynman-Kleinert approximation of the density operator. These dynamics are used to improve the Feynman-Kleinert implementation of the classical Wigner approximation for the evaluation of quantum time correlation functions known as Feynman-Kleinert linearized path-integral. As shown, both classes of dynamics are able to recover the exact classical and high temperature limits of the quantum time correlation function, while a subset is able to recover the exact harmonic limit. A comparison of the approximate quantum time correlation functions obtained from both classes of dynamics is made with the exact results for the challenging model problems of the quartic and double-well potentials. It is found that these dynamics provide a great improvement over the classical Wigner approximation, in which purely classical dynamics are used. In a special case, our first method becomes identical to centroid molecular dynamics.

  11. A new class of ensemble conserving algorithms for approximate quantum dynamics: Theoretical formulation and model problems.

    PubMed

    Smith, Kyle K G; Poulsen, Jens Aage; Nyman, Gunnar; Rossky, Peter J

    2015-06-28

    We develop two classes of quasi-classical dynamics that are shown to conserve the initial quantum ensemble when used in combination with the Feynman-Kleinert approximation of the density operator. These dynamics are used to improve the Feynman-Kleinert implementation of the classical Wigner approximation for the evaluation of quantum time correlation functions known as Feynman-Kleinert linearized path-integral. As shown, both classes of dynamics are able to recover the exact classical and high temperature limits of the quantum time correlation function, while a subset is able to recover the exact harmonic limit. A comparison of the approximate quantum time correlation functions obtained from both classes of dynamics is made with the exact results for the challenging model problems of the quartic and double-well potentials. It is found that these dynamics provide a great improvement over the classical Wigner approximation, in which purely classical dynamics are used. In a special case, our first method becomes identical to centroid molecular dynamics.

  12. Filling effects, persistence, and safety of dermal fillers formulated with stem cells in an animal model.

    PubMed

    Nowacki, Maciej; Pietkun, Katarzyna; Pokrywczyńska, Marta; Rasmus, Marta; Warda, Karolina; Kloskowski, Tomasz; Jundziłł, Arkadiusz; Gagat, Maciej; Grzanka, Alina; Bodnar, Magdalena; Marszałek, Andrzej; Drewa, Tomasz; Czajkowski, Rafał

    2014-11-01

    Research is scarce regarding the effectiveness of dermal fillers containing autologous stem cells. The authors sought to determine the local and systemic effects of adipose-derived stem cells (ADSCs) as a component of dermal fillers in an animal model. Wistar rats were injected with 1 of the following dermal fillers: ADSCs combined with hyaluronic acid (ADSC-HA), ADSCs combined with fish collagen (ADSC-COL), HA alone (CONTROL-HA), or COL alone (CONTROL-COL). Fillers were injected into the glabella, dorsum, and chest of each animal. The ADSCs were labeled with PKH26 to assess cell migration. Filling effects (FEs) were measured immediately after injection and at 1.5 months and 3 months after injection. Skin specimens were stained with hematoxylin and eosin to assess localization and persistence of ADSCs. Mean FEs in animals implanted with ADSCs were greater and persisted longer than those of controls. No inflammatory responses were observed in any group. Three months after injection, PKH26-positive cells comprised nearly 70% of cells at the injection site in animals treated with ADSC-HA. PKH26 fluorescence also was detected in the spleen but not in the brain, kidney, or lung. Stem cells have the potential to improve the aesthetic effects and longevity of dermal fillers. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

  13. Subgrid scale and backscatter model for magnetohydrodynamic turbulence based on closure theory: theoretical formulation.

    PubMed

    Zhou, Ye; Schilling, Oleg; Ghosh, Sanjoy

    2002-08-01

    The spectral eddy and backscatter viscosity and the spectral eddy and backscatter resistivity for incompressible, three-dimensional, isotropic, nonhelical magnetohydrodynamic (MHD) turbulence are constructed using the eddy-damped quasinormal Markovian statistical closure model developed by Pouquet, Frisch, and Léorat [J. Fluid Mech. 77, 321 (1976)] in terms of primitive variables. The approach used is an extension of the methodology developed by Leslie and Quarini [J. Fluid Mech. 91, 65 (1979)] for fluid turbulence to MHD turbulence. The eddy and backscatter viscosities and the eddy and backscatter resistivities are calculated numerically for assumed kinetic and magnetic energy spectra, E(v)(k) and E(B)(k), with a production subrange and a k(-5/3) inertial subrange for the two cases r(A)=1 and r(A)=1 / 2, where r(A)=E(v)(k)/E(B)(k) is the Alfvén ratio. It is shown that the effects of the unresolved subgrid scales on the resolved-scale velocity and magnetic field consist of an eddy damping and backscatter. The eddy viscosity and resistivity, and the backscatter viscosity and resistivity (the correlation function of the stochastic velocity and magnetic backscatter force) are shown to have a dependence on k/k(c), where k(c) is the cutoff wave number, which is very similar to the dependence calculated in the pure (i.e., nonmagnetic) Navier-Stokes turbulence case. The eddy viscosity and resistivity, and the backscatter viscosity and resistivity numerically calculated here can be used to develop improved subgrid-scale parametrizations for spectral large-eddy simulations of homogenous MHD turbulence.

  14. Evaluation of a new formulation of demineralized bone matrix putty in a rabbit posterolateral spinal fusion model.

    PubMed

    Kiely, Paul D; Brecevich, Antonio T; Taher, Fadi; Nguyen, Joseph T; Cammisa, Frank P; Abjornson, Celeste

    2014-09-01

    Alternatives to autologous bone graft (ABG) with osteoconductive, osteoinductive, and osteogenic potential continue to prove elusive. Demineralized bone matrix (DBM) however, with its osteoconductive and osteoinductive potential remains a viable option to ABG in posterolateral spine fusion. To compare the efficacy of a new formulation of DBM putty with that of ABG in a rabbit posterolateral spinal fusion model. Efficacy of a new formulation of DBM was studied in an experimental animal posterolateral spinal fusion model. Twenty-four male New Zealand White rabbits underwent bilateral posterolateral spine arthrodesis of the L5-L6 intertransverse processes, using either ABG (control group, n=12) or DBM (DBM made from rabbit bone) putty (test group, n=12). The animals were killed 12 weeks after surgery and the lumbar spines were excised. Fusion success was evaluated by manual palpation, high resolution X-rays, microcomputed tomography imaging, biomechanical four-point bending tests, and histology. Two animals were lost because of anesthetic related issues. Manual palpation to assess fusion success in the explanted lumbar spines showed no statistical significant difference in successful fusion in 81.8% (9/11) of DBM group and 72.7% (8/11) of ABG group (p=.99). Reliability of these assessments was measured between three independent observers and found near perfect agreement (intraclass correlation cofficient: 0.92 and 0.94, respectively). Fusion using high resolution X-rays was solid in 10 of the DBM group and 9 of the ABG group (p=.59). Biomechanical testing showed no significant difference in stiffness between the control and test groups on flexion, extension, and left lateral and right lateral bends, with p values accounting for .79, .42, .75, and .52, respectively. The bone volume/total volume was greater than 85% in the DBM treated fusion masses. Histologic evaluation revealed endochondral ossification in both groups, but the fusion masses were more mature in the DBM

  15. Addition of Amino Acids to Further Stabilize Lyophilized Sucrose-Based Protein Formulations: I. Screening of 15 Amino Acids in Two Model Proteins.

    PubMed

    Forney-Stevens, Kelly M; Bogner, Robin H; Pikal, Michael J

    2016-02-01

    In small amounts, the low molecular weight excipients-sorbitol and glycerol-have been shown to stabilize lyophilized sucrose-based protein formulations. The purpose of this study was to explore the use of amino acids as low molecular weight excipients to similarly enhance stability. Model proteins, recombinant human serum albumin and α-chymotrypsin, were formulated with sucrose in combination with one of 15 amino acid additives. Each formulation was lyophilized at 1:1:0.3 (w/w) protein-sucrose-amino acid. Percent total soluble aggregate was measured by size-exclusion chromatography before and after storage at 50 °C for 2 months. Classical thought might suggest that the addition of the amino acids to the sucrose-protein formulations would be destabilizing because of a decrease in the system's glass transition temperature. However, significant improvement in storage stability was observed for almost all formulations at the ratio of amino acid used. Weak correlations were found between the extent of stabilization and both amino acid molar volume and side-chain charge. The addition of amino acids at a modest level generally improves storage stability, often by more than a 50% increase, for lyophilized sucrose-based protein formulations.

  16. Linkage analysis with an alternative formulation for the mixed model of inheritance: The finite polygenic mixed model

    SciTech Connect

    Stricker, C.; Fernando, R.L.; Elston, R.C.

    1995-12-01

    This paper presents an extension of the finite polygenic mixed model of Fernando et al. to linkage analysis. The finite polygenic mixed model, extended for linkage analysis, leads to a likelihood that can be calculated using efficient algorithms developed for oligogenic models. For comparison, linkage analysis of 5 simulated 4021-member pedigrees was performed using the usual mixed model of inheritance, approximated by Hasstedt, and the finite polygenic mixed model extended for linkage analysis presented here. Maximum likelihood estimates of the finite polygenic mixed model could be inferred to be closer to the simulated values in these pedigrees. 31 refs., 2 tabs.

  17. Linkage Analysis with an Alternative Formulation for the Mixed Model of Inheritance: The Finite Polygenic Mixed Model

    PubMed Central

    Stricker, C.; Fernando, R. L.; Elston, R. C.

    1995-01-01

    This paper presents an extension of the finite polygenic mixed model of FERNANDO et al. (1994) to linkage analysis. The finite polygenic mixed model, extended for linkage analysis, leads to a likelihood that can be calculated using efficient algorithms developed for oligogenic models. For comparison, linkage analysis of 5 simulated 4021-member pedigrees was performed using the usual mixed model of inheritance, approximated by HASSTEDT (1982), and the finite polygenic mixed model extended for linkage analysis presented here. Maximum likelihood estimates of the finite polygenic mixed model could be inferred to be closer to the simulated values in these pedigrees. PMID:8601502

  18. New spot-on formulation containing chlorpyrifos for controlling horn flies on cattle: laboratory model of insecticide release and field trial.

    PubMed

    Juan, Laura W; Zerba, Eduardo N; Mariategui, Pedro; Speicys, Claudio; Tarelli, Guillermo; Demyda, Sebastián; Masuh, Héctor Mario

    2010-09-01

    A highly viscous formulation containing chlorpyrifos (RET) was evaluated under laboratory, pre-field, and field conditions, and compared against ear tags with organophosphorus insecticides. Laboratory bioassays were performed using Musca domestica L. and a thin layer chromatography (TLC) plate of reversed phase silica gel modeling a lipophilic surface. Insects were exposed to the insecticide vapors of both formulations, directly and indirectly to test for lateral diffusion. Knockdown time 50% (KT(50)) values were determined as toxicological indicators of insecticide release. Minimum KT(50) values of the direct effect of both formulations on horn flies were reached 4 weeks after being applied. The KT(50) effect of migrated insecticides showed that RET formulation had a maximal effectiveness between the fourth and tenth last week. The KT(50) effect of the insecticide migrating from ear tags decreased during the last 2 weeks of the experiment, and the KT(50) effect of the laterally migrated insecticide was significantly higher for the RET formulation during this period. A pre-field bioassay was performed by exposing pieces of rabbit leather with both formulations and recording the KT(50). At the end of the experiment, the KT(50) effect of laterally migrated insecticide was significantly higher for the RET formulation. Regarding vapor emission, as a general trend the KT(50) effect of ear tags was greater than for the RET formulation. To evaluate the horn fly infestation in the field bioassays, photographs of the animal were taken. The results shows that RET provided significant control for 11 weeks while the ear tags provided protection until the 12th week.

  19. Modeling of elastic and plastic waves for HCP single crystals in a 3D formulation based on zinc single crystal

    NASA Astrophysics Data System (ADS)

    Krivosheina, Marina; Kobenko, Sergey; Tuch, Elena; Kozlova, Maria

    2016-11-01

    This paper investigates elastic and plastic waves in HCP single crystals through the numerical simulation of strain processes in anisotropic materials based on a zinc single crystal. Velocity profiles for compression waves in the back surfaces of single-crystal zinc plates with impact loading oriented in 0001 and 10 1 ¯0 are presented in this work as a part of results obtained in numerical simulations. The mathematical model implemented in this study reflects the following characteristics of the mechanical properties inherent in anisotropic (transtropic) materials: varying degree of anisotropy of elastic and plastic properties, which includes reverse anisotropy, dependence of distribution of all types of waves on the velocity orientation, and the anisotropy of compressibility. Another feature of elastic and plastic waves in HCP single crystals is that the shock wave does not split into an elastic precursor and "plastic" compression shock wave, which is inherent in zinc single crystals with loading oriented in 0001. The study compares numerical results obtained in a three-dimensional formulation with the results of velocity profiles from the back surfaces of target plates obtained in real experiments. These results demonstrate that the mathematical model is capable of describing the properties of the above-mentioned anisotropic (transtropic) materials.

  20. Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models

    PubMed Central

    Jain, Meenu; Gamage, Nipuni-Dhanesha H.; Alsulami, Meshal; Shankar, Adarsh; Achyut, Bhagelu R.; Angara, Kartik; Rashid, Mohammad H.; Iskander, Asm; Borin, Thaiz F.; Wenbo, Zhi; Ara, Roxan; Ali, Meser M.; Lebedyeva, Iryna; Chwang, Wilson B.; Guo, Austin; Bagher-Ebadian, Hassan; Arbab, Ali S.

    2017-01-01

    Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPßCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups (p < 0.05). Similar growth inhibition was observed in syngeneic GL261 GBM (p < 0.05). Survival studies using patient derived xenografts of GBM811, showed prolonged survival to 26 weeks in animals treated with focal radiation, in combination with HET0016 and TMZ (p < 0.05). We observed reduced expression of markers of cell proliferation (Ki-67), decreased neovascularization (laminin and αSMA), in addition to inflammation and angiogenesis markers in the treatment group (p < 0.05). Our results indicate that HPßCD-HET0016 is effective in inhibiting tumor growth through decreasing proliferation, and neovascularization. Furthermore, HPßCD-HET0016 significantly prolonged survival in PDX GBM811 model. PMID:28139732

  1. High-order accurate finite-volume formulations for the pressure gradient force in layered ocean models

    NASA Astrophysics Data System (ADS)

    Engwirda, Darren; Kelley, Maxwell; Marshall, John

    2017-08-01

    Discretisation of the horizontal pressure gradient force in layered ocean models is a challenging task, with non-trivial interactions between the thermodynamics of the fluid and the geometry of the layers often leading to numerical difficulties. We present two new finite-volume schemes for the pressure gradient operator designed to address these issues. In each case, the horizontal acceleration is computed as an integration of the contact pressure force that acts along the perimeter of an associated momentum control-volume. A pair of new schemes are developed by exploring different control-volume geometries. Non-linearities in the underlying equation-of-state definitions and thermodynamic profiles are treated using a high-order accurate numerical integration framework, designed to preserve hydrostatic balance in a non-linear manner. Numerical experiments show that the new methods achieve high levels of consistency, maintaining hydrostatic and thermobaric equilibrium in the presence of strongly-sloping layer geometries, non-linear equations-of-state and non-uniform vertical stratification profiles. These results suggest that the new pressure gradient formulations may be appropriate for general circulation models that employ hybrid vertical coordinates and/or terrain-following representations.

  2. Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models.

    PubMed

    Jain, Meenu; Gamage, Nipuni-Dhanesha H; Alsulami, Meshal; Shankar, Adarsh; Achyut, Bhagelu R; Angara, Kartik; Rashid, Mohammad H; Iskander, Asm; Borin, Thaiz F; Wenbo, Zhi; Ara, Roxan; Ali, Meser M; Lebedyeva, Iryna; Chwang, Wilson B; Guo, Austin; Bagher-Ebadian, Hassan; Arbab, Ali S

    2017-01-31

    Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPßCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups (p < 0.05). Similar growth inhibition was observed in syngeneic GL261 GBM (p < 0.05). Survival studies using patient derived xenografts of GBM811, showed prolonged survival to 26 weeks in animals treated with focal radiation, in combination with HET0016 and TMZ (p < 0.05). We observed reduced expression of markers of cell proliferation (Ki-67), decreased neovascularization (laminin and αSMA), in addition to inflammation and angiogenesis markers in the treatment group (p < 0.05). Our results indicate that HPßCD-HET0016 is effective in inhibiting tumor growth through decreasing proliferation, and neovascularization. Furthermore, HPßCD-HET0016 significantly prolonged survival in PDX GBM811 model.

  3. Plan, formulate, discuss and correlate a NASTRAN finite element vibrations model of the Boeing Model 360 helicopter airframe

    NASA Technical Reports Server (NTRS)

    Gabel, R.; Lang, P. F.; Smith, L. A.; Reed, D. A.

    1989-01-01

    Boeing Helicopter, together with other United States helicopter manufacturers, participated in a finite element applications program to emplace in the United States a superior capability to utilize finite element analysis models in support of helicopter airframe design. The activities relating to planning and creating a finite element vibrations model of the Boeing Model 36-0 composite airframe are summarized, along with the subsequent analytical correlation with ground shake test data.

  4. Multicomponent simulation of wastewater-derived nitrogen and carbon in shallow unconfined aquifers. I. Model formulation and performance.

    PubMed

    MacQuarrie, K T; Sudicky, E A

    2001-01-01

    One of the most common methods to dispose of domestic wastewater involves the release of septic effluent from drains located in the unsaturated zone. Nitrogen from such systems is currently of concern because of nitrate contamination of drinking water supplies and eutrophication of coastal waters. The objectives of this study are to develop and assess the performance of a mechanistic flow and reactive transport model which couples the most relevant physical, geochemical and biochemical processes involved in wastewater plume evolution in sandy aquifers. The numerical model solves for variably saturated groundwater flow and reactive transport of multiple carbon- and nitrogen-containing species in a three-dimensional porous medium. The reactive transport equations are solved using the Strang splitting method which is shown to be accurate for Monod and first- and second-order kinetic reactions, and two to four times more efficient than sequential iterative splitting. The reaction system is formulated as a fully kinetic chemistry problem, which allows for the use of several special-purpose ordinary differential equation (ODE) solvers. For reaction systems containing both fast and slow kinetic reactions, such as the combined nitrogen-carbon system, it is found that a specialized stiff explicit solver fails to obtain a solution. An implicit solver is more robust and its computational performance is improved by scaling of the fastest reaction rates. The model is used to simulate wastewater migration in a 1-m-long unsaturated column and the results show significant oxidation of dissolved organic carbon (DOC), the generation of nitrate by nitrification, and a slight decrease in pH.

  5. Three dimensional thermal pollution models. Volume 1: Review of mathematical formulations. [waste heat discharge from power plants and effects on ecosystems

    NASA Technical Reports Server (NTRS)

    Lee, S. S.; Sengupta, S.

    1978-01-01

    A mathematical model package for thermal pollution analyses and prediction is presented. These models, intended as user's manuals, are three dimensional and time dependent using the primitive equation approach. Although they have sufficient generality for application at sites with diverse topographical features; they also present specific instructions regarding data preparation for program execution and sample problems. The mathematical formulation of these models is presented including assumptions, approximations, governing equations, boundary and initial conditions, numerical method of solution, and same results.

  6. A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging.

    PubMed

    Bornmann, C; Graeser, R; Esser, N; Ziroli, V; Jantscheff, P; Keck, T; Unger, C; Hopt, U T; Adam, U; Schaechtele, C; Massing, U; von Dobschuetz, E

    2008-03-01

    Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (Ø: 36 nm: 47% entrapment). Its anti-tumoral activity was tested on MIA PaCa-2 cells growing orthotopically in nude mice. Bioluminescence measurement mediated by the stable integration of the luciferase gene was employed to randomize the mice, and monitor tumor growth. GemLip (4 and 8 mg/kg), Gemcitabine (240 mg/kg), and empty liposomes (equivalent to 8 mg/kg GemLip) were injected intravenously once weekly for 5 weeks. GemLip (8 mg/kg) stopped tumor growth, as measured via in vivo bioluminescence, reducing the primary tumor size by 68% (SD +/- 8%; p < 0.02), whereas Gemcitabine hardly affected tumor size (-7%; +/- 1.5%). In 80% of animals, luciferase activity in the liver indicated the presence of metastases. All treatments, including the empty liposomes, reduced the metastatic burden. Thus, GemLip shows promising antitumoral activity in this model. Surprisingly, empty liposomes attenuate the spread of metastases similar to Gemcitabine and GemLip. Further, luciferase marked tumor cells are a powerful tool to observe tumor growth in vivo, and to detect and quantify metastases.

  7. Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations.

    PubMed

    Roberts, Matthew; Ford, James L; MacLeod, Graeme S; Fell, John T; Smith, George W; Rowe, Philip H

    2003-09-01

    The sticking of three model ibuprofen-lactose formulations with respect to compaction force and the surface quality of the upper punch were assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Two sets of 12.5-mm flat-faced punches were used to evaluate the influence of surface quality. A third set of chrome-plated tooling was also used. Surface profiles (Taylor Hobson Talysurf 120) of the normal tooling upper punches indicated a large difference in quality. The punches were subsequently classified as old (Ra = 0.33 microm) or new (Ra = 0.04 microm) where Ra is the mean of all positive deviations from zero. Surface profiles of sample tablets were also obtained. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. Punch surface roughness, compaction force and the blend composition were all significant factors contributing to sticking. Chrome plating of punch faces increased sticking at a low compaction force but decreased sticking at higher forces. Surface roughness of the tablets did not correlate with the corresponding data for sticking, indicating that this is not a suitable method of quantifying sticking.

  8. Two source energy balance model to calculate E, T, and ET: Comparison of Priestly-Taylor and Penman-Monteith formulations and two time scaling methods

    USDA-ARS?s Scientific Manuscript database

    The two source energy balance (TSEB) model calculates the energy balance of the soil–canopy–atmosphere continuum, where turbulent fluxes are based on the Priestley–Taylor equation. The TSEB was revised recently using the Penman–Monteith equation to replace the Priestley–Taylor formulation, thus bett...

  9. Corrigendum to: Multi-scale defect interactions in high-rate brittle material failure. Part I: Model formulation and application to AlON

    NASA Astrophysics Data System (ADS)

    Tonge, A. L.; Ramesh, K. T.

    2017-09-01

    A minor error was present in one equation in the original paper, ;Multi-scale defect interactions in high-rate brittle material failure. Part I: Model formulation and application to AlON; and in the corresponding computational implementation. The correction is provided here. None of the primary conclusions of the original paper are affected.

  10. Effects of Erxian decoction, a Chinese medicinal formulation, on serum lipid profile in a rat model of menopause

    PubMed Central

    2011-01-01

    Background The prevalence and risk of cardiovascular disease increase after menopause in correlation with the progression of abnormality in the serum lipid profile and the deprivation of estrogen. Erxian decoction (EXD), a Chinese medicinal formulation for treating menopausal syndrome, stimulates ovarian estrogen biosynthesis. This study investigates whether EXD improves the serum lipid profile in a menopausal rat model. Methods Twenty-month-old female Sprague Dawley rats were treated with EXD and its constituent fractions. Premarin was administered for comparison. After eight weeks of treatment, rats were sacrificed and the serum levels of total cholesterol, triglyceride, high-density-lipoprotein cholesterol and low-density-lipoprotein cholesterol were determined. The hepatic protein levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase and low-density-lipoprotein receptor were assessed with Western blot. Results The serum levels of total cholesterol and low-density-lipoprotein cholesterol were significantly lower in the EXD-treated group than in the constituent fractions of EXD or premarin groups. However, the serum levels of triglyceride and high-density-lipoprotein cholesterol were not significantly different from the control groups. Results from Western blot suggest that EXD significantly down-regulated the protein level of 3-hydroxy-3-methyl-glutaryl-CoA reductase and up-regulated low-density-lipoprotein receptor. Conclusion EXD improves serum lipid profile in a menopausal rat model through the suppression of the serum levels of total cholesterol and low-density-lipoprotein cholesterol, possibly through the down-regulation of the 3-hydroxy-3-methyl-glutaryl-CoA and up-regulation of the low-density-lipoprotein receptor. PMID:22047073

  11. Dose-response relationships of three amphotericin B formulations in a non-neutropenic murine model of invasive aspergillosis.

    PubMed

    Mouton, J W; te Dorsthorst, D T A; Meis, J F G M; Verweij, P E

    2009-12-01

    New lipid-associated formulations of amphotericin B (AmB) have been developed in order to reduce toxicity and enhance the efficacy of AmB by allowing administration of higher doses of the drug. We determined the in vivo dose-response relationships of 1 day and 7 day treatment of AmB, Ambisome (AmBi) and Abelcet (ABLC) in a non-neutropenic murine model of invasive aspergillosis by using survival as an endpoint. Female CD-1 mice were infected intravenously 48 h prior to start therapy with Aspergillus fumigatus (1 x 10(7) conidia/mouse). Groups of 10 mice were treated iv for 1 day or 7 days with increasing 2-fold doses of AmB, ABLC and AmBi up to a maximum of 20 mg/kg/day. Mortality was determined twice daily until day 15. Results were analyzed using product-moment survival analysis and by determining the dose response relationships on day 15. Survival at day 15 of mice with 7 day AmBi or ABLC treatment was significantly better than that of controls or AmB. The ED50s of AmBi and ABLC were 0.06 (95% CI: 0.03-0.127) mg/kg and 0.21 (0.06-0.66) mg/kg respectively. In addition, the maximum effect was higher for AmBi than ABLC, 90% survival versus 68%, respectively. Most of the effects of treatment with AmBi were reached after 1 day of treatment, indicating that the first dose given is most important in predicting survival. This study shows that AmBi and ABLC were significantly more efficacious than AmB in a non-neutropenic murine model of invasive aspergillosis, and that the effect observed was primarily dependent on the first dose administered.

  12. A comparative study on the antibacterial photodynamic efficiency of a curcumin derivative and a formulation on a porcine skin model.

    PubMed

    Tortik, Nicole; Steinbacher, Peter; Maisch, Tim; Spaeth, Andreas; Plaetzer, Kristjan

    2016-02-01

    The propagation of pathogens resistant to antibiotics around the globe has induced an urgent call for action: alternatives to conventional antibiotic therapy have to be developed to prevent a post-antibiotic catastrophe. This study focuses on the enhancement of Photodynamic Inactivation (PDI) of Gram(+) versus Gram(-) bacteria comparing a cationic derivative of curcumin (SACUR-3) to curcumin bound to polyvinylpyrrolidone (PVP-CUR) using an ex vivo porcine skin model to simulate an application on the human skin and foodstuff. Porcine skin samples were inoculated with either Staphylococcus aureus or Escherichia coli and treated with either SACUR-3 or PVP-CUR at concentrations of 50 or 100 μM, respectively. Subsequent to blue light illumination (435 nm, 33.8 J cm(-2)) quantitative analyses were performed by counting the colony forming units. Furthermore, the localization of both photoactive compounds in the porcine skin was determined by fluorescence microscopy. PDI of S. aureus resulted in a reduction of 2.2 log10 steps if employing 50 μM of SACUR-3 and of 1.7 log10 steps with 50 μM of PVP-CUR. Phototoxicity towards E. coli was 3.3 log10 steps using 100 μM of SACUR-3 and 0.3 log10 steps for 100 μM of PVP-CUR. Both compounds do not exceed the stratum corneum of the skin. A direct comparison of both approaches yields that the cationic curcumin derivative SACUR-3 is effective against Gram(+) and Gram(-) pathogens, whereas the formulation of PVP-CUR has a photokilling effect on the Gram(+) model strain only, but leaves the approval of curcumin as a food additive E100 unaffected. Our results suggest the applicability of SACUR-3-based PDI in dermatology, hand hygiene and food production.

  13. A grid-based distributed flood forecasting model for use with weather radar data: Part 1. Formulation

    NASA Astrophysics Data System (ADS)

    Bell, V. A.; Moore, R. J.

    A practical methodology for distributed rainfall-runoff modelling using grid square weather radar data is developed for use in real-time flood forecasting. The model, called the Grid Model, is configured so as to share the same grid as used by the weather radar, thereby exploiting the distributed rainfall estimates to the full. Each grid square in the catchment is conceptualised as a storage which receives water as precipitation and generates water by overflow and drainage. This water is routed across the catchment using isochrone pathways. These are derived from a digital terrain model assuming two fixed velocities of travel for land and river pathways which are regarded as model parameters to be optimised. Translation of water between isochrones is achieved using a discrete kinematic routing procedure, parameterised through a single dimensionless wave speed parameter, which advects the water and incorporates diffusion effects through the discrete space-time formulation. The basic model routes overflow and drainage separately through a parallel system of kinematic routing reaches, characterised by different wave speeds but using the same isochrone-based space discretisation; these represent fast and slow pathways to the basin outlet, respectively. A variant allows the slow pathway to have separate isochrones calculated using Darcy velocities controlled by the hydraulic gradient as estimated by the local gradient of the terrain. Runoff production within a grid square is controlled by its absorption capacity which is parameterised through a simple linkage function to the mean gradient in the square, as calculated from digital terrain data. This allows absorption capacity to be specified differently for every grid square in the catchment through the use of only two regional parameters and a DTM measurement of mean gradient for each square. An extension of this basic idea to consider the distribution of gradient within the square leads analytically to a Pareto

  14. Identification of suitable formulations for high dose oral studies in rats using in vitro solubility measurements, the maximum absorbable dose model, and historical data sets.

    PubMed

    Wuelfing, W Peter; Kwong, Elizabeth; Higgins, John

    2012-05-07

    The ability to define compound solubility targets that are predictive of good oral absorption at high dose preclinical studies (≥ 100 mg compound/kg animal) is of use in drug discovery and development. Two different approaches to identify these targets in preclinical formulations are evaluated herein. The first approach is the use of solubility values from in vitro formulation dilutions using biorelevant parameters for rats. These dilution/solubility results are applied to the maximum absorbable dose (MAD) model to predict compound exposure (AUC) from oral doses and allow the fraction of dose absorbed (F(abs)) calculation. The results from 26 such in vitro evaluations are compared to in vivo studies and discussed. The second approach is the analysis of in vivo AUC proportionality between 10 and 100 mg/kg doses for 28 compounds where only the compound solubility in neat formulation is known. Both assessments suggest similar threshold targets to remove solubility as an absorption limitation for any given compound. Specifically, compound solubility should be >2 mg/mL in aqueous surfactants and >15 mg/mL in cosolvent (PEG400) or pH-adjusted aqueous formulations. The results are a starting place for formulation rule-of-thumb solubility targets applied in discovery and development settings.

  15. A Melting Layer Model for Passive/Active Microwave Remote Sensing Applications. Part 1; Model Formulation and Comparison with Observations

    NASA Technical Reports Server (NTRS)

    Olson, William S.; Bauer, Peter; Viltard, Nicolas F.; Johnson, Daniel E.; Tao, Wei-Kuo

    2000-01-01

    In this study, a 1-D steady-state microphysical model which describes the vertical distribution of melting precipitation particles is developed. The model is driven by the ice-phase precipitation distributions just above the freezing level at applicable gridpoints of "parent" 3-D cloud-resolving model (CRM) simulations. It extends these simulations by providing the number density and meltwater fraction of each particle in finely separated size categories through the melting layer. The depth of the modeled melting layer is primarily determined by the initial material density of the ice-phase precipitation. The radiative properties of melting precipitation at microwave frequencies are calculated based upon different methods for describing the dielectric properties of mixed phase particles. Particle absorption and scattering efficiencies at the Tropical Rainfall Measuring Mission Microwave Imager frequencies (10.65 to 85.5 GHz) are enhanced greatly for relatively small (approx. 0.1) meltwater fractions. The relatively large number of partially-melted particles just below the freezing level in stratiform regions leads to significant microwave absorption, well-exceeding the absorption by rain at the base of the melting layer. Calculated precipitation backscatter efficiencies at the Precipitation Radar frequency (13.8 GHz) increase in proportion to the particle meltwater fraction, leading to a "bright-band" of enhanced radar reflectivities in agreement with previous studies. The radiative properties of the melting layer are determined by the choice of dielectric models and the initial water contents and material densities of the "seeding" ice-phase precipitation particles. Simulated melting layer profiles based upon snow described by the Fabry-Szyrmer core-shell dielectric model and graupel described by the Maxwell-Garnett water matrix dielectric model lead to reasonable agreement with radar-derived melting layer optical depth distributions. Moreover, control profiles

  16. Use of Modeling and Simulation Tools for Understanding the Impact of Formulation on the Absorption of a Low Solubility Compound: Ciprofloxacin.

    PubMed

    Martinez, Marilyn; Mistry, Bipin; Lukacova, Viera; Polli, Jim; Hoag, Stephen; Dowling, Thomas; Kona, Ravikanth; Fahmy, Raafat

    2016-07-01

    This study explored the utility of mechanistic absorption models to describe the in vivo performance of a low solubility/low permeability compound in normal healthy subjects. Sixteen healthy human volunteers received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by HPLC. In vitro ciprofloxacin release from the oral tablets was tested under a variety of conditions. A mechanistic model was used to explore in vivo dissolution and intestinal absorption. Although dissolution rate influenced the location of drug release, absorption challenges appeared to be associated with permeability limitations in the lower small intestine and colon. The apparent relationship between drug solubilization within the upper small intestinal and formulation overall bioavailability suggested the presence of an intestinal absorption window in many individuals. Failure to absorb drug within this window appeared to be linked with the likelihood of in vivo drug precipitation. Challenges encountered during this modeling exercise included large intersubject variability in product in vivo dissolution and the apparent limitations in ciprofloxacin absorption. Although transporter activity was not included as a model parameter, this evaluation demonstrated how identifying the location of drug absorption across several formulations provided an opportunity to identify factors to consider when formulating similar low solubility/low permeability compounds. The use of mechanistic models was invaluable for our understanding of in vivo product performance and for the assessment of individual profiles rather than means. The latter was essential for understanding the potential challenges that may be encountered when introducing a formulation into a patient population.

  17. A stochastic, Lagrangian model of sinking biogenic aggregates in the ocean (SLAMS 1.0): model formulation, validation and sensitivity

    NASA Astrophysics Data System (ADS)

    Jokulsdottir, Tinna; Archer, David

    2016-04-01

    We present a new mechanistic model, stochastic, Lagrangian aggregate model of sinking particles (SLAMS) for the biological pump in the ocean, which tracks the evolution of individual particles as they aggregate, disaggregate, sink, and are altered by chemical and biological processes. SLAMS considers the impacts of ballasting by mineral phases, binding of aggregates by transparent exopolymer particles (TEP), zooplankton grazing and the fractal geometry (porosity) of the aggregates. Parameterizations for age-dependent organic carbon (orgC) degradation kinetics, and disaggregation driven by zooplankton grazing and TEP degradation, are motivated by observed particle fluxes and size spectra throughout the water column. The model is able to explain observed variations in orgC export efficiency and rain ratio from the euphotic zone and to the sea floor as driven by sea surface temperature and the primary production rate and seasonality of primary production. The model provides a new mechanistic framework with which to predict future changes on the flux attenuation of orgC in response to climate change forcing.

  18. Modelling ice layer formation using a preferential flow formulation in the physics based multi-layer SNOWPACK model

    NASA Astrophysics Data System (ADS)

    Wever, Nander; Würzer, Sebastian; Fierz, Charles; Lehning, Michael

    2016-04-01

    For physics based snow cover models, simulating the formation of dense ice layers inside the snowpack has been a long time challenge. In spite of their small vertical extend, the presence of ice lenses inside the snowpack can have a profound impact on vapor, heat and liquid water flow. These effects may ultimately influence processes on larger scales when, for example, looking at hydrological processes or wet snow avalanche formation. Also microwave emission signals from the snowpack are strongly influenced by the presence of ice layers. Recent laboratory experiments and modelling techniques of liquid water flow in snow have advanced the understanding of liquid water flow in snow, in particular the formation of preferential flow paths. We present a modelling approach in the one-dimensional, multi-layer snow cover model SNOWPACK for preferential flow that is based on a dual-domain approach (i.e., separation into a matrix flow and a preferential flow domain) and solving Richards equation for both. In recently published laboratory experiments, water ponding inside the snowpack has been identified to initiate preferential flow. Those studies also quantified the part of the snowpack involved in preferential flow as a function of grain size. By combining these concepts with an empirical function to determine refreezing of preferential flow water inside the snowpack, we are able to simulate preferential water flow in the model. We found that preferential flow paths arriving at a layer transition in the snowpack may lead to ponding conditions. Subsequent refreezing then may form dense ice layers (>700 kg/m3). We compare the simulations to 14 years of biweekly snow profiles made at the Weissfluhjoch study plot at 2540m altitude in the Eastern Swiss Alps. We show that we are able to reproduce several ice lenses that were observed in the field, whereas some profiles remain challenging to simulate.

  19. Artificial neural networks to model formulation-property correlations in the process of inline-compounding on an injection moulding machine

    NASA Astrophysics Data System (ADS)

    Moritzer, Elmar; Müller, Ellen; Martin, Yannick; Kleeschulte, Rainer

    2015-05-01

    Today the global market poses great challenges for industrial product development. Complexity, diversity of variants, flexibility and individuality are just some of the features that products have to offer today. In addition, the product series have shorter lifetimes. Because of their high capacity for adaption, polymers are increasingly able to displace traditional materials such as wood, glass and metals from various fields of application. Polymers can only be used to substitute other materials, however, if they are optimally suited to the applications in question. Hence, product-specific material development is becoming increasingly important. Integrating the compounding step in the injection moulding process permits a more efficient and faster development process for a new polymer formulation, making it possible to create new product-specific materials. This process is called inline-compounding on an injection moulding machine. The entire process sequence is supported by software from Bayer Technology called Product Design Workbench (PDWB), which provides assistance in all the individual steps from data management, via analysis and model compilation, right through to the optimization of the formulation and the design of experiments. The software is based on artificial neural networks and can model the formulation-property correlations and thus enable different formulations to be optimized. In the study presented, the workflow and the modelling with the software are presented.

  20. Evaluating the Suitability of Using Rat Models for Preclinical Efficacy and Side Effects with Inhaled Corticosteroids Nanosuspension Formulations

    NASA Astrophysics Data System (ADS)

    Chiang, Po-Chang; Hu, Yiding; Blom, Jason D.; Thompson, David C.

    2010-06-01

    Inhaled corticosteroids (ICS) are often prescribed as first-line therapy for patients with asthma Despite their efficacy and improved safety profile compared with oral corticosteroids, the potential for systemic side effects continues to cause concern. In order to reduce the potential for systemic side effects, the pharmaceutical industry has begun efforts to generate new drugs with pulmonary-targeted topical efficacy. One of the major challenges of this approach is to differentiate both efficacy and side effects (pulmonary vs. systemic) in a preclinical animal model. In this study, fluticasone and ciclesonide were used as tool compounds to explore the possibility of demonstrating both efficacy and side effects in a rat model using pulmonary delivery via intratracheal (IT) instillation with nanosuspension formulations. The inhibition of neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and cytokine (TNFα) production were utilized to assess pulmonary efficacy, while adrenal and thymus involution as well as plasma corticosterone suppression was measured to assess systemic side effects. Based on neutrophil infiltration and cytokine production data, the ED50s for ciclesonide and fluticasone were calculated to be 0.1 and 0.03 mg, respectively. At the ED50, the average adrenal involution was 7.6 ± 5.3% for ciclesonide versus 16.6 ± 5.1% for fluticasone, while the average thymus involution was 41.0 ± 4.3% for ciclesonide versus 59.5 ± 5.8% for fluticasone. However, the differentiation became less significant when the dose was pushed to the EDmax (0.3 mg for ciclesonide, 0.1 mg for fluticasone). Overall, the efficacy and side effect profiles of the two compounds exhibited differentiation at low to mid doses (0.03-0.1 mg ciclesonide, 0.01-0.03 mg fluticasone), while this differentiation diminished at the maximum efficacious dose (0.3 mg ciclesonide, 0.1 mg fluticasone), likely due to overdosing in this model. We conclude that the rat LPS model using IT

  1. In vivo toxicity and bioavailability of Taxol and a paclitaxel/beta-cyclodextrin formulation in a rat model during HIPEC.

    PubMed

    Bouquet, W; Ceelen, W; Adriaens, E; Almeida, A; Quinten, T; De Vos, F; Pattyn, P; Peeters, M; Remon, J P; Vervaet, C

    2010-09-01

    Peritoneal carcinomatosis (PC) remains a dreaded clinical syndrome and a common evolution of gastrointestinal and ovarian cancers. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has emerged as a promising strategy in the management of PC. In this study, a novel paclitaxel (Pac) formulation was investigated for its toxicity and bioavailability during HIPEC compared with Taxol. The maximum tolerated dose (MTD) after HIPEC of both formulations (Taxol and Pac/RAME-beta-CD) was determined. MTD was defined as the highest nonlethal dose with a reduction in body weight of < or = 10% over 2 weeks. Blood parameters (red blood cell and white blood cell count, creatinine, ALT, and GGT) were evaluated over 20 days. Bioavailability of both Pac formulations after HIPEC was determined under normothermic (37 degrees C) and hyperthermic (41 degrees C) conditions for 90 min. Following HIPEC, both formulations had a similar MTD: 0.24 mg paclitaxel per ml. Red blood cell count decreased to a minimum after 10 days and was not fully recovered after 20 days for both formulations. White blood cell monitoring showed a significant increase in neutrocytes at day 10 and 15 for the Pac/RAME-beta-CD formulation. Liver and kidney parameters did not change significantly. Bioavailability data of Pac/RAME-beta-CD showed a 40-fold increase of the area under the curve (AUC) of plasma concentrations compared with Taxol. Hyperthermia yielded no significant differences in bioavailability data. These results showed that both formulations had a similar toxicity profile but differed significantly in bioavailability.

  2. Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat model

    PubMed Central

    Desai, Bhavna N.; Maharjan, Radha H.; Nampoothiri, Laxmipriya P.

    2012-01-01

    Background: Polycystic ovarian syndrome (PCOS), characterized by ovulatory infertility and hyperandrogenism, is associated with metabolic complications such as dyslipidemia, insulin resistance and endothelial dysfunction. Almost 70% PCOS women have abnormal serum lipid levels (dyslipidemia) and 50% of these women are obese. Several classes of pharmacological agents have been used to manage dyslipidemia. However, studies have shown adverse effects associated with these drugs. In the light of alternate therapy, many medicinal herbs have been reported to show hypoglycemic, anti-hyperlipidemic potential. Aloe barbadensis Mill. or Aloe vera is reported as one such herb. This study was to evaluate the lipid correcting effect of Aloe vera gel (AVG) in a PCOS rat model. Materials and Methods: PCOS was induced in Charles Foster female rats by oral administration of non-steroidal aromatase inhibitor letrozole (0.5 mg/kg body weight, 21 days). All rats were hyperglycemic and 90% rats also showed elevated plasma triglycerides, elevated LDL cholesterol levels, and lowered plasma HDL cholesterol levels indicative of a dyslipidemic profile. PCOS positive rats with an aberrant lipid profile were selected for treatment. An AVG formulation (1 ml (10 mg)/day, 30 days) was administered orally. Results and Conclusion: AVG treated PCOS rats exhibited significant reduction in plasma triglyceride and LDL cholesterol levels, with an increase in HDL cholesterol. The gel treatment also caused reversion of abnormal estrous cyclicity, glucose intolerance, and lipid metabolizing enzyme activities, bringing them to normal. In conclusion, AVG has phyto components with anti-hyperlipidemic effects and it has shown efficacy in management of not only PCOS but also the associated metabolic complication : dyslipidemia. PMID:22518083

  3. Glass Property Models and Constraints for Estimating the Glass to be Produced at Hanford by Implementing Current Advanced Glass Formulation Efforts

    SciTech Connect

    Vienna, John D.; Kim, Dong-Sang; Skorski, Daniel C.; Matyas, Josef

    2013-07-01

    Recent glass formulation and melter testing data have suggested that significant increases in waste loading in HLW and LAW glasses are possible over current system planning estimates. The data (although limited in some cases) were evaluated to determine a set of constraints and models that could be used to estimate the maximum loading of specific waste compositions in glass. It is recommended that these models and constraints be used to estimate the likely HLW and LAW glass volumes that would result if the current glass formulation studies are successfully completed. It is recognized that some of the models are preliminary in nature and will change in the coming years. Plus the models do not currently address the prediction uncertainties that would be needed before they could be used in plant operations. The models and constraints are only meant to give an indication of rough glass volumes and are not intended to be used in plant operation or waste form qualification activities. A current research program is in place to develop the data, models, and uncertainty descriptions for that purpose. A fundamental tenet underlying the research reported in this document is to try to be less conservative than previous studies when developing constraints for estimating the glass to be produced by implementing current advanced glass formulation efforts. The less conservative approach documented herein should allow for the estimate of glass masses that may be realized if the current efforts in advanced glass formulations are completed over the coming years and are as successful as early indications suggest they may be. Because of this approach there is an unquantifiable uncertainty in the ultimate glass volume projections due to model prediction uncertainties that has to be considered along with other system uncertainties such as waste compositions and amounts to be immobilized, split factors between LAW and HLW, etc.

  4. Orographically Forced Planetary Waves in the Northern Hemisphere Winter: Steady State Model with Wave-Coupled Lower Boundary Formulation.

    NASA Astrophysics Data System (ADS)

    Chen, Shyh-Chin; Trenberth, Kevin E.

    1988-02-01

    A planetary wave model has been developed in which the orographic forcing at the lower boundary arising from the kinematically induced vertical motion is due to the total flow impinging on the mountains rather than just the zonal mean basic state component of the flow over the mountains used in previous models. Consequently, the effects of the vertical motions produced by the eddies at the lower boundary are included and are found to be as large, if not larger, than the zonal mean component. The model remains linear mathematically, but all the planetary waves become coupled through the lower boundary condition (LBC) and the model wave equations have to be solved for simultaneously. A contrast is drawn between the wave-coupled solutions and the solutions using the traditional lower boundary formulation in which the planetary waves are decoupled.The model is symmetric about the equator and uses the linear balance set of equations on the sphere, with full spherical geometry and spherical harmonic function representation, truncated to include four zonal modes and up to mode 15 in the meridional direction. There are 11 levels in the vertical with the highest computational level at 5 mb. The model is linearized about a realistic observed January zonal-mean basic state and forced by the Northern Hemisphere orography and a wintertime calculated diabatic heating. In this paper, diabatic heating effects are not included and only the impact of the new LBC is examined in detail.The wave-coupled LBC has significant impact on the forced planetary waves and consequently on the Eliassen-Palm fluxes. The most noticeable responses of the planetary waves at the boundary when the wave-coupled LBC is used are in the vicinity of the Himalayas. The boundary eddies set up perturbation easterlies that locally offset the imposed zonal mean westerlies by forcing the flow to go around the mountains. Thus the wave-coupled LBC allows the total flow at the lower boundary to circumvent the

  5. Formulation and Validation of Model for Calculating the Number of Probe Cars Considering Traffic Information Update Frequency

    NASA Astrophysics Data System (ADS)

    Fushiki, Takumi; Yokota, Takayoshi; Kimita, Kazuya; Kumagai, Masatoshi

    Probe cars are very effective tools in traffic information gathering. Probe cars can collect the traffic condition data without using roadside sensors but with only using their own equipped sensors. By using probe cars, it is expected that the accuracy of traffic information will be improved and the area coverage of the traffic information service will be increased, and many experimental probe car data collection projects have been implemented. However, the number of probe cars required for adequate information update frequency has not been theoretically discussed. This paper formulates the probabilistic relationships among the traffic volume of probe cars, the area coverage, and the update frequency of traffic information provision. This formulation calculates the adequate number of probe cars to realize traffic information services in advance considering two major service factors: area coverage and update frequency. This paper also validates the theoretical formulation with experimental probe car data collected in a taxi monitoring system.

  6. A fully coupled Thermo-Hydro-Mechanical Double Porosity Formulation for Modeling Multiphysics Problems in Geological Media

    NASA Astrophysics Data System (ADS)

    Sanchez, M. J.; Gens, A.; Jarecki, Z.; Olivella, S.

    2012-12-01

    This work presents a coupled Thermo-Hydro-Mechanical (THM) formulation developed to handle multiphysic problems in porous media with two dominant void levels. The proposed framework assumes the presence of two porous media linked through a mass transfer term between them. In many cases, the use of a double porosity formulation is more realistic because it is possible to take explicitly into account the different physical phenomena that take place in each void level, and also their mutual interactions. The formulation is especially suitable for cases in which the material exhibits a strong coupling between the mechanical and the hydraulic problem in both media. The problem is approached using a multi-phase, multi-species formulation that expresses mathematically the main coupled thermo-hydro-mechanical phenomena in terms of: balance equations, constitutive equations and equilibrium restrictions. In its more general form, the proposed approach allows the consideration of multiphase flow in the two pore levels coupled with the mechanical problem. The formulation presented is quite open and general, and able to incorporate different constitutive laws for each basic structural level considered; for the mechanical, hydraulic and thermal problems. The double structure formulation has been implemented in the finite element program CODE_BRIGHT and it has been used to analyze a variety of engineering problems associated with the design of radioactive waste disposal in deep geological media and petroleum engineering problems. This work presents two case studies; one is related to oil production in a heterogeneous reservoir, and the other case focuses on the analysis of a repository for nuclear waste in a clayed formation. Both cases show the potential of the proposed formation to tackle coupled multiphysics problems in porous media.