Thermodynamically Constrained Averaging Theory (TCAT) Two-Phase Flow Model: Derivation, Closure, and Simulation Results

NASA Astrophysics Data System (ADS)

Weigand, T. M.; Miller, C. T.; Dye, A. L.; Gray, W. G.; McClure, J. E.; Rybak, I.

2015-12-01

The thermodynamically constrained averaging theory (TCAT) has been usedto formulate general classes of porous medium models, including newmodels for two-fluid-phase flow. The TCAT approach provides advantagesthat include a firm connection between the microscale, or pore scale,and the macroscale; a thermodynamically consistent basis; explicitinclusion of factors such as interfacial areas, contact angles,interfacial tension, and curvatures; and dynamics of interface movementand relaxation to an equilibrium state. In order to render the TCATmodel solvable, certain closure relations are needed to relate fluidpressure, interfacial areas, curvatures, and relaxation rates. In thiswork, we formulate and solve a TCAT-based two-fluid-phase flow model. We detail the formulation of the model, which is a specific instancefrom a hierarchy of two-fluid-phase flow models that emerge from thetheory. We show the closure problem that must be solved. Using recentresults from high-resolution microscale simulations, we advance a set ofclosure relations that produce a closed model. Lastly, we solve the model using a locally conservative numerical scheme and compare the TCAT model to the traditional model.

Retrospective estimation of breeding phenology of American Goldfinch (Carduelis tristis) using pattern oriented modeling

EPA Science Inventory

Avian seasonal productivity is often modeled as a time-limited stochastic process. Many mathematical formulations have been proposed, including individual based models, continuous-time differential equations, and discrete Markov models. All such models typically include paramete...

Origin of the sensitivity in modeling the glide behaviour of dislocations

DOE PAGES

Pei, Zongrui; Stocks, George Malcolm

2018-03-26

The sensitivity in predicting glide behaviour of dislocations has been a long-standing problem in the framework of the Peierls-Nabarro model. The predictions of both the model itself and the analytic formulas based on it are too sensitive to the input parameters. In order to reveal the origin of this important problem in materials science, a new empirical-parameter-free formulation is proposed in the same framework. Unlike previous formulations, it includes only a limited small set of parameters all of which can be determined by convergence tests. Under special conditions the new formulation is reduced to its classic counterpart. In the lightmore » of this formulation, new relationships between Peierls stresses and the input parameters are identified, where the sensitivity is greatly reduced or even removed.« less

Models and techniques for evaluating the effectiveness of aircraft computing systems

NASA Technical Reports Server (NTRS)

Meyer, J. F.

1978-01-01

The development of system models that can provide a basis for the formulation and evaluation of aircraft computer system effectiveness, the formulation of quantitative measures of system effectiveness, and the development of analytic and simulation techniques for evaluating the effectiveness of a proposed or existing aircraft computer are described. Specific topics covered include: system models; performability evaluation; capability and functional dependence; computation of trajectory set probabilities; and hierarchical modeling of an air transport mission.

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.

Chaotic hybrid inflation with a gauged B -L

NASA Astrophysics Data System (ADS)

Carpenter, Linda M.; Raby, Stuart

2014-11-01

In this paper we present a novel formulation of chaotic hybrid inflation in supergravity. The model includes a waterfall field which spontaneously breaks a gauged U1 (B- L) at a GUT scale. This allows for the possibility of future model building which includes the standard formulation of baryogenesis via leptogenesis with the waterfall field decaying into right-handed neutrinos. We have not considered the following issues in this short paper, i.e. supersymmetry breaking, dark matter or the gravitino or moduli problems. Our focus is on showing the compatibility of the present model with Planck, WMAP and Bicep2 data.

Transient modeling/analysis of hyperbolic heat conduction problems employing mixed implicit-explicit alpha method

NASA Technical Reports Server (NTRS)

Tamma, Kumar K.; D'Costa, Joseph F.

1991-01-01

This paper describes the evaluation of mixed implicit-explicit finite element formulations for hyperbolic heat conduction problems involving non-Fourier effects. In particular, mixed implicit-explicit formulations employing the alpha method proposed by Hughes et al. (1987, 1990) are described for the numerical simulation of hyperbolic heat conduction models, which involves time-dependent relaxation effects. Existing analytical approaches for modeling/analysis of such models involve complex mathematical formulations for obtaining closed-form solutions, while in certain numerical formulations the difficulties include severe oscillatory solution behavior (which often disguises the true response) in the vicinity of the thermal disturbances, which propagate with finite velocities. In view of these factors, the alpha method is evaluated to assess the control of the amount of numerical dissipation for predicting the transient propagating thermal disturbances. Numerical test models are presented, and pertinent conclusions are drawn for the mixed-time integration simulation of hyperbolic heat conduction models involving non-Fourier effects.

Numerical simulation of steady three-dimensional flows in axial turbomachinery bladerows

NASA Astrophysics Data System (ADS)

Basson, Anton Herman

The formulation for and application of a numerical model for low Mach number steady three-dimensional flows in axial turbomachinery blade rows is presented. The formulation considered here includes an efficient grid generation scheme (particularly suited to computational grids for the analysis of turbulent turbomachinery flows) and a semi-implicit, pressure-based computational fluid dynamics scheme that directly includes artificial dissipation, applicable to viscous and inviscid flows. The grid generation technique uses a combination of algebraic and elliptic methods, in conjunction with the Minimal Residual Method, to economically generate smooth structured grids. For typical H-grids in turbomachinery bladerows, when compared to a purely elliptic grid generation scheme, the presented grid generation scheme produces grids with much improved smoothness near the leading and trailing edges, allows the use of small near wall grid spacing required by low Reynolds number turbulence models, and maintains orthogonality of the grid near the solid boundaries even for high flow angle cascades. A specialized embedded H-grid for application particularly to tip clearance flows is presented. This topology smoothly discretizes the domain without modifying the tip shape, while requiring only minor modifications to H-grid flow solvers. Better quantitative modeling of the tip clearance vortex structure than that obtained with a pinched tip approximation is demonstrated. The formulation of artificial dissipation terms for a semi-implicit, pressure-based (SIMPLE type) flow solver, is presented. It is applied to both the Euler and the Navier-Stokes equations, expressed in generalized coordinates using a non-staggered grid. This formulation is compared to some SIMPLE and time marching formulations, revealing the artificial dissipation inherent in some commonly used semi-implicit formulations. The effect of the amount of dissipation on the accuracy of the solution and the convergence rate is quantitatively demonstrated for a number of flow cases. The ability of the formulation to model complex steady turbomachinery flows is demonstrated, e.g. for pressure driven secondary flows, turbine nozzle wakes, turbulent boundary layers. The formulation's modeling of blade surface heat transfer is assessed. The numerical model is used to investigate the structure of phenomena associated with tip clearance flows in a turbine nozzle.

Characterization of Rocket Propellant Combustion Products. Chemical Characterization and Computer Modeling of the Exhaust Products from Four Propellant Formulations

DTIC Science & Technology

1990-12-31

health hazards from weapons combustion products, to include rockets and missiles, became evident, Research to elucidate significant health effects of...CO/CO2 ratios was low for all but one of dhe formulations, In general, if the model were to be used in its present state for health risk assessments...35 Part 2: Modeling for Health Hazard Prediction Introduction ................................................. 37 Results and D iscussion

Simulation of Two-Phase Flow Based on a Thermodynamically Constrained Averaging Theory Flow Model

NASA Astrophysics Data System (ADS)

Weigand, T. M.; Dye, A. L.; McClure, J. E.; Farthing, M. W.; Gray, W. G.; Miller, C. T.

2014-12-01

The thermodynamically constrained averaging theory (TCAT) has been used to formulate general classes of porous medium models, including new models for two-fluid-phase flow. The TCAT approach provides advantages that include a firm connection between the microscale, or pore scale, and the macroscale; a thermodynamically consistent basis; explicit inclusion of factors such as interfacial areas, contact angles, interfacial tension, and curvatures; and dynamics of interface movement and relaxation to an equilibrium state. In order to render the TCAT model solvable, certain closure relations are needed to relate fluid pressure, interfacial areas, curvatures, and relaxation rates. In this work, we formulate and solve a TCAT-based two-fluid-phase flow model. We detail the formulation of the model, which is a specific instance from a hierarchy of two-fluid-phase flow models that emerge from the theory. We show the closure problem that must be solved. Using recent results from high-resolution microscale simulations, we advance a set of closure relations that produce a closed model. Lastly, we use locally conservative spatial discretization and higher order temporal discretization methods to approximate the solution to this new model and compare the solution to the traditional model.

Mathematical formulation of the Applications Technology Satellite-F (ATS-F) orbital maneuver control program (CNTRLF)

NASA Technical Reports Server (NTRS)

Goorevich, C. E.

1975-01-01

The mathematical formulation is presented of CNTRLF, the maneuver control program for the Applications Technology Satellite-F (ATS-F). The purpose is to specify the mathematical models that are included in the design of CNTRLF.

Crazing in Polymeric and Composite Systems

DTIC Science & Technology

1990-04-23

these physical variations into consideration in any mathematical modeling and formulation in analyzing the stresses from the time when crazes incept to...as boundary tractions with great strength; any governing mathematical formulation must include this feature for any adequate analysis. Crazes of...constants the mathematical model describing the crazing mechanism have been successful [25-29]. References 1 J. A. Sauer, J. Marin and C. C. Hsiao, J. App

Antiferromagnetism and DX2-Y2-WAVE Pairing in the Colored Hubbard Model

NASA Astrophysics Data System (ADS)

Baier, Tobias; Bick, Eike

2001-08-01

We introduce a new formulation of the 2d Hubbard model on a square lattice (the "colored" Hubbard model). In this formulation interesting physical nonlocal properties as antiferromagnetic or dx2-y2-wave superconducting behavior are included in an explicit way. Analyzing the phase diagram in a mean field approximation numerically, we show that our approach yields results which are in qualitative agreement with experiment.

Collisionless solar wind protons: A comparison of kinetic and hydrodynamic descriptions

NASA Technical Reports Server (NTRS)

Leer, E.; Holzer, T. E.

1971-01-01

Kinetic and hydrodynamic descriptions of a collisionless solar wind proton gas are compared. Heat conduction and viscosity are neglected in the hydrodynamic formulation but automatically included in the kinetic formulation. The results of the two models are very nearly the same, indicating that heat conduction and viscosity are not important in the solar wind proton gas beyond about 0.1 AU. It is concluded that the hydrodynamic equations provide a valid description of the collisionless solar wind protons, and hence that future models of the quiet solar wind should be based on a hydrodynamic formulation.

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

Pei, Zongrui; Stocks, George Malcolm

The sensitivity in predicting glide behaviour of dislocations has been a long-standing problem in the framework of the Peierls-Nabarro model. The predictions of both the model itself and the analytic formulas based on it are too sensitive to the input parameters. In order to reveal the origin of this important problem in materials science, a new empirical-parameter-free formulation is proposed in the same framework. Unlike previous formulations, it includes only a limited small set of parameters all of which can be determined by convergence tests. Under special conditions the new formulation is reduced to its classic counterpart. In the lightmore » of this formulation, new relationships between Peierls stresses and the input parameters are identified, where the sensitivity is greatly reduced or even removed.« less

Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores.

PubMed

Peachman, Kristina K; Li, Qin; Matyas, Gary R; Shivachandra, Sathish B; Lovchik, Julie; Lyons, Rick C; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

2012-01-01

In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development.

Modeling human target acquisition in ground-to-air weapon systems

NASA Technical Reports Server (NTRS)

Phatak, A. V.; Mohr, R. L.; Vikmanis, M.; Wei, K. C.

1982-01-01

The problems associated with formulating and validating mathematical models for describing and predicting human target acquisition response are considered. In particular, the extension of the human observer model to include the acquisition phase as well as the tracking segment is presented. Relationship of the Observer model structure to the more complex Standard Optimal Control model formulation and to the simpler Transfer Function/Noise representation is discussed. Problems pertinent to structural identifiability and the form of the parameterization are elucidated. A systematic approach toward the identification of the observer acquisition model parameters from ensemble tracking error data is presented.

New approach to analyzing soil-building systems

USGS Publications Warehouse

Safak, E.

1998-01-01

A new method of analyzing seismic response of soil-building systems is introduced. The method is based on the discrete-time formulation of wave propagation in layered media for vertically propagating plane shear waves. Buildings are modeled as an extension of the layered soil media by assuming that each story in the building is another layer. The seismic response is expressed in terms of wave travel times between the layers, and the wave reflection and transmission coefficients at layer interfaces. The calculation of the response is reduced to a pair of simple finite-difference equations for each layer, which are solved recursively starting from the bedrock. Compared with commonly used vibration formulation, the wave propagation formulation provides several advantages, including the ability to incorporate soil layers, simplicity of the calculations, improved accuracy in modeling the mass and damping, and better tools for system identification and damage detection.A new method of analyzing seismic response of soil-building systems is introduced. The method is based on the discrete-time formulation of wave propagation in layered media for vertically propagating plane shear waves. Buildings are modeled as an extension of the layered soil media by assuming that each story in the building is another layer. The seismic response is expressed in terms of wave travel times between the layers, and the wave reflection and transmission coefficients at layer interfaces. The calculation of the response is reduced to a pair of simple finite-difference equations for each layer, which are solved recursively starting from the bedrock. Compared with commonly used vibration formulation, the wave propagation formulation provides several advantages, including the ability to incorporate soil layers, simplicity of the calculations, improved accuracy in modeling the mass and damping, and better tools for system identification and damage detection.

Antimicrobial effects of a new therapeutic liquid dentifrice formulation on oral bacteria including odorigenic species.

PubMed

Sreenivasan, P K; Furgang, D; Zhang, Y; DeVizio, W; Fine, D H

2005-03-01

The control of oral malodor is well-recognized in efforts to improve oral health. Antimicrobial formulations can mitigate oral malodor, however, procedures to assess effects on oral bacteria including those implicated in halitosis are unavailable. This investigation examined the antimicrobial effects of a new liquid triclosan/copolymer dentifrice (test) formulation that demonstrated significant inhibition of oral malodor in previous organoleptic clinical studies. Procedures compared antimicrobial effects of the test and control formulations on a range of oral micro-organisms including members implicated in halitosis, substantive antimicrobial effects of formulations with hydroxyapatite as a surrogate for human teeth and ex vivo effects on oral bacteria from human volunteers. With Actinomyces viscosus, as a model system, the test formulation demonstrated a dose-dependent effect. At these concentrations the test formulation provided significant antimicrobial effects on 13 strains of oral bacteria including those implicated in bad breath at selected posttreatment time points. Treatment of hydroxyapatite by the test dentifrice resulted in a significant and substantive antimicrobial effect vs. controls. Oral bacteria from subjects treated ex vivo with the test dentifrice resulted in significant reductions in cultivable oral bacteria and odorigenic bacteria producing hydrogen sulfide. In summary, microbiological methods adapted to study odorigenic bacteria demonstrate the significant antimicrobial effects of the test (triclosan/copolymer) dentifrice with laboratory and clinical strains of oral bacteria implicated in bad breath.

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.

Detached-Eddy Simulation Based on the V2-F Model

NASA Technical Reports Server (NTRS)

Jee, Sol Keun; Shariff, Karim R.

2012-01-01

Detached-eddy simulation (DES) based on the v(sup 2)-f Reynolds-averaged Navier-Stokes (RANS) model is developed and tested. The v(sup 2)-f model incorporates the anisotropy of near-wall turbulence which is absent in other RANS models commonly used in the DES community. The v(sup 2)-f RANS model is modified in order the proposed v(sup 2)-f-based DES formulation reduces to a transport equation for the subgrid-scale kinetic energy isotropic turbulence. First, three coefficients in the elliptic relaxation equation are modified, which is tested in channel flows with friction Reynolds number up to 2000. Then, the proposed v(sup 2)-f DES model formulation is derived. The constant, C(sub DES), required in the DES formulation was calibrated by simulating both decaying and statistically-steady isotropic turbulence. After C(sub DES) was calibrated, the v(sub 2)-f DES formulation is tested for flow around a circular cylinder at a Reynolds number of 3900, in which case turbulence develops after separation. Simulations indicate that this model represents the turbulent wake nearly as accurately as the dynamic Smagorinsky model. Spalart-Allmaras-based DES is also included in the cylinder flow simulation for comparison.

Reconceptualizing emetophobia: a cognitive-behavioral formulation and research agenda.

PubMed

Boschen, Mark J

2007-01-01

Fear of vomiting (emetophobia) is a poorly understood anxiety disorder, with little research published into its conceptualization or treatment. The current article uses established cognitive and behavioral models of other anxiety disorders as a basis from which to propose a detailed model of emetophobia. The model proposes that emetophobia results from a constellation of factors including a general anxiety-vulnerability factor, a tendency to somatize anxiety as gastrointestinal distress, a tendency to catastrophically misappraise nausea and other gastrointestinal symptoms, hypervigilance to gastrointestinal cues, beliefs about the unacceptability of vomiting, negatively reinforced avoidance behavior, and selective confirmation biases. A formulation-based treatment package for emetophobia is outlined, including arousal management skills, distraction/attention training, exposure and cognitive restructuring.

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.

Stable Algorithm For Estimating Airdata From Flush Surface Pressure Measurements

NASA Technical Reports Server (NTRS)

Whitmore, Stephen, A. (Inventor); Cobleigh, Brent R. (Inventor); Haering, Edward A., Jr. (Inventor)

2001-01-01

An airdata estimation and evaluation system and method, including a stable algorithm for estimating airdata from nonintrusive surface pressure measurements. The airdata estimation and evaluation system is preferably implemented in a flush airdata sensing (FADS) system. The system and method of the present invention take a flow model equation and transform it into a triples formulation equation. The triples formulation equation eliminates the pressure related states from the flow model equation by strategically taking the differences of three surface pressures, known as triples. This triples formulation equation is then used to accurately estimate and compute vital airdata from nonintrusive surface pressure measurements.

Applied Routh approximation

NASA Technical Reports Server (NTRS)

Merrill, W. C.

1978-01-01

The Routh approximation technique for reducing the complexity of system models was applied in the frequency domain to a 16th order, state variable model of the F100 engine and to a 43d order, transfer function model of a launch vehicle boost pump pressure regulator. The results motivate extending the frequency domain formulation of the Routh method to the time domain in order to handle the state variable formulation directly. The time domain formulation was derived and a characterization that specifies all possible Routh similarity transformations was given. The characterization was computed by solving two eigenvalue-eigenvector problems. The application of the time domain Routh technique to the state variable engine model is described, and some results are given. Additional computational problems are discussed, including an optimization procedure that can improve the approximation accuracy by taking advantage of the transformation characterization.

Design of an expert system for the development and formulation of push-pull osmotic pump tablets containing poorly water-soluble drugs.

PubMed

Zhang, Zhi-hong; Dong, Hong-ye; Peng, Bo; Liu, Hong-fei; Li, Chun-lei; Liang, Min; Pan, Wei-san

2011-05-30

The purpose of this article was to build an expert system for the development and formulation of push-pull osmotic pump tablets (PPOP). Hundreds of PPOP formulations were studied according to different poorly water-soluble drugs and pharmaceutical acceptable excipients. The knowledge base including database and rule base was built based on the reported results of hundreds of PPOP formulations containing different poorly water-soluble drugs and pharmaceutical excipients and the experiences available from other researchers. The prediction model of release behavior was built using back propagation (BP) neural network, which is good at nonlinear mapping and learning function. Formulation design model was established based on the prediction model of release behavior, which was the nucleus of the inference engine. Finally, the expert system program was constructed by VB.NET associating with SQL Server. Expert system is one of the most popular aspects in artificial intelligence. To date there is no expert system available for the formulation of controlled release dosage forms yet. Moreover, osmotic pump technology (OPT) is gradually getting consummate all over the world. It is meaningful to apply expert system on OPT. Famotidine, a water insoluble drug was chosen as the model drug to validate the applicability of the developed expert system. Copyright © 2011 Elsevier B.V. All rights reserved.

Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

PubMed

Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike

2016-09-01

Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.

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.

Generalized Effective Medium Theory for Particulate Nanocomposite Materials

PubMed Central

Siddiqui, Muhammad Usama; Arif, Abul Fazal M.

2016-01-01

The thermal conductivity of particulate nanocomposites is strongly dependent on the size, shape, orientation and dispersion uniformity of the inclusions. To correctly estimate the effective thermal conductivity of the nanocomposite, all these factors should be included in the prediction model. In this paper, the formulation of a generalized effective medium theory for the determination of the effective thermal conductivity of particulate nanocomposites with multiple inclusions is presented. The formulated methodology takes into account all the factors mentioned above and can be used to model nanocomposites with multiple inclusions that are randomly oriented or aligned in a particular direction. The effect of inclusion dispersion non-uniformity is modeled using a two-scale approach. The applications of the formulated effective medium theory are demonstrated using previously published experimental and numerical results for several particulate nanocomposites. PMID:28773817

pyomocontrib_simplemodel v. 1.0

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

Hart, William

2017-03-02

Pyomo supports the formulation and analysis of mathematical models for complex optimization applications. This library extends the API of Pyomo to include a simple modeling representation: a list of objectives and constraints.

Modeling of fatigue crack induced nonlinear ultrasonics using a highly parallelized explicit local interaction simulation approach

NASA Astrophysics Data System (ADS)

Shen, Yanfeng; Cesnik, Carlos E. S.

2016-04-01

This paper presents a parallelized modeling technique for the efficient simulation of nonlinear ultrasonics introduced by the wave interaction with fatigue cracks. The elastodynamic wave equations with contact effects are formulated using an explicit Local Interaction Simulation Approach (LISA). The LISA formulation is extended to capture the contact-impact phenomena during the wave damage interaction based on the penalty method. A Coulomb friction model is integrated into the computation procedure to capture the stick-slip contact shear motion. The LISA procedure is coded using the Compute Unified Device Architecture (CUDA), which enables the highly parallelized supercomputing on powerful graphic cards. Both the explicit contact formulation and the parallel feature facilitates LISA's superb computational efficiency over the conventional finite element method (FEM). The theoretical formulations based on the penalty method is introduced and a guideline for the proper choice of the contact stiffness is given. The convergence behavior of the solution under various contact stiffness values is examined. A numerical benchmark problem is used to investigate the new LISA formulation and results are compared with a conventional contact finite element solution. Various nonlinear ultrasonic phenomena are successfully captured using this contact LISA formulation, including the generation of nonlinear higher harmonic responses. Nonlinear mode conversion of guided waves at fatigue cracks is also studied.

Designing herbicide formulation characteristics to maximize efficacy and minimize rice injury in paddy environments.

PubMed

Cryer, S A; Mann, R K; Erhardt-Zabik, S; Keeney, F N; Handy, P R

2001-06-01

Mathematical descriptors, coupled with experimental observations, are used to quantify differential uptake of an experimental herbicide in Japonica and Indica rice (Oryza sativa, non-target) and barnyardgrass (Echinochloa crus-galli, target). Partitioning, degradation, plant uptake and metabolism are described using mass-balance conservation equations in the form of kinetic approximations. Estimated environmental concentrations, governed by the pesticide formulation, are described using superimposed analytical solutions for the one-dimensional diffusion equation in spherical coordinates and by a finite difference representation of the two-dimensional diffusion equation in Cartesian coordinates. Formulation attributes from granules include active ingredient release rates, particle sizes, pesticide loading, and granule spacing. The diffusion model for pesticide transport is coupled with the compartment model to follow the fate and transport of a pesticide from its initial application location to various environmental matrices of interest. Formulation effects, partitioning and degradation in the various environmental matrices, differential plant uptake and metabolism, and dose-response information for plants are accounted for. This novel model provides a mechanism for selecting formulation delivery systems that optimize specific attributes (such as weed control or the therapeutic index) for risk-assessment procedures. In this report we describe how this methodology was used to explore the factors affecting herbicide efficacy and to define an optimal release rate for a granule formulation.

Propeller Study. Part 2: the Design of Propellers for Minimum Noise

NASA Technical Reports Server (NTRS)

Ormsbee, A. I.; Woan, C. J.

1977-01-01

The design of propellers which are efficient and yet produce minimum noise requires accurate determinations of both the flow over the propeller. Topics discussed in relating aerodynamic propeller design and propeller acoustics include the necessary approximations and assumptions involved, the coordinate systems and their transformations, the geometry of the propeller blade, and the problem formulations including the induced velocity, required in the determination of mean lines of blade sections, and the optimization of propeller noise. The numerical formulation for the lifting-line model are given. Some applications and numerical results are included.

Factors Influencing Progressive Failure Analysis Predictions for Laminated Composite Structure

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.

2008-01-01

Progressive failure material modeling methods used for structural analysis including failure initiation and material degradation are presented. Different failure initiation criteria and material degradation models are described that define progressive failure formulations. These progressive failure formulations are implemented in a user-defined material model for use with a nonlinear finite element analysis tool. The failure initiation criteria include the maximum stress criteria, maximum strain criteria, the Tsai-Wu failure polynomial, and the Hashin criteria. The material degradation model is based on the ply-discounting approach where the local material constitutive coefficients are degraded. Applications and extensions of the progressive failure analysis material model address two-dimensional plate and shell finite elements and three-dimensional solid finite elements. Implementation details are described in the present paper. Parametric studies for laminated composite structures are discussed to illustrate the features of the progressive failure modeling methods that have been implemented and to demonstrate their influence on progressive failure analysis predictions.

Modelling of structural flexiblity in multibody railroad vehicle systems

NASA Astrophysics Data System (ADS)

Escalona, José L.; Sugiyama, Hiroyuki; Shabana, Ahmed A.

2013-07-01

This paper presents a review of recent research investigations on the computer modelling of flexible bodies in railroad vehicle systems. The paper will also discuss the influence of the structural flexibility of various components, including the wheelset, the truck frames, tracks, pantograph/catenary systems, and car bodies, on the dynamics of railroad vehicles. While several formulations and computer techniques for modelling structural flexibility are discussed in this paper, a special attention is paid to the floating frame of reference formulation which is widely used and leads to reduced-order finite-element models for flexible bodies by employing component modes synthesis techniques. Other formulations and numerical methods such as semi-analytical approaches, absolute nodal coordinate formulation, finite-segment method, boundary elements method, and discrete elements method are also discussed. This investigation is motivated by the fact that the structural flexibility can have a significant effect on the overall dynamics of railroad vehicles, ride comfort, vibration suppression and noise level reduction, lateral stability, track response to vehicle forces, stress analysis, wheel-rail contact forces, wear and crashworthiness.

Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin

PubMed Central

Meagher, Alison K.; Forrest, Alan; Dalhoff, Axel; Stass, Heino; Schentag, Jerome J.

2004-01-01

The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma. A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes. A “mixture model” was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment. Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively. The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios. PMID:15155200

Improved solar models constructed with a formulation of convection for stellar structure and evolution calculations without the mixing-length theory approximations

NASA Technical Reports Server (NTRS)

Lydon, Thomas J.; Fox, Peter A.; Sofia, Sabatino

1993-01-01

We have updated a previous attempt to incorporate within a solar model a treatment of convection based upon numerical simulations of convection rather than mixing-length theory (MLT). We have modified our formulation of convection for a better treatment of the kinetic energy flux. Our solar model has been updated to include a complete range of OPAL opacities, the Debye-Hueckel correction to the equation of state, helium diffusion due to gravitational settling, and atmospheres by Kurucz. We construct a series of models using both MLT and our revised formulation of convection and the compared results to measurements of the solar radius, the solar luminosity, and the depth of the solar convection zone as inferred from helioseismology. We find X(solar) = 0.702 +/- 0.005, Y(solar) = 0.278 +/- 0.005, and Z(solar) = 0.0193 +/- 0.0005.

A generalized nonlocal vector calculus

NASA Astrophysics Data System (ADS)

Alali, Bacim; Liu, Kuo; Gunzburger, Max

2015-10-01

A nonlocal vector calculus was introduced in Du et al. (Math Model Meth Appl Sci 23:493-540, 2013) that has proved useful for the analysis of the peridynamics model of nonlocal mechanics and nonlocal diffusion models. A formulation is developed that provides a more general setting for the nonlocal vector calculus that is independent of particular nonlocal models. It is shown that general nonlocal calculus operators are integral operators with specific integral kernels. General nonlocal calculus properties are developed, including nonlocal integration by parts formula and Green's identities. The nonlocal vector calculus introduced in Du et al. (Math Model Meth Appl Sci 23:493-540, 2013) is shown to be recoverable from the general formulation as a special example. This special nonlocal vector calculus is used to reformulate the peridynamics equation of motion in terms of the nonlocal gradient operator and its adjoint. A new example of nonlocal vector calculus operators is introduced, which shows the potential use of the general formulation for general nonlocal models.

InSTREAM: the individual-based stream trout research and environmental assessment model

Treesearch

Steven F. Railsback; Bret C. Harvey; Stephen K. Jackson; Roland H. Lamberson

2009-01-01

This report documents Version 4.2 of InSTREAM, including its formulation, software, and application to research and management problems. InSTREAM is a simulation model designed to understand how stream and river salmonid populations respond to habitat alteration, including altered flow, temperature, and turbidity regimes and changes in channel morphology. The model...

Recent advances in the modelling of crack growth under fatigue loading conditions

NASA Technical Reports Server (NTRS)

Dekoning, A. U.; Tenhoeve, H. J.; Henriksen, T. K.

1994-01-01

Fatigue crack growth associated with cyclic (secondary) plastic flow near a crack front is modelled using an incremental formulation. A new description of threshold behaviour under small load cycles is included. Quasi-static crack extension under high load excursions is described using an incremental formulation of the R-(crack growth resistance)- curve concept. The integration of the equations is discussed. For constant amplitude load cycles the results will be compared with existing crack growth laws. It will be shown that the model also properly describes interaction effects of fatigue crack growth and quasi-static crack extension. To evaluate the more general applicability the model is included in the NASGRO computer code for damage tolerance analysis. For this purpose the NASGRO program was provided with the CORPUS and the STRIP-YIELD models for computation of the crack opening load levels. The implementation is discussed and recent results of the verification are presented.

Modeling erosion and sedimentation coupled with hydrological and overland flow processes at the watershed scale

NASA Astrophysics Data System (ADS)

Kim, Jongho; Ivanov, Valeriy Y.; Katopodes, Nikolaos D.

2013-09-01

A novel two-dimensional, physically based model of soil erosion and sediment transport coupled to models of hydrological and overland flow processes has been developed. The Hairsine-Rose formulation of erosion and deposition processes is used to account for size-selective sediment transport and differentiate bed material into original and deposited soil layers. The formulation is integrated within the framework of the hydrologic and hydrodynamic model tRIBS-OFM, Triangulated irregular network-based, Real-time Integrated Basin Simulator-Overland Flow Model. The integrated model explicitly couples the hydrodynamic formulation with the advection-dominated transport equations for sediment of multiple particle sizes. To solve the system of equations including both the Saint-Venant and the Hairsine-Rose equations, the finite volume method is employed based on Roe's approximate Riemann solver on an unstructured grid. The formulation yields space-time dynamics of flow, erosion, and sediment transport at fine scale. The integrated model has been successfully verified with analytical solutions and empirical data for two benchmark cases. Sensitivity tests to grid resolution and the number of used particle sizes have been carried out. The model has been validated at the catchment scale for the Lucky Hills watershed located in southeastern Arizona, USA, using 10 events for which catchment-scale streamflow and sediment yield data were available. Since the model is based on physical laws and explicitly uses multiple types of watershed information, satisfactory results were obtained. The spatial output has been analyzed and the driving role of topography in erosion processes has been discussed. It is expected that the integrated formulation of the model has the promise to reduce uncertainties associated with typical parameterizations of flow and erosion processes. A potential for more credible modeling of earth-surface processes is thus anticipated.

Identification and stochastic control of helicopter dynamic modes

NASA Technical Reports Server (NTRS)

Molusis, J. A.; Bar-Shalom, Y.

1983-01-01

A general treatment of parameter identification and stochastic control for use on helicopter dynamic systems is presented. Rotor dynamic models, including specific applications to rotor blade flapping and the helicopter ground resonance problem are emphasized. Dynamic systems which are governed by periodic coefficients as well as constant coefficient models are addressed. The dynamic systems are modeled by linear state variable equations which are used in the identification and stochastic control formulation. The pure identification problem as well as the stochastic control problem which includes combined identification and control for dynamic systems is addressed. The stochastic control problem includes the effect of parameter uncertainty on the solution and the concept of learning and how this is affected by the control's duel effect. The identification formulation requires algorithms suitable for on line use and thus recursive identification algorithms are considered. The applications presented use the recursive extended kalman filter for parameter identification which has excellent convergence for systems without process noise.

VALIDITY OF A TWO-DIMENSIONAL MODEL FOR VARIABLE-DENSITY HYDRODYNAMIC CIRCULATION

EPA Science Inventory

A three-dimensional model of temperatures and currents has been formulated to assist in the analysis and interpretation of the dynamics of stratified lakes. In this model, nonlinear eddy coefficients for viscosity and conductivities are included. A two-dimensional model (one vert...

A Generalized Formulation of Demand Response under Market Environments

NASA Astrophysics Data System (ADS)

Nguyen, Minh Y.; Nguyen, Duc M.

2015-06-01

This paper presents a generalized formulation of Demand Response (DR) under deregulated electricity markets. The problem is scheduling and controls the consumption of electrical loads according to the market price to minimize the energy cost over a day. Taking into account the modeling of customers' comfort (i.e., preference), the formulation can be applied to various types of loads including what was traditionally classified as critical loads (e.g., air conditioning, lights). The proposed DR scheme is based on Dynamic Programming (DP) framework and solved by DP backward algorithm in which the stochastic optimization is used to treat the uncertainty, if any occurred in the problem. The proposed formulation is examined with the DR problem of different loads, including Heat Ventilation and Air Conditioning (HVAC), Electric Vehicles (EVs) and a newly DR on the water supply systems of commercial buildings. The result of simulation shows significant saving can be achieved in comparison with their traditional (On/Off) scheme.

Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

PubMed

Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

2001-01-01

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

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.

Formulation of additional observables for ENTREE

NASA Technical Reports Server (NTRS)

Findlay, J. T.; Heck, M. L.

1980-01-01

The S-band X and Y angles, SAMS, and TACAN range and bearing were incorporated into the ENTREE software for use by experimenters at LaRC for entry trajectory reconstruction purposes. Background discussions present the need for this added capability. Formulations for the various observables are presented. Both north-south and east-west antenna mounts were provided for in the S-band angle computations. Sub-vehicle terrain height variations are included in the SAMS model. Local magnetic variations were incorporated for the TACAN bearing computations. Observable formulations are discussed in detail along with the partial computations.

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines

PubMed Central

Wang, Shixia; Chou, Te-hui; Hackett, Anthony; Efros, Veronica; Wang, Yan; Han, Dong; Wallace, Aaron; Chen, Yuxin; Hu, Guangnan; Liu, Shuying; Clapham, Paul; Arthos, James; Montefiori, David; Lu, Shan

2017-01-01

ABSTRACT Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater than 50% of the viruses included in a high throughput PhenoSense neutralization assay when these immuongens were tested as a DNA prime followed by a fixed 5-valent gp120 protein vaccine boost. The new polyvalent formulation, using five gp120 immunogens selected from this subgroup, elicited improved quality of antibody responses in rabbits than the previous DP6-001 formulation. More significantly, this new polyvalent formulation elicited higher antibody responses against a panel of gp70V1/V2 antigens expressing V1/V2 sequences from diverse subtypes. Bioinformatics analysis supports the design of a 4-valent or 5-valent formulation using gp120 immunogens from this screening study to achieve a broad coverage against 16 HIV-1 subtypes. PMID:28933684

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.

Modeled hydraulic redistribution by Helianthus annuus L. matches observed data only after model modification to include nighttime transpiration

NASA Astrophysics Data System (ADS)

Neumann, R. B.; Cardon, Z. G.; Rockwell, F. E.; Teshera-Levye, J.; Zwieniecki, M.; Holbrook, N. M.

2013-12-01

The movement of water from moist to dry soil layers through the root systems of plants, referred to as hydraulic redistribution (HR), occurs throughout the world and is thought to influence carbon and water budgets and ecosystem functioning. The realized hydrologic, biogeochemical, and ecological consequences of HR depend on the amount of redistributed water, while the ability to assess these impacts requires models that correctly capture HR magnitude and timing. Using several soil types and two eco-types of Helianthus annuus L. in split-pot experiments, we examined how well the widely used HR modeling formulation developed by Ryel et al. (2002) could match experimental determination of HR across a range of water potential driving gradients. H. annuus carries out extensive nighttime transpiration, and though over the last decade it has become more widely recognized that nighttime transpiration occurs in multiple species and many ecosystems, the original Ryel et al. (2002) formulation does not include the effect of nighttime transpiration on HR. We developed and added a representation of nighttime transpiration into the formulation, and only then was the model able to capture the dynamics and magnitude of HR we observed as soils dried and nighttime stomatal behavior changed, both influencing HR.

User-Defined Material Model for Progressive Failure Analysis

NASA Technical Reports Server (NTRS)

Knight, Norman F. Jr.; Reeder, James R. (Technical Monitor)

2006-01-01

An overview of different types of composite material system architectures and a brief review of progressive failure material modeling methods used for structural analysis including failure initiation and material degradation are presented. Different failure initiation criteria and material degradation models are described that define progressive failure formulations. These progressive failure formulations are implemented in a user-defined material model (or UMAT) for use with the ABAQUS/Standard1 nonlinear finite element analysis tool. The failure initiation criteria include the maximum stress criteria, maximum strain criteria, the Tsai-Wu failure polynomial, and the Hashin criteria. The material degradation model is based on the ply-discounting approach where the local material constitutive coefficients are degraded. Applications and extensions of the progressive failure analysis material model address two-dimensional plate and shell finite elements and three-dimensional solid finite elements. Implementation details and use of the UMAT subroutine are described in the present paper. Parametric studies for composite structures are discussed to illustrate the features of the progressive failure modeling methods that have been implemented.

Isotretinoin Oil-Based Capsule Formulation Optimization

PubMed Central

Tsai, Pi-Ju; Huang, Chi-Te; Lee, Chen-Chou; Li, Chi-Lin; Huang, Yaw-Bin; Tsai, Yi-Hung; Wu, Pao-Chu

2013-01-01

The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X 1), hydrogenated coconut oil (X 2), and soybean oil (X 3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X 1 X 2, X 1 X 3, and X 2 X 3) showed more potential influence than that of the main factors (X 1, X 2, and X 3). An optimal predicted formulation with Y 10 min, Y 30 min, Y 60 min, and Y 90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X 1, X 2, and X 3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f 2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile. PMID:24068886

Hamiltonian formulation of systems with balanced loss-gain and exactly solvable models

NASA Astrophysics Data System (ADS)

Ghosh, Pijush K.; Sinha, Debdeep

2018-01-01

A Hamiltonian formulation of generic many-body systems with balanced loss and gain is presented. It is shown that a Hamiltonian formulation is possible only if the balancing of loss and gain terms occurs in a pairwise fashion. It is also shown that with the choice of a suitable co-ordinate, the Hamiltonian can always be reformulated in the background of a pseudo-Euclidean metric. If the equations of motion of some of the well-known many-body systems like Calogero models are generalized to include balanced loss and gain, it appears that the same may not be amenable to a Hamiltonian formulation. A few exactly solvable systems with balanced loss and gain, along with a set of integrals of motion are constructed. The examples include a coupled chain of nonlinear oscillators and a many-particle Calogero-type model with four-body inverse square plus two-body pair-wise harmonic interactions. For the case of nonlinear oscillators, stable solution exists even if the loss and gain parameter has unbounded upper range. Further, the range of the parameter for which the stable solutions are obtained is independent of the total number of the oscillators. The set of coupled nonlinear equations are solved exactly for the case when the values of all the constants of motions except the Hamiltonian are equal to zero. Exact, analytical classical solutions are presented for all the examples considered.

Lattice Boltzmann Methods to Address Fundamental Boiling and Two-Phase Problems

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

Uddin, Rizwan

2012-01-01

This report presents the progress made during the fourth (no cost extension) year of this three-year grant aimed at the development of a consistent Lattice Boltzmann formulation for boiling and two-phase flows. During the first year, a consistent LBM formulation for the simulation of a two-phase water-steam system was developed. Results of initial model validation in a range of thermo-dynamic conditions typical for Boiling Water Reactors (BWRs) were shown. Progress was made on several fronts during the second year. Most important of these included the simulation of the coalescence of two bubbles including the surface tension effects. Work during themore » third year focused on the development of a new lattice Boltzmann model, called the artificial interface lattice Boltzmann model (AILB model) for the 3 simulation of two-phase dynamics. The model is based on the principle of free energy minimization and invokes the Gibbs-Duhem equation in the formulation of non-ideal forcing function. This was reported in detail in the last progress report. Part of the efforts during the last (no-cost extension) year were focused on developing a parallel capability for the 2D as well as for the 3D codes developed in this project. This will be reported in the final report. Here we report the work carried out on testing the AILB model for conditions including the thermal effects. A simplified thermal LB model, based on the thermal energy distribution approach, was developed. The simplifications are made after neglecting the viscous heat dissipation and the work done by pressure in the original thermal energy distribution model. Details of the model are presented here, followed by a discussion of the boundary conditions, and then results for some two-phase thermal problems.« less

Modeling of intragranular misorientation and grain fragmentation in polycrystalline materials using the viscoplastic self-consistent formulation

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

Zecevic, Miroslav; Lebensohn, Ricardo A.; McCabe, Rodney J.

In this paper, the recently established methodology to use known algorithmic expressions of the second moments of the stress field in the grains of a polycrystalline aggregate for calculating average fluctuations of lattice rotation rates and the associated average intragranular misorientation distributions using the mean-field viscoplastic self-consistent (VPSC) formulation is extended to solve the coupled problem of considering the effect of intragranular misorientations on stress and rotation rate fluctuations. In turn, these coupled expressions are used to formulate and implement a grain fragmentation (GF) model in VPSC. Case studies, including tension and plane-strain compression of face-centered cubic polycrystals are usedmore » to illustrate the capabilities of the new model. GF-VPSC predictions of intragranular misorientation distributions and texture evolution are compared with experiments and full-field numerical simulations, showing good agreement. In particular, the inclusion of misorientation spreads reduced the intensity of the deformed texture and thus improved the texture predictions. Finally and moreover, considering that intragranular misorientations act as driving forces for recrystallization, the new GF-VPSC formulation is shown to enable modeling of microstructure evolution during deformation and recrystallization, in a computationally efficient manner.« less

Modeling of intragranular misorientation and grain fragmentation in polycrystalline materials using the viscoplastic self-consistent formulation

DOE PAGES

Zecevic, Miroslav; Lebensohn, Ricardo A.; McCabe, Rodney J.; ...

2018-06-15

In this paper, the recently established methodology to use known algorithmic expressions of the second moments of the stress field in the grains of a polycrystalline aggregate for calculating average fluctuations of lattice rotation rates and the associated average intragranular misorientation distributions using the mean-field viscoplastic self-consistent (VPSC) formulation is extended to solve the coupled problem of considering the effect of intragranular misorientations on stress and rotation rate fluctuations. In turn, these coupled expressions are used to formulate and implement a grain fragmentation (GF) model in VPSC. Case studies, including tension and plane-strain compression of face-centered cubic polycrystals are usedmore » to illustrate the capabilities of the new model. GF-VPSC predictions of intragranular misorientation distributions and texture evolution are compared with experiments and full-field numerical simulations, showing good agreement. In particular, the inclusion of misorientation spreads reduced the intensity of the deformed texture and thus improved the texture predictions. Finally and moreover, considering that intragranular misorientations act as driving forces for recrystallization, the new GF-VPSC formulation is shown to enable modeling of microstructure evolution during deformation and recrystallization, in a computationally efficient manner.« less

Modeling vehicle operating speed on urban roads in Montreal: a panel mixed ordered probit fractional split model.

PubMed

Eluru, Naveen; Chakour, Vincent; Chamberlain, Morgan; Miranda-Moreno, Luis F

2013-10-01

Vehicle operating speed measured on roadways is a critical component for a host of analysis in the transportation field including transportation safety, traffic flow modeling, roadway geometric design, vehicle emissions modeling, and road user route decisions. The current research effort contributes to the literature on examining vehicle speed on urban roads methodologically and substantively. In terms of methodology, we formulate a new econometric model framework for examining speed profiles. The proposed model is an ordered response formulation of a fractional split model. The ordered nature of the speed variable allows us to propose an ordered variant of the fractional split model in the literature. The proposed formulation allows us to model the proportion of vehicles traveling in each speed interval for the entire segment of roadway. We extend the model to allow the influence of exogenous variables to vary across the population. Further, we develop a panel mixed version of the fractional split model to account for the influence of site-specific unobserved effects. The paper contributes substantively by estimating the proposed model using a unique dataset from Montreal consisting of weekly speed data (collected in hourly intervals) for about 50 local roads and 70 arterial roads. We estimate separate models for local roads and arterial roads. The model estimation exercise considers a whole host of variables including geometric design attributes, roadway attributes, traffic characteristics and environmental factors. The model results highlight the role of various street characteristics including number of lanes, presence of parking, presence of sidewalks, vertical grade, and bicycle route on vehicle speed proportions. The results also highlight the presence of site-specific unobserved effects influencing the speed distribution. The parameters from the modeling exercise are validated using a hold-out sample not considered for model estimation. The results indicate that the proposed panel mixed ordered probit fractional split model offers promise for modeling such proportional ordinal variables. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cognitive-Perceptual Factors in the Political Alienation Process: A Test of Six Models.

ERIC Educational Resources Information Center

Long, Samuel

The effectiveness of sex research models which measure adolescents' feelings of political alienation is investigated and discussed and a new model is formulated. The six models include life dissatisfaction, personal depreciation, critical perceptions of political reality, irrational beliefs, perceptions of political threat, and cognitive…

Screening vaccine formulations for biological activity using fresh human whole blood

PubMed Central

Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression. PMID:24401565

Screening vaccine formulations for biological activity using fresh human whole blood.

PubMed

Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.

Pile group program for full material modeling and progressive failure.

DOT National Transportation Integrated Search

2008-12-01

Strain wedge (SW) model formulation has been used, in previous work, to evaluate the response of a single pile or a group of piles (including its : pile cap) in layered soils to lateral loading. The SW model approach provides appropriate prediction f...

A fluidized bed technique for estimating soil critical shear stress

USDA-ARS?s Scientific Manuscript database

Soil erosion models, depending on how they are formulated, always have erodibilitiy parameters in the erosion equations. For a process-based model like the Water Erosion Prediction Project (WEPP) model, the erodibility parameters include rill and interrill erodibility and critical shear stress. Thes...

Self-Identity Development Model of Oppressed People: Inclusive Model for All?

ERIC Educational Resources Information Center

Highlen, Pamela S.; And Others

The Self-Identity Development Model of Oppressed People (SIDMOP) is a synthesis of several areas of psychology, including developmental, cross cultural, and spiritual literatures. SIDMOP provides an all-inclusive model of identity development for oppressed minorities in the United States, regardless of ethnicity. The model was formulated from the…

Tracking Skill Acquisition with Cognitive Diagnosis Models: A Higher-Order, Hidden Markov Model with Covariates

ERIC Educational Resources Information Center

Wang, Shiyu; Yang, Yan; Culpepper, Steven Andrew; Douglas, Jeffrey A.

2018-01-01

A family of learning models that integrates a cognitive diagnostic model and a higher-order, hidden Markov model in one framework is proposed. This new framework includes covariates to model skill transition in the learning environment. A Bayesian formulation is adopted to estimate parameters from a learning model. The developed methods are…

Recent advances in herbal medicines treating Parkinson's disease.

PubMed

Li, Xu-Zhao; Zhang, Shuai-Nan; Liu, Shu-Min; Lu, Fang

2013-01-01

Herbal medicines have attracted considerable attention in recent years, which are used to treat Parkinson's disease (PD) in China based on traditional Chinese medicine or modern pharmacological theories. We summarized and analyzed the anti-Parkinsonian activities of herbal medicines and herbal formulations investigated in PD models and provide future references for basic and clinical investigations. All the herbal medicines and herbal formulations were tested on PD models in vitro and in vivo. The relevant compounds and herbal extracts with anti-Parkinsonian activities were included and analyzed according to their genera or pharmacological activities. A total of 38 herbal medicines and 11 herbal formulations were analyzed. The relevant compounds, herbal extracts and formulations were reported to be effective on PD models by modulating multiple key events or signaling pathways implicated in the pathogenesis of PD. The plant species of these herbal medicines belong to 24 genera and 18 families, such as Acanthopanax, Alpinia and Astragalus, etc. These herbal medicines can be an alternative and valuable source for anti-Parkinsonian drug discovery. The plant species in these genera and families may be the most promising candidates for further investigation and deserve further consideration in clinical trials. Active components in some of the herbal extracts and the compatibility law of herbal formulations remain to be further investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

A Population Pharmacokinetic Model for a Solid Oral Tablet Formulation of Posaconazole.

PubMed

van Iersel, Marlou L P S; Rossenu, Stefaan; de Greef, Rik; Waskin, Hetty

2018-04-30

A delayed-release solid tablet formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid tablet formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final pharmacokinetic model was used to simulate posaconazole exposure in patients at high risk for invasive fungal diseases treated with the proposed posaconazole dose of 300 mg twice daily on day 1, followed by 300 mg daily for 27 days. A one-compartment pharmacokinetic model with sequential zero-order and first-order absorption and a first-order disposition from the central compartment adequately described the pharmacokinetic profile of the posaconazole solid tablet formulation. Significant covariates included disease state (acute myeloid leukemia/myelodysplasia vs allogeneic hematopoietic stem cell transplantation), body weight, and formulation on bioavailability; food status on first-order absorption rate; and dosing regimen (single dose vs multiple doses) on clearance. Except for body weight, the impact of these covariates on posaconazole exposure was considered clinically irrelevant. This population pharmacokinetic analysis confirmed that the proposed dose of the posaconazole solid tablet formulation provides adequate target therapeutic exposure (>0.5 mg/l) to a broad range of patients at high risk for invasive fungal disease. Copyright © 2018 American Society for Microbiology.

A three-dimensional multiphase flow model for assesing NAPL contamination in porous and fractured media, 1. Formulation

NASA Astrophysics Data System (ADS)

Huyakorn, P. S.; Panday, S.; Wu, Y. S.

1994-06-01

A three-dimensional, three-phase numerical model is presented for stimulating the movement on non-aqueous-phase liquids (NAPL's) through porous and fractured media. The model is designed for practical application to a wide variety of contamination and remediation scenarios involving light or dense NAPL's in heterogeneous subsurface systems. The model formulation is first derived for three-phase flow of water, NAPL and air (or vapor) in porous media. The formulation is then extended to handle fractured systems using the dual-porosity and discrete-fracture modeling approaches The model accommodates a wide variety of boundary conditions, including withdrawal and injection well conditions which are treated rigorously using fully implicit schemes. The three-phase of formulation collapses to its simpler forms when air-phase dynamics are neglected, capillary effects are neglected, or two-phase-air-liquid, liquid-liquid systems with one or two active phases are considered. A Galerkin procedure with upstream weighting of fluid mobilities, storage matrix lumping, and fully implicit treatment of nonlinear coefficients and well conditions is used. A variety of nodal connectivity schemes leading to finite-difference, finite-element and hybrid spatial approximations in three dimensions are incorporated in the formulation. Selection of primary variables and evaluation of the terms of the Jacobian matrix for the Newton-Raphson linearized equations is discussed. The various nodal lattice options, and their significance to the computational time and memory requirements with regards to the block-Orthomin solution scheme are noted. Aggressive time-stepping schemes and under-relaxation formulas implemented in the code further alleviate the computational burden.

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...

Multiple commodities in statistical microeconomics: Model and market

NASA Astrophysics Data System (ADS)

Baaquie, Belal E.; Yu, Miao; Du, Xin

2016-11-01

A statistical generalization of microeconomics has been made in Baaquie (2013). In Baaquie et al. (2015), the market behavior of single commodities was analyzed and it was shown that market data provides strong support for the statistical microeconomic description of commodity prices. The case of multiple commodities is studied and a parsimonious generalization of the single commodity model is made for the multiple commodities case. Market data shows that the generalization can accurately model the simultaneous correlation functions of up to four commodities. To accurately model five or more commodities, further terms have to be included in the model. This study shows that the statistical microeconomics approach is a comprehensive and complete formulation of microeconomics, and which is independent to the mainstream formulation of microeconomics.

Recent developments in learning control and system identification for robots and structures

NASA Technical Reports Server (NTRS)

Phan, M.; Juang, J.-N.; Longman, R. W.

1990-01-01

This paper reviews recent results in learning control and learning system identification, with particular emphasis on discrete-time formulation, and their relation to adaptive theory. Related continuous-time results are also discussed. Among the topics presented are proportional, derivative, and integral learning controllers, time-domain formulation of discrete learning algorithms. Newly developed techniques are described including the concept of the repetition domain, and the repetition domain formulation of learning control by linear feedback, model reference learning control, indirect learning control with parameter estimation, as well as related basic concepts, recursive and non-recursive methods for learning identification.

Application of protease technology in dermatology: rationale for incorporation into skin care with initial observations on formulations designed for skin cleansing, maintenance of hydration, and restoration of the epidermal permeability barrier.

PubMed

Del Rosso, James Q

2013-06-01

This article reviews background on proteases and their functions, their physiological significance in skin, and the potential implications of incorporating specific proteases and protease blends into dermatological products, including skin care formulations. The history of protease blend formulations used in wound model studies and for other disorders is reviewed. In vitro data with use of a specific 3-protease blend with evaluation of the impact on various skin proteins and peptides is also discussed in this article.

Modelled hydraulic redistribution by sunflower (Helianthus annuus L.) matches observed data only after including night-time transpiration.

PubMed

Neumann, Rebecca B; Cardon, Zoe G; Teshera-Levye, Jennifer; Rockwell, Fulton E; Zwieniecki, Maciej A; Holbrook, N Michele

2014-04-01

The movement of water from moist to dry soil layers through the root systems of plants, referred to as hydraulic redistribution (HR), occurs throughout the world and is thought to influence carbon and water budgets and ecosystem functioning. The realized hydrologic, biogeochemical and ecological consequences of HR depend on the amount of redistributed water, whereas the ability to assess these impacts requires models that correctly capture HR magnitude and timing. Using several soil types and two ecotypes of sunflower (Helianthus annuus L.) in split-pot experiments, we examined how well the widely used HR modelling formulation developed by Ryel et al. matched experimental determination of HR across a range of water potential driving gradients. H. annuus carries out extensive night-time transpiration, and although over the last decade it has become more widely recognized that night-time transpiration occurs in multiple species and many ecosystems, the original Ryel et al. formulation does not include the effect of night-time transpiration on HR. We developed and added a representation of night-time transpiration into the formulation, and only then was the model able to capture the dynamics and magnitude of HR we observed as soils dried and night-time stomatal behaviour changed, both influencing HR. © 2013 John Wiley & Sons Ltd.

A defect stream function, law of the wall/wake method for compressible turbulent boundary layers

NASA Technical Reports Server (NTRS)

Barnwell, Richard W.; Dejarnette, Fred R.; Wahls, Richard A.

1989-01-01

The application of the defect stream function to the solution of the two-dimensional, compressible boundary layer is examined. A law of the wall/law of the wake formulation for the inner part of the boundary layer is presented which greatly simplifies the computational task near the wall and eliminates the need for an eddy viscosity model in this region. The eddy viscosity model in the outer region is arbitrary. The modified Crocco temperature-velocity relationship is used as a simplification of the differential energy equation. Formulations for both equilibrium and nonequilibrium boundary layers are presented including a constrained zero-order form which significantly reduces the computational workload while retaining the significant physics of the flow. A formulation for primitive variables is also presented. Results are given for the constrained zero-order and second-order equilibrium formulations and are compared with experimental data. A compressible wake function valid near the wall has been developed from the present results.

Cournot games with network effects for electric power markets

NASA Astrophysics Data System (ADS)

Spezia, Carl John

The electric utility industry is moving from regulated monopolies with protected service areas to an open market with many wholesale suppliers competing for consumer load. This market is typically modeled by a Cournot game oligopoly where suppliers compete by selecting profit maximizing quantities. The classical Cournot model can produce multiple solutions when the problem includes typical power system constraints. This work presents a mathematical programming formulation of oligopoly that produces unique solutions when constraints limit the supplier outputs. The formulation casts the game as a supply maximization problem with power system physical limits and supplier incremental profit functions as constraints. The formulation gives Cournot solutions identical to other commonly used algorithms when suppliers operate within the constraints. Numerical examples demonstrate the feasibility of the theory. The results show that the maximization formulation will give system operators more transmission capacity when compared to the actions of suppliers in a classical constrained Cournot game. The results also show that the profitability of suppliers in constrained networks depends on their location relative to the consumers' load concentration.

Hamiltonian closures in fluid models for plasmas

NASA Astrophysics Data System (ADS)

Tassi, Emanuele

2017-11-01

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

The Effect of Math Modeling on Student's Emerging Understanding

ERIC Educational Resources Information Center

Sokolowski, Andrzej

2015-01-01

This study investigated the effects of applying mathematical modeling on revising students' preconception of the process of optimizing area enclosed by a string of a fixed length. A group of 28 high school pre-calculus students were immersed in modeling activity that included direct measurements, data collecting, and formulating algebraic…

Assumptions to the Annual Energy Outlook

EIA Publications

2017-01-01

This report presents the major assumptions of the National Energy Modeling System (NEMS) used to generate the projections in the Annual Energy Outlook, including general features of the model structure, assumptions concerning energy markets, and the key input data and parameters that are the most significant in formulating the model results.

Time domain contact model for tyre/road interaction including nonlinear contact stiffness due to small-scale roughness

NASA Astrophysics Data System (ADS)

Andersson, P. B. U.; Kropp, W.

2008-11-01

Rolling resistance, traction, wear, excitation of vibrations, and noise generation are all attributes to consider in optimisation of the interaction between automotive tyres and wearing courses of roads. The key to understand and describe the interaction is to include a wide range of length scales in the description of the contact geometry. This means including scales on the order of micrometres that have been neglected in previous tyre/road interaction models. A time domain contact model for the tyre/road interaction that includes interfacial details is presented. The contact geometry is discretised into multiple elements forming pairs of matching points. The dynamic response of the tyre is calculated by convolving the contact forces with pre-calculated Green's functions. The smaller-length scales are included by using constitutive interfacial relations, i.e. by using nonlinear contact springs, for each pair of contact elements. The method is presented for normal (out-of-plane) contact and a method for assessing the stiffness of the nonlinear springs based on detailed geometry and elastic data of the tread is suggested. The governing equations of the nonlinear contact problem are solved with the Newton-Raphson iterative scheme. Relations between force, indentation, and contact stiffness are calculated for a single tread block in contact with a road surface. The calculated results have the same character as results from measurements found in literature. Comparison to traditional contact formulations shows that the effect of the small-scale roughness is large; the contact stiffness is only up to half of the stiffness that would result if contact is made over the whole element directly to the bulk of the tread. It is concluded that the suggested contact formulation is a suitable model to include more details of the contact interface. Further, the presented result for the tread block in contact with the road is a suitable input for a global tyre/road interaction model that is also based on the presented contact formulation.

A Novel Centrality Measure for Network-wide Cyber Vulnerability Assessment

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

Sathanur, Arun V.; Haglin, David J.

In this work we propose a novel formulation that models the attack and compromise on a cyber network as a combination of two parts - direct compromise of a host and the compromise occurring through the spread of the attack on the network from a compromised host. The model parameters for the nodes are a concise representation of the host profiles that can include the risky behaviors of the associated human users while the model parameters for the edges are based on the existence of vulnerabilities between each pair of connected hosts. The edge models relate to the summary representationsmore » of the corresponding attack-graphs. This results in a formulation based on Random Walk with Restart (RWR) and the resulting centrality metric can be solved for in an efficient manner through the use of sparse linear solvers. Thus the formulation goes beyond mere topological considerations in centrality computations by summarizing the host profiles and the attack graphs into the model parameters. The computational efficiency of the method also allows us to also quantify the uncertainty in the centrality measure through Monte Carlo analysis.« less

Anti Inflammatory and Anti Arthritic Activity of Different Milk Based Formulation of Curcumin in Rat Model.

PubMed

Sumeet, Gupta; Rachna, Kumria; Samrat, Chauhan; Ipshita, Chattopadhyaya; Vikas, Jhawat; Manu, Sharma

2018-02-14

Inflammation is the key mediator for arthritis. Plant based products are most useful for treating various disorders, but at the same time drug absorption is utmost important for effective therapy. The present aim of our study was to find out the therapeutic concern in pharmacokinetic and pharmacodynamic parameters in an arthritis induced rat model. Carregenan and complete Freud's adjuvant, both were used for an arthritis induction as an animal model. Formulation of curcumin was prepared in different quality of milk brand, high fat milk with ghee and in an aqueous suspension. They were administered orally to the rats for 21 days continuously. Different pharmacodyanmic parameters were analyzed which include percentage inhibition of inflammation, cytokines (IL-6 and TNF-α), hematological levels, X-Rays and histology condition. Pharmacokinetics was also determined like Cmax, Tmax and Kel using HPLC method. The result concludes that, curcumin in full fat milk with ghee and full fat curcumin formulation treated group showed a higher statistical significant effect in the prevention of inflammation in both the models. The presence of curcumin in plasma was higher only in full fat with ghee formulation and full fat milk formulation treated group when compared to the other groups. Hence, it concludes that the presence of adjuvant act as an enhancer can increase the bioavailability of curcumin for achieving maximum effectiveness. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Application of Artificial Neural Networks in the Design and Optimization of a Nanoparticulate Fingolimod Delivery System Based on Biodegradable Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate).

PubMed

Shahsavari, Shadab; Rezaie Shirmard, Leila; Amini, Mohsen; Abedin Dokoosh, Farid

2017-01-01

Formulation of a nanoparticulate Fingolimod delivery system based on biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) was optimized according to artificial neural networks (ANNs). Concentration of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PVA and amount of Fingolimod is considered as the input value, and the particle size, polydispersity index, loading capacity, and entrapment efficacy as output data in experimental design study. In vitro release study was carried out for best formulation according to statistical analysis. ANNs are employed to generate the best model to determine the relationships between various values. In order to specify the model with the best accuracy and proficiency for the in vitro release, a multilayer percepteron with different training algorithm has been examined. Three training model formulations including Levenberg-Marquardt (LM), gradient descent, and Bayesian regularization were employed for training the ANN models. It is demonstrated that the predictive ability of each training algorithm is in the order of LM > gradient descent > Bayesian regularization. Also, optimum formulation was achieved by LM training function with 15 hidden layers and 20 neurons. The transfer function of the hidden layer for this formulation and the output layer were tansig and purlin, respectively. Also, the optimization process was developed by minimizing the error among the predicted and observed values of training algorithm (about 0.0341). Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Numerical simulation of large-scale bed load particle tracer advection-dispersion in rivers with free bars

USGS Publications Warehouse

Iwasaki, Toshiki; Nelson, Jonathan M.; Shimizu, Yasuyuki; Parker, Gary

2017-01-01

Asymptotic characteristics of the transport of bed load tracer particles in rivers have been described by advection-dispersion equations. Here we perform numerical simulations designed to study the role of free bars, and more specifically single-row alternate bars, on streamwise tracer particle dispersion. In treating the conservation of tracer particle mass, we use two alternative formulations for the Exner equation of sediment mass conservation: the flux-based formulation, in which bed elevation varies with the divergence of the bed load transport rate, and the entrainment-based formulation, in which bed elevation changes with the net deposition rate. Under the condition of no net bed aggradation/degradation, a 1-D flux-based deterministic model that does not describe free bars yields no streamwise dispersion. The entrainment-based 1-D formulation, on the other hand, models stochasticity via the probability density function (PDF) of particle step length, and as a result does show tracer dispersion. When the formulation is generalized to 2-D to include free alternate bars, however, both models yield almost identical asymptotic advection-dispersion characteristics, in which streamwise dispersion is dominated by randomness inherent in free bar morphodynamics. This randomness can result in a heavy-tailed PDF of waiting time. In addition, migrating bars may constrain the travel distance through temporary burial, causing a thin-tailed PDF of travel distance. The superdiffusive character of streamwise particle dispersion predicted by the model is attributable to the interaction of these two effects.

Numerical simulation of large-scale bed load particle tracer advection-dispersion in rivers with free bars

NASA Astrophysics Data System (ADS)

Iwasaki, Toshiki; Nelson, Jonathan; Shimizu, Yasuyuki; Parker, Gary

2017-04-01

Asymptotic characteristics of the transport of bed load tracer particles in rivers have been described by advection-dispersion equations. Here we perform numerical simulations designed to study the role of free bars, and more specifically single-row alternate bars, on streamwise tracer particle dispersion. In treating the conservation of tracer particle mass, we use two alternative formulations for the Exner equation of sediment mass conservation: the flux-based formulation, in which bed elevation varies with the divergence of the bed load transport rate, and the entrainment-based formulation, in which bed elevation changes with the net deposition rate. Under the condition of no net bed aggradation/degradation, a 1-D flux-based deterministic model that does not describe free bars yields no streamwise dispersion. The entrainment-based 1-D formulation, on the other hand, models stochasticity via the probability density function (PDF) of particle step length, and as a result does show tracer dispersion. When the formulation is generalized to 2-D to include free alternate bars, however, both models yield almost identical asymptotic advection-dispersion characteristics, in which streamwise dispersion is dominated by randomness inherent in free bar morphodynamics. This randomness can result in a heavy-tailed PDF of waiting time. In addition, migrating bars may constrain the travel distance through temporary burial, causing a thin-tailed PDF of travel distance. The superdiffusive character of streamwise particle dispersion predicted by the model is attributable to the interaction of these two effects.

Dimensional analysis of MINMOD leads to definition of the disposition index of glucose regulation and improved simulation algorithm.

PubMed

Nittala, Aparna; Ghosh, Soumitra; Stefanovski, Darko; Bergman, Richard; Wang, Xujing

2006-07-14

Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) together with its mathematical model, the minimal model (MINMOD), have become important clinical tools to evaluate the metabolic control of glucose in humans. Dimensional analysis of the model is up to now not available. A formal dimensional analysis of MINMOD was carried out and the degree of freedom of MINMOD was examined. Through re-expressing all state variable and parameters in terms of their reference scales, MINMOD was transformed into a dimensionless format. Previously defined physiological indices including insulin sensitivity, glucose effectiveness, and first and second phase insulin responses were re-examined in this new formulation. Further, the parameter estimation from FSIVGTT was implemented using both the dimensional and the dimensionless formulations of MINMOD, and the performances were compared utilizing Monte Carlo simulation as well as real human FSIVGTT data. The degree of freedom (DOF) of MINMOD was found to be 7. The model was maximally simplified in the dimensionless formulation that normalizes the variation in glucose and insulin during FSIVGTT. In the new formulation, the disposition index (Dl), a composite parameter known to be important in diabetes pathology, was naturally defined as one of the dimensionless parameters in the system. The numerical simulation using the dimensionless formulation led to a 1.5-5 fold gain in speed, and significantly improved accuracy and robustness in parameter estimation compared to the dimensional implementation. Dimensional analysis of MINMOD led to simplification of the model, direct identification of the important composite factors in the dynamics of glucose metabolic control, and better simulations algorithms.

An Advanced One-Dimensional Finite Element Model for Incompressible Thermally Expandable Flow

DOE PAGES

Hu, Rui

2017-03-27

Here, this paper provides an overview of a new one-dimensional finite element flow model for incompressible but thermally expandable flow. The flow model was developed for use in system analysis tools for whole-plant safety analysis of sodium fast reactors. Although the pressure-based formulation was implemented, the use of integral equations in the conservative form ensured the conservation laws of the fluid. A stabilization scheme based on streamline-upwind/Petrov-Galerkin and pressure-stabilizing/Petrov-Galerkin formulations is also introduced. The flow model and its implementation have been verified by many test problems, including density wave propagation, steep gradient problems, discharging between tanks, and the conjugate heatmore » transfer in a heat exchanger.« less

An Advanced One-Dimensional Finite Element Model for Incompressible Thermally Expandable Flow

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

Hu, Rui

Here, this paper provides an overview of a new one-dimensional finite element flow model for incompressible but thermally expandable flow. The flow model was developed for use in system analysis tools for whole-plant safety analysis of sodium fast reactors. Although the pressure-based formulation was implemented, the use of integral equations in the conservative form ensured the conservation laws of the fluid. A stabilization scheme based on streamline-upwind/Petrov-Galerkin and pressure-stabilizing/Petrov-Galerkin formulations is also introduced. The flow model and its implementation have been verified by many test problems, including density wave propagation, steep gradient problems, discharging between tanks, and the conjugate heatmore » transfer in a heat exchanger.« less

Program Evaluation: An Overview.

ERIC Educational Resources Information Center

McCluskey, Lawrence

1973-01-01

Various models of educational evaluation are presented. These include: (1) the classical type model, which contains the following guidelines: formulate objectives, classify objectives, define objectives in behavioral terms, suggest situations in which achievement of objectives will be shown, develop or select appraisal techniques, and gather and…

An Etiological Approach to Sexual Offender Assessment: CAse Formulation Incorporating Risk Assessment (CAFIRA).

PubMed

Craig, Leam A; Rettenberger, Martin

2018-05-19

Case formulations (CF) have been the cornerstone of effective practice in clinical psychology since the 1950s and now form one of the core competencies in clinical and forensic assessment. The use of CFs within forensic settings is becoming more relevant when working with offenders who have experienced significant trauma, suffered from personality disorder, and have displayed sexually abusive behavior. Furthermore, most North American and European jurisdictions insist that expert witnesses adopt an idiosyncratic approach to risk assessment and consider the characteristics of the individual as part of a wider formulation of the problem behavior. This article focuses specifically on CF incorporating risk assessment procedures of sexual offenders. While empirical support for the use of risk analysis and formulation in managing offending behavior generally, and sexual offending behavior in particular, is limited, there is mounting evidence to suggest that CF can improve understanding of an individual's problem sexual behaviors. We argue that by integrating risk formulations into the CF provides a conceptually robust link between the etiologically development of the problem sexual behavior and effective assessment and risk management of sexual offenders. As forensic treatment programs increasingly moved toward strength-based approaches, in keeping with the Risk-Need-Responsivity principles Andrews and Bonta (2004), and the Good Lives Model Ward and Stewart (Prof Psychol Res Pract 34:353-60, 2003) of offender rehabilitation, the use of CFs in the assessment, treatment, and management of sexual offenders is indispensable. We present an etiological framework for understanding risk in an individual sexual offender by integrating a case formulation model to include the use of (static, stable, and acute) actuarial and clinical risk assessment measures as well as protective risk factors, referred to as the CAse Formulation Incorporating Risk Assessment (CAFIRA) model.

Low Mach number fluctuating hydrodynamics for electrolytes

NASA Astrophysics Data System (ADS)

Péraud, Jean-Philippe; Nonaka, Andy; Chaudhri, Anuj; Bell, John B.; Donev, Aleksandar; Garcia, Alejandro L.

2016-11-01

We formulate and study computationally the low Mach number fluctuating hydrodynamic equations for electrolyte solutions. We are interested in studying transport in mixtures of charged species at the mesoscale, down to scales below the Debye length, where thermal fluctuations have a significant impact on the dynamics. Continuing our previous work on fluctuating hydrodynamics of multicomponent mixtures of incompressible isothermal miscible liquids [A. Donev et al., Phys. Fluids 27, 037103 (2015), 10.1063/1.4913571], we now include the effect of charged species using a quasielectrostatic approximation. Localized charges create an electric field, which in turn provides additional forcing in the mass and momentum equations. Our low Mach number formulation eliminates sound waves from the fully compressible formulation and leads to a more computationally efficient quasi-incompressible formulation. We demonstrate our ability to model saltwater (NaCl) solutions in both equilibrium and nonequilibrium settings. We show that our algorithm is second order in the deterministic setting and for length scales much greater than the Debye length gives results consistent with an electroneutral approximation. In the stochastic setting, our model captures the predicted dynamics of equilibrium and nonequilibrium fluctuations. We also identify and model an instability that appears when diffusive mixing occurs in the presence of an applied electric field.

A Streamline-Upwind Petrov-Galerkin Finite Element Scheme for Non-Ionized Hypersonic Flows in Thermochemical Nonequilibrium

NASA Technical Reports Server (NTRS)

Kirk, Benjamin S.; Bova, Stephen W.; Bond, Ryan B.

2011-01-01

Presentation topics include background and motivation; physical modeling including governing equations and thermochemistry; finite element formulation; results of inviscid thermal nonequilibrium chemically reacting flow and viscous thermal equilibrium chemical reacting flow; and near-term effort.

Development of a Rubber-Based Product Using a Mixture Experiment: A Challenging Case Study

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

Kaya, Yahya; Piepel, Gregory F.; Caniyilmaz, Erdal

2013-07-01

Many products used in daily life are made by blending two or more components. The properties of such products typically depend on the relative proportions of the components. Experimental design, modeling, and data analysis methods for mixture experiments provide for efficiently determining the component proportions that will yield a product with desired properties. This article presents a case study of the work performed to develop a new rubber formulation for an o-ring (a circular gasket) with requirements specified on 10 product properties. Each step of the study is discussed, including: 1) identifying the objective of the study and requirements formore » properties of the o-ring, 2) selecting the components to vary and specifying the component constraints, 3) constructing a mixture experiment design, 4) measuring the responses and assessing the data, 5) developing property-composition models, 6) selecting the new product formulation, and 7) confirming the selected formulation in manufacturing. The case study includes some challenging and new aspects, which are discussed in the article.« less

Heat and mass transfer in combustion - Fundamental concepts and analytical techniques

NASA Technical Reports Server (NTRS)

Law, C. K.

1984-01-01

Fundamental combustion phenomena and the associated flame structures in laminar gaseous flows are discussed on physical bases within the framework of the three nondimensional parameters of interest to heat and mass transfer in chemically-reacting flows, namely the Damkoehler number, the Lewis number, and the Arrhenius number which is the ratio of the reaction activation energy to the characteristic thermal energy. The model problems selected for illustration are droplet combustion, boundary layer combustion, and the propagation, flammability, and stability of premixed flames. Fundamental concepts discussed include the flame structures for large activation energy reactions, S-curve interpretation of the ignition and extinctin states, reaction-induced local-similarity and non-similarity in boundary layer flows, the origin and removal of the cold boundary difficulty in modeling flame propagation, and effects of flame stretch and preferential diffusion on flame extinction and stability. Analytical techniques introduced include the Shvab-Zeldovich formulation, the local Shvab-Zeldovich formulation, flame-sheet approximation and the associated jump formulation, and large activation energy matched asymptotic analysis. Potentially promising research areas are suggested.

Two tradeoffs between economy and reliability in loss of load probability constrained unit commitment

NASA Astrophysics Data System (ADS)

Liu, Yuan; Wang, Mingqiang; Ning, Xingyao

2018-02-01

Spinning reserve (SR) should be scheduled considering the balance between economy and reliability. To address the computational intractability cursed by the computation of loss of load probability (LOLP), many probabilistic methods use simplified formulations of LOLP to improve the computational efficiency. Two tradeoffs embedded in the SR optimization model are not explicitly analyzed in these methods. In this paper, two tradeoffs including primary tradeoff and secondary tradeoff between economy and reliability in the maximum LOLP constrained unit commitment (UC) model are explored and analyzed in a small system and in IEEE-RTS System. The analysis on the two tradeoffs can help in establishing new efficient simplified LOLP formulations and new SR optimization models.

Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

PubMed Central

Hayashi, Tomoko; Crain, Brian; Corr, Maripat; Chan, Michael; Cottam, Howard B; Maj, Roberto; Barberis, Alcide; Leoni, Lorenzo; Carson, Dennis A

2013-01-01

Objective To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Methods Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD). Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Results Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC. Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. Conclusion The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects. PMID:20337728

Sound scattering by several zooplankton groups. II. Scattering models.

PubMed

Stanton, T K; Chu, D; Wiebe, P H

1998-01-01

Mathematical scattering models are derived and compared with data from zooplankton from several gross anatomical groups--fluidlike, elastic shelled, and gas bearing. The models are based upon the acoustically inferred boundary conditions determined from laboratory backscattering data presented in part I of this series [Stanton et al., J. Acoust. Soc. Am. 103, 225-235 (1998)]. The models use a combination of ray theory, modal-series solution, and distorted wave Born approximation (DWBA). The formulations, which are inherently approximate, are designed to include only the dominant scattering mechanisms as determined from the experiments. The models for the fluidlike animals (euphausiids in this case) ranged from the simplest case involving two rays, which could qualitatively describe the structure of target strength versus frequency for single pings, to the most complex case involving a rough inhomogeneous asymmetrically tapered bent cylinder using the DWBA-based formulation which could predict echo levels over all angles of incidence (including the difficult region of end-on incidence). The model for the elastic shelled body (gastropods in this case) involved development of an analytical model which takes into account irregularities and discontinuities of the shell. The model for gas-bearing animals (siphonophores) is a hybrid model which is composed of the summation of the exact solution to the gas sphere and the approximate DWBA-based formulation for arbitrarily shaped fluidlike bodies. There is also a simplified ray-based model for the siphonophore. The models are applied to data involving single pings, ping-to-ping variability, and echoes averaged over many pings. There is reasonable qualitative agreement between the predictions and single ping data, and reasonable quantitative agreement between the predictions and variability and averages of echo data.

Significance of Bioturbated Layer (BTL) and Deep Groundwater Storage on Runoff in Steep Saprolitic Tropical Lowlands Catchment

NASA Astrophysics Data System (ADS)

Cheng, Y.; Ogden, F. L.; Zhu, J.

2016-12-01

Bioturbated soil layers (BTLs) play a significant role in hydrological response and provisioning of ecosystem services in steep, saprolitic, tropical lowlands catchments. In this study, a new physically-based model formulation was developed for testing of runoff generation hypotheses. A main feature in the model formulation is explicit simulation of hydrological processes in the BTL including macropores, which our field observations show are ubiquitous, and deep groundwater stores that provide streamflow during the dry season The numerical model developed includes two main flow paths in the BTL, including one-dimensional (1D) vertical infiltration and two-dimensional (2D) lateral flows in both macropores and the soil matrix. Hydrological processes incorporated along with the BTL processes include intercepted rainfall, evapotranspiration, 2D surface flow and 1D deep groundwater discharge. This model was first tested in a 6.5 ha secondary succession catchment, that is under study by the Smithsonian Tropical Research Institute, Agua Salud project in Panama, which is dominated by steep slopes. With the incorporation of lateral macropore flow mechanism in the BTL, the model performs better than only including soil matrix flow in the BTL especially in simulating baseflow dynamics, which illustrates the importance of preferential flow from the BTL to stream discharge dynamics. The increase in the BTL thickness promotes more flow through the BTL and increases storage in both the BTL and the deep groundwater reservoir, but decreases the total streamflow and overland flow. Lateral macropore diameter distribution influences flows more than the macropore number or distribution type. The model has thus far passed falsification tests during the early wet season. Complexity in subsurface storage and base flow generation offer a new challenge for this model. The overall objective is to develop a model formulation that is useful in practical applications related to land-use management, provisioning of ecosystem services, and water security in similar tropical settings with distinct dry and wet seasons or in the humid tropics during periods of drought.

Mesoscale Modeling, Forecasting and Remote Sensing Research.

DTIC Science & Technology

remote sensing , cyclonic scale diagnostic studies and mesoscale numerical modeling and forecasting are summarized. Mechanisms involved in the release of potential instability are discussed and simulated quantitatively, giving particular attention to the convective formulation. The basic mesoscale model is documented including the equations, boundary condition, finite differences and initialization through an idealized frontal zone. Results of tests including a three dimensional test with real data, tests of convective/mesoscale interaction and tests with a detailed

A Process Model of Principal Selection.

ERIC Educational Resources Information Center

Flanigan, J. L.; And Others

A process model to assist school district superintendents in the selection of principals is presented in this paper. Components of the process are described, which include developing an action plan, formulating an explicit job description, advertising, assessing candidates' philosophy, conducting interview analyses, evaluating response to stress,…

Models and techniques for evaluating the effectiveness of aircraft computing systems

NASA Technical Reports Server (NTRS)

Meyer, J. F.

1978-01-01

Progress in the development of system models and techniques for the formulation and evaluation of aircraft computer system effectiveness is reported. Topics covered include: analysis of functional dependence: a prototype software package, METAPHOR, developed to aid the evaluation of performability; and a comprehensive performability modeling and evaluation exercise involving the SIFT computer.

Numerical Simulation of Bow Waves and Transom-Stern Flows

NASA Astrophysics Data System (ADS)

Dommermuth, Douglas G.; Schlageter, Eric A.; Talcott, John C.; Wyatt, Donald C.; Novikov, Evgeny A.

1997-11-01

A stratified-flow formulation is used to model the breaking bow wave and the separated transom-stern flow that are generated by a ship moving with forward speed. The interface of the air with the water is identified as the zero level-set of a three-dimensional function. The ship is modeled using a body-force technique on a cartesian grid. The three-dimensional body-force is generated using a surface panelization of the entire ship, including the above-water geometry up to and including the deck. The effects of surface tension are modeled as a source term that is concentrated at the air-water interface. The effects of gravity are modeled as a volumetric force. The three-dimensional, unsteady, Navier-Stokes equations are expressed in primitive-variable form. A LES formulation with a Smagorinsky sub-grid-scale model is used to model turbulence. Numerical convergence is demonstrated using 128x64x65, 256x128x129, and 512x256x257 grid points. The numerical results compare well to whisker-probe measurements of the free-surface elevation generated by a naval combatant.

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.

Rethinking the logistic approach for population dynamics of mutualistic interactions.

PubMed

García-Algarra, Javier; Galeano, Javier; Pastor, Juan Manuel; Iriondo, José María; Ramasco, José J

2014-12-21

Mutualistic communities have an internal structure that makes them resilient to external perturbations. Late research has focused on their stability and the topology of the relations between the different organisms to explain the reasons of the system robustness. Much less attention has been invested in analyzing the systems dynamics. The main population models in use are modifications of the r-K formulation of logistic equation with additional terms to account for the benefits produced by the interspecific interactions. These models have shortcomings as the so-called r-K formulation diverges under some conditions. In this work, we introduce a model for population dynamics under mutualism that preserves the original logistic formulation. It is mathematically simpler than the widely used type II models, although it shows similar complexity in terms of fixed points and stability of the dynamics. We perform an analytical stability analysis and numerical simulations to study the model behavior in general interaction scenarios including tests of the resilience of its dynamics under external perturbations. Despite its simplicity, our results indicate that the model dynamics shows an important richness that can be used to gain further insights in the dynamics of mutualistic communities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stochastic Modeling of Airlines' Scheduled Services Revenue

NASA Technical Reports Server (NTRS)

Hamed, M. M.

1999-01-01

Airlines' revenue generated from scheduled services account for the major share in the total revenue. As such, predicting airlines' total scheduled services revenue is of great importance both to the governments (in case of national airlines) and private airlines. This importance stems from the need to formulate future airline strategic management policies, determine government subsidy levels, and formulate governmental air transportation policies. The prediction of the airlines' total scheduled services revenue is dealt with in this paper. Four key components of airline's scheduled services are considered. These include revenues generated from passenger, cargo, mail, and excess baggage. By addressing the revenue generated from each schedule service separately, air transportation planners and designers arc able to enhance their ability to formulate specific strategies for each component. Estimation results clearly indicate that the four stochastic processes (scheduled services components) are represented by different Box-Jenkins ARIMA models. The results demonstrate the appropriateness of the developed models and their ability to provide air transportation planners with future information vital to the planning and design processes.

Stochastic Modeling of Airlines' Scheduled Services Revenue

NASA Technical Reports Server (NTRS)

Hamed, M. M.

1999-01-01

Airlines' revenue generated from scheduled services account for the major share in the total revenue. As such, predicting airlines' total scheduled services revenue is of great importance both to the governments (in case of national airlines) and private airlines. This importance stems from the need to formulate future airline strategic management policies, determine government subsidy levels, and formulate governmental air transportation policies. The prediction of the airlines' total scheduled services revenue is dealt with in this paper. Four key components of airline's scheduled services are considered. These include revenues generated from passenger, cargo, mail, and excess baggage. By addressing the revenue generated from each schedule service separately, air transportation planners and designers are able to enhance their ability to formulate specific strategies for each component. Estimation results clearly indicate that the four stochastic processes (scheduled services components) are represented by different Box-Jenkins ARIMA models. The results demonstrate the appropriateness of the developed models and their ability to provide air transportation planners with future information vital to the planning and design processes.

Including fluid shear viscosity in a structural acoustic finite element model using a scalar fluid representation

PubMed Central

Cheng, Lei; Li, Yizeng; Grosh, Karl

2013-01-01

An approximate boundary condition is developed in this paper to model fluid shear viscosity at boundaries of coupled fluid-structure system. The effect of shear viscosity is approximated by a correction term to the inviscid boundary condition, written in terms of second order in-plane derivatives of pressure. Both thin and thick viscous boundary layer approximations are formulated; the latter subsumes the former. These approximations are used to develop a variational formation, upon which a viscous finite element method (FEM) model is based, requiring only minor modifications to the boundary integral contributions of an existing inviscid FEM model. Since this FEM formulation has only one degree of freedom for pressure, it holds a great computational advantage over the conventional viscous FEM formulation which requires discretization of the full set of linearized Navier-Stokes equations. The results from thick viscous boundary layer approximation are found to be in good agreement with the prediction from a Navier-Stokes model. When applicable, thin viscous boundary layer approximation also gives accurate results with computational simplicity compared to the thick boundary layer formulation. Direct comparison of simulation results using the boundary layer approximations and a full, linearized Navier-Stokes model are made and used to evaluate the accuracy of the approximate technique. Guidelines are given for the parameter ranges over which the accurate application of the thick and thin boundary approximations can be used for a fluid-structure interaction problem. PMID:23729844

A generalized multi-dimensional mathematical model for charging and discharging processes in a supercapacitor

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

Allu, Srikanth; Velamur Asokan, Badri; Shelton, William A

A generalized three dimensional computational model based on unied formulation of electrode- electrolyte-electrode system of a electric double layer supercapacitor has been developed. The model accounts for charge transport across the solid-liquid system. This formulation based on volume averaging process is a widely used concept for the multiphase ow equations ([28] [36]) and is analogous to porous media theory typically employed for electrochemical systems [22] [39] [12]. This formulation is extended to the electrochemical equations for a supercapacitor in a consistent fashion, which allows for a single-domain approach with no need for explicit interfacial boundary conditions as previously employed ([38]).more » In this model it is easy to introduce the spatio-temporal variations, anisotropies of physical properties and it is also conducive for introducing any upscaled parameters from lower length{scale simulations and experiments. Due to the irregular geometric congurations including porous electrode, the charge transport and subsequent performance characteristics of the super-capacitor can be easily captured in higher dimensions. A generalized model of this nature also provides insight into the applicability of 1D models ([38]) and where multidimensional eects need to be considered. In addition, simple sensitivity analysis on key input parameters is performed in order to ascertain the dependence of the charge and discharge processes on these parameters. Finally, we demonstarted how this new formulation can be applied to non-planar supercapacitors« less

Including fluid shear viscosity in a structural acoustic finite element model using a scalar fluid representation.

PubMed

Cheng, Lei; Li, Yizeng; Grosh, Karl

2013-08-15

An approximate boundary condition is developed in this paper to model fluid shear viscosity at boundaries of coupled fluid-structure system. The effect of shear viscosity is approximated by a correction term to the inviscid boundary condition, written in terms of second order in-plane derivatives of pressure. Both thin and thick viscous boundary layer approximations are formulated; the latter subsumes the former. These approximations are used to develop a variational formation, upon which a viscous finite element method (FEM) model is based, requiring only minor modifications to the boundary integral contributions of an existing inviscid FEM model. Since this FEM formulation has only one degree of freedom for pressure, it holds a great computational advantage over the conventional viscous FEM formulation which requires discretization of the full set of linearized Navier-Stokes equations. The results from thick viscous boundary layer approximation are found to be in good agreement with the prediction from a Navier-Stokes model. When applicable, thin viscous boundary layer approximation also gives accurate results with computational simplicity compared to the thick boundary layer formulation. Direct comparison of simulation results using the boundary layer approximations and a full, linearized Navier-Stokes model are made and used to evaluate the accuracy of the approximate technique. Guidelines are given for the parameter ranges over which the accurate application of the thick and thin boundary approximations can be used for a fluid-structure interaction problem.

Rival approaches to mathematical modelling in immunology

NASA Astrophysics Data System (ADS)

Andrew, Sarah M.; Baker, Christopher T. H.; Bocharov, Gennady A.

2007-08-01

In order to formulate quantitatively correct mathematical models of the immune system, one requires an understanding of immune processes and familiarity with a range of mathematical techniques. Selection of an appropriate model requires a number of decisions to be made, including a choice of the modelling objectives, strategies and techniques and the types of model considered as candidate models. The authors adopt a multidisciplinary perspective.

PKPD model of interleukin-21 effects on thermoregulation in monkeys--application and evaluation of stochastic differential equations.

PubMed

Overgaard, Rune Viig; Holford, Nick; Rytved, Klaus A; Madsen, Henrik

2007-02-01

To describe the pharmacodynamic effects of recombinant human interleukin-21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms of heat regulation. A major effort was devoted to compare the use of ordinary differential equations (ODEs) with stochastic differential equations (SDEs) in pharmacokinetic pharmacodynamic (PKPD) modelling. A temperature model was formulated including circadian rhythm, metabolism, heat loss, and a thermoregulatory set-point. This model was formulated as a mixed-effects model based on SDEs using NONMEM. The effects of IL-21 were on the set-point and the circadian rhythm of metabolism. The model was able to describe a complex set of IL-21 induced phenomena, including 1) disappearance of the circadian rhythm, 2) no effect after first dose, and 3) high variability after second dose. SDEs provided a more realistic description with improved simulation properties, and further changed the model into one that could not be falsified by the autocorrelation function. The IL-21 induced effects on thermoregulation in cynomolgus monkeys are explained by a biologically plausible model. The quality of the model was improved by the use of SDEs.

Crashworthiness of light aircraft fuselage structures: A numerical and experimental investigation

NASA Technical Reports Server (NTRS)

Nanyaro, A. P.; Tennyson, R. C.; Hansen, J. S.

1984-01-01

The dynamic behavior of aircraft fuselage structures subject to various impact conditions was investigated. An analytical model was developed based on a self-consistent finite element (CFE) formulation utilizing shell, curved beam, and stringer type elements. Equations of motion were formulated and linearized (i.e., for small displacements), although material nonlinearity was retained to treat local plastic deformation. The equations were solved using the implicit Newmark-Beta method with a frontal solver routine. Stiffened aluminum fuselage models were also tested in free flight using the UTIAS pendulum crash test facility. Data were obtained on dynamic strains, g-loads, and transient deformations (using high speed photography in the latter case) during the impact process. Correlations between tests and predicted results are presented, together with computer graphics, based on the CFE model. These results include level and oblique angle impacts as well as the free-flight crash test. Comparisons with a hybrid, lumped mass finite element computer model demonstrate that the CFE formulation provides the test overall agreement with impact test data for comparable computing costs.

Studies in the demand for short haul air transportation

NASA Technical Reports Server (NTRS)

Kanafani, A.; Gosling, G.; Taghavi, S.

1975-01-01

Demand is analyzed in a short haul air transportation corridor. Emphasis is placed on traveler selection from available routes. Model formulations, estimation techniques, and traffic data handling are included.

Wall functions for the kappa-epsilon turbulence model in generalized nonorthogonal curvilinear coordinates

NASA Technical Reports Server (NTRS)

Sondak, D. L.; Pletcher, R. H.; Vandalsem, W. R.

1992-01-01

A k-epsilon turbulence model suitable for compressible flow, including the new wall function formulation, has been incorporated into an existing compressible Reynolds-averaged Navier-Stokes code, F3D. The low Reynolds number k-epsilon model of Chien (1982) was added for comparison with the present method. A number of features were added to the F3D code including improved far-field boundary conditions and viscous terms in the streamwise direction. A series of computations of increasing complexity was run to test the effectiveness of the new formulation. Flow over a flat plate was computed by using both orthogonal and nonorthogonal grids, and the friction coefficients and velocity profiles compared with a semi-empirical equation. Flow over a body of revolution at zero angle of attack was then computed to test the method's ability to handle flow over a curved surface. Friction coefficients and velocity profiles were compared to test data. All models gave good results on a relatively fine grid, but only the wall function formulation was effective with coarser grids. Finally, in order to demonstrate the method's ability to handle complex flow fields, separated flow over a prolate spheroid at angle of attack was computed, and results were compared to test data. The results were also compared to a k-epsilon model by Kim and Patel (1991), in which one equation model patched in at the wall was employed. Both models gave reasonable solutions, but improvement is required for accurate prediction of friction coefficients in the separated regions.

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 element implementations of the proposed constitutive formulations are employed to simulate an underground salt cavern used for compressed air energy storage with OpenGeoSys [1]. Transient convergence and stress fields are evaluated for typical fluctuating operation pressure regimes.

Multi-Objective Trajectory Optimization of a Hypersonic Reconnaissance Vehicle with Temperature Constraints

NASA Astrophysics Data System (ADS)

Masternak, Tadeusz J.

This research determines temperature-constrained optimal trajectories for a scramjet-based hypersonic reconnaissance vehicle by developing an optimal control formulation and solving it using a variable order Gauss-Radau quadrature collocation method with a Non-Linear Programming (NLP) solver. The vehicle is assumed to be an air-breathing reconnaissance aircraft that has specified takeoff/landing locations, airborne refueling constraints, specified no-fly zones, and specified targets for sensor data collections. A three degree of freedom scramjet aircraft model is adapted from previous work and includes flight dynamics, aerodynamics, and thermal constraints. Vehicle control is accomplished by controlling angle of attack, roll angle, and propellant mass flow rate. This model is incorporated into an optimal control formulation that includes constraints on both the vehicle and mission parameters, such as avoidance of no-fly zones and coverage of high-value targets. To solve the optimal control formulation, a MATLAB-based package called General Pseudospectral Optimal Control Software (GPOPS-II) is used, which transcribes continuous time optimal control problems into an NLP problem. In addition, since a mission profile can have varying vehicle dynamics and en-route imposed constraints, the optimal control problem formulation can be broken up into several "phases" with differing dynamics and/or varying initial/final constraints. Optimal trajectories are developed using several different performance costs in the optimal control formulation: minimum time, minimum time with control penalties, and maximum range. The resulting analysis demonstrates that optimal trajectories that meet specified mission parameters and constraints can be quickly determined and used for larger-scale operational and campaign planning and execution.

Robust global identifiability theory using potentials--Application to compartmental models.

PubMed

Wongvanich, N; Hann, C E; Sirisena, H R

2015-04-01

This paper presents a global practical identifiability theory for analyzing and identifying linear and nonlinear compartmental models. The compartmental system is prolonged onto the potential jet space to formulate a set of input-output equations that are integrals in terms of the measured data, which allows for robust identification of parameters without requiring any simulation of the model differential equations. Two classes of linear and non-linear compartmental models are considered. The theory is first applied to analyze the linear nitrous oxide (N2O) uptake model. The fitting accuracy of the identified models from differential jet space and potential jet space identifiability theories is compared with a realistic noise level of 3% which is derived from sensor noise data in the literature. The potential jet space approach gave a match that was well within the coefficient of variation. The differential jet space formulation was unstable and not suitable for parameter identification. The proposed theory is then applied to a nonlinear immunological model for mastitis in cows. In addition, the model formulation is extended to include an iterative method which allows initial conditions to be accurately identified. With up to 10% noise, the potential jet space theory predicts the normalized population concentration infected with pathogens, to within 9% of the true curve. Copyright © 2015 Elsevier Inc. All rights reserved.

Discrete stochastic analogs of Erlang epidemic models.

PubMed

Getz, Wayne M; Dougherty, Eric R

2018-12-01

Erlang differential equation models of epidemic processes provide more realistic disease-class transition dynamics from susceptible (S) to exposed (E) to infectious (I) and removed (R) categories than the ubiquitous SEIR model. The latter is itself is at one end of the spectrum of Erlang SE[Formula: see text]I[Formula: see text]R models with [Formula: see text] concatenated E compartments and [Formula: see text] concatenated I compartments. Discrete-time models, however, are computationally much simpler to simulate and fit to epidemic outbreak data than continuous-time differential equations, and are also much more readily extended to include demographic and other types of stochasticity. Here we formulate discrete-time deterministic analogs of the Erlang models, and their stochastic extension, based on a time-to-go distributional principle. Depending on which distributions are used (e.g. discretized Erlang, Gamma, Beta, or Uniform distributions), we demonstrate that our formulation represents both a discretization of Erlang epidemic models and generalizations thereof. We consider the challenges of fitting SE[Formula: see text]I[Formula: see text]R models and our discrete-time analog to data (the recent outbreak of Ebola in Liberia). We demonstrate that the latter performs much better than the former; although confining fits to strict SEIR formulations reduces the numerical challenges, but sacrifices best-fit likelihood scores by at least 7%.

Assessments of a Turbulence Model Based on Menter's Modification to Rotta's Two-Equation Model

NASA Technical Reports Server (NTRS)

Abdol-Hamid, Khaled S.

2013-01-01

The main objective of this paper is to construct a turbulence model with a more reliable second equation simulating length scale. In the present paper, we assess the length scale equation based on Menter s modification to Rotta s two-equation model. Rotta shows that a reliable second equation can be formed in an exact transport equation from the turbulent length scale L and kinetic energy. Rotta s equation is well suited for a term-by-term modeling and shows some interesting features compared to other approaches. The most important difference is that the formulation leads to a natural inclusion of higher order velocity derivatives into the source terms of the scale equation, which has the potential to enhance the capability of Reynolds-averaged Navier-Stokes (RANS) to simulate unsteady flows. The model is implemented in the PAB3D solver with complete formulation, usage methodology, and validation examples to demonstrate its capabilities. The detailed studies include grid convergence. Near-wall and shear flows cases are documented and compared with experimental and Large Eddy Simulation (LES) data. The results from this formulation are as good or better than the well-known SST turbulence model and much better than k-epsilon results. Overall, the study provides useful insights into the model capability in predicting attached and separated flows.

Mathematical and experimental investigations of modeling, simulation and experiment to promote the life-cycle of polymer modified asphalt.

DOT National Transportation Integrated Search

2014-07-01

The formulation of constitutive equations for asphaltic pavement is based on rheological models which include the asphalt mixture, additives, and the bitumen. In terms of the asphalt, the rheology addresses the flow and permanent deformation in time,...

Extension and Validation of a Hybrid Particle-Finite Element Method for Hypervelocity Impact Simulation. Chapter 2

NASA Technical Reports Server (NTRS)

Fahrenthold, Eric P.; Shivarama, Ravishankar

2004-01-01

The hybrid particle-finite element method of Fahrenthold and Horban, developed for the simulation of hypervelocity impact problems, has been extended to include new formulations of the particle-element kinematics, additional constitutive models, and an improved numerical implementation. The extended formulation has been validated in three dimensional simulations of published impact experiments. The test cases demonstrate good agreement with experiment, good parallel speedup, and numerical convergence of the simulation results.

Implications of fault constitutive properties for earthquake prediction

USGS Publications Warehouse

Dieterich, J.H.; Kilgore, B.

1996-01-01

The rate- and state-dependent constitutive formulation for fault slip characterizes an exceptional variety of materials over a wide range of sliding conditions. This formulation provides a unified representation of diverse sliding phenomena including slip weakening over a characteristic sliding distance D(c), apparent fracture energy at a rupture front, time- dependent healing after rapid slip, and various other transient and slip rate effects. Laboratory observations and theoretical models both indicate that earthquake nucleation is accompanied by long intervals of accelerating slip. Strains from the nucleation process on buried faults generally could not be detected if laboratory values of D, apply to faults in nature. However, scaling of D(c) is presently an open question and the possibility exists that measurable premonitory creep may precede some earthquakes. Earthquake activity is modeled as a sequence of earthquake nucleation events. In this model, earthquake clustering arises from sensitivity of nucleation times to the stress changes induced by prior earthquakes. The model gives the characteristic Omori aftershock decay law and assigns physical interpretation to aftershock parameters. The seismicity formulation predicts large changes of earthquake probabilities result from stress changes. Two mechanisms for foreshocks are proposed that describe observed frequency of occurrence of foreshock-mainshock pairs by time and magnitude. With the first mechanism, foreshocks represent a manifestation of earthquake clustering in which the stress change at the time of the foreshock increases the probability of earthquakes at all magnitudes including the eventual mainshock. With the second model, accelerating fault slip on the mainshock nucleation zone triggers foreshocks.

Implications of fault constitutive properties for earthquake prediction.

PubMed

Dieterich, J H; Kilgore, B

1996-04-30

The rate- and state-dependent constitutive formulation for fault slip characterizes an exceptional variety of materials over a wide range of sliding conditions. This formulation provides a unified representation of diverse sliding phenomena including slip weakening over a characteristic sliding distance Dc, apparent fracture energy at a rupture front, time-dependent healing after rapid slip, and various other transient and slip rate effects. Laboratory observations and theoretical models both indicate that earthquake nucleation is accompanied by long intervals of accelerating slip. Strains from the nucleation process on buried faults generally could not be detected if laboratory values of Dc apply to faults in nature. However, scaling of Dc is presently an open question and the possibility exists that measurable premonitory creep may precede some earthquakes. Earthquake activity is modeled as a sequence of earthquake nucleation events. In this model, earthquake clustering arises from sensitivity of nucleation times to the stress changes induced by prior earthquakes. The model gives the characteristic Omori aftershock decay law and assigns physical interpretation to aftershock parameters. The seismicity formulation predicts large changes of earthquake probabilities result from stress changes. Two mechanisms for foreshocks are proposed that describe observed frequency of occurrence of foreshock-mainshock pairs by time and magnitude. With the first mechanism, foreshocks represent a manifestation of earthquake clustering in which the stress change at the time of the foreshock increases the probability of earthquakes at all magnitudes including the eventual mainshock. With the second model, accelerating fault slip on the mainshock nucleation zone triggers foreshocks.

Finite Element Methods and Multiphase Continuum Theory for Modeling 3D Air-Water-Sediment Interactions

NASA Astrophysics Data System (ADS)

Kees, C. E.; Miller, C. T.; Dimakopoulos, A.; Farthing, M.

2016-12-01

The last decade has seen an expansion in the development and application of 3D free surface flow models in the context of environmental simulation. These models are based primarily on the combination of effective algorithms, namely level set and volume-of-fluid methods, with high-performance, parallel computing. These models are still computationally expensive and suitable primarily when high-fidelity modeling near structures is required. While most research on algorithms and implementations has been conducted in the context of finite volume methods, recent work has extended a class of level set schemes to finite element methods on unstructured methods. This work considers models of three-phase flow in domains containing air, water, and granular phases. These multi-phase continuum mechanical formulations show great promise for applications such as analysis of coastal and riverine structures. This work will consider formulations proposed in the literature over the last decade as well as new formulations derived using the thermodynamically constrained averaging theory, an approach to deriving and closing macroscale continuum models for multi-phase and multi-component processes. The target applications require the ability to simulate wave breaking and structure over-topping, particularly fully three-dimensional, non-hydrostatic flows that drive these phenomena. A conservative level set scheme suitable for higher-order finite element methods is used to describe the air/water phase interaction. The interaction of these air/water flows with granular materials, such as sand and rubble, must also be modeled. The range of granular media dynamics targeted including flow and wave transmision through the solid media as well as erosion and deposition of granular media and moving bed dynamics. For the granular phase we consider volume- and time-averaged continuum mechanical formulations that are discretized with the finite element method and coupled to the underlying air/water flow via operator splitting (fractional step) schemes. Particular attention will be given to verification and validation of the numerical model and important qualitative features of the numerical methods including phase conservation, wave energy dissipation, and computational efficiency in regimes of interest.

Tracking trade transactions in water resource systems: A node-arc optimization formulation

NASA Astrophysics Data System (ADS)

Erfani, Tohid; Huskova, Ivana; Harou, Julien J.

2013-05-01

We formulate and apply a multicommodity network flow node-arc optimization model capable of tracking trade transactions in complex water resource systems. The model uses a simple node to node network connectivity matrix and does not require preprocessing of all possible flow paths in the network. We compare the proposed node-arc formulation with an existing arc-path (flow path) formulation and explain the advantages and difficulties of both approaches. We verify the proposed formulation model on a hypothetical water distribution network. Results indicate the arc-path model solves the problem with fewer constraints, but the proposed formulation allows using a simple network connectivity matrix which simplifies modeling large or complex networks. The proposed algorithm allows converting existing node-arc hydroeconomic models that broadly represent water trading to ones that also track individual supplier-receiver relationships (trade transactions).

Coastal Modeling System: Mathematical Formulations and Numerical Methods

DTIC Science & Technology

2014-03-01

sediment transport , and morphology change. The CMS was designed and developed for coastal inlets and navigation applications, including channel...numerical methods of hydrodynamic, salinity and sediment transport , and morphology change model CMS-Flow. The CMS- Flow uses the Finite Volume...and the influence of coastal structures. The implicit hydrodynamic model is coupled to a nonequilibrium transport model of multiple-sized total

Modeling of Economy Considering Crisis

NASA Astrophysics Data System (ADS)

Petrov, Lev F.

2009-09-01

We discuss main modeling's problems of economy dynamic processes and the reason forecast's absence of economic crisis. We present a structure of complexity level of system and models and discuss expected results concerning crisis phenomena. We formulate the basic perspective directions of the mathematical modeling of economy, including possibility of the analysis of the pre crisis, crisis and post crisis phenomena in economic systems.

Dynamical influences on thermospheric composition: implications for semi-empirical models

NASA Astrophysics Data System (ADS)

Sutton, E. K.; Solomon, S. C.

2014-12-01

The TIE-GCM was recently augmented to include helium and argon, two approximately inert species that can be used as tracers of dynamics in the thermosphere. The former species is treated as a major species due to its large abundance near the upper boundary. The effects of exospheric transport are also included in order to simulate realistic seasonal and latitudinal helium distributions. The latter species is treated as a classical minor species, imparting absolutely no forces on the background atmosphere. In this study, we examine the interplay of the various dynamical terms - i.e. background circulation, molecular and Eddy diffusion - as they drive departures from the distributions that would be expected under the assumption of diffusive equilibrium. As this has implications on the formulation of all empirical thermospheric models, we use this understanding to address the following questions: (1) how do errors caused by the assumption of diffusive equilibrium manifest within empirical models of the thermosphere? and (2) where and when does an empirical model's output disagree with its underlying datasets due to the inherent limitations of said model's formulation?

Theory of electron-impact ionization of atoms

NASA Astrophysics Data System (ADS)

Kadyrov, A. S.; Mukhamedzhanov, A. M.; Stelbovics, A. T.; Bray, I.

2004-12-01

The existing formulations of electron-impact ionization of a hydrogenic target suffer from a number of formal problems including an ambiguous and phase-divergent definition of the ionization amplitude. An alternative formulation of the theory is given. An integral representation for the ionization amplitude which is free of ambiguity and divergence problems is derived and is shown to have four alternative, but equivalent, forms well suited for practical calculations. The extension to amplitudes of all possible scattering processes taking place in an arbitrary three-body system follows. A well-defined conventional post form of the breakup amplitude valid for arbitrary potentials including the long-range Coulomb interaction is given. Practical approaches are based on partial-wave expansions, so the formulation is also recast in terms of partial waves and partial-wave expansions of the asymptotic wave functions are presented. In particular, expansions of the asymptotic forms of the total scattering wave function, developed from both the initial and the final state, for electron-impact ionization of hydrogen are given. Finally, the utility of the present formulation is demonstrated on some well-known model problems.

Morphodynamic Modeling Using The SToRM Computational System

NASA Astrophysics Data System (ADS)

Simoes, F.

2016-12-01

The framework of the work presented here is the open source SToRM (System for Transport and River Modeling) eco-hydraulics modeling system, which is one of the models released with the iRIC hydraulic modeling graphical software package (http://i-ric.org/). SToRM has been applied to the simulation of various complex environmental problems, including natural waterways, steep channels with regime transition, and rapidly varying flood flows with wetting and drying fronts. In its previous version, however, channel bed was treated as static and the ability of simulating sediment transport rates or bed deformation was not included. The work presented here reports SToRM's newly developed extensions to expand the system's capability to calculate morphological changes in alluvial river systems. The sediment transport module of SToRM has been developed based on the general recognition that meaningful advances depend on physically solid formulations and robust and accurate numerical solution methods. The basic concepts of mass and momentum conservation are used, where the feedback mechanisms between the flow of water, the sediment in transport, and the bed changes are directly incorporated in the governing equations used in the mathematical model. This is accomplished via a non-capacity transport formulation based on the work of Cao et al. [Z. Cao et al., "Non-capacity or capacity model for fluvial sediment transport," Water Management, 165(WM4):193-211, 2012], where the governing equations are augmented with source/sink terms due to water-sediment interaction. The same unsteady, shock-capturing numerical schemes originally used in SToRM were adapted to the new physics, using a control volume formulation over unstructured computational grids. The presentation will include a brief overview of these methodologies, and the result of applications of the model to a number of relevant physical test cases with movable bed, where computational results are compared to experimental data.

Investigation of an artificial intelligence technology--Model trees. Novel applications for an immediate release tablet formulation database.

PubMed

Shao, Q; Rowe, R C; York, P

2007-06-01

This study has investigated an artificial intelligence technology - model trees - as a modelling tool applied to an immediate release tablet formulation database. The modelling performance was compared with artificial neural networks that have been well established and widely applied in the pharmaceutical product formulation fields. The predictability of generated models was validated on unseen data and judged by correlation coefficient R(2). Output from the model tree analyses produced multivariate linear equations which predicted tablet tensile strength, disintegration time, and drug dissolution profiles of similar quality to neural network models. However, additional and valuable knowledge hidden in the formulation database was extracted from these equations. It is concluded that, as a transparent technology, model trees are useful tools to formulators.

Using the Global Forest Products Model (GFPM version 2016 with BPMPD)

Treesearch

Joseph Buongiorno; Shushuai   Zhu

2016-01-01

 The GFPM is an economic model of global production, consumption and trade of forest products. The original formulation and several applications are described in Buongiorno et al. (2003). However, subsequent versions, including the GFPM 2016 reflect significant changes and extensions. The GFPM 2016 software uses the...

REGIONAL-SCALE (1000 KM) MODEL OF PHOTOCHEMICAL AIR POLLUTION. PART 2. INPUT PROCESSOR NETWORK DESIGN

EPA Science Inventory

Detailed specifications are given for a network of data processors and submodels that can generate the parameter fields required by the regional oxidant model formulated in Part 1 of this report. Operations performed by the processor network include simulation of the motion and d...

Equilibrium Conformations of Concentric-tube Continuum Robots

PubMed Central

Rucker, D. Caleb; Webster, Robert J.; Chirikjian, Gregory S.; Cowan, Noah J.

2013-01-01

Robots consisting of several concentric, preshaped, elastic tubes can work dexterously in narrow, constrained, and/or winding spaces, as are commonly found in minimally invasive surgery. Previous models of these “active cannulas” assume piecewise constant precurvature of component tubes and neglect torsion in curved sections of the device. In this paper we develop a new coordinate-free energy formulation that accounts for general preshaping of an arbitrary number of component tubes, and which explicitly includes both bending and torsion throughout the device. We show that previously reported models are special cases of our formulation, and then explore in detail the implications of torsional flexibility for the special case of two tubes. Experiments demonstrate that this framework is more descriptive of physical prototype behavior than previous models; it reduces model prediction error by 82% over the calibrated bending-only model, and 17% over the calibrated transmissional torsion model in a set of experiments. PMID:25125773

Multi-phase-field modeling of anisotropic crack propagation for polycrystalline materials

NASA Astrophysics Data System (ADS)

Nguyen, Thanh-Tung; Réthoré, Julien; Yvonnet, Julien; Baietto, Marie-Christine

2017-08-01

A new multi-phase-field method is developed for modeling the fracture of polycrystals at the microstructural level. Inter and transgranular cracking, as well as anisotropic effects of both elasticity and preferential cleavage directions within each randomly oriented crystal are taken into account. For this purpose, the proposed phase field formulation includes: (a) a smeared description of grain boundaries as cohesive zones avoiding defining an additional phase for grains; (b) an anisotropic phase field model; (c) a multi-phase field formulation where each preferential cleavage direction is associated with a damage (phase field) variable. The obtained framework allows modeling interactions and competition between grains and grain boundary cracks, as well as their effects on the effective response of the material. The proposed model is illustrated through several numerical examples involving a full description of complex crack initiation and propagation within 2D and 3D models of polycrystals.

The use of linear programming to determine whether a formulated complementary food product can ensure adequate nutrients for 6- to 11-month-old Cambodian infants.

PubMed

Skau, Jutta K H; Bunthang, Touch; Chamnan, Chhoun; Wieringa, Frank T; Dijkhuizen, Marjoleine A; Roos, Nanna; Ferguson, Elaine L

2014-01-01

A new software tool, Optifood, developed by the WHO and based on linear programming (LP) analysis, has been developed to formulate food-based recommendations. This study discusses the use of Optifood for predicting whether formulated complementary food (CF) products can ensure dietary adequacy for target populations in Cambodia. Dietary data were collected by 24-h recall in a cross-sectional survey of 6- to 11-mo-old infants (n = 78). LP model parameters were derived from these data, including a list of foods, median serving sizes, and dietary patterns. Five series of LP analyses were carried out to model the target population's baseline diet and 4 formulated CF products [WinFood (WF), WinFood-Lite (WF-L), Corn-Soy-Blend Plus (CSB+), and Corn-Soy-Blend Plus Plus (CSB++)], which were added to the diet in portions of 33 g/d dry weight (DW) for infants aged 6-8 mo and 40 g/d DW for infants aged 9-11 mo. In each series of analyses, the nutritionally optimal diet and theoretical range, in diet nutrient contents, were determined. The LP analysis showed that baseline diets could not achieve the Recommended Nutrient Intake (RNI) for thiamin, riboflavin, niacin, folate, vitamin B-12, calcium, iron, and zinc (range: 14-91% of RNI in the optimal diets) and that none of the formulated CF products could cover the nutrient gaps for thiamin, niacin, iron, and folate (range: 22-86% of the RNI). Iron was the key limiting nutrient, for all modeled diets, achieving a maximum of only 48% of the RNI when CSB++ was included in the diet. Only WF and WF-L filled the nutrient gap for calcium. WF-L, CSB+, and CSB++ filled the nutrient gap for zinc (9- to 11-mo-olds). The formulated CF products improved the nutrient adequacy of complementary feeding diets but could not entirely cover the nutrient gaps. These results emphasize the value of using LP to evaluate special CF products during the intervention planning phase. The WF study was registered at controlled-trials.com as ISRCTN19918531.

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

PubMed

Kamesh, Reddi; Rani, Kalipatnapu Yamuna

2017-12-01

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.

Low Mach number fluctuating hydrodynamics for electrolytes

DOE PAGES

Péraud, Jean-Philippe; Nonaka, Andy; Chaudhri, Anuj; ...

2016-11-18

Here, we formulate and study computationally the low Mach number fluctuating hydrodynamic equations for electrolyte solutions. We are also interested in studying transport in mixtures of charged species at the mesoscale, down to scales below the Debye length, where thermal fluctuations have a significant impact on the dynamics. Continuing our previous work on fluctuating hydrodynamics of multicomponent mixtures of incompressible isothermal miscible liquids (A. Donev, et al., Physics of Fluids, 27, 3, 2015), we now include the effect of charged species using a quasielectrostatic approximation. Localized charges create an electric field, which in turn provides additional forcing in the massmore » and momentum equations. Our low Mach number formulation eliminates sound waves from the fully compressible formulation and leads to a more computationally efficient quasi-incompressible formulation. Furthermore, we demonstrate our ability to model saltwater (NaCl) solutions in both equilibrium and nonequilibrium settings. We show that our algorithm is second-order in the deterministic setting, and for length scales much greater than the Debye length gives results consistent with an electroneutral/ambipolar approximation. In the stochastic setting, our model captures the predicted dynamics of equilibrium and nonequilibrium fluctuations. We also identify and model an instability that appears when diffusive mixing occurs in the presence of an applied electric field.« less

Protein labeling reactions in electrochemical microchannel flow: Numerical simulation and uncertainty propagation

NASA Astrophysics Data System (ADS)

Debusschere, Bert J.; Najm, Habib N.; Matta, Alain; Knio, Omar M.; Ghanem, Roger G.; Le Maître, Olivier P.

2003-08-01

This paper presents a model for two-dimensional electrochemical microchannel flow including the propagation of uncertainty from model parameters to the simulation results. For a detailed representation of electroosmotic and pressure-driven microchannel flow, the model considers the coupled momentum, species transport, and electrostatic field equations, including variable zeta potential. The chemistry model accounts for pH-dependent protein labeling reactions as well as detailed buffer electrochemistry in a mixed finite-rate/equilibrium formulation. Uncertainty from the model parameters and boundary conditions is propagated to the model predictions using a pseudo-spectral stochastic formulation with polynomial chaos (PC) representations for parameters and field quantities. Using a Galerkin approach, the governing equations are reformulated into equations for the coefficients in the PC expansion. The implementation of the physical model with the stochastic uncertainty propagation is applied to protein-labeling in a homogeneous buffer, as well as in two-dimensional electrochemical microchannel flow. The results for the two-dimensional channel show strong distortion of sample profiles due to ion movement and consequent buffer disturbances. The uncertainty in these results is dominated by the uncertainty in the applied voltage across the channel.

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.

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. Consistently with the two-region model working hypotheses, we subdivide the pore space into two volumes, which we select according to the features of the local micro-scale velocity field. Assuming separation of the scales, the mathematical development associated with the averaging method in the two volumes leads to a generalized two-equation model. The final (upscaled) formulation includes the standard first order mass exchange term together with additional terms, which we discuss. Our developments allow to identify the assumptions which are usually implicitly embedded in the usual adoption of a two region mobile-mobile model. All macro-scale properties introduced in this model can be determined explicitly from the pore-scale geometry and hydrodynamics through the solution of a set of closure equations. We pursue here an unsteady closure of the problem, leading to the occurrence of nonlocal (in time) terms in the upscaled system of equations. We provide the solution of the closure problems for a simple application documenting the time dependent and the asymptotic behavior of the system.

Boron and Poloxamer (F68 and F127) Containing Hydrogel Formulation for Burn Wound Healing.

PubMed

Demirci, Selami; Doğan, Ayşegül; Karakuş, Emre; Halıcı, Zekai; Topçu, Atila; Demirci, Elif; Sahin, Fikrettin

2015-11-01

Burn injuries, the most common and destructive forms of wounds, are generally accompanied with life-threatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process. Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.

GWM-a ground-water management process for the U.S. Geological Survey modular ground-water model (MODFLOW-2000)

USGS Publications Warehouse

Ahlfeld, David P.; Barlow, Paul M.; Mulligan, Anne E.

2005-01-01

GWM is a Ground?Water Management Process for the U.S. Geological Survey modular three?dimensional ground?water model, MODFLOW?2000. GWM uses a response?matrix approach to solve several types of linear, nonlinear, and mixed?binary linear ground?water management formulations. Each management formulation consists of a set of decision variables, an objective function, and a set of constraints. Three types of decision variables are supported by GWM: flow?rate decision variables, which are withdrawal or injection rates at well sites; external decision variables, which are sources or sinks of water that are external to the flow model and do not directly affect the state variables of the simulated ground?water system (heads, streamflows, and so forth); and binary variables, which have values of 0 or 1 and are used to define the status of flow?rate or external decision variables. Flow?rate decision variables can represent wells that extend over one or more model cells and be active during one or more model stress periods; external variables also can be active during one or more stress periods. A single objective function is supported by GWM, which can be specified to either minimize or maximize the weighted sum of the three types of decision variables. Four types of constraints can be specified in a GWM formulation: upper and lower bounds on the flow?rate and external decision variables; linear summations of the three types of decision variables; hydraulic?head based constraints, including drawdowns, head differences, and head gradients; and streamflow and streamflow?depletion constraints. The Response Matrix Solution (RMS) Package of GWM uses the Ground?Water Flow Process of MODFLOW to calculate the change in head at each constraint location that results from a perturbation of a flow?rate variable; these changes are used to calculate the response coefficients. For linear management formulations, the resulting matrix of response coefficients is then combined with other components of the linear management formulation to form a complete linear formulation; the formulation is then solved by use of the simplex algorithm, which is incorporated into the RMS Package. Nonlinear formulations arise for simulated conditions that include water?table (unconfined) aquifers or head?dependent boundary conditions (such as streams, drains, or evapotranspiration from the water table). Nonlinear formulations are solved by sequential linear programming; that is, repeated linearization of the nonlinear features of the management problem. In this approach, response coefficients are recalculated for each iteration of the solution process. Mixed?binary linear (or mildly nonlinear) formulations are solved by use of the branch and bound algorithm, which is also incorporated into the RMS Package. Three sample problems are provided to demonstrate the use of GWM for typical ground?water flow management problems. These sample problems provide examples of how GWM input files are constructed to specify the decision variables, objective function, constraints, and solution process for a GWM run. The GWM Process runs with the MODFLOW?2000 Global and Ground?Water Flow Processes, but in its current form GWM cannot be used with the Observation, Sensitivity, Parameter?Estimation, or Ground?Water Transport Processes. The GWM Process is written with a modular structure so that new objective functions, constraint types, and solution algorithms can be added.

A report from the pediatric formulations task force: perspectives on the state of child-friendly oral dosage forms.

PubMed

Zajicek, Anne; Fossler, Michael J; Barrett, Jeffrey S; Worthington, Jeffrey H; Ternik, Robert; Charkoftaki, Georgia; Lum, Susan; Breitkreutz, Jörg; Baltezor, Mike; Macheras, Panos; Khan, Mansoor; Agharkar, Shreeram; MacLaren, David Douglas

2013-10-01

Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially children, because of large tablet or capsule size, poor palatability, and lack of correct dosage strength. The clinical result is often lack of adherence and therapeutic failure. The American Association of Pharmaceutical Scientists formed a Pediatric Formulations Task Force, consisting of members with various areas of expertise including pediatrics, formulation development, clinical pharmacology, and regulatory science, in order to identify pediatric, manufacturing, and regulatory issues and areas of needed research and regulatory guidance. Dosage form and palatability standards for all pediatric ages, relative bioavailability requirements, and small batch manufacturing capabilities and creation of a viable economic model were identified as particular needs. This assessment is considered an important first step for a task force seeking creative approaches to providing more appropriate oral formulations for children.

An Experimental and Modeling Study of Evaporation from Bare Soils Subjected to Natural Boundary Conditions at the Land-Atmospheric Interface

NASA Astrophysics Data System (ADS)

Smits, K. M.; Ngo, V. V.; Cihan, A.; Sakaki, T.; Illangasekare, T. H.; kathleen m smits

2011-12-01

Bare soil evaporation is a key process for water exchange between the land and the atmosphere and an important component of the water balance in semiarid and arid regions. However, there is no agreement on the best methodology to determine evaporation under different boundary conditions. Because it is difficult to measure evaporation from soil,with the exception of using lysimeters, numerous formulations have been proposed to establish a relationship between the rate of evaporation and soil moisture and/or soil temperature and thermal properties. Different formulations vary in how they partition available energy and include, among others, a classical bulk aerodynamic formulation which requires knowledge of the relative humidity at the soil surface and a more non-traditional heat balance method which requires knowledge of soil temperature and soil thermal properties. A need exists to systematically compare existing methods to experimental data under highly controlled conditions not achievable in the field. The goal of this work is to perform controlled experiments under transient conditions of soil moisture, temperature and wind at the land/atmospheric interface to test different conceptual and mathematical formulations for evaporation rate estimates and to develop appropriate numerical models to be used in simulations. In this study, to better understand the coupled water-vapor-heat flow processes in the shallow subsurface near the land surface, we modified a previously developed theory that allows non-equilibrium liquid/gas phase change with gas phase vapor diffusion to better account for evaporation under dry soil conditions. This theory was used to compare estimates of evaporation based on different formulations of the bulk aerodynamic and heat balance methods. In order to experimentally validate the numerical formulations/code, we performed a series of two-dimensional physical model experiments under varying boundary conditions using test sand for which the hydraulic and thermal properties were well characterized. We developed a unique two dimensional cell apparatus equipped with a network of sensors for automated and continuous monitoring of soil moisture, soil and air temperature and relative humidity, and wind velocity. Precision data under well-controlled transient heat and wind boundary conditions was generated. Results from numerical simulations were compared with experimental data. Results demonstrate the importance of properly characterizing soil thermal properties and accounting for dry soil conditions to properly estimate evaporation. Initial comparisons of various formulations of evaporation demonstrate the need for joint evaluation of heat and mass transfer for better modeling accuracy. Detailed comparisons are still underway. This knowledge is applicable to many current hydrologic and environmental problems to include climate modeling and the simulation of contaminant transport and volatilization in the shallow subsurface.

Effects of drug-carrier interactions on drug dissolution from binary and ternary matrices

NASA Astrophysics Data System (ADS)

Iqbal, Zafar

For nearly five decades, pharmaceutical researchers have studied solid solutions of drugs in polymers as a potential means to enhance the dissolution of drugs with poor aqueous solubility. This has become of greater importance in recent years because most new potential drug compounds (new chemical entities) exhibit poor water solubility and present great challenges to scientists who must design dosage forms from which the drugs are bioavailable. During the formulation of a solid solution, the drug undergoes physical but not chemical alterations that increase its chemical potential in the formulation relative to that of the pure drug in its stable form. This increased chemical potential is responsible for enhanced dissolution as well as physical instabilities, such as amorphous to crystalline conversions and precipitation within the solid state. The chemical potential is derived from the Gibbs free energy, so it is reasonable to explain the behavior of solid solution systems in terms of thermodynamics. Solid solutions and dispersions have been extensively studied by pharmaceutical scientists, both with regard to manufacturing aspects and the proposal of various models in attempts to explain the physical bases for how these systems work. Recently, Dave and Bellantone proposed a model based on the thermodynamic changes resulting from the formulation of binary solid solutions of a drug in the polymer PVP. Their model introduced a modification of the F-H theory, which was used to quantify the drug-polymer interaction energies and calculate the entropy of mixing of the drug and polymer. In this work, the model of Dave and Bellantone was extended to include three-component systems, consisting of one drug mixed in a carrier matrix consisting of mixture of two polymers or a polymer and a surfactant. For this research, solid solutions were formed using various drug weight fractions in the formulations. The study focused on the following points: (1) Prepare solid solution formulations and perform appropriate physical characterizations. (2) Characterize the increase in drug dissolution rates resulting from solid solution formulations. (3) Relate the initial dissolution rates to the drug solubility. (4) Explain the solubility enhancement from solid solution dosage in terms of the drug polymer interactions using the extended thermodynamic model. Two poorly water soluble drugs, levonorgestrel (LEVO) and ethinyl estradiol (EE) were formulated in seven solid solution preparations comprised of four carrier systems. Materials used as carriers included various combinations of the polymers PVP K-30, Copovidone (COP), Poloxamer 182, and the surfactant TweenRTM 20. Additionally, ibuprofen (IBU) was used in three formulations consisting of various combinations of PVP K-30, Copovidone and TweenRTM 20. Formulations with various drug weight fractions (0.5%--30%) were prepared using the solvent evaporation technique. Each formulation was tested for dissolution using intrinsic dissolution apparatus (USP). The solid solutions were compressed into tablets into the sample die that maintained a constant surface area during the dissolution process. DSC, XRD and NIRS scans identified that the crystalline peaks of the drug disappeared with the addition of the polymer for all ratios of EE, indicating the formation of solid solutions (to within the limits of detection of the equipment). This was also observed for the LEVO dispersions up to 10% drug loading. At higher drug loading, solutions were formed but some small degree crystallinity was also present. For each experiment, the initial dissolution rates were obtained from the slope of the mass dissolved vs. time plots taken at early times, and volume normalized initial dissolution rates RV were calculated by dividing the initial dissolution rate by the volume fraction of the drug in the formulation. Comparison of the RV values for the various formulations with a reference RV (typically that of the pure drug or of the formulation with the highest polymer content) allowed calculation of relative volume normalized dissolution rates (RNV). The various RNV were used in the thermodynamic model for data analyses and to determine the interactions between the drug and carrier molecules. It was generally seen that RNV increased with decreased drug fraction, and was adequately modeled by the equations derived from the extended thermodynamic model. It was concluded that the model proposed for the binary and ternary systems successfully represented the mechanism of drug-polymer interaction and the energy changes taken place within the dispersion systems. The dissolution data analysis and subsequent understanding of physical modifications in the dispersion systems characterized by XRD, NIRS and DSC further substantiated the findings. The understanding of the fundamental physical might help scientists to predict the effects of mixing various drugs and polymers, and the effects of varying ratios.

Multi-stage rescheduling of generation, load shedding and short-term transmission capacity for emergency state control

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

Krogh, B.; Chow, J.H.; Javid, H.S.

1983-05-01

A multi-stage formulation of the problem of scheduling generation, load shedding and short term transmission capacity for the alleviation of a viability emergency is presented. The formulation includes generation rate of change constraints, a linear network solution, and a model of the short term thermal overload capacity of transmission lines. The concept of rotating transmission line overloads for emergency state control is developed. The ideas are illustrated by a numerical example.

A new class of finite element variational multiscale turbulence models for incompressible magnetohydrodynamics

DOE PAGES

Sondak, D.; Shadid, J. N.; Oberai, A. A.; ...

2015-04-29

New large eddy simulation (LES) turbulence models for incompressible magnetohydrodynamics (MHD) derived from the variational multiscale (VMS) formulation for finite element simulations are introduced. The new models include the variational multiscale formulation, a residual-based eddy viscosity model, and a mixed model that combines both of these component models. Each model contains terms that are proportional to the residual of the incompressible MHD equations and is therefore numerically consistent. Moreover, each model is also dynamic, in that its effect vanishes when this residual is small. The new models are tested on the decaying MHD Taylor Green vortex at low and highmore » Reynolds numbers. The evaluation of the models is based on comparisons with available data from direct numerical simulations (DNS) of the time evolution of energies as well as energy spectra at various discrete times. Thus a numerical study, on a sequence of meshes, is presented that demonstrates that the large eddy simulation approaches the DNS solution for these quantities with spatial mesh refinement.« less

Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations.

PubMed

Garidel, Patrick; Pevestorf, Benjamin; Bahrenburg, Sven

2015-11-01

We studied the stability of freeze-dried therapeutic protein formulations over a range of initial concentrations (from 40 to 160 mg/mL) and employed a variety of formulation strategies (including buffer-free freeze dried formulations, or BF-FDF). Highly concentrated, buffer-free liquid formulations of therapeutic monoclonal antibodies (mAbs) have been shown to be a viable alternative to conventionally buffered preparations. We considered whether it is feasible to use the buffer-free strategy in freeze-dried formulations, as an answer to some of the known drawbacks of conventional buffers. We therefore conducted an accelerated stability study (24 weeks at 40 °C) to assess the feasibility of stabilizing freeze-dried formulations without "classical" buffer components. Factors monitored included pH stability, protein integrity, and protein aggregation. Because the protein solutions are inherently self-buffering, and the system's buffer capacity scales with protein concentration, we included highly concentrated buffer-free freeze-dried formulations in the study. The tested formulations ranged from "fully formulated" (containing both conventional buffer and disaccharide stabilizers) to "buffer-free" (including formulations with only disaccharide lyoprotectant stabilizers) to "excipient-free" (with neither added buffers nor stabilizers). We evaluated the impacts of varying concentrations, buffering schemes, pHs, and lyoprotectant additives. At the end of 24 weeks, no change in pH was observed in any of the buffer-free formulations. Unbuffered formulations were found to have shorter reconstitution times and lower opalescence than buffered formulations. Protein stability was assessed by visual inspection, sub-visible particle analysis, protein monomer content, charge variants analysis, and hydrophobic interaction chromatography. All of these measures found the stability of buffer-free formulations that included a disaccharide stabilizer comparable to buffer-based formulations, especially at protein concentrations up to and including 115 mg/mL. Copyright © 2015 Elsevier B.V. All rights reserved.

Power Demand in Walking and Pace Optimization.

ERIC Educational Resources Information Center

Bellemans, A.

1981-01-01

Presents an elementary formulation of the work expenditure corresponding to walking, the most common physical exercise. The model described is included in a physics course for freshmen in physical education and physical therapy. (Author/JN)

Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans.

PubMed

Solomon, Keith R; Wilks, Martin F; Bachman, Ammie; Boobis, Alan; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard; Embry, Michelle R

2016-11-01

When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs.

Gastroprotective strategies in chronic NSAID users: a cost-effectiveness analysis comparing single-tablet formulations with individual components.

PubMed

de Groot, N L; Spiegel, B M R; van Haalen, H G M; de Wit, N J; Siersema, P D; van Oijen, M G H

2013-01-01

To evaluate the cost-effectiveness of competing gastroprotective strategies, including single-tablet formulations, in the prevention of gastrointestinal (GI) complications in patients with chronic arthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs). We performed a cost-utility analysis to compare eight gastroprotective strategies including NSAIDs, cyclooxygenase-2 inhibitors, proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol, and single-tablet formulations. We derived estimates for outcomes and costs from medical literature. The primary outcome was incremental cost per quality-adjusted life-year gained. We performed sensitivity analyses to assess the effect of GI complications, compliance rates, and drug costs. For average-risk patients, NSAID + PPI cotherapy was most cost-effective. The NSAID/PPI single-tablet formulation became cost-effective only when its price decreased from €0.78 to €0.56 per tablet, or when PPI compliance fell below 51% in the NSAID + PPI strategy. All other strategies were more costly and less effective. The model was highly sensitive to the GI complication risk, costs of PPI and NSAID/PPI single-tablet formulation, and compliance to PPI. In patients with a threefold higher risk of GI complications, both NSAID + PPI cotherapy and single-tablet formulation were cost-effective. NSAID + PPI cotherapy is the most cost-effective strategy in all patients with chronic arthritis irrespective of their risk for GI complications. For patients with increased GI risk, the NSAID/PPI single-tablet formulation is also cost-effective. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

A developmental, biopsychosocial model for the treatment of children with gender identity disorder.

PubMed

Zucker, Kenneth J; Wood, Hayley; Singh, Devita; Bradley, Susan J

2012-01-01

This article provides a summary of the therapeutic model and approach used in the Gender Identity Service at the Centre for Addiction and Mental Health in Toronto. The authors describe their assessment protocol, describe their current multifactorial case formulation model, including a strong emphasis on developmental factors, and provide clinical examples of how the model is used in the treatment.

Model verification of large structural systems

NASA Technical Reports Server (NTRS)

Lee, L. T.; Hasselman, T. K.

1977-01-01

A methodology was formulated, and a general computer code implemented for processing sinusoidal vibration test data to simultaneously make adjustments to a prior mathematical model of a large structural system, and resolve measured response data to obtain a set of orthogonal modes representative of the test model. The derivation of estimator equations is shown along with example problems. A method for improving the prior analytic model is included.

Application of recursive Gibbs-Appell formulation in deriving the equations of motion of N-viscoelastic robotic manipulators in 3D space using Timoshenko Beam Theory

NASA Astrophysics Data System (ADS)

Korayem, M. H.; Shafei, A. M.

2013-02-01

The goal of this paper is to describe the application of Gibbs-Appell (G-A) formulation and the assumed modes method to the mathematical modeling of N-viscoelastic link manipulators. The paper's focus is on obtaining accurate and complete equations of motion which encompass the most related structural properties of lightweight elastic manipulators. In this study, two important damping mechanisms, namely, the structural viscoelasticity (Kelvin-Voigt) effect (as internal damping) and the viscous air effect (as external damping) have been considered. To include the effects of shear and rotational inertia, the assumption of Timoshenko beam (TB) theory (TBT) has been applied. Gravity, torsion, and longitudinal elongation effects have also been included in the formulations. To systematically derive the equations of motion and improve the computational efficiency, a recursive algorithm has been used in the modeling of the system. In this algorithm, all the mathematical operations are carried out by only 3×3 and 3×1 matrices. Finally, a computational simulation for a manipulator with two elastic links is performed in order to verify the proposed method.

Finding optimal vaccination strategies under parameter uncertainty using stochastic programming.

PubMed

Tanner, Matthew W; Sattenspiel, Lisa; Ntaimo, Lewis

2008-10-01

We present a stochastic programming framework for finding the optimal vaccination policy for controlling infectious disease epidemics under parameter uncertainty. Stochastic programming is a popular framework for including the effects of parameter uncertainty in a mathematical optimization model. The problem is initially formulated to find the minimum cost vaccination policy under a chance-constraint. The chance-constraint requires that the probability that R(*)

Peridynamics with LAMMPS : a user guide.

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

Lehoucq, Richard B.; Silling, Stewart Andrew; Plimpton, Steven James

2008-01-01

Peridynamics is a nonlocal formulation of continuum mechanics. The discrete peridynamic model has the same computational structure as a molecular dynamic model. This document details the implementation of a discrete peridynamic model within the LAMMPS molecular dynamic code. This document provides a brief overview of the peridynamic model of a continuum, then discusses how the peridynamic model is discretized, and overviews the LAMMPS implementation. A nontrivial example problem is also included.

The Finite Strain Johnson Cook Plasticity and Damage Constitutive Model in ALEGRA.

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

Sanchez, Jason James

A finite strain formulation of the Johnson Cook plasticity and damage model and it's numerical implementation into the ALEGRA code is presented. The goal of this work is to improve the predictive material failure capability of the Johnson Cook model. The new implementation consists of a coupling of damage and the stored elastic energy as well as the minimum failure strain criteria for spall included in the original model development. This effort establishes the necessary foundation for a thermodynamically consistent and complete continuum solid material model, for which all intensive properties derive from a common energy. The motivation for developingmore » such a model is to improve upon ALEGRA's present combined model framework. Several applications of the new Johnson Cook implementation are presented. Deformation driven loading paths demonstrate the basic features of the new model formulation. Use of the model produces good comparisons with experimental Taylor impact data. Localized deformation leading to fragmentation is produced for expanding ring and exploding cylinder applications.« less

Turbulence and fire-spotting effects into wild-land fire simulators

NASA Astrophysics Data System (ADS)

Kaur, Inderpreet; Mentrelli, Andrea; Bosseur, Frédéric; Filippi, Jean-Baptiste; Pagnini, Gianni

2016-10-01

This paper presents a mathematical approach to model the effects and the role of phenomena with random nature such as turbulence and fire-spotting into the existing wildfire simulators. The formulation proposes that the propagation of the fire-front is the sum of a drifting component (obtained from an existing wildfire simulator without turbulence and fire-spotting) and a random fluctuating component. The modelling of the random effects is embodied in a probability density function accounting for the fluctuations around the fire perimeter which is given by the drifting component. In past, this formulation has been applied to include these random effects into a wildfire simulator based on an Eulerian moving interface method, namely the Level Set Method (LSM), but in this paper the same formulation is adapted for a wildfire simulator based on a Lagrangian front tracking technique, namely the Discrete Event System Specification (DEVS). The main highlight of the present study is the comparison of the performance of a Lagrangian and an Eulerian moving interface method when applied to wild-land fire propagation. Simple idealised numerical experiments are used to investigate the potential applicability of the proposed formulation to DEVS and to compare its behaviour with respect to the LSM. The results show that DEVS based wildfire propagation model qualitatively improves its performance (e.g., reproducing flank and back fire, increase in fire spread due to pre-heating of the fuel by hot air and firebrands, fire propagation across no fuel zones, secondary fire generation, ...) when random effects are included according to the present formulation. The performance of DEVS and LSM based wildfire models is comparable and the only differences which arise among the two are due to the differences in the geometrical construction of the direction of propagation. Though the results presented here are devoid of any validation exercise and provide only a proof of concept, they show a strong inclination towards an intended operational use. The existing LSM or DEVS based operational simulators like WRF-SFIRE and ForeFire respectively can serve as an ideal basis for the same.

Crash Certification by Analysis - Are We There Yet?

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Fasanella, Edwin L.; Lyle, Karen H.

2006-01-01

This paper addresses the issue of crash certification by analysis. This broad topic encompasses many ancillary issues including model validation procedures, uncertainty in test data and analysis models, probabilistic techniques for test-analysis correlation, verification of the mathematical formulation, and establishment of appropriate qualification requirements. This paper will focus on certification requirements for crashworthiness of military helicopters; capabilities of the current analysis codes used for crash modeling and simulation, including some examples of simulations from the literature to illustrate the current approach to model validation; and future directions needed to achieve "crash certification by analysis."

Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo.

PubMed

Buscema, Marzia; Matviykiv, Sofiya; Mészáros, Tamás; Gerganova, Gabriela; Weinberger, Andreas; Mettal, Ute; Mueller, Dennis; Neuhaus, Frederik; Stalder, Etienne; Ishikawa, Takashi; Urbanics, Rudolf; Saxer, Till; Pfohl, Thomas; Szebeni, János; Zumbuehl, Andreas; Müller, Bert

2017-10-28

Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear-responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC-Pad formulations in human and porcine sera, along with the nanopharmaceutical-mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad-PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Multi-objective trajectory optimization for the space exploration vehicle

NASA Astrophysics Data System (ADS)

Qin, Xiaoli; Xiao, Zhen

2016-07-01

The research determines temperature-constrained optimal trajectory for the space exploration vehicle by developing an optimal control formulation and solving it using a variable order quadrature collocation method with a Non-linear Programming(NLP) solver. The vehicle is assumed to be the space reconnaissance aircraft that has specified takeoff/landing locations, specified no-fly zones, and specified targets for sensor data collections. A three degree of freedom aircraft model is adapted from previous work and includes flight dynamics, and thermal constraints.Vehicle control is accomplished by controlling angle of attack, roll angle, and propellant mass flow rate. This model is incorporated into an optimal control formulation that includes constraints on both the vehicle and mission parameters, such as avoidance of no-fly zones and exploration of space targets. In addition, the vehicle models include the environmental models(gravity and atmosphere). How these models are appropriately employed is key to gaining confidence in the results and conclusions of the research. Optimal trajectories are developed using several performance costs in the optimal control formation,minimum time,minimum time with control penalties,and maximum distance.The resulting analysis demonstrates that optimal trajectories that meet specified mission parameters and constraints can be quickly determined and used for large-scale space exloration.

Modeling Ignition of HMX with the Gibbs Formulation

NASA Astrophysics Data System (ADS)

Lee, Kibaek; Stewart, D. Scott

2017-06-01

We present a HMX model with the Gibbs formulation in which stress tensor and temperature are assumed to be in local equilibrium, but phase/chemical changes are not assumed to be in equilibrium. We assume multi-components for HMX including beta- and delta-phase, liquid, and gas phase of HMX and its gas products. Isotropic small strain solid model, modified Fried Howard liquid EOS, and ideal gas EOS are used for its relevant component. Phase/chemical changes are characterized as reactions and are in individual reaction rate. Maxwell-Stefan model is used for diffusion. Excited gas products in the local domain lead unreacted HMX solid to the ignition event. Density of the mixture, stress, strain, displacement, mass fractions, and temperature are considered in 1D domain with time histories. Office of Naval Research and Air Force Office of Scientific Research.

Oral biopharmaceutics tools - time for a new initiative - an introduction to the IMI project OrBiTo.

PubMed

Lennernäs, H; Aarons, L; Augustijns, P; Beato, S; Bolger, M; Box, K; Brewster, M; Butler, J; Dressman, J; Holm, R; Julia Frank, K; Kendall, R; Langguth, P; Sydor, J; Lindahl, A; McAllister, M; Muenster, U; Müllertz, A; Ojala, K; Pepin, X; Reppas, C; Rostami-Hodjegan, A; Verwei, M; Weitschies, W; Wilson, C; Karlsson, C; Abrahamsson, B

2014-06-16

OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes. Copyright © 2013 Elsevier B.V. All rights reserved.

Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Haj-Ahmad, Rita; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-01

Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio-surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano-fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano-structured coatings (for all formulations) were <200nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM-loaded PNIPAM coating releasing most drug after 24h (89.8%). Kinetic modelling (Higuchi, Korsmeyer-Peppas) was indicative of quasi-Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating method demonstrates sustained drug release yielding promising results; suggesting both novel device and method to enhance drug activity at the eyes surface which will reduce formulation drainage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

A New Formulation of the Filter-Error Method for Aerodynamic Parameter Estimation in Turbulence

NASA Technical Reports Server (NTRS)

Grauer, Jared A.; Morelli, Eugene A.

2015-01-01

A new formulation of the filter-error method for estimating aerodynamic parameters in nonlinear aircraft dynamic models during turbulence was developed and demonstrated. The approach uses an estimate of the measurement noise covariance to identify the model parameters, their uncertainties, and the process noise covariance, in a relaxation method analogous to the output-error method. Prior information on the model parameters and uncertainties can be supplied, and a post-estimation correction to the uncertainty was included to account for colored residuals not considered in the theory. No tuning parameters, needing adjustment by the analyst, are used in the estimation. The method was demonstrated in simulation using the NASA Generic Transport Model, then applied to the subscale T-2 jet-engine transport aircraft flight. Modeling results in different levels of turbulence were compared with results from time-domain output error and frequency- domain equation error methods to demonstrate the effectiveness of the approach.

From puddles to planet: modeling approaches to vector-borne diseases at varying resolution and scale.

PubMed

Eckhoff, Philip A; Bever, Caitlin A; Gerardin, Jaline; Wenger, Edward A; Smith, David L

2015-08-01

Since the original Ross-Macdonald formulations of vector-borne disease transmission, there has been a broad proliferation of mathematical models of vector-borne disease, but many of these models retain most to all of the simplifying assumptions of the original formulations. Recently, there has been a new expansion of mathematical frameworks that contain explicit representations of the vector life cycle including aquatic stages, multiple vector species, host heterogeneity in biting rate, realistic vector feeding behavior, and spatial heterogeneity. In particular, there are now multiple frameworks for spatially explicit dynamics with movements of vector, host, or both. These frameworks are flexible and powerful, but require additional data to take advantage of these features. For a given question posed, utilizing a range of models with varying complexity and assumptions can provide a deeper understanding of the answers derived from models. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

An efficient formulation of robot arm dynamics for control and computer simulation

NASA Astrophysics Data System (ADS)

Lee, C. S. G.; Nigam, R.

This paper describes an efficient formulation of the dynamic equations of motion of industrial robots based on the Lagrange formulation of d'Alembert's principle. This formulation, as applied to a PUMA robot arm, results in a set of closed form second order differential equations with cross product terms. They are not as efficient in computation as those formulated by the Newton-Euler method, but provide a better analytical model for control analysis and computer simulation. Computational complexities of this dynamic model together with other models are tabulated for discussion.

A New Formulation for Fresh Snow Density over Antarctica for the regional climate model Modèle Atmosphérique Régionale (MAR).

NASA Astrophysics Data System (ADS)

Tedesco, M.; Datta, R.; Fettweis, X.; Agosta, C.

2015-12-01

Surface-layer snow density is important to processes contributing to surface mass balance, but is highly variable over Antarctica due to a wide range of near-surface climate conditions over the continent. Formulations for fresh snow density have typically either used fixed values or been modeled empirically using field data that is limited to specific seasons or regions. There is also currently limited work exploring how the sensitivity to fresh snow density in regional climate models varies with resolution. Here, we present a new formulation compiled from (a) over 1600 distinct density profiles from multiple sources across Antarctica and (b) near-surface variables from the regional climate model Modèle Atmosphérique Régionale (MAR). Observed values represent coastal areas as well as the plateau, in both West and East Antarctica (although East Antarctica is dominant). However, no measurements are included from the Antarctic Peninsula, which is both highly topographically variable and extends to lower latitudes than the remainder of the continent. In order to assess the applicability of this fresh snow density formulation to the Antarctic Peninsula at high resolutions, a version of MAR is run for several years both at low-resolution at the continental scale and at a high resolution for the Antarctic Peninsula alone. This setup is run both with and without the new fresh density formulation to quantify the sensitivity of the energy balance and SMB components to fresh snow density. Outputs are compared with near-surface atmospheric variables available from AWS stations (provided by the University of Wisconsin Madison) as well as net accumulation values from the SAMBA database (provided from the Laboratoire de Glaciologie et Géophysique de l'Environnement).

Multi-scale diffuse interface modeling of multi-component two-phase flow with partial miscibility

NASA Astrophysics Data System (ADS)

Kou, Jisheng; Sun, Shuyu

2016-08-01

In this paper, we introduce a diffuse interface model to simulate multi-component two-phase flow with partial miscibility based on a realistic equation of state (e.g. Peng-Robinson equation of state). Because of partial miscibility, thermodynamic relations are used to model not only interfacial properties but also bulk properties, including density, composition, pressure, and realistic viscosity. As far as we know, this effort is the first time to use diffuse interface modeling based on equation of state for modeling of multi-component two-phase flow with partial miscibility. In numerical simulation, the key issue is to resolve the high contrast of scales from the microscopic interface composition to macroscale bulk fluid motion since the interface has a nanoscale thickness only. To efficiently solve this challenging problem, we develop a multi-scale simulation method. At the microscopic scale, we deduce a reduced interfacial equation under reasonable assumptions, and then we propose a formulation of capillary pressure, which is consistent with macroscale flow equations. Moreover, we show that Young-Laplace equation is an approximation of this capillarity formulation, and this formulation is also consistent with the concept of Tolman length, which is a correction of Young-Laplace equation. At the macroscopical scale, the interfaces are treated as discontinuous surfaces separating two phases of fluids. Our approach differs from conventional sharp-interface two-phase flow model in that we use the capillary pressure directly instead of a combination of surface tension and Young-Laplace equation because capillarity can be calculated from our proposed capillarity formulation. A compatible condition is also derived for the pressure in flow equations. Furthermore, based on the proposed capillarity formulation, we design an efficient numerical method for directly computing the capillary pressure between two fluids composed of multiple components. Finally, numerical tests are carried out to verify the effectiveness of the proposed multi-scale method.

Multi-scale diffuse interface modeling of multi-component two-phase flow with partial miscibility

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

Kou, Jisheng; Sun, Shuyu, E-mail: shuyu.sun@kaust.edu.sa; School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an 710049

2016-08-01

In this paper, we introduce a diffuse interface model to simulate multi-component two-phase flow with partial miscibility based on a realistic equation of state (e.g. Peng–Robinson equation of state). Because of partial miscibility, thermodynamic relations are used to model not only interfacial properties but also bulk properties, including density, composition, pressure, and realistic viscosity. As far as we know, this effort is the first time to use diffuse interface modeling based on equation of state for modeling of multi-component two-phase flow with partial miscibility. In numerical simulation, the key issue is to resolve the high contrast of scales from themore » microscopic interface composition to macroscale bulk fluid motion since the interface has a nanoscale thickness only. To efficiently solve this challenging problem, we develop a multi-scale simulation method. At the microscopic scale, we deduce a reduced interfacial equation under reasonable assumptions, and then we propose a formulation of capillary pressure, which is consistent with macroscale flow equations. Moreover, we show that Young–Laplace equation is an approximation of this capillarity formulation, and this formulation is also consistent with the concept of Tolman length, which is a correction of Young–Laplace equation. At the macroscopical scale, the interfaces are treated as discontinuous surfaces separating two phases of fluids. Our approach differs from conventional sharp-interface two-phase flow model in that we use the capillary pressure directly instead of a combination of surface tension and Young–Laplace equation because capillarity can be calculated from our proposed capillarity formulation. A compatible condition is also derived for the pressure in flow equations. Furthermore, based on the proposed capillarity formulation, we design an efficient numerical method for directly computing the capillary pressure between two fluids composed of multiple components. Finally, numerical tests are carried out to verify the effectiveness of the proposed multi-scale method.« less

Development and Testing of a Fully Adaptable Membrane Bioreactor Fouling Model for a Sidestream Configuration System

PubMed Central

Paul, Parneet

2013-01-01

A dead-end filtration model that includes the three main fouling mechanisms mentioned in Hermia (i.e., cake build-up, complete pore blocking, and pore constriction) and that was based on a constant trans-membrane pressure (TMP) operation was extensively modified so it could be used for a sidestream configuration membrane bioreactor (MBR) situation. Modifications and add-ons to this basic model included: alteration so that it could be used for varying flux and varying TMP operations; inclusion of a backwash mode; it described pore constriction (i.e., irreversible fouling) in relation to the concentration of soluble microbial products (SMP) in the liquor; and, it could be used in a cross flow scenario by the addition of scouring terms in the model formulation. The additional terms in this modified model were checked against an already published model to see if they made sense, physically speaking. Next this modified model was calibrated and validated in Matlab© using data collected by carrying out flux stepping tests on both a pilot sidestream MBR plant, and then a pilot membrane filtration unit. The model fit proved good, especially for the pilot filtration unit data. In conclusion, this model formulation is of the right level of complexity to be used for most practical MBR situations. PMID:24958618

Sustainability in Supply Chain Management: Aggregate Planning from Sustainability Perspective.

PubMed

Türkay, Metin; Saraçoğlu, Öztürk; Arslan, Mehmet Can

2016-01-01

Supply chain management that considers the flow of raw materials, products and information has become a focal issue in modern manufacturing and service systems. Supply chain management requires effective use of assets and information that has far reaching implications beyond satisfaction of customer demand, flow of goods, services or capital. Aggregate planning, a fundamental decision model in supply chain management, refers to the determination of production, inventory, capacity and labor usage levels in the medium term. Traditionally standard mathematical programming formulation is used to devise the aggregate plan so as to minimize the total cost of operations. However, this formulation is purely an economic model that does not include sustainability considerations. In this study, we revise the standard aggregate planning formulation to account for additional environmental and social criteria to incorporate triple bottom line consideration of sustainability. We show how these additional criteria can be appended to traditional cost accounting in order to address sustainability in aggregate planning. We analyze the revised models and interpret the results on a case study from real life that would be insightful for decision makers.

Sustainability in Supply Chain Management: Aggregate Planning from Sustainability Perspective

PubMed Central

Türkay, Metin; Saraçoğlu, Öztürk; Arslan, Mehmet Can

2016-01-01

Supply chain management that considers the flow of raw materials, products and information has become a focal issue in modern manufacturing and service systems. Supply chain management requires effective use of assets and information that has far reaching implications beyond satisfaction of customer demand, flow of goods, services or capital. Aggregate planning, a fundamental decision model in supply chain management, refers to the determination of production, inventory, capacity and labor usage levels in the medium term. Traditionally standard mathematical programming formulation is used to devise the aggregate plan so as to minimize the total cost of operations. However, this formulation is purely an economic model that does not include sustainability considerations. In this study, we revise the standard aggregate planning formulation to account for additional environmental and social criteria to incorporate triple bottom line consideration of sustainability. We show how these additional criteria can be appended to traditional cost accounting in order to address sustainability in aggregate planning. We analyze the revised models and interpret the results on a case study from real life that would be insightful for decision makers. PMID:26807848

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...

Development of poloxamer gel formulations via hot-melt extrusion technology.

PubMed

Mendonsa, Nicole S; Murthy, S Narasimha; Hashemnejad, Seyed Meysam; Kundu, Santanu; Zhang, Feng; Repka, Michael A

2018-02-15

Poloxamer gels are conventionally prepared by the "hot" or the "cold" process. But these techniques have some disadvantages such as high energy consumption, requires expensive equipment and often have scale up issues. Therefore, the objective of this work was to develop poloxamer gels by hot-melt extrusion technology. The model drug selected was ketoprofen. The formulations developed were 30% and 40% poloxamer gels. Of these formulations, the 30% poloxamer gels were selected as ideal gels. DSC and XRD studies showed an amorphous nature of the drug after extrusion. It was observed from the permeation studies that with increasing poloxamer concentration, a decrease in drug permeation was obtained. Other studies conducted for the formulations included in-vitro release studies, texture analysis, rheological studies and pH measurements. In conclusion, the hot-melt extrusion technology could be successfully employed to develop poloxamer gels by overcoming the drawbacks associated with the conventional techniques. Published by Elsevier B.V.

Formulation and method for preparing gels comprising hydrous aluminum oxide

DOEpatents

Collins, Jack L.

2014-06-17

Formulations useful for preparing hydrous aluminum oxide gels contain a metal salt including aluminum, an organic base, and a complexing agent. Methods for preparing gels containing hydrous aluminum oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including aluminum, an organic base, and a complexing agent.

Formulation and method for preparing gels comprising hydrous cerium oxide

DOEpatents

Collins, Jack L; Chi, Anthony

2013-05-07

Formulations useful for preparing hydrous cerium oxide gels contain a metal salt including cerium, an organic base, and a complexing agent. Methods for preparing gels containing hydrous cerium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including cerium, an organic base, and a complexing agent.

Reciprocity theory of homogeneous reactions

NASA Astrophysics Data System (ADS)

Agbormbai, Adolf A.

1990-03-01

The reciprocity formalism is applied to the homogeneous gaseous reactions in which the structure of the participating molecules changes upon collision with one another, resulting in a change in the composition of the gas. The approach is applied to various classes of dissociation, recombination, rearrangement, ionizing, and photochemical reactions. It is shown that for the principle of reciprocity to be satisfied it is necessary that all chemical reactions exist in complementary pairs which consist of the forward and backward reactions. The backward reaction may be described by either the reverse or inverse process. The forward and backward processes must satisfy the same reciprocity equation. Because the number of dynamical variables is usually unbalanced on both sides of a chemical equation, it is necessary that this balance be established by including as many of the dynamical variables as needed before the reciprocity equation can be formulated. Statistical transformation models of the reactions are formulated. The models are classified under the titles free exchange, restricted exchange and simplified restricted exchange. The special equations for the forward and backward processes are obtained. The models are consistent with the H theorem and Le Chatelier's principle. The models are also formulated in the context of the direct simulation Monte Carlo method.

Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations.

PubMed

Holm, René; Olesen, Niels Erik; Alexandersen, Signe Dalgaard; Dahlgaard, Birgitte N; Westh, Peter; Mu, Huiling

2016-05-25

Preservatives are inactivated when added to conserve aqueous cyclodextrin (CD) formulations due to complex formation between CDs and the preservative. To maintain the desired conservation effect the preservative needs to be added in apparent surplus to account for this inactivation. The purpose of the present work was to establish a mathematical model, which defines this surplus based upon knowledge of stability constants and the minimal concentration of preservation to inhibit bacterial growth. The stability constants of benzoic acid, methyl- and propyl-paraben with different frequently used βCDs were determined by isothermal titration calorimetry. Based upon this knowledge mathematical models were constructed to account for the equilibrium systems and to calculate the required concentration of the preservations, which was evaluated experimentally based upon the USP/Ph. Eur./JP monograph. The mathematical calculations were able to predict the needed concentration of preservation in the presence of CDs; it clearly demonstrated the usefulness of including all underlying chemical equilibria in a mathematical model, such that the formulation design can be based on quantitative arguments. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluating the effects of real power losses in optimal power flow based storage integration

DOE PAGES

Castillo, Anya; Gayme, Dennice

2017-03-27

This study proposes a DC optimal power flow (DCOPF) with losses formulation (the `-DCOPF+S problem) and uses it to investigate the role of real power losses in OPF based grid-scale storage integration. We derive the `- DCOPF+S problem by augmenting a standard DCOPF with storage (DCOPF+S) problem to include quadratic real power loss approximations. This procedure leads to a multi-period nonconvex quadratically constrained quadratic program, which we prove can be solved to optimality using either a semidefinite or second order cone relaxation. Our approach has some important benefits over existing models. It is more computationally tractable than ACOPF with storagemore » (ACOPF+S) formulations and the provably exact convex relaxations guarantee that an optimal solution can be attained for a feasible problem. Adding loss approximations to a DCOPF+S model leads to a more accurate representation of locational marginal prices, which have been shown to be critical to determining optimal storage dispatch and siting in prior ACOPF+S based studies. Case studies demonstrate the improved accuracy of the `-DCOPF+S model over a DCOPF+S model and the computational advantages over an ACOPF+S formulation.« less

On the Frozen Soil Scheme for High Latitude Regions

NASA Astrophysics Data System (ADS)

Ganji, A.; Sushama, L.

2014-12-01

Regional and global climate model simulated streamflows for high-latitude regions show systematic biases, particularly in the timing and magnitude of spring peak flows. Though these biases could be related to the snow water equivalent and spring temperature biases in models, a good part of these biases is due to the unaccounted effects of non-uniform infiltration capacity of the frozen ground and other related processes. In this paper, the frozen scheme in the Canadian Land Surface Scheme (CLASS), which is used in the Canadian regional and global climate models, is modified to include fractional permeable area, supercooled liquid water and a new formulation for hydraulic conductivity. Interflow is also included in these experiments presented in this study to better explain the steamflows after snow melt season. The impact of these modifications on the regional hydrology, particularly streamflow, is assessed by comparing three simulations, performed with the original and two modified versions of CLASS, driven by atmospheric forcing data from the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis data (ERA-Interim), for the 1990-2001 period, over a northeast Canadian domain. The two modified versions of CLASS differ in the soil hydraulic conductivity and matric potential formulations, with one version being based on formulations from a previous study and the other one is newly proposed. Results suggest statistically significant decreases in infiltration for the simulation with the new hydraulic conductivity and matric potential formulations and fractional permeable area concept, compared to the original version of CLASS, which is also reflected in the increased spring surface runoff and streamflows in this simulation with modified CLASS, over most of the study domain. The simulated spring peaks and their timing in this simulation is also in better agreement to those observed.

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.

Implications of fault constitutive properties for earthquake prediction.

PubMed Central

Dieterich, J H; Kilgore, B

1996-01-01

The rate- and state-dependent constitutive formulation for fault slip characterizes an exceptional variety of materials over a wide range of sliding conditions. This formulation provides a unified representation of diverse sliding phenomena including slip weakening over a characteristic sliding distance Dc, apparent fracture energy at a rupture front, time-dependent healing after rapid slip, and various other transient and slip rate effects. Laboratory observations and theoretical models both indicate that earthquake nucleation is accompanied by long intervals of accelerating slip. Strains from the nucleation process on buried faults generally could not be detected if laboratory values of Dc apply to faults in nature. However, scaling of Dc is presently an open question and the possibility exists that measurable premonitory creep may precede some earthquakes. Earthquake activity is modeled as a sequence of earthquake nucleation events. In this model, earthquake clustering arises from sensitivity of nucleation times to the stress changes induced by prior earthquakes. The model gives the characteristic Omori aftershock decay law and assigns physical interpretation to aftershock parameters. The seismicity formulation predicts large changes of earthquake probabilities result from stress changes. Two mechanisms for foreshocks are proposed that describe observed frequency of occurrence of foreshock-mainshock pairs by time and magnitude. With the first mechanism, foreshocks represent a manifestation of earthquake clustering in which the stress change at the time of the foreshock increases the probability of earthquakes at all magnitudes including the eventual mainshock. With the second model, accelerating fault slip on the mainshock nucleation zone triggers foreshocks. Images Fig. 3 PMID:11607666

Three dimensional thermal pollution models. Volume 3: Free surface models. [waste heat discharge from power plants and effects on ecosystems

NASA Technical Reports Server (NTRS)

Lee, S. S.; Sengupta, S.

1978-01-01

Two sets of programs, named Nasum 2 and Nasum 3 are presented in detail. Nasum 2 is a far field formulation and is used without including the plant thermal discharge. Nasum 3 uses horizontal stretching to provide higher resolution at thermal discharge joints; and includes far field influences such as varying tides and ambient currents far from point of discharge.

Kubo–Greenwood approach to conductivity in dense plasmas with average atom models

DOE PAGES

Starrett, C. E.

2016-04-13

In this study, a new formulation of the Kubo–Greenwood conductivity for average atom models is given. The new formulation improves upon previous treatments by explicitly including the ionic-structure factor. Calculations based on this new expression lead to much improved agreement with ab initio results for DC conductivity of warm dense hydrogen and beryllium, and for thermal conductivity of hydrogen. We also give and test a slightly modified Ziman–Evans formula for the resistivity that includes a non-free electron density of states, thus removing an ambiguity in the original Ziman–Evans formula. Again, results based on this expression are in good agreement withmore » ab initio simulations for warm dense beryllium and hydrogen. However, for both these expressions, calculations of the electrical conductivity of warm dense aluminum lead to poor agreement at low temperatures compared to ab initio simulations.« less

MODFLOW-NWT – Robust handling of dry cells using a Newton Formulation of MODFLOW-2005

USGS Publications Warehouse

Hunt, Randal J.; Feinstein, Daniel T.

2012-01-01

The first versions of the widely used groundwater flow model MODFLOW (McDonald and Harbaugh 1988) had a sure but inflexible way of handling unconfined finite-difference aquifer cells where the water table dropped below the bottom of the cell—these "dry cells" were turned inactive for the remainder of the simulation. Problems with this formulation were easily seen, including the potential for inadvertent loss of simulated recharge in the model (Doherty 2001; Painter et al. 2008), and rippling of dry cells through the solution that unacceptably changed the groundwater flow system (Juckem et al. 2006). Moreover, solving problems of the natural world often required the ability to reactivate dry cells when the water table rose above the cell bottom. This seemingly simple desire resulted in a two-decade attempt to include the simulation flexibility while avoiding numerical instability.

A systematic description of shocks in gamma-ray bursts - I. Formulation

NASA Astrophysics Data System (ADS)

Ziaeepour, Houri

2009-07-01

Since the suggestion of relativistic shocks as the origin of gamma-ray bursts (GRBs) in the early 1990s, the mathematical formulation of this process has stayed at a phenomenological level. One of the reasons for the slow development of theoretical works has been the simple power-law behaviour of the afterglows hours or days after the prompt gamma-ray emission. It was believed that they could be explained with these formulations. Nowadays, with the launch of the Swift satellite and implementation of robotic ground follow-ups, GRBs and their afterglow can be observed at multi-wavelengths from a few tens of seconds after trigger onwards. These observations have led to the discovery of features unexplainable by the simple formulation of the shocks and emission processes used up to now. Some of these features can be inherent in the nature and activities of the GRBs' central engines which are not yet well understood. On the other hand, the devil is in the detail and others may be explained with a more detailed formulation of these phenomena and without ad hoc addition of new processes. Such a formulation is the goal of this work. We present a consistent formulation of the kinematics and dynamics of the collision between two spherical relativistic shells, their energy dissipation and their coalescence. It can be applied to both internal and external shocks. Notably, we propose two phenomenological models for the evolution of the emitting region during the collision. One of these models is more suitable for the prompt/internal shocks and late external shocks, and the other for the afterglow/external collisions as well as the onset of internal shocks. We calculate a number of observables such as flux, lag between energy bands and hardness ratios. One of our aims has been a formulation complex enough to include the essential processes, but simple enough such that the data can be directly compared with the theory to extract the value and evolution of physical quantities. To accomplish this goal, we also suggest a procedure for extracting parameters of the model from data. In a companion paper, we numerically calculate the evolution of some simulated models and compare their features with the properties of the observed GRBs.

SBKF Modeling and Analysis Plan: Buckling Analysis of Compression-Loaded Orthogrid and Isogrid Cylinders

NASA Technical Reports Server (NTRS)

Lovejoy, Andrew E.; Hilburger, Mark W.

2013-01-01

This document outlines a Modeling and Analysis Plan (MAP) to be followed by the SBKF analysts. It includes instructions on modeling and analysis formulation and execution, model verification and validation, identifying sources of error and uncertainty, and documentation. The goal of this MAP is to provide a standardized procedure that ensures uniformity and quality of the results produced by the project and corresponding documentation.

Evaluation of CFD Turbulent Heating Prediction Techniques and Comparison With Hypersonic Experimental Data

NASA Technical Reports Server (NTRS)

Dilley, Arthur D.; McClinton, Charles R. (Technical Monitor)

2001-01-01

Results from a study to assess the accuracy of turbulent heating and skin friction prediction techniques for hypersonic applications are presented. The study uses the original and a modified Baldwin-Lomax turbulence model with a space marching code. Grid converged turbulent predictions using the wall damping formulation (original model) and local damping formulation (modified model) are compared with experimental data for several flat plates. The wall damping and local damping results are similar for hot wall conditions, but differ significantly for cold walls, i.e., T(sub w) / T(sub t) < 0.3, with the wall damping heating and skin friction 10-30% above the local damping results. Furthermore, the local damping predictions have reasonable or good agreement with the experimental heating data for all cases. The impact of the two formulations on the van Driest damping function and the turbulent eddy viscosity distribution for a cold wall case indicate the importance of including temperature gradient effects. Grid requirements for accurate turbulent heating predictions are also studied. These results indicate that a cell Reynolds number of 1 is required for grid converged heating predictions, but coarser grids with a y(sup +) less than 2 are adequate for design of hypersonic vehicles. Based on the results of this study, it is recommended that the local damping formulation be used with the Baldwin-Lomax and Cebeci-Smith turbulence models in design and analysis of Hyper-X and future hypersonic vehicles.

Formulation and method for preparing gels comprising hydrous hafnium oxide

DOEpatents

Collins, Jack L; Hunt, Rodney D; Montgomery, Frederick C

2013-08-06

Formulations useful for preparing hydrous hafnium oxide gels contain a metal salt including hafnium, an acid, an organic base, and a complexing agent. Methods for preparing gels containing hydrous hafnium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including hafnium, an acid, an organic base, and a complexing agent.

Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia.

PubMed

Obradovic, M; Mrhar, A; Kos, M

2007-12-01

The aim of the present analysis was to evaluate the cost-effectiveness of alternative treatments for outpatients with chronic schizophrenia from the healthcare payer's perspective. Decision analysis was used to evaluate the cost-effectiveness of the following antipsychotic drugs: amisulpride, aripiprazole, haloperidol (oral formulation), haloperidol (depot formulation), olanzapine, quetiapine, risperidone (oral formulation), risperidone (depot formulation) and ziprazidone. Clinical and economic outcomes were modelled over 1-year time horizon. Effectiveness was measured as a percentage of patients in remission. Clinical parameters used in the model included compliance rates, rehospitalisation rates for compliant and non-compliant patients, duration and frequency of hospitalisation, and adverse event rates. One-way sensitivity analysis was performed to test the robustness of the model. The most effective treatment was treatment with olanzapine where 64.1% of patients remained in remission. The least effective treatment was treatment with quetiapine where 32.7% of patients remained in remission. Overall costs ranged from 3,726.78 Euro for haloperidol to 8,157.03 Euro for risperidone in depot formulation. Inpatient costs represented the major part of costs for most of antipsychotic drugs. Typical antipsychotic drugs had substantially smaller outpatient costs (6.5%) compared with atypical antipsychotics (37.9%). In the base case scenario the non-dominated treatment strategies were haloperidol, haloperidol decanoate and olanzapine. Additionally, risperidone can also be considered to be part of the efficient frontier based on the sensitivity analysis results. Among second-generation antipsychotics, which have a better safety profile than first-generation antipsychotics, olanzapine and risperidone showed to be the most cost-effective treatment strategies for outpatient treatment of chronic schizophrenia.

Space-time variation of respiratory cancers in South Carolina: a flexible multivariate mixture modeling approach to risk estimation.

PubMed

Carroll, Rachel; Lawson, Andrew B; Kirby, Russell S; Faes, Christel; Aregay, Mehreteab; Watjou, Kevin

2017-01-01

Many types of cancer have an underlying spatiotemporal distribution. Spatiotemporal mixture modeling can offer a flexible approach to risk estimation via the inclusion of latent variables. In this article, we examine the application and benefits of using four different spatiotemporal mixture modeling methods in the modeling of cancer of the lung and bronchus as well as "other" respiratory cancer incidences in the state of South Carolina. Of the methods tested, no single method outperforms the other methods; which method is best depends on the cancer under consideration. The lung and bronchus cancer incidence outcome is best described by the univariate modeling formulation, whereas the "other" respiratory cancer incidence outcome is best described by the multivariate modeling formulation. Spatiotemporal multivariate mixture methods can aid in the modeling of cancers with small and sparse incidences when including information from a related, more common type of cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

A Practical Framework Toward Prediction of Breaking Force and Disintegration of Tablet Formulations Using Machine Learning Tools.

PubMed

Akseli, Ilgaz; Xie, Jingjin; Schultz, Leon; Ladyzhynsky, Nadia; Bramante, Tommasina; He, Xiaorong; Deanne, Rich; Horspool, Keith R; Schwabe, Robert

2017-01-01

Enabling the paradigm of quality by design requires the ability to quantitatively correlate material properties and process variables to measureable product performance attributes. Conventional, quality-by-test methods for determining tablet breaking force and disintegration time usually involve destructive tests, which consume significant amount of time and labor and provide limited information. Recent advances in material characterization, statistical analysis, and machine learning have provided multiple tools that have the potential to develop nondestructive, fast, and accurate approaches in drug product development. In this work, a methodology to predict the breaking force and disintegration time of tablet formulations using nondestructive ultrasonics and machine learning tools was developed. The input variables to the model include intrinsic properties of formulation and extrinsic process variables influencing the tablet during manufacturing. The model has been applied to predict breaking force and disintegration time using small quantities of active pharmaceutical ingredient and prototype formulation designs. The novel approach presented is a step forward toward rational design of a robust drug product based on insight into the performance of common materials during formulation and process development. It may also help expedite drug product development timeline and reduce active pharmaceutical ingredient usage while improving efficiency of the overall process. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of Different Flours on the Formation of Hydroxymethylfurfural, Furfural, and Dicarbonyl Compounds in Heated Glucose/Flour Systems

PubMed Central

Mesías, Marta; Morales, Francisco J.

2017-01-01

Traditional cereal-based foods usually include wheat flour in their formulations; however, the search for new products with new ingredients providing different properties to foods is widely pursued by food companies. Replacement of wheat by other flours can modify both nutritional properties and organoleptic characteristics of the final baked food, but can also impact the formation of potentially harmful compounds. The effect of the type of flour on the formation of furfurals and dicarbonyl compounds was studied in a dough model system during baking that contains water or glucose in order to promote the Maillard reaction and caramelization. The formation of methylglyoxal and glyoxal was significantly reduced in spelt and teff formulations compared to wheat flour formulations, respectively. In contrast, samples formulated with oat, teff, and rye showed a significant increase in the levels of 3-deoxyglucosone. Similarly, spelt and teff formulations presented significantly higher concentrations of hydroxymethylfurfural, and spelt, teff, and rye presented higher concentrations of furfural. Therefore, the formation of process contaminants and undesirable compounds in new food products formulated with different flours replacing the traditional wheat flour should be considered carefully in terms of food safety. PMID:28231092

Effect of Different Flours on the Formation of Hydroxymethylfurfural, Furfural, and Dicarbonyl Compounds in Heated Glucose/Flour Systems.

PubMed

Mesías, Marta; Morales, Francisco J

2017-02-16

Traditional cereal-based foods usually include wheat flour in their formulations; however, the search for new products with new ingredients providing different properties to foods is widely pursued by food companies. Replacement of wheat by other flours can modify both nutritional properties and organoleptic characteristics of the final baked food, but can also impact the formation of potentially harmful compounds. The effect of the type of flour on the formation of furfurals and dicarbonyl compounds was studied in a dough model system during baking that contains water or glucose in order to promote the Maillard reaction and caramelization. The formation of methylglyoxal and glyoxal was significantly reduced in spelt and teff formulations compared to wheat flour formulations, respectively. In contrast, samples formulated with oat, teff, and rye showed a significant increase in the levels of 3-deoxyglucosone. Similarly, spelt and teff formulations presented significantly higher concentrations of hydroxymethylfurfural, and spelt, teff, and rye presented higher concentrations of furfural. Therefore, the formation of process contaminants and undesirable compounds in new food products formulated with different flours replacing the traditional wheat flour should be considered carefully in terms of food safety.

Efficient extraction of vaccines formulated in aluminum hydroxide gel by including surfactants in the extraction buffer

PubMed Central

Zhu, Daming; Huang, Shuhui; McClellan, Holly; Dai, Weili; Syed, Najam R; Gebregeorgis, Elizabeth; Mullen, Gregory E. D.; Long, Carole; Martin, Laura B.; Narum, David; Duffy, Patrick; Miller, Louis H.; Saul, Allan

2011-01-01

Efficient antigen extraction from vaccines formulated on aluminum hydroxide gels is a critical step for the evaluation of the quality of vaccines following formulation. It has been shown in our laboratory that the efficiency of antigen extraction from vaccines formulated on Alhydrogel decreased significantly with increased storage time. To increase antigen extraction efficiency, the present study determined the effect of surfactants on antigen recovery from vaccine formulations. The Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated on Alhydrogel and stored at 2-8 °C for three years was used as a model in this study. The AMA1 on Alhydrogel was extracted in the presence or absence of 30 mM sodium dodecyl sulfate (SDS) or 20 mM cetylpyridinium chloride in the extraction buffer (0.60 M citrate, 0.55 M phosphate, pH 8.5) using our standard antigen extraction protocols. Extracted AMA1 antigen was analyzed by 4-20% Tris-glycine SDS-PAGE followed by silver staining or western blotting. The results showed that inclusion of SDS or cetylpyridinium chloride in extraction buffer increased the antigen recovery dramatically and can be used for efficient characterization of Alhydrogel vaccines. PMID:22107848

Enhancement of oral bioavailability of atorvastatin calcium by self-emulsifying drug delivery systems (SEDDS).

PubMed

Kadu, Pawan J; Kushare, Sachin S; Thacker, Dhaval D; Gattani, Surendra G

2011-02-01

The aim of the present study was to formulate a self-emulsifying drug delivery system of atorvastatin calcium and its characterization including in vitro and in vivo potential. The solubility of atorvastatin calcium was determined in various vehicles such as Captex 355, Captex 355 EP/NF, Ethyl oleate, Capmul MCM, Capmul PG-8, Gelucire 44/14, Tween 80, Tween 20, and PEG 400. Pseudoternary phase diagrams were plotted on the basis of solubility data of drug in various components to evaluate the microemulsification region. Formulation development and screening was carried out based on results obtained from phase diagrams and characteristics of resultant microemulsion. Prepared formulations were tested for microemulsifying properties and evaluated for clarity, precipitation, viscosity determination, drug content and in vitro dissolution. The optimized formulation further evaluated for particle size distribution, zeta potential, stability studies and in vivo potential. In vivo performance of the optimized formulation was evaluated using a Triton-induced hypercholesterolemia model in male Albino Wistar rats. The formulation significantly reduced serum lipid levels as compared with atorvastatin calcium. Thus studies illustrated the potential use for the delivery of hydrophobic drug such as atorvastatin calcium by oral route.

Spray combustion model improvement study, 1

NASA Technical Reports Server (NTRS)

Chen, C. P.; Kim, Y. M.; Shang, H. M.

1993-01-01

This study involves the development of numerical and physical modeling in spray combustion. These modeling efforts are mainly motivated to improve the physical submodels of turbulence, combustion, atomization, dense spray effects, and group vaporization. The present mathematical formulation can be easily implemented in any time-marching multiple pressure correction methodologies such as MAST code. A sequence of validation cases includes the nonevaporating, evaporating and_burnin dense_sprays.

Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept

PubMed Central

Bolduc, David L.; Villa, Vilmar; Sandgren, David J.; Ledney, G. David; Blakely, William F.; Bünger, Rolf

2014-01-01

Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS) injury (i.e., response category three or RC3) in a rhesus monkey total-body irradiation (TBI) model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0) and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP) (Macaca mulatta) given 6.5-Gy 60Co Υ-rays (0.4 Gy min−1) TBI. A correlation matrix was formulated with the RC3 severity level designated as the “dependent variable” and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets) in formulating the “CBC” RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry “CBC-SCHEM” RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness. PMID:25165485

Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

PubMed Central

Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

2013-01-01

Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated “free” drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. PMID:23769419

A hybrid formulation for the numerical simulation of condensed phase explosives

NASA Astrophysics Data System (ADS)

Michael, L.; Nikiforakis, N.

2016-07-01

In this article we present a new formulation and an associated numerical algorithm, for the simulation of combustion and transition to detonation of condensed-phase commercial- and military-grade explosives, which are confined by (or in general interacting with one or more) compliant inert materials. Examples include confined rate-stick problems and interaction of shock waves with gas cavities or solid particles in explosives. This formulation is based on an augmented Euler approach to account for the mixture of the explosive and its products, and a multi-phase diffuse interface approach to solve for the immiscible interaction between the mixture and the inert materials, so it is in essence a hybrid (augmented Euler and multi-phase) model. As such, it has many of the desirable features of the two approaches and, critically for our applications of interest, it provides the accurate recovery of temperature fields across all components. Moreover, it conveys a lot more physical information than augmented Euler, without the complexity of full multi-phase Baer-Nunziato-type models or the lack of robustness of augmented Euler models in the presence of more than two components. The model can sustain large density differences across material interfaces without the presence of spurious oscillations in velocity and pressure, and it can accommodate realistic equations of state and arbitrary (pressure- or temperature-based) reaction-rate laws. Under certain conditions, we show that the formulation reduces to well-known augmented Euler or multi-phase models, which have been extensively validated and used in practice. The full hybrid model and its reduced forms are validated against problems with exact (or independently-verified numerical) solutions and evaluated for robustness for rate-stick and shock-induced cavity collapse case-studies.

A New Formulation for Hybrid LES-RANS Computations

NASA Technical Reports Server (NTRS)

Woodruff, Stephen L.

2013-01-01

Ideally, a hybrid LES-RANS computation would employ LES only where necessary to make up for the failure of the RANS model to provide sufficient accuracy or to provide time-dependent information. Current approaches are fairly restrictive in the placement of LES and RANS regions; an LES-RANS transition in a boundary layer, for example, yields an unphysical log-layer shift. A hybrid computation is formulated here to allow greater control over the placement of LES and RANS regions and the transitions between them. The concept of model invariance is introduced, which provides a basis for interpreting hybrid results within an LES-RANS transition zone. Consequences of imposing model invariance include the addition of terms to the governing equations that compensate for unphysical gradients created as the model changes between RANS and LES. Computational results illustrate the increased accuracy of the approach and its insensitivity to the location of the transition and to the blending function employed.

Modeling Day-to-day Flow Dynamics on Degradable Transport Network

PubMed Central

Gao, Bo; Zhang, Ronghui; Lou, Xiaoming

2016-01-01

Stochastic link capacity degradations are common phenomena in transport network which can cause travel time variations and further can affect travelers’ daily route choice behaviors. This paper formulates a deterministic dynamic model, to capture the day-to-day (DTD) flow evolution process in the presence of degraded link capacity degradations. The aggregated network flow dynamics are driven by travelers’ study of uncertain travel time and their choice of risky routes. This paper applies the exponential-smoothing filter to describe travelers’ study of travel time variations, and meanwhile formulates risk attitude parameter updating equation to reflect travelers’ endogenous risk attitude evolution schema. In addition, this paper conducts theoretical analyses to investigate several significant mathematical characteristics implied in the proposed DTD model, including fixed point existence, uniqueness, stability and irreversibility. Numerical experiments are used to demonstrate the effectiveness of the DTD model and verify some important dynamic system properties. PMID:27959903

Tunneling-assisted transport of carriers through heterojunctions.

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

Wampler, William R.; Myers, Samuel M.; Modine, Normand A.

The formulation of carrier transport through heterojunctions by tunneling and thermionic emission is derived from first principles. The treatment of tunneling is discussed at three levels of approximation: numerical solution of the one-band envelope equation for an arbitrarily specified potential profile; the WKB approximation for an arbitrary potential; and, an analytic formulation assuming constant internal field. The effects of spatially varying carrier chemical potentials over tunneling distances are included. Illustrative computational results are presented. The described approach is used in exploratory physics models of irradiated heterojunction bipolar transistors within Sandia's QASPR program.

An Advanced Multiple Alternatives Modeling Formulation for Determining Graduated Fiscal Support Strategies for Operational and Planned Educational Programs.

ERIC Educational Resources Information Center

Wholeben, Brent Edward

A rationale is presented for viewing the decision-making process inherent in determining budget reductions for educational programs as most effectively modeled by a graduated funding approach. The major tenets of the graduated budget reduction approach to educational fiscal policy include the development of multiple alternative reduction plans, or…

Comparative studies of binding potential of Prunus armeniaca and Prunus domestica gums in tablets formulations.

PubMed

Rahim, Haroon; Khan, Mir Azam; Sadiq, Abdul; Khan, Shahzeb; Chishti, Kamran Ahmad; Rahman, Inayat U

2015-05-01

The current study was undertaken to compare the binding potential of Prunus armeniaca L. and Prunus domestica L. gums in tablets' formulations. Tablet batches (F-1 to F-9) were prepared Diclofenac sodium as model drug using 5%, 7.5% and 10% of each Prunus armeniaca L., Prunus domestica L. gums as binder. PVP K30 was used as a standard binder. Magnesium stearate was used as lubricant. Flow properties of granules (like bulk density, tapped density, Carr's index, Hausner's ratio, angle of repose) as well as the physical parameters of compressed tablets including hardness, friability, thickness and disintegration time were determined. Flow parameters of granules of all the batches were found good. Physical parameters (drug content, weight variation, thickness, hardness, friability, disintegration time) of formulated tablets were found within limit when tested. The dissolution studies showed that tablets formulations containing each Prunus domestica showed better binding capacity compared to Prunus armeniaca gum. The binding potential increased as the concentration of gums increased. The FTIR spectroscopic investigation showed that the formulations containing plant gum are compatible with the drug and other excipients used.

Flight Dynamics of Flexible Aircraft with Aeroelastic and Inertial Force Interactions

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Tuzcu, Ilhan

2009-01-01

This paper presents an integrated flight dynamic modeling method for flexible aircraft that captures coupled physics effects due to inertial forces, aeroelasticity, and propulsive forces that are normally present in flight. The present approach formulates the coupled flight dynamics using a structural dynamic modeling method that describes the elasticity of a flexible, twisted, swept wing using an equivalent beam-rod model. The structural dynamic model allows for three types of wing elastic motion: flapwise bending, chordwise bending, and torsion. Inertial force coupling with the wing elasticity is formulated to account for aircraft acceleration. The structural deflections create an effective aeroelastic angle of attack that affects the rigid-body motion of flexible aircraft. The aeroelastic effect contributes to aerodynamic damping forces that can influence aerodynamic stability. For wing-mounted engines, wing flexibility can cause the propulsive forces and moments to couple with the wing elastic motion. The integrated flight dynamics for a flexible aircraft are formulated by including generalized coordinate variables associated with the aeroelastic-propulsive forces and moments in the standard state-space form for six degree-of-freedom flight dynamics. A computational structural model for a generic transport aircraft has been created. The eigenvalue analysis is performed to compute aeroelastic frequencies and aerodynamic damping. The results will be used to construct an integrated flight dynamic model of a flexible generic transport aircraft.

High-throughput screening and stability optimization of anti-streptavidin IgG1 and IgG2 formulations.

PubMed

Alekseychyk, Larysa; Su, Cheng; Becker, Gerald W; Treuheit, Michael J; Razinkov, Vladimir I

2014-10-01

Selection of a suitable formulation that provides adequate product stability is an important aspect of the development of biopharmaceutical products. Stability of proteins includes not only resistance to chemical modifications but also conformational and colloidal stabilities. While chemical degradation of antibodies is relatively easy to detect and control, propensity for conformational changes and/or aggregation during manufacturing or long-term storage is difficult to predict. In many cases, the formulation factors that increase one type of stability may significantly decrease another type under the same or different conditions. Often compromise is necessary to minimize the adverse effects of an antibody formulation by careful optimization of multiple factors responsible for overall stability. In this study, high-throughput stress and characterization techniques were applied to 96 formulations of anti-streptavidin antibodies (an IgG1 and an IgG2) to choose optimal formulations. Stress and analytical methods applied in this study were 96-well plate based using an automated liquid handling system to prepare the different formulations and sample plates. Aggregation and clipping propensity were evaluated by temperature and mechanical stresses. Multivariate regression analysis of high-throughput data was performed to find statistically significant formulation factors that alter measured parameters such as monomer percentage or unfolding temperature. The results of the regression models were used to maximize the stabilities of antibodies under different formulations and to find the optimal formulation space for each molecule. Comparison of the IgG1 and IgG2 data indicated an overall greater stability of the IgG1 molecule under the conditions studied. The described method can easily be applied to both initial preformulation screening and late-stage formulation development of biopharmaceutical products. © 2014 Society for Laboratory Automation and Screening.

The Martian dust cycle: A proposed model

NASA Technical Reports Server (NTRS)

Greeley, Ronald

1987-01-01

Despite more than a decade of study of martian dust storms, many of their characteristics and associated processes remain enigmatic, including the mechanisms for dust raising, modes of settling, and the nature of dust deposits. However, observations of Mars dust, considerations of terrestrial analogs, theoretical models, and laboratory simulations permit the formulation of a Martian Dust Cycle Model, which consists of three main processes: (1) suspension threshold, (2) transportation, and (3) deposition; two associated processes are also included: (4) dust removal and (5) the addition of new dust to the cycle. Although definitions vary, dust includes particles less than 4 to approx. 60 microns in diameter, which by terrestrial usage includes silt, loess, clay, and aerosolic dust particles. The dust cycle model is explained.

Enhanced model of gear transmission dynamics for condition monitoring applications: Effects of torque, friction and bearing clearance

NASA Astrophysics Data System (ADS)

Fernandez-del-Rincon, A.; Garcia, P.; Diez-Ibarbia, A.; de-Juan, A.; Iglesias, M.; Viadero, F.

2017-02-01

Gear transmissions remain as one of the most complex mechanical systems from the point of view of noise and vibration behavior. Research on gear modeling leading to the obtaining of models capable of accurately reproduce the dynamic behavior of real gear transmissions has spread out the last decades. Most of these models, although useful for design stages, often include simplifications that impede their application for condition monitoring purposes. Trying to filling this gap, the model presented in this paper allows us to simulate gear transmission dynamics including most of these features usually neglected by the state of the art models. This work presents a model capable of considering simultaneously the internal excitations due to the variable meshing stiffness (including the coupling among successive tooth pairs in contact, the non-linearity linked with the contacts between surfaces and the dissipative effects), and those excitations consequence of the bearing variable compliance (including clearances or pre-loads). The model can also simulate gear dynamics in a realistic torque dependent scenario. The proposed model combines a hybrid formulation for calculation of meshing forces with a non-linear variable compliance approach for bearings. Meshing forces are obtained by means of a double approach which combines numerical and analytical aspects. The methodology used provides a detailed description of the meshing forces, allowing their calculation even when gear center distance is modified due to shaft and bearing flexibilities, which are unavoidable in real transmissions. On the other hand, forces at bearing level were obtained considering a variable number of supporting rolling elements, depending on the applied load and clearances. Both formulations have been developed and applied to the simulation of the vibration of a sample transmission, focusing the attention on the transmitted load, friction meshing forces and bearing preloads.

Affine group formulation of the Standard Model coupled to gravity

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

Chou, Ching-Yi, E-mail: l2897107@mail.ncku.edu.tw; Ita, Eyo, E-mail: ita@usna.edu; Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw

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 themore » 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.« less

Constitutive Modeling of the Facesheet to Core Interface in Honeycomb Sandwich Panels Subject to Mode I Delamination

NASA Technical Reports Server (NTRS)

Hoewer, Daniel; Lerch, Bradley A.; Bednarcyk, Brett A.; Pineda, Evan Jorge; Reese, Stefanie; Simon, Jaan-Willem

2017-01-01

A new cohesive zone traction-separation law, which includes the effects of fiber bridging, has been developed, implemented with a finite element (FE) model, and applied to simulate the delamination between the facesheet and core of a composite honeycomb sandwich panel. The proposed traction-separation law includes a standard initial cohesive component, which accounts for the initial interfacial stiffness and energy release rate, along with a new component to account for the fiber bridging contribution to the delamination process. Single cantilever beam tests on aluminum honeycomb sandwich panels with carbon fiber reinforced polymer facesheets were used to characterize and evaluate the new formulation and its finite element implementation. These tests, designed to evaluate the mode I toughness of the facesheet to core interface, exhibited significant fiber bridging and large crack process zones, giving rise to a concave downward concave upward pre-peak shape in the load-displacement curve. Unlike standard cohesive formulations, the proposed formulation captures this observed shape, and its results have been shown to be in excellent quantitative agreement with experimental load-displacement and apparent critical energy release rate results, representative of a payload fairing structure, as well as local strain fields measured with digital image correlation.

A Source-Term Based Boundary Layer Bleed/Effusion Model for Passive Shock Control

NASA Technical Reports Server (NTRS)

Baurle, Robert A.; Norris, Andrew T.

2011-01-01

A modeling framework for boundary layer effusion has been developed based on the use of source (or sink) terms instead of the usual practice of specifying bleed directly as a boundary condition. This framework allows the surface boundary condition (i.e. isothermal wall, adiabatic wall, slip wall, etc.) to remain unaltered in the presence of bleed. This approach also lends itself to easily permit the addition of empirical models for second order effects that are not easily accounted for by simply defining effective transpiration values. Two effusion models formulated for supersonic flows have been implemented into this framework; the Doerffer/Bohning law and the Slater formulation. These models were applied to unit problems that contain key aspects of the flow physics applicable to bleed systems designed for hypersonic air-breathing propulsion systems. The ability of each model to predict bulk bleed properties was assessed, as well as the response of the boundary layer as it passes through and downstream of a porous bleed system. The model assessment was performed with and without the presence of shock waves. Three-dimensional CFD simulations that included the geometric details of the porous plate bleed systems were also carried out to supplement the experimental data, and provide additional insights into the bleed flow physics. Overall, both bleed formulations fared well for the tests performed in this study. However, the sample of test problems considered in this effort was not large enough to permit a comprehensive validation of the models.

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.

Multidisciplinary Optimization of Tilt Rotor Blades Using Comprehensive Composite Modeling Technique

NASA Technical Reports Server (NTRS)

Chattopadhyay, Aditi; McCarthy, Thomas R.; Rajadas, John N.

1997-01-01

An optimization procedure is developed for addressing the design of composite tilt rotor blades. A comprehensive technique, based on a higher-order laminate theory, is developed for the analysis of the thick composite load-carrying sections, modeled as box beams, in the blade. The theory, which is based on a refined displacement field, is a three-dimensional model which approximates the elasticity solution so that the beam cross-sectional properties are not reduced to one-dimensional beam parameters. Both inplane and out-of-plane warping are included automatically in the formulation. The model can accurately capture the transverse shear stresses through the thickness of each wall while satisfying stress free boundary conditions on the inner and outer surfaces of the beam. The aerodynamic loads on the blade are calculated using the classical blade element momentum theory. Analytical expressions for the lift and drag are obtained based on the blade planform with corrections for the high lift capability of rotor blades. The aerodynamic analysis is coupled with the structural model to formulate the complete coupled equations of motion for aeroelastic analyses. Finally, a multidisciplinary optimization procedure is developed to improve the aerodynamic, structural and aeroelastic performance of the tilt rotor aircraft. The objective functions include the figure of merit in hover and the high speed cruise propulsive efficiency. Structural, aerodynamic and aeroelastic stability criteria are imposed as constraints on the problem. The Kreisselmeier-Steinhauser function is used to formulate the multiobjective function problem. The search direction is determined by the Broyden-Fletcher-Goldfarb-Shanno algorithm. The optimum results are compared with the baseline values and show significant improvements in the overall performance of the tilt rotor blade.

Improvements and validation of the erythropoiesis control model for bed rest simulation

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1977-01-01

The most significant improvement in the model is the explicit formulation of separate elements representing erythropoietin production and red cell production. Other modifications include bone marrow time-delays, capability to shift oxyhemoglobin affinity and an algorithm for entering experimental data as time-varying driving functions. An area of model development is suggested by applying the model to simulating onset, diagnosis and treatment of a hematologic disorder. Recommendations for further improvements in the model and suggestions for experimental application are also discussed. A detailed analysis of the hematologic response to bed rest including simulation of the recent Baylor Medical College bed rest studies is also presented.

Neyman, Markov processes and survival analysis.

PubMed

Yang, Grace

2013-07-01

J. Neyman used stochastic processes extensively in his applied work. One example is the Fix and Neyman (F-N) competing risks model (1951) that uses finite homogeneous Markov processes to analyse clinical trials with breast cancer patients. We revisit the F-N model, and compare it with the Kaplan-Meier (K-M) formulation for right censored data. The comparison offers a way to generalize the K-M formulation to include risks of recovery and relapses in the calculation of a patient's survival probability. The generalization is to extend the F-N model to a nonhomogeneous Markov process. Closed-form solutions of the survival probability are available in special cases of the nonhomogeneous processes, like the popular multiple decrement model (including the K-M model) and Chiang's staging model, but these models do not consider recovery and relapses while the F-N model does. An analysis of sero-epidemiology current status data with recurrent events is illustrated. Fix and Neyman used Neyman's RBAN (regular best asymptotic normal) estimates for the risks, and provided a numerical example showing the importance of considering both the survival probability and the length of time of a patient living a normal life in the evaluation of clinical trials. The said extension would result in a complicated model and it is unlikely to find analytical closed-form solutions for survival analysis. With ever increasing computing power, numerical methods offer a viable way of investigating the problem.

Discrete-time moment closure models for epidemic spreading in populations of interacting individuals.

PubMed

Frasca, Mattia; Sharkey, Kieran J

2016-06-21

Understanding the dynamics of spread of infectious diseases between individuals is essential for forecasting the evolution of an epidemic outbreak or for defining intervention policies. The problem is addressed by many approaches including stochastic and deterministic models formulated at diverse scales (individuals, populations) and different levels of detail. Here we consider discrete-time SIR (susceptible-infectious-removed) dynamics propagated on contact networks. We derive a novel set of 'discrete-time moment equations' for the probability of the system states at the level of individual nodes and pairs of nodes. These equations form a set which we close by introducing appropriate approximations of the joint probabilities appearing in them. For the example case of SIR processes, we formulate two types of model, one assuming statistical independence at the level of individuals and one at the level of pairs. From the pair-based model we then derive a model at the level of the population which captures the behavior of epidemics on homogeneous random networks. With respect to their continuous-time counterparts, the models include a larger number of possible transitions from one state to another and joint probabilities with a larger number of individuals. The approach is validated through numerical simulation over different network topologies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Wind Power Ramping Product for Increasing Power System Flexibility

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

Cui, Mingjian; Zhang, Jie; Wu, Hongyu

With increasing penetrations of wind power, system operators are concerned about a potential lack of system flexibility and ramping capacity in real-time dispatch stages. In this paper, a modified dispatch formulation is proposed considering the wind power ramping product (WPRP). A swinging door algorithm (SDA) and dynamic programming are combined and used to detect WPRPs in the next scheduling periods. The detected WPRPs are included in the unit commitment (UC) formulation considering ramping capacity limits, active power limits, and flexible ramping requirements. The modified formulation is solved by mixed integer linear programming. Numerical simulations on a modified PJM 5-bus Systemmore » show the effectiveness of the model considering WPRP, which not only reduces the production cost but also does not affect the generation schedules of thermal units.« less

Computational methods in the prediction of advanced subsonic and supersonic propeller induced noise: ASSPIN users' manual

NASA Technical Reports Server (NTRS)

Dunn, M. H.; Tarkenton, G. M.

1992-01-01

This document describes the computational aspects of propeller noise prediction in the time domain and the use of high speed propeller noise prediction program ASSPIN (Advanced Subsonic and Supersonic Propeller Induced Noise). These formulations are valid in both the near and far fields. Two formulations are utilized by ASSPIN: (1) one is used for subsonic portions of the propeller blade; and (2) the second is used for transonic and supersonic regions on the blade. Switching between the two formulations is done automatically. ASSPIN incorporates advanced blade geometry and surface pressure modelling, adaptive observer time grid strategies, and contains enhanced numerical algorithms that result in reduced computational time. In addition, the ability to treat the nonaxial inflow case has been included.

On the Vertical Distribution of Local and Remote Sources of Water for Precipitation

NASA Technical Reports Server (NTRS)

Bosilovich, Michael G.

2001-01-01

The vertical distribution of local and remote sources of water for precipitation and total column water over the United States are evaluated in a general circulation model simulation. The Goddard Earth Observing System (GEOS) general circulation model (GCM) includes passive constituent tracers to determine the geographical sources of the water in the column. Results show that the local percentage of precipitable water and local percentage of precipitation can be very different. The transport of water vapor from remote oceanic sources at mid and upper levels is important to the total water in the column over the central United States, while the access of locally evaporated water in convective precipitation processes is important to the local precipitation ratio. This result resembles the conceptual formulation of the convective parameterization. However, the formulations of simple models of precipitation recycling include the assumption that the ratio of the local water in the column is equal to the ratio of the local precipitation. The present results demonstrate the uncertainty in that assumption, as locally evaporated water is more concentrated near the surface.

Study of Gaussian Doped Double Gate JunctionLess (GD-DG-JL) transistor including source drain depletion length: Model for sub-threshold behavior

NASA Astrophysics Data System (ADS)

Kumari, Vandana; Kumar, Ayush; Saxena, Manoj; Gupta, Mridula

2018-01-01

The sub-threshold model formulation of Gaussian Doped Double Gate JunctionLess (GD-DG-JL) FET including source/drain depletion length is reported in the present work under the assumption that the ungated regions are fully depleted. To provide deeper insight into the device performance, the impact of gaussian straggle, channel length, oxide and channel thickness and high-k gate dielectric has been studied using extensive TCAD device simulation.

Mathematical Modeling of Diverse Phenomena

NASA Technical Reports Server (NTRS)

Howard, J. C.

1979-01-01

Tensor calculus is applied to the formulation of mathematical models of diverse phenomena. Aeronautics, fluid dynamics, and cosmology are among the areas of application. The feasibility of combining tensor methods and computer capability to formulate problems is demonstrated. The techniques described are an attempt to simplify the formulation of mathematical models by reducing the modeling process to a series of routine operations, which can be performed either manually or by computer.

Program Evaluation: A Review and Synthesis.

ERIC Educational Resources Information Center

Webber, Charles F.

This paper reviews models of program evaluation. Major topics and issues found in the evaluation literature include quantitative versus qualitative approaches, identification and involvement of stakeholders, formulation of research questions, collection of data, analysis and interpretation of data, reporting of results, evaluation utilization, and…

Flocking and Turning: a New Model for Self-organized Collective Motion

NASA Astrophysics Data System (ADS)

Cavagna, Andrea; Del Castello, Lorenzo; Giardina, Irene; Grigera, Tomas; Jelic, Asja; Melillo, Stefania; Mora, Thierry; Parisi, Leonardo; Silvestri, Edmondo; Viale, Massimiliano; Walczak, Aleksandra M.

2015-02-01

Birds in a flock move in a correlated way, resulting in large polarization of velocities. A good understanding of this collective behavior exists for linear motion of the flock. Yet observing actual birds, the center of mass of the group often turns giving rise to more complicated dynamics, still keeping strong polarization of the flock. Here we propose novel dynamical equations for the collective motion of polarized animal groups that account for correlated turning including solely social forces. We exploit rotational symmetries and conservation laws of the problem to formulate a theory in terms of generalized coordinates of motion for the velocity directions akin to a Hamiltonian formulation for rotations. We explicitly derive the correspondence between this formulation and the dynamics of the individual velocities, thus obtaining a new model of collective motion. In the appropriate overdamped limit we recover the well-known Vicsek model, which dissipates rotational information and does not allow for polarized turns. Although the new model has its most vivid success in describing turning groups, its dynamics is intrinsically different from previous ones in a wide dynamical regime, while reducing to the hydrodynamic description of Toner and Tu at very large length-scales. The derived framework is therefore general and it may describe the collective motion of any strongly polarized active matter system.

A Three-Dimensional Finite-Element Model for Simulating Water Flow in Variably Saturated Porous Media

NASA Astrophysics Data System (ADS)

Huyakorn, Peter S.; Springer, Everett P.; Guvanasen, Varut; Wadsworth, Terry D.

1986-12-01

A three-dimensional finite-element model for simulating water flow in variably saturated porous media is presented. The model formulation is general and capable of accommodating complex boundary conditions associated with seepage faces and infiltration or evaporation on the soil surface. Included in this formulation is an improved Picard algorithm designed to cope with severely nonlinear soil moisture relations. The algorithm is formulated for both rectangular and triangular prism elements. The element matrices are evaluated using an "influence coefficient" technique that avoids costly numerical integration. Spatial discretization of a three-dimensional region is performed using a vertical slicing approach designed to accommodate complex geometry with irregular boundaries, layering, and/or lateral discontinuities. Matrix solution is achieved using a slice successive overrelaxation scheme that permits a fairly large number of nodal unknowns (on the order of several thousand) to be handled efficiently on small minicomputers. Six examples are presented to verify and demonstrate the utility of the proposed finite-element model. The first four examples concern one- and two-dimensional flow problems used as sample problems to benchmark the code. The remaining examples concern three-dimensional problems. These problems are used to illustrate the performance of the proposed algorithm in three-dimensional situations involving seepage faces and anisotropic soil media.

How does variation in rainfall affect simulated tropical tree mortality, functional diversity and coexistence?

NASA Astrophysics Data System (ADS)

Powell, T.; Kueppers, L. M.; Koven, C.; Johnson, D. J.; Faybishenko, B.; McDowell, N. G.; Chambers, J. Q.

2016-12-01

Land surface models that include demographic and plant hydrodynamic processes are promising tools for characterizing how different drought scenarios may affect carbon cycling of tropical forests. The Ecosystem Demography (ED2) model, now formulated with such features, was used to evaluate how different drought scenarios affect mortality patterns, functional diversity and coexistence of four plant functional types (PFTs) of tropical trees at Barro Colorado Island (BCI), Panama. The four PFTs simulated were early- versus late-successional groups subdivided into drought-tolerant versus -intolerant groups. The hydrodynamic formulation enables the four PFTs to compete mechanistically along two largely orthogonal resource gradients of water and light. The model simulations produced considerable differences in the aboveground biomass response to contrasting drying scenarios that included longer dry seasons, El Nino related droughts, and drier dry seasons. The emergent mortality dynamics reflect the physiological trade-off between water-use and carbon fixation formulated by the hydrodynamic regulation over stomatal conductance. During dry periods, the model predicts increased mortality rates of pioneer trees compared to generalists and drought-intolerant trees compared to -tolerant trees. The model also predicts that surviving cohorts in the smallest size classes of drought-intolerant trees are occasionally primed for release from competition following acute droughts. Observations at BCI showed increased mortality rates for large trees (i.e. >30 cm dbh) during the 1982 El Nino drought, but not subsequent El Nino related droughts. The causes of the elevated mortality rates are explored with the model. Coexistence of four plant functional types in the model is highly sensitive to the parameterization of stem hydraulic conductivity; but, surprisingly not very sensitive to shifts in rainfall patterns. These results demonstrate (a) that plant hydrodynamics are critical for simulating dynamic mortality patterns between drought-tolerant and -intolerant PFTs in order to increase representation of functional diversity in land surface models, and (b) that more demographic, plant hydraulic and deeper soil moisture observations are required to constrain hydrodynamic parameter selection.

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Using spatiotemporal statistical models to estimate animal abundance and infer ecological dynamics from survey counts

USGS Publications Warehouse

Conn, Paul B.; Johnson, Devin S.; Ver Hoef, Jay M.; Hooten, Mevin B.; London, Joshua M.; Boveng, Peter L.

2015-01-01

Ecologists often fit models to survey data to estimate and explain variation in animal abundance. Such models typically require that animal density remains constant across the landscape where sampling is being conducted, a potentially problematic assumption for animals inhabiting dynamic landscapes or otherwise exhibiting considerable spatiotemporal variation in density. We review several concepts from the burgeoning literature on spatiotemporal statistical models, including the nature of the temporal structure (i.e., descriptive or dynamical) and strategies for dimension reduction to promote computational tractability. We also review several features as they specifically relate to abundance estimation, including boundary conditions, population closure, choice of link function, and extrapolation of predicted relationships to unsampled areas. We then compare a suite of novel and existing spatiotemporal hierarchical models for animal count data that permit animal density to vary over space and time, including formulations motivated by resource selection and allowing for closed populations. We gauge the relative performance (bias, precision, computational demands) of alternative spatiotemporal models when confronted with simulated and real data sets from dynamic animal populations. For the latter, we analyze spotted seal (Phoca largha) counts from an aerial survey of the Bering Sea where the quantity and quality of suitable habitat (sea ice) changed dramatically while surveys were being conducted. Simulation analyses suggested that multiple types of spatiotemporal models provide reasonable inference (low positive bias, high precision) about animal abundance, but have potential for overestimating precision. Analysis of spotted seal data indicated that several model formulations, including those based on a log-Gaussian Cox process, had a tendency to overestimate abundance. By contrast, a model that included a population closure assumption and a scale prior on total abundance produced estimates that largely conformed to our a priori expectation. Although care must be taken to tailor models to match the study population and survey data available, we argue that hierarchical spatiotemporal statistical models represent a powerful way forward for estimating abundance and explaining variation in the distribution of dynamical populations.

A geometric nonlinear degenerated shell element using a mixed formulation with independently assumed strain fields. Final Report; Ph.D. Thesis, 1989

NASA Technical Reports Server (NTRS)

Graf, Wiley E.

1991-01-01

A mixed formulation is chosen to overcome deficiencies of the standard displacement-based shell model. Element development is traced from the incremental variational principle on through to the final set of equilibrium equations. Particular attention is paid to developing specific guidelines for selecting the optimal set of strain parameters. A discussion of constraint index concepts and their predictive capability related to locking is included. Performance characteristics of the elements are assessed in a wide variety of linear and nonlinear plate/shell problems. Despite limiting the study to geometric nonlinear analysis, a substantial amount of additional insight concerning the finite element modeling of thin plate/shell structures is provided. For example, in nonlinear analysis, given the same mesh and load step size, mixed elements converge in fewer iterations than equivalent displacement-based models. It is also demonstrated that, in mixed formulations, lower order elements are preferred. Additionally, meshes used to obtain accurate linear solutions do not necessarily converge to the correct nonlinear solution. Finally, a new form of locking was identified associated with employing elements designed for biaxial bending in uniaxial bending applications.

A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model

PubMed Central

’t Hart, Bert A.; Dunham, Jordon; Faber, Bart W.; Laman, Jon D.; van Horssen, Jack; Bauer, Jan; Kap, Yolanda S.

2017-01-01

The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund’s adjuvant (IFA)]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes. PMID:28744286

An improved snow scheme for the ECMWF land surface model: Description and offline validation

Treesearch

Emanuel Dutra; Gianpaolo Balsamo; Pedro Viterbo; Pedro M. A. Miranda; Anton Beljaars; Christoph Schar; Kelly Elder

2010-01-01

A new snow scheme for the European Centre for Medium-Range Weather Forecasts (ECMWF) land surface model has been tested and validated. The scheme includes a new parameterization of snow density, incorporating a liquid water reservoir, and revised formulations for the subgrid snow cover fraction and snow albedo. Offline validation (covering a wide range of spatial and...

The Role of Vocational Educators in Planning Vocational Assessment Activities for Handicapped Students: An Indepth Review of a Six Step Model.

ERIC Educational Resources Information Center

Stodden, Robert A.; Boone, Rosalie

1986-01-01

Discusses the role of teachers in providing vocational assessment to disabled students. Steps in this process include (1) establish planning team and conduct information search, (2) define purpose, (3) establish basic considerations, (4) formulate assessment model, (5) establish implementation focus, and (6) pilot test and evaluate assessment…

Iterative Methods to Solve Linear RF Fields in Hot Plasma

NASA Astrophysics Data System (ADS)

Spencer, Joseph; Svidzinski, Vladimir; Evstatiev, Evstati; Galkin, Sergei; Kim, Jin-Soo

2014-10-01

Most magnetic plasma confinement devices use radio frequency (RF) waves for current drive and/or heating. Numerical modeling of RF fields is an important part of performance analysis of such devices and a predictive tool aiding design and development of future devices. Prior attempts at this modeling have mostly used direct solvers to solve the formulated linear equations. Full wave modeling of RF fields in hot plasma with 3D nonuniformities is mostly prohibited, with memory demands of a direct solver placing a significant limitation on spatial resolution. Iterative methods can significantly increase spatial resolution. We explore the feasibility of using iterative methods in 3D full wave modeling. The linear wave equation is formulated using two approaches: for cold plasmas the local cold plasma dielectric tensor is used (resolving resonances by particle collisions), while for hot plasmas the conductivity kernel (which includes a nonlocal dielectric response) is calculated by integrating along test particle orbits. The wave equation is discretized using a finite difference approach. The initial guess is important in iterative methods, and we examine different initial guesses including the solution to the cold plasma wave equation. Work is supported by the U.S. DOE SBIR program.

Math modeling for helicopter simulation of low speed, low altitude and steeply descending flight

NASA Technical Reports Server (NTRS)

Sheridan, P. F.; Robinson, C.; Shaw, J.; White, F.

1982-01-01

A math model was formulated to represent some of the aerodynamic effects of low speed, low altitude, and steeply descending flight. The formulation is intended to be consistent with the single rotor real time simulation model at NASA Ames Research Center. The effect of low speed, low altitude flight on main rotor downwash was obtained by assuming a uniform plus first harmonic inflow model and then by using wind tunnel data in the form of hub loads to solve for the inflow coefficients. The result was a set of tables for steady and first harmonic inflow coefficients as functions of ground proximity, angle of attack, and airspeed. The aerodynamics associated with steep descending flight in the vortex ring state were modeled by replacing the steady induced downwash derived from momentum theory with an experimentally derived value and by including a thrust fluctuations effect due to vortex shedding. Tables of the induced downwash and the magnitude of the thrust fluctuations were created as functions of angle of attack and airspeed.

The Multimedia Environmental Pollutant Assessment System (MEPAS){reg_sign}: Atmospheric pathway formulations. Revision

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

Droppo, J.G.; Buck, J.W.

1996-03-01

The Multimedia Environmental Pollutant Assessment System (MEPAS) is an integrated software implementation of physics-based fate and transport models for health and environmental risk assessments of both radioactive and hazardous pollutants. This atmospheric component report is one of a series of formulation reports that document the MEPAS mathematical models. MEPAS is a multimedia model; pollutant transport is modeled within, through, and between multiple media (air, soil, groundwater, and surface water). The estimated concentrations in the various media are used to compute exposures and impacts to the environment, to maximum individuals, and to populations. The MEPAS atmospheric component for the air mediamore » documented in this report includes models for emission from a source to the air, initial plume rise and dispersion, airborne pollutant transport and dispersion, and deposition to soils and crops. The material in this report is documentation for MEPAS Versions 3.0 and 3.1 and the MEPAS version used in the Remedial Action Assessment System (RAAS) Version 1.0.« less

Development and evaluation of in situ gel of pregabalin

PubMed Central

Madan, Jyotsana R; Adokar, Bhushan R; Dua, Kamal

2015-01-01

Aim and Background: Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice. Materials and Methods: In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 32 full factorial design. Results: The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm2). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release. Conclusion: Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy. PMID:26682193

Potential formulation of sleep dynamics

NASA Astrophysics Data System (ADS)

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

2009-02-01

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

Influence of cellulose derivative and ethylene glycol on optimization of lornoxicam transdermal formulation.

PubMed

Shahzad, Yasser; Khan, Qalandar; Hussain, Talib; Shah, Syed Nisar Hussain

2013-10-01

Lornoxicam containing topically applied lotions were formulated and optimized with the aim to deliver it transdermally. The formulated lotions were evaluated for pH, viscosity and in vitro permeation studies through silicone membrane using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of variables, namely hydroxypropyl methylcellulose (HPMC) and ethylene glycol (EG) on permeation of lornoxicam from topically applied lotion formulations. The best fit quadratic model revealed that low level of HPMC and intermediate level of EG in the formulation was optimum for enhancing the drug flux across silicone membrane. FT-IR analysis confirmed absence of drug-polymer interactions. Selected optimized lotion formulation was then subjected to accelerated stability testing, sensatory perception testing and in vitro permeation across rabbit skin. The drug flux from the optimized lotion across rabbit skin was significantly better that that from the control formulation. Furthermore, sensatory perception test rated a higher acceptability while lotion was stable over stability testing period. Therefore, use of Box-Wilson statistical design successfully elaborated the influence of formulation variables on permeation of lornoxicam form topical formulations, thus, helped in optimization of the lotion formulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Physiologically based pharmacokinetic model of amphotericin B disposition in rats following administration of deoxycholate formulation (Fungizone®): pooled analysis of published data.

PubMed

Kagan, Leonid; Gershkovich, Pavel; Wasan, Kishor M; Mager, Donald E

2011-06-01

The time course of tissue distribution of amphotericin B (AmB) has not been sufficiently characterized despite its therapeutic importance and an apparent disconnect between plasma pharmacokinetics and clinical outcomes. The goals of this work were to develop and evaluate a physiologically based pharmacokinetic (PBPK) model to characterize the disposition properties of AmB administered as deoxycholate formulation in healthy rats and to examine the utility of the PBPK model for interspecies scaling of AmB pharmacokinetics. AmB plasma and tissue concentration-time data, following single and multiple intravenous administration of Fungizone® to rats, from several publications were combined for construction of the model. Physiological parameters were fixed to literature values. Various structural models for single organs were evaluated, and the whole-body PBPK model included liver, spleen, kidney, lung, heart, gastrointestinal tract, plasma, and remainder compartments. The final model resulted in a good simultaneous description of both single and multiple dose data sets. Incorporation of three subcompartments for spleen and kidney tissues was required for capturing a prolonged half-life in these organs. The predictive performance of the final PBPK model was assessed by evaluating its utility in predicting pharmacokinetics of AmB in mice and humans. Clearance and permeability-surface area terms were scaled with body weight. The model demonstrated good predictions of plasma AmB concentration-time profiles for both species. This modeling framework represents an important basis that may be further utilized for characterization of formulation- and disease-related factors in AmB pharmacokinetics and pharmacodynamics.

Design and evaluation of a novel nanoparticulate-based formulation encapsulating a HIP complex of lysozyme.

PubMed

Gaudana, Ripal; Gokulgandhi, Mitan; Khurana, Varun; Kwatra, Deep; Mitra, Ashim K

2013-01-01

Formulation development of protein therapeutics using polymeric nanoparticles has found very little success in recent years. Major formulation challenges include rapid denaturation, susceptibility to lose bioactivity in presence of organic solvents and poor encapsulation in polymeric matrix. In the present study, we have prepared hydrophobic ion pairing (HIP) complex of lysozyme, a model protein, using dextran sulfate (DS) as a complexing polymer. We have optimized the process of formation and dissociation of HIP complex between lysozyme and DS. The effect of HIP complexation on enzymatic activity of lysozyme was also studied. Nanoparticles were prepared and characterized using spontaneous emulsion solvent diffusion method. Furthermore, we have also investigated release of lysozyme from nanoparticles along with its enzymatic activity. Results of this study indicate that nanoparticles can sustain the release of lysozyme without compromising its enzymatic activity. HIP complexation using a polymer may also be employed to formulate sustained release dosage forms of other macromolecules with enhanced encapsulation efficiency.

Lagrangian formulation of the general relativistic Poynting-Robertson effect

NASA Astrophysics Data System (ADS)

De Falco, Vittorio; Battista, Emmanuele; Falanga, Maurizio

2018-04-01

We propose the Lagrangian formulation for describing the motion of a test particle in a general relativistic, stationary, and axially symmetric spacetime. The test particle is also affected by a radiation field, modeled as a coherent flux of photons traveling along the null geodesics of the background spacetime, including the general relativistic Poynting-Robertson effect. The innovative part of this work is to prove the existence of the potential linked to the dissipative action caused by the Poynting-Robertson effect in general relativity through the help of an integrating factor, depending on the energy of the system. Generally, such kinds of inverse problems involving dissipative effects might not admit a Lagrangian formulation; especially, in general relativity, there are no examples of such attempts in the literature so far. We reduce this general relativistic Lagrangian formulation to the classic case in the weak-field limit. This approach facilitates further studies in improving the treatment of the radiation field, and it contains, for example, some implications for a deeper comprehension of the gravitational waves.

The Vocational Significance of Black Identity: Cultural Formulation Approach to Career Assessment and Career Counseling

PubMed Central

Byars-Winston, Angela M.

2010-01-01

Scholarship is emerging on intervention models that purposefully attend to cultural variables throughout the career assessment and career counseling process (Swanson & Fouad, in press). One heuristic model that offers promise to advance culturally-relevant vocational practice with African Americans is the Outline for Cultural Formulation (American Psychiatric Association, 1994). This article explicates the Outline for Cultural Formulation in career assessment and career counseling with African Americans integrating the concept of cultural identity into the entire model. The article concludes with an illustration of the Outline for Cultural Formulation model with an African American career client. PMID:20495668

Computational prediction of formulation strategies for beyond-rule-of-5 compounds.

PubMed

Bergström, Christel A S; Charman, William N; Porter, Christopher J H

2016-06-01

The physicochemical properties of some contemporary drug candidates are moving towards higher molecular weight, and coincidentally also higher lipophilicity in the quest for biological selectivity and specificity. These physicochemical properties move the compounds towards beyond rule-of-5 (B-r-o-5) chemical space and often result in lower water solubility. For such B-r-o-5 compounds non-traditional delivery strategies (i.e. those other than conventional tablet and capsule formulations) typically are required to achieve adequate exposure after oral administration. In this review, we present the current status of computational tools for prediction of intestinal drug absorption, models for prediction of the most suitable formulation strategies for B-r-o-5 compounds and models to obtain an enhanced understanding of the interplay between drug, formulation and physiological environment. In silico models are able to identify the likely molecular basis for low solubility in physiologically relevant fluids such as gastric and intestinal fluids. With this baseline information, a formulation scientist can, at an early stage, evaluate different orally administered, enabling formulation strategies. Recent computational models have emerged that predict glass-forming ability and crystallisation tendency and therefore the potential utility of amorphous solid dispersion formulations. Further, computational models of loading capacity in lipids, and therefore the potential for formulation as a lipid-based formulation, are now available. Whilst such tools are useful for rapid identification of suitable formulation strategies, they do not reveal drug localisation and molecular interaction patterns between drug and excipients. For the latter, Molecular Dynamics simulations provide an insight into the interplay between drug, formulation and intestinal fluid. These different computational approaches are reviewed. Additionally, we analyse the molecular requirements of different targets, since these can provide an early signal that enabling formulation strategies will be required. Based on the analysis we conclude that computational biopharmaceutical profiling can be used to identify where non-conventional gateways, such as prediction of 'formulate-ability' during lead optimisation and early development stages, are important and may ultimately increase the number of orally tractable contemporary targets. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Numerical Analysis of Solids at Failure

DTIC Science & Technology

2011-08-20

failure analyses include the formulation of invariant finite elements for thin Kirchhoff rods, and preliminary initial studies of growth in...analysis of the failure of other structural/mechanical systems, including the finite element modeling of thin Kirchhoff rods and the constitutive...algorithm based on the connectivity graph of the underlying finite element mesh. In this setting, the discontinuities are defined by fronts propagating

Linear programming: an alternative approach for developing formulations for emergency food products.

PubMed

Sheibani, Ershad; Dabbagh Moghaddam, Arasb; Sharifan, Anousheh; Afshari, Zahra

2018-03-01

To minimize the mortality rates of individuals affected by disasters, providing high-quality food relief during the initial stages of an emergency is crucial. The goal of this study was to develop a formulation for a high-energy, nutrient-dense prototype using linear programming (LP) model as a novel method for developing formulations for food products. The model consisted of the objective function and the decision variables, which were the formulation costs and weights of the selected commodities, respectively. The LP constraints were the Institute of Medicine and the World Health Organization specifications of the content of nutrients in the product. Other constraints related to the product's sensory properties were also introduced to the model. Nonlinear constraints for energy ratios of nutrients were linearized to allow their use in the LP. Three focus group studies were conducted to evaluate the palatability and other aspects of the optimized formulation. New constraints were introduced to the LP model based on the focus group evaluations to improve the formulation. LP is an appropriate tool for designing formulations of food products to meet a set of nutritional requirements. This method is an excellent alternative to the traditional 'trial and error' method in designing formulations. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

LES models for incompressible magnetohydrodynamics derived from the variational multiscale formulation

NASA Astrophysics Data System (ADS)

Sondak, David; Oberai, Assad

2012-10-01

Novel large eddy simulation (LES) models are developed for incompressible magnetohydrodynamics (MHD). These models include the application of the variational multiscale formulation (VMS) of LES to the equations of incompressible MHD, a new residual-based eddy viscosity model (RBEVM,) and a mixed LES model that combines the strengths of both of these models. The new models result in a consistent numerical method that is relatively simple to implement. A dynamic procedure for 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 and state-of-the art LES turbulence models as well as direct numerical simulations (DNS). These 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 A. Pouquet et al., for which the ratio of DNS modes to LES modes is 262,144. Additionally, we extend these models to a finite element setting in which boundary conditions play a role. A classic problem on which we test these models is turbulent channel flow, which in the case of MHD, is called Hartmann flow.

Evaluating the predictability of the in vitro transfer model and in vivo rat studies as a surrogate to investigate the supersaturation and precipitation behaviour of different Albendazole formulations for humans.

PubMed

Ruff, Aaron; Holm, René; Kostewicz, Edmund S

2017-07-15

The present study investigated the ability of the in vitro transfer model and an in vivo pharmacokinetic study in rats to investigate the supersaturation and precipitation behaviour of albendazole (ABZ) relative to data from a human intestinal aspiration study reported in the literature. Two lipid based formulation systems, a hydroxypropyl-β-cyclodextrin (HPβCD) solution and the addition of a crystallization inhibitor (HPMC-E5) on the behaviour of ABZ was investigated. These formulations were investigated to represent differences in their ability to facilitate supersaturation within the small intestine. Overall, both the in vitro transfer model and the in vivo rat study were able to rank order the formulations (as aqueous suspension±HPMC

Field testing model predictions of foam coverage and bubble content in the surf zone

NASA Astrophysics Data System (ADS)

Shi, F.; Kirby, J. T.; Ma, G.; Holman, R. A.; Chickadel, C. C.

2012-12-01

Field-scale modeling of surfzone bubbles and foam coverage is challenging in terms of the computational intensity of multi-phase bubble models based on Navier-Stokes/VOF formulation. In this study, we developed the NHWAVE-bubble package, which includes a 3D non-hydrostatic wave model NHWAVE (Ma et al., 2012), a multi-phase bubble model and a foam model. NHWAVE uses a surface and bottom following sigma coordinate system, making it more applicable to 3D modeling of nearshore waves and circulation in a large-scale field domain. It has been extended to include a multiphase description of polydisperse bubble populations following the approach applied in a 3D VOF model by Ma et al. (2012). A model of a foam layer on the water surface is specified in the model package using a shallow water formulation based on a balance of drag forces due to wind and water column motion. Foam mass conservation includes source and sink terms representing outgassing of the water column, direct foam generation due to surface agitation, and erosion due to bubble bursting. The model is applied in a field scale domain at FRF, Duck, NC where optical data in either visible band (ARGUS) or infrared band were collected during 2010 Surf Zone Optics experiments. The decay of image brightness or intensity following the passage of wave crests is presumably tied to both decay of bubble populations and foam coverage after passage of a broken wave crest. Infrared imagery is likely to provide more detailed information which could separate active breaking from passive foam decay on the surface. Model results will be compared with the measurements with an attention to distinguishing between active generation and passive decay of the foam signature on the water surface.

Tailoring the mucoadhesive and sustained release characteristics of mesalamine loaded formulations for local treatment of distal forms of ulcerative colitis.

PubMed

Ali, Hany S M; Hanafy, Ahmed F; El Achy, Samar N

2016-10-10

Direct delivery of sustained therapeutic levels of mesalamine (MS) via rectal systems to manage distal forms of ulcerative colitis was studied. The High molecular weight hydroxypropyl methylcellulose (HPMC K4M) polymer was combined with hydrophilic surfactants to control polymer hydration process allowing optimization of the mucoadhesive and controlled drug release properties for the rectal systems. Physical mixtures and granules of MS and HPMC K4M were prepared and in vitro characterized using scanning electron microscope, differential scanning calorimetry and X-ray diffraction techniques. Rectal formulations were prepared utilizing MS-HPMC K4M mixtures in different polyethylene glycol (PEG) combination bases. The developed rectal formulations were investigated for physical, mucoadhesion, in-vitro drug release and swelling characteristics. Results revealed acceptable physical characteristics of the prepared formulations with good content uniformity and minimum weight variation. Sustained release patterns of MS form HPMC K4M based formulations were observed. Formulations prepared using high proportions of the polymer or PEG 400 showed higher extent of mucoadhesion, swelling and greatly extended drug release time. Efficacy of an optimized formulation was assessed using the acetic acid induced colitis model in rats and compared to a reference polymer-free formulation of the drug. Clinical evaluation included bleeding from rectum, consistency of animal stool and colon/body weight ratio. Furthermore, histopathological analysis was carried out to evaluate the degree of inflammation and mucosal damage. Overall results showed a significant enhancement in the clinical pictures and colon histopathology of animals treated by the sustained release mucoadhesive formulation compared to the reference polymer free formulation and the non-treated colitis group. Copyright © 2016 Elsevier B.V. All rights reserved.

XFEM modeling of hydraulic fracture in porous rocks with natural fractures

NASA Astrophysics Data System (ADS)

Wang, Tao; Liu, ZhanLi; Zeng, QingLei; Gao, Yue; Zhuang, Zhuo

2017-08-01

Hydraulic fracture (HF) in porous rocks is a complex multi-physics coupling process which involves fluid flow, diffusion and solid deformation. In this paper, the extended finite element method (XFEM) coupling with Biot theory is developed to study the HF in permeable rocks with natural fractures (NFs). In the recent XFEM based computational HF models, the fluid flow in fractures and interstitials of the porous media are mostly solved separately, which brings difficulties in dealing with complex fracture morphology. In our new model the fluid flow is solved in a unified framework by considering the fractures as a kind of special porous media and introducing Poiseuille-type flow inside them instead of Darcy-type flow. The most advantage is that it is very convenient to deal with fluid flow inside the complex fracture network, which is important in shale gas extraction. The weak formulation for the new coupled model is derived based on virtual work principle, which includes the XFEM formulation for multiple fractures and fractures intersection in porous media and finite element formulation for the unified fluid flow. Then the plane strain Kristianovic-Geertsma-de Klerk (KGD) model and the fluid flow inside the fracture network are simulated to validate the accuracy and applicability of this method. The numerical results show that large injection rate, low rock permeability and isotropic in-situ stresses tend to lead to a more uniform and productive fracture network.

A hydroelastic model of hydrocephalus

NASA Astrophysics Data System (ADS)

Smillie, Alan; Sobey, Ian; Molnar, Zoltan

2005-09-01

We combine elements of poroelasticity and of fluid mechanics to construct a mathematical model of the human brain and ventricular system. The model is used to study hydrocephalus, a pathological condition in which the normal flow of the cerebrospinal fluid is disturbed, causing the brain to become deformed. Our model extends recent work in this area by including flow through the aqueduct, by incorporating boundary conditions that we believe accurately represent the anatomy of the brain and by including time dependence. This enables us to construct a quantitative model of the onset, development and treatment of this condition. We formulate and solve the governing equations and boundary conditions for this model and give results that are relevant to clinical observations.

Optimization of Primary Drying in Lyophilization during Early Phase Drug Development using a Definitive Screening Design with Formulation and Process Factors.

PubMed

Goldman, Johnathan M; More, Haresh T; Yee, Olga; Borgeson, Elizabeth; Remy, Brenda; Rowe, Jasmine; Sadineni, Vikram

2018-06-08

Development of optimal drug product lyophilization cycles is typically accomplished via multiple engineering runs to determine appropriate process parameters. These runs require significant time and product investments, which are especially costly during early phase development when the drug product formulation and lyophilization process are often defined simultaneously. Even small changes in the formulation may require a new set of engineering runs to define lyophilization process parameters. In order to overcome these development difficulties, an eight factor definitive screening design (DSD), including both formulation and process parameters, was executed on a fully human monoclonal antibody (mAb) drug product. The DSD enables evaluation of several interdependent factors to define critical parameters that affect primary drying time and product temperature. From these parameters, a lyophilization development model is defined where near optimal process parameters can be derived for many different drug product formulations. This concept is demonstrated on a mAb drug product where statistically predicted cycle responses agree well with those measured experimentally. This design of experiments (DoE) approach for early phase lyophilization cycle development offers a workflow that significantly decreases the development time of clinically and potentially commercially viable lyophilization cycles for a platform formulation that still has variable range of compositions. Copyright © 2018. Published by Elsevier Inc.

Development of rectal self-emulsifying suspension of a moisture-labile water-soluble drug.

PubMed

Kauss, Tina; Gaubert, Alexandra; Tabaran, Luc; Tonelli, Giovanni; Phoeung, Thida; Langlois, Marie-Hélène; White, Nick; Cartwright, Anthony; Gomes, Melba; Gaudin, Karen

2018-01-30

Self-emulsifying drug delivery systems, commonly used for oral delivery of poorly soluble compounds, were used to formulate water soluble but moisture labile compounds for rectal application. The objective was to use the oily phase of the system to formulate a liquid, non-aqueous product while obtaining the advantages of self-emulsification, rapid contact with the rectal mucosa and rapid absorption post-administration. Ceftriaxone was used as a model drug and the human bile salt sodium chenodeoxycholate was used as an absorption enhancer. After preliminary screening of 23 excipients, based on their emulsification ability and emulsion fineness in binary and ternary mixtures, a full factorial design was used to screen different formulations of three preselected excipients. The optimal formulation contained 60% of excipients, namely Capryol 90, Kolliphor EL and Kolliphor PS20 in 4 : 6 : 6 ratio and 40% of a powder blend that included 500 mg of ceftriaxone. Characterization of the system showed that it complied with the requirements for rectal administration, in particular rapid emulsification in a small quantity of liquid. Rabbit bioavailability showed rapid absorption of ceftriaxone, achieving 128% bioavailability compared to powder control formulation. These results demonstrated the potential of self-emulsifying formulations for rectal administration of Class 3 BCS drugs. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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.

A review of cognitive therapy in acute medical settings. Part I: therapy model and assessment.

PubMed

Levin, Tomer T; White, Craig A; Kissane, David W

2013-04-01

Although cognitive therapy (CT) has established outpatient utility, there is no integrative framework for using CT in acute medical settings where most psychosomatic medicine (P-M) clinicians practice. Biopsychosocial complexity challenges P-M clinicians who want to use CT as the a priori psychotherapeutic modality. For example, how should clinicians modify the data gathering and formulation process to support CT in acute settings? Narrative review methodology is used to describe the framework for a CT informed interview, formulation, and assessment in acute medical settings. Because this review is aimed largely at P-M trainees and educators, exemplary dialogues model the approach (specific CT strategies for common P-M scenarios appear in the companion article.) Structured data gathering needs to be tailored by focusing on cognitive processes informed by the cognitive hypothesis. Agenda setting, Socratic questioning, and adaptations to the mental state examination are necessary. Specific attention is paid to the CT formulation, Folkman's Cognitive Coping Model, self-report measures, data-driven evaluations, and collaboration (e.g., sharing the formulation with the patient.) Integrative CT-psychopharmacological approaches and the importance of empathy are emphasized. The value of implementing psychotherapy in parallel with data gathering because of time urgency is advocated, but this is a significant departure from usual outpatient approaches in which psychotherapy follows evaluation. This conceptual approach offers a novel integrative framework for using CT in acute medical settings, but future challenges include demonstrating clinical outcomes and training P-M clinicians so as to demonstrate fidelity.

Estrogen receptor β-selective phytoestrogenic formulation prevents physical and neurological changes in a preclinical model of human menopause.

PubMed

Zhao, Liqin; Mao, Zisu; Schneider, Lon S; Brinton, Roberta D

2011-10-01

As an alternative to estrogen therapy, the efficacy of an estrogen receptor β-selective phytoestrogenic (phyto-β-SERM) formulation to regulate climacteric symptoms and decline in brain responses associated with ovarian hormone loss in menopause was assessed. A phyto-β-SERM formulation-containing diet was compared with a commercial soy extract diet and a phytoestrogen-free base/control diet in an ovariectomized (OVX) mouse model of human menopause. Two treatment studies were conducted: (1) a 2-month study assessed the effects of experimental diets on tail skin temperature as a model of menopausal hot flashes, and (2) a 9-month study assessed the long-term impact of the diets on overall health, hair thinning/loss, spatial working memory, and associated protein expression in the hippocampus. The phyto-β-SERM diet prevented OVX-induced menopause-like changes including the rise in skin temperature, hair thinning/loss, deficit in spatial memory function, and reversed OVX-induced decline in the expression of hippocampal proteins involved in neural plasticity and β-amyloid degradation/clearance. The soy extract diet had no effect or exacerbated OVX-induced changes. Overall, the phyto-β-SERM diet induced physical and neurological responses comparable with ovary-intact mice, suggesting the therapeutic potential of the phyto-β-SERM formulation for the prevention/alleviation of climacteric symptoms and decline in brain responses induced by ovarian hormone loss, which provides the basis for further work in postmenopausal women.

Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

PubMed Central

Wang, Wenrui; Zhu, Rongrong; Xie, Qian; Li, Ang; Xiao, Yu; Li, Kun; Liu, Hui; Cui, Daxiang; Chen, Yihan; Wang, Shilong

2012-01-01

Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy. PMID:22888226

Experimenting with Mathematical Biology

ERIC Educational Resources Information Center

Sanft, Rebecca; Walter, Anne

2016-01-01

St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

Optimal Sequential Rules for Computer-Based Instruction.

ERIC Educational Resources Information Center

Vos, Hans J.

1998-01-01

Formulates sequential rules for adapting the appropriate amount of instruction to learning needs in the context of computer-based instruction. Topics include Bayesian decision theory, threshold and linear-utility structure, psychometric model, optimal sequential number of test questions, and an empirical example of sequential instructional…

Involving Clients in Welfare Policy-making.

ERIC Educational Resources Information Center

O'Donnell, Sandra

1993-01-01

Describes how, through support of private philanthropy, welfare recipients have been involved in implementing welfare-to-work policy, including Job Opportunities in Business Sector provisions of Family Support Act, in Illinois since 1986. Describes client roles in problem formulation, model program development, policy development, and policy…

SfM with MRFs: discrete-continuous optimization for large-scale structure from motion.

PubMed

Crandall, David J; Owens, Andrew; Snavely, Noah; Huttenlocher, Daniel P

2013-12-01

Recent work in structure from motion (SfM) has built 3D models from large collections of images downloaded from the Internet. Many approaches to this problem use incremental algorithms that solve progressively larger bundle adjustment problems. These incremental techniques scale poorly as the image collection grows, and can suffer from drift or local minima. We present an alternative framework for SfM based on finding a coarse initial solution using hybrid discrete-continuous optimization and then improving that solution using bundle adjustment. The initial optimization step uses a discrete Markov random field (MRF) formulation, coupled with a continuous Levenberg-Marquardt refinement. The formulation naturally incorporates various sources of information about both the cameras and points, including noisy geotags and vanishing point (VP) estimates. We test our method on several large-scale photo collections, including one with measured camera positions, and show that it produces models that are similar to or better than those produced by incremental bundle adjustment, but more robustly and in a fraction of the time.

A scheme for computing surface layer turbulent fluxes from mean flow surface observations

NASA Technical Reports Server (NTRS)

Hoffert, M. I.; Storch, J.

1978-01-01

A physical model and computational scheme are developed for generating turbulent surface stress, sensible heat flux and humidity flux from mean velocity, temperature and humidity at some fixed height in the atmospheric surface layer, where conditions at this reference level are presumed known from observations or the evolving state of a numerical atmospheric circulation model. The method is based on coupling the Monin-Obukov surface layer similarity profiles which include buoyant stability effects on mean velocity, temperature and humidity to a force-restore formulation for the evolution of surface soil temperature to yield the local values of shear stress, heat flux and surface temperature. A self-contained formulation is presented including parameterizations for solar and infrared radiant fluxes at the surface. Additional parameters needed to implement the scheme are the thermal heat capacity of the soil per unit surface area, surface aerodynamic roughness, latitude, solar declination, surface albedo, surface emissivity and atmospheric transmissivity to solar radiation.

A formulation of convection for stellar structure and evolution calculations without the mixing-length theory approximations. I - Application to the sun

NASA Technical Reports Server (NTRS)

Lydon, Thomas J.; Fox, Peter A.; Sofia, Sabatino

1992-01-01

The problem of treating convective energy transport without MLT approximations is approached here by formulating the results of numerical simulations of convection in terms of energy fluxes. This revised treatment of convective transport can be easily incorporated within existing stellar structure codes. As an example, the technique is applied to the sun. The treatment does not include any free parameters, making the models extremely sensitive to the accuracy of the treatments of opacities, chemical abundances, treatments of the solar atmosphere, and the equation of state.

A Damage Model for the Simulation of Delamination in Advanced Composites under Variable-Mode Loading

NASA Technical Reports Server (NTRS)

Turon, A.; Camanho, P. P.; Costa, J.; Davila, C. G.

2006-01-01

A thermodynamically consistent damage model is proposed for the simulation of progressive delamination in composite materials under variable-mode ratio. The model is formulated in the context of Damage Mechanics. A novel constitutive equation is developed to model the initiation and propagation of delamination. A delamination initiation criterion is proposed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. The formulation accounts for crack closure effects to avoid interfacial penetration of two adjacent layers after complete decohesion. The model is implemented in a finite element formulation, and the numerical predictions are compared with experimental results obtained in both composite test specimens and structural components.

Adjacent-Categories Mokken Models for Rater-Mediated Assessments

PubMed Central

Wind, Stefanie A.

2016-01-01

Molenaar extended Mokken’s original probabilistic-nonparametric scaling models for use with polytomous data. These polytomous extensions of Mokken’s original scaling procedure have facilitated the use of Mokken scale analysis as an approach to exploring fundamental measurement properties across a variety of domains in which polytomous ratings are used, including rater-mediated educational assessments. Because their underlying item step response functions (i.e., category response functions) are defined using cumulative probabilities, polytomous Mokken models can be classified as cumulative models based on the classifications of polytomous item response theory models proposed by several scholars. In order to permit a closer conceptual alignment with educational performance assessments, this study presents an adjacent-categories variation on the polytomous monotone homogeneity and double monotonicity models. Data from a large-scale rater-mediated writing assessment are used to illustrate the adjacent-categories approach, and results are compared with the original formulations. Major findings suggest that the adjacent-categories models provide additional diagnostic information related to individual raters’ use of rating scale categories that is not observed under the original formulation. Implications are discussed in terms of methods for evaluating rating quality. PMID:29795916

An uncertainty analysis of the flood-stage upstream from a bridge.

PubMed

Sowiński, M

2006-01-01

The paper begins with the formulation of the problem in the form of a general performance function. Next the Latin hypercube sampling (LHS) technique--a modified version of the Monte Carlo method is briefly described. The essential uncertainty analysis of the flood-stage upstream from a bridge starts with a description of the hydraulic model. This model concept is based on the HEC-RAS model developed for subcritical flow under a bridge without piers in which the energy equation is applied. The next section contains the characteristic of the basic variables including a specification of their statistics (means and variances). Next the problem of correlated variables is discussed and assumptions concerning correlation among basic variables are formulated. The analysis of results is based on LHS ranking lists obtained from the computer package UNCSAM. Results fot two examples are given: one for independent and the other for correlated variables.

An Enhanced Engineering Perspective of Global Climate Systems and Statistical Formulation of Terrestrial CO2 Exchanges

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

Dai, Yuanshun; Baek, Seung H.; Garcia-Diza, Alberto

2012-01-01

This paper designs a comprehensive approach based on the engineering machine/system concept, to model, analyze, and assess the level of CO2 exchange between the atmosphere and terrestrial ecosystems, which is an important factor in understanding changes in global climate. The focus of this article is on spatial patterns and on the correlation between levels of CO2 fluxes and a variety of influencing factors in eco-environments. The engineering/machine concept used is a system protocol that includes the sequential activities of design, test, observe, and model. This concept is applied to explicitly include various influencing factors and interactions associated with CO2 fluxes.more » To formulate effective models of a large and complex climate system, this article introduces a modeling technique that will be referred to as Stochastic Filtering Analysis of Variance (SFANOVA). The CO2 flux data observed from some sites of AmeriFlux are used to illustrate and validate the analysis, prediction and globalization capabilities of the proposed engineering approach and the SF-ANOVA technology. The SF-ANOVA modeling approach was compared to stepwise regression, ridge regression, and neural networks. The comparison indicated that the proposed approach is a valid and effective tool with similar accuracy and less complexity than the other procedures.« less

Models, Data, and War: a Critique of the Foundation for Defense Analyses.

DTIC Science & Technology

1980-03-12

scientific formulation 6 An "objective" solution 8 Analysis of a squishy problem 9 A judgmental formulation 9 A potential for distortion 11 A subjective...inextricably tied to those judgments. Different analysts, with apparently identical knowledge of a real world problem, may develop plausible formulations ...configured is a concrete theoretical statement." 2/ The formulation of a computer model--conceiving a mathematical representation of the real world

Variable thickness transient ground-water flow model. Volume 1. Formulation

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

Reisenauer, A.E.

1979-12-01

Mathematical formulation for the variable thickness transient (VTT) model of an aquifer system is presented. The basic assumptions are described. Specific data requirements for the physical parameters are discussed. The boundary definitions and solution techniques of the numerical formulation of the system of equations are presented.

European perspectives on pediatric formulations.

PubMed

Breitkreutz, Jörg

2008-11-01

The 2007 European Union (EU) regulation on medicinal products for pediatric use may change the present unsatisfying situation in the EU by stimulating research and development of medicines for use in children through rewards and incentives. This commentary reflects on the new EU regulations and guidelines, with special attention paid to the impact on pediatric formulation science. The focus of this article is on the EU perspective for pediatric formulations and highlights the differences compared with the pediatric drug formulation situation in the United States. Materials for this article were gathered during a literature search of MEDLINE and Chemical Abstracts (1970-October 2008) using the following terms: paediatric/pediatric drug formulations, age-appropriate dosage forms, child-appropriate medicines, and paediatric/pediatric regulation. Since the EU legislation on medicines for children came into force in 2007, a great emphasis has been placed on creating new organizations, scientific networks, and programs dealing with pediatric medicines and child-appropriate drug formulations. Although the US legislation was an appropriate model, the EU introduced some novel measures to improve the current situation, such as the Paediatric Investigation Plan and the Paediatric Use Marketing Authorisation. For globally operating pharmaceutical companies, the peculiarities of the European market have a strong impact on their product development strategies. Because the European approach demands early investigations into drug formulations for children, various issues must be resolved, including the following: choosing formulations for each age group, determining which excipients may be used in the formulation and which delivery device is appropriate, and predicting the taste sensation of an oral formulation. Numerous initiatives and networks are evolving in Europe. An important future task will be the coordination of these activities and the linking to other groups working on pediatric formulations outside the EU. Similar to the research in pediatric drug formulations that was stimulated by the US legislation and incentives of the last decade, the 2007 EU legislation promises improvements in the availability of child-appropriate drugs in Europe.

Development of In Vitro-In Vivo Correlation/Relationship Modeling Approaches for Immediate Release Formulations Using Compartmental Dynamic Dissolution Data from “Golem”: A Novel Apparatus

PubMed Central

Tuszyński, Paweł K.; Polak, Sebastian; Jachowicz, Renata; Mendyk, Aleksander; Dohnal, Jiří

2015-01-01

Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data. PMID:26120580

SMA Hybrid Composites for Dynamic Response Abatement Applications

NASA Technical Reports Server (NTRS)

Turner, Travis L.

2000-01-01

A recently developed constitutive model and a finite element formulation for predicting the thermomechanical response of Shape Memory Alloy (SMA) hybrid composite (SMAHC) structures is briefly described. Attention is focused on constrained recovery behavior in this study, but the constitutive formulation is also capable of modeling restrained or free recovery. Numerical results are shown for glass/epoxy panel specimens with embedded Nitinol actuators subjected to thermal and acoustic loads. Control of thermal buckling, random response, sonic fatigue, and transmission loss are demonstrated and compared to conventional approaches including addition of conventional composite layers and a constrained layer damping treatment. Embedded SMA actuators are shown to be significantly more effective in dynamic response abatement applications than the conventional approaches and are attractive for combination with other passive and/or active approaches.

Compressible cavitation with stochastic field method

NASA Astrophysics Data System (ADS)

Class, Andreas; Dumond, Julien

2012-11-01

Non-linear phenomena can often be well described using probability density functions (pdf) and pdf transport models. Traditionally the simulation of pdf transport requires Monte-Carlo codes based on Lagrange particles or prescribed pdf assumptions including binning techniques. Recently, in the field of combustion, a novel formulation called the stochastic field method solving pdf transport based on Euler fields has been proposed which eliminates the necessity to mix Euler and Lagrange techniques or prescribed pdf assumptions. In the present work, part of the PhD Design and analysis of a Passive Outflow Reducer relying on cavitation, a first application of the stochastic field method to multi-phase flow and in particular to cavitating flow is presented. The application considered is a nozzle subjected to high velocity flow so that sheet cavitation is observed near the nozzle surface in the divergent section. It is demonstrated that the stochastic field formulation captures the wide range of pdf shapes present at different locations. The method is compatible with finite-volume codes where all existing physical models available for Lagrange techniques, presumed pdf or binning methods can be easily extended to the stochastic field formulation.

Isogeometric Kirchhoff-Love shell formulations for biological membranes

PubMed Central

Tepole, Adrián Buganza; Kabaria, Hardik; Bletzinger, Kai-Uwe; Kuhl, Ellen

2015-01-01

Computational modeling of thin biological membranes can aid the design of better medical devices. Remarkable biological membranes include skin, alveoli, blood vessels, and heart valves. Isogeometric analysis is ideally suited for biological membranes since it inherently satisfies the C1-requirement for Kirchhoff-Love kinematics. Yet, current isogeometric shell formulations are mainly focused on linear isotropic materials, while biological tissues are characterized by a nonlinear anisotropic stress-strain response. Here we present a thin shell formulation for thin biological membranes. We derive the equilibrium equations using curvilinear convective coordinates on NURBS tensor product surface patches. We linearize the weak form of the generic linear momentum balance without a particular choice of a constitutive law. We then incorporate the constitutive equations that have been designed specifically for collagenous tissues. We explore three common anisotropic material models: Mooney-Rivlin, May Newmann-Yin, and Gasser-Ogden-Holzapfel. Our work will allow scientists in biomechanics and mechanobiology to adopt the constitutive equations that have been developed for solid three-dimensional soft tissues within the framework of isogeometric thin shell analysis. PMID:26251556

Study of a Simulation Tool to Determine Achievable Control Dynamics and Control Power Requirements with Perfect Tracking

NASA Technical Reports Server (NTRS)

Ostroff, Aaron J.

1998-01-01

This paper contains a study of two methods for use in a generic nonlinear simulation tool that could be used to determine achievable control dynamics and control power requirements while performing perfect tracking maneuvers over the entire flight envelope. The two methods are NDI (nonlinear dynamic inversion) and the SOFFT(Stochastic Optimal Feedforward and Feedback Technology) feedforward control structure. Equivalent discrete and continuous SOFFT feedforward controllers have been developed. These equivalent forms clearly show that the closed-loop plant model loop is a plant inversion and is the same as the NDI formulation. The main difference is that the NDI formulation has a closed-loop controller structure whereas SOFFT uses an open-loop command model. Continuous, discrete, and hybrid controller structures have been developed and integrated into the formulation. Linear simulation results show that seven different configurations all give essentially the same response, with the NDI hybrid being slightly different. The SOFFT controller gave better tracking performance compared to the NDI controller when a nonlinear saturation element was added. Future plans include evaluation using a nonlinear simulation.

Therapeutic effect of orally administered microencapsulated oxaliplatin for colorectal cancer

PubMed Central

Urbanska, Aleksandra M.; Karagiannis, Emmanouil D.; Guajardo, Gonzalo; Langer, Robert S.; Anderson, Daniel G.

2013-01-01

Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality. PMID:22472433

Mixed formulation for frictionless contact problems

NASA Technical Reports Server (NTRS)

Noor, Ahmed K.; Kim, Kyun O.

1989-01-01

Simple mixed finite element models and a computational precedure are presented for the solution of frictionless contact problems. The analytical formulation is based on a form of Reissner's large rotation theory of the structure with the effects of transverse shear deformation included. The contact conditions are incorporated into the formulation by using a perturbed Lagrangian approach with the fundamental unknowns consisting of the internal forces (stress resultants), the generalized displacements, and the Lagrange multipliers associated with the contact conditions. The element characteristic array are obtained by using a modified form of the two-field Hellinger-Reissner mixed variational principle. The internal forces and the Lagrange multipliers are allowed to be discontinuous at interelement boundaries. The Newton-Raphson iterative scheme is used for the solution of the nonlinear algebraic equations, and the determination of the contact area and the contact pressures.

Nonlinear transient analysis via energy minimization

NASA Technical Reports Server (NTRS)

Kamat, M. P.; Knight, N. F., Jr.

1978-01-01

The formulation basis for nonlinear transient analysis of finite element models of structures using energy minimization is provided. Geometric and material nonlinearities are included. The development is restricted to simple one and two dimensional finite elements which are regarded as being the basic elements for modeling full aircraft-like structures under crash conditions. The results indicate the effectiveness of the technique as a viable tool for this purpose.

Preface to the special volume on the second Sandia Fracture Challenge

DOE PAGES

Kramer, Sharlotte Lorraine Bolyard; Boyce, Brad

2016-01-01

In this study, ductile failure of structural metals is a pervasive issue for applications such as automotive manufacturing, transportation infrastructures, munitions and armor, and energy generation. Experimental investigation of all relevant failure scenarios is intractable, requiring reliance on computation models. Our confidence in model predictions rests on unbiased assessments of the entire predictive capability, including the mathematical formulation, numerical implementation, calibration, and execution.

Development of an Active Topical Skin Protectant (aTSP)

DTIC Science & Technology

2016-02-01

therapeutic compounds was clearly needed. Euthymic hairless guinea pigs [Crl:IAF/HA(hr/hr)Br] were selected for development at the USAMRICD. Vapor HD...hairless guinea pig offered several advantages over haired guinea pigs as a cutaneous vesicant animal model. These advantages included greater...the hairless guinea pig model. Many TSP formulations were evaluated and rank ordered. The supply of hairless guinea pigs , however, was interrupted

Improvement of the Pharmacokinetics and In Vivo Antibacterial Efficacy of a Novel Type IIa Topoisomerase Inhibitor by Formulation in Liposomes

PubMed Central

Newman, Joseph; Goteti, Kosalaram; Beaudoin, Marie-Eve; Harrison, Rane; Hopkins, Sussie; Agrawal, Nikunj; Rivin, Olga

2013-01-01

Several useful properties of liposome-based formulations of various existing antibacterial drugs have been reported. These properties include lower MICs, improved pharmacokinetics, lower toxicity, selective distribution to infected tissues, and enhanced in vivo efficacy. Here we report in vivo studies of a liposomal formulation of a member of a novel class of antibacterial type II topoisomerase inhibitors, others of which have progressed to early phases of clinical trials. The free (i.e., nonliposomal) compound has broad-spectrum MICs but suboptimal pharmacokinetics in rats and mice, characterized by a high volume of distribution and rapid clearance. The liposomal formulation of the compound had essentially unchanged MICs but greatly reduced volume of distribution and clearance in rats and mice. In an in vivo mouse model of Staphylococcus aureus infection of one thigh, the liposomal compound localized preferentially to the infected thigh, whereas the free compound showed no preference for the infected versus the uninfected thigh. Most importantly, the liposomal compound had enhanced efficacy at clearing the infection compared with the free compound. Delivery of this class of compounds as liposomal formulations may offer clinical advantages compared with free compounds. PMID:23877679

[Application of an artificial neural network in the design of sustained-release dosage forms].

PubMed

Wei, X H; Wu, J J; Liang, W Q

2001-09-01

To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

Diffuse-Interface Methods in Fluid Mechanics

NASA Technical Reports Server (NTRS)

Anderson, D. M.; McFadden, G. B.; Wheeler, A. A.

1997-01-01

The authors review the development of diffuse-interface models of hydrodynamics and their application to a wide variety of interfacial phenomena. The authors discuss the issues involved in formulating diffuse-interface models for single-component and binary fluids. Recent applications and computations using these models are discussed in each case. Further, the authors address issues including sharp-interface analyses that relate these models to the classical free-boundary problem, related computational approaches to describe interfacial phenomena, and related approaches describing fully-miscible fluids.

Culture, cultural factors and psychiatric diagnosis: review and projections.

PubMed

Alarcón, Renato D

2009-10-01

This paper aims to provide conceptual justifications for the inclusion of culture and cultural factors in psychiatric diagnosis, and logistic suggestions as to the content and use of this approach. A discussion of the scope and limitations of current diagnostic practice, criticisms from different quarters, and the role and relevance of culture in the diagnostic encounter, precede the examination of advantages and disadvantages of the approach. The cultural content of psychiatric diagnosis should include the main, well-recognized cultural variables, adequate family data, explanatory models, and strengths and weaknesses of every individual patient. The practical aspects include the acceptance of "cultural discordances" as a component of an updated definition of mental disorder, and the use of a refurbished cultural formulation. Clinical "telescoping" strategies to obtain relevant cultural data during the diagnostic interview, and areas of future research (including field trials on the cultural formulation and on "culture bound syndromes"), are outlined.

Program to Optimize Simulated Trajectories (POST). Volume 1: Formulation manual

NASA Technical Reports Server (NTRS)

Brauer, G. L.; Cornick, D. E.; Habeger, A. R.; Petersen, F. M.; Stevenson, R.

1975-01-01

A general purpose FORTRAN program for simulating and optimizing point mass trajectories (POST) of aerospace vehicles is described. The equations and the numerical techniques used in the program are documented. Topics discussed include: coordinate systems, planet model, trajectory simulation, auxiliary calculations, and targeting and optimization.

Diflerent formulations of microbial respiratory losses and microbial efficiency have pronounced short and long term consequences for soil C dynamics and soil respiration

NASA Astrophysics Data System (ADS)

Ballantyne, F.; Billings, S. A.

2016-12-01

Much of the variability in projections of Earth's future C balance derives from uncertainty in how to formulate and parameterize models of biologically mediated transformations of soil organic C (SOC). Over the past decade, models of belowground decomposition have incorporated more realism, namely microbial biomass and exoenzyme pools, but it remains unclear whether microbially mediated decomposition is accurately formulated. Different models and different assumptions about how microbial efficiency, defined in terms of respiratory losses, varies with temperature exert great influence on SOC and CO2 flux projections for the future. Here, we incorporate a physiologically realistic formulation of CO2 loss from microbes, distinct from extant formulations and logically consistent with microbial C uptake and losses, into belowground dynamics and contrast its projections for SOC pools and CO2 flux from soils to those from the phenomenological formulations of efficiency in current models. We quantitatively describe how short and long term SOC dynamics are influenced by different mathematical formulations of efficiency, and that our lack of knowledge regarding loss rates from SOC and microbial biomass pools, specific respiration rate and maximum substrate uptake rate severely constrains our ability to confidently parameterize microbial SOC modules in Earth System Models. Both steady-state SOC and microbial biomass C pools, as well as transient responses to perturbations, can differ substantially depending on how microbial efficiency is derived. In particular, the discrepancy between SOC stocks for different formulations of efficiency varies from negligible to more than two orders of magnitude, depending on the relative values of respiratory versus non-respiratory losses from microbial biomass. Mass-specific respiration and proportional loss rates from soil microbes emerge as key determinants of the consequences of different formulations of efficiency for C flux in soils.

Dynamics and rheology of finitely extensible polymer coils: An overview

NASA Astrophysics Data System (ADS)

Yao, Donggang

2017-05-01

One contemporary research issue in non-Newtonian fluid mechanics is to accurately and effectively model viscoelastic polymer flow of practical relevance. In the past several years, we have been working on the formulation of a finitely extensible coil model for polymer flow, particularly including these elements: (1) decoupled equations for kinematical and dynamical variables, (2) logarithmic relaxation at large deformation, (3) rotational retardation, (4) controllable straining, and (5) finite stretch. In this paper, we provide a constructive overview of this nonlinear coil formulation focusing on integration of these elements in a single, unified constitutive model with a minimal number of model parameters that are linked with corresponding physical processes. We also use this opportunity to share the rationale and thought process in the model development. In one particular implement of the general formulation, three parameters are used to tackle with the principal dynamics of a deforming polymer coil: one for finite stretch dictated by a ceiling stretch of the coil, the second one for rotational recovery/retardation, and the third one for adjusting stretch hardening of the rubbery coil. The new model, even in a single mode, is able to simultaneously predict practical material functions in simple shear and coaxial extension and to fit well to representative experimental data. Particularly in the steady-state (or quasi-steady state) flow case, a nearly closed-form stress to velocity gradient relationship can be derived with which shear thinning and elongational thickening can be simultaneously considered while computational advantages of a classical GNF model is retained. The model also fits reasonably well to representative experimental transient data for both shear and extension.

In vitro models for the prediction of in vivo performance of oral dosage forms.

PubMed

Kostewicz, Edmund S; Abrahamsson, Bertil; Brewster, Marcus; Brouwers, Joachim; Butler, James; Carlert, Sara; Dickinson, Paul A; Dressman, Jennifer; Holm, René; Klein, Sandra; Mann, James; McAllister, Mark; Minekus, Mans; Muenster, Uwe; Müllertz, Anette; Verwei, Miriam; Vertzoni, Maria; Weitschies, Werner; Augustijns, Patrick

2014-06-16

Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation…) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient. As part of the basis for the OrBiTo project, this review summarizes the current status of predictive in vitro assessment tools for formulation behavior. Both pharmacopoeia-listed apparatus and more advanced tools are discussed. Special attention is paid to major issues limiting the predictive power of traditional tools, including the simulation of dynamic changes in gastrointestinal conditions, the adequate reproduction of gastrointestinal motility, the simulation of supersaturation and precipitation, and the implementation of the solubility-permeability interplay. It is anticipated that the innovative in vitro biopharmaceutical tools arising from the OrBiTo project will lead to improved predictions for in vivo behavior of drug formulations in the GI tract. Copyright © 2013 Elsevier B.V. All rights reserved.

A robust approach to chance constrained optimal power flow with renewable generation

DOE PAGES

Lubin, Miles; Dvorkin, Yury; Backhaus, Scott N.

2016-09-01

Optimal Power Flow (OPF) dispatches controllable generation at minimum cost subject to operational constraints on generation and transmission assets. The uncertainty and variability of intermittent renewable generation is challenging current deterministic OPF approaches. Recent formulations of OPF use chance constraints to limit the risk from renewable generation uncertainty, however, these new approaches typically assume the probability distributions which characterize the uncertainty and variability are known exactly. We formulate a robust chance constrained (RCC) OPF that accounts for uncertainty in the parameters of these probability distributions by allowing them to be within an uncertainty set. The RCC OPF is solved usingmore » a cutting-plane algorithm that scales to large power systems. We demonstrate the RRC OPF on a modified model of the Bonneville Power Administration network, which includes 2209 buses and 176 controllable generators. In conclusion, deterministic, chance constrained (CC), and RCC OPF formulations are compared using several metrics including cost of generation, area control error, ramping of controllable generators, and occurrence of transmission line overloads as well as the respective computational performance.« less

Wound Healing Activity of Topical Application Forms Based on Ayurveda

PubMed Central

Datta, Hema Sharma; Mitra, Shankar Kumar; Patwardhan, Bhushan

2011-01-01

The traditional Indian medicine—Ayurveda, describes various herbs, fats, oils and minerals with anti-aging as well as wound healing properties. With aging, numerous changes occur in skin, including decrease in tissue cell regeneration, decrease in collagen content, loss of skin elasticity and mechanical strength. We prepared five topical anti-aging formulations using cow ghee, flax seed oil, Phyllanthus emblica fruits, Shorea robusta resin, Yashada bhasma as study materials. For preliminary efficacy evaluation of the anti-aging activity we chose excision and incision wound healing animal models and studied the parameters including wound contraction, collagen content and skin breaking strength which in turn is indicative of the tissue cell regeneration capacity, collagenation capacity and mechanical strength of skin. The group treated with the formulations containing Yashada bhasma along with Shorea robusta resin and flax seed oil showed significantly better wound contraction (P < .01), higher collagen content (P < .05) and better skin breaking strength (P < .01) as compared to control group; thus proposing them to be effective prospective anti-aging formulations. PMID:19252191

Rate-independent dissipation in phase-field modelling of displacive transformations

NASA Astrophysics Data System (ADS)

Tůma, K.; Stupkiewicz, S.; Petryk, H.

2018-05-01

In this paper, rate-independent dissipation is introduced into the phase-field framework for modelling of displacive transformations, such as martensitic phase transformation and twinning. The finite-strain phase-field model developed recently by the present authors is here extended beyond the limitations of purely viscous dissipation. The variational formulation, in which the evolution problem is formulated as a constrained minimization problem for a global rate-potential, is enhanced by including a mixed-type dissipation potential that combines viscous and rate-independent contributions. Effective computational treatment of the resulting incremental problem of non-smooth optimization is developed by employing the augmented Lagrangian method. It is demonstrated that a single Lagrange multiplier field suffices to handle the dissipation potential vertex and simultaneously to enforce physical constraints on the order parameter. In this way, the initially non-smooth problem of evolution is converted into a smooth stationarity problem. The model is implemented in a finite-element code and applied to solve two- and three-dimensional boundary value problems representative for shape memory alloys.

Modeling of Longitudinal Unsteady Aerodynamics of a Wing-Tail Combination

NASA Technical Reports Server (NTRS)

Klein, Vladislav

1999-01-01

Aerodynamic equations for the longitudinal motion of an aircraft with a horizontal tail were developed. In this development emphasis was given on obtaining model structure suitable for model identification from experimental data. The resulting aerodynamic models included unsteady effects in the form of linear indicial functions. These functions represented responses in the lift on the wing and tail alone, and interference between those two lifting surfaces. The effect of the wing on the tail was formulated for two different expressions concerning the downwash angle at the tail. The first expression used the Cowley-Glauert approximation known-as "lag-in-downwash," the second took into account growth of the wing circulation and delay in the development of the lift on the tail. Both approaches were demonstrated in two examples using the geometry of a fighter aircraft and a large transport. It was shown that the differences in the two downwash formulations would increase for an aircraft with long tail arm performing low-speed, rapid maneuvers.

The influence of polymeric excipients on the process of pharmaceutical availability of therapeutic agents from a model drug form. Part I. In formulations with controlled disintegration and release time.

PubMed

Nachajski, Michal Jakub; Zgoda, Marian Mikołaj

2010-01-01

Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

A Kinematic Calibration Process for Flight Robotic Arms

NASA Technical Reports Server (NTRS)

Collins, Curtis L.; Robinson, Matthew L.

2013-01-01

The Mars Science Laboratory (MSL) robotic arm is ten times more massive than any Mars robotic arm before it, yet with similar accuracy and repeatability positioning requirements. In order to assess and validate these requirements, a higher-fidelity model and calibration processes were needed. Kinematic calibration of robotic arms is a common and necessary process to ensure good positioning performance. Most methodologies assume a rigid arm, high-accuracy data collection, and some kind of optimization of kinematic parameters. A new detailed kinematic and deflection model of the MSL robotic arm was formulated in the design phase and used to update the initial positioning and orientation accuracy and repeatability requirements. This model included a higher-fidelity link stiffness matrix representation, as well as a link level thermal expansion model. In addition, it included an actuator backlash model. Analytical results highlighted the sensitivity of the arm accuracy to its joint initialization methodology. Because of this, a new technique for initializing the arm joint encoders through hardstop calibration was developed. This involved selecting arm configurations to use in Earth-based hardstop calibration that had corresponding configurations on Mars with the same joint torque to ensure repeatability in the different gravity environment. The process used to collect calibration data for the arm included the use of multiple weight stand-in turrets with enough metrology targets to reconstruct the full six-degree-of-freedom location of the rover and tool frames. The follow-on data processing of the metrology data utilized a standard differential formulation and linear parameter optimization technique.

Using a Mechanistic Reactive Transport Model to Represent Soil Organic Matter Dynamics and Climate Sensitivity

NASA Astrophysics Data System (ADS)

Guerry, N.; Riley, W. J.; Maggi, F.; Torn, M. S.; Kleber, M.

2011-12-01

The nature of long term Soil Organic Matter (SOM) dynamics is uncertain and the mechanisms involved are crudely represented in site, regional, and global models. Recent work challenging the paradigm that SOM is stabilized because of its sequential transformations to more intrinsically recalcitrant compounds motivated us to develop a mechanistic modeling framework that can be used to test hypotheses of SOM dynamics. We developed our C cycling model in TOUGHREACT, an established 3-dimensional reactive transport solver that accounts for multiple phases (aqueous, gaseous, sorbed), multiple species, advection and diffusion, and multiple microbial populations. Energy and mass exchange through the soil boundaries are accounted for via ground heat flux, rainfall, C sources (e.g., exudation, woody, leaf, root litter) and C losses (e.g., CO2 emissions and DOC deep percolation). SOM is categorized according to the various types of compounds commonly found in the above mentioned C sources and microbial byproducts, including poly- and monosaccharides, lignin, amino compounds, organic acids, nucleic acids, lipids, and phenols. Each of these compounds is accounted for by one or more representative species in the model. A reaction network was developed to describe the microbially-mediated processes and chemical interactions of these species, including depolymerization, microbial assimilation, respiration and deposition of byproducts, and incorporation of dead biomass into SOM stocks. Enzymatic reactions are characterized by Michaelis-Menten kinetics, with maximum reaction rates determined by the species' O/C ratio. Microbial activity is further regulated by soil moisture content, O2 availability, pH, and temperature. For the initial set of simulations, literature values were used to constrain microbial Monod parameters, Michaelis-Menten parameters, sorption parameters, physical protection, partitioning of microbial byproducts, and partitioning of litter inputs, although there is substantial uncertainty in how these relationships should be represented. We also developed several other model formulations, including one that represents SOM in pools of varying decomposability, but lacking explicit protection mechanisms. We tested the model against several observational and experimental datasets. An important conclusion of our analysis is that although several of the model structural formulations were able to represent the bulk SOM observations, including 14C vertical profiles, the temperature, moisture, and soil chemistry sensitivity of decomposition varied strongly between each formulation. Finally, we applied the model to design observations that would be required to better constrain process representation and improve predictions of changes in SOM under changing climate.

Case formulation and management using pattern-based formulation (PBF) methodology: clinical case 1.

PubMed

Fernando, Irosh; Cohen, Martin

2014-02-01

A tool for psychiatric case formulation known as pattern-based formulation (PBF) has been recently introduced. This paper presents an application of this methodology in formulating and managing complex clinical cases. The symptomatology of the clinical presentation has been parsed into individual clinical phenomena and interpreted by selecting explanatory models. The clinical presentation demonstrates how PBF has been used as a clinical tool to guide clinicians' thinking, that takes a structured approach to manage multiple issues using a broad range of management strategies. In doing so, the paper also introduces a number of patterns related to the observed clinical phenomena that can be re-used as explanatory models when formulating other clinical cases. It is expected that this paper will assist clinicians, and particularly trainees, to better understand PBF methodology and apply it to improve their formulation skills.

Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer

PubMed Central

Godugu, Chandraiah; Doddapaneni, Ravi; Safe, Stephen H.; Singh, Mandip

2017-01-01

The present study demonstrates the promising anticancer effects of novel C-substituted diindolylmethane (DIM) derivatives DIM-10 and DIM-14 in aggressive TNBC models. In vitro studies demonstrated that these compounds possess strong anticancer effects. Caco-2 permeability studies resulted in poor permeability and poor oral bioavailability was demonstrated by pharmacokinetic studies. Nano structured lipid carrier (NLC) formulations were prepared to increase the clinical acceptance of these compounds. Significant increase in oral bioavailability was observed with NLC formulations. Compared to DIM-10, DIM-10 NLC formulation showed increase in Cmax and AUC values by 4.73 and 11.19-folds, respectively. Similar pattern of increase was observed with DIM-14 NLC formulations. In dogs DIM-10 NLC formulations showed an increase of 2.65 and 2.94-fold in Cmax and AUC, respectively. The anticancer studies in MDA-MB-231 orthotopic TNBC models demonstrated significant reduction in tumor volumes in DIM-10 and DIM-14 NLC treated animals. Our studies suggest that NLC formulation of both DIM-10 and 14 is effective in TNBC models. PMID:27586082

Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trials

PubMed Central

Othman, Ahmed A; Nothaft, Wolfram; Awni, Walid M; Dutta, Sandeep

2013-01-01

Aim To characterize quantitatively the relationship between ABT-102, a potent and selective TRPV1 antagonist, exposure and its effects on body temperature in humans using a population pharmacokinetic/pharmacodynamic modelling approach. Methods Serial pharmacokinetic and body temperature (oral or core) measurements from three double-blind, randomized, placebo-controlled studies [single dose (2, 6, 18, 30 and 40 mg, solution formulation), multiple dose (2, 4 and 8 mg twice daily for 7 days, solution formulation) and multiple-dose (1, 2 and 4 mg twice daily for 7 days, solid dispersion formulation)] were analyzed. nonmem was used for model development and the model building steps were guided by pre-specified diagnostic and statistical criteria. The final model was qualified using non-parametric bootstrap and visual predictive check. Results The developed body temperature model included additive components of baseline, circadian rhythm (cosine function of time) and ABT-102 effect (Emax function of plasma concentration) with tolerance development (decrease in ABT-102 Emax over time). Type of body temperature measurement (oral vs. core) was included as a fixed effect on baseline, amplitude of circadian rhythm and residual error. The model estimates (95% bootstrap confidence interval) were: baseline oral body temperature, 36.3 (36.3, 36.4)°C; baseline core body temperature, 37.0 (37.0, 37.1)°C; oral circadian amplitude, 0.25 (0.22, 0.28)°C; core circadian amplitude, 0.31 (0.28, 0.34)°C; circadian phase shift, 7.6 (7.3, 7.9) h; ABT-102 Emax, 2.2 (1.9, 2.7)°C; ABT-102 EC50, 20 (15, 28) ng ml−1; tolerance T50, 28 (20, 43) h. Conclusions At exposures predicted to exert analgesic activity in humans, the effect of ABT-102 on body temperature is estimated to be 0.6 to 0.8°C. This effect attenuates within 2 to 3 days of dosing. PMID:22966986

The flow of plasma in the solar terrestrial environment

NASA Technical Reports Server (NTRS)

Schunk, R. W.

1992-01-01

The overall goal of our NASA Theory Program is to study the coupling, time delays, and feedback mechanisms between the various regions of the solar-terrestrial system in a self-consistent, quantitative manner. To accomplish this goal, it will eventually be necessary to have time-dependent macroscopic models of the different regions of the solar-terrestrial system and we are continually working toward this goal. However, our immediate emphasis is on the near-earth plasma environment, including the ionosphere, the plasmasphere, and the polar wind. In this area, we have developed unique global models that allow us to study the coupling between the different regions. Another important aspect of our NASA Theory Program concerns the effect that localized structure has on the macroscopic flow in the ionosphere, plasmasphere, thermosphere, and polar wind. The localized structure can be created by structured magnetospheric inputs (i.e., structured plasma convection, particle precipitation or Birkeland current patterns) or time variations in these inputs due to storms and substorms. Also, some of the plasma flows that we predict with our macroscopic models may be unstable, and another one of our goals is to examine the stability of our predicted flows. Because time-dependent, three-dimensional numerical models of the solar-terrestrial environment generally require extensive computer resources, they are usually based on relatively simple mathematical formulations (i.e., simple MHD or hydrodynamic formulation). Therefore, another long-range goal of our NASA Theory Program is to study the conditions under which various mathematical formulations can be applied to specific solar-terrestrial regions. This may involve a detailed comparison of kinetic, semikinetic, and hydrodynamic predictions for a given polar wind scenario or it may involve the comparison of a small-scale particle-in-cell (PIC) simulation of a plasma expansion event with a similar macroscopic expansion event. The different mathematical formulations have different strengths and weaknesses and a careful comparison of model predictions for similar geophysical situations will provide insight into when the various models can be used with confidence.

Update of the Polar SWIFT model for polar stratospheric ozone loss (Polar SWIFT version 2)

NASA Astrophysics Data System (ADS)

Wohltmann, Ingo; Lehmann, Ralph; Rex, Markus

2017-07-01

The Polar SWIFT model is a fast scheme for calculating the chemistry of stratospheric ozone depletion in polar winter. It is intended for use in global climate models (GCMs) and Earth system models (ESMs) to enable the simulation of mutual interactions between the ozone layer and climate. To date, climate models often use prescribed ozone fields, since a full stratospheric chemistry scheme is computationally very expensive. Polar SWIFT is based on a set of coupled differential equations, which simulate the polar vortex-averaged mixing ratios of the key species involved in polar ozone depletion on a given vertical level. These species are O3, chemically active chlorine (ClOx), HCl, ClONO2 and HNO3. The only external input parameters that drive the model are the fraction of the polar vortex in sunlight and the fraction of the polar vortex below the temperatures necessary for the formation of polar stratospheric clouds. Here, we present an update of the Polar SWIFT model introducing several improvements over the original model formulation. In particular, the model is now trained on vortex-averaged reaction rates of the ATLAS Chemistry and Transport Model, which enables a detailed look at individual processes and an independent validation of the different parameterizations contained in the differential equations. The training of the original Polar SWIFT model was based on fitting complete model runs to satellite observations and did not allow for this. A revised formulation of the system of differential equations is developed, which closely fits vortex-averaged reaction rates from ATLAS that represent the main chemical processes influencing ozone. In addition, a parameterization for the HNO3 change by denitrification is included. The rates of change of the concentrations of the chemical species of the Polar SWIFT model are purely chemical rates of change in the new version, whereas in the original Polar SWIFT model, they included a transport effect caused by the original training on satellite data. Hence, the new version allows for an implementation into climate models in combination with an existing stratospheric transport scheme. Finally, the model is now formulated on several vertical levels encompassing the vertical range in which polar ozone depletion is observed. The results of the Polar SWIFT model are validated with independent Microwave Limb Sounder (MLS) satellite observations and output from the original detailed chemistry model of ATLAS.

Some Applications of Piece-Wise Smooth Dynamical Systems

NASA Astrophysics Data System (ADS)

Janovská, Drahoslava; Hanus, Tomáš; Biák, Martin

2010-09-01

The Filippov systems theory is applied to selected problems from biology and chemical engineering, namely we explore and simulate Bazykin's ecological model, an ideal closed gas-liquid system including its dimensionless formulation. The last investigated system is a CSTR with an outfall and the CSTR with a reactor volume control.

DocCube: Multi-Dimensional Visualization and Exploration of Large Document Sets.

ERIC Educational Resources Information Center

Mothe, Josiane; Chrisment, Claude; Dousset, Bernard; Alaux, Joel

2003-01-01

Describes a user interface that provides global visualizations of large document sets to help users formulate the query that corresponds to their information needs. Highlights include concept hierarchies that users can browse to specify and refine information needs; knowledge discovery in databases and texts; and multidimensional modeling.…

The structure of shock wave in a gas consisting of ideally elastic, rigid spherical molecules

NASA Technical Reports Server (NTRS)

Cheremisin, F. G.

1972-01-01

Principal approaches are examined to the theoretical study of the shock layer structure. The choice of a molecular model is discussed and three procedures are formulated. These include a numerical calculation method, solution of the kinetic relaxation equation, and solution of the Boltzmann equation.

Formulation of consumables management models: Consumables flight planning worksheet update. [space shuttles

NASA Technical Reports Server (NTRS)

Newman, C. M.

1977-01-01

The updated consumables flight planning worksheet (CFPWS) is documented. The update includes: (1) additional consumables: ECLSS ammonia, APU propellant, HYD water; (2) additional on orbit activity for development flight instrumentation (DFI); (3) updated use factors for all consumables; and (4) sources and derivations of the use factors.

Undergraduate Nurse Variables that Predict Academic Achievement and Clinical Competence in Nursing

ERIC Educational Resources Information Center

Blackman, Ian; Hall, Margaret; Darmawan, I Gusti Ngurah.

2007-01-01

A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for undergraduate nursing students. Sixteen latent variables were considered including the students' background, gender, type of first language, age, their previous successes with their undergraduate nursing studies and status given for…

The impact of in-canopy wind profile formulations on heat flux estimation using the remote sensing-based two-source model for an open orchard canopy in southern Italy

NASA Astrophysics Data System (ADS)

Cammalleri, C.; Anderson, M. C.; Ciraolo, G.; D'Urso, G.; Kustas, W. P.; La Loggia, G.; Minacapilli, M.

2010-07-01

For open orchard and vineyard canopies containing significant fractions of exposed soil (>50%), typical of Mediterranean agricultural regions, the energy balance of the vegetation elements is strongly influenced by heat exchange with the bare soil/substrate. For these agricultural systems a "two-source" approach, where radiation and turbulent exchange between the soil and canopy elements are explicitly modelled, appears to be the only suitable methodology for reliably assessing energy fluxes. In strongly clumped canopies, the effective wind speed profile inside and below the canopy layer can highly influence the partitioning of energy fluxes between the soil and vegetation components. To assess the impact of in-canopy wind profile on model flux estimates, an analysis of three different formulations is presented, including algorithms from Goudriaan (1977), Massman (1987) and Lalic et al. (2003). The in-canopy wind profile formulations are applied to the thermal-based Two-Source Energy Balance (TSEB) model developed by Norman et al. (1995) and modified by Kustas and Norman (1999). High resolution airborne remote sensing images, collected over an agricultural area located in the western part of Sicily (Italy) comprised primarily of vineyards, olive and citrus orchards, are used to derive all the input parameters need to apply the TSEB. The images were acquired from June to October 2008 and include a relatively wide range of meteorological and soil moisture conditions. A preliminary sensitivity analysis of the three wind profile algorithms highlight the dependence of wind speed just above the soil/substrate to leaf area index and canopy height over the typical canopy properties range of these agricultural area. It is found that differences in wind just above surface among the models is most significant under sparse and medium fractional cover conditions (20-60%). The TSEB model heat flux estimates are compared with micrometeorological measurements from a small aperture scintillometer and an eddy covariance tower collected over an olive orchard characterized by moderate fractional vegetation cover (≈35%) and relatively tall crop height (≈3.5 m). TSEB fluxes for the 7 image acquisition dates generated using both the Massman and Goudriaan in-canopy wind profile formulations give close agreement with measured fluxes, while the Lalic et al. equations yield poor results. The Massman wind profile scheme slightly outperforms that of Goudriaan, but it requires an additional parameter describing the roughness of the underlying vegetative surface. This parameter is not directly obtainable using remote sensing, hence this study suggests that the Goudriaan formulation for landscape applications is most suitable when detailed site-specific information regarding canopy architecture is unavailable.

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Formulation and characterization of alprazolam-loaded nanoliposomes: screening of process variables and optimizing characteristics using RSM.

PubMed

Hashemi, Seyed Hesamoddin; Montazer, Majid; Naghdi, Nasser; Toliyat, Tayebeh

2018-02-01

This research study aimed to develop a novel sustained release formulation of alprazolam that can also be used for transdermal delivery. This was carried out, for the first time, through encapsulation of alprazolam in nanoliposomes using ethanol injection. In order to obtain the best formulation, four process variables, including the solvent/nonsolvent volume ratio, phospholipid concentration, alprazolam concentration, and cholesterol content were considered as key factors. Response surface methodology (RSM) and a central composite design (CCD) model were used to investigate the effect of these factors on vesicle size (VS) and encapsulation efficiency (EE) as the major properties of nanoliposomes. Experimental data were statistically analyzed, and two significant quadratic models were developed to test the VS and EE responses. The findings indicate that alprazolam and phospholipid concentrations have a significant effect on the mean VS. However, EE was significantly affected by both the alprazolam and phospholipid concentrations and the cholesterol content. The optimized formulation for preparation of alprazolam-loaded nanoliposomes with appropriate VS and EE was suggested. Small unilamellar vesicles (SUVs), ranging in size from 50 to 100 nm were clearly observed in the transmission electron microscopy (TEM) images, which is appropriate for transdermal delivery of alprazolam. The study of the prepared nanoliposomes over 28 days at 4 °C confirmed the stability of the formulations containing cholesterol. The results of an in vitro release study of alprazolam-loaded nanoliposomes in phosphate buffered saline (PBS), pH 7.4 for 24 h at 37 °C using dialysis, indicated the sustained release of alprazolam due to encapsulation.

Validation of numerical models for flow simulation in labyrinth seals

NASA Astrophysics Data System (ADS)

Frączek, D.; Wróblewski, W.

2016-10-01

CFD results were compared with the results of experiments for the flow through the labyrinth seal. RANS turbulence models (k-epsilon, k-omega, SST and SST-SAS) were selected for the study. Steady and transient results were analyzed. ANSYS CFX was used for numerical computation. The analysis included flow through sealing section with the honeycomb land. Leakage flows and velocity profiles in the seal were compared. In addition to the comparison of computational models, the divergence of modeling and experimental results has been determined. Tips for modeling these problems were formulated.

Evaporation from soils subjected to natural boundary conditions at the land-atmospheric interface

NASA Astrophysics Data System (ADS)

Smits, K.; Illngasekare, T.; Ngo, V.; Cihan, A.

2012-04-01

Bare soil evaporation is a key process for water exchange between the land and the atmosphere and an important component of the water balance in semiarid and arid regions. However, there is no agreement on the best methodology to determine evaporation under different boundary conditions at the land surface. This becomes critical in developing models that couples land to the atmosphere. Because it is difficult to measure evaporation from soil, with the exception of using lysimeters, numerous formulations have been proposed to establish a relationship between the rate of evaporation and soil moisture and/or soil temperature and thermal properties. Different formulations vary in how they partition available energy. A need exists to systematically compare existing methods to experimental data under highly controlled conditions not achievable in the field. The goal of this work is to perform controlled experiments under transient conditions of soil moisture, temperature and wind at the land/atmospheric interface to test different conceptual and mathematical formulations for the soil surface boundary conditions to develop appropriate numerical models to be used in simulations. In this study, to better understand the coupled water-vapor-heat flow processes in the shallow subsurface near the land surface, we modified a previously developed theory by Smits et al. [2011] that allows non-equilibrium liquid/gas phase change with gas phase vapor diffusion to better account for dry soil conditions. The model did not implement fitting parameters such as a vapor enhancement factor that is commonly introduced into the vapor diffusion coefficient as an arbitrary multiplication factor. In order to experimentally test the numerical formulations/code, we performed a two-dimensional physical model experiment under varying boundary conditions using test sand for which the hydraulic and thermal properties were well characterized. Precision data under well-controlled transient heat and wind boundary conditions was generated and results from numerical simulations were compared with experimental data. Results demonstrate that the boundary condition approaches varied in their ability to capture stage 1- and stage 2- evaporation. Results also demonstrated the importance of properly characterizing soil thermal properties and accounting for dry soil conditions. The contribution of film flow to hydraulic conductivity for the layer above the drying front is dominant compared to that of capillary flow, demonstrating the importance of including film flow in modeling efforts for dry soils, especially for fine grained soils. Comparisons of different formulations of the surface boundary condition validate the need for joint evaluation of heat and mass transfer for better modeling accuracy. This knowledge is applicable to many current hydrologic and environmental problems to include climate modeling and the simulation of contaminant transport and volatilization in the shallow subsurface. Smits, K. M., A. Cihan, T. Sakaki, and T. H. Illangasekare (2011). Evaporation from soils under thermal boundary conditions: Experimental and modeling investigation to compare equilibrium- and nonequilibrium-based approaches, Water Resour. Res., 47, W05540, doi:10.1029/2010WR009533.

CONSTRUCTION OF EDUCATIONAL THEORY MODELS.

ERIC Educational Resources Information Center

MACCIA, ELIZABETH S.; AND OTHERS

THIS STUDY DELINEATED MODELS WHICH HAVE POTENTIAL USE IN GENERATING EDUCATIONAL THEORY. A THEORY MODELS METHOD WAS FORMULATED. BY SELECTING AND ORDERING CONCEPTS FROM OTHER DISCIPLINES, THE INVESTIGATORS FORMULATED SEVEN THEORY MODELS. THE FINAL STEP OF DEVISING EDUCATIONAL THEORY FROM THE THEORY MODELS WAS PERFORMED ONLY TO THE EXTENT REQUIRED TO…

Dynamical computation of constrained flexible systems using a modal Udwadia-Kalaba formulation: Application to musical instruments.

PubMed

Antunes, J; Debut, V

2017-02-01

Most musical instruments consist of dynamical subsystems connected at a number of constraining points through which energy flows. For physical sound synthesis, one important difficulty deals with enforcing these coupling constraints. While standard techniques include the use of Lagrange multipliers or penalty methods, in this paper, a different approach is explored, the Udwadia-Kalaba (U-K) formulation, which is rooted on analytical dynamics but avoids the use of Lagrange multipliers. This general and elegant formulation has been nearly exclusively used for conceptual systems of discrete masses or articulated rigid bodies, namely, in robotics. However its natural extension to deal with continuous flexible systems is surprisingly absent from the literature. Here, such a modeling strategy is developed and the potential of combining the U-K equation for constrained systems with the modal description is shown, in particular, to simulate musical instruments. Objectives are twofold: (1) Develop the U-K equation for constrained flexible systems with subsystems modelled through unconstrained modes; and (2) apply this framework to compute string/body coupled dynamics. This example complements previous work [Debut, Antunes, Marques, and Carvalho, Appl. Acoust. 108, 3-18 (2016)] on guitar modeling using penalty methods. Simulations show that the proposed technique provides similar results with a significant improvement in computational efficiency.

Dynamic analysis of nonlinear rotor-housing systems

NASA Technical Reports Server (NTRS)

Noah, Sherif T.

1988-01-01

Nonlinear analysis methods are developed which will enable the reliable prediction of the dynamic behavior of the space shuttle main engine (SSME) turbopumps in the presence of bearing clearances and other local nonlinearities. A computationally efficient convolution method, based on discretized Duhamel and transition matrix integral formulations, is developed for the transient analysis. In the formulation, the coupling forces due to the nonlinearities are treated as external forces acting on the coupled subsystems. Iteration is utilized to determine their magnitudes at each time increment. The method is applied to a nonlinear generic model of the high pressure oxygen turbopump (HPOTP). As compared to the fourth order Runge-Kutta numerical integration methods, the convolution approach proved to be more accurate and more highly efficient. For determining the nonlinear, steady-state periodic responses, an incremental harmonic balance method was also developed. The method was successfully used to determine dominantly harmonic and subharmonic responses fo the HPOTP generic model with bearing clearances. A reduction method similar to the impedance formulation utilized with linear systems is used to reduce the housing-rotor models to their coordinates at the bearing clearances. Recommendations are included for further development of the method, for extending the analysis to aperiodic and chaotic regimes and for conducting critical parameteric studies of the nonlinear response of the current SSME turbopumps.

A Diffuse Interface Model with Immiscibility Preservation

PubMed Central

Tiwari, Arpit; Freund, Jonathan B.; Pantano, Carlos

2013-01-01

A new, simple, and computationally efficient interface capturing scheme based on a diffuse interface approach is presented for simulation of compressible multiphase flows. Multi-fluid interfaces are represented using field variables (interface functions) with associated transport equations that are augmented, with respect to an established formulation, to enforce a selected interface thickness. The resulting interface region can be set just thick enough to be resolved by the underlying mesh and numerical method, yet thin enough to provide an efficient model for dynamics of well-resolved scales. A key advance in the present method is that the interface regularization is asymptotically compatible with the thermodynamic mixture laws of the mixture model upon which it is constructed. It incorporates first-order pressure and velocity non-equilibrium effects while preserving interface conditions for equilibrium flows, even within the thin diffused mixture region. We first quantify the improved convergence of this formulation in some widely used one-dimensional configurations, then show that it enables fundamentally better simulations of bubble dynamics. Demonstrations include both a spherical bubble collapse, which is shown to maintain excellent symmetry despite the Cartesian mesh, and a jetting bubble collapse adjacent a wall. Comparisons show that without the new formulation the jet is suppressed by numerical diffusion leading to qualitatively incorrect results. PMID:24058207

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.

Formulation and Application of the Generalized Multilevel Facets Model

ERIC Educational Resources Information Center

Wang, Wen-Chung; Liu, Chih-Yu

2007-01-01

In this study, the authors develop a generalized multilevel facets model, which is not only a multilevel and two-parameter generalization of the facets model, but also a multilevel and facet generalization of the generalized partial credit model. Because the new model is formulated within a framework of nonlinear mixed models, no efforts are…

Extensive preclinical investigation of polymersomal formulation of doxorubicin versus Doxil-mimic formulation.

PubMed

Alibolandi, Mona; Abnous, Khalil; Mohammadi, Marzieh; Hadizadeh, Farzin; Sadeghi, Fatemeh; Taghavi, Sahar; Jaafari, Mahmoud Reza; Ramezani, Mohammad

2017-10-28

Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate after one injection of formulations (5mg/kg, 10mg/kg or 15mg/kg) demonstrated better efficacy at lower dose for PolyDOX. Analysis of Kaplan Meier curve was in favor of both formulations in their treatment-dose. Pathological and hematological surveys of mice treated with both formulations did not show considerable difference except for a small atrophy in liver observed after successive administration of Doxil-mimic. It could be concluded that PolyDOX can potentially limit off-site effects of Doxil due to its biodegradability and sustained release properties while it exhibited favorable safety profile comparable to Doxil. Copyright © 2017 Elsevier B.V. All rights reserved.

Pectin-based oral drug delivery to the colon.

PubMed

Sande, Sverre Arne

2005-05-01

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.

PubMed

Whaley, Kevin J; Hanes, Justin; Shattock, Robin; Cone, Richard A; Friend, David R

2010-12-01

The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

The effect of operating and formulation variables on the morphology of spray-dried protein particles.

PubMed

Maa, Y F; Costantino, H R; Nguyen, P A; Hsu, C C

1997-08-01

The purpose of this research was to investigate the shape and morphology of various spray-dried protein powders as a function of spray-drying conditions and protein formulations. A benchtop spray dryer was used to spray dry three model proteins in formulation with a sugar or a surfactant. Physical characterizations of the powder included morphology (scanning electron microscopy), particle size, residual moisture, and X-ray powder diffraction analyses. A significant change in particle shape from irregular (e.g., "donut") to spherical was observed as the outlet temperature of the dryer was decreased. The drying air outlet temperature was shown to depend on various operating parameters and was found to correlate with the drying rate of atomized droplets in the drying chamber. The morphology of spray-dried protein particles was also affected by formulation. In protein:sugar formulations, spray-dried particles exhibited a smooth surface regardless of the protein-to-lactose ratio, whereas roughness was observed when mannitol was present at > 30% of total solids, due to recrystallization. Protein particles containing trehalose at concentrations > 50% were highly agglomerated. The presence of surfactant resulted in noticeably smoother, more spherical particles. The shape and the morphology of spray-dried powders are affected by spray drying conditions and protein formulation. This study provides information useful for development of dry proteins for fine powder (e.g., aerosol) applications.

In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

PubMed

Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

2012-11-01

In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Tulane/Xavier Vaccine Peptide Program

DTIC Science & Technology

2013-07-01

include a dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. Nasal...pulmonary delivery: dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. (3) Confirm...include a dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. Nasal

The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases.

PubMed

Salmonson, Heléne; Sjöberg, Gunilla; Brogren, Jacob

2018-01-01

The use of the standard procedure for managing overdoses with immediate release (IR) paracetamol is questionable when applied to overdoses with modified release (MR) formulations. This study describes the pharmacokinetics of paracetamol and the clinical outcomes following overdoses with a MR formulation. Medical records including laboratory analyses concerning overdoses of MR paracetamol from 2009 to 2015 were collected retrospectively. Inclusion criteria were ingestion of a toxic dose, known time of intake and documented measurements of serum paracetamol and liver function tests. Graphical analysis, descriptive statistics and population pharmacokinetic modelling were used to describe data. Fifty-three cases were identified. Median age was 26 years (range 13-68), median dose was 20 g (range 10-166) and 74% were females. The pharmacokinetic analysis showed a complex, dose dependent serum versus time profile with prolonged absorption and delayed serum peak concentrations with increasing dose. Ten patients had persistently high serum levels for 24 h or more, six of them had a second peak 8-19 h after ingestion. Seven of 34 patients receiving N-acetylcysteine (NAC) within 8 h had alanine aminotransferase (ALT) above reference range. Three of them developed hepatotoxicity (ALT >1000 IU/l). The pharmacokinetic and clinical analysis showed that the standard treatment protocol, including risk assessment and NAC regimen, used for IR paracetamol poisoning not appear suitable for MR formulation. Individual and tailored treatment may be valuable but further studies are warranted to determine optimal regimen of overdoses with MR formulation.

Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

2015-01-01

This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

PubMed Central

Wang, Lin; Sassi, Alexandra Beumer; Patton, Dorothy; Isaacs, Charles; Moncla, B. J.; Gupta, Phalguni; Rohan, Lisa Cencia

2015-01-01

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae. PMID:22149387

A boundary element method for steady incompressible thermoviscous flow

NASA Technical Reports Server (NTRS)

Dargush, G. F.; Banerjee, P. K.

1991-01-01

A boundary element formulation is presented for moderate Reynolds number, steady, incompressible, thermoviscous flows. The governing integral equations are written exclusively in terms of velocities and temperatures, thus eliminating the need for the computation of any gradients. Furthermore, with the introduction of reference velocities and temperatures, volume modeling can often be confined to only a small portion of the problem domain, typically near obstacles or walls. The numerical implementation includes higher order elements, adaptive integration and multiregion capability. Both the integral formulation and implementation are discussed in detail. Several examples illustrate the high level of accuracy that is obtainable with the current method.

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PubMed

Mittapalli, Rajendar K; Marroum, Patrick; Qiu, Yihong; Apfelbaum, Kathleen; Xiong, Hao

2017-07-01

To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (A e0-24h ) and maximum urinary excretion rate (R max ) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

The MV model of the color glass condensate for a finite number of sources including Coulomb interactions

DOE PAGES

McLerran, Larry; Skokov, Vladimir V.

2016-09-19

We modify the McLerran–Venugopalan model to include only a finite number of sources of color charge. In the effective action for such a system of a finite number of sources, there is a point-like interaction and a Coulombic interaction. The point interaction generates the standard fluctuation term in the McLerran–Venugopalan model. The Coulomb interaction generates the charge screening originating from well known evolution in x. Such a model may be useful for computing angular harmonics of flow measured in high energy hadron collisions for small systems. In this study we provide a basic formulation of the problem on a lattice.

Enthalpy of Mixing in Al–Tb Liquid

DOE PAGES

Zhou, Shihuai; Tackes, Carl; Napolitano, Ralph

2017-06-21

The liquid-phase enthalpy of mixing for Al$-$Tb alloys is measured for 3, 5, 8, 10, and 20 at% Tb at selected temperatures in the range from 1364 to 1439 K. Methods include isothermal solution calorimetry and isoperibolic electromagnetic levitation drop calorimetry. Mixing enthalpy is determined relative to the unmixed pure (Al and Tb) components. The required formation enthalpy for the Al3Tb phase is computed from first-principles calculations. Finally, based on our measurements, three different semi-empirical solution models are offered for the excess free energy of the liquid, including regular, subregular, and associate model formulations. These models are also compared withmore » the Miedema model prediction of mixing enthalpy.« less

Wave-propagation formulation of seismic response of multistory buildings

USGS Publications Warehouse

Safak, E.

1999-01-01

This paper presents a discrete-time wave-propagation method to calculate the seismic response of multistory buildings, founded on layered soil media and subjected to vertically propagating shear waves. Buildings are modeled as an extension of the layered soil media by considering each story as another layer in the wave-propagation path. The seismic response is expressed in terms of wave travel times between the layers and wave reflection and transmission coefficients at layer interfaces. The method accounts for the filtering effects of the concentrated foundation and floor masses. Compared with commonly used vibration formulation, the wave-propagation formulation provides several advantages, including simplicity, improved accuracy, better representation of damping, the ability to incorporate the soil layers under the foundation, and providing better tools for identification and damage detection from seismic records. Examples are presented to show the versatility and the superiority of the method.

Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: challenges and opportunities.

PubMed

Dasari, Vijayendra; Bhatt, Kunal H; Smith, Corey; Khanna, Rajiv

2017-04-01

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a number of clinical manifestations. Primary EBV infection in young adolescents often manifests as acute infectious mononucleosis and latent infection is associated with multiple lymphoid and epithelial cancers and autoimmune disorders, particularly multiple sclerosis. Areas covered: Over the last decade, our understanding of pathogenesis and immune regulation of EBV-associated diseases has provided an important platform for the development of novel vaccine formulations. In this review, we discuss developmental strategies for prophylactic and therapeutic EBV vaccines which have been assessed in preclinical and clinical settings. Expert commentary: Major roadblocks in EBV vaccine development include no precise understanding of the clinical correlates of protection, uncertainty about adjuvant selection and the unavailability of appropriate animal models. Recent development of new EBV vaccine formulations provides exciting opportunities for the formal clinical assessment of novel formulations.

Systems and methods for energy cost optimization in a building system

DOEpatents

Turney, Robert D.; Wenzel, Michael J.

2016-09-06

Methods and systems to minimize energy cost in response to time-varying energy prices are presented for a variety of different pricing scenarios. A cascaded model predictive control system is disclosed comprising an inner controller and an outer controller. The inner controller controls power use using a derivative of a temperature setpoint and the outer controller controls temperature via a power setpoint or power deferral. An optimization procedure is used to minimize a cost function within a time horizon subject to temperature constraints, equality constraints, and demand charge constraints. Equality constraints are formulated using system model information and system state information whereas demand charge constraints are formulated using system state information and pricing information. A masking procedure is used to invalidate demand charge constraints for inactive pricing periods including peak, partial-peak, off-peak, critical-peak, and real-time.

TRIM—3D: a three-dimensional model for accurate simulation of shallow water flow

USGS Publications Warehouse

Casulli, Vincenzo; Bertolazzi, Enrico; Cheng, Ralph T.

1993-01-01

A semi-implicit finite difference formulation for the numerical solution of three-dimensional tidal circulation is discussed. The governing equations are the three-dimensional Reynolds equations in which the pressure is assumed to be hydrostatic. A minimal degree of implicitness has been introduced in the finite difference formula so that the resulting algorithm permits the use of large time steps at a minimal computational cost. This formulation includes the simulation of flooding and drying of tidal flats, and is fully vectorizable for an efficient implementation on modern vector computers. The high computational efficiency of this method has made it possible to provide the fine details of circulation structure in complex regions that previous studies were unable to obtain. For proper interpretation of the model results suitable interactive graphics is also an essential tool.

The role of modern control theory in the design of controls for aircraft turbine engines

NASA Technical Reports Server (NTRS)

Zeller, J.; Lehtinen, B.; Merrill, W.

1982-01-01

The development, applications, and current research in modern control theory (MCT) are reviewed, noting the importance for fuel-efficient operation of turbines with variable inlet guide vanes, compressor stators, and exhaust nozzle area. The evolution of multivariable propulsion control design is examined, noting a basis in a matrix formulation of the differential equations defining the process, leading to state space formulations. Reports and papers which appeared from 1970-1982 which dealt with problems in MCT applications to turbine engine control design are outlined, including works on linear quadratic regulator methods, frequency domain methods, identification, estimation, and model reduction, detection, isolation, and accommodation, and state space control, adaptive control, and optimization approaches. Finally, NASA programs in frequency domain design, sensor failure detection, computer-aided control design, and plant modeling are explored

A spatial operator algebra for manipulator modeling and control

NASA Technical Reports Server (NTRS)

Rodriguez, G.; Kreutz, K.; Milman, M.

1988-01-01

A powerful new spatial operator algebra for modeling, control, and trajectory design of manipulators is discussed along with its implementation in the Ada programming language. Applications of this algebra to robotics include an operator representation of the manipulator Jacobian matrix; the robot dynamical equations formulated in terms of the spatial algebra, showing the complete equivalence between the recursive Newton-Euler formulations to robot dynamics; the operator factorization and inversion of the manipulator mass matrix which immediately results in O(N) recursive forward dynamics algorithms; the joint accelerations of a manipulator due to a tip contact force; the recursive computation of the equivalent mass matrix as seen at the tip of a manipulator; and recursive forward dynamics of a closed chain system. Finally, additional applications and current research involving the use of the spatial operator algebra are discussed in general terms.

Dynamic rupture modeling with laboratory-derived constitutive relations

USGS Publications Warehouse

Okubo, P.G.

1989-01-01

A laboratory-derived state variable friction constitutive relation is used in the numerical simulation of the dynamic growth of an in-plane or mode II shear crack. According to this formulation, originally presented by J.H. Dieterich, frictional resistance varies with the logarithm of the slip rate and with the logarithm of the frictional state variable as identified by A.L. Ruina. Under conditions of steady sliding, the state variable is proportional to (slip rate)-1. Following suddenly introduced increases in slip rate, the rate and state dependencies combine to produce behavior which resembles slip weakening. When rupture nucleation is artificially forced at fixed rupture velocity, rupture models calculated with the state variable friction in a uniformly distributed initial stress field closely resemble earlier rupture models calculated with a slip weakening fault constitutive relation. Model calculations suggest that dynamic rupture following a state variable friction relation is similar to that following a simpler fault slip weakening law. However, when modeling the full cycle of fault motions, rate-dependent frictional responses included in the state variable formulation are important at low slip rates associated with rupture nucleation. -from Author

Data-Driven Modeling and Prediction of Arctic Sea Ice

NASA Astrophysics Data System (ADS)

Kondrashov, Dmitri; Chekroun, Mickael; Ghil, Michael

2016-04-01

We present results of data-driven predictive analyses of sea ice over the main Arctic regions. Our approach relies on the Multilayer Stochastic Modeling (MSM) framework of Kondrashov, Chekroun and Ghil [Physica D, 2015] and it leads to probabilistic prognostic models of sea ice concentration (SIC) anomalies on seasonal time scales. This approach is applied to monthly time series of state-of-the-art data-adaptive decompositions of SIC and selected climate variables over the Arctic. We evaluate the predictive skill of MSM models by performing retrospective forecasts with "no-look ahead" for up to 6-months ahead. It will be shown in particular that the memory effects included intrinsically in the formulation of our non-Markovian MSM models allow for improvements of the prediction skill of large-amplitude SIC anomalies in certain Arctic regions on the one hand, and of September Sea Ice Extent, on the other. Further improvements allowed by the MSM framework will adopt a nonlinear formulation and explore next-generation data-adaptive decompositions, namely modification of Principal Oscillation Patterns (POPs) and rotated Multichannel Singular Spectrum Analysis (M-SSA).

N-mix for fish: estimating riverine salmonid habitat selection via N-mixture models

USGS Publications Warehouse

Som, Nicholas A.; Perry, Russell W.; Jones, Edward C.; De Juilio, Kyle; Petros, Paul; Pinnix, William D.; Rupert, Derek L.

2018-01-01

Models that formulate mathematical linkages between fish use and habitat characteristics are applied for many purposes. For riverine fish, these linkages are often cast as resource selection functions with variables including depth and velocity of water and distance to nearest cover. Ecologists are now recognizing the role that detection plays in observing organisms, and failure to account for imperfect detection can lead to spurious inference. Herein, we present a flexible N-mixture model to associate habitat characteristics with the abundance of riverine salmonids that simultaneously estimates detection probability. Our formulation has the added benefits of accounting for demographics variation and can generate probabilistic statements regarding intensity of habitat use. In addition to the conceptual benefits, model application to data from the Trinity River, California, yields interesting results. Detection was estimated to vary among surveyors, but there was little spatial or temporal variation. Additionally, a weaker effect of water depth on resource selection is estimated than that reported by previous studies not accounting for detection probability. N-mixture models show great promise for applications to riverine resource selection.

Simulating Flying Insects Using Dynamics and Data-Driven Noise Modeling to Generate Diverse Collective Behaviors

PubMed Central

Ren, Jiaping; Wang, Xinjie; Manocha, Dinesh

2016-01-01

We present a biologically plausible dynamics model to simulate swarms of flying insects. Our formulation, which is based on biological conclusions and experimental observations, is designed to simulate large insect swarms of varying densities. We use a force-based model that captures different interactions between the insects and the environment and computes collision-free trajectories for each individual insect. Furthermore, we model the noise as a constructive force at the collective level and present a technique to generate noise-induced insect movements in a large swarm that are similar to those observed in real-world trajectories. We use a data-driven formulation that is based on pre-recorded insect trajectories. We also present a novel evaluation metric and a statistical validation approach that takes into account various characteristics of insect motions. In practice, the combination of Curl noise function with our dynamics model is used to generate realistic swarm simulations and emergent behaviors. We highlight its performance for simulating large flying swarms of midges, fruit fly, locusts and moths and demonstrate many collective behaviors, including aggregation, migration, phase transition, and escape responses. PMID:27187068

Multibody dynamic analysis using a rotation-free shell element with corotational frame

NASA Astrophysics Data System (ADS)

Shi, Jiabei; Liu, Zhuyong; Hong, Jiazhen

2018-03-01

Rotation-free shell formulation is a simple and effective method to model a shell with large deformation. Moreover, it can be compatible with the existing theories of finite element method. However, a rotation-free shell is seldom employed in multibody systems. Using a derivative of rigid body motion, an efficient nonlinear shell model is proposed based on the rotation-free shell element and corotational frame. The bending and membrane strains of the shell have been simplified by isolating deformational displacements from the detailed description of rigid body motion. The consistent stiffness matrix can be obtained easily in this form of shell model. To model the multibody system consisting of the presented shells, joint kinematic constraints including translational and rotational constraints are deduced in the context of geometric nonlinear rotation-free element. A simple node-to-surface contact discretization and penalty method are adopted for contacts between shells. A series of analyses for multibody system dynamics are presented to validate the proposed formulation. Furthermore, the deployment of a large scaled solar array is presented to verify the comprehensive performance of the nonlinear shell model.

Gamma-Ray Bursts and Fast Transients. Multi-wavelength Observations and Multi-messenger Signals

NASA Astrophysics Data System (ADS)

Willingale, R.; Mészáros, P.

2017-07-01

The current status of observations and theoretical models of gamma-ray bursts and some other related transients, including ultra-long bursts and tidal disruption events, is reviewed. We consider the impact of multi-wavelength data on the formulation and development of theoretical models for the prompt and afterglow emission including the standard fireball model utilizing internal shocks and external shocks, photospheric emission, the role of the magnetic field and hadronic processes. In addition, we discuss some of the prospects for non-photonic multi-messenger detection and for future instrumentation, and comment on some of the outstanding issues in the field.

An operational GLS model for hydrologic regression

USGS Publications Warehouse

Tasker, Gary D.; Stedinger, J.R.

1989-01-01

Recent Monte Carlo studies have documented the value of generalized least squares (GLS) procedures to estimate empirical relationships between streamflow statistics and physiographic basin characteristics. This paper presents a number of extensions of the GLS method that deal with realities and complexities of regional hydrologic data sets that were not addressed in the simulation studies. These extensions include: (1) a more realistic model of the underlying model errors; (2) smoothed estimates of cross correlation of flows; (3) procedures for including historical flow data; (4) diagnostic statistics describing leverage and influence for GLS regression; and (5) the formulation of a mathematical program for evaluating future gaging activities. ?? 1989.

From cells to tissue: A continuum model of epithelial mechanics

NASA Astrophysics Data System (ADS)

Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

2017-08-01

A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

Manpower Mix for Health Services

PubMed Central

Shuman, Larry J.; Young, John P.; Naddor, Eliezer

1971-01-01

A model is formulated to determine the mix of manpower and technology needed to provide health services of acceptable quality at a minimum total cost to the community. Total costs include both the direct costs associated with providing the services and with developing additional manpower and the indirect costs (shortage costs) resulting from not providing needed services. The model is applied to a hypothetical neighborhood health center, and its sensitivity to alternative policies is investigated by cost-benefit analyses. Possible extensions of the model to include dynamic elements in health delivery systems are discussed, as is its adaptation for use in hospital planning, with a changed objective function. PMID:5095652

Propagation of seismic waves in tall buildings

USGS Publications Warehouse

Safak, E.

1998-01-01

A discrete-time wave propagation formulation of the seismic response of tall buildings is introduced. The building is modeled as a layered medium, similar to a layered soil medium, and is subjected to vertically propagating seismic shear waves. Soil layers and the bedrock under the foundation are incorporated in the formulation as additional layers. Seismic response is expressed in terms of the wave travel times between the layers, and the wave reflection and transmission coefficients at the layer interfaces. The equations account for the frequency-dependent filtering effects of the foundation and floor masses. The calculation of seismic response is reduced to a pair of simple finite-difference equations for each layer, which can be solved recursively starting from the bedrock. Compared to the commonly used vibration formulation, the wave propagation formulation provides several advantages, including simplified calculations, better representation of damping, ability to account for the effects of the soil layers under the foundation, and better tools for identification and damage detection from seismic records. Examples presented show the versatility of the method. ?? 1998 John Wiley & Sons, Ltd.

Stability of nonuniform rotor blades in hover using a mixed formulation

NASA Technical Reports Server (NTRS)

Stephens, W. B.; Hodges, D. H.; Avila, J. H.; Kung, R. M.

1980-01-01

A mixed formulation for calculating static equilibrium and stability eigenvalues of nonuniform rotor blades in hover is presented. The static equilibrium equations are nonlinear and are solved by an accurate and efficient collocation method. The linearized perturbation equations are solved by a one step, second order integration scheme. The numerical results correlate very well with published results from a nearly identical stability analysis based on a displacement formulation. Slight differences in the results are traced to terms in the equations that relate moments to derivatives of rotations. With the present ordering scheme, in which terms of the order of squares of rotations are neglected with respect to unity, it is not possible to achieve completely equivalent models based on mixed and displacement formulations. The one step methods reveal that a second order Taylor expansion is necessary to achieve good convergence for nonuniform rotating blades. Numerical results for a hypothetical nonuniform blade, including the nonlinear static equilibrium solution, were obtained with no more effort or computer time than that required for a uniform blade.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

PubMed

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-08-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

PubMed Central

Kim, Tae Hee; Mount, Christopher W; Dulken, Benjamin W; Ramos, Jenelyn; Fu, Caroline J; Khant, Htet A; Chiu, Wah; Gombotz, Wayne R; Pun, Suzie H

2012-01-01

Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles comprised of poly (ethylene oxide)-poly-[(R)-3-hydroxybutyrate]-poly (ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by non-invasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability was attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components. PMID:22118658

Turbofan forced mixer lobe flow modeling. 2: Three-dimensional inviscid mixer analysis (FLOMIX)

NASA Technical Reports Server (NTRS)

Barber, T.

1988-01-01

A three-dimensional potential analysis (FLOMIX) was formulated and applied to the inviscid flow over a turbofan foced mixer. The method uses a small disturbance formulation to analytically uncouple the circumferential flow from the radial and axial flow problem, thereby reducing the analysis to the solution of a series of axisymmetric problems. These equations are discretized using a flux volume formulation along a Cartesian grid. The method extends earlier applications of the Cartesian method to complex cambered geometries. The effects of power addition are also included within the potential formulation. Good agreement is obtained with an alternate small disturbance analysis for a high penetration symmetric mixer in a planar duct. In addition, calculations showing pressure distributions and induced secondary vorticity fields are presented for practical trubofan mixer configurations, and where possible, comparison was made with available experimental data. A detailed description of the required data input and coordinate definition is presented along with a sample data set for a practical forced mixer configuration. A brief description of the program structure and subroutines is also provided.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology

PubMed Central

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-01-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer’s disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD. PMID:28763060

A geometrically exact formulation for three-dimensional numerical simulation of the umbilical cable in a deep-sea ROV system

NASA Astrophysics Data System (ADS)

Quan, Wei-cai; Zhang, Zhu-ying; Zhang, Ai-qun; Zhang, Qi-feng; Tian, Yu

2015-04-01

This paper proposes a geometrically exact formulation for three-dimensional static and dynamic analyses of the umbilical cable in a deep-sea remotely operated vehicle (ROV) system. The presented formulation takes account of the geometric nonlinearities of large displacement, effects of axial load and bending stiffness for modeling of slack cables. The resulting nonlinear second-order governing equations are discretized spatially by the finite element method and solved temporally by the generalized- α implicit time integration algorithm, which is adapted to the case of varying coefficient matrices. The ability to consider three-dimensional union action of ocean current and ship heave motion upon the umbilical cable is the key feature of this analysis. The presented formulation is firstly validated, and then three numerical examples for the umbilical cable in a deep-sea ROV system are demonstrated and discussed, including the steady configurations only under the action of depth-dependent ocean current, the dynamic responses in the case of the only ship heave motion, and in the case of the combined action of the ship heave motion and ocean current.

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

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

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 processmore » 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.« less

Novel residual-based large eddy simulation turbulence models for incompressible magnetohydrodynamics

NASA Astrophysics Data System (ADS)

Sondak, David

The goal of this work was to develop, introduce, and test a promising computational paradigm for the development of turbulence models for incompressible magnetohydrodynamics (MHD). MHD governs the behavior of an electrically conducting fluid in the presence of an external electromagnetic (EM) field. The incompressible MHD model is used in many engineering and scientific disciplines from the development of nuclear fusion as a sustainable energy source to the study of space weather and solar physics. Many interesting MHD systems exhibit the phenomenon of turbulence which remains an elusive problem from all scientific perspectives. This work focuses on the computational perspective and proposes techniques that enable the study of systems involving MHD turbulence. Direct numerical simulation (DNS) is not a feasible approach for studying MHD turbulence. In this work, turbulence models for incompressible MHD were developed from the variational multiscale (VMS) formulation wherein the solution fields were decomposed into resolved and unresolved components. The unresolved components were modeled with a term that is proportional to the residual of the resolved scales. Two additional MHD models were developed based off of the VMS formulation: a residual-based eddy viscosity (RBEV) model and a mixed model that partners the VMS formulation with the RBEV model. These models are endowed with several special numerical and physics features. Included in the numerical features is the internal numerical consistency of each of the models. Physically, the new models are able to capture desirable MHD physics such as the inverse cascade of magnetic energy and the subgrid dynamo effect. The models were tested with a Fourier-spectral numerical method and the finite element method (FEM). The primary test problem was the Taylor-Green vortex. Results comparing the performance of the new models to DNS were obtained. The performance of the new models was compared to classic and cutting-edge dynamic Smagorinsky eddy viscosity (DSEV) models. The new models typically outperform the classical models.

Non-Parabolic Hydrodynamic Formulations for the Simulation of Inhomogeneous Semiconductor Devices

NASA Technical Reports Server (NTRS)

Smith, A. W.; Brennan, K. F.

1996-01-01

Hydrodynamic models are becoming prevalent design tools for small scale devices and other devices in which high energy effects can dominate transport. Most current hydrodynamic models use a parabolic band approximation to obtain fairly simple conservation equations. Interest in accounting for band structure effects in hydrodynamic device simulation has begun to grow since parabolic models cannot fully describe the transport in state of the art devices due to the distribution populating non-parabolic states within the band. This paper presents two different non-parabolic formulations or the hydrodynamic model suitable for the simulation of inhomogeneous semiconductor devices. The first formulation uses the Kane dispersion relationship ((hk)(exp 2)/2m = W(1 + alphaW). The second formulation makes use of a power law ((hk)(exp 2)/2m = xW(exp y)) for the dispersion relation. Hydrodynamic models which use the first formulation rely on the binomial expansion to obtain moment equations with closed form coefficients. This limits the energy range over which the model is valid. The power law formulation readily produces closed form coefficients similar to those obtained using the parabolic band approximation. However, the fitting parameters (x,y) are only valid over a limited energy range. The physical significance of the band non-parabolicity is discussed as well as the advantages/disadvantages and approximations of the two non-parabolic models. A companion paper describes device simulations based on the three dispersion relationships; parabolic, Kane dispersion and power law dispersion.

Non-parabolic hydrodynamic formulations for the simulation of inhomogeneous semiconductor devices

NASA Technical Reports Server (NTRS)

Smith, Arlynn W.; Brennan, Kevin F.

1995-01-01

Hydrodynamic models are becoming prevalent design tools for small scale devices and other devices in which high energy effects can dominate transport. Most current hydrodynamic models use a parabolic band approximation to obtain fairly simple conservation equations. Interest in accounting for band structure effects in hydrodynamic device simulation has begun to grow since parabolic models can not fully describe the transport in state of the art devices due to the distribution populating non-parabolic states within the band. This paper presents two different non-parabolic formulations of the hydrodynamic model suitable for the simulation of inhomogeneous semiconductor devices. The first formulation uses the Kane dispersion relationship (hk)(exp 2)/2m = W(1 + alpha(W)). The second formulation makes use of a power law ((hk)(exp 2)/2m = xW(sup y)) for the dispersion relation. Hydrodynamic models which use the first formulation rely on the binomial expansion to obtain moment equations with closed form coefficients. This limits the energy range over which the model is valid. The power law formulation readily produces closed form coefficients similar to those obtained using the parabolic band approximation. However, the fitting parameters (x,y) are only valid over a limited energy range. The physical significance of the band non-parabolicity is discussed as well as the advantages/disadvantages and approximations of the two non-parabolic models. A companion paper describes device simulations based on the three dispersion relationships: parabolic, Kane dispersion, and power low dispersion.

Addressing Hydro-economic Modeling Limitations - A Limited Foresight Sacramento Valley Model and an Open-source Modeling Platform

NASA Astrophysics Data System (ADS)

Harou, J. J.; Hansen, K. M.

2008-12-01

Increased scarcity of world water resources is inevitable given the limited supply and increased human pressures. The idea that "some scarcity is optimal" must be accepted for rational resource use and infrastructure management decisions to be made. Hydro-economic systems models are unique at representing the overlap of economic drivers, socio-political forces and distributed water resource systems. They demonstrate the tangible benefits of cooperation and integrated flexible system management. Further improvement of models, quality control practices and software will be needed for these academic policy tools to become accepted into mainstream water resource practice. Promising features include: calibration methods, limited foresight optimization formulations, linked simulation-optimization approaches (e.g. embedding pre-existing calibrated simulation models), spatial groundwater models, stream-aquifer interactions and stream routing, etc.. Conventional user-friendly decision support systems helped spread simulation models on a massive scale. Hydro-economic models must also find a means to facilitate construction, distribution and use. Some of these issues and model features are illustrated with a hydro-economic optimization model of the Sacramento Valley. Carry-over storage value functions are used to limit hydrologic foresight of the multi- period optimization model. Pumping costs are included in the formulation by tracking regional piezometric head of groundwater sub-basins. To help build and maintain this type of network model, an open-source water management modeling software platform is described and initial project work is discussed. The objective is to generically facilitate the connection of models, such as those developed in a modeling environment (GAMS, MatLab, Octave, "), to a geographic user interface (drag and drop node-link network) and a database (topology, parameters and time series). These features aim to incrementally move hydro- economic models in the direction of more practical implementation.

Towards a Neurodevelopmental Model of Clinical Case Formulation

PubMed Central

Solomon, Marjorie; Hessl, David; Chiu, Sufen; Olsen, Emily; Hendren, Robert

2009-01-01

Rapid advances in molecular genetics and neuroimaging over the last 10-20 years have been a catalyst for research in neurobiology, developmental psychopathology, and translational neuroscience. Methods of study in psychiatry, previously described as “slow maturing,” now are becoming sufficiently sophisticated to more effectively investigate the biology of higher mental processes. Despite these technological advances, the recognition that psychiatric disorders are disorders of neurodevelopment, and the importance of case formulation to clinical practice, a neurodevelopmental model of case formulation has not yet been articulated. The goals of this manuscript, which is organized as a clinical case conference, are to begin to articulate a neurodevelopmental model of case formulation, to illustrate its value, and finally to explore how clinical psychiatric practice might evolve in the future if this model were employed. PMID:19248925

Geometrically nonlinear analysis of laminated elastic structures

NASA Technical Reports Server (NTRS)

Reddy, J. N.

1984-01-01

Laminated composite plates and shells that can be used to model automobile bodies, aircraft wings and fuselages, and pressure vessels among many other were analyzed. The finite element method, a numerical technique for engineering analysis of structures, is used to model the geometry and approximate the solution. Various alternative formulations for analyzing laminated plates and shells are developed and their finite element models are tested for accuracy and economy in computation. These include the shear deformation laminate theory and degenerated 3-D elasticity theory for laminates.

Hamilton's Equations with Euler Parameters for Rigid Body Dynamics Modeling. Chapter 3

NASA Technical Reports Server (NTRS)

Shivarama, Ravishankar; Fahrenthold, Eric P.

2004-01-01

A combination of Euler parameter kinematics and Hamiltonian mechanics provides a rigid body dynamics model well suited for use in strongly nonlinear problems involving arbitrarily large rotations. The model is unconstrained, free of singularities, includes a general potential energy function and a minimum set of momentum variables, and takes an explicit state space form convenient for numerical implementation. The general formulation may be specialized to address particular applications, as illustrated in several three dimensional example problems.

Integrable Time-Dependent Quantum Hamiltonians

NASA Astrophysics Data System (ADS)

Sinitsyn, Nikolai A.; Yuzbashyan, Emil A.; Chernyak, Vladimir Y.; Patra, Aniket; Sun, Chen

2018-05-01

We formulate a set of conditions under which the nonstationary Schrödinger equation with a time-dependent Hamiltonian is exactly solvable analytically. The main requirement is the existence of a non-Abelian gauge field with zero curvature in the space of system parameters. Known solvable multistate Landau-Zener models satisfy these conditions. Our method provides a strategy to incorporate time dependence into various quantum integrable models while maintaining their integrability. We also validate some prior conjectures, including the solution of the driven generalized Tavis-Cummings model.

Decentralized control of Markovian decision processes: Existence Sigma-admissable policies

NASA Technical Reports Server (NTRS)

Greenland, A.

1980-01-01

The problem of formulating and analyzing Markov decision models having decentralized information and decision patterns is examined. Included are basic examples as well as the mathematical preliminaries needed to understand Markov decision models and, further, to superimpose decentralized decision structures on them. The notion of a variance admissible policy for the model is introduced and it is proved that there exist (possibly nondeterministic) optional policies from the class of variance admissible policies. Directions for further research are explored.

Decontamination formulations for disinfection and sterilization

DOEpatents

Tucker, Mark D.; Engler, Daniel E.

2007-09-18

Aqueous decontamination formulations that neutralize biological pathogens for disinfection and sterilization applications. Examples of suitable applications include disinfection of food processing equipment, disinfection of areas containing livestock, mold remediation, sterilization of medical instruments and direct disinfection of food surfaces, such as beef carcasses. The formulations include at least one reactive compound, bleaching activator, inorganic base, and water. The formulations can be packaged as a two-part kit system, and can have a pH value in the range of 7-8.

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

PubMed

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

2017-10-02

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

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

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.

Space-based solar power conversion and delivery systems study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Hazelrigg, G. A., Jr.

1976-01-01

The technical and economic aspects of satellite solar power systems are presented with a focus on the current configuration 5000 MW system. The technical studies include analyses of the orbital system structures, control and stationkeeping, and the formulation of program plans and costs for input to the economic analyses. The economic analyses centered about the development and use of a risk analysis model for a system cost assessment, identification of critical issues and technologies, and to provide information for programmatic decision making. A preliminary economic examination of some utility interface issues is included. Under the present state-of-knowledge, it is possible to formulate a program plan for the development of a satellite solar power system that can be economically justified. The key area of technological uncertainty is man's ability to fabricate and assemble large structures in space.

Colliding Winds in Symbiotic Binary Systems. I. Analytic and Numerical Solutions

NASA Astrophysics Data System (ADS)

Kenny, H. T.; Taylor, A. R.

2005-01-01

We present new formulations of binary colliding wind models appropriate to symbiotic star systems. The derived models differ from previous formulations in assuming mixing of the shocked material from both incoming streams, rather than postulating a self-sustaining contact discontinuity. The CWb model (colliding winds, binary) extends the work of Girard and Willson by the derivation of an adiabatic temperature, the consideration of radiative cooling, the inclusion of thermal pressures in the incoming winds, and the treatment of interaction shells of finite thickness and density. The finite thickness of the interaction shell allows for calculation of its radiative intensity distribution. The CWc model (colliding winds, concentric) is a similar extension of the model of Kwok, Purton, and Fitzgerald. It is derived in a manner parallel to that of the CWb model, thereby facilitating a unification of the two models. A unified model is desired since wind collisions in symbiotic systems should include aspects of both CWb and CWc interactions. Two examples of model applications are presented: a comparison of the flux densities arising from colliding winds (CWb model) with those arising from the ionization of the surrounding medium (STB model) in the galactic population of symbiotic stars, and model imaging of the symbiotic nova HM Sge.

The Radius and Entropy of a Magnetized, Rotating, Fully Convective Star: Analysis with Depth-dependent Mixing Length Theories

NASA Astrophysics Data System (ADS)

Ireland, Lewis G.; Browning, Matthew K.

2018-04-01

Some low-mass stars appear to have larger radii than predicted by standard 1D structure models; prior work has suggested that inefficient convective heat transport, due to rotation and/or magnetism, may ultimately be responsible. We examine this issue using 1D stellar models constructed using Modules for Experiments in Stellar Astrophysics (MESA). First, we consider standard models that do not explicitly include rotational/magnetic effects, with convective inhibition modeled by decreasing a depth-independent mixing length theory (MLT) parameter α MLT. We provide formulae linking changes in α MLT to changes in the interior specific entropy, and hence to the stellar radius. Next, we modify the MLT formulation in MESA to mimic explicitly the influence of rotation and magnetism, using formulations suggested by Stevenson and MacDonald & Mullan, respectively. We find rapid rotation in these models has a negligible impact on stellar structure, primarily because a star’s adiabat, and hence its radius, is predominantly affected by layers near the surface; convection is rapid and largely uninfluenced by rotation there. Magnetic fields, if they influenced convective transport in the manner described by MacDonald & Mullan, could lead to more noticeable radius inflation. Finally, we show that these non-standard effects on stellar structure can be fabricated using a depth-dependent α MLT: a non-magnetic, non-rotating model can be produced that is virtually indistinguishable from one that explicitly parameterizes rotation and/or magnetism using the two formulations above. We provide formulae linking the radially variable α MLT to these putative MLT reformulations.

Value of the dorsal cutaneous guinea pig model in selecting topical antiviral formulations for the treatment of recurrent herpes simplex type 1 disease.

PubMed

Poli, G; Dall'Ara, P; Binda, S; Santus, G; Poli, A; Cocilovo, A; Ponti, W

2001-01-01

Recurrent herpes simplex labialis represents a disease still difficult to treat, despite the availability of many established antiviral drugs used in clinical research since 30 years ago. Although differences between the human disease and that obtained in experimental animal suggest caution in predicting an effective clinical response from the experimental results, some of the animal models seem to be useful in optimising the topical formulation of single antiviral drugs. In the present work the dorsal cutaneous guinea pig model was used to compare 5 different topical antiviral formulations with clinical promise (active molecule: 5% w/w micronized aciclovir, CAS 59277-89-3), using both roll-on and lipstick application systems. The aim being to evaluate which vehicle (water, oil, low melting and high melting fatty base) and application system (roll-on, lipstick) enhances the skin penetration and the antiviral activity of the drug, after an experimental intradermal infection with Herpes simplex virus type 1 (HSV-1). As reference, a commercial formulation (5% aciclovir ointment) was used. The cumulative results of this study showed that the formulation A, containing 5% aciclovir in an aqueous base in a roll-on application system, has the better antiviral efficacy in reducing the severity of cutaneous lesions and the viral titer; among the lipsticks preparations, the formulation D, containing 5% aciclovir in a low melting fatty base, demonstrates a very strong antiviral activity, though slightly less than formulation A. This experimental work confirms the validity of the dorsal cutaneous guinea pig model as a rapid and efficient method to compare the antiviral efficacy of new formulations, with clinical promise, to optimise the topical formulation of the active antiviral drugs.

JPL Innovation Foundry

NASA Technical Reports Server (NTRS)

Sherwood, Brent; McCleese, Daniel J.

2012-01-01

NASA supports the community of mission principal investigators by helping them ideate, mature, and propose concepts for new missions. As NASA's Federally Funded Research and Development Center (FFRDC), JPL is a primary resource for providing this service. The environmental context for the formulation lifecycle evolves continuously. Contemporary trends include: more competitors; more-complex mission ideas; scarcer formulation resources; and higher standards for technical evaluation. Derived requirements for formulation support include: stable, clear, reliable methods tailored for each stage of the formulation lifecycle; on-demand access to standout technical and programmatic subject-matter experts; optimized, outfitted facilities; smart access to learning embodied in a vast oeuvre of prior formulation work; hands-on method coaching. JPL has retooled its provision of integrated formulation lifecycle support to PIs, teams, and program offices in response to this need. This mission formulation enterprise is the JPL Innovation Foundry.

Age- and bite-structured models for vector-borne diseases.

PubMed

Rock, K S; Wood, D A; Keeling, M J

2015-09-01

The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host-vector model, whereas other controls including treatment of humans may be more effective than previously thought. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

NASA Radiation Track Image GUI for Assessing Space Radiation Biological Effects

NASA Technical Reports Server (NTRS)

Ponomarev, Artem L.; Cucinotta, Francis A.

2006-01-01

The high-charge high-energy (HZE) ion components of the galactic cosmic rays when compared to terrestrial forms of radiations present unique challenges to biological systems. In this paper we present a deoxyribonucleic acid (DNA) breakage model to visualize and analyze the impact of chromatin domains and DNA loops on clustering of DNA damage from X rays, protons, and HZE ions. Our model of DNA breakage is based on a stochastic process of DNA double-strand break (DSB) formulation that includes the amorphous model of the radiation track and a polymer model of DNA packed in the cell nucleus. Our model is a Monte-Carlo simulation based on a randomly located DSB cluster formulation that accomodates both high- and low-linear energy transfer radiations. We demonstrate that HZE ions have a strong impact on DSB clustering, both along the chromosome length and in the nucleus volume. The effects of chromosomal domains and DNA loops on the DSB fragment-size distribution and the spatial distribution of DSB in the nucleus were studied. We compare our model predictions with the spatial distribution of DSB obtained from experiments. The implications of our model predictions for radiation protection are discussed.

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.

A comprehensive evaluation of different radiation models in a gas turbine combustor under conditions of oxy-fuel combustion with dry recycle

NASA Astrophysics Data System (ADS)

Kez, V.; Liu, F.; Consalvi, J. L.; Ströhle, J.; Epple, B.

2016-03-01

The oxy-fuel combustion is a promising CO2 capture technology from combustion systems. This process is characterized by much higher CO2 concentrations in the combustion system compared to that of the conventional air-fuel combustion. To accurately predict the enhanced thermal radiation in oxy-fuel combustion, it is essential to take into account the non-gray nature of gas radiation. In this study, radiation heat transfer in a 3D model gas turbine combustor under two test cases at 20 atm total pressure was calculated by various non-gray gas radiation models, including the statistical narrow-band (SNB) model, the statistical narrow-band correlated-k (SNBCK) model, the wide-band correlated-k (WBCK) model, the full spectrum correlated-k (FSCK) model, and several weighted sum of gray gases (WSGG) models. Calculations of SNB, SNBCK, and FSCK were conducted using the updated EM2C SNB model parameters. Results of the SNB model are considered as the benchmark solution to evaluate the accuracy of the other models considered. Results of SNBCK and FSCK are in good agreement with the benchmark solution. The WBCK model is less accurate than SNBCK or FSCK. Considering the three formulations of the WBCK model, the multiple gases formulation is the best choice regarding the accuracy and computational cost. The WSGG model with the parameters of Bordbar et al. (2014) [20] is the most accurate of the three investigated WSGG models. Use of the gray WSSG formulation leads to significant deviations from the benchmark data and should not be applied to predict radiation heat transfer in oxy-fuel combustion systems. A best practice to incorporate the state-of-the-art gas radiation models for high accuracy of radiation heat transfer calculations at minimal increase in computational cost in CFD simulation of oxy-fuel combustion systems for pressure path lengths up to about 10 bar m is suggested.

Computerized Instructional Adaptive Testing Model: Formulation and Validation.

DTIC Science & Technology

1980-02-01

AD-AO1 855 CONTROL DATA EDUCATION CO MINNEAPOLIS MN F/6 5/9MPUTERIZED INSTRUCTIONAL ADAPTIVE TESTING MODELS FORMULATION --EC(U) FEB 80 S J KALISCH...final report wus submitted by Control Data Education Company, 8100 34th Avenue, South, Minneapolis, Minnesota 55440, under contract F33615-17-C.0071... DATA EDUCATION CO MINNEAPOLIS MN p/e 5/9 I COMPULTERIZED :LSTUCTIONAL ADAPTIVE TESTING MODELS FORMULATION --EIC(U) FEB 80 S J KALISCH F33615-77-C-0O71

WARP3D-Release 10.8: Dynamic Nonlinear Analysis of Solids using a Preconditioned Conjugate Gradient Software Architecture

NASA Technical Reports Server (NTRS)

Koppenhoefer, Kyle C.; Gullerud, Arne S.; Ruggieri, Claudio; Dodds, Robert H., Jr.; Healy, Brian E.

1998-01-01

This report describes theoretical background material and commands necessary to use the WARP3D finite element code. WARP3D is under continuing development as a research code for the solution of very large-scale, 3-D solid models subjected to static and dynamic loads. Specific features in the code oriented toward the investigation of ductile fracture in metals include a robust finite strain formulation, a general J-integral computation facility (with inertia, face loading), an element extinction facility to model crack growth, nonlinear material models including viscoplastic effects, and the Gurson-Tver-gaard dilatant plasticity model for void growth. The nonlinear, dynamic equilibrium equations are solved using an incremental-iterative, implicit formulation with full Newton iterations to eliminate residual nodal forces. The history integration of the nonlinear equations of motion is accomplished with Newmarks Beta method. A central feature of WARP3D involves the use of a linear-preconditioned conjugate gradient (LPCG) solver implemented in an element-by-element format to replace a conventional direct linear equation solver. This software architecture dramatically reduces both the memory requirements and CPU time for very large, nonlinear solid models since formation of the assembled (dynamic) stiffness matrix is avoided. Analyses thus exhibit the numerical stability for large time (load) steps provided by the implicit formulation coupled with the low memory requirements characteristic of an explicit code. In addition to the much lower memory requirements of the LPCG solver, the CPU time required for solution of the linear equations during each Newton iteration is generally one-half or less of the CPU time required for a traditional direct solver. All other computational aspects of the code (element stiffnesses, element strains, stress updating, element internal forces) are implemented in the element-by- element, blocked architecture. This greatly improves vectorization of the code on uni-processor hardware and enables straightforward parallel-vector processing of element blocks on multi-processor hardware.

A stochastic dynamic model for human error analysis in nuclear power plants

NASA Astrophysics Data System (ADS)

Delgado-Loperena, Dharma

Nuclear disasters like Three Mile Island and Chernobyl indicate that human performance is a critical safety issue, sending a clear message about the need to include environmental press and competence aspects in research. This investigation was undertaken to serve as a roadmap for studying human behavior through the formulation of a general solution equation. The theoretical model integrates models from two heretofore-disassociated disciplines (behavior specialists and technical specialists), that historically have independently studied the nature of error and human behavior; including concepts derived from fractal and chaos theory; and suggests re-evaluation of base theory regarding human error. The results of this research were based on comprehensive analysis of patterns of error, with the omnipresent underlying structure of chaotic systems. The study of patterns lead to a dynamic formulation, serving for any other formula used to study human error consequences. The search for literature regarding error yielded insight for the need to include concepts rooted in chaos theory and strange attractors---heretofore unconsidered by mainstream researchers who investigated human error in nuclear power plants or those who employed the ecological model in their work. The study of patterns obtained from the rupture of a steam generator tube (SGTR) event simulation, provided a direct application to aspects of control room operations in nuclear power plant operations. In doing so, the conceptual foundation based in the understanding of the patterns of human error analysis can be gleaned, resulting in reduced and prevent undesirable events.

Comparison of two transonic noise prediction formulations using the aircraft noise prediction program

NASA Technical Reports Server (NTRS)

Spence, Peter L.

1987-01-01

This paper addresses recently completed work on using Farassat's Formulation 3 noise prediction code with the Aircraft Noise Prediction Program (ANOPP). Software was written to link aerodynamic loading generated by the Propeller Loading (PLD) module within ANOPP with formulation 3. Included are results of comparisons between Formulation 3 with ANOPP's existing noise prediction modules, Subsonic Propeller Noise (SPN) and Transonic Propeller Noise (TPN). Four case studies are investigated. Results of the comparison studies show excellent agreement for the subsonic cases. Differences found in the comparisons made under transonic conditions are strictly numerical and can be explained by the way in which the time derivative is calculated in Formulation 3. Also included is a section on how to execute Formulation 3 with ANOPP.

Modeling void growth and movement with phase change in thermal energy storage canisters

NASA Technical Reports Server (NTRS)

Darling, Douglas; Namkoong, David; Skarda, J. R. L.

1993-01-01

A scheme was developed to model the thermal hydrodynamic behavior of thermal energy storage salts. The model included buoyancy, surface tension, viscosity, phases change with density difference, and void growth and movement. The energy, momentum, and continuity equations were solved using a finite volume formulation. The momentum equation was divided into two pieces. The void growth and void movement are modeled between the two pieces of the momentum equations. Results showed this scheme was able to predict the behavior of thermal energy storage salts.

A two-field modified Lagrangian formulation for robust simulations of extrinsic cohesive zone models

NASA Astrophysics Data System (ADS)

Cazes, F.; Coret, M.; Combescure, A.

2013-06-01

This paper presents the robust implementation of a cohesive zone model based on extrinsic cohesive laws (i.e. laws involving an infinite initial stiffness). To this end, a two-field Lagrangian weak formulation in which cohesive tractions are chosen as the field variables along the crack's path is presented. Unfortunately, this formulation cannot model the infinite compliance of the broken elements accurately, and no simple criterion can be defined to determine the loading-unloading change of state at the integration points of the cohesive elements. Therefore, a modified Lagrangian formulation using a fictitious cohesive traction instead of the classical cohesive traction as the field variable is proposed. Thanks to this change of variable, the cohesive law becomes an increasing function of the equivalent displacement jump, which eliminates the problems mentioned previously. The ability of the proposed formulations to simulate fracture accurately and without field oscillations is investigated through three numerical test examples.

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

Development of Numerical Extended Hydrodynamics for Transition-Regime Non-Equilibrium Flows Encountered in Semiconductor Manufacturing Processes

NASA Technical Reports Server (NTRS)

Groth, Clinton P. T.; Roe, Philip L.

1998-01-01

Six months of funding was received for the proposed three year research program (funding for the period from March 1, 1997 to August 31, 1997). Although the official starting date for the project was March 1, 1997, no funding for the project was received until July 1997. In the funded research period, considerable progress was made on Phase I of the proposed research program. The initial research efforts concentrated on applying the 10-, 20-, and 35-moment Gaussian-based closures to a series of standard two-dimensional non-reacting single species test flow problems, such as the flat plate, couette, channel, and rearward facing step flows, and to some other two-dimensional flows having geometries similar to those encountered in chemical-vapor deposition (CVD) reactors. Eigensystem analyses for these systems for the case of two spatial dimensions was carried out and efficient formulations of approximate Riemann solvers have been formulated using these eigenstructures. Formulations to include rotational non-equilibrium effects into the moment closure models for the treatment of polyatomic gases were explored, as the original formulations of the closure models were developed strictly for gases composed of monatomic molecules. The development of a software library and computer code for solving relaxing hyperbolic systems in two spatial dimensions of the type arising from the closure models was also initiated. The software makes use of high-resolution upwind finite-volumes schemes, multi-stage point implicit time stepping, and automatic adaptive mesh refinement (AMR) to solve the governing conservation equations for the moment closures. The initial phase of the code development was completed and a numerical investigation of the solutions of the 10-moment closure model for the simple two-dimensional test cases mentioned above was initiated. Predictions of the 10-moment model were compared to available theoretical solutions and the results of direct-simulation Monte Carlo (DSMC) calculations. The first results of this study were presented at a meeting last year.

Non-destructive monitoring of creaming of oil-in-water emulsion-based formulations using magnetic resonance imaging.

PubMed

Onuki, Yoshinori; Horita, Akihiro; Kuribayashi, Hideto; Okuno, Yoshihide; Obata, Yasuko; Takayama, Kozo

2014-07-01

A non-destructive method for monitoring creaming of emulsion-based formulations is in great demand because it allows us to understand fully their instability mechanisms. This study was aimed at demonstrating the usefulness of magnetic resonance (MR) techniques, including MR imaging (MRI) and MR spectroscopy (MRS), for evaluating the physicochemical stability of emulsion-based formulations. Emulsions that are applicable as the base of practical skin creams were used as test samples. Substantial creaming was developed by centrifugation, which was then monitored by MRI. The creaming oil droplet layer and aqueous phase were clearly distinguished by quantitative MRI by measuring T1 and the apparent diffusion coefficient. Components in a selected volume in the emulsions could be analyzed using MRS. Then, model emulsions having different hydrophilic-lipophilic balance (HLB) values were tested, and the optimal HLB value for a stable dispersion was determined. In addition, the MRI examination enables the detection of creaming occurring in a polyethylene tube, which is commonly used for commercial products, without losing any image quality. These findings strongly indicate that MR techniques are powerful tools to evaluate the physicochemical stability of emulsion-based formulations. This study will make a great contribution to the development and quality control of emulsion-based formulations.

Groundwater management under uncertainty using a stochastic multi-cell model

NASA Astrophysics Data System (ADS)

Joodavi, Ata; Zare, Mohammad; Ziaei, Ali Naghi; Ferré, Ty P. A.

2017-08-01

The optimization of spatially complex groundwater management models over long time horizons requires the use of computationally efficient groundwater flow models. This paper presents a new stochastic multi-cell lumped-parameter aquifer model that explicitly considers uncertainty in groundwater recharge. To achieve this, the multi-cell model is combined with the constrained-state formulation method. In this method, the lower and upper bounds of groundwater heads are incorporated into the mass balance equation using indicator functions. This provides expressions for the means, variances and covariances of the groundwater heads, which can be included in the constraint set in an optimization model. This method was used to formulate two separate stochastic models: (i) groundwater flow in a two-cell aquifer model with normal and non-normal distributions of groundwater recharge; and (ii) groundwater management in a multiple cell aquifer in which the differences between groundwater abstractions and water demands are minimized. The comparison between the results obtained from the proposed modeling technique with those from Monte Carlo simulation demonstrates the capability of the proposed models to approximate the means, variances and covariances. Significantly, considering covariances between the heads of adjacent cells allows a more accurate estimate of the variances of the groundwater heads. Moreover, this modeling technique requires no discretization of state variables, thus offering an efficient alternative to computationally demanding methods.

MARC calculations for the second WIPP structural benchmark problem

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

Morgan, H.S.

1981-05-01

This report describes calculations made with the MARC structural finite element code for the second WIPP structural benchmark problem. Specific aspects of problem implementation such as element choice, slip line modeling, creep law implementation, and thermal-mechanical coupling are discussed in detail. Also included are the computational results specified in the benchmark problem formulation.

Using Microcomputer-Based Logistics Models to Enhance Supportability Assessment for the USAF Productivity, Reliability, Availability and Maintainability (PRAM) Program Office: A Tailored Approach

DTIC Science & Technology

1989-09-01

goes on to discuss how the innovation process should function within an organization, including five specific phases for successfully managing ... innovation : the recognition of opportunity; idea formulation; product defin- ition; prototype solution; and finally, technology utiliza- tion and diffusion

Fundamental Studies Connected with Electrochemical Energy Storage

NASA Technical Reports Server (NTRS)

Buck, E.; Sen, R.

1974-01-01

Papers are presented which deal with electrochemical research activities. Emphasis is placed on electrochemical energy storage devices. Topics discussed include: adsorption of dendrite inhibitors on zinc; proton discharge process; electron and protron transfer; quantum mechanical formulation of electron transfer rates; and theory of electrochemical kinetics in terms of two models of activation; thermal and electrostatic.

Modeling Spring Mass System with System Dynamics Approach in Middle School Education

ERIC Educational Resources Information Center

Nuhoglu, Hasret

2008-01-01

System Dynamics is a well formulated methodology for analyzing the components of a system including causeeffect relationships and their underlying mathematics and logic, time delays, and feedback loops. It began in the business and manufacturing world, but is now affecting education and many other disciplines. Having inspired by successful policy…

Modeling Spring Mass System with System Dynamics Approach in Middle School Education

ERIC Educational Resources Information Center

Nuhoglu, Hasret

2008-01-01

System Dynamics is a well formulated methodology for analyzing the components of a system including cause-effect relationships and their underlying mathematics and logic, time delays, and feedback loops. It began in the business and manufacturing world, but is now affecting education and many other disciplines. Having inspired by successful policy…

Toward a Productive and Creative Curriculum in Architecture

ERIC Educational Resources Information Center

Wang, Tsungjuang

2009-01-01

A model of curriculum development that enables students of architecture in the developing nation of Taiwan to draw on their own life experiences in formulating their own architectural education is proposed. Such an ideology recognizes that while education certainly includes the acquisition of the technical skills needed to ply one's trade, its…

Density-dependent microbial turnover improves soil carbon model predictions of long-term litter manipulations

NASA Astrophysics Data System (ADS)

Georgiou, Katerina; Abramoff, Rose; Harte, John; Riley, William; Torn, Margaret

2017-04-01

Climatic, atmospheric, and land-use changes all have the potential to alter soil microbial activity via abiotic effects on soil or mediated by changes in plant inputs. Recently, many promising microbial models of soil organic carbon (SOC) decomposition have been proposed to advance understanding and prediction of climate and carbon (C) feedbacks. Most of these models, however, exhibit unrealistic oscillatory behavior and SOC insensitivity to long-term changes in C inputs. Here we diagnose the sources of instability in four models that span the range of complexity of these recent microbial models, by sequentially adding complexity to a simple model to include microbial physiology, a mineral sorption isotherm, and enzyme dynamics. We propose a formulation that introduces density-dependence of microbial turnover, which acts to limit population sizes and reduce oscillations. We compare these models to results from 24 long-term C-input field manipulations, including the Detritus Input and Removal Treatment (DIRT) experiments, to show that there are clear metrics that can be used to distinguish and validate the inherent dynamics of each model structure. We find that widely used first-order models and microbial models without density-dependence cannot readily capture the range of long-term responses observed across the DIRT experiments as a direct consequence of their model structures. The proposed formulation improves predictions of long-term C-input changes, and implies greater SOC storage associated with CO2-fertilization-driven increases in C inputs over the coming century compared to common microbial models. Finally, we discuss our findings in the context of improving microbial model behavior for inclusion in Earth System Models.

Metropolitan Washington Area Water Supply Study. Appendix B. Plan Formulation, Assessment, and Evaluation.

DTIC Science & Technology

1983-09-01

which serve as aquifers. The aquifers include, in ascending order, the Patuxent, the Patapso, the Magothy , and the Aquia Formations. These aquifer...consist typically of sand layers of varying thickness interbedded with clays. The general thickness of the Patuxent, Patapsco, Magothy and Aquia in the...Aquifers. This was accomplished using a digital simulation model originally developed by the USGS for the Magothy Aquifer. The model uses a finite

Continuing data analysis of the AS/E grazing incidence X-ray telescope experiment on the OSO-4 satellite

NASA Technical Reports Server (NTRS)

Vaiana, G.; Haggerty, R.; Kahler, S.; Krieger, A.; Landini, M.; Timothy, A.; Webb, D.

1973-01-01

The work to correct and extend the calculation of the theoretical solar X-ray spectrum produced during earlier OSO-4 data analysis is reported along with the work to formulate models of active regions, and compare these models with the experimental values. An atlas of solar X-ray photographs is included, and solar X-ray observations are correlated with the solar wind.

Minimizing Security Forces Response Times Through the Use of Facility Location Methodologies

DTIC Science & Technology

2005-03-01

etc. In his book Network and Discrete Location: Models, Algorithms, and Applications author Mark S. Daskin provides a comprehensive introduction to...the art and science of locating facilities. ( Daskin , 1995) The book espouses to be a hands-on guide to using and developing facility location models...method used in this research is from Daskin (1995). The formulation presented by Daskin includes a multiplicative weighting factor for the amount

Nebulization of Cyclic Arginine-Glycine-(D)-Aspartic Acid-Peptide Grafted and Drug Encapsulated Liposomes for Inhibition of Acute Lung Injury.

PubMed

Desu, Hari R; Thoma, Laura A; Wood, George C

2018-03-13

Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo. In vivo ALI model was simulated through intra-tracheal instillation of IL-1β solution (100 μg/mL in PBS, pH 7.2, 200 μL) in male Sprague-Dawley rats. Various formulations were tested in ALI induced rats. These formulations include plain liposomes (PL), methylprednisolone sodium succinate solution (MPS solution), cRGD-peptide grafted liposomes (L cRGD ) and methylprednisolone sodium succinate encapsulated and cRGD-peptide grafted liposomes (MPS-L cRGD ). Formulations were nebulized in vivo in rats using micro-pump nebulizer. Liposome formulations exhibited higher levels of drug concentration in lungs. The physicochemical parameters demonstrated that the liposome formulations were stable. On the basis of aerodynamic droplet-size, nebulized formulations were estimated to deposit in different regions of respiratory tract, especially alveolar region, Among the formulations, MPS-L cRGD caused significant reduction of edema, neutrophil infiltration and inflammation biochemical marker levels. From the results, it can be inferred that nebulization of targeted liposomes had facilitated spatial and temporal modulation of drug delivery resulting in alleviation of ALI.

Establishing a theory for deuteron-induced surrogate reactions

NASA Astrophysics Data System (ADS)

Potel, G.; Nunes, F. M.; Thompson, I. J.

2015-09-01

Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the prior formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the 93Nb(d ,p )X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states. Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. Finally, we make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.

Establishing a theory for deuteron induced surrogate reactions

DOE PAGES

Potel, G.; Nunes, F. M.; Thompson, I. J.

2015-09-18

Background: Deuteron-induced reactions serve as surrogates for neutron capture into compound states. Although these reactions are of great applicability, no theoretical efforts have been invested in this direction over the last decade. Purpose: The goal of this work is to establish on firm grounds a theory for deuteron-induced neutron-capture reactions. This includes formulating elastic and inelastic breakup in a consistent manner. Method: We describe this process both in post- and prior-form distorted wave Born approximation following previous works and discuss the differences in the formulation. While the convergence issues arising in the post formulation can be overcome in the priormore » formulation, in this case one still needs to take into account additional terms due to nonorthogonality. Results: We apply our method to the Nb93(d,p)X at Ed=15 and 25 MeV and are able to obtain a good description of the data. We then look at the various partial wave contributions, as well as elastic versus inelastic contributions. We also connect our formulation with transfer to neutron bound states.Conclusions: Our calculations demonstrate that the nonorthogonality term arising in the prior formulation is significant and is at the heart of the long-standing controversy between the post and the prior formulations of the theory. We also show that the cross sections for these reactions are angular-momentum dependent and therefore the commonly used Weisskopf limit is inadequate. We finally make important predictions for the relative contributions of elastic breakup and nonelastic breakup and call for elastic-breakup measurements to further constrain our model.« less

Multi-dimensional upwinding-based implicit LES for the vorticity transport equations

NASA Astrophysics Data System (ADS)

Foti, Daniel; Duraisamy, Karthik

2017-11-01

Complex turbulent flows such as rotorcraft and wind turbine wakes are characterized by the presence of strong coherent structures that can be compactly described by vorticity variables. The vorticity-velocity formulation of the incompressible Navier-Stokes equations is employed to increase numerical efficiency. Compared to the traditional velocity-pressure formulation, high order numerical methods and sub-grid scale models for the vorticity transport equation (VTE) have not been fully investigated. Consistent treatment of the convection and stretching terms also needs to be addressed. Our belief is that, by carefully designing sharp gradient-capturing numerical schemes, coherent structures can be more efficiently captured using the vorticity-velocity formulation. In this work, a multidimensional upwind approach for the VTE is developed using the generalized Riemann problem-based scheme devised by Parish et al. (Computers & Fluids, 2016). The algorithm obtains high resolution by augmenting the upwind fluxes with transverse and normal direction corrections. The approach is investigated with several canonical vortex-dominated flows including isolated and interacting vortices and turbulent flows. The capability of the technique to represent sub-grid scale effects is also assessed. Navy contract titled ``Turbulence Modelling Across Disparate Length Scales for Naval Computational Fluid Dynamics Applications,'' through Continuum Dynamics, Inc.

The Spectrophotometric Analysis and Modeling of Sunscreens

NASA Astrophysics Data System (ADS)

Walters, Christina; Keeney, Allen; Wigal, Carl T.; Johnston, Cynthia R.; Cornelius, Richard D.

1997-01-01

Sunscreens and their SPF (Sun Protection Factor) values are the focus of this experiment that includes spectrophotometric measurements and molecular modeling. Students suspend weighed amounts of sunscreen lotions graded SPF 4, 6, 8, 15, 30, and 45 in water and dissolve aliquots of the aqueous suspensions in propanol. The expected relationship of absorbance proportional to log10(SPF) applies at 312 nm where a maximum in absorbance occurs for the sunscreen solutions. Results at 330 nm give similar results and are more accessible using spectrometers routinely available in the introductory laboratory. Sunscreens constitute a suitable class of compounds to use for modeling electronic spectra, and using the computer for the active ingredients ethylhexyl para-methoxycinnamate, oxybenzone, 2-ethylhexyl salicylate, and octocrylene found in commercially available formulations typically predicts the absorption maxima within 10 nm. This experiment lets students explore which compounds have the potential to function as sunscreen agents and thereby see the importance of a knowledge of chemistry to the formulation of household items.

A rapid learning and dynamic stepwise updating algorithm for flat neural networks and the application to time-series prediction.

PubMed

Chen, C P; Wan, J Z

1999-01-01

A fast learning algorithm is proposed to find an optimal weights of the flat neural networks (especially, the functional-link network). Although the flat networks are used for nonlinear function approximation, they can be formulated as linear systems. Thus, the weights of the networks can be solved easily using a linear least-square method. This formulation makes it easier to update the weights instantly for both a new added pattern and a new added enhancement node. A dynamic stepwise updating algorithm is proposed to update the weights of the system on-the-fly. The model is tested on several time-series data including an infrared laser data set, a chaotic time-series, a monthly flour price data set, and a nonlinear system identification problem. The simulation results are compared to existing models in which more complex architectures and more costly training are needed. The results indicate that the proposed model is very attractive to real-time processes.

Skin Effect Modeling in Conductors of Arbitrary Shape Through a Surface Admittance Operator and the Contour Integral Method

NASA Astrophysics Data System (ADS)

Patel, Utkarsh R.; Triverio, Piero

2016-09-01

An accurate modeling of skin effect inside conductors is of capital importance to solve transmission line and scattering problems. This paper presents a surface-based formulation to model skin effect in conductors of arbitrary cross section, and compute the per-unit-length impedance of a multiconductor transmission line. The proposed formulation is based on the Dirichlet-Neumann operator that relates the longitudinal electric field to the tangential magnetic field on the boundary of a conductor. We demonstrate how the surface operator can be obtained through the contour integral method for conductors of arbitrary shape. The proposed algorithm is simple to implement, efficient, and can handle arbitrary cross-sections, which is a main advantage over the existing approach based on eigenfunctions, which is available only for canonical conductor's shapes. The versatility of the method is illustrated through a diverse set of examples, which includes transmission lines with trapezoidal, curved, and V-shaped conductors. Numerical results demonstrate the accuracy, versatility, and efficiency of the proposed technique.

Analytical methodology for determination of helicopter IFR precision approach requirements. [pilot workload and acceptance level

NASA Technical Reports Server (NTRS)

Phatak, A. V.

1980-01-01

A systematic analytical approach to the determination of helicopter IFR precision approach requirements is formulated. The approach is based upon the hypothesis that pilot acceptance level or opinion rating of a given system is inversely related to the degree of pilot involvement in the control task. A nonlinear simulation of the helicopter approach to landing task incorporating appropriate models for UH-1H aircraft, the environmental disturbances and the human pilot was developed as a tool for evaluating the pilot acceptance hypothesis. The simulated pilot model is generic in nature and includes analytical representation of the human information acquisition, processing, and control strategies. Simulation analyses in the flight director mode indicate that the pilot model used is reasonable. Results of the simulation are used to identify candidate pilot workload metrics and to test the well known performance-work-load relationship. A pilot acceptance analytical methodology is formulated as a basis for further investigation, development and validation.

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

PubMed

Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

2010-01-01

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

Structure-Property Relationships of Architectural Coatings by Neutron Methods

NASA Astrophysics Data System (ADS)

Nakatani, Alan

2015-03-01

Architectural coatings formulations are multi-component mixtures containing latex polymer binder, pigment, rheology modifiers, surfactants, and colorants. In order to achieve the desired flow properties for these formulations, measures of the underlying structure of the components as a function of shear rate and the impact of formulation variables on the structure is necessary. We have conducted detailed measurements to understand the evolution under shear of local microstructure and larger scale mesostructure in model architectural coatings formulations by small angle neutron scattering (SANS) and ultra small angle neutron scattering (USANS), respectively. The SANS results show an adsorbed layer of rheology modifier molecules exist on the surface of the latex particles. However, the additional hydrodynamic volume occupied by the adsorbed surface layer is insufficient to account for the observed viscosity by standard hard sphere suspension models (Krieger-Dougherty). The USANS results show the presence of latex aggregates, which are fractal in nature. These fractal aggregates are the primary structures responsible for coatings formulation viscosity. Based on these results, a new model for the viscosity of coatings formulations has been developed, which is capable of reproducing the observed viscosity behavior.

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.

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.

Super-Group Field Cosmology in Batalin-Vilkovisky Formulation

NASA Astrophysics Data System (ADS)

Upadhyay, Sudhaker

2016-09-01

In this paper we study the third quantized super-group field cosmology, a model in multiverse scenario, in Batalin-Vilkovisky (BV) formulation. Further, we propose the superfield/super-antifield dependent BRST symmetry transformations. Within this formulation we establish connection between the two different solutions of the quantum master equation within the BV formulation.

Magnetic Field Satellite (Magsat) data processing system specifications

NASA Technical Reports Server (NTRS)

Berman, D.; Gomez, R.; Miller, A.

1980-01-01

The software specifications for the MAGSAT data processing system (MDPS) are presented. The MDPS is divided functionally into preprocessing of primary input data, data management, chronicle processing, and postprocessing. Data organization and validity, and checks of spacecraft and instrumentation are dicussed. Output products of the MDPS, including various plots and data tapes, are described. Formats for important tapes are presented. Dicussions and mathematical formulations for coordinate transformations and field model coefficients are included.

Modeling of materials supply, demand and prices

NASA Technical Reports Server (NTRS)

1982-01-01

The societal, economic, and policy tradeoffs associated with materials processing and utilization, are discussed. The materials system provides the materials engineer with the system analysis required for formulate sound materials processing, utilization, and resource development policies and strategies. Materials system simulation and modeling research program including assessments of materials substitution dynamics, public policy implications, and materials process economics was expanded. This effort includes several collaborative programs with materials engineers, economists, and policy analysts. The technical and socioeconomic issues of materials recycling, input-output analysis, and technological change and productivity are examined. The major thrust areas in materials systems research are outlined.

Generalized in vitro-in vivo relationship (IVIVR) model based on artificial neural networks

PubMed Central

Mendyk, Aleksander; Tuszyński, Paweł K; Polak, Sebastian; Jachowicz, Renata

2013-01-01

Background The aim of this study was to develop a generalized in vitro-in vivo relationship (IVIVR) model based on in vitro dissolution profiles together with quantitative and qualitative composition of dosage formulations as covariates. Such a model would be of substantial aid in the early stages of development of a pharmaceutical formulation, when no in vivo results are yet available and it is impossible to create a classical in vitro-in vivo correlation (IVIVC)/IVIVR. Methods Chemoinformatics software was used to compute the molecular descriptors of drug substances (ie, active pharmaceutical ingredients) and excipients. The data were collected from the literature. Artificial neural networks were used as the modeling tool. The training process was carried out using the 10-fold cross-validation technique. Results The database contained 93 formulations with 307 inputs initially, and was later limited to 28 in a course of sensitivity analysis. The four best models were introduced into the artificial neural network ensemble. Complete in vivo profiles were predicted accurately for 37.6% of the formulations. Conclusion It has been shown that artificial neural networks can be an effective predictive tool for constructing IVIVR in an integrated generalized model for various formulations. Because IVIVC/IVIVR is classically conducted for 2–4 formulations and with a single active pharmaceutical ingredient, the approach described here is unique in that it incorporates various active pharmaceutical ingredients and dosage forms into a single model. Thus, preliminary IVIVC/IVIVR can be available without in vivo data, which is impossible using current IVIVC/IVIVR procedures. PMID:23569360

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

2018-04-01

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.

Transient and residual stresses in large castings, taking time effects into account

NASA Astrophysics Data System (ADS)

Thorborg, J.; Klinkhammer, J.; Heitzer, M.

2012-07-01

Casting of large scale steel and iron parts leads to long solidification and cooling times. Solid mechanical calculations for these castings have to take the time scale of the process into account, in order to predict the transient and residual stress levels with a reasonable accuracy. This paper presents a study on the modelling of the thermo-mechanical conditions in the cast material using a unified approach to describe the constitutive behaviour. This means a classical splitting of the mechanical strain into an elastic and an inelastic contribution, where the inelastic strain is only formulated in the deviatoric space in terms of the J2 invariant. At high temperatures, creep is pronounced. Since the cooling time is long, the model includes a type of Norton's power law to integrate the significant contribution of creep to the inelastic strains. At these temperature levels, annealing effects are also dominant and hence no hardening is modelled. However, at intermediate and lower temperature levels, hardening is more pronounced and isotropic hardening is considered. Different hardening models have been studied and selected based on their ability to describe the behaviour at the different temperature levels. At the lower temperature levels, time effects decrease and the formulation reduces to a time independent formulation, like classical J2-flow theory. Several tensile and creep experiments have been made at different temperature levels to provide input data for selecting the appropriate contributions to the material model. The measurements have furthermore been used as input for extracting material data for the model. The numerical model is applied on different industrial examples to verify the agreement between measured and calculated deformations.

On Displacement Height, from Classical to Practical Formulation: Stress, Turbulent Transport and Vorticity Considerations

NASA Astrophysics Data System (ADS)

Sogachev, Andrey; Kelly, Mark

2016-03-01

Displacement height ( d) is an important parameter in the simple modelling of wind speed and vertical fluxes above vegetative canopies, such as forests. Here we show that, aside from implicit definition through a (displaced) logarithmic profile, accepted formulations for d do not consistently predict flow properties above a forest. Turbulent transport can affect the displacement height, and is an integral part of what is called the roughness sublayer. We develop a more general approach for estimation of d, through production of turbulent kinetic energy and turbulent transport, and show how previous stress-based formulations for displacement height can be seen as simplified cases of a more general definition including turbulent transport. Further, we also give a simplified and practical form for d that is in agreement with the general approach, exploiting the concept of vortex thickness scale from mixing-layer theory. We assess the new and previous displacement height formulations by using flow statistics derived from the atmospheric boundary-layer Reynolds-averaged Navier-Stokes model SCADIS as well as from wind-tunnel observations, for different vegetation types and flow regimes in neutral conditions. The new formulations tend to produce smaller d than stress-based forms, falling closer to the classic logarithmically-defined displacement height. The new, more generally defined, displacement height appears to be more compatible with profiles of components of the turbulent kinetic energy budget, accounting for the combined effects of turbulent transport and shear production. The Coriolis force also plays a role, introducing wind-speed dependence into the behaviour of the roughness sublayer; this affects the turbulent transport, shear production, stress, and wind speed, as well as the displacement height, depending on the character of the forest. We further show how our practical (`mixing-layer') form for d matches the new turbulence-based relation, as well as correspondence to previous (stress-based) formulations.

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

DOE PAGES

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan; ...

2017-03-03

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

Encapsulation, controlled release, and antitumor efficacy of cisplatin delivered in liposomes composed of sterol-modified phospholipids

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

Kieler-Ferguson, Heidi M.; Chan, Darren; Sockolosky, Jonathan

Here, we employed a recently introduced class of sterol-modified lipids (SML) to produce m-PEG-DSPE containing liposome compositions with a range of cis-platinum content release rates. SML have a cholesterol succinate attached to the phosphatidylglycerol head group and a fatty acid at the 2 position. These compositions were compared to the well-studied liposome phospholipid compositions: mPEG-DSPE/Hydrogenated Soy PC/cholesterol or mPEG-DSPE/POPC/cholesterol to determine the effect of the cis-platinum release extent on C26 tumor proliferation in the BALB/c colon carcinoma mouse model. The release rates of cis-platinum from liposomes composed of SML are a function of the acyl chain length. SML-liposomes with shortermore » acyl chain lengths C-8 provided more rapid cisplatin release, lower in vitro IC50, and were easier to formulate compared to liposomes using traditional phospholipid compositions. Similar to other liposome cis-platinum formulations, the half-life of m-PEG-DSPE SML liposome cisplatin is substantially longer than the free drug. This resulted in a higher tumor cisplatin concentration at 48 h post-dosing compared to the free drug and higher Pt-DNA adducts in the tumor. Moreover, the maximum tolerated dose of the liposome formulations where up to four fold greater than the free drug. Using X-ray fluorescence spectroscopy on tumor sections, we compared the location of platinum, to the location of a fluorescence lipid incorporated in the liposomes. The liposome platinum co-localized with the fluorescent lipid and both were non-uniformly distributed in the tumor. Non-encapsulated Cis-platinum, albeit at a low concentration, was more uniformly distributed thorough the tumor. Three liposome formulations, including the well studied hydrogenated HSPC composition, had better antitumor activity in the murine colon 26 carcinoma model as compared to the free drug at the same dose but the SML liposome platinum formulations did not perform better than the HSPC formulation.« less

A study of the impact of freezing on the lyophilization of a concentrated formulation with a high fill depth.

PubMed

Liu, Jinsong; Viverette, Todd; Virgin, Marlin; Anderson, Mitch; Paresh, Dalal

2005-01-01

The objective of this study was to evaluate the impact of freezing on the lyophilization of a concentrated formulation with a high fill depth. A model system consisting of a 15-mL fill of 15% (w/w) sulfobutylether 7-beta-cyclodextrin (SBECD) solution in a 30-mL vial was selected for this study. Various freezing methods including single-step freezing, two-step freezing with a super-cooling holding, annealing, vacuum-induced freezing, changing ice habit using tert-butyl-alcohol (TBA), ice nucleation with silver iodide (AgI), as well as combinations of some of the methods, were used in the lyophilization of this model system. This work demonstrated that the freezing process had a significant impact on primary drying rate and product quality of a concentrated formulation with a high fill depth. Annealing, vacuum-induced freezing, and addition of either TBA or an ice nucleating agent (AgI) to the formulation accelerated the subsequent ice sublimation process. Two-step freezing or addition of TBA improved the product quality by eliminating vertical heterogeneity within the cake. The combination of two-step freezing in conjunction with an annealing step was shown to be a method of choice for freezing in the lyophilization of a product with a high fill depth. In addition to being an effective method of freezing, it is most applicable for scaling up. An alternative approach is to add a certain amount of TBA to the formulation, if the TBA-formulation interaction or regulatory concerns can be demonstrated as not being an issue. An evaluation of vial size performed in this study showed that although utilizing large-diameter vials to reduce the fill depth can greatly shorten the cycle time of a single batch, it will substantially decrease the product throughput in a large-scale freeze-dryer.

Review: Optimization methods for groundwater modeling and management

NASA Astrophysics Data System (ADS)

Yeh, William W.-G.

2015-09-01

Optimization methods have been used in groundwater modeling as well as for the planning and management of groundwater systems. This paper reviews and evaluates the various optimization methods that have been used for solving the inverse problem of parameter identification (estimation), experimental design, and groundwater planning and management. Various model selection criteria are discussed, as well as criteria used for model discrimination. The inverse problem of parameter identification concerns the optimal determination of model parameters using water-level observations. In general, the optimal experimental design seeks to find sampling strategies for the purpose of estimating the unknown model parameters. A typical objective of optimal conjunctive-use planning of surface water and groundwater is to minimize the operational costs of meeting water demand. The optimization methods include mathematical programming techniques such as linear programming, quadratic programming, dynamic programming, stochastic programming, nonlinear programming, and the global search algorithms such as genetic algorithms, simulated annealing, and tabu search. Emphasis is placed on groundwater flow problems as opposed to contaminant transport problems. A typical two-dimensional groundwater flow problem is used to explain the basic formulations and algorithms that have been used to solve the formulated optimization problems.

Augmented switching linear dynamical system model for gas concentration estimation with MOX sensors in an open sampling system.

PubMed

Di Lello, Enrico; Trincavelli, Marco; Bruyninckx, Herman; De Laet, Tinne

2014-07-11

In this paper, we introduce a Bayesian time series model approach for gas concentration estimation using Metal Oxide (MOX) sensors in Open Sampling System (OSS). Our approach focuses on the compensation of the slow response of MOX sensors, while concurrently solving the problem of estimating the gas concentration in OSS. The proposed Augmented Switching Linear System model allows to include all the sources of uncertainty arising at each step of the problem in a single coherent probabilistic formulation. In particular, the problem of detecting on-line the current sensor dynamical regime and estimating the underlying gas concentration under environmental disturbances and noisy measurements is formulated and solved as a statistical inference problem. Our model improves, with respect to the state of the art, where system modeling approaches have been already introduced, but only provided an indirect relative measures proportional to the gas concentration and the problem of modeling uncertainty was ignored. Our approach is validated experimentally and the performances in terms of speed of and quality of the gas concentration estimation are compared with the ones obtained using a photo-ionization detector.

Augmented Switching Linear Dynamical System Model for Gas Concentration Estimation with MOX Sensors in an Open Sampling System

PubMed Central

Di Lello, Enrico; Trincavelli, Marco; Bruyninckx, Herman; De Laet, Tinne

2014-01-01

In this paper, we introduce a Bayesian time series model approach for gas concentration estimation using Metal Oxide (MOX) sensors in Open Sampling System (OSS). Our approach focuses on the compensation of the slow response of MOX sensors, while concurrently solving the problem of estimating the gas concentration in OSS. The proposed Augmented Switching Linear System model allows to include all the sources of uncertainty arising at each step of the problem in a single coherent probabilistic formulation. In particular, the problem of detecting on-line the current sensor dynamical regime and estimating the underlying gas concentration under environmental disturbances and noisy measurements is formulated and solved as a statistical inference problem. Our model improves, with respect to the state of the art, where system modeling approaches have been already introduced, but only provided an indirect relative measures proportional to the gas concentration and the problem of modeling uncertainty was ignored. Our approach is validated experimentally and the performances in terms of speed of and quality of the gas concentration estimation are compared with the ones obtained using a photo-ionization detector. PMID:25019637

Theoretical studies in isoelectric focusing. [mathematical modeling and computer simulation for biologicals purification process

NASA Technical Reports Server (NTRS)

Mosher, R. A.; Palusinski, O. A.; Bier, M.

1982-01-01

A mathematical model has been developed which describes the steady state in an isoelectric focusing (IEF) system with ampholytes or monovalent buffers. The model is based on the fundamental equations describing the component dissociation equilibria, mass transport due to diffusion and electromigration, electroneutrality, and the conservation of charge. The validity and usefulness of the model has been confirmed by using it to formulate buffer systems in actual laboratory experiments. The model has been recently extended to include the evolution of transient states not only in IEF but also in other modes of electrophoresis.

Computing Linear Mathematical Models Of Aircraft

NASA Technical Reports Server (NTRS)

Duke, Eugene L.; Antoniewicz, Robert F.; Krambeer, Keith D.

1991-01-01

Derivation and Definition of Linear Aircraft Model (LINEAR) computer program provides user with powerful, and flexible, standard, documented, and verified software tool for linearization of mathematical models of aerodynamics of aircraft. Intended for use in software tool to drive linear analysis of stability and design of control laws for aircraft. Capable of both extracting such linearized engine effects as net thrust, torque, and gyroscopic effects, and including these effects in linear model of system. Designed to provide easy selection of state, control, and observation variables used in particular model. Also provides flexibility of allowing alternate formulations of both state and observation equations. Written in FORTRAN.

Analytical and experimental comparisons of electromechanical vibration response of a piezoelectric bimorph beam for power harvesting

NASA Astrophysics Data System (ADS)

Lumentut, M. F.; Howard, I. M.

2013-03-01

Power harvesters that extract energy from vibrating systems via piezoelectric transduction show strong potential for powering smart wireless sensor devices in applications of health condition monitoring of rotating machinery and structures. This paper presents an analytical method for modelling an electromechanical piezoelectric bimorph beam with tip mass under two input base transverse and longitudinal excitations. The Euler-Bernoulli beam equations were used to model the piezoelectric bimorph beam. The polarity-electric field of the piezoelectric element is excited by the strain field caused by base input excitation, resulting in electrical charge. The governing electromechanical dynamic equations were derived analytically using the weak form of the Hamiltonian principle to obtain the constitutive equations. Three constitutive electromechanical dynamic equations based on independent coefficients of virtual displacement vectors were formulated and then further modelled using the normalised Ritz eigenfunction series. The electromechanical formulations include both the series and parallel connections of the piezoelectric bimorph. The multi-mode frequency response functions (FRFs) under varying electrical load resistance were formulated using Laplace transformation for the multi-input mechanical vibrations to provide the multi-output dynamic displacement, velocity, voltage, current and power. The experimental and theoretical validations reduced for the single mode system were shown to provide reasonable predictions. The model results from polar base excitation for off-axis input motions were validated with experimental results showing the change to the electrical power frequency response amplitude as a function of excitation angle, with relevance for practical implementation.

Recent experience in simultaneous control-structure optimization

NASA Technical Reports Server (NTRS)

Salama, M.; Ramaker, R.; Milman, M.

1989-01-01

To show the feasibility of simultaneous optimization as design procedure, low order problems were used in conjunction with simple control formulations. The numerical results indicate that simultaneous optimization is not only feasible, but also advantageous. Such advantages come at the expense of introducing complexities beyond those encountered in structure optimization alone, or control optimization alone. Examples include: larger design parameter space, optimization may combine continuous and combinatoric variables, and the combined objective function may be nonconvex. Future extensions to include large order problems, more complex objective functions and constraints, and more sophisticated control formulations will require further research to ensure that the additional complexities do not outweigh the advantages of simultaneous optimization. Some areas requiring more efficient tools than currently available include: multiobjective criteria and nonconvex optimization. Efficient techniques to deal with optimization over combinatoric and continuous variables, and with truncation issues for structure and control parameters of both the model space as well as the design space need to be developed.

Nonlinear probabilistic finite element models of laminated composite shells

NASA Technical Reports Server (NTRS)

Engelstad, S. P.; Reddy, J. N.

1993-01-01

A probabilistic finite element analysis procedure for laminated composite shells has been developed. A total Lagrangian finite element formulation, employing a degenerated 3-D laminated composite shell with the full Green-Lagrange strains and first-order shear deformable kinematics, forms the modeling foundation. The first-order second-moment technique for probabilistic finite element analysis of random fields is employed and results are presented in the form of mean and variance of the structural response. The effects of material nonlinearity are included through the use of a rate-independent anisotropic plasticity formulation with the macroscopic point of view. Both ply-level and micromechanics-level random variables can be selected, the latter by means of the Aboudi micromechanics model. A number of sample problems are solved to verify the accuracy of the procedures developed and to quantify the variability of certain material type/structure combinations. Experimental data is compared in many cases, and the Monte Carlo simulation method is used to check the probabilistic results. In general, the procedure is quite effective in modeling the mean and variance response of the linear and nonlinear behavior of laminated composite shells.

A displacement-pressure finite element formulation for analyzing the sound transmission in ducted shear flows with finite poroelastic lining.

PubMed

Nennig, Benoit; Tahar, Mabrouk Ben; Perrey-Debain, Emmanuel

2011-07-01

In the present work, the propagation of sound in a lined duct containing sheared mean flow is studied. Walls of the duct are acoustically treated with absorbent poroelastic foams. The propagation of elasto-acoustic waves in the liner is described by Biot's model. In the fluid domain, the propagation of sound in a sheared mean flow is governed by the Galbrun's equation. The problem is solved using a mixed displacement-pressure finite element formulation in both domains. A 3D implementation of the model has been performed and is illustrated on axisymmetric examples. Convergence and accuracy of the numerical model are shown for the particular case of the modal propagation in a infinite duct containing a uniform flow. Practical examples concerning the sound attenuation through dissipative silencers are discussed. In particular, effects of the refraction effects in the shear layer as well as the mounting conditions of the foam on the transmission loss are shown. The presence of a perforate screen at the air-porous interface is also considered and included in the model. © 2011 Acoustical Society of America

Resolvent-based modeling of passive scalar dynamics in wall-bounded turbulence

NASA Astrophysics Data System (ADS)

Dawson, Scott; Saxton-Fox, Theresa; McKeon, Beverley

2017-11-01

The resolvent formulation of the Navier-Stokes equations expresses the system state as the output of a linear (resolvent) operator acting upon a nonlinear forcing. Previous studies have demonstrated that a low-rank approximation of this linear operator predicts many known features of incompressible wall-bounded turbulence. In this work, this resolvent model for wall-bounded turbulence is extended to include a passive scalar field. This formulation allows for a number of additional simplifications that reduce model complexity. Firstly, it is shown that the effect of changing scalar diffusivity can be approximated through a transformation of spatial wavenumbers and temporal frequencies. Secondly, passive scalar dynamics may be studied through the low-rank approximation of a passive scalar resolvent operator, which is decoupled from velocity response modes. Thirdly, this passive scalar resolvent operator is amenable to approximation by semi-analytic methods. We investigate the extent to which this resulting hierarchy of models can describe and predict passive scalar dynamics and statistics in wall-bounded turbulence. The support of AFOSR under Grant Numbers FA9550-16-1-0232 and FA9550-16-1-0361 is gratefully acknowledged.

Integrated Formulation of Beacon-Based Exception Analysis for Multimissions

NASA Technical Reports Server (NTRS)

Mackey, Ryan; James, Mark; Park, Han; Zak, Mickail

2003-01-01

Further work on beacon-based exception analysis for multimissions (BEAM), a method of real-time, automated diagnosis of a complex electromechanical systems, has greatly expanded its capability and suitability of application. This expanded formulation, which fully integrates physical models and symbolic analysis, is described. The new formulation of BEAM expands upon previous advanced techniques for analysis of signal data, utilizing mathematical modeling of the system physics, and expert-system reasoning,

Volatilisation of pesticides under field conditions: inverse modelling and pesticide fate models.

PubMed

Houbraken, Michael; van den Berg, Frederik; Butler Ellis, Clare M; Dekeyser, Donald; Nuyttens, David; De Schampheleire, Mieke; Spanoghe, Pieter

2016-07-01

A substantial fraction of the applied crop protection products on crops is lost to the atmosphere. Models describing the prediction of volatility and potential fate of these substances in the environment have become an important tool in the pesticide authorisation procedure at the EU level. The main topic of this research is to assess the rate and extent of volatilisation of ten pesticides after application on field crops. For eight of the ten pesticides, the volatilisation rates modelled with PEARL (Pesticide Emission Assessment at Regional and Local scales) corresponded well to the calculated rates modelled with ADMS (Atmospheric Dispersion Modelling System). For the other pesticides, large differences were found between the models. Formulation might affect the volatilisation potential of pesticides. Increased leaf wetness increased the volatilisation of propyzamide and trifloxystrobin at the end of the field trial. The reliability of pesticide input parameters, in particular the vapour pressure, is discussed. Volatilisation of propyzamide, pyrimethanil, chlorothalonil, diflufenican, tolylfluanid, cyprodinil and E- and Z-dimethomorph from crops under realistic environmental conditions can be modelled with the PEARL model, as corroborated against field observations. Suggested improvements to the volatilisation component in PEARL should include formulation attributes and leaf wetness at the time of pesticide application. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Finite element solution of optimal control problems with inequality constraints

NASA Technical Reports Server (NTRS)

Bless, Robert R.; Hodges, Dewey H.

1990-01-01

A finite-element method based on a weak Hamiltonian form of the necessary conditions is summarized for optimal control problems. Very crude shape functions (so simple that element numerical quadrature is not necessary) can be used to develop an efficient procedure for obtaining candidate solutions (i.e., those which satisfy all the necessary conditions) even for highly nonlinear problems. An extension of the formulation allowing for discontinuities in the states and derivatives of the states is given. A theory that includes control inequality constraints is fully developed. An advanced launch vehicle (ALV) model is presented. The model involves staging and control constraints, thus demonstrating the full power of the weak formulation to date. Numerical results are presented along with total elapsed computer time required to obtain the results. The speed and accuracy in obtaining the results make this method a strong candidate for a real-time guidance algorithm.

Gauge-free gyrokinetic theory

NASA Astrophysics Data System (ADS)

Burby, Joshua; Brizard, Alain

2017-10-01

Test-particle gyrocenter equations of motion play an essential role in the diagnosis of turbulent strongly-magnetized plasmas, and are playing an increasingly-important role in the formulation of kinetic-gyrokinetic hybrid models. Previous gyrocenter models required the knowledge of the perturbed electromagnetic potentials, which are not directly observable quantities (since they are gauge-dependent). A new gauge-free formulation of gyrocenter motion is presented, which enables gyrocenter trajectories to be determined using only measured values of the directly-observable electromagnetic field. Our gauge-free gyrokinetic theory is general enough to allow for gyroradius-scale fluctuations in both the electric and magnetic field. In addition, we provide gauge-free expressions for the charge and current densities produced by a distribution of gyrocenters, which explicitly include guiding-center and gyrocenter polarization and magnetization effects. This research was supported by the U.S. DOE Contract Nos. DE-SC0014032 (AB) and DE-AC05-06OR23100 (JB).

Warning systems in risk management.

PubMed

Paté-Cornell, M E

1986-06-01

A method is presented here that allows probabilistic evaluation and optimization of warning systems, and comparison of their performance and cost-effectiveness with those of other means of risk management. The model includes an assessment of the signals, and of human response, given the memory that people have kept of the quality of previous alerts. The trade-off between the rate of false alerts and the length of the lead time is studied to account for the long-term effects of "crying wolf" and the effectiveness of emergency actions. An explicit formulation of the system's benefits, including inputs from a signal model, a response model, and a consequence model, is given to allow optimization of the warning threshold and of the system's sensitivity.

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

Trehalose limits BSA aggregation in spray-dried formulations at high temperatures: implications in preparing polymer implants for long-term protein delivery.

PubMed

Rajagopal, Karthikan; Wood, Joseph; Tran, Benjamin; Patapoff, Thomas W; Nivaggioli, Thierry

2013-08-01

Polymer implants are promising systems for sustained release applications but their utility for protein delivery has been hindered because of concerns over drug stability at elevated temperatures required for processing. Using bovine serum albumin (BSA) as a model, we have assessed whether proteins can be formulated for processing at elevated temperatures. Specifically, the effect of trehalose and histidine-HCl buffer on BSA stability in a spray-dried formulation has been investigated at temperatures ranging from 80°C to 110°C. When both the sugar and buffer are present, aggregation is suppressed even when exposed to 100°C, the extrusion temperature of poly(lactide-co-glycolide) (PLGA), a bioresorbable polymer. Estimation of aggregation rate constants (k) indicate that though both trehalose and histidine-HCl buffer contribute to BSA stability, the effect because of trehalose alone is more pronounced. BSA-loaded PLGA implants were prepared using hot-melt extrusion process and in vitro release was conducted in phosphate buffered saline at 37°C. Comparison of drug released from implants prepared using four different formulations confirmed that maximal release was achieved from the formulation in which BSA was least aggregated. These studies demonstrate that when trehalose and histidine-HCl buffer are included in spray-dried formulations, BSA stability is maintained both during processing at 100°C and long-term residence within implants. Copyright © 2013 Wiley Periodicals, Inc.

The effects of heat on skin barrier function and in vivo dermal absorption.

PubMed

Oliveira, Gabriela; Leverett, Jesse C; Emamzadeh, Mandana; Lane, Majella E

2014-04-10

Enhanced delivery of ingredients across the stratum corneum (SC) is of great interest for improving the efficacy of topically applied formulations. Various methods for improving dermal penetration have been reported including galvanic devices and micro-needles. From a safety perspective it is important that such approaches do not compromise SC barrier function. This study investigates the influence of topically applied heat in vivo on the dermal uptake and penetration of a model active, allantoin from gel and lotion formulations. A custom designed device was used to deliver 42°C for 30s daily to human subjects after application of two formulations containing allantoin. The results were compared with sites treated with formulations containing no active and no heat, and a control site. In addition to penetration of allantoin, the integrity of the SC was monitored using trans-epidermal water loss (TEWL) measurements. The results showed that just 30s of 42°C topically applied heat was enough to cause significantly more penetration of allantoin from the lotion formulation compared with no application of heat. TEWL data indicated that the integrity of the skin was not compromised by the treatment. However, the application of heat did not promote enhanced penetration of the active from the gel formulation. Vehicle composition is therefore an important factor when considering thermal enhancement strategies for targeting actives to the skin. Copyright © 2014 Elsevier B.V. All rights reserved.

Psychiatrists' judgments about antipsychotic benefit and risk outcomes and formulation in schizophrenia treatment.

PubMed

Markowitz, Michael A; Levitan, Bennett S; Mohamed, Ateesha F; Johnson, F R; Bridges, John F P; Alphs, Larry; Citrome, Leslie

2014-09-01

The objectives were to quantify psychiatrists' judgments of the benefits and risks of antipsychotic treatments of patients with schizophrenia and to evaluate how patient adherence history affects these judgments. Weights assigned by respondents to risks, benefits, and alternative drug formulations in the treatment of schizophrenia were assessed via a Web-based survey by using a discrete-choice experiment. Respondents in the United States and the United Kingdom chose among alternative scenarios characterized by various levels of improvement in positive symptoms, negative symptoms, social functioning, weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia and by formulation. The effect of patient adherence history on respondents' judgments was also assessed. Random-parameters logit and bivariate probit models were estimated. The sample included 394 psychiatrists. Improvement in positive symptoms from "no improvement" to "very much improved" was the most preferred outcome over the range of improvements included and was assigned a relative importance score of 10. Other outcomes, in decreasing order of importance, were improvement in negative symptoms from "no improvement" to "very much improved" (5.2; 95% confidence interval [CI]=4.2-6.2), social functioning from "severe problems" to "mild problems" (4.6, CI=3.8-5.4), no hyperglycemia (1.9, CI=1.5-2.4), <15% weight gain (1.5, CI=.9-2.0), no hyperprolactinemia (1.3, CI=.8-1.6), and no EPS (1.1, CI=.7-1.5). As adherence decreased, formulation became more important than modest efficacy changes and injections were preferred to daily pills (p<.05). Psychiatrists favored treatments that primarily improve positive symptoms. Choice of formulation became more important as likely adherence declined.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

PubMed Central

Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

2016-01-01

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN LANGUAGE SUMMARY Fixed-dose combinations for treating pulmonary tuberculosis What are fixed-dose combinations and how might they improve care of people with tuberculosis Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence. We conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB. What the research says We searched for relevant trials up to 20 November 2015, and included 13 randomized controlled trials that enrolled 5824 people. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. There is probably little or no difference in FDCs compared to single-drug formulations for treatment failure (moderate quality evidence); relapse may be more frequent (low quality evidence); and the number of deaths were similar (moderate quality evidence). There is little or no difference in sputum smear or culture conversion (high quality evidence), and no difference was shown for serious adverse events (moderate quality evidence) or adverse events that led to discontinuation of therapy (low quality evidence). Authors' conclusions We concluded that fixed-dose combinations have similar efficacy to single-drug formulations for treating people with newly diagnosed pulmonary TB. PMID:27186634

On improving cold region hydrological processes in the Canadian Land Surface Scheme

NASA Astrophysics Data System (ADS)

Ganji, Arman; Sushama, Laxmi; Verseghy, Diana; Harvey, Richard

2017-01-01

Regional and global climate model simulated streamflows for high-latitude regions show systematic biases, particularly in the timing and magnitude of spring peak flows. Though these biases could be related to the snow water equivalent and spring temperature biases in models, a good part of these biases is due to the unaccounted effects of non-uniform infiltration capacity of the frozen ground and other related processes. In this paper, the treatment of frozen water in the Canadian Land Surface Scheme (CLASS), which is used in the Canadian regional and global climate models, is modified to include fractional permeable area, supercooled liquid water and a new formulation for hydraulic conductivity. The impact of these modifications on the regional hydrology, particularly streamflow, is assessed by comparing three simulations performed with the original and two modified versions of CLASS, driven by atmospheric forcing data from the European Centre for Medium-Range Weather Forecast (ECMWF) reanalysis (ERA-Interim) for the 1990-2001 period over a northeast Canadian domain. The two modified versions of CLASS differ in the soil hydraulic conductivity and matric potential formulations, with one version being based on formulations from a previous study and the other one is newly proposed. Results suggest statistically significant decreases in infiltration and therefore soil moisture during the snowmelt season for the simulation with the new hydraulic conductivity and matric potential formulations and fractional permeable area concept compared to the original version of CLASS, which is also reflected in the increased spring surface runoff and streamflows in this simulation with modified CLASS over most of the study domain. The simulated spring peaks and their timing in this simulation are also in better agreement to those observed. This study thus demonstrates the importance of treatment of frozen water for realistic simulation of streamflows.

From theory to experimental design-Quantifying a trait-based theory of predator-prey dynamics.

PubMed

Laubmeier, A N; Wootton, Kate; Banks, J E; Bommarco, Riccardo; Curtsdotter, Alva; Jonsson, Tomas; Roslin, Tomas; Banks, H T

2018-01-01

Successfully applying theoretical models to natural communities and predicting ecosystem behavior under changing conditions is the backbone of predictive ecology. However, the experiments required to test these models are dictated by practical constraints, and models are often opportunistically validated against data for which they were never intended. Alternatively, we can inform and improve experimental design by an in-depth pre-experimental analysis of the model, generating experiments better targeted at testing the validity of a theory. Here, we describe this process for a specific experiment. Starting from food web ecological theory, we formulate a model and design an experiment to optimally test the validity of the theory, supplementing traditional design considerations with model analysis. The experiment itself will be run and described in a separate paper. The theory we test is that trophic population dynamics are dictated by species traits, and we study this in a community of terrestrial arthropods. We depart from the Allometric Trophic Network (ATN) model and hypothesize that including habitat use, in addition to body mass, is necessary to better model trophic interactions. We therefore formulate new terms which account for micro-habitat use as well as intra- and interspecific interference in the ATN model. We design an experiment and an effective sampling regime to test this model and the underlying assumptions about the traits dominating trophic interactions. We arrive at a detailed sampling protocol to maximize information content in the empirical data obtained from the experiment and, relying on theoretical analysis of the proposed model, explore potential shortcomings of our design. Consequently, since this is a "pre-experimental" exercise aimed at improving the links between hypothesis formulation, model construction, experimental design and data collection, we hasten to publish our findings before analyzing data from the actual experiment, thus setting the stage for strong inference.

Nanogel Carrier Design for Targeted Drug Delivery

PubMed Central

Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

2014-01-01

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

Power function decay of hydraulic conductivity for a TOPMODEL-based infiltration routine

NASA Astrophysics Data System (ADS)

Wang, Jun; Endreny, Theodore A.; Hassett, James M.

2006-11-01

TOPMODEL rainfall-runoff hydrologic concepts are based on soil saturation processes, where soil controls on hydrograph recession have been represented by linear, exponential, and power function decay with soil depth. Although these decay formulations have been incorporated into baseflow decay and topographic index computations, only the linear and exponential forms have been incorporated into infiltration subroutines. This study develops a power function formulation of the Green and Ampt infiltration equation for the case where the power n = 1 and 2. This new function was created to represent field measurements in the New York City, USA, Ward Pound Ridge drinking water supply area, and provide support for similar sites reported by other researchers. Derivation of the power-function-based Green and Ampt model begins with the Green and Ampt formulation used by Beven in deriving an exponential decay model. Differences between the linear, exponential, and power function infiltration scenarios are sensitive to the relative difference between rainfall rates and hydraulic conductivity. Using a low-frequency 30 min design storm with 4.8 cm h-1 rain, the n = 2 power function formulation allows for a faster decay of infiltration and more rapid generation of runoff. Infiltration excess runoff is rare in most forested watersheds, and advantages of the power function infiltration routine may primarily include replication of field-observed processes in urbanized areas and numerical consistency with power function decay of baseflow and topographic index distributions. Equation development is presented within a TOPMODEL-based Ward Pound Ridge rainfall-runoff simulation. Copyright

On Raviart-Thomas and VMS formulations for flow in heterogeneous materials.

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

Turner, Daniel Zack

It is well known that the continuous Galerkin method (in its standard form) is not locally conservative, yet many stabilized methods are constructed by augmenting the standard Galerkin weak form. In particular, the Variational Multiscale (VMS) method has achieved popularity for combating numerical instabilities that arise for mixed formulations that do not otherwise satisfy the LBB condition. Among alternative methods that satisfy local and global conservation, many employ Raviart-Thomas function spaces. The lowest order Raviart-Thomas finite element formulation (RT0) consists of evaluating fluxes over the midpoint of element edges and constant pressures within the element. Although the RT0 element posesmore » many advantages, it has only been shown viable for triangular or tetrahedral elements (quadrilateral variants of this method do not pass the patch test). In the context of heterogenous materials, both of these methods have been used to model the mixed form of the Darcy equation. This work aims, in a comparative fashion, to evaluate the strengths and weaknesses of either approach for modeling Darcy flow for problems with highly varying material permeabilities and predominantly open flow boundary conditions. Such problems include carbon sequestration and enhanced oil recovery simulations for which the far-field boundary is typically described with some type of pressure boundary condition. We intend to show the degree to which the VMS formulation violates local mass conservation for these types of problems and compare the performance of the VMS and RT0 methods at boundaries between disparate permeabilities.« less

Modelling drug degradation in a spray dried polymer dispersion using a modified Arrhenius equation.

PubMed

Patterson, Adele; Ferreira, Ana P; Banks, Elizabeth; Skeene, Kirsty; Clarke, Graham; Nicholson, Sarah; Rawlinson-Malone, Clare

2015-01-15

The Pharmaceutical industry is increasingly utilizing amorphous technologies to overcome solubility challenges. A common approach is the use of drug in polymer dispersions to prevent recrystallization of the amorphous drug. Understanding the factors affecting chemical and physical degradation of the drug within these complex systems, e.g., temperature and relative humidity, is an important step in the selection of a lead formulation, and development of appropriate packaging/storage control strategies. The Arrhenius equation has been used as the basis of a number of models to predict the chemical stability of formulated product. In this work, we investigate the increase in chemical degradation seen for one particular spray dried dispersion formulation using hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Samples, prepared using polymers with different substitution levels, were placed on storage for 6 months under a range of different temperature and relative humidity conditions and the degradant level monitored using high-performance liquid chromatography (HPLC). While the data clearly illustrates the impact of temperature and relative humidity on the degradant levels detected, it also highlighted that these terms do not account for all the variability in the data. An extension of the Arrhenius equation to include a term for the polymer chemistry, specifically the degree of succinoyl substitution on the polymer backbone, was shown to improve the fit of the model to the data. Copyright © 2014 Elsevier B.V. All rights reserved.

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation.

PubMed

Brouillet, F; Bataille, B; Cartilier, L

2008-05-22

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.

Advance finite element modeling of rotor blade aeroelasticity

NASA Technical Reports Server (NTRS)

Straub, F. K.; Sangha, K. B.; Panda, B.

1994-01-01

An advanced beam finite element has been developed for modeling rotor blade dynamics and aeroelasticity. This element is part of the Element Library of the Second Generation Comprehensive Helicopter Analysis System (2GCHAS). The element allows modeling of arbitrary rotor systems, including bearingless rotors. It accounts for moderately large elastic deflections, anisotropic properties, large frame motion for maneuver simulation, and allows for variable order shape functions. The effects of gravity, mechanically applied and aerodynamic loads are included. All kinematic quantities required to compute airloads are provided. In this paper, the fundamental assumptions and derivation of the element matrices are presented. Numerical results are shown to verify the formulation and illustrate several features of the element.

Documentation for the MODFLOW 6 Groundwater Flow Model

USGS Publications Warehouse

Langevin, Christian D.; Hughes, Joseph D.; Banta, Edward R.; Niswonger, Richard G.; Panday, Sorab; Provost, Alden M.

2017-08-10

This report documents the Groundwater Flow (GWF) Model for a new version of MODFLOW called MODFLOW 6. The GWF Model for MODFLOW 6 is based on a generalized control-volume finite-difference approach in which a cell can be hydraulically connected to any number of surrounding cells. Users can define the model grid using one of three discretization packages, including (1) a structured discretization package for defining regular MODFLOW grids consisting of layers, rows, and columns, (2) a discretization by ver­tices package for defining layered unstructured grids consisting of layers and cells, and (3) a general unstruc­tured discretization package for defining flexible grids comprised of cells and their connection properties. For layered grids, a new capability is available for removing thin cells and vertically connecting cells overlying and underlying the thin cells. For complex problems involving water-table conditions, an optional Newton-Raphson formulation, based on the formulations in MODFLOW-NWT and MODFLOW-USG, can be acti­vated. Use of the Newton-Raphson formulation will often improve model convergence and allow solutions to be obtained for difficult problems that cannot be solved using the traditional wetting and drying approach. The GWF Model is divided into “packages,” as was done in previous MODFLOW versions. A package is the part of the model that deals with a single aspect of simulation. Packages included with the GWF Model include those related to internal calculations of groundwater flow (discretization, initial conditions, hydraulic conduc­tance, and storage), stress packages (constant heads, wells, recharge, rivers, general head boundaries, drains, and evapotranspiration), and advanced stress packages (streamflow routing, lakes, multi-aquifer wells, and unsaturated zone flow). An additional package is also available for moving water available in one package into the individual features of the advanced stress packages. The GWF Model also has packages for obtaining and controlling output from the model. This report includes detailed explanations of physical and mathematical concepts on which the GWF Model and its packages are based.Like its predecessors, MODFLOW 6 is based on a highly modular structure; however, this structure has been extended into an object-oriented framework. The framework includes a robust and generalized numeri­cal solution object, which can be used to solve many different types of models. The numerical solution object has several different matrix preconditioning options as well as several methods for solving the linear system of equations. In this new framework, the GWF Model itself is an object as are each of the GWF Model packages. A benefit of the object-oriented structure is that multiple objects of the same type can be used in a single sim­ulation. Thus, a single forward run with MODFLOW 6 may contain multiple GWF Models. GWF Models can be hydraulically connected using GWF-GWF Exchange objects. Connecting GWF models in different ways permits the user to utilize a local grid refinement strategy consisting of parent and child models or to couple adjacent GWF Models. An advantage of the approach implemented in MODFLOW 6 is that multiple models and their exchanges can be incorporated into a single numerical solution object. With this design, models can be tightly coupled at the matrix level.

Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides.

PubMed

Defarge, N; Spiroux de Vendômois, J; Séralini, G E

2018-01-01

The major pesticides of the world are glyphosate-based herbicides (GBH), and their toxicity is highly debated. To understand their mode of action, the comparative herbicidal and toxicological effects of glyphosate (G) alone and 14 of its formulations were studied in this work, as a model for pesticides. GBH are mixtures of water, with commonly 36-48% G claimed as the active principle. As with other pesticides, 10-20% of GBH consist of chemical formulants. We previously identified these by mass spectrometry and found them to be mainly families of petroleum-based oxidized molecules, such as POEA, and other contaminants. We exposed plants and human cells to the components of formulations, both mixed and separately, and measured toxicity and human cellular endocrine disruption below the direct toxicity experimentally measured threshold. G was only slightly toxic on plants at the recommended dilutions in agriculture, in contrast with the general belief. In the short term, the strong herbicidal and toxic properties of its formulations were exerted by the POEA formulant family alone. The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G. In this work, we also identified by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel, which are known to be toxic and endocrine disruptors, as contaminants in 22 pesticides, including 11 G-based ones. This could also explain some of the adverse effects of the pesticides. In in vivo chronic regulatory experiments that are used to establish the acceptable daily intakes of pesticides, G or other declared active ingredients in pesticides are assessed alone, without the formulants. Considering these new data, this assessment method appears insufficient to ensure safety. These results, taken together, shed a new light on the toxicity of these major herbicides and of pesticides in general.

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design.

PubMed

Emami, J; Mohiti, H; Hamishehkar, H; Varshosaz, J

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7(®) software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the application of SLNs in pulmonary delivery system of budesonide.

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design

PubMed Central

Emami, J.; Mohiti, H.; Hamishehkar, H.; Varshosaz, J.

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7® software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the application of SLNs in pulmonary delivery system of budesonide. PMID:26430454

Constitutive modeling of superalloy single crystals with verification testing

NASA Technical Reports Server (NTRS)

Jordan, Eric; Walker, Kevin P.

1985-01-01

The goal is the development of constitutive equations to describe the elevated temperature stress-strain behavior of single crystal turbine blade alloys. The program includes both the development of a suitable model and verification of the model through elevated temperature-torsion testing. A constitutive model is derived from postulated constitutive behavior on individual crystallographic slip systems. The behavior of the entire single crystal is then arrived at by summing up the slip on all the operative crystallographic slip systems. This type of formulation has a number of important advantages, including the prediction orientation dependence and the ability to directly represent the constitutive behavior in terms which metallurgists use in describing the micromechanisms. Here, the model is briefly described, followed by the experimental set-up and some experimental findings to date.

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. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Finite Rotation Analysis of Highly Thin and Flexible Structures

NASA Technical Reports Server (NTRS)

Clarke, Greg V.; Lee, Keejoo; Lee, Sung W.; Broduer, Stephen J. (Technical Monitor)

2001-01-01

Deployable space structures such as sunshields and solar sails are extremely thin and highly flexible with limited bending rigidity. For analytical investigation of their responses during deployment and operation in space, these structures can be modeled as thin shells. The present work examines the applicability of the solid shell element formulation to modeling of deployable space structures. The solid shell element formulation that models a shell as a three-dimensional solid is convenient in that no rotational parameters are needed for the description of kinematics of deformation. However, shell elements may suffer from element locking as the thickness becomes smaller unless special care is taken. It is shown that, when combined with the assumed strain formulation, the solid shell element formulation results in finite element models that are free of locking even for extremely thin structures. Accordingly, they can be used for analysis of highly flexible space structures undergoing geometrically nonlinear finite rotations.

Thirty Years of Evolution in Instructional Technology, as Reflected in a Textbook

ERIC Educational Resources Information Center

Smaldino, Sharon E.; Lowther, Deborah L.; Russell, James D.

2011-01-01

This article describes how a textbook has traced 30 years of evolution in instructional technology. One of the book's key continuing features is the ASSURE Model. To connect technology to learning, the Classroom Link was developed. As standards were formulated for teachers and students, they were included in the textbook. Other evolutionary…

Toward a Conceptualization of Perceived Work-Family Fit and Balance: A Demands and Resources Approach

ERIC Educational Resources Information Center

Voydanoff, Patricia

2005-01-01

Using person-environment fit theory, this article formulates a conceptual model that links work, family, and boundary-spanning demands and resources to work and family role performance and quality. Linking mechanisms include 2 dimensions of perceived work-family fit (work demands--family resources fit and family demands--work resources fit) and a…

A Conformal, Fully-Conservative Approach for Predicting Blast Effects on Ground Vehicles

DTIC Science & Technology

2014-02-09

hydrocode. Again, a very detailed model of the pick-up truck was used. The results demonstrated that the soil type and moisture content affect both...dynamics code with the capability to model soil and blast using a multi- species formulation with advanced equations of state. The two-way coupling...of the blast, the effects of soil , which could have a high water content, must also be included. An attractive strategy, which is much less costly

High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system and in vivo evaluation.

PubMed

Sakai, Kenichi; Obata, Kouki; Yoshikawa, Mayumi; Takano, Ryusuke; Shibata, Masaki; Maeda, Hiroyuki; Mizutani, Akihiko; Terada, Katsuhide

2012-10-01

To design a high drug loading formulation of self-microemulsifying/micelle system. A poorly-soluble model drug (CH5137291), 8 hydrophilic surfactants (HS), 10 lipophilic surfactants (LS), 5 oils, and PEG400 were used. A high loading formulation was designed by a following stepwise approach using a high-throughput formulation screening (HTFS) system: (1) an oil/solvent was selected by solubility of the drug; (2) a suitable HS for highly loading was selected by the screenings of emulsion/micelle size and phase stability in binary systems (HS, oil/solvent) with increasing loading levels; (3) a LS that formed a broad SMEDDS/micelle area on a phase diagram containing the HS and oil/solvent was selected by the same screenings; (4) an optimized formulation was selected by evaluating the loading capacity of the crystalline drug. Aqueous solubility behavior and oral absorption (Beagle dog) of the optimized formulation were compared with conventional formulations (jet-milled, PEG400). As an optimized formulation, d-α-tocopheryl polyoxyethylene 1000 succinic ester: PEG400 = 8:2 was selected, and achieved the target loading level (200 mg/mL). The formulation formed fine emulsion/micelle (49.1 nm), and generated and maintained a supersaturated state at a higher level compared with the conventional formulations. In the oral absorption test, the area under the plasma concentration-time curve of the optimized formulation was 16.5-fold higher than that of the jet-milled formulation. The high loading formulation designed by the stepwise approach using the HTFS system improved the oral absorption of the poorly-soluble model drug.

Development of decision tools to assess migration from plastic materials in contact with food.

PubMed

Gillet, G; Vitrac, O; Tissier, D; Saillard, P; Desobry, S

2009-12-01

Testing the specific migration limits of all substances intentionally added to polymer material according to European Union (EU) regulation is a time-consuming and expensive task. Although mathematical modeling offers an interesting alternative, it can significantly overestimate the migration in situations which are strongly conservative due to significant uncertainty in transport properties. In addition, its application is of little use for end-users or enforcement laboratories, which do not have access to the formulation. This paper revises the paradigm of migration modeling by combining modeling with deformulation experiments and iterative modeling in the framework of decision theory. The complete approach is illustrated for polyolefins in contact with 50% ethanol for eight typical migrants, including hindered phenolic antioxidants and low molecular weight surrogates. Results from a French ACTIA project on the identification of formulation fingerprints and on the prediction of partition coefficients with alcoholic and aqueous stimulants is described. When the true migration was close but still lower than the limit of concern, the proposed compact decision tree, including up to four sources of uncertainty, showed that the chance of demonstrating compliance was about 3 : 4 in the presence of one source of uncertainty, whereas it fell below 2 : 4 and 1 : 4 with two and three sources of uncertainty, respectively. The recommendations for further food packaging safety surveys and future developments are discussed.

Comparison of Turbulent Thermal Diffusivity and Scalar Variance Models

NASA Technical Reports Server (NTRS)

Yoder, Dennis A.

2016-01-01

In this study, several variable turbulent Prandtl number formulations are examined for boundary layers, pipe flow, and axisymmetric jets. The model formulations include simple algebraic relations between the thermal diffusivity and turbulent viscosity as well as more complex models that solve transport equations for the thermal variance and its dissipation rate. Results are compared with available data for wall heat transfer and profile measurements of mean temperature, the root-mean-square (RMS) fluctuating temperature, turbulent heat flux and turbulent Prandtl number. For wall-bounded problems, the algebraic models are found to best predict the rise in turbulent Prandtl number near the wall as well as the log-layer temperature profile, while the thermal variance models provide a good representation of the RMS temperature fluctuations. In jet flows, the algebraic models provide no benefit over a constant turbulent Prandtl number approach. Application of the thermal variance models finds that some significantly overpredict the temperature variance in the plume and most underpredict the thermal growth rate of the jet. The models yield very similar fluctuating temperature intensities in jets from straight pipes and smooth contraction nozzles, in contrast to data that indicate the latter should have noticeably higher values. For the particular low subsonic heated jet cases examined, changes in the turbulent Prandtl number had no effect on the centerline velocity decay.

Cross-sectional mapping for refined beam elements with applications to shell-like structures

NASA Astrophysics Data System (ADS)

Pagani, A.; de Miguel, A. G.; Carrera, E.

2017-06-01

This paper discusses the use of higher-order mapping functions for enhancing the physical representation of refined beam theories. Based on the Carrera unified formulation (CUF), advanced one-dimensional models are formulated by expressing the displacement field as a generic expansion of the generalized unknowns. According to CUF, a novel physically/geometrically consistent model is devised by employing Legendre-like polynomial sets to approximate the generalized unknowns at the cross-sectional level, whereas a local mapping technique based on the blending functions method is used to describe the exact physical boundaries of the cross-section domain. Classical and innovative finite element methods, including hierarchical p-elements and locking-free integration schemes, are utilized to solve the governing equations of the unified beam theory. Several numerical applications accounting for small displacements/rotations and strains are discussed, including beam structures with cross-sectional curved edges, cylindrical shells, and thin-walled aeronautical wing structures with reinforcements. The results from the proposed methodology are widely assessed by comparisons with solutions from the literature and commercial finite element software tools. The attention is focussed on the high computational efficiency and the marked capabilities of the present beam model, which can deal with a broad spectrum of structural problems with unveiled accuracy in terms of geometrical representation of the domain boundaries.

Epidemic patch models applied to pandemic influenza: contact matrix, stochasticity, robustness of predictions.

PubMed

Lunelli, Antonella; Pugliese, Andrea; Rizzo, Caterina

2009-07-01

Due to the recent emergence of H5N1 virus, the modelling of pandemic influenza has become a relevant issue. Here we present an SEIR model formulated to simulate a possible outbreak in Italy, analysing its structure and, more generally, the effect of including specific details into a model. These details regard population heterogeneities, such as age and spatial distribution, as well as stochasticity, that regulates the epidemic dynamics when the number of infectives is low. We discuss and motivate the specific modelling choices made when building the model and investigate how the model details influence the predicted dynamics. Our analysis may help in deciding which elements of complexity are worth including in the design of a deterministic model for pandemic influenza, in a balance between, on the one hand, keeping the model computationally efficient and the number of parameters low and, on the other hand, maintaining the necessary realistic features.

The impact of in-canopy wind profile formulations on heat flux estimation in an open orchard using the remote sensing-based two-source model

NASA Astrophysics Data System (ADS)

Cammalleri, C.; Anderson, M. C.; Ciraolo, G.; Durso, G.; Kustas, W. P.; La Loggia, G.; Minacapilli, M.

2010-12-01

For open orchard and vineyard canopies containing significant fractions of exposed soil (>50%), typical of Mediterranean agricultural regions, the energy balance of the vegetation elements is strongly influenced by heat exchange with the bare soil/substrate. For these agricultural systems a "two-source" approach, where radiation and turbulent exchange between the soil and canopy elements are explicitly modelled, appears to be the only suitable methodology for reliably assessing energy fluxes. In strongly clumped canopies, the effective wind speed profile inside and below the canopy layer can strongly influence the partitioning of energy fluxes between the soil and vegetation components. To assess the impact of in-canopy wind profile on model flux estimates, an analysis of three different formulations is presented, including algorithms from Goudriaan (1977), Massman (1987) and Lalic et al. (2003). The in-canopy wind profile formulations are applied to the thermal-based two-source energy balance (TSEB) model developed by Norman et al. (1995) and modified by Kustas and Norman (1999). High resolution airborne remote sensing images, collected over an agricultural area located in the western part of Sicily (Italy) comprised primarily of vineyards, olive and citrus orchards, are used to derive all the input parameters needed to apply the TSEB. The images were acquired from June to October 2008 and include a relatively wide range of meteorological and soil moisture conditions. A preliminary sensitivity analysis of the three wind profile algorithms highlights the dependence of wind speed just above the soil/substrate to leaf area index and canopy height over the typical range of canopy properties encountered in these agricultural areas. It is found that differences among the models in wind just above the soil surface are most significant under sparse and medium fractional cover conditions (15-50%). The TSEB model heat flux estimates are compared with micro-meteorological measurements from a small aperture scintillometer and an eddy covariance tower collected over an olive orchard characterized by moderate fractional vegetation cover (≍35%) and relatively tall crop (≍3.5 m). TSEB fluxes for the 7 image acquisition dates generated using both the Massman and Goudriaan in-canopy wind profile formulations give close agreement with measured fluxes, while the Lalic et al. equations yield poor results. The Massman wind profile scheme slightly outperforms that of Goudriaan, but it requires an additional parameter accounting for the roughness sub-layer of the underlying vegetative surface. The analysis also suggests that within-canopy wind profile model discrepancies become important, in terms of impact on modelled sensible heat flux, only for sparse canopies with moderate vegetation coverage.

Formulation of Efficient Finite Element Prediction Models.

DTIC Science & Technology

1980-01-01

vorticity-divergence FEM formulation. This paper will compare these FEM formulations by considering the Vgeostrophic adjustment process with the linearized...by Fourier transforming the terms that are independent of t in (2.12)-(2.14) or (2.19)-(2.21). However, in this paper the final state will be...filtering in a baroclinic primitive equation model. 17 L . , 5. Conclusions The objective of this paper is to determine the response of various finite

The influence of API concentration on the roller compaction process: modeling and prediction of the post compacted ribbon, granule and tablet properties using multivariate data analysis.

PubMed

Boersen, Nathan; Carvajal, M Teresa; Morris, Kenneth R; Peck, Garnet E; Pinal, Rodolfo

2015-01-01

While previous research has demonstrated roller compaction operating parameters strongly influence the properties of the final product, a greater emphasis might be placed on the raw material attributes of the formulation. There were two main objectives to this study. First, to assess the effects of different process variables on the properties of the obtained ribbons and downstream granules produced from the rolled compacted ribbons. Second, was to establish if models obtained with formulations of one active pharmaceutical ingredient (API) could predict the properties of similar formulations in terms of the excipients used, but with a different API. Tolmetin and acetaminophen, chosen for their different compaction properties, were roller compacted on Fitzpatrick roller compactor using the same formulation. Models created using tolmetin and tested using acetaminophen. The physical properties of the blends, ribbon, granule and tablet were characterized. Multivariate analysis using partial least squares was used to analyze all data. Multivariate models showed that the operating parameters and raw material attributes were essential in the prediction of ribbon porosity and post-milled particle size. The post compacted ribbon and granule attributes also significantly contributed to the prediction of the tablet tensile strength. Models derived using tolmetin could reasonably predict the ribbon porosity of a second API. After further processing, the post-milled ribbon and granules properties, rather than the physical attributes of the formulation were needed to predict downstream tablet properties. An understanding of the percolation threshold of the formulation significantly improved the predictive ability of the models.

Nonlinear micromechanics-based finite element analysis of the interfacial behaviour of FRP-strengthened reinforced concrete beams

NASA Astrophysics Data System (ADS)

Abd El Baky, Hussien

This research work is devoted to theoretical and numerical studies on the flexural behaviour of FRP-strengthened concrete beams. The objectives of this research are to extend and generalize the results of simple experiments, to recommend new design guidelines based on accurate numerical tools, and to enhance our comprehension of the bond performance of such beams. These numerical tools can be exploited to bridge the existing gaps in the development of analysis and modelling approaches that can predict the behaviour of FRP-strengthened concrete beams. The research effort here begins with the formulation of a concrete model and development of FRP/concrete interface constitutive laws, followed by finite element simulations for beams strengthened in flexure. Finally, a statistical analysis is carried out taking the advantage of the aforesaid numerical tools to propose design guidelines. In this dissertation, an alternative incremental formulation of the M4 microplane model is proposed to overcome the computational complexities associated with the original formulation. Through a number of numerical applications, this incremental formulation is shown to be equivalent to the original M4 model. To assess the computational efficiency of the incremental formulation, the "arc-length" numerical technique is also considered and implemented in the original Bazant et al. [2000] M4 formulation. Finally, the M4 microplane concrete model is coded in FORTRAN and implemented as a user-defined subroutine into the commercial software package ADINA, Version 8.4. Then this subroutine is used with the finite element package to analyze various applications involving FRP strengthening. In the first application a nonlinear micromechanics-based finite element analysis is performed to investigate the interfacial behaviour of FRP/concrete joints subjected to direct shear loadings. The intention of this part is to develop a reliable bond--slip model for the FRP/concrete interface. The bond--slip relation is developed considering the interaction between the interfacial normal and shear stress components along the bonded length. A new approach is proposed to describe the entire tau-s relationship based on three separate models. The first model captures the shear response of an orthotropic FRP laminate. The second model simulates the shear characteristics of an adhesive layer, while the third model represents the shear nonlinearity of a thin layer inside the concrete, referred to as the interfacial layer. The proposed bond--slip model reflects the geometrical and material characteristics of the FRP, concrete, and adhesive layers. Two-dimensional and three-dimensional nonlinear displacement-controlled finite element (FE) models are then developed to investigate the flexural and FRP/concrete interfacial responses of FRP-strengthened reinforced concrete beams. The three-dimensional finite element model is created to accommodate cases of beams having FRP anchorage systems. Discrete interface elements are proposed and used to simulate the FRP/concrete interfacial behaviour before and after cracking. The FE models are capable of simulating the various failure modes, including debonding of the FRP either at the plate end or at intermediate cracks. Particular attention is focused on the effect of crack initiation and propagation on the interfacial behaviour. This study leads to an accurate and refined interpretation of the plate-end and intermediate crack debonding failure mechanisms for FRP-strengthened beams with and without FRP anchorage systems. Finally, the FE models are used to conduct a parametric study to generalize the findings of the FE analysis. The variables under investigation include two material characteristics; namely, the concrete compressive strength and axial stiffness of the FRP laminates as well as three geometric properties; namely, the steel reinforcement ratio, the beam span length and the beam depth. The parametric study is followed by a statistical analysis for 43 strengthened beams involving the five aforementioned variables. The response surface methodology (RSM) technique is employed to optimize the accuracy of the statistical models while minimizing the numbers of finite element runs. In particular, a face-centred design (FCD) is applied to evaluate the influence of the critical variables on the debonding load and debonding strain limits in the FRP laminates. Based on these statistical models, a nonlinear statistical regression analysis is used to propose design guidelines for the FRP flexural strengthening of reinforced concrete beams. (Abstract shortened by UMI.)

Three-dimensional waveform sensitivity kernels

NASA Astrophysics Data System (ADS)

Marquering, Henk; Nolet, Guust; Dahlen, F. A.

1998-03-01

The sensitivity of intermediate-period (~10-100s) seismic waveforms to the lateral heterogeneity of the Earth is computed using an efficient technique based upon surface-wave mode coupling. This formulation yields a general, fully fledged 3-D relationship between data and model without imposing smoothness constraints on the lateral heterogeneity. The calculations are based upon the Born approximation, which yields a linear relation between data and model. The linear relation ensures fast forward calculations and makes the formulation suitable for inversion schemes; however, higher-order effects such as wave-front healing are neglected. By including up to 20 surface-wave modes, we obtain Fréchet, or sensitivity, kernels for waveforms in the time frame that starts at the S arrival and which includes direct and surface-reflected body waves. These 3-D sensitivity kernels provide new insights into seismic-wave propagation, and suggest that there may be stringent limitations on the validity of ray-theoretical interpretations. Even recently developed 2-D formulations, which ignore structure out of the source-receiver plane, differ substantially from our 3-D treatment. We infer that smoothness constraints on heterogeneity, required to justify the use of ray techniques, are unlikely to hold in realistic earth models. This puts the use of ray-theoretical techniques into question for the interpretation of intermediate-period seismic data. The computed 3-D sensitivity kernels display a number of phenomena that are counter-intuitive from a ray-geometrical point of view: (1) body waves exhibit significant sensitivity to structure up to 500km away from the source-receiver minor arc; (2) significant near-surface sensitivity above the two turning points of the SS wave is observed; (3) the later part of the SS wave packet is most sensitive to structure away from the source-receiver path; (4) the sensitivity of the higher-frequency part of the fundamental surface-wave mode is wider than for its faster, lower-frequency part; (5) delayed body waves may considerably influence fundamental Rayleigh and Love waveforms. The strong sensitivity of waveforms to crustal structure due to fundamental-mode-to-body-wave scattering precludes the use of phase-velocity filters to model body-wave arrivals. Results from the 3-D formulation suggest that the use of 2-D and 1-D techniques for the interpretation of intermediate-period waveforms should seriously be reconsidered.

Elliptic Relaxation of a Tensor Representation for the Redistribution Terms in a Reynolds Stress Turbulence Model

NASA Technical Reports Server (NTRS)

Carlson, J. R.; Gatski, T. B.

2002-01-01

A formulation to include the effects of wall proximity in a second-moment closure model that utilizes a tensor representation for the redistribution terms in the Reynolds stress equations is presented. The wall-proximity effects are modeled through an elliptic relaxation process of the tensor expansion coefficients that properly accounts for both correlation length and time scales as the wall is approached. Direct numerical simulation data and Reynolds stress solutions using a full differential approach are compared for the case of fully developed channel flow.

The mathematical modeling of rapid solidification processing. Ph.D. Thesis. Final Report

NASA Technical Reports Server (NTRS)

Gutierrez-Miravete, E.

1986-01-01

The detailed formulation of and the results obtained from a continuum mechanics-based mathematical model of the planar flow melt spinning (PFMS) rapid solidification system are presented and discussed. The numerical algorithm proposed is capable of computing the cooling and freezing rates as well as the fluid flow and capillary phenomena which take place inside the molten puddle formed in the PFMS process. The FORTRAN listings of some of the most useful computer programs and a collection of appendices describing the basic equations used for the modeling are included.

Elliptic Relaxation of a Tensor Representation of the Pressure-Strain and Dissipation Rate

NASA Technical Reports Server (NTRS)

Carlson, John R.; Gatski, Thomas B.

2002-01-01

A formulation to include the effects of wall-proximity in a second moment closure model is presented that utilizes a tensor representation for the redistribution term in the Reynolds stress equations. The wall-proximity effects are modeled through an elliptic relaxation process of the tensor expansion coefficients that properly accounts for both correlation length and time scales as the wall is approached. DNS data and Reynolds stress solutions using a full differential approach at channel Reynolds number of 590 are compared to the new model.

Influence of humidity on the phase behavior of API/polymer formulations.

PubMed

Prudic, Anke; Ji, Yuanhui; Luebbert, Christian; Sadowski, Gabriele

2015-08-01

Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25°C and at different values of relative humidity (RH=25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as a function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Strategies for bringing drug delivery tools into discovery.

PubMed

Kwong, Elizabeth; Higgins, John; Templeton, Allen C

2011-06-30

The past decade has yielded a significant body of literature discussing approaches for development and discovery collaboration in the pharmaceutical industry. As a result, collaborations between discovery groups and development scientists have increased considerably. The productivity of pharma companies to deliver new drugs to the market, however, has not increased and development costs continue to rise. Inability to predict clinical and toxicological response underlies the high attrition rate of leads at every step of drug development. A partial solution to this high attrition rate could be provided by better preclinical pharmacokinetics measurements that inform PD response based on key pathways that drive disease progression and therapeutic response. A critical link between these key pharmacology, pharmacokinetics and toxicology studies is the formulation. The challenges in pre-clinical formulation development include limited availability of compounds, rapid turn-around requirements and the frequent un-optimized physical properties of the lead compounds. Despite these challenges, this paper illustrates some successes resulting from close collaboration between formulation scientists and discovery teams. This close collaboration has resulted in development of formulations that meet biopharmaceutical needs from early stage preclinical in vivo model development through toxicity testing and development risk assessment of pre-clinical drug candidates. Published by Elsevier B.V.

A scalable variational inequality approach for flow through porous media models with pressure-dependent viscosity

NASA Astrophysics Data System (ADS)

Mapakshi, N. K.; Chang, J.; Nakshatrala, K. B.

2018-04-01

Mathematical models for flow through porous media typically enjoy the so-called maximum principles, which place bounds on the pressure field. It is highly desirable to preserve these bounds on the pressure field in predictive numerical simulations, that is, one needs to satisfy discrete maximum principles (DMP). Unfortunately, many of the existing formulations for flow through porous media models do not satisfy DMP. This paper presents a robust, scalable numerical formulation based on variational inequalities (VI), to model non-linear flows through heterogeneous, anisotropic porous media without violating DMP. VI is an optimization technique that places bounds on the numerical solutions of partial differential equations. To crystallize the ideas, a modification to Darcy equations by taking into account pressure-dependent viscosity will be discretized using the lowest-order Raviart-Thomas (RT0) and Variational Multi-scale (VMS) finite element formulations. It will be shown that these formulations violate DMP, and, in fact, these violations increase with an increase in anisotropy. It will be shown that the proposed VI-based formulation provides a viable route to enforce DMP. Moreover, it will be shown that the proposed formulation is scalable, and can work with any numerical discretization and weak form. A series of numerical benchmark problems are solved to demonstrate the effects of heterogeneity, anisotropy and non-linearity on DMP violations under the two chosen formulations (RT0 and VMS), and that of non-linearity on solver convergence for the proposed VI-based formulation. Parallel scalability on modern computational platforms will be illustrated through strong-scaling studies, which will prove the efficiency of the proposed formulation in a parallel setting. Algorithmic scalability as the problem size is scaled up will be demonstrated through novel static-scaling studies. The performed static-scaling studies can serve as a guide for users to be able to select an appropriate discretization for a given problem size.

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

The flow of plasma in the solar terrestrial environment

NASA Technical Reports Server (NTRS)

Schunk, Robert W.; Banks, P.; Barakat, A. R.; Crain, D. J.; Demars, H. G.; Lemaire, J.; Ma, T.-Z.; Rasmussen, C. E.; Richards, P.; Sica, R.

1990-01-01

The overall goal of our NASA Theory Program was to study the coupling, time delays, and feedback mechanisms between the various regions of the solar-terrestrial system in a self-consistent, quantitative manner. To accomplish this goal, it will eventually be necessary to have time-dependent macroscopic models of the different regions of the solar-terrestrial system and we are continually working toward this goal. However, with the funding from this NASA program, we concentrated on the near-earth plasma environment, including the ionosphere, the plasmasphere, and the polar wind. In this area, we developed unique global models that allowed us to study the coupling between the different regions. These results are highlighted in the next section. Another important aspect of our NASA Theory Program concerned the effect that localized 'structure' had on the macroscopic flow in the ionosphere, plasmasphere, thermosphere, and polar wind. The localized structure can be created by structured magnetospheric inputs (i.e., structured plasma convection, particle precipitation or Birkland current patterns) or time variations in these input due to storms and substorms. Also, some of the plasma flows that we predicted with our macroscopic models could be unstable, and another one of our goals was to examine the stability of our predicted flows. Because time-dependent, three-dimensional numerical models of the solar-terrestrial environment generally require extensive computer resources, they are usually based on relatively simple mathematical formulations (i.e., simple MHD or hydrodynamic formulations). Therefore, another goal of our NASA Theory Program was to study the conditions under which various mathematical formulations can be applied to specific solar-terrestrial regions. This could involve a detailed comparison of kinetic, semi-kinetic, and hydrodynamic predictions for a given polar wind scenario or it could involve the comparison of a small-scale particle-in-cell (PIC) simulation of a plasma expansion event with a similar macroscopic expansion event. The different mathematical formulations have different strengths and weaknesses and a careful comparison of model predictions for similar geophysical situations provides insight into when the various models can be used with confidence.

The flow of plasma in the solar terrestrial environment

NASA Technical Reports Server (NTRS)

Schunk, Robert W.

1991-01-01

The overall goal of our NASA Theory Program is to study the coupling, time delays, and feedback mechanisms between the various regions of the solar-terrestrial system in a self-consistent, quantitative, manner. To accomplish this goal, it will eventually be necessary to have time-dependent macroscopic models of the different regions of the solar-terrestrial system and we are continually working toward this goal. However, our immediate emphasis is on the near-earth plasma environment, including the ionosphere, the plasmasphere, and the polar wind. In this area, we have developed unique global models that allow us to study the coupling between the different regions. These results are highlighted. Another important aspect of our NASA Theory Program concerns the effect that localized structure has on the macroscopic flow in the ionosphere, plasmasphere, thermosphere and polar wind. The localized structure can be created by structured magnetospheric inputs (i.e., structured plasma convection, particle precipitation or Birkeland current patterns) or time variations in these inputs due to storms and substorms. Also, some of the plasma flows that we predict with our macroscopic models may be unstable. Another one of our goals is to examine the stability of our predicted flows. Because time-dependent three-dimensional numerical models of the solar-terrestrial environment generally require extensive computer resources, they are usually based on relatively simple mathematical formulations (i.e., simple MHD or hydrodynamic formulations). Therefore, another long-range goal of our NASA Theory Program is to study the conditions under which various mathematical formulations can be applied to specific solar-terrestrial regions. This may involve a detailed comparison of kinetic, semikinetic, and hydrodynamic predictions for a given polar wind scenario or it may involve the comparison of a small-scale particle-in-cell (PIC) simulation of a plasma expansion event with a similar macroscopic expansion event. The different mathematical formulations have different strengths and weaknesses and a careful comparison of model predictions for similar geophysical situations will provide insight into when the various models can be used with confidence.

Formulation and clinical evaluation of topical dosage forms of Indian Penny Wort, walnut and turmeric in eczema.

PubMed

Khiljee, Sonia; Rehman, Nisarur; Khiljee, Tanzila; Loebenberg, Raimar; Ahmad, Rao Saeed

2015-11-01

Eczema is characterized by itching, lichenification, scaling, oedema and erythema. Current management strategies include corticosteroids, which are limited due to side effects. Many herbal remedies are used traditionally but unfortunately have not been validated in controlled clinical trials. Three popular traditional treatments of eczema include Indian pennywort, Walnut and Turmeric. In this study three topical formulations (micro emulsion, gel and ointment) were prepared from extracts of Indian pennywort, Walnut and Turmeric. These formulations were monitored for stability for a period of three months. Controlled clinical trials were conducted on 360 eczema patients. Clinical parameters observed were degree of erythema, oedema, scaling, itching and lichenification. Effects of each formulation on these clinical parameters were compared with placebo formulations. Micro emulsion formulations in all cases proved to be more effective in reducing semi quantitative scores of erythema and oedema. Itching was relieved more by gel formulation. The ointment showed more efficacy towards scaling and lichenification. Comparison of the effects of placebo and the specific formulations was performed by chi-square statistics and found to be highly significant. In summary it is concluded that all the formulations could be used as promising source for treatment of eczema.

Completed Beltrami-Michell Formulation for Analyzing Radially Symmetrical Bodies

NASA Technical Reports Server (NTRS)

Kaljevic, Igor; Saigal, Sunil; Hopkins, Dale A.; Patnaik, Surya N.

1994-01-01

A force method formulation, the completed Beltrami-Michell formulation (CBMF), has been developed for analyzing boundary value problems in elastic continua. The CBMF is obtained by augmenting the classical Beltrami-Michell formulation with novel boundary compatibility conditions. It can analyze general elastic continua with stress, displacement, or mixed boundary conditions. The CBMF alleviates the limitations of the classical formulation, which can solve stress boundary value problems only. In this report, the CBMF is specialized for plates and shells. All equations of the CBMF, including the boundary compatibility conditions, are derived from the variational formulation of the integrated force method (IFM). These equations are defined only in terms of stresses. Their solution for kinematically stable elastic continua provides stress fields without any reference to displacements. In addition, a stress function formulation for plates and shells is developed by augmenting the classical Airy's formulation with boundary compatibility conditions expressed in terms of the stress function. The versatility of the CBMF and the augmented stress function formulation is demonstrated through analytical solutions of several mixed boundary value problems. The example problems include a composite circular plate and a composite circular cylindrical shell under the simultaneous actions of mechanical and thermal loads.

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPP improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.

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.

Preliminary model and validation of molten carbonate fuel cell kinetics under sulphur poisoning

NASA Astrophysics Data System (ADS)

Audasso, E.; Nam, S.; Arato, E.; Bosio, B.

2017-06-01

MCFC represents an effective technology to deal with CO2 capture and relative applications. If used for these purposes, due to the working conditions and the possible feeding, MCFC must cope with a different number of poisoning gases such as sulphur compounds. In literature, different works deal with the development of kinetic models to describe MCFC performance to help both industrial applications and laboratory simulations. However, in literature attempts to realize a proper model able to consider the effects of poisoning compounds are scarce. The first aim of the present work is to provide a semi-empirical kinetic formulation capable to take into account the effects that sulphur compounds (in particular SO2) have on the MCFC performance. The second aim is to provide a practical example of how to effectively include the poisoning effects in kinetic models to simulate fuel cells performances. To test the reliability of the proposed approach, the obtained formulation is implemented in the kinetic core of the SIMFC (SIMulation of Fuel Cells) code, an MCFC 3D model realized by the Process Engineering Research Team (PERT) of the University of Genova. Validation is performed through data collected at the Korea Institute of Science and Technology in Seoul.

Study of multi-dimensional radiative energy transfer in molecular gases

NASA Technical Reports Server (NTRS)

Liu, Jiwen; Tiwari, S. N.

1993-01-01

The Monte Carlo method (MCM) is applied to analyze radiative heat transfer in nongray gases. The nongray model employed is based on the statistical arrow band model with an exponential-tailed inverse intensity distribution. Consideration of spectral correlation results in some distinguishing features of the Monte Carlo formulations. Validation of the Monte Carlo formulations has been conducted by comparing results of this method with other solutions. Extension of a one-dimensional problem to a multi-dimensional problem requires some special treatments in the Monte Carlo analysis. Use of different assumptions results in different sets of Monte Carlo formulations. The nongray narrow band formulations provide the most accurate results.