Science.gov

Sample records for cfd-based mechanistic deposit

  1. A CFD-Based Study of the Feasibility of Adapting an Erosion Burner Rig for Examining the Effect of CMAS Deposition Corrosion on Environmental Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Miller, Robert A.; Kuczmarski, Maria A.

    2015-01-01

    Thermodynamic and computational fluid dynamics modeling has been conducted to examine the feasibility of adapting the NASA-Glenn erosion burner rigs for use in studies of corrosion of environmental barrier coatings by the deposition of molten CMAS. The effect of burner temperature, Mach number, particle preheat, duct heating, particle size, and particle phase (crystalline vs. glass) were analyzed. Detailed strategies for achieving complete melting of CMAS particles were developed, thereby greatly improving the probability of future successful experimental outcomes.

  2. Deposition, characterization, patterning and mechanistic study of inorganic resists for next-generation nanolithography

    NASA Astrophysics Data System (ADS)

    Luo, Feixiang

    The semiconductor industry has witnessed a continuous decrease in the size of logic, memory and other computer chip components since its birth over half a century ago. The shrinking (scaling) of components has to a large extent been enabled by the development of micro- and now nano-lithographic techniques. This thesis focuses on one central component of lithography, the resist, which is essentially a thin film that when appropriately exposed enables a pattern to be printed onto a surface. Smaller features require an ever more precisely focused photon, electron or ion beam with which to expose the resist. The likely next generation source of radiation that will enable sub-20nm features to be written will employ extreme ultraviolet radiation (EUV), 92eV (13.5nm). The work discussed here involves a novel class of inorganic resists (including a solution processed Hf-based resist called HafSOx), as the organic resists that have dominated the microlithography industry for the past few decades have approached fundamental scaling limits. In order to maintain the high throughput required by high volume semiconductor manufacturing, metal oxide resists have been proposed and developed to meet the resolution and sensitivity in EUV lithography. One can think of our resists as the nano-lithographic analog to the silver halide film that dominated the photographic print industry for a century. In this thesis, we mainly describe our work on HafSOx, a "first generation" metal oxide EUV resist system. HafSOx thin films can be deposited by spin-coating a mixed solution of HfOCl2, H2O 2, and H2SO4. Various materials characterization techniques have been employed to achieve a comprehensive understanding of film composition and structure at both surface and bulk level, as well as a mechanistic understanding of the film radiation chemistry. Taking advantage of the high energy x-rays used in the XPS experiment, we developed an experiment to dynamically monitor the photochemistry within the

  3. Mechanistic modeling study on process optimization and precursor utilization with atmospheric spatial atomic layer deposition

    SciTech Connect

    Deng, Zhang; He, Wenjie; Duan, Chenlong; Chen, Rong; Shan, Bin

    2016-01-15

    Spatial atomic layer deposition (SALD) is a promising technology with the aim of combining the advantages of excellent uniformity and conformity of temporal atomic layer deposition (ALD), and an industrial scalable and continuous process. In this manuscript, an experimental and numerical combined model of atmospheric SALD system is presented. To establish the connection between the process parameters and the growth efficiency, a quantitative model on reactant isolation, throughput, and precursor utilization is performed based on the separation gas flow rate, carrier gas flow rate, and precursor mass fraction. The simulation results based on this model show an inverse relation between the precursor usage and the carrier gas flow rate. With the constant carrier gas flow, the relationship of precursor usage and precursor mass fraction follows monotonic function. The precursor concentration, regardless of gas velocity, is the determinant factor of the minimal residual time. The narrow gap between precursor injecting heads and the substrate surface in general SALD system leads to a low Péclet number. In this situation, the gas diffusion act as a leading role in the precursor transport in the small gap rather than the convection. Fluid kinetics from the numerical model is independent of the specific structure, which is instructive for the SALD geometry design as well as its process optimization.

  4. Generalized Mechanistic Model for the Chemical Vapor Deposition of 2D Transition Metal Dichalcogenide Monolayers.

    PubMed

    Govind Rajan, Ananth; Warner, Jamie H; Blankschtein, Daniel; Strano, Michael S

    2016-04-26

    Transition metal dichalcogenides (TMDs) like molybdenum disulfide (MoS2) and tungsten disulfide (WS2) are layered materials capable of growth to one monolayer thickness via chemical vapor deposition (CVD). Such CVD methods, while powerful, are notoriously difficult to extend across different reactor types and conditions, with subtle variations often confounding reproducibility, particularly for 2D TMD growth. In this work, we formulate the first generalized TMD synthetic theory by constructing a thermodynamic and kinetic growth mechanism linked to CVD reactor parameters that is predictive of specific geometric shape, size, and aspect ratio from triangular to hexagonal growth, depending on specific CVD reactor conditions. We validate our model using experimental data from Wang et al. (Chem. Mater. 2014, 26, 6371-6379) that demonstrate the systemic evolution of MoS2 morphology down the length of a flow CVD reactor where variations in gas phase concentrations can be accurately estimated using a transport model (CSulfur = 9-965 μmol/m(3); CMoO3 = 15-16 mmol/m(3)) under otherwise isothermal conditions (700 °C). A stochastic model which utilizes a site-dependent activation energy barrier based on the intrinsic TMD bond energies and a series of Evans-Polanyi relations leads to remarkable, quantitative agreement with both shape and size evolution along the reactor. The model is shown to extend to the growth of WS2 at 800 °C and MoS2 under varied process conditions. Finally, a simplified theory is developed to translate the model into a "kinetic phase diagram" of the growth process. The predictive capability of this model and its extension to other TMD systems promise to significantly increase the controlled synthesis of such materials.

  5. New Flutter Analysis Technique for CFD-based Unsteady Aeroelasticity

    NASA Technical Reports Server (NTRS)

    Pak, Chan-gi; Jutte, Christine V.

    2009-01-01

    This paper presents a flutter analysis technique for the transonic flight regime. The technique uses an iterative approach to determine the critical dynamic pressure for a given mach number. Unlike other CFD-based flutter analysis methods, each iteration solves for the critical dynamic pressure and uses this value in subsequent iterations until the value converges. This process reduces the iterations required to determine the critical dynamic pressure. To improve the accuracy of the analysis, the technique employs a known structural model, leaving only the aerodynamic model as the unknown. The aerodynamic model is estimated using unsteady aeroelastic CFD analysis combined with a parameter estimation routine. The technique executes as follows. The known structural model is represented as a finite element model. Modal analysis determines the frequencies and mode shapes for the structural model. At a given mach number and dynamic pressure, the unsteady CFD analysis is performed. The output time history of the surface pressure is converted to a nodal aerodynamic force vector. The forces are then normalized by the given dynamic pressure. A multi-input multi-output parameter estimation software, ERA, estimates the aerodynamic model through the use of time histories of nodal aerodynamic forces and structural deformations. The critical dynamic pressure is then calculated using the known structural model and the estimated aerodynamic model. This output is used as the dynamic pressure in subsequent iterations until the critical dynamic pressure is determined. This technique is demonstrated on the Aerostructures Test Wing-2 model at NASA's Dryden Flight Research Center.

  6. Mechanistic considerations of the pyrolytic formation of metal boride thin films by chemical vapor deposition from borane precursors

    SciTech Connect

    Tan, Y.; Kher, S.S.; Spencer, J.T.

    1995-12-31

    The formation of metal boride thin films by CVD is an area of potentially significant technological consequence. Interest in these materials is primarily due to their breadth of unique physical properties and to their wide structural diversity. Recently, we have explored the use of a number of boron-containing CVC precursors to prepare a wide variety of both pure metal and metal boride thin film materials. The highly efficient formation of polycrystalline transition metal and lanthanide metal boride thin films from borane precursors has now been well demonstrated through this CVD chemistry. The fundamentally important chemical processes and reactions in the CVD of boranes in forming metal boride films has, however, remained mostly a mystery. In order to rationally design new precursors and tailor the deposited solid state materials, an understanding of these fundamental processes is critical. In our recent work, which will be reported here, we have begun detailed mechanistic studies into the CVD of metal borides. These reactions have been found to occur both in the gas phase and on the surface of the reactor. A variety of studies have provided valuable insights into these complexes chemical reactions including labeling, thermal, product distribution, surface analysis, kinetic and other investigations.

  7. Simultaneous Excitation of Multiple-Input Multiple-Output CFD-Based Unsteady Aerodynamic Systems

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.

    2008-01-01

    A significant improvement to the development of CFD-based unsteady aerodynamic reduced-order models (ROMs) is presented. This improvement involves the simultaneous excitation of the structural modes of the CFD-based unsteady aerodynamic system that enables the computation of the unsteady aerodynamic state-space model using a single CFD execution, independent of the number of structural modes. Four different types of inputs are presented that can be used for the simultaneous excitation of the structural modes. Results are presented for a flexible, supersonic semi-span configuration using the CFL3Dv6.4 code.

  8. Simultaneous Excitation of Multiple-Input Multiple-Output CFD-Based Unsteady Aerodynamic Systems

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.

    2007-01-01

    A significant improvement to the development of CFD-based unsteady aerodynamic reduced-order models (ROMs) is presented. This improvement involves the simultaneous excitation of the structural modes of the CFD-based unsteady aerodynamic system that enables the computation of the unsteady aerodynamic state-space model using a single CFD execution, independent of the number of structural modes. Four different types of inputs are presented that can be used for the simultaneous excitation of the structural modes. Results are presented for a flexible, supersonic semi-span configuration using the CFL3Dv6.4 code.

  9. REVIEW OF EXPERIMENTAL CAPABILITIES AND HYDRODYNAMIC DATA FOR VALIDATION OF CFD-BASED PREDICTIONS FOR SLURRY BUBBLE COLUMN REACTORS

    SciTech Connect

    Donna Post Guillen; Daniel S. Wendt; Steven P. Antal; Michael Z. Podowski

    2007-11-01

    The purpose of this paper is to document the review of several open-literature sources of both experimental capabilities and published hydrodynamic data to aid in the validation of a Computational Fluid Dynamics (CFD) based model of a slurry bubble column (SBC). The review included searching the Web of Science, ISI Proceedings, and Inspec databases, internet searches as well as other open literature sources. The goal of this study was to identify available experimental facilities and relevant data. Integral (i.e., pertaining to the SBC system), as well as fundamental (i.e., separate effects are considered), data are included in the scope of this effort. The fundamental data is needed to validate the individual mechanistic models or closure laws used in a Computational Multiphase Fluid Dynamics (CMFD) simulation of a SBC. The fundamental data is generally focused on simple geometries (i.e., flow between parallel plates or cylindrical pipes) or custom-designed tests to focus on selected interfacial phenomena. Integral data covers the operation of a SBC as a system with coupled effects. This work highlights selected experimental capabilities and data for the purpose of SBC model validation, and is not meant to be an exhaustive summary.

  10. REVIEW OF EXPERIMENTAL CAPABILITIES AND HYDRODYNAMIC DATA FOR VALIDATION OF CFD BASED PREDICTIONS FOR SLURRY BUBBLE COLUMN REACTORS

    SciTech Connect

    Donna Post Guillen; Daniel S. Wendt

    2007-11-01

    The purpose of this paper is to document the review of several open-literature sources of both experimental capabilities and published hydrodynamic data to aid in the validation of a Computational Fluid Dynamics (CFD) based model of a slurry bubble column (SBC). The review included searching the Web of Science, ISI Proceedings, and Inspec databases, internet searches as well as other open literature sources. The goal of this study was to identify available experimental facilities and relevant data. Integral (i.e., pertaining to the SBC system), as well as fundamental (i.e., separate effects are considered), data are included in the scope of this effort. The fundamental data is needed to validate the individual mechanistic models or closure laws used in a Computational Multiphase Fluid Dynamics (CMFD) simulation of a SBC. The fundamental data is generally focused on simple geometries (i.e., flow between parallel plates or cylindrical pipes) or custom-designed tests to focus on selected interfacial phenomena. Integral data covers the operation of a SBC as a system with coupled effects. This work highlights selected experimental capabilities and data for the purpose of SBC model validation, and is not meant to be an exhaustive summary.

  11. Flight Behaviors of a Complex Projectile Using a Coupled Computational Fluid Dynamics (CFD)-based Simulation Technique: Free Motion

    DTIC Science & Technology

    2015-09-01

    Dynamics (CFD)-based Simulation Technique: Free Motion by Jubaraj Sahu and Frank Fresconi Approved for public release...Technique: Free Motion by Jubaraj Sahu and Frank Fresconi Weapons and Materials Research Directorate, ARL Approved for public...Projectile Using a Coupled Computational Fluid Dynamics (CFD)-based Simulation Technique: Free Motion 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  12. Assessment of CFD-based Response Surface Model for Ares I Supersonic Ascent Aerodynamics

    NASA Technical Reports Server (NTRS)

    Hanke, Jeremy L.

    2011-01-01

    The Ascent Force and Moment Aerodynamic (AFMA) Databases (DBs) for the Ares I Crew Launch Vehicle (CLV) were typically based on wind tunnel (WT) data, with increments provided by computational fluid dynamics (CFD) simulations for aspects of the vehicle that could not be tested in the WT tests. During the Design Analysis Cycle 3 analysis for the outer mold line (OML) geometry designated A106, a major tunnel mishap delayed the WT test for supersonic Mach numbers (M) greater than 1.6 in the Unitary Plan Wind Tunnel at NASA Langley Research Center, and the test delay pushed the final delivery of the A106 AFMA DB back by several months. The aero team developed an interim database based entirely on the already completed CFD simulations to mitigate the impact of the delay. This CFD-based database used a response surface methodology based on radial basis functions to predict the aerodynamic coefficients for M > 1.6 based on only the CFD data from both WT and flight Reynolds number conditions. The aero team used extensive knowledge of the previous AFMA DB for the A103 OML to guide the development of the CFD-based A106 AFMA DB. This report details the development of the CFD-based A106 Supersonic AFMA DB, constructs a prediction of the database uncertainty using data available at the time of development, and assesses the overall quality of the CFD-based DB both qualitatively and quantitatively. This assessment confirms that a reasonable aerodynamic database can be constructed for launch vehicles at supersonic conditions using only CFD data if sufficient knowledge of the physics and expected behavior is available. This report also demonstrates the applicability of non-parametric response surface modeling using radial basis functions for development of aerodynamic databases that exhibit both linear and non-linear behavior throughout a large data space.

  13. Classification of processes for the atomic layer deposition of metals based on mechanistic information from density functional theory calculations

    NASA Astrophysics Data System (ADS)

    Elliott, S. D.; Dey, G.; Maimaiti, Y.

    2017-02-01

    Reaction cycles for the atomic layer deposition (ALD) of metals are presented, based on the incomplete data that exist about their chemical mechanisms, particularly from density functional theory (DFT) calculations. ALD requires self-limiting adsorption of each precursor, which results from exhaustion of adsorbates from previous ALD pulses and possibly from inactivation of the substrate through adsorption itself. Where the latter reaction does not take place, an "abbreviated cycle" still gives self-limiting ALD, but at a much reduced rate of deposition. Here, for example, ALD growth rates are estimated for abbreviated cycles in H2-based ALD of metals. A wide variety of other processes for the ALD of metals are also outlined and then classified according to which a reagent supplies electrons for reduction of the metal. Detailed results on computing the mechanism of copper ALD by transmetallation are summarized and shown to be consistent with experimental growth rates. Potential routes to the ALD of other transition metals by using complexes of non-innocent diazadienyl ligands as metal sources are also evaluated using DFT.

  14. Classification of processes for the atomic layer deposition of metals based on mechanistic information from density functional theory calculations.

    PubMed

    Elliott, S D; Dey, G; Maimaiti, Y

    2017-02-07

    Reaction cycles for the atomic layer deposition (ALD) of metals are presented, based on the incomplete data that exist about their chemical mechanisms, particularly from density functional theory (DFT) calculations. ALD requires self-limiting adsorption of each precursor, which results from exhaustion of adsorbates from previous ALD pulses and possibly from inactivation of the substrate through adsorption itself. Where the latter reaction does not take place, an "abbreviated cycle" still gives self-limiting ALD, but at a much reduced rate of deposition. Here, for example, ALD growth rates are estimated for abbreviated cycles in H2-based ALD of metals. A wide variety of other processes for the ALD of metals are also outlined and then classified according to which a reagent supplies electrons for reduction of the metal. Detailed results on computing the mechanism of copper ALD by transmetallation are summarized and shown to be consistent with experimental growth rates. Potential routes to the ALD of other transition metals by using complexes of non-innocent diazadienyl ligands as metal sources are also evaluated using DFT.

  15. Directing the deposition of ferromagnetic cobalt onto Pt-tipped CdSe@CdS nanorods: synthetic and mechanistic insights.

    PubMed

    Hill, Lawrence J; Bull, Mathew M; Sung, Younghun; Simmonds, Adam G; Dirlam, Philip T; Richey, Nathaniel E; DeRosa, Sean E; Shim, In-Bo; Guin, Debanjan; Costanzo, Philip J; Pinna, Nicola; Willinger, Marc-Georg; Vogel, Walter; Char, Kookheon; Pyun, Jeffrey

    2012-10-23

    A methodology providing access to dumbbell-tipped, metal-semiconductor and metal oxide-semiconductor heterostructured nanorods has been developed. The synthesis and characterization of CdSe@CdS nanorods incorporating ferromagnetic cobalt nanoinclusions at both nanorod termini (i.e., dumbbell morphology) are presented. The key step in the synthesis of these heterostructured nanorods was the decoration of CdSe@CdS nanorods with platinum nanoparticle tips, which promoted the deposition of metallic CoNPs onto Pt-tipped CdSe@CdS nanorods. Cobalt nanoparticle tips were then selectively oxidized to afford CdSe@CdS nanorods with cobalt oxide domains at both termini. In the case of longer cobalt-tipped nanorods, heterostructured nanorods were observed to self-organize into complex dipolar assemblies, which formed as a consequence of magnetic associations of terminal CoNP tips. Colloidal polymerization of these cobalt-tipped nanorods afforded fused nanorod assemblies from the oxidation of cobalt nanoparticle tips at the ends of nanorods via the nanoscale Kirkendall effect. Wurtzite CdS nanorods survived both the deposition of metallic CoNP tips and conversion into cobalt oxide phases, as confirmed by both XRD and HRTEM analysis. A series of CdSe@CdS nanorods of four different lengths ranging from 40 to 174 nm and comparable diameters (6-7 nm) were prepared and modified with both cobalt and cobalt oxide tips. The total synthesis of these heterostructured nanorods required five steps from commercially available reagents. Key synthetic considerations are discussed, with particular emphasis on reporting isolated yields of all intermediates and products from scale up of intermediate precursors.

  16. Recent Enhancements to the Development of CFD-Based Aeroelastic Reduced-Order Models

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.

    2007-01-01

    Recent enhancements to the development of CFD-based unsteady aerodynamic and aeroelastic reduced-order models (ROMs) are presented. These enhancements include the simultaneous application of structural modes as CFD input, static aeroelastic analysis using a ROM, and matched-point solutions using a ROM. The simultaneous application of structural modes as CFD input enables the computation of the unsteady aerodynamic state-space matrices with a single CFD execution, independent of the number of structural modes. The responses obtained from a simultaneous excitation of the CFD-based unsteady aerodynamic system are processed using system identification techniques in order to generate an unsteady aerodynamic state-space ROM. Once the unsteady aerodynamic state-space ROM is generated, a method for computing the static aeroelastic response using this unsteady aerodynamic ROM and a state-space model of the structure, is presented. Finally, a method is presented that enables the computation of matchedpoint solutions using a single ROM that is applicable over a range of dynamic pressures and velocities for a given Mach number. These enhancements represent a significant advancement of unsteady aerodynamic and aeroelastic ROM technology.

  17. Development of Unsteady Aerodynamic State-Space Models from CFD-Based Pulse Responses

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Raveh, Daniella E.

    2001-01-01

    A method for computing discrete-time state-space models of linearized unsteady aerodynamic behavior directly from aeroelastic CFD codes is presented. The method involves the treatment of CFD-based pulse responses as Markov parameters for use in a system identification /realization algorithm. Results are presented for the AGARD 445.6 Aeroelastic Wing with four aeroelastic modes at a Mach number of 0.96 using the EZNSS Euler/Navier-Stokes flow solver with aeroelastic capability. The System/Observer/Controller Identification Toolbox (SOCIT) algorithm, based on the Ho-Kalman realization algorithm, is used to generate 15th- and 32nd-order discrete-time state-space models of the unsteady aerodynamic response of the wing over the entire frequency range of interest.

  18. CFD-based method of determining form factor k for different ship types and different drafts

    NASA Astrophysics Data System (ADS)

    Wang, Jinbao; Yu, Hai; Zhang, Yuefeng; Xiong, Xiaoqing

    2016-09-01

    The value of form factor k at different drafts is important in predicting full-scale total resistance and speed for different types of ships. In the ITTC community, most organizations predict form factor k using a low-speed model test. However, this method is problematic for ships with bulbous bows and transom. In this article, a Computational Fluid Dynamics (CFD)-based method is introduced to obtain k for different type of ships at different drafts, and a comparison is made between the CFD method and the model test. The results show that the CFD method produces reasonable k values. A grid generating method and turbulence model are briefly discussed in the context of obtaining a consistent k using CFD.

  19. TADS: A CFD-based turbomachinery and analysis design system with GUI. Volume 2: User's manual

    NASA Technical Reports Server (NTRS)

    Myers, R. A.; Topp, D. A.; Delaney, R. A.

    1995-01-01

    The primary objective of this study was the development of a computational fluid dynamics (CFD) based turbomachinery airfoil analysis and design system, controlled by a graphical user interface (GUI). The computer codes resulting from this effort are referred to as the Turbomachinery Analysis and Design System (TADS). This document is intended to serve as a user's manual for the computer programs which comprise the TADS system. TADS couples a throughflow solver (ADPAC) with a quasi-3D blade-to-blade solver (RVCQ3D) in an interactive package. Throughflow analysis capability was developed in ADPAC through the addition of blade force and blockage terms to the governing equations. A GUI was developed to simplify user input and automate the many tasks required to perform turbomachinery analysis and design. The coupling of various programs was done in a way that alternative solvers or grid generators could be easily incorporated into the TADS framework.

  20. CFD-based multi-objective optimization method for ship design

    NASA Astrophysics Data System (ADS)

    Tahara, Yusuke; Tohyama, Satoshi; Katsui, Tokihiro

    2006-10-01

    This paper concerns development and demonstration of a computational fluid dynamics (CFD)-based multi-objective optimization method for ship design. Three main components of the method, i.e. computer-aided design (CAD), CFD, and optimizer modules are functionally independent and replaceable. The CAD used in the present study is NAPA system, which is one of the leading CAD systems in ship design. The CFD method is FLOWPACK version 2004d, a Reynolds-averaged Navier-Stokes (RaNS) solver developed by the present authors. The CFD method is implemented into a self-propulsion simulator, where the RaNS solver is coupled with a propeller-performance program. In addition, a maneuvering simulation model is developed and applied to predict ship maneuverability performance. Two nonlinear optimization algorithms are used in the present study, i.e. the successive quadratic programming and the multi-objective genetic algorithm, while the former is mainly used to verify the results from the latter. For demonstration of the present method, a multi-objective optimization problem is formulated where ship propulsion and maneuverability performances are considered. That is, the aim is to simultaneously minimize opposite hydrodynamic performances in design tradeoff. In the following, an overview of the present method is given, and results are presented and discussed for tanker stern optimization problem including detailed verification work on the present numerical schemes.

  1. Developing an Accurate CFD Based Gust Model for the Truss Braced Wing Aircraft

    NASA Technical Reports Server (NTRS)

    Bartels, Robert E.

    2013-01-01

    The increased flexibility of long endurance aircraft having high aspect ratio wings necessitates attention to gust response and perhaps the incorporation of gust load alleviation. The design of civil transport aircraft with a strut or truss-braced high aspect ratio wing furthermore requires gust response analysis in the transonic cruise range. This requirement motivates the use of high fidelity nonlinear computational fluid dynamics (CFD) for gust response analysis. This paper presents the development of a CFD based gust model for the truss braced wing aircraft. A sharp-edged gust provides the gust system identification. The result of the system identification is several thousand time steps of instantaneous pressure coefficients over the entire vehicle. This data is filtered and downsampled to provide the snapshot data set from which a reduced order model is developed. A stochastic singular value decomposition algorithm is used to obtain a proper orthogonal decomposition (POD). The POD model is combined with a convolution integral to predict the time varying pressure coefficient distribution due to a novel gust profile. Finally the unsteady surface pressure response of the truss braced wing vehicle to a one-minus-cosine gust, simulated using the reduced order model, is compared with the full CFD.

  2. Multiphase CFD-based models for chemical looping combustion process: Fuel reactor modeling

    SciTech Connect

    Jung, Jonghwun; Gamwo, I.K.

    2008-04-21

    Chemical looping combustion (CLC) is a flameless two-step fuel combustion that produces a pure CO2 stream, ready for compression and sequestration. The process is composed of two interconnected fluidized bed reactors. The air reactor which is a conventional circulating fluidized bed and the fuel reactor which is a bubbling fluidized bed. The basic principle is to avoid the direct contact of air and fuel during the combustion by introducing a highly-reactive metal particle, referred to as oxygen carrier, to transport oxygen from the air to the fuel. In the process, the products from combustion are kept separated from the rest of the flue gases namely nitrogen and excess oxygen. This process eliminates the energy intensive step to separate the CO2 from nitrogen-rich flue gas that reduce the thermal efficiency. Fundamental knowledge of multiphase reactive fluid dynamic behavior of the gas–solid flow is essential for the optimization and operation of a chemical looping combustor. Our recent thorough literature review shows that multiphase CFD-based models have not been adapted to chemical looping combustion processes in the open literature. In this study, we have developed the reaction kinetics model of the fuel reactor and implemented the kinetic model into a multiphase hydrodynamic model, MFIX, developed earlier at the National Energy Technology Laboratory. Simulated fuel reactor flows revealed high weight fraction of unburned methane fuel in the flue gas along with CO2 and H2O. This behavior implies high fuel loss at the exit of the reactor and indicates the necessity to increase the residence time, say by decreasing the fuel flow rate, or to recirculate the unburned methane after condensing and removing CO2.

  3. Development of CFD-Based Simulation Tools for In-Situ Thermal Processing of Oil Shale/Sands

    SciTech Connect

    None, None

    2012-02-01

    In our research, we are taking the novel approach of developing and applying high performance computing, computational fluid dynamics (CFD)-based simulation tools to a modified in-situ process for production of oil from oil shale. The simulation tools being developed capture the relevant physical processes and data from a large-scale system. The modified in-situ application is a pilot-scale heat transfer process inside Red Leaf Resources EcoShale capsule. We demonstrate the need to understand fluid flow behavior in the convective channels of the rubblized shale bed as convective heating greatly decreases the time required to heat the oil shale to the production temperature when compared with conductive heating alone. We have developed and implemented a geometry creation strategy for a representative section of the EcoShale capsule, developed a meshing approach to deal with the complicated geometry and produce a well-behaved mesh, analyzed the effects of boundary conditions on the simulation results, and devised a new operator splitting solution algorithm that reduces computational costs by taking advantage of the differing convective and conductive time scales occurring in the simulation. These simulation tools can be applied to a wide range of processes involving convective fluid flow heating in rubblized beds.

  4. TADS: A CFD-based turbomachinery and analysis design system with GUI. Volume 1: Method and results

    NASA Technical Reports Server (NTRS)

    Topp, D. A.; Myers, R. A.; Delaney, R. A.

    1995-01-01

    The primary objective of this study was the development of a computational fluid dynamics (CFD) based turbomachinery airfoil analysis and design system, controlled by a graphical user interface (GUI). The computer codes resulting from this effort are referred to as the Turbomachinery Analysis and Design System (TADS). This document describes the theoretical basis and analytical results from the TADS system. TADS couples a throughflow solver (ADPAC) with a quasi-3D blade-to-blade solver (RVCQ3D) in an interactive package. Throughflow analysis capability was developed in ADPAC through the addition of blade force and blockage terms to the governing equations. A GUI was developed to simplify user input and automate the many tasks required to perform turbomachinery analysis and design. The coupling of various programs was done in a way that alternative solvers or grid generators could be easily incorporated into the TADS framework. Results of aerodynamic calculations using the TADS system are presented for a highly loaded fan, a compressor stator, a low-speed turbine blade, and a transonic turbine vane.

  5. TADS--A CFD-Based Turbomachinery Analysis and Design System with GUI: User's Manual. 2.0

    NASA Technical Reports Server (NTRS)

    Koiro, M. J.; Myers, R. A.; Delaney, R. A.

    1999-01-01

    The primary objective of this study was the development of a Computational Fluid Dynamics (CFD) based turbomachinery airfoil analysis and design system, controlled by a Graphical User Interface (GUI). The computer codes resulting from this effort are referred to as TADS (Turbomachinery Analysis and Design System). This document is intended to serve as a User's Manual for the computer programs which comprise the TADS system, developed under Task 18 of NASA Contract NAS3-27350, ADPAC System Coupling to Blade Analysis & Design System GUI and Task 10 of NASA Contract NAS3-27394, ADPAC System Coupling to Blade Analysis & Design System GUI, Phase II-Loss, Design and, Multi-stage Analysis. TADS couples a throughflow solver (ADPAC) with a quasi-3D blade-to-blade solver (RVCQ3D) in an interactive package. Throughflow analysis and design capability was developed in ADPAC through the addition of blade force and blockage terms to the governing equations. A GUI was developed to simplify user input and automate the many tasks required to perform turbomachinery analysis and design. The coupling of the various programs was done in such a way that alternative solvers or grid generators could be easily incorporated into the TADS framework. Results of aerodynamic calculations using the TADS system are presented for a highly loaded fan, a compressor stator, a low speed turbine blade and a transonic turbine vane.

  6. TADS: A CFD-Based Turbomachinery Analysis and Design System with GUI: Methods and Results. 2.0

    NASA Technical Reports Server (NTRS)

    Koiro, M. J.; Myers, R. A.; Delaney, R. A.

    1999-01-01

    The primary objective of this study was the development of a Computational Fluid Dynamics (CFD) based turbomachinery airfoil analysis and design system, controlled by a Graphical User Interface (GUI). The computer codes resulting from this effort are referred to as TADS (Turbomachinery Analysis and Design System). This document is the Final Report describing the theoretical basis and analytical results from the TADS system developed under Task 10 of NASA Contract NAS3-27394, ADPAC System Coupling to Blade Analysis & Design System GUI, Phase II-Loss, Design and. Multi-stage Analysis. TADS couples a throughflow solver (ADPAC) with a quasi-3D blade-to-blade solver (RVCQ3D) or a 3-D solver with slip condition on the end walls (B2BADPAC) in an interactive package. Throughflow analysis and design capability was developed in ADPAC through the addition of blade force and blockage terms to the governing equations. A GUI was developed to simplify user input and automate the many tasks required to perform turbomachinery analysis and design. The coupling of the various programs was done in such a way that alternative solvers or grid generators could be easily incorporated into the TADS framework. Results of aerodynamic calculations using the TADS system are presented for a multistage compressor, a multistage turbine, two highly loaded fans, and several single stage compressor and turbine example cases.

  7. CFD-based surrogate modeling of liquid rocket engine components via design space refinement and sensitivity assessment

    NASA Astrophysics Data System (ADS)

    Mack, Yolanda

    Computational fluid dynamics (CFD) can be used to improve the design and optimization of rocket engine components that traditionally rely on empirical calculations and limited experimentation. CFD based-design optimization can be made computationally affordable through the use of surrogate modeling which can then facilitate additional parameter sensitivity assessments. The present study investigates surrogate-based adaptive design space refinement (DSR) using estimates of surrogate uncertainty to probe the CFD analyses and to perform sensitivity assessments for complex fluid physics associated with liquid rocket engine components. Three studies were conducted. First, a surrogate-based preliminary design optimization was conducted to improve the efficiency of a compact radial turbine for an expander cycle rocket engine while maintaining low weight. Design space refinement was used to identify function constraints and to obtain a high accuracy surrogate model in the region of interest. A merit function formulation for multi-objective design point selection reduced the number of design points by an order of magnitude while maintaining good surrogate accuracy among the best trade-off points. Second, bluff body-induced flow was investigated to identify the physics and surrogate modeling issues related to the flow's mixing dynamics. Multiple surrogates and DSR were instrumental in identifying designs for which the CFD model was deficient and to help to pinpoint the nature of the deficiency. Next, a three-dimensional computational model was developed to explore the wall heat transfer of a GO2/GH2 shear coaxial single element injector. The interactions between turbulent recirculating flow structures, chemical kinetics, and heat transfer are highlighted. Finally, a simplified computational model of multi-element injector flows was constructed to explore the sensitivity of wall heating and improve combustion efficiency to injector element spacing. Design space refinement

  8. Variability in the Propagation Phase of CFD-Based Noise Prediction: Summary of Results From Category 8 of the BANC-III Workshop

    NASA Technical Reports Server (NTRS)

    Lopes, Leonard; Redonnet, Stephane; Imamura, Taro; Ikeda, Tomoaki; Zawodny, Nikolas; Cunha, Guilherme

    2015-01-01

    The usage of Computational Fluid Dynamics (CFD) in noise prediction typically has been a two part process: accurately predicting the flow conditions in the near-field and then propagating the noise from the near-field to the observer. Due to the increase in computing power and the cost benefit when weighed against wind tunnel testing, the usage of CFD to estimate the local flow field of complex geometrical structures has become more routine. Recently, the Benchmark problems in Airframe Noise Computation (BANC) workshops have provided a community focus on accurately simulating the local flow field near the body with various CFD approaches. However, to date, little effort has been given into assessing the impact of the propagation phase of noise prediction. This paper includes results from the BANC-III workshop which explores variability in the propagation phase of CFD-based noise prediction. This includes two test cases: an analytical solution of a quadrupole source near a sphere and a computational solution around a nose landing gear. Agreement between three codes was very good for the analytic test case, but CFD-based noise predictions indicate that the propagation phase can introduce 3dB or more of variability in noise predictions.

  9. Mechanistic facility safety and source term analysis

    SciTech Connect

    PLYS, M.G.

    1999-06-09

    A PC-based computer program was created for facility safety and source term analysis at Hanford The program has been successfully applied to mechanistic prediction of source terms from chemical reactions in underground storage tanks, hydrogen combustion in double contained receiver tanks, and proccss evaluation including the potential for runaway reactions in spent nuclear fuel processing. Model features include user-defined facility room, flow path geometry, and heat conductors, user-defined non-ideal vapor and aerosol species, pressure- and density-driven gas flows, aerosol transport and deposition, and structure to accommodate facility-specific source terms. Example applications are presented here.

  10. From mechanistic to functional behaviorism.

    PubMed

    Moxley, R A

    1992-11-01

    A shift from mechanistic behaviorism to functional behaviorism is presented against the background of two historical traditions, one with an emphasis on form, the other with an emphasis on function. Skinner's work, which made more contributions to a functional behaviorism than to a mechanistic behaviorism, exemplifies this shift. The two traditions and an account of Skinner's development of functional relations are presented in order to show Skinner's contributions to aligning modern behavior analysis with the functional tradition.

  11. Food for Thought ... Mechanistic Validation

    PubMed Central

    Hartung, Thomas; Hoffmann, Sebastian; Stephens, Martin

    2013-01-01

    Summary Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st Century, either by high-throughput testing in the ToxCast/ Tox21 project or omics-based testing in the Human Toxome Project. This article explores the mostly neglected assessment of a test's scientific basis, which moves mechanism and causality to the foreground when validating/qualifying tests. Such mechanistic validation faces the problem of establishing causality in complex systems. However, pragmatic adaptations of the Bradford Hill criteria, as well as bioinformatic tools, are emerging. As critical infrastructures of the organism are perturbed by a toxic mechanism we argue that by focusing on the target of toxicity and its vulnerability, in addition to the way it is perturbed, we can anchor the identification of the mechanism and its verification. PMID:23665802

  12. HTGR Mechanistic Source Terms White Paper

    SciTech Connect

    Wayne Moe

    2010-07-01

    The primary purposes of this white paper are: (1) to describe the proposed approach for developing event specific mechanistic source terms for HTGR design and licensing, (2) to describe the technology development programs required to validate the design methods used to predict these mechanistic source terms and (3) to obtain agreement from the NRC that, subject to appropriate validation through the technology development program, the approach for developing event specific mechanistic source terms is acceptable

  13. Rational and Mechanistic Perspectives on Reinforcement Learning

    ERIC Educational Resources Information Center

    Chater, Nick

    2009-01-01

    This special issue describes important recent developments in applying reinforcement learning models to capture neural and cognitive function. But reinforcement learning, as a theoretical framework, can apply at two very different levels of description: "mechanistic" and "rational." Reinforcement learning is often viewed in mechanistic terms--as…

  14. Negative mechanistic reasoning in medical intervention assessment.

    PubMed

    Jerkert, Jesper

    2015-12-01

    Traditionally, mechanistic reasoning has been assigned a negligible role in standard EBM (evidence-based medicine) literature, although some recent authors have argued for an upgrade. Even so, the mechanistic reasoning that has received attention has almost exclusively been positive--both in an epistemic sense of claiming that there is a mechanistic chain and in a health-related sense of there being claimed benefits for the patient. Negative mechanistic reasoning has been neglected, both in the epistemic and in the health-related sense. I distinguish three main types of negative mechanistic reasoning and subsume them under a new definition of mechanistic reasoning in the context of assessing medical interventions. This definition is wider than a previous suggestion in the literature. Each negative type corresponds to a range of evidential strengths, and it is argued that there are differences with respect to typical evidential strengths. The variety of negative mechanistic reasoning should be acknowledged in EBM, and it presents a serious challenge to proponents of so-called medical hierarchies of evidence.

  15. Mechanistic models in computational social science

    NASA Astrophysics Data System (ADS)

    Holme, Petter; Liljeros, Fredrik

    2015-09-01

    Quantitative social science is not only about regression analysis or, in general, data inference. Computer simulations of social mechanisms have an over 60 years long history. They have been used for many different purposes—to test scenarios, to test the consistency of descriptive theories (proof-of-concept models), to explore emergent phenomena, for forecasting, etc. In this essay, we sketch these historical developments, the role of mechanistic models in the social sciences and the influences from the natural and formal sciences. We argue that mechanistic computational models form a natural common ground for social and natural sciences, and look forward to possible future information flow across the social-natural divide.

  16. Applying mechanistic models in bioprocess development.

    PubMed

    Lencastre Fernandes, Rita; Bodla, Vijaya Krishna; Carlquist, Magnus; Heins, Anna-Lena; Eliasson Lantz, Anna; Sin, Gürkan; Gernaey, Krist V

    2013-01-01

    The available knowledge on the mechanisms of a bioprocess system is central to process analytical technology. In this respect, mechanistic modeling has gained renewed attention, since a mechanistic model can provide an excellent summary of available process knowledge. Such a model therefore incorporates process-relevant input (critical process variables)-output (product concentration and product quality attributes) relations. The model therefore has great value in planning experiments, or in determining which critical process variables need to be monitored and controlled tightly. Mechanistic models should be combined with proper model analysis tools, such as uncertainty and sensitivity analysis. When assuming distributed inputs, the resulting uncertainty in the model outputs can be decomposed using sensitivity analysis to determine which input parameters are responsible for the major part of the output uncertainty. Such information can be used as guidance for experimental work; i.e., only parameters with a significant influence on model outputs need to be determined experimentally. The use of mechanistic models and model analysis tools is demonstrated in this chapter. As a practical case study, experimental data from Saccharomyces cerevisiae fermentations are used. The data are described with the well-known model of Sonnleitner and Käppeli (Biotechnol Bioeng 28:927-937, 1986) and the model is analyzed further. The methods used are generic, and can be transferred easily to other, more complex case studies as well.

  17. Mechanistic Indicators of Childhood Asthma (MICA) Study

    EPA Science Inventory

    The Mechanistic Indicators of Childhood Asthma (MICA) Study has been designed to incorporate state-of-the-art technologies to examine the physiological and environmental factors that interact to increase the risk of asthmatic responses. MICA is primarily a clinically-bases obser...

  18. Reductive photocarboxylation of phenanthrene: A mechanistic investigation

    SciTech Connect

    Nikolaitchik, A.V.; Rodgers, M.A.J.; Neckers, D.C.

    1996-02-09

    Mechanistic aspects of photochemicl reactions between phenathrene and carbon dioxide while in the presence of N,N-dimethylaniline was studied. Five products were produced as characterized by NMR and GC-MS. The authors related changes in product yields to changes in reaction conditions. 31 refs., 6 figs., 3 tabs.

  19. Testing mechanistic models of growth in insects.

    PubMed

    Maino, James L; Kearney, Michael R

    2015-11-22

    Insects are typified by their small size, large numbers, impressive reproductive output and rapid growth. However, insect growth is not simply rapid; rather, insects follow a qualitatively distinct trajectory to many other animals. Here we present a mechanistic growth model for insects and show that increasing specific assimilation during the growth phase can explain the near-exponential growth trajectory of insects. The presented model is tested against growth data on 50 insects, and compared against other mechanistic growth models. Unlike the other mechanistic models, our growth model predicts energy reserves per biomass to increase with age, which implies a higher production efficiency and energy density of biomass in later instars. These predictions are tested against data compiled from the literature whereby it is confirmed that insects increase their production efficiency (by 24 percentage points) and energy density (by 4 J mg(-1)) between hatching and the attainment of full size. The model suggests that insects achieve greater production efficiencies and enhanced growth rates by increasing specific assimilation and increasing energy reserves per biomass, which are less costly to maintain than structural biomass. Our findings illustrate how the explanatory and predictive power of mechanistic growth models comes from their grounding in underlying biological processes.

  20. Exploring Organic Mechanistic Puzzles with Molecular Modeling

    ERIC Educational Resources Information Center

    Horowitz, Gail; Schwartz, Gary

    2004-01-01

    The molecular modeling was used to reinforce more general skills such as deducing and drawing reaction mechanisms, analyzing reaction kinetics and thermodynamics and drawing reaction coordinate energy diagrams. This modeling was done through the design of mechanistic puzzles, involving reactions not familiar to the students.

  1. Testing mechanistic models of growth in insects

    PubMed Central

    Maino, James L.; Kearney, Michael R.

    2015-01-01

    Insects are typified by their small size, large numbers, impressive reproductive output and rapid growth. However, insect growth is not simply rapid; rather, insects follow a qualitatively distinct trajectory to many other animals. Here we present a mechanistic growth model for insects and show that increasing specific assimilation during the growth phase can explain the near-exponential growth trajectory of insects. The presented model is tested against growth data on 50 insects, and compared against other mechanistic growth models. Unlike the other mechanistic models, our growth model predicts energy reserves per biomass to increase with age, which implies a higher production efficiency and energy density of biomass in later instars. These predictions are tested against data compiled from the literature whereby it is confirmed that insects increase their production efficiency (by 24 percentage points) and energy density (by 4 J mg−1) between hatching and the attainment of full size. The model suggests that insects achieve greater production efficiencies and enhanced growth rates by increasing specific assimilation and increasing energy reserves per biomass, which are less costly to maintain than structural biomass. Our findings illustrate how the explanatory and predictive power of mechanistic growth models comes from their grounding in underlying biological processes. PMID:26609084

  2. Mechanistic fracture criteria for the failure of human cortical bone

    SciTech Connect

    Nalla, Ravi K.; Kinney, John H.; Ritchie, Robert O.

    2002-12-13

    A mechanistic understanding of fracture in human bone is critical to predicting fracture risk associated with age and disease. Despite extensive work, a mechanistic framework for describing how the underlying microstructure affects the failure mode in bone is lacking.

  3. Toward mechanistic classification of enzyme functions.

    PubMed

    Almonacid, Daniel E; Babbitt, Patricia C

    2011-06-01

    Classification of enzyme function should be quantitative, computationally accessible, and informed by sequences and structures to enable use of genomic information for functional inference and other applications. Large-scale studies have established that divergently evolved enzymes share conserved elements of structure and common mechanistic steps and that convergently evolved enzymes often converge to similar mechanisms too, suggesting that reaction mechanisms could be used to develop finer-grained functional descriptions than provided by the Enzyme Commission (EC) system currently in use. Here we describe how evolution informs these structure-function mappings and review the databases that store mechanisms of enzyme reactions along with recent developments to measure ligand and mechanistic similarities. Together, these provide a foundation for new classifications of enzyme function.

  4. New mechanistic interpretations for nitrone reactivity.

    PubMed

    Merino, Pedro; Tejero, Tomás; Delso, Ignacio; Matute, Rosa

    2017-03-22

    The reactivity of nitrones in cycloadditions and related reactions is revisited by introducing a topological perspective. In particular, the study of electron localization function (ELF) along a reaction pathway allows evaluating bond reorganization showing that in several cases the bonds are formed in a sequential way, the second one being formed once the first one is already formed. Both classical 1,3-dipolar cycloadditions and Mannich-type reactions revealed unexpected features often underestimated in classical mechanistic studies.

  5. Mechanistic studies of carbon monoxide reduction

    SciTech Connect

    Geoffroy, G.L.

    1990-06-12

    The progress made during the current grant period (1 January 1988--1 April 1990) in three different areas of research is summarized. The research areas are: (1) oxidatively-induced double carbonylation reactions to form {alpha}-ketoacyl complexes and studies of the reactivity of the resulting compounds, (2) mechanistic studies of the carbonylation of nitroaromatics to form isocyanates, carbamates, and ureas, and (3) studies of the formation and reactivity of unusual metallacycles and alkylidene ligands supported on binuclear iron carbonyl fragments. 18 refs., 5 figs., 1 tab.

  6. Composite Nanomechanics: A Mechanistic Properties Prediction

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Handler, Louis M.; Manderscheid, Jane M.

    2007-01-01

    A unique mechanistic theory is described to predict the properties of nanocomposites. The theory is based on composite micromechanics with progressive substructuring down to a nanoscale slice of a nanofiber where all the governing equations are formulated. These equations have been programmed in a computer code. That computer code is used to predict 25 properties of a mononanofiber laminate. The results are presented graphically and discussed with respect to their practical significance. Most of the results show smooth distributions. Results for matrix-dependent properties show bimodal through-the-thickness distribution with discontinuous changes from mode to mode.

  7. Composite Nanomechanics: A Mechanistic Properties Prediction

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Handler, Louis M.; Manderscheid, Jane M.

    2007-01-01

    A unique mechanistic theory is described to predict the properties of nanocomposites. The theory is based on composite micromechanics with progressive substructuring down to a nanoscale slice of a nanofiber where all the governing equations are formulated. These equations hav e been programmed in a computer code. That computer code is used to predict 25 properties of a mononanofiber laminate. The results are pr esented graphically and discussed with respect to their practical sig nificance. Most of the results show smooth distributions. Results for matrix-dependent properties show bimodal through-the-thickness distr ibution with discontinuous changes from mode to mode.

  8. CFD based draft tube hydraulic design optimization

    NASA Astrophysics Data System (ADS)

    McNabb, J.; Devals, C.; Kyriacou, S. A.; Murry, N.; Mullins, B. F.

    2014-03-01

    The draft tube design of a hydraulic turbine, particularly in low to medium head applications, plays an important role in determining the efficiency and power characteristics of the overall machine, since an important proportion of the available energy, being in kinetic form leaving the runner, needs to be recovered by the draft tube into static head. For large units, these efficiency and power characteristics can equate to large sums of money when considering the anticipated selling price of the energy produced over the machine's life-cycle. This same draft tube design is also a key factor in determining the overall civil costs of the powerhouse, primarily in excavation and concreting, which can amount to similar orders of magnitude as the price of the energy produced. Therefore, there is a need to find the optimum compromise between these two conflicting requirements. In this paper, an elaborate approach is described for dealing with this optimization problem. First, the draft tube's detailed geometry is defined as a function of a comprehensive set of design parameters (about 20 of which a subset is allowed to vary during the optimization process) and are then used in a non-uniform rational B-spline based geometric modeller to fully define the wetted surfaces geometry. Since the performance of the draft tube is largely governed by 3D viscous effects, such as boundary layer separation from the walls and swirling flow characteristics, which in turn governs the portion of the available kinetic energy which will be converted into pressure, a full 3D meshing and Navier-Stokes analysis is performed for each design. What makes this even more challenging is the fact that the inlet velocity distribution to the draft tube is governed by the runner at each of the various operating conditions that are of interest for the exploitation of the powerhouse. In order to determine these inlet conditions, a combined steady-state runner and an initial draft tube analysis, using a stage interface between them, must first be performed for each operating condition. Due to the computationally intensive nature of the evaluation process, the efficiency of the optimization algorithm becomes important. Therefore, a state-of-the-art hierarchical-metamodel-assisted evolutionary algorithm is used.

  9. Appropriateness of mechanistic and non-mechanistic models for the application of ultrafiltration to mixed waste

    SciTech Connect

    Foust, Henry; Ghosehajra, Malay

    2007-07-01

    This study asks two questions: (1) How appropriate is the use of a basic filtration equation to the application of ultrafiltration of mixed waste, and (2) How appropriate are non-parametric models for permeate rates (volumes)? To answer these questions, mechanistic and non-mechanistic approaches are developed for permeate rates and volumes associated with an ultrafiltration/mixed waste system in dia-filtration mode. The mechanistic approach is based on a filtration equation which states that t/V vs. V is a linear relationship. The coefficients associated with this linear regression are composed of physical/chemical parameters of the system and based the mass balance equation associated with the membrane and associated developing cake layer. For several sets of data, a high correlation is shown that supports the assertion that t/V vs. V is a linear relationship. It is also shown that non-mechanistic approaches, i.e., the use of regression models to are not appropriate. One models considered is Q(p) = a*ln(Cb)+b. Regression models are inappropriate because the scale-up from a bench scale (pilot scale) study to full-scale for permeate rates (volumes) is not simply the ratio of the two membrane surface areas. (authors)

  10. Tear gas: an epidemiological and mechanistic reassessment

    PubMed Central

    Rothenberg, Craig; Achanta, Satyanarayana; Svendsen, Erik R.

    2016-01-01

    Deployments of tear gas and pepper spray have rapidly increased worldwide. Large amounts of tear gas have been used in densely populated cities, including Cairo, Istanbul, Rio de Janeiro, Manama (Bahrain), and Hong Kong. In the United States, tear gas was used extensively during recent riots in Ferguson, Missouri. Whereas tear gas deployment systems have rapidly improved—with aerial drone systems tested and requested by law enforcement—epidemiological and mechanistic research have lagged behind and have received little attention. Case studies and recent epidemiological studies revealed that tear gas agents can cause lung, cutaneous, and ocular injuries, with individuals affected by chronic morbidities at high risk for complications. Mechanistic studies identified the ion channels TRPV1 and TRPA1 as targets of capsaicin in pepper spray, and of the tear gas agents chloroacetophenone, CS, and CR. TRPV1 and TRPA1 localize to pain‐sensing peripheral sensory neurons and have been linked to acute and chronic pain, cough, asthma, lung injury, dermatitis, itch, and neurodegeneration. In animal models, transient receptor potential inhibitors show promising effects as potential countermeasures against tear gas injuries. On the basis of the available data, a reassessment of the health risks of tear gas exposures in the civilian population is advised, and development of new countermeasures is proposed. PMID:27391380

  11. Tear gas: an epidemiological and mechanistic reassessment.

    PubMed

    Rothenberg, Craig; Achanta, Satyanarayana; Svendsen, Erik R; Jordt, Sven-Eric

    2016-08-01

    Deployments of tear gas and pepper spray have rapidly increased worldwide. Large amounts of tear gas have been used in densely populated cities, including Cairo, Istanbul, Rio de Janeiro, Manama (Bahrain), and Hong Kong. In the United States, tear gas was used extensively during recent riots in Ferguson, Missouri. Whereas tear gas deployment systems have rapidly improved-with aerial drone systems tested and requested by law enforcement-epidemiological and mechanistic research have lagged behind and have received little attention. Case studies and recent epidemiological studies revealed that tear gas agents can cause lung, cutaneous, and ocular injuries, with individuals affected by chronic morbidities at high risk for complications. Mechanistic studies identified the ion channels TRPV1 and TRPA1 as targets of capsaicin in pepper spray, and of the tear gas agents chloroacetophenone, CS, and CR. TRPV1 and TRPA1 localize to pain-sensing peripheral sensory neurons and have been linked to acute and chronic pain, cough, asthma, lung injury, dermatitis, itch, and neurodegeneration. In animal models, transient receptor potential inhibitors show promising effects as potential countermeasures against tear gas injuries. On the basis of the available data, a reassessment of the health risks of tear gas exposures in the civilian population is advised, and development of new countermeasures is proposed.

  12. Reaction Coordinates and Mechanistic Hypothesis Tests

    NASA Astrophysics Data System (ADS)

    Peters, Baron

    2016-05-01

    Reaction coordinates are integral to several classic rate theories that can (a) predict kinetic trends across conditions and homologous reactions, (b) extract activation parameters with a clear physical interpretation from experimental rates, and (c) enable efficient calculations of free energy barriers and rates. New trajectory-based rare events methods can provide rates directly from dynamical trajectories without a reaction coordinate. Trajectory-based frameworks can also generate ideal (but abstract) reaction coordinates such as committors and eigenfunctions of the master equation. However, rates and mechanistic insights obtained from trajectory-based methods and abstract coordinates are not readily generalized across simulation conditions or reaction families. We discuss methods for identifying physically meaningful reaction coordinates, including committor analysis, variational transition state theory, Kramers-Langer-Berezhkovskii-Szabo theory, and statistical inference methods that can use path sampling data to screen, mix, and optimize thousands of trial coordinates. Special focus is given to likelihood maximization and inertial likelihood maximization approaches.

  13. Mechanistic investigations of the ethylene tetramerisation reaction.

    PubMed

    Overett, Matthew J; Blann, Kevin; Bollmann, Annette; Dixon, John T; Haasbroek, Daleen; Killian, Esna; Maumela, Hulisani; McGuinness, David S; Morgan, David H

    2005-08-03

    The unprecedented selective tetramerisation of ethylene to 1-octene was recently reported. In the present study various mechanistic aspects of this novel transformation were investigated. The unusually high 1-octene selectivity in chromium-catalyzed ethylene tetramerisation reactions is caused by the unique extended metallacyclic mechanism in operation. Both 1-octene and higher 1-alkenes are formed by further ethylene insertion into a metallacycloheptane intermediate, whereas 1-hexene is formed by elimination from this species as in other reported trimerisation reactions. This is supported by deuterium labeling studies, analysis of the molar distribution of 1-alkene products, and identification of secondary co-oligomerization reaction products. In addition, the formation of two C6 cyclic products, methylenecyclopentane and methylcyclopentane, is discussed, and a bimetallic disproportionation mechanism to account for the available data is proposed.

  14. Mechanistic issues in asparagine synthetase catalysis.

    PubMed

    Richards, N G; Schuster, S M

    1998-01-01

    The enzymatic synthesis of asparagine is an ATP-dependent process that utilizes the nitrogen atom derived from either glutamine or ammonia. Despite a long history of kinetic and mechanistic investigation, there is no universally accepted catalytic mechanism for this seemingly straightforward carboxyl group activating enzyme, especially as regards those steps immediately preceding amide bond formation. This chapter considers four issues dealing with the mechanism: (a) the structural organization of the active site(s) partaking in glutamine utilization and aspartate activation; (b) the relationship of asparagine synthetase to other amidotransferases; (c) the way in which ATP is used to activate the beta-carboxyl group; and (d) the detailed mechanism by which nitrogen is transferred.

  15. Obesity, Diabetes and Cancer: A Mechanistic Perspective

    PubMed Central

    Cifarelli, V; Hursting, SD

    2016-01-01

    Nearly 35% of adults and 20% of children in the United States are obese, defined as having a body mass index (BMI) ≥ 30 kg/m2. Obesity is an established risk factor for many cancers, and obesity-associated metabolic perturbations often manifest in Type 2 diabetes mellitus and/or the metabolic syndrome. As part of the growth-promoting, proinflammatory microenvironment of the obese and/or diabetic state, crosstalk between macrophages, adipocytes, and epithelial cells occurs via metabolically-regulated hormones, cytokines, and other mediators to enhance cancer risk and/or progression. This review synthesizes the evidence on key biological mechanisms underlying the associations between obesity, diabetes and cancer, with particular emphasis on enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent mechanistic targets for disrupting the obesity-diabetes-cancer link, and several diabetes drugs, such as metformin and rosiglitazone, are being intensely studied for repurposing as cancer chemopreventive agents.

  16. Mechanistic interplay between ceramide and insulin resistance

    PubMed Central

    Reali, Federico; Morine, Melissa J.; Kahramanoğulları, Ozan; Raichur, Suryaprakash; Schneider, Hans-Christoph; Crowther, Daniel; Priami, Corrado

    2017-01-01

    Recent research adds to a growing body of literature on the essential role of ceramides in glucose homeostasis and insulin signaling, while the mechanistic interplay between various components of ceramide metabolism remains to be quantified. We present an extended model of C16:0 ceramide production through both the de novo synthesis and the salvage pathways. We verify our model with a combination of published models and independent experimental data. In silico experiments of the behavior of ceramide and related bioactive lipids in accordance with the observed transcriptomic changes in obese/diabetic murine macrophages at 5 and 16 weeks support the observation of insulin resistance only at the later phase. Our analysis suggests the pivotal role of ceramide synthase, serine palmitoyltransferase and dihydroceramide desaturase involved in the de novo synthesis and the salvage pathways in influencing insulin resistance versus its regulation. PMID:28112248

  17. Intriguing mechanistic labyrinths in gold(i) catalysis

    PubMed Central

    Obradors, Carla

    2014-01-01

    Many mechanistically intriguing reactions have been developed in the last decade using gold(i) as catalyst. Here we review the main mechanistic proposals in gold-catalysed activation of alkynes and allenes, in which this metal plays a central role by stabilising a variety of complex cationic intermediates. PMID:24176910

  18. A systematic approach for identifying and presenting mechanistic evidence in human health assessments

    PubMed Central

    Kushman, Mary E.; Kraft, Andrew D.; Guyton, Kathryn Z.; Chiu, Weihsueh A.; Makris, Susan L.; Rusyn, Ivan

    2013-01-01

    Clear documentation of literature search and presentation methodologies can improve transparency in chemical hazard assessments. We sought to improve clarity for the scientific support for cancer mechanisms of action using a systematic approach to literature retrieval, selection, and presentation of studies. The general question was “What are the mechanisms by which a chemical may cause carcinogenicity in the target tissue?” Di(2-ethylhexyl)phthalate was used as a case study chemical with a complex database of >3,000 publications. Relevant mechanistic events were identified from published reviews. The PubMed search strategy included relevant synonyms and wildcards for DEHP and its metabolites, mechanistic events, and species of interest. Tiered exclusion/inclusion criteria for study pertinence were defined, and applied to the retrieved literature. Manual curation was conducted for mechanistic events with large literature databases. Literature trees documented identification and selection of the literature evidence. The selected studies were summarized in evidence tables accompanied by succinct narratives. Primary publications were deposited into the Health and Environmental Research Online (http://hero.epa.gov/) database and identified by pertinence criteria and key terms to permit organized retrieval. This approach contributes to human health assessment by effectively managing a large volume of literature, improving transparency, and facilitating subsequent synthesis of information across studies. PMID:23959061

  19. Mechanistically based mapping of human cardiac fibrillation

    PubMed Central

    Zaman, Junaid A. B.

    2016-01-01

    Abstract The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper ‘On dynamic equilibrium in the heart’, Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms – sources in preferred cardiac regions or spatially diffuse self‐sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non‐uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non‐coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation. PMID:26607671

  20. Mechanistic simulation of line-edge roughness

    NASA Astrophysics Data System (ADS)

    Biafore, John J.; Smith, Mark D.; Robertson, Stewart A.; Graves, Trey

    2007-03-01

    Physically-based photoresist models, such as those in PROLITH, have been very successful in describing photolithography from a continuum standpoint. These models allow engineers to accurately predict the final resist CD on the wafer and to analyze process robustness. However, as the critical dimension continues to shrink, yield-limiting phenomena are observed that are related to the molecular nature and reaction kinetics of photoresist materials. An example of these phenomena is line-edge roughness (LER). In this paper, the origin of LER is hypothesized to be caused by fluctuations occurring in the initial position of the reactants, fluctuations during the exposure process (shot noise) and fluctuations occurring during thermally-induced reaction-diffusion (post-exposure bake). We have developed a lattice-based mechanistic simulator to better understand the stochastic nature of reactant initial position, the exposure step, the importance of the discrete nature of the reactants, the coupling to the deprotection kinetics and the deep complexity evident in the diffusion-limited acid-quencher reaction.

  1. Mechanistic Reactive Burn Modeling of Solid Explosives

    SciTech Connect

    Y.Horie; Y.Hamate; D.Greening

    2003-04-01

    This report describes a computational framework for reactive burn modeling of solid explosives and the development of a test case where physical mechanisms represent RDX or RDX-based materials. The report is a sequel to LA-13794-MS, ''A Unifying Framework for Hot Spots and the Ignition of Energetic Materials,'' where we proposed a new approach to the building of a general purpose model that captures the essential features of the three primary origins of hot-spot formation: void collapse, shear banding, friction. The purpose of the present report is to describe the continuing task of coupling the unifying hot-spot model to hydrodynamic calculations to develop a mechanistic reactive burn model. The key components of the coupling include energy localization, the growth of hot spots, overall hot-spot behavior, and a phase-averaged mixture equation of state (EOS) in a Mie-Grueneisen form. The nucleation and growth of locally heated regions is modeled by a phenomenological treatment as well as a statistical model based on an exponential size distribution. The Mie-Grueneisen form of the EOS is one of many possible choices and is not a critical selection for implementing the model. In this report, model calculations are limited to proof-of-concept illustrations for shock loading. Results include (1) shock ignition and growth-to-detonation, (2) double shock ignition, and (3) quenching and reignition. A comparative study of Pop-plots is discussed based on the statistical model.

  2. Mechanistic Indicators of Childhood Asthma (MICA): piloting ...

    EPA Pesticide Factsheets

    Background: Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma; however appropriately designed studies are critical for these methods to reach their full potential. Objective: We used a case-control study to investigate whether genomic data (blood gene expression), viewed together with a spectrum of exposure effects and susceptibility markers (blood, urine and nail), can provide a mechanistic explanation for the increased susceptibility of asthmatics to ambient air pollutants. Methods: We studied 205 non-asthmatic and asthmatic children, (9-12 years of age) who participated in a clinical study in Detroit, Michigan. The study combines a traditional epidemiological design with an integrative approach to investigate the environmental exposure of children to indoor-outdoor air. The study includes measurements of internal dose (metals, allergen specific IgE, PAH and VOC metabolites) and clinical measures of health outcome (immunological, cardiovascular and respiratory). Results: Expected immunological indications of asthma have been obtained. In addition, initial results from our analyses point to the complex nature of childhood health and risk factors linked to metabolic syndrome (obesity, blood pressure and dyslipidemia). For example, 31% and 34% of the asthmatic MICA subjects were either overweight (BMI > 25) o

  3. Ligand interactions with galactose oxidase: mechanistic insights.

    PubMed Central

    Whittaker, M M; Whittaker, J W

    1993-01-01

    Interactions between galactose oxidase and small molecules have been explored using a combination of optical absorption, circular dichroism, and electron paramagnetic resonance (EPR) spectroscopies to detect complex formation and characterize the products. Anions bind directly to the cupric center in both active and inactive galactose oxidase, converting to complexes with optical and EPR spectra that are distinctly different from those of the starting aquo enzyme. Azide binding is coupled to stoichiometric proton uptake by the enzyme, reflecting the generation of a strong base (pKa > 9) in the active site anion adduct. At low temperature, the aquo enzyme converts to a form that exhibits the characteristic optical and EPR spectra of an anion complex, apparently reflecting deprotonation of the coordinated water. Anion binding results in a loss of the optical transition arising from coordinated tyrosine, implying displacement of the axial tyrosine ligand on forming the adduct. Nitric oxide binds to galactose oxidase, forming a specific complex exhibiting an unusual EPR spectrum with all g values below 2. The absence of Cu splitting in this spectrum and the observation that the cupric EPR signal from the active site metal ion is not significantly decreased in the complex suggest a nonmetal interaction site for NO in galactose oxidase. These results have been interpreted in terms of a mechanistic scheme where substrate binding displaces a tyrosinate ligand from the active site cupric ion, generating a base that may serve to deprotonate the coordinated hydroxyl group of the substrate, activating it for oxidation. The protein-NO interactions may probe a nonmetal O2 binding site in this enzyme. PMID:8386015

  4. Application of Mechanistic Toxicology Data to Ecological Risk Assessments

    EPA Science Inventory

    The ongoing evolution of knowledge and tools in the areas of molecular biology, bioinformatics, and systems biology holds significant promise for reducing uncertainties associated with ecological risk assessment. As our understanding of the mechanistic basis of responses of organ...

  5. Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

    DTIC Science & Technology

    2015-10-01

    efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include...1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI 5b. GRANT

  6. Explanation and inference: mechanistic and functional explanations guide property generalization.

    PubMed

    Lombrozo, Tania; Gwynne, Nicholas Z

    2014-01-01

    The ability to generalize from the known to the unknown is central to learning and inference. Two experiments explore the relationship between how a property is explained and how that property is generalized to novel species and artifacts. The experiments contrast the consequences of explaining a property mechanistically, by appeal to parts and processes, with the consequences of explaining the property functionally, by appeal to functions and goals. The findings suggest that properties that are explained functionally are more likely to be generalized on the basis of shared functions, with a weaker relationship between mechanistic explanations and generalization on the basis of shared parts and processes. The influence of explanation type on generalization holds even though all participants are provided with the same mechanistic and functional information, and whether an explanation type is freely generated (Experiment 1), experimentally provided (Experiment 2), or experimentally induced (Experiment 2). The experiments also demonstrate that explanations and generalizations of a particular type (mechanistic or functional) can be experimentally induced by providing sample explanations of that type, with a comparable effect when the sample explanations come from the same domain or from a different domains. These results suggest that explanations serve as a guide to generalization, and contribute to a growing body of work supporting the value of distinguishing mechanistic and functional explanations.

  7. From formamide to purine: an energetically viable mechanistic reaction pathway.

    PubMed

    Wang, Jing; Gu, Jiande; Nguyen, Minh Tho; Springsteen, Greg; Leszczynski, Jerzy

    2013-02-28

    A step-by-step mechanistic pathway following the transformation of formamide to purine through a five-membered ring intermediate has been explored by density functional theory computations. The highlight of the mechanistic route detailed here is that the proposed pathway represents the simplest reaction pathway. All necessary reactants are generated from a single starting compound, formamide, through energetically viable reactions. Several important reaction steps are involved in this mechanistic route: formylation-dehydration, Leuckart reduction, five- and six-membered ring-closure, and deamination. On the basis of the study of noncatalytic pathways, catalytic water has been found to provide energetically viable step-by-step mechanistic pathways. Among these reaction steps, five-member ring-closure is the rate-determining step. The energy barrier (ca. 42 kcal/mol) of this rate-control step is somewhat lower than the rate-determining step (ca. 44 kcal/mol) for a pyrimidine-based pathway reported previously. The mechanistic pathway reported herein is less energetically demanding than for previously proposed routes to adenine.

  8. Explanation and inference: mechanistic and functional explanations guide property generalization

    PubMed Central

    Lombrozo, Tania; Gwynne, Nicholas Z.

    2014-01-01

    The ability to generalize from the known to the unknown is central to learning and inference. Two experiments explore the relationship between how a property is explained and how that property is generalized to novel species and artifacts. The experiments contrast the consequences of explaining a property mechanistically, by appeal to parts and processes, with the consequences of explaining the property functionally, by appeal to functions and goals. The findings suggest that properties that are explained functionally are more likely to be generalized on the basis of shared functions, with a weaker relationship between mechanistic explanations and generalization on the basis of shared parts and processes. The influence of explanation type on generalization holds even though all participants are provided with the same mechanistic and functional information, and whether an explanation type is freely generated (Experiment 1), experimentally provided (Experiment 2), or experimentally induced (Experiment 2). The experiments also demonstrate that explanations and generalizations of a particular type (mechanistic or functional) can be experimentally induced by providing sample explanations of that type, with a comparable effect when the sample explanations come from the same domain or from a different domains. These results suggest that explanations serve as a guide to generalization, and contribute to a growing body of work supporting the value of distinguishing mechanistic and functional explanations. PMID:25309384

  9. Predicting interactions from mechanistic information: Can omic data validate theories?

    SciTech Connect

    Borgert, Christopher J.

    2007-09-01

    To address the most pressing and relevant issues for improving mixture risk assessment, researchers must first recognize that risk assessment is driven by both regulatory requirements and scientific research, and that regulatory concerns may expand beyond the purely scientific interests of researchers. Concepts of 'mode of action' and 'mechanism of action' are used in particular ways within the regulatory arena, depending on the specific assessment goals. The data requirements for delineating a mode of action and predicting interactive toxicity in mixtures are not well defined from a scientific standpoint due largely to inherent difficulties in testing certain underlying assumptions. Understanding the regulatory perspective on mechanistic concepts will be important for designing experiments that can be interpreted clearly and applied in risk assessments without undue reliance on extrapolation and assumption. In like fashion, regulators and risk assessors can be better equipped to apply mechanistic data if the concepts underlying mechanistic research and the limitations that must be placed on interpretation of mechanistic data are understood. This will be critically important for applying new technologies to risk assessment, such as functional genomics, proteomics, and metabolomics. It will be essential not only for risk assessors to become conversant with the language and concepts of mechanistic research, including new omic technologies, but also, for researchers to become more intimately familiar with the challenges and needs of risk assessment.

  10. Mechanistic micro-structural theory of soft tissues growth and remodeling: tissues with unidirectional fibers.

    PubMed

    Lanir, Yoram

    2015-04-01

    A new mechanistic theory was developed for soft tissues growth and remodeling (G&R). The theory considers tissues with unidirectional fibers. It is based on the loading-dependent local turnover events of each constituent and on the resulting evolution of the tissue micro-structure, the tissue dimensions and its mechanical properties. The theory incorporates the specific mechanical properties and turnover kinetics of each constituent, thereby establishing a general framework which can serve for future integration of additional mechanisms involved in G&R. The feasibility of the theory was examined by considering a specific realization of tissues with one fibrous constituent (collagen fibers), assuming a specific loading-dependent first-order fiber's turnover kinetics and the fiber's deposition characteristics. The tissue was subjected to a continuous constant rate growth. Model parameters were adopted from available data. The resulting predictions show qualitative agreement with a number of well-known features of tissues including the fibers' non-uniform recruitment density distribution, the associated tissue convex nonlinear stress-stretch relationship, and the development of tissue pre-stretch and pre-stress states. These results show that mechanistic micro-structural modeling of soft tissue G&R based on first principles can successfully capture the evolution of observed tissues' structure and size, and of their associated mechanical properties.

  11. Why did Jacques Monod make the choice of mechanistic determinism?

    PubMed

    Loison, Laurent

    2015-06-01

    The development of molecular biology placed in the foreground a mechanistic and deterministic conception of the functioning of macromolecules. In this article, I show that this conception was neither obvious, nor necessary. Taking Jacques Monod as a case study, I detail the way he gradually came loose from a statistical understanding of determinism to finally support a mechanistic understanding. The reasons of the choice made by Monod at the beginning of the 1950s can be understood only in the light of the general theoretical schema supported by the concept of mechanistic determinism. This schema articulates three fundamental notions for Monod, namely that of the rigidity of the sequence of the genetic program, that of the intrinsic stability of macromolecules (DNA and proteins), and that of the specificity of molecular interactions.

  12. Radical behaviorism and scientific frameworks. From mechanistic to relational accounts.

    PubMed

    Chiesa, M

    1992-11-01

    A substantial portion of B. F. Skinner's scholarship was devoted to developing methods and terms for a scientific study of behavior. Three concepts central to scientific accounts--cause, explanation, and theory--are examined to illustrate the distinction between mechanistic and relational frameworks and radical behaviorism's relationship to those frameworks. Informed by a scientific tradition that explicitly rejects mechanistic interpretations, radical behaviorism provides a distinctive stance in contemporary psychology. The present analysis suggests that radical behaviorism makes closer contact with the "new world view" advocated by physicists and philosophers of science than does much of contemporary psychology.

  13. Recommended Tritium Oxide Deposition Velocity For Use In Savannah River Site Safety Analyses

    SciTech Connect

    Lee, P. L.; Murphy, C. E.; Viner, B. J.; Hunter, C. H.

    2012-07-31

    This report documents the results of examining the deposition velocity of water to forests, the residence time of HTO in forests, and the relation between deposition velocity and residence time with specific consideration given to the topography and experimental work performed at SRS. A simple mechanistic model is used to obtain plausible deposition velocity and residence time values where experimental data are not available and recommendations are made for practical application in a safety analysis model.

  14. A simple mechanistic model to interpret the effects of narcotics.

    PubMed

    Baas, J; Spurgeon, D; Broerse, M

    2015-01-01

    In this research we will show the advantages of using a time-independent dose metric in a mechanistic model to evaluate toxic effects for different narcotic compounds on different species. We will show how different already existing QSARs can be combined within a mechanistic framework to 1) make predictions of lethal thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a mechanistic framework solves some conceptual problems in current approaches and 4) show how such a framework can be used to be of aid in an experimental setup in predicting the outcome of a survival experiment. The approach we chose is based on the simplest mechanistic model available, a scaled one-compartment model to describe uptake and elimination and hazard model to link the exposure to effects on survival. Within this theoretical framework a prediction for an internal threshold for effects on survival of 3 mmol/kg bw can be made, which should be similar for different species and independent of the partitioning characteristics of the toxicant. To demonstrate this, a threshold for 51 different species was derived, which indeed appeared to lie in a relatively small range, typically between 1 and 10 mmol/kg bw.

  15. Bridging Mechanistic and Phenomenological Models of Complex Biological Systems

    PubMed Central

    Transtrum, Mark K.; Qiu, Peng

    2016-01-01

    The inherent complexity of biological systems gives rise to complicated mechanistic models with a large number of parameters. On the other hand, the collective behavior of these systems can often be characterized by a relatively small number of phenomenological parameters. We use the Manifold Boundary Approximation Method (MBAM) as a tool for deriving simple phenomenological models from complicated mechanistic models. The resulting models are not black boxes, but remain expressed in terms of the microscopic parameters. In this way, we explicitly connect the macroscopic and microscopic descriptions, characterize the equivalence class of distinct systems exhibiting the same range of collective behavior, and identify the combinations of components that function as tunable control knobs for the behavior. We demonstrate the procedure for adaptation behavior exhibited by the EGFR pathway. From a 48 parameter mechanistic model, the system can be effectively described by a single adaptation parameter τ characterizing the ratio of time scales for the initial response and recovery time of the system which can in turn be expressed as a combination of microscopic reaction rates, Michaelis-Menten constants, and biochemical concentrations. The situation is not unlike modeling in physics in which microscopically complex processes can often be renormalized into simple phenomenological models with only a few effective parameters. The proposed method additionally provides a mechanistic explanation for non-universal features of the behavior. PMID:27187545

  16. Mechanistically Consistent Reduced Models of Synthetic Gene Networks

    PubMed Central

    Mier-y-Terán-Romero, Luis; Silber, Mary; Hatzimanikatis, Vassily

    2013-01-01

    Designing genetic networks with desired functionalities requires an accurate mathematical framework that accounts for the essential mechanistic details of the system. Here, we formulate a time-delay model of protein translation and mRNA degradation by systematically reducing a detailed mechanistic model that explicitly accounts for the ribosomal dynamics and the cleaving of mRNA by endonucleases. We exploit various technical and conceptual advantages that our time-delay model offers over the mechanistic model to probe the behavior of a self-repressing gene over wide regions of parameter space. We show that a heuristic time-delay model of protein synthesis of a commonly used form yields a notably different prediction for the parameter region where sustained oscillations occur. This suggests that such heuristics can lead to erroneous results. The functional forms that arise from our systematic reduction can be used for every system that involves transcription and translation and they could replace the commonly used heuristic time-delay models for these processes. The results from our analysis have important implications for the design of synthetic gene networks and stress that such design must be guided by a combination of heuristic models and mechanistic models that include all relevant details of the process. PMID:23663853

  17. DEVELOPMENT AND VALIDATION OF A MECHANISTIC GROUND SPRAYER MODEL

    EPA Science Inventory

    In the last ten years the Spray Drift Task Force (SDTF), U.S. Environmental Protection Agency (EPA), USDA Agricultural Research Service, and USDA Forest Service cooperated in the refinement and evaluation of a mechanistically-based aerial spray model (contained within AGDISP and ...

  18. MECHANISTIC AND SOURCE UNDERSTANDING OF PCDD/F FORMATION

    EPA Science Inventory

    The paper discusses mechanistic and source understanding of polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) formation. (NOTE: Considerable research effort has been expended over the last 15-plus years to understand how combustion sources result in formation of PCDDs/F...

  19. Does Mechanistic Thinking Improve Student Success in Organic Chemistry?

    ERIC Educational Resources Information Center

    Grove, Nathaniel P.; Cooper, Melanie M.; Cox, Elizabeth L.

    2012-01-01

    The use of the curved-arrow notation to depict electron flow during mechanistic processes is one of the most important representational conventions in the organic chemistry curriculum. Our previous research documented a disturbing trend: when asked to predict the products of a series of reactions, many students do not spontaneously engage in…

  20. Rearrangements of Allylic Sulfinates to Sulfones: A Mechanistic Study

    ERIC Educational Resources Information Center

    Ball, David B.; Mollard, Paul; Voigtritter, Karl R.; Ball, Jenelle L.

    2010-01-01

    Most current organic chemistry textbooks are organized by functional groups and those of us who teach organic chemistry use functional-group organization in our courses but ask students to learn organic chemistry from a mechanistic approach. To enrich and extend the chemical understanding and knowledge of pericyclic-type reactions for chemistry…

  1. Ferritin Diversity: Mechanistic Studies, Disease Implications, and Materials Chemistry

    NASA Astrophysics Data System (ADS)

    Hilton, Robert J.

    2011-07-01

    The study of ferritin includes a rich history of discoveries and scientific progress. Initially, the composition of ferritin was determined. Soon, it was shown that ferritin is a spherical, hollow protein. Eventually, over several decades of research, the structure and some function of this interesting protein was elucidated. However, the ferritin field was not completely satisfied. Today, for example, researchers are interested in refining the details of ferritin function, in discovering the role of ferritin in a variety of diseases, and in using ferritin for materials chemistry applications. The work presented in this dissertation highlights the progress that we have made in each of these three areas: (1) Mechanistic studies: The buffer used during horse spleen ferritin iron loading significantly influences the mineralization process and the quantity of iron deposited in ferritin. The ferrihydrite core of ferritin is crystalline and ordered when iron is loaded into ferritin in the presence of imidazole buffer. On the other hand, when iron is loaded into ferritin in the presence of MOPS buffer, the ferrihydrite core is less crystalline and less ordered, and a smaller amount of total iron is loaded in ferritin. We also show that iron can be released from the ferritin core in a non-reductive manner. The rate of Fe3+ release from horse spleen ferritin was measured using the Fe3+-specific chelator desferoxamine. We show that iron release occurs by three kinetic events. (2) Disease studies: In order to better understand iron disruption during disease states, we performed in vitro assays that mimicked chronic kidney disease. We tested the hypothesis that elevated levels of serum phosphate interrupted normal iron binding by transferrin and ferritin. Results show that phosphate competes for iron, forming an iron(III)-phosphate complex that is inaccessible to either transferrin or ferritin. Ferritin samples separated from the iron(III)-phosphate complex shows that as the

  2. A framework for recognizing mechanistic reasoning in student scientific inquiry

    NASA Astrophysics Data System (ADS)

    Russ, Rosemary S.

    A central ambition of science education reform is to help students develop abilities for scientific inquiry. Education research is thus rightly focused on defining what constitutes "inquiry" and developing tools for assessing it. There has been progress with respect to particular aspects of inquiry, namely student abilities for controlled experimentation and scientific argumentation. However, we suggest that in addition to these frameworks for assessing the structure of inquiry we need frameworks for analyzing the substance of that inquiry. In this work we draw attention to and evaluate the substance of student mechanistic reasoning. Both within the history and philosophy of science and within science education research, scientific inquiry is characterized in part as understanding the causal mechanisms that underlie natural phenomena. The challenge for science education, however, is that there has not been the same progress with respect to making explicit what constitutes mechanistic reasoning as there has been in making explicit other aspects of inquiry. This dissertation attempts to address this challenge. We adapt an account of mechanism in professional research science to develop a framework for reliably recognizing mechanistic reasoning in student discourse. The coding scheme articulates seven specific aspects of mechanistic reasoning and can be used to systematically analyze narrative data for patterns in student thinking. It provides a tool for detecting quality reasoning that may be overlooked by more traditional assessments. We apply the mechanism coding scheme to video and written data from a range of student inquiries, from large group discussions among first grade students to the individual problem solving of graduate students. While the primary result of this work is the coding scheme itself and the finding that it provides a reliable means of analyzing transcript data for evidence of mechanistic thinking, the rich descriptions we develop in each case

  3. Mechanistic pathway modeling for industrial biotechnology: challenging but worthwhile.

    PubMed

    Wiechert, Wolfgang; Noack, Stephan

    2011-10-01

    Mechanistic (also called kinetic) models quantitatively describe dynamic and steady states of biochemical pathways. They are based on network structure (stoichiometry), regulatory information (enzyme inhibitors and activators) and the corresponding reaction kinetics. Although this approach to understand and predict the behavior of biochemical networks has now been in use for almost half a century, its experimental foundation has dramatically changed in the data-rich age of systems biology. Large mechanistic models, ranging up to the genome scale, are now being built and lots of data are available to validate and test them. From the broad scope of possible modeling applications, this survey focuses on the recent developments and central problems of metabolic network modeling in the field of bioprocess development for industrial biotechnology.

  4. Mechanistic model for catalytic recombination during aerobraking maneuvers

    NASA Technical Reports Server (NTRS)

    Willey, Ronald J.

    1989-01-01

    Several mechanistic models are developed to predict recombination coefficients for use in heat shield design for reusable surface insulation (RSI) on aerobraking vehicles such as space shuttles. The models are applied over a temperature range of 300 to 1800 K and a stagnation pressure range of 0 to 3,000 Pa. A four parameter model in temperature was found to work best; however, several models (including those with atom concentrations at the surface) were also investigated. Mechanistic models developed with atom concentration terms may be applicable when sufficient data becomes available. The requirement is shown for recombination experiments in the 300 to 1000 K and 1500 to 1850 K temperature range, with deliberate concentration variations.

  5. Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

    PubMed Central

    Krishna, Katla Sai; Biswas, Sanchita; Navin, Chelliah V.; Yamane, Dawit G.; Miller, Jeffrey T.; Kumar, Challa S.S.R.

    2013-01-01

    Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst. PMID:24327099

  6. From the exposome to mechanistic understanding of chemical ...

    EPA Pesticide Factsheets

    BACKGROUND: Current definitions of the exposome expand beyond the initial idea to consider the totality of exposure and aim to relate to biological effects. While the exposome has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. OBJECTIVES: We explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept - a framework to structure and organize the sequence of toxicological events from an initial molecular interaction of a chemical to an adverse outcome.METHODS: This review was informed by a Workshop organized by the Integrated Project EXPOSOME at the UFZ Helmholtz Centre for Environmental Research in Leipzig, Germany. DISCUSSION: The exposome encompasses all chemicals, including exogenous chemicals and endogenous compounds that are produced in response to external factors. By complementing the exposome research with the AOP concept, we can achieve a better mechanistic understanding, weigh the importance of various components of the exposome, and determine primary risk drivers. The ability to interpret multiple exposures and mixture effects at the mechanistic level requires a more holistic approach facilitated by the exposome concept.CONCLUSION: Incorporating the AOP conc

  7. Mechanistic species distribution modeling reveals a niche shift during invasion.

    PubMed

    Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

    2017-04-02

    Niche shifts of non-native plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by re-analyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially-invaded ranges of individual populations. Northern-origin populations that were established outside the generally-accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially-invaded range northwards and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

  8. Mechanistic modeling of CHF in forced-convection subcooled boiling

    SciTech Connect

    Podowski, M.Z.; Alajbegovic, A.; Kurul, N.; Drew, D.A.; Lahey, R.T. Jr.

    1997-05-01

    Because of the complexity of phenomena governing boiling heat transfer, the approach to solve practical problems has traditionally been based on experimental correlations rather than mechanistic models. The recent progress in computational fluid dynamics (CFD), combined with improved experimental techniques in two-phase flow and heat transfer, makes the use of rigorous physically-based models a realistic alternative to the current simplistic phenomenological approach. The objective of this paper is to present a new CFD model for critical heat flux (CHF) in low quality (in particular, in subcooled boiling) forced-convection flows in heated channels.

  9. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling

    PubMed Central

    Shang, Yi; Filizola, Marta

    2015-01-01

    Opioid receptors are important drug targets for pain management, addiction, and mood disorders. Although substantial research on these important subtypes of G protein-coupled receptors has been conducted over the past two decades to discover ligands with higher specificity and diminished side effects, currently used opioid therapeutics remain suboptimal. Luckily, recent advances in structural biology of opioid receptors provide unprecedented insights into opioid receptor pharmacology and signaling. We review here a few recent studies that have used the crystal structures of opioid receptors as a basis for revealing mechanistic details of signal transduction mediated by these receptors, and for the purpose of drug discovery. PMID:25981301

  10. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling.

    PubMed

    Shang, Yi; Filizola, Marta

    2015-09-15

    Opioid receptors are important drug targets for pain management, addiction, and mood disorders. Although substantial research on these important subtypes of G protein-coupled receptors has been conducted over the past two decades to discover ligands with higher specificity and diminished side effects, currently used opioid therapeutics remain suboptimal. Luckily, recent advances in structural biology of opioid receptors provide unprecedented insights into opioid receptor pharmacology and signaling. We review here a few recent studies that have used the crystal structures of opioid receptors as a basis for revealing mechanistic details of signal transduction mediated by these receptors, and for the purpose of drug discovery.

  11. Mechanistic equations for membrane transport of multicomponent solutions.

    PubMed

    Suchanek, G

    2006-03-01

    In the present article, mechanistic equations for membrane transport of N + 1-component solutions have been derived. The major specific investigation result is the introduction - for ternary solutions - of two diffusion coefficients omega(d1) and omega(d2) for solutes, as well as two cross coefficients omega(d12) and omega(d21) for these solutes. The latter parameters may be treated as coefficients of interdiffusion. The expansion of the description of substance transport to include the N + 1-component solutions does not formulate any additional physical phenomena other than those which are formulated by the transport equations for three-component solutions.

  12. [Mechanistic examination of organometallic electron transfer reactions: Annual report, 1989

    SciTech Connect

    Not Available

    1989-12-31

    Our mechanistic examination of electron transfer reactions between organometallic complexes has required data from our stopped-flow infrared spectrophotometer that was constructed in the first year. Our research on organometallic electron transfer reaction mechanisms was recognized by an invitation to the Symposium on Organometallic Reaction Mechanisms at the National ACS meeting in Miami. We have obtained a reasonable understanding of the electron transfer reactions between metal cations and anions and between metal carbonyl anions and metal carbonyl dimers. In addition we have begun to obtain data on the outer sphere electron transfer between metal carbonyl anions and coordination complexes and on reactions involving cluster anions.

  13. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    PubMed Central

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  14. Modeling of batch sorber system: kinetic, mechanistic, and thermodynamic modeling

    NASA Astrophysics Data System (ADS)

    Mishra, Vishal

    2016-09-01

    The present investigation has dealt with the biosorption of copper and zinc ions on the surface of egg-shell particles in the liquid phase. Various rate models were evaluated to elucidate the kinetics of copper and zinc biosorptions, and the results indicated that the pseudo-second-order model was more appropriate than the pseudo-first-order model. The curve of the initial sorption rate versus the initial concentration of copper and zinc ions also complemented the results of the pseudo-second-order model. Models used for the mechanistic modeling were the intra-particle model of pore diffusion and Bangham's model of film diffusion. The results of the mechanistic modeling together with the values of pore and film diffusivities indicated that the preferential mode of the biosorption of copper and zinc ions on the surface of egg-shell particles in the liquid phase was film diffusion. The results of the intra-particle model showed that the biosorption of the copper and zinc ions was not dominated by the pore diffusion, which was due to macro-pores with open-void spaces present on the surface of egg-shell particles. The thermodynamic modeling reproduced the fact that the sorption of copper and zinc was spontaneous, exothermic with the increased order of the randomness at the solid-liquid interface.

  15. Noncanonical IFN Signaling: Mechanistic Linkage of Genetic and Epigenetic Events

    PubMed Central

    Ahmed, Chulbul M.

    2016-01-01

    The canonical model of cytokine signaling via the JAK/STAT pathway dominates our view of signal transduction but provides no insight into the significance of the simultaneous presence of activated JAKs and STATs in the nucleus of cells treated with cytokines. Such a mechanistic shortcoming challenges the usefulness of the model in its present form. Focusing on the interferon (IFN) cytokines, we have developed a noncanonical model of IFN signaling that naturally connects activated JAKs and STATs at or near response elements of genes that are activated by the IFNs. Specifically, cells treated with IFNγ showed association of activated STAT1α and JAK2 at the GAS element of genes activated by IFNγ. For IFNα treated cells, the association involved activated STAT1α and TYK2 JAK kinase at the ISRE promoter. The power of the noncanonical model is that it provides mechanistic insight into specific gene activation at the level of the associated epigenetics, akin to that of steroid/steroid receptor signaling. PMID:28077919

  16. From Data Patterns to Mechanistic Models in Acute Critical Illness

    PubMed Central

    Aerts, Jean-Marie; Haddad, Wassim M.; An, Gary; Vodovotz, Yoram

    2014-01-01

    The complexity of the physiologic and inflammatory response in acute critical illness has stymied the accurate diagnosis and development of therapies. The Society for Complex Acute Illness was formed a decade ago with the goal of leveraging multiple complex systems approaches in order to address this unmet need. Two main paths of development have characterized the Society’s approach: i) data pattern analysis, either defining the diagnostic/prognostic utility of complexity metrics of physiological signals or multivariate analyses of molecular and genetic data, and ii) mechanistic mathematical and computational modeling, all being performed with an explicit translational goal. Here, we summarize the progress to date on each of these approaches, along with pitfalls inherent in the use of each approach alone. We suggest that the next decade holds the potential to merge these approaches, connecting patient diagnosis to treatment via mechanism-based dynamical system modeling and feedback control, and allowing extrapolation from physiologic signals to biomarkers to novel drug candidates. As a predicate example, we focus on the role of data-driven and mechanistic models in neuroscience, and the impact that merging these modeling approaches can have on general anesthesia. PMID:24768566

  17. Photosynthetic water oxidation vs. mitochondrial oxygen reduction: distinct mechanistic parallels.

    PubMed

    Silverstein, Todd P

    2011-08-01

    The photosynthetic oxygen evolving complex (PSII-OEC) and the mitochondrial cytochrome c oxidase (CcO) not only catalyze anti-parallel reactions (the OEC oxidizes water to dioxygen, whereas CcO reduces dioxygen to water), they also share a number of uncanny molecular and mechanistic similarities. Both feature a redox-active polymetallic cluster that includes a key tyrosine, and both utilize a two-phase mechanism. In one phase the polymetallic cluster undergoes four sequential one-electron transfers: In the PSII-OEC, four successive photooxidations of the photosystem II reaction center P680 (to P680(+)) allows acceptance of 4 × 1e- from the Mn(4)Ca cluster; in CcO, four reduced cytochrome c Fe(2+) cations donate 4 × 1e- to the bimetallic center. In the second phase for each enzyme, the polymetallic cluster undergoes a single four-electron transfer with the O(2)/2 H(2)O redox couple. Intriguing mechanistic similarities between these two complex redox enzymes first delineated over a decade ago by Hoganson/Proshlyakov/Babcock et al. are updated and expanded in this article.

  18. The coefficient of restitution of pressurized balls: a mechanistic model

    NASA Astrophysics Data System (ADS)

    Georgallas, Alex; Landry, Gaëtan

    2016-01-01

    Pressurized, inflated balls used in professional sports are regulated so that their behaviour upon impact can be anticipated and allow the game to have its distinctive character. However, the dynamics governing the impacts of such balls, even on stationary hard surfaces, can be extremely complex. The energy transformations, which arise from the compression of the gas within the ball and from the shear forces associated with the deformation of the wall, are examined in this paper. We develop a simple mechanistic model of the dependence of the coefficient of restitution, e, upon both the gauge pressure, P_G, of the gas and the shear modulus, G, of the wall. The model is validated using the results from a simple series of experiments using three different sports balls. The fits to the data are extremely good for P_G > 25 kPa and consistent values are obtained for the value of G for the wall material. As far as the authors can tell, this simple, mechanistic model of the pressure dependence of the coefficient of restitution is the first in the literature. *%K Coefficient of Restitution, Dynamics, Inflated Balls, Pressure, Impact Model

  19. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    PubMed

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

  20. New web-based applications for mechanistic case diagramming.

    PubMed

    Dee, Fred R; Haugen, Thomas H; Kreiter, Clarence D

    2014-01-01

    The goal of mechanistic case diagraming (MCD) is to provide students with more in-depth understanding of cause and effect relationships and basic mechanistic pathways in medicine. This will enable them to better explain how observed clinical findings develop from preceding pathogenic and pathophysiological events. The pedagogic function of MCD is in relating risk factors, disease entities and morphology, signs and symptoms, and test and procedure findings in a specific case scenario with etiologic pathogenic and pathophysiological sequences within a flow diagram. In this paper, we describe the addition of automation and predetermined lists to further develop the original concept of MCD as described by Engelberg in 1992 and Guerrero in 2001. We demonstrate that with these modifications, MCD is effective and efficient in small group case-based teaching for second-year medical students (ratings of ~3.4 on a 4.0 scale). There was also a significant correlation with other measures of competency, with a 'true' score correlation of 0.54. A traditional calculation of reliability showed promising results (α =0.47) within a low stakes, ungraded environment. Further, we have demonstrated MCD's potential for use in independent learning and TBL. Future studies are needed to evaluate MCD's potential for use in medium stakes assessment or self-paced independent learning and assessment. MCD may be especially relevant in returning students to the application of basic medical science mechanisms in the clinical years.

  1. Deposition head for laser

    DOEpatents

    Lewis, Gary K.; Less, Richard M.

    1999-01-01

    A deposition head for use as a part of apparatus for forming articles from materials in particulate form in which the materials are melted by a laser beam and deposited at points along a tool path to form an article of the desired shape and dimensions. The deposition head delivers the laser beam and powder to a deposition zone, which is formed at the tip of the deposition head. A controller comprised of a digital computer directs movement of the deposition zone along the tool path and provides control signals to adjust apparatus functions, such as the speed at which the deposition head moves along the tool path.

  2. Novel interconnect deposition technology

    NASA Astrophysics Data System (ADS)

    Speckman, D. M.; Wendt, J. P.

    1991-12-01

    A new series of experiments was initiated to improve current interconnect deposition technology for integrated circuits. Preliminary aluminum deposition experiments were carried out using trimethylamine(alane) as the precursor, and some mildly reflective, uniform aluminum films were successfully deposited on glass slides, suggesting that chemical vapor deposition (CVD) will be a practicable deposition technique for advanced integrated circuit interconnect films. CVD studies of aluminum and zirconium- and hafnium-diboride thin films are continuing.

  3. Emerging mechanistic targets in lung injury induced by combustion-generated particles.

    PubMed

    Fariss, Marc W; Gilmour, M Ian; Reilly, Christopher A; Liedtke, Wolfgang; Ghio, Andrew J

    2013-04-01

    The mechanism for biological effect following exposure to combustion-generated particles is incompletely defined. The identification of pathways regulating the acute toxicological effects of these particles provides specific targets for therapeutic manipulation in an attempt to impact disease following exposures. Transient receptor potential (TRP) cation channels were identified as "particle sensors" in that their activation was coupled with the initiation of protective responses limiting airway deposition and inflammatory responses, which promote degradation and clearance of the particles. TRPA1, V1, V4, and M8 have a capacity to mediate adverse effects after exposure to combustion-generated particulate matter (PM); relative contributions of each depend upon particle composition, dose, and deposition. Exposure of human bronchial epithelial cells to an organic extract of diesel exhaust particle was followed by TRPV4 mediating Ca(++) influx, increased RAS expression, mitogen-activated protein kinase signaling, and matrix metalloproteinase-1 activation. These novel pathways of biological effect can be targeted by compounds that specifically inhibit critical signaling reactions. In addition to TRPs and calcium biochemistry, humic-like substances (HLS) and cell/tissue iron equilibrium were identified as potential mechanistic targets in lung injury after particle exposure. In respiratory epithelial cells, iron sequestration by HLS in wood smoke particle (WSP) was associated with oxidant generation, cell signaling, transcription factor activation, and release of inflammatory mediators. Similar to WSP, cytotoxic insoluble nanosized spherical particles composed of HLS were isolated from cigarette smoke condensate. Therapies that promote bioelimination of HLS and prevent the disruption of iron homeostasis could function to reduce the harmful effects of combustion-generated PM exposure.

  4. Deposit model for volcanogenic uranium deposits

    USGS Publications Warehouse

    Breit, George N.; Hall, Susan M.

    2011-01-01

    The International Atomic Energy Agency's tabulation of volcanogenic uranium deposits lists 100 deposits in 20 countries, with major deposits in Russia, Mongolia, and China. Collectively these deposits are estimated to contain uranium resources of approximately 500,000 tons of uranium, which amounts to 6 percent of the known global resources. Prior to the 1990s, these deposits were considered to be small (less than 10,000 tons of uranium) with relatively low to moderate grades (0.05 to 0.2 weight percent of uranium). Recent availability of information on volcanogenic uranium deposits in Asia highlighted the large resource potential of this deposit type. For example, the Streltsovskoye district in eastern Russia produced more than 100,000 tons of uranium as of 2005; with equivalent resources remaining. Known volcanogenic uranium deposits within the United States are located in Idaho, Nevada, Oregon, and Utah. These deposits produced an estimated total of 800 tons of uranium during mining from the 1950s through the 1970s and have known resources of 30,000 tons of uranium. The most recent estimate of speculative resources proposed an endowment of 200,000 tons of uranium.

  5. Myocardial steatosis as a possible mechanistic link between diastolic dysfunction and coronary microvascular dysfunction in women.

    PubMed

    Wei, Janet; Nelson, Michael D; Szczepaniak, Edward W; Smith, Laura; Mehta, Puja K; Thomson, Louise E J; Berman, Daniel S; Li, Debiao; Bairey Merz, C Noel; Szczepaniak, Lidia S

    2016-01-01

    Women with coronary microvascular dysfunction (CMD) and no obstructive coronary artery disease (CAD) have increased rates of heart failure with preserved ejection fraction (HFpEF). The mechanisms of HFpEF are not well understood. Ectopic fat deposition in the myocardium, termed myocardial steatosis, is frequently associated with diastolic dysfunction in other metabolic diseases. We investigated the prevalence of myocardial steatosis and diastolic dysfunction in women with CMD and subclinical HFpEF. In 13 women, including eight reference controls and five women with CMD and evidence of subclinical HFpEF (left ventricular end-diastolic pressure >12 mmHg), we measured myocardial triglyceride content (TG) and diastolic function, by proton magnetic resonance spectroscopy and magnetic resonance tissue tagging, respectively. When compared with reference controls, women with CMD had higher myocardial TG content (0.83 ± 0.12% vs. 0.43 ± 0.06%; P = 0.025) and lower diastolic circumferential strain rate (168 ± 12 vs. 217 ± 15%/s; P = 0.012), with myocardial TG content correlating inversely with diastolic circumferential strain rate (r = -0.779; P = 0.002). This study provides proof-of-concept that myocardial steatosis may play an important mechanistic role in the development of diastolic dysfunction in women with CMD and no obstructive CAD. Detailed longitudinal studies are warranted to explore specific treatment strategies targeting myocardial steatosis and its effect on diastolic function.

  6. Myocardial steatosis as a possible mechanistic link between diastolic dysfunction and coronary microvascular dysfunction in women

    PubMed Central

    Nelson, Michael D.; Szczepaniak, Edward W.; Smith, Laura; Mehta, Puja K.; Thomson, Louise E. J.; Berman, Daniel S.; Li, Debiao; Bairey Merz, C. Noel; Szczepaniak, Lidia S.

    2015-01-01

    Women with coronary microvascular dysfunction (CMD) and no obstructive coronary artery disease (CAD) have increased rates of heart failure with preserved ejection fraction (HFpEF). The mechanisms of HFpEF are not well understood. Ectopic fat deposition in the myocardium, termed myocardial steatosis, is frequently associated with diastolic dysfunction in other metabolic diseases. We investigated the prevalence of myocardial steatosis and diastolic dysfunction in women with CMD and subclinical HFpEF. In 13 women, including eight reference controls and five women with CMD and evidence of subclinical HFpEF (left ventricular end-diastolic pressure >12 mmHg), we measured myocardial triglyceride content (TG) and diastolic function, by proton magnetic resonance spectroscopy and magnetic resonance tissue tagging, respectively. When compared with reference controls, women with CMD had higher myocardial TG content (0.83 ± 0.12% vs. 0.43 ± 0.06%; P = 0.025) and lower diastolic circumferential strain rate (168 ± 12 vs. 217 ± 15%/s; P = 0.012), with myocardial TG content correlating inversely with diastolic circumferential strain rate (r = −0.779; P = 0.002). This study provides proof-of-concept that myocardial steatosis may play an important mechanistic role in the development of diastolic dysfunction in women with CMD and no obstructive CAD. Detailed longitudinal studies are warranted to explore specific treatment strategies targeting myocardial steatosis and its effect on diastolic function. PMID:26519031

  7. Mechanistic Insights on the Photosensitized Chemistry of a Fatty Acid at the Air/Water Interface

    PubMed Central

    2016-01-01

    Interfaces are ubiquitous in the environment and many atmospheric key processes, such as gas deposition, aerosol, and cloud formation are, at one stage or another, strongly impacted by physical and chemical processes occurring at interfaces. Here, the photoinduced chemistry of an air/water interface coated with nonanoic acid—a fatty acid surfactant we use as a proxy for chemically complex natural aqueous surface microlayers—was investigated as a source of volatile and semivolatile reactive organic species. The carboxylic acid coating significantly increased the propensity of photosensitizers, chosen to mimic those observed in real environmental waters, to partition to the interface and enhance reactivity there. Photochemical formation of functionalized and unsaturated compounds was systematically observed upon irradiation of these coated surfaces. The role of a coated interface appears to be critical in providing a concentrated medium allowing radical–radical reactions to occur in parallel with molecular oxygen additions. Mechanistic insights are provided from extensive analysis of products observed in both gas and aqueous phases by online switchable reagent ion-time of flight-mass spectrometry and by off-line ultraperformance liquid chromatography coupled to a Q Exactive high resolution mass spectrometer through heated electrospray ionization, respectively. PMID:27611489

  8. A new mechanistic framework to predict OCS fluxes in soils

    NASA Astrophysics Data System (ADS)

    Sauze, Joana; Ogee, Jérôme; Launois, Thomas; Kesselmeier, Jürgen; Van Diest, Heidi; Wingate, Lisa

    2015-04-01

    A better description of the amplitude of photosynthetic and respiratory gross CO2 fluxes at large scales is needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulfide (COS) is the most abundant sulphur gas in the atmosphere and has been proposed as a new tracer of gross photosynthesis, as the uptake of COS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. However, soils also exchange COS with the atmosphere and there is growing evidence that this flux must also be accounted for in atmospheric budgets. In this context a new mechanistic description of soil-atmosphere COS exchange is clearly needed. Soils can take up COS from the atmosphere as the soil biota also contain CA, and COS emissions from soils have also been reported in agricultural fields or anoxic soils. Previous studies have also shown that soil COS fluxes present an optimum soil water content and soil temperature. Here we propose a new mechanistic framework to predict the fluxes of COS between the soils and the atmosphere. We describe the COS soil budget by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of COS by CA is total and irreversible. To describe COS diffusion through the soil matrix, we use different formulations of soil air-filled pore space and temperature, depending on the turbulence level above the soil surface. Using this model we are able to explain the observed presence of an optimum temperature for soil COS uptake and show how this optimum can shift to cooler temperatures in the presence of soil COS emissions. Our model can also explain the observed optimum with soil moisture content previously described in the literature (e.g. Van Diest & Kesselmeier, 2008) as a result of diffusional constraints on COS hydrolysis. These diffusional constraints are also responsible for the response of COS uptake to soil

  9. Conservative or reactive? Mechanistic chemical perspectives on organic matter stability

    NASA Astrophysics Data System (ADS)

    Koch, Boris

    2016-04-01

    Carbon fixation by terrestrial and marine primary production has a fundamental seasonal effect on the atmospheric carbon content and it profoundly contributes to long-term carbon storage in form of organic matter (OM) in soils, water, and sediments. The efficacy of this sequestration process strongly depends on the degree of OM persistence. Therefore, one of the key issues in dissolved and particulate OM research is to assess the stability of reservoirs and to quantify their contribution to global carbon fluxes. Incubation experiments are helpful to assess OM stability during the first, early diagenetic turnover induced by sunlight or microbes. However, net carbon fluxes within the global carbon cycle also act on much longer time scales, which are not amenable in experiments. It is therefore critical to improve our mechanistic understanding to be able to assess potential future changes in the organic matter cycle. This session contribution highlights some achievements and open questions in the field. An improved mechanistic understanding of OM turnover particularly depends on the molecular characterization of biogeochemical processes and their kinetics: (i) in soils and sediments, aggregation/disaggregation of OM is primarily controlled by its molecular composition. Hence, the chemical composition determines the transfer of organic carbon from the large particulate to the small dissolved organic matter reservoir - an important substrate for microbial metabolism. (ii) In estuaries, dissolved organic carbon gradients usually suggest conservative behavior, whereas molecular-level studies reveal a substantial chemical modification of terrestrial DOM along the land-ocean interface. (iii) In the ocean, previous studies have shown that the recalcitrance of OM depends on bulk concentration and energy yield. However, ultrahigh resolution mass spectrometry in combination with radiocarbon analyses also emphasized that stability is tightly connected to molecular composition

  10. Perspectives on the Application of Mechanistic Information in Chemical Hazard and Dose-Response Assessments

    EPA Science Inventory

    This overview summarizes several EPA Assessment publications reviewing approaches for applying mechanistic information in human health risk assessment and exploring opportunities for progress in this area.

  11. Quantifying fat, oil, and grease deposit formation kinetics.

    PubMed

    Iasmin, Mahbuba; Dean, Lisa O; Ducoste, Joel J

    2016-01-01

    Fat, oil, and grease (FOG) deposits formed in sanitary sewers are calcium-based saponified solids that are responsible for a significant number of nationwide sanitary sewer overflows (SSOs) across United States. In the current study, the kinetics of lab-based saponified solids were determined to understand the kinetics of FOG deposit formation in sewers for two types of fat (Canola and Beef Tallow) and two types of calcium sources (calcium chloride and calcium sulfate) under three pH (7 ± 0.5, 10 ± 0.5, and ≈14) and two temperature conditions (22 ± 0.5 and 45 ± 0.5 °C). The results of this study displayed quick reactions of a fraction of fats with calcium ions to form calcium based saponified solids. Results further showed that increased palmitic fatty acid content in source fats, the magnitude of the pH, and temperature significantly affect the FOG deposit formation and saponification rates. The experimental data of the kinetics were compared with two empirical models: a) Cotte saponification model and b) Foubert crystallization model and a mass-action based mechanistic model that included alkali driven hydrolysis of triglycerides. Results showed that the mass action based mechanistic model was able to predict changes in the rate of formation of saponified solids under the different experimental conditions compared to both empirical models. The mass-action based saponification model also revealed that the hydrolysis of Beef Tallow was slower compared to liquid Canola fat resulting in smaller quantities of saponified solids. This mechanistic saponification model, with its ability to track the saponified solids chemical precursors, may provide an initial framework to predict the spatial formation of FOG deposits in municipal sewers using system wide sewer collection modeling software.

  12. Mechanistic characterization of chloride interferences in electrothermal atomization systems

    USGS Publications Warehouse

    Shekiro, J.M.; Skogerboe, R.K.; Taylor, H.E.

    1988-01-01

    A computer-controlled spectrometer with a photodiode array detector has been used for wavelength and temperature resolved characterization of the vapor produced by an electrothermal atomizer. The system has been used to study the chloride matrix interference on the atomic absorption spectrometric determination of manganese and copper. The suppression of manganese and copper atom populations by matrix chlorides such as those of calcium and magnesium is due to the gas-phase formation of an analyte chloride species followed by the diffusion of significant fractions of these species from the atom cell prior to completion of the atomization process. The analyte chloride species cannot be formed when matrix chlorides with metal-chloride bond dissociation energies above those of the analyte chlorides are the principal entitles present. The results indicate that multiple wavelength spectrometry used to obtain temperature-resolved spectra is a viable tool in the mechanistic characterization of interference effects observed with electrothermal atomization systems. ?? 1988 American Chemical Society.

  13. Atrial Fibrillation and Hypertension: Mechanistic, Epidemiologic, and Treatment Parallels.

    PubMed

    Ogunsua, Adedotun A; Shaikh, Amir Y; Ahmed, Mohamed; McManus, David D

    2015-01-01

    Atrial fibrillation (AF) is an increasingly prevalent condition and the most common sustained arrhythmia encountered in ambulatory and hospital practice. Several clinical risk factors for AF include age, sex, valvular heart disease, obesity, sleep apnea, heart failure, and hypertension (HTN). Of all the risk factors, HTN is the most commonly encountered condition in patients with incident AF. Hypertension is associated with a 1.8-fold increase in the risk of developing new-onset AF and a 1.5-fold increase in the risk of progression to permanent AF. Hypertension predisposes to cardiac structural changes that influence the development of AF such as atrial remodeling. The renin angiotensin aldosterone system has been demonstrated to be a common mechanistic link in the pathogenesis of HTN and AF. Importantly, HTN is one of the few modifiable AF risk factors, and guideline-directed management of HTN may reduce the incidence of AF.

  14. Mechanistic determinants of biotherapeutics absorption following SC administration.

    PubMed

    Richter, Wolfgang F; Bhansali, Suraj G; Morris, Marilyn E

    2012-09-01

    The subcutaneous (SC) route is of growing interest for the administration of biotherapeutics. Key products on the biotherapeutic market such as insulins, but also several immunoglobulins or Fc-fusion proteins, are administered SC. Despite the importance of the SC route, the available knowledge about the processes involved in the SC absorption of biotherapeutics is limited. This review summarizes available information on the physiology of the SC tissue and on the pharmacokinetic processes after SC administration including "first pass catabolism" at the administration site as well as transport in the extracellular matrix of the SC tissue, followed by absorption into the blood circulation or the lymphatic system. Both monoclonal antibodies and other biotherapeutics are discussed. Determinants of absorption after SC administration are summarized including compound properties such as charge or molecular weight. Scale-up of animal data to humans is discussed, including the current shortcomings of empirical scaling approaches and the lack of suitable mechanistic approaches.

  15. Enhancer function: mechanistic and genome-wide insights come together.

    PubMed

    Plank, Jennifer L; Dean, Ann

    2014-07-03

    Enhancers establish spatial or temporal patterns of gene expression that are critical for development, yet our understanding of how these DNA cis-regulatory elements function from a distance to increase transcription of their target genes and shape the cellular transcriptome has been gleaned primarily from studies of individual genes or gene families. High-throughput sequencing studies place enhancer-gene interactions within the 3D context of chromosome folding, inviting a new look at enhancer function and stimulating provocative new questions. Here, we integrate these whole-genome studies with recent mechanistic studies to illuminate how enhancers physically interact with target genes, how enhancer activity is regulated during development, and the role of noncoding RNAs transcribed from enhancers in their function.

  16. Mechanistic modeling confronts the complexity of molecular cell biology.

    PubMed

    Phair, Robert D

    2014-11-05

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist-electrical engineer-systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build-and subject to exhaustive experimental tests-models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.

  17. A mechanistic interpretation of the resonant wave-particle interaction

    NASA Astrophysics Data System (ADS)

    Chim, Chi Yung; O'Neil, Thomas M.

    2016-05-01

    This paper provides a simple mechanistic interpretation of the resonant wave-particle interaction of Landau. For the simple case of a Langmuir wave in a Vlasov plasma, the non-resonant electrons satisfy an oscillator equation that is driven resonantly by the bare electric field from the resonant electrons, and in the case of wave damping, this complex driver field is of a phase to reduce the oscillation amplitude. The wave-particle resonant interaction also occurs in waves governed by 2D E × B drift dynamics, such as a diocotron wave. In this case, the bare electric field from the resonant electrons causes E × B drift motion back in the core plasma, reducing the amplitude of the wave.

  18. From patterns to emerging processes in mechanistic urban ecology.

    PubMed

    Shochat, Eyal; Warren, Paige S; Faeth, Stanley H; McIntyre, Nancy E; Hope, Diane

    2006-04-01

    Rapid urbanization has become an area of crucial concern in conservation owing to the radical changes in habitat structure and loss of species engendered by urban and suburban development. Here, we draw on recent mechanistic ecological studies to argue that, in addition to altered habitat structure, three major processes contribute to the patterns of reduced species diversity and elevated abundance of many species in urban environments. These activities, in turn, lead to changes in animal behavior, morphology and genetics, as well as in selection pressures on animals and plants. Thus, the key to understanding urban patterns is to balance studying processes at the individual level with an integrated examination of environmental forces at the ecosystem scale.

  19. Mechanistic model for void distribution in flashing flow

    SciTech Connect

    Riznic, J.; Ishii, M.; Afgan, N.

    1987-01-01

    A problem of discharging of an initially subcooled liquid from a high pressure condition into a low pressure environment is quite important in several industrial systems such as nuclear reactors and chemical reactors. A new model for the flashing process is proposed here based on the wall nucleation theory, bubble growth model and drift-flux bubble transport model. In order to calculate the bubble number density, the bubble number transport equation with a distributed source from the wall nucleation sites is used. The model predictions in terms of the void fraction are compared to Moby Dick and BNL experimental data. It shows that satisfactory agreements could be obtained from the present model without any floating parameter to be adjusted with data. This result indicates that, at least for the experimental conditions considered here, the mechanistic prediction of the flashing phenomenon is possible based on the present wall nucleation based model. 43 refs., 4 figs.

  20. Micelle confined mechanistic pathway for 4-nitrophenol reduction.

    PubMed

    Roy, Anindita; Debnath, Biplab; Sahoo, Ramkrishna; Aditya, Teresa; Pal, Tarasankar

    2017-05-01

    The model 4-nitrophenol reduction has been carried out by different groups in presence of metallic or even non-metallic catalyst elaborating different mechanistic aspects. In the present investigation, we have thoroughly studied the hydrogenation of 4-nitrophenol in a completely metal free homogeneous condition. The introduction of a non-fluorescent probe unequivocally generates a fluorescent molecule that indirectly justifies the anion radical stabilization in the micelle. The reduction mechanism under metal-free condition was proposed and the concept of stabilization of anion radical transition state of 4-nitrophenol at the positively charged Stern layer of anionic micelle was established. The plausible reduction mechanism has also enlightened the graphene-like conducting property of Stern layer of the homogeneous micellar system. Furthermore, the confinement effect for catalysis has also been authenticated by supporting experimental evidences. The borrowed concept of catalysis in confinement drives the catalytic study to a new era of catalysis.

  1. Calorie restriction and cancer prevention: a mechanistic perspective

    PubMed Central

    2013-01-01

    Calorie restriction (CR) is one of the most potent broadly acting dietary interventions for inducing weight loss and for inhibiting cancer in experimental models. Translation of the mechanistic lessons learned from research on CR to cancer prevention strategies in human beings is important given the high prevalence of excess energy intake, obesity, and metabolic syndrome in many parts of the world and the established links between obesity-associated metabolic perturbations and increased risk or progression of many types of cancer. This review synthesizes findings on the biological mechanisms underlying many of the anticancer effects of CR, with emphasis on the impact of CR on growth factor signaling pathways, inflammation, cellular and systemic energy homeostasis pathways, vascular perturbations, and the tumor microenvironment. These CR-responsive pathways and processes represent targets for translating CR research into effective cancer prevention strategies in human beings. PMID:24280167

  2. Assembly Line Polyketide Synthases: Mechanistic Insights and Unsolved Problems

    PubMed Central

    2015-01-01

    Two hallmarks of assembly line polyketide synthases have motivated an interest in these unusual multienzyme systems, their stereospecificity and their capacity for directional biosynthesis. In this review, we summarize the state of knowledge regarding the mechanistic origins of these two remarkable features, using the 6-deoxyerythronolide B synthase as a prototype. Of the 10 stereocenters in 6-deoxyerythronolide B, the stereochemistry of nine carbon atoms is directly set by ketoreductase domains, which catalyze epimerization and/or diastereospecific reduction reactions. The 10th stereocenter is established by the sequential action of three enzymatic domains. Thus, the problem has been reduced to a challenge in mainstream enzymology, where fundamental gaps remain in our understanding of the structural basis for this exquisite stereochemical control by relatively well-defined active sites. In contrast, testable mechanistic hypotheses for the phenomenon of vectorial biosynthesis are only just beginning to emerge. Starting from an elegant theoretical framework for understanding coupled vectorial processes in biology [Jencks, W. P. (1980) Adv. Enzymol. Relat. Areas Mol. Biol. 51, 75–106], we present a simple model that can explain assembly line polyketide biosynthesis as a coupled vectorial process. Our model, which highlights the important role of domain–domain interactions, not only is consistent with recent observations but also is amenable to further experimental verification and refinement. Ultimately, a definitive view of the coordinated motions within and between polyketide synthase modules will require a combination of structural, kinetic, spectroscopic, and computational tools and could be one of the most exciting frontiers in 21st Century enzymology. PMID:24779441

  3. Informing phenomenological structural bone remodelling with a mechanistic poroelastic model.

    PubMed

    Villette, Claire C; Phillips, Andrew T M

    2016-02-01

    Studies suggest that fluid motion in the extracellular space may be involved in the cellular mechanosensitivity at play in the bone tissue adaptation process. Previously, the authors developed a mesoscale predictive structural model of the femur using truss elements to represent trabecular bone, relying on a phenomenological strain-based bone adaptation algorithm. In order to introduce a response to bending and shear, the authors considered the use of beam elements, requiring a new formulation of the bone adaptation drivers. The primary goal of the study presented here was to isolate phenomenological drivers based on the results of a mechanistic approach to be used with a beam element representation of trabecular bone in mesoscale structural modelling. A single-beam model and a microscale poroelastic model of a single trabecula were developed. A mechanistic iterative adaptation algorithm was implemented based on fluid motion velocity through the bone matrix pores to predict the remodelled geometries of the poroelastic trabecula under 42 different loading scenarios. Regression analyses were used to correlate the changes in poroelastic trabecula thickness and orientation to the initial strain outputs of the beam model. Linear (R(2) > 0.998) and third-order polynomial (R(2) > 0.98) relationships were found between change in cross section and axial strain at the central axis, and between beam reorientation and ratio of bending strain to axial strain, respectively. Implementing these relationships into the phenomenological predictive algorithm for the mesoscale structural femur has the potential to produce a model combining biofidelic structure and mechanical behaviour with computational efficiency.

  4. Parameter and uncertainty estimation for mechanistic, spatially explicit epidemiological models

    NASA Astrophysics Data System (ADS)

    Finger, Flavio; Schaefli, Bettina; Bertuzzo, Enrico; Mari, Lorenzo; Rinaldo, Andrea

    2014-05-01

    Epidemiological models can be a crucially important tool for decision-making during disease outbreaks. The range of possible applications spans from real-time forecasting and allocation of health-care resources to testing alternative intervention mechanisms such as vaccines, antibiotics or the improvement of sanitary conditions. Our spatially explicit, mechanistic models for cholera epidemics have been successfully applied to several epidemics including, the one that struck Haiti in late 2010 and is still ongoing. Calibration and parameter estimation of such models represents a major challenge because of properties unusual in traditional geoscientific domains such as hydrology. Firstly, the epidemiological data available might be subject to high uncertainties due to error-prone diagnosis as well as manual (and possibly incomplete) data collection. Secondly, long-term time-series of epidemiological data are often unavailable. Finally, the spatially explicit character of the models requires the comparison of several time-series of model outputs with their real-world counterparts, which calls for an appropriate weighting scheme. It follows that the usual assumption of a homoscedastic Gaussian error distribution, used in combination with classical calibration techniques based on Markov chain Monte Carlo algorithms, is likely to be violated, whereas the construction of an appropriate formal likelihood function seems close to impossible. Alternative calibration methods, which allow for accurate estimation of total model uncertainty, particularly regarding the envisaged use of the models for decision-making, are thus needed. Here we present the most recent developments regarding methods for parameter and uncertainty estimation to be used with our mechanistic, spatially explicit models for cholera epidemics, based on informal measures of goodness of fit.

  5. Toxic Neuropathies: Mechanistic Insights Based On A Chemical Perspective

    PubMed Central

    LoPachin, Richard M.; Gavin, Terrence

    2014-01-01

    2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies. PMID:25218479

  6. CFD Based Computations of Flexible Helicopter Blades for Stability Analysis

    NASA Technical Reports Server (NTRS)

    Guruswamy, Guru P.

    2011-01-01

    As a collaborative effort among government aerospace research laboratories an advanced version of a widely used computational fluid dynamics code, OVERFLOW, was recently released. This latest version includes additions to model flexible rotating multiple blades. In this paper, the OVERFLOW code is applied to improve the accuracy of airload computations from the linear lifting line theory that uses displacements from beam model. Data transfers required at every revolution are managed through a Unix based script that runs jobs on large super-cluster computers. Results are demonstrated for the 4-bladed UH-60A helicopter. Deviations of computed data from flight data are evaluated. Fourier analysis post-processing that is suitable for aeroelastic stability computations are performed.

  7. CFD-based Modeling of Inflight Mercury Capture

    SciTech Connect

    Madsen, J.I.; O'Brien, T.J.

    2007-01-01

    A numerical model of sorbent injection and in-flight mercury capture is presented. There are few existing models of mercury capture, and these typically make gross assumptions of plug gas flow, no velocity slip between particle and gas phase, and uniform sorbent dispersion. All of these assumptions are overcome with the current model, which combines the physics of mass transfer at the microscopic sorbent scale with macroscopic flow conditions provided via Computational Fluid Dynamics (CFD) simulations. The implication is a cost-efficient tool for design of injection systems that maximize capture efficiency. The modeling framework will be presented along with results based on simulation of sites from the DOE/NETL sorbent injection field test program.

  8. CFD-Based Design Optimization for Single Element Rocket Injector

    NASA Technical Reports Server (NTRS)

    Vaidyanathan, Rajkumar; Tucker, Kevin; Papila, Nilay; Shyy, Wei

    2003-01-01

    To develop future Reusable Launch Vehicle concepts, we have conducted design optimization for a single element rocket injector, with overall goals of improving reliability and performance while reducing cost. Computational solutions based on the Navier-Stokes equations, finite rate chemistry, and the k-E turbulence closure are generated with design of experiment techniques, and the response surface method is employed as the optimization tool. The design considerations are guided by four design objectives motivated by the consideration in both performance and life, namely, the maximum temperature on the oxidizer post tip, the maximum temperature on the injector face, the adiabatic wall temperature, and the length of the combustion zone. Four design variables are selected, namely, H2 flow angle, H2 and O2 flow areas with fixed flow rates, and O2 post tip thickness. In addition to establishing optimum designs by varying emphasis on the individual objectives, better insight into the interplay between design variables and their impact on the design objectives is gained. The investigation indicates that improvement in performance or life comes at the cost of the other. Best compromise is obtained when improvements in both performance and life are given equal importance.

  9. CFD-Based Design Optimization Tool Developed for Subsonic Inlet

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The traditional approach to the design of engine inlets for commercial transport aircraft is a tedious process that ends with a less-than-optimum design. With the advent of high-speed computers and the availability of more accurate and reliable computational fluid dynamics (CFD) solvers, numerical optimization processes can effectively be used to design an aerodynamic inlet lip that enhances engine performance. The designers' experience at Boeing Corporation showed that for a peak Mach number on the inlet surface beyond some upper limit, the performance of the engine degrades excessively. Thus, our objective was to optimize efficiency (minimize the peak Mach number) at maximum cruise without compromising performance at other operating conditions. Using a CFD code NPARC, the NASA Lewis Research Center, in collaboration with Boeing, developed an integrated procedure at Lewis to find the optimum shape of a subsonic inlet lip and a numerical optimization code, ADS. We used a GRAPE-based three-dimensional grid generator to help automate the optimization procedure. The inlet lip shape at the crown and the keel was described as a superellipse, and the superellipse exponents and radii ratios were considered as design variables. Three operating conditions: cruise, takeoff, and rolling takeoff, were considered in this study. Three-dimensional Euler computations were carried out to obtain the flow field. At the initial design, the peak Mach numbers for maximum cruise, takeoff, and rolling takeoff conditions were 0.88, 1.772, and 1.61, respectively. The acceptable upper limits on the takeoff and rolling takeoff Mach numbers were 1.55 and 1.45. Since the initial design provided by Boeing was found to be optimum with respect to the maximum cruise condition, the sum of the peak Mach numbers at takeoff and rolling takeoff were minimized in the current study while the maximum cruise Mach number was constrained to be close to that at the existing design. With this objective, the optimum design satisfied the upper limits at takeoff and rolling takeoff while retaining the desirable cruise performance. Further studies are being conducted to include static and cross-wind operating conditions in the design optimization procedure. This work was carried out in collaboration with Dr. E.S. Reddy of NYMA, Inc.

  10. Nonlinear Krylov acceleration for CFD-based aeroelasticity

    NASA Astrophysics Data System (ADS)

    Feng, Z.; Soulaı¨Mani, A.; Saad, Y.

    2009-01-01

    A nonlinear computational aeroelasticity model based on the Euler equations of compressible flows and the linear elastodynamic equations for structures is developed. The Euler equations are solved on dynamic meshes using the ALE kinematic description. Thus, the mesh constitutes another field governed by pseudo-elastodynamic equations. The three fields are discretized using proper finite element formulations which satisfy the geometric conservation law. A matcher module is incorporated for the purpose of pairing the grids on the fluid-structure interface and for transferring the loads and displacements between the fluid and structure solvers. Two solution strategies (Gauss-Seidel and Schur-complement) for solving the non-linear aeroelastic system are discussed. By using second-order time discretization scheme, we are able to utilize large time steps in the computations. The numerical results on the AGARD 445.6 aeroelastic wing compare well with the experimental results and show that the Schur-complement coupling algorithm is more robust than the Gauss-Seidel algorithm for relatively large oscillation amplitudes.

  11. A Mechanistic Approach for the Prediction of Critical Power in BWR Fuel Bundles

    NASA Astrophysics Data System (ADS)

    Chandraker, Dinesh Kumar; Vijayan, Pallipattu Krishnan; Sinha, Ratan Kumar; Aritomi, Masanori

    The critical power corresponding to the Critical Heat Flux (CHF) or dryout condition is an important design parameter for the evaluation of safety margins in a nuclear fuel bundle. The empirical approaches for the prediction of CHF in a rod bundle are highly geometric specific and proprietary in nature. The critical power experiments are very expensive and technically challenging owing to the stringent simulation requirements for the rod bundle tests involving radial and axial power profiles. In view of this, the mechanistic approach has gained momentum in the thermal hydraulic community. The Liquid Film Dryout (LFD) in an annular flow is the mechanism of CHF under BWR conditions and the dryout modeling has been found to predict the CHF quite accurately for a tubular geometry. The successful extension of the mechanistic model of dryout to the rod bundle application is vital for the evaluation of critical power in the rod bundle. The present work proposes the uniform film flow approach around the rod by analyzing individual film of the subchannel bounded by rods with different heat fluxes resulting in different film flow rates around a rod and subsequently distributing the varying film flow rates of a rod to arrive at the uniform film flow rate as it has been found that the liquid film has a strong tendency to be uniform around the rod. The FIDOM-Rod code developed for the dryout prediction in BWR assemblies provides detailed solution of the multiple liquid films in a subchannel. The approach of uniform film flow rate around the rod simplifies the liquid film cross flow modeling and was found to provide dryout prediction with a good accuracy when compared with the experimental data of 16, 19 and 37 rod bundles under BWR conditions. The critical power has been predicted for a newly designed 54 rod bundle of the Advanced Heavy Water Reactor (AHWR). The selected constitutive models for the droplet entrainment and deposition rates validated for the dryout in tube were

  12. Biomimetic thin film deposition

    NASA Astrophysics Data System (ADS)

    Rieke, P. C.; Campbell, A. A.; Tarasevich, B. J.; Fryxell, G. E.; Bentjen, S. B.

    1991-04-01

    Surfaces derivatized with organic functional groups were used to promote the deposition of thin films of inorganic minerals. These derivatized surfaces were designed to mimic the nucleation proteins that control mineral deposition during formation of bone, shell, and other hard tissues in living organisms. By the use of derivatized substrates control was obtained over the phase of mineral deposited, the orientation of the crystal lattice and the location of deposition. These features are of considerable importance in many technically important thin films, coatings, and composite materials. Methods of derivatizing surfaces are considered and examples of controlled mineral deposition are presented.

  13. Dry deposition velocities

    SciTech Connect

    Sehmel, G.A.

    1984-03-01

    Dry deposition velocities are very difficult to predict accurately. In this article, reported values of dry deposition velocities are summarized. This summary includes values from the literature on field measurements of gas and particle dry deposition velocities, and the uncertainties inherent in extrapolating field results to predict dry deposition velocities are discussed. A new method is described for predicting dry deposition velocity using a least-squares correlation of surface mass transfer resistances evaluated in wind tunnel experiments. 14 references, 4 figures, 1 table.

  14. Development of a mechanistic model for forced convection subcooled boiling

    NASA Astrophysics Data System (ADS)

    Shaver, Dillon R.

    The focus of this work is on the formulation, implementation, and testing of a mechanistic model of subcooled boiling. Subcooled boiling is the process of vapor generation on a heated wall when the bulk liquid temperature is still below saturation. This is part of a larger effort by the US DoE's CASL project to apply advanced computational tools to the simulation of light water reactors. To support this effort, the formulation of the dispersed field model is described and a complete model of interfacial forces is formulated. The model has been implemented in the NPHASE-CMFD computer code with a K-epsilon model of turbulence. The interfacial force models are built on extensive work by other authors, and include novel formulations of the turbulent dispersion and lift forces. The complete model of interfacial forces is compared to experiments for adiabatic bubbly flows, including both steady-state and unsteady conditions. The same model is then applied to a transient gas/liquid flow in a complex geometry of fuel channels in a sodium fast reactor. Building on the foundation of the interfacial force model, a mechanistic model of forced-convection subcooled boiling is proposed. This model uses the heat flux partitioning concept and accounts for condensation of bubbles attached to the wall. This allows the model to capture the enhanced heat transfer associated with boiling before the point of net generation of vapor, a phenomenon consistent with existing experimental observations. The model is compared to four different experiments encompassing flows of light water, heavy water, and R12 at different pressures, in cylindrical channels, an internally heated annulus, and a rectangular channel. The experimental data includes axial and radial profiles of both liquid temperature and vapor volume fraction, and the agreement can be considered quite good. The complete model is then applied to simulations of subcooled boiling in nuclear reactor subchannels consistent with the

  15. A new mechanistic framework to predict OCS fluxes from soils

    NASA Astrophysics Data System (ADS)

    Ogée, Jérôme; Sauze, Joana; Kesselmeier, Jürgen; Genty, Bernard; Van Diest, Heidi; Launois, Thomas; Wingate, Lisa

    2016-04-01

    Estimates of photosynthetic and respiratory fluxes at large scales are needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulfide (OCS) is the most abundant sulfur gas in the atmosphere and has been proposed as a new tracer of photosynthetic gross primary productivity (GPP), as the uptake of OCS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. However soils also exchange OCS with the atmosphere, which complicates the retrieval of GPP from atmospheric budgets. Indeed soils can take up large amounts of OCS from the atmosphere as soil microorganisms also contain CA, and OCS emissions from soils have been reported in agricultural fields or anoxic soils. To date no mechanistic framework exists to describe this exchange of OCS between soils and the atmosphere, but empirical results, once upscaled to the global scale, indicate that OCS consumption by soils dominates OCS emission and its contribution to the atmospheric budget is large, at about one third of the OCS uptake by vegetation, also with a large uncertainty. Here, we propose a new mechanistic model of the exchange of OCS between soils and the atmosphere that builds on our knowledge of soil CA activity from CO2 oxygen isotopes. In this model the OCS soil budget is described by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of OCS by CA is total and irreversible. Using this model we are able to explain the observed presence of an optimum temperature for soil OCS uptake and show how this optimum can shift to cooler temperatures in the presence of soil OCS emission. Our model can also explain the observed optimum with soil moisture content previously described in the literature as a result of diffusional constraints on OCS hydrolysis. These diffusional constraints are also responsible for the response of OCS uptake to soil weight and

  16. Modeling Bird Migration under Climate Change: A Mechanistic Approach

    NASA Technical Reports Server (NTRS)

    Smith, James A.

    2009-01-01

    How will migrating birds respond to changes in the environment under climate change? What are the implications for migratory success under the various accelerated climate change scenarios as forecast by the Intergovernmental Panel on Climate Change? How will reductions or increased variability in the number or quality of wetland stop-over sites affect migratory bird species? The answers to these questions have important ramifications for conservation biology and wildlife management. Here, we describe the use of continental scale simulation modeling to explore how spatio-temporal changes along migratory flyways affect en-route migration success. We use an individually based, biophysical, mechanistic, bird migration model to simulate the movement of shorebirds in North America as a tool to study how such factors as drought and wetland loss may impact migratory success and modify migration patterns. Our model is driven by remote sensing and climate data and incorporates important landscape variables. The energy budget components of the model include resting, foraging, and flight, but presently predation is ignored. Results/Conclusions We illustrate our model by studying the spring migration of sandpipers through the Great Plains to their Arctic breeding grounds. Why many species of shorebirds have shown significant declines remains a puzzle. Shorebirds are sensitive to stop-over quality and spacing because of their need for frequent refueling stops and their opportunistic feeding patterns. We predict bird "hydrographs that is, stop-over frequency with latitude, that are in agreement with the literature. Mean stop-over durations predicted from our model for nominal cases also are consistent with the limited, but available data. For the shorebird species simulated, our model predicts that shorebirds exhibit significant plasticity and are able to shift their migration patterns in response to changing drought conditions. However, the question remains as to whether this

  17. Kinetic and Mechanistic Investigations of Atom Abstraction Reactions

    NASA Astrophysics Data System (ADS)

    Stevens, Philip Stanford

    1990-01-01

    reaction does not contribute significantly to the observed ozone depletion over Antarctica. These deviations bring the predictive power of the trends into question. The valuable mechanistic insight gained from trend comparisons is shown to outweigh the loss of predictive power, as these trends provide a benchmark for the mechanistic understanding of atom abstraction reactions.

  18. Circadian rhythms and addiction: Mechanistic insights and future directions

    PubMed Central

    Logan, Ryan W.; Williams, Wilbur P.; McClung, Colleen A.

    2014-01-01

    Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction, and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction. PMID:24731209

  19. Diffusion theory in biology: a relic of mechanistic materialism.

    PubMed

    Agutter, P S; Malone, P C; Wheatley, D N

    2000-01-01

    Diffusion theory explains in physical terms how materials move through a medium, e.g. water or a biological fluid. There are strong and widely acknowledged grounds for doubting the applicability of this theory in biology, although it continues to be accepted almost uncritically and taught as a basis of both biology and medicine. Our principal aim is to explore how this situation arose and has been allowed to continue seemingly unchallenged for more than 150 years. The main shortcomings of diffusion theory will be briefly reviewed to show that the entrenchment of this theory in the corpus of biological knowledge needs to be explained, especially as there are equally valid historical grounds for presuming that bulk fluid movement powered by the energy of cell metabolism plays a prominent note in the transport of molecules in the living body. First, the theory's evolution, notably from its origins in connection with the mechanistic materialist philosophy of mid nineteenth century physiology, is discussed. Following this, the entrenchment of the theory in twentieth century biology is analyzed in relation to three situations: the mechanism of oxygen transport between air and mammalian tissues; the structure and function of cell membranes; and the nature of the intermediary metalbolism, with its implicit presumptions about the intracellular organization and the movement of molecules within it. In our final section, we consider several historically based alternatives to diffusion theory, all of which have their precursors in nineteenth and twentieth century philosophy of science.

  20. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

    PubMed Central

    Yap, Wei Hsum; Lim, Yang Mooi

    2015-01-01

    Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs) are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX) enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS). The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB)/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli. PMID:26491566

  1. A mechanistic stochastic framework for regulating bacterial cell division

    PubMed Central

    Ghusinga, Khem Raj; Vargas-Garcia, Cesar A.; Singh, Abhyudai

    2016-01-01

    How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells add a fixed size (volume) from birth to division, irrespective of their size at birth. To mechanistically explain the adder principle, we consider a timekeeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that the noise in division timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distribution of the added volume when scaled by its mean becomes invariant of the growth rate. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for controlling size. PMID:27456660

  2. AIR POLLUTION, INFLAMMATION AND PRETERM BIRTH: A POTENTIAL MECHANISTIC LINK

    PubMed Central

    Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A.; Sánchez, Brisa N.; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G.; O´Neill, Marie S.

    2014-01-01

    Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. PMID:24382337

  3. Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of thymoquinone.

    PubMed

    Kundu, Juthika; Chun, Kyung-Soo; Aruoma, Okezie I; Kundu, Joydeb Kumar

    2014-10-01

    The bioactive natural products (plant secondary metabolites) are widely known to possess therapeutic value for the prevention and treatment of various chronic diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone; TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic pharmacological activities including antioxidant, anti-inflammatory, antidiabetic and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of animal models and has been shown to arrest the growth of various cancer cells in culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity and oxidative damage of cellular macromolecules, attenuation of inflammation, induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor angiogenesis, and suppression of migration, invasion and metastasis of cancer cells. TQ shows synergistic and/or potentiating anticancer effects when combined with clinically used chemotherapeutic agents. At the molecular level, TQ targets various components of intracellular signaling pathways, particularly a variety of upstream kinases and transcription factors, which are aberrantly activated during the course of tumorigenesis.

  4. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems

    PubMed Central

    Lomnitz, Jason G.; Savageau, Michael A.

    2016-01-01

    An overarching goal in molecular biology is to gain an understanding of the mechanistic basis underlying biochemical systems. Success is critical if we are to predict effectively the outcome of drug treatments and the development of abnormal phenotypes. However, data from most experimental studies is typically noisy and sparse. This allows multiple potential mechanisms to account for experimental observations, and often devising experiments to test each is not feasible. Here, we introduce a novel strategy that discriminates among putative models based on their repertoire of qualitatively distinct phenotypes, without relying on knowledge of specific values for rate constants and binding constants. As an illustration, we apply this strategy to two synthetic gene circuits exhibiting anomalous behaviors. Our results show that the conventional models, based on their well-characterized components, cannot account for the experimental observations. We examine a total of 40 alternative hypotheses and show that only 5 have the potential to reproduce the experimental data, and one can do so with biologically relevant parameter values. PMID:27578053

  5. Mechanistic evaluation of virus clearance by depth filtration.

    PubMed

    Venkiteshwaran, Adith; Fogle, Jace; Patnaik, Purbasa; Kowle, Ron; Chen, Dayue

    2015-01-01

    Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence of systematic studies. It is generally believed that both electrostatic interactions and sized based mechanical entrapment contribute to virus clearance by depth filtration. In order to establish whether the effectiveness of virus clearance correlates with the charge characteristics of a given depth filter, a counter-ion displacement technique was employed to determine the ionic capacity for several depth filters. Two depth filters (Millipore B1HC and X0HC) with significant differences in ionic capacities were selected and evaluated for their ability to eliminate viruses. The high ionic capacity X0HC filter showed complete porcine parvovirus (PPV) clearance (eliminating the spiked viruses to below the limit of detection) under low conductivity conditions (≤2.5 mS/cm), achieving a log10 reduction factor (LRF) of > 4.8. On the other hand, the low ionic capacity B1HC filter achieved only ∼2.1-3.0 LRF of PPV clearance under the same conditions. These results indicate that parvovirus clearance by these two depth filters are mainly achieved via electrostatic interactions between the filters and PPV. When much larger xenotropic murine leukemia virus (XMuLV) was used as the model virus, complete retrovirus clearance was obtained under all conditions evaluated for both depth filters, suggesting the involvement of mechanisms other than just electrostatic interactions in XMuLV clearance.

  6. Simplified mechanistic models of gene regulation for analysis and design

    PubMed Central

    Hancock, Edward J.; Stan, Guy-Bart; Arpino, James A. J.; Papachristodoulou, Antonis

    2015-01-01

    Simplified mechanistic models of gene regulation are fundamental to systems biology and essential for synthetic biology. However, conventional simplified models typically have outputs that are not directly measurable and are based on assumptions that do not often hold under experimental conditions. To resolve these issues, we propose a ‘model reduction’ methodology and simplified kinetic models of total mRNA and total protein concentration, which link measurements, models and biochemical mechanisms. The proposed approach is based on assumptions that hold generally and include typical cases in systems and synthetic biology where conventional models do not hold. We use novel assumptions regarding the ‘speed of reactions’, which are required for the methodology to be consistent with experimental data. We also apply the methodology to propose simplified models of gene regulation in the presence of multiple protein binding sites, providing both biological insights and an illustration of the generality of the methodology. Lastly, we show that modelling total protein concentration allows us to address key questions on gene regulation, such as efficiency, burden, competition and modularity. PMID:26063825

  7. Mechanistic explanation, cognitive systems demarcation, and extended cognition.

    PubMed

    van Eck, Dingmar; Looren de Jong, Huib

    2016-10-01

    Approaches to the Internalism-Externalism controversy in the philosophy of mind often involve both (broadly) metaphysical and explanatory considerations. Whereas originally most emphasis seems to have been placed on metaphysical concerns, recently the explanation angle is getting more attention. Explanatory considerations promise to offer more neutral grounds for cognitive systems demarcation than (broadly) metaphysical ones. However, it has been argued that explanation-based approaches are incapable of determining the plausibility of internalist-based conceptions of cognition vis-à-vis externalist ones. On this perspective, improved metaphysics is the route along which to solve the Internalist-Externalist stalemate. In this paper we challenge this claim. Although we agree that explanation-orientated approaches have indeed so far failed to deliver solid means for cognitive system demarcation, we elaborate a more promising explanation-oriented framework to address this issue. We argue that the mutual manipulability account of constitutive relevance in mechanisms, extended with the criterion of 'fat-handedness', is capable of plausibly addressing the cognitive systems demarcation problem, and thus able to decide on the explanatory traction of Internalist vs. Externalist conceptions, on a case-by-case basis. Our analysis also highlights why some other recent mechanistic takes on the problem of cognitive systems demarcation have been unsuccessful. We illustrate our claims with a case on gestures and learning.

  8. A mechanistic physicochemical model of carbon dioxide transport in blood.

    PubMed

    O'Neill, David P; Robbins, Peter A

    2017-02-01

    A number of mathematical models have been produced that, given the Pco2 and Po2 of blood, will calculate the total concentrations for CO2 and O2 in blood. However, all these models contain at least some empirical features, and thus do not represent all of the underlying physicochemical processes in an entirely mechanistic manner. The aim of this study was to develop a physicochemical model of CO2 carriage by the blood to determine whether our understanding of the physical chemistry of the major chemical components of blood together with their interactions is sufficiently strong to predict the physiological properties of CO2 carriage by whole blood. Standard values are used for the ionic composition of the blood, the plasma albumin concentration, and the hemoglobin concentration. All Km values required for the model are taken from the literature. The distribution of bicarbonate, chloride, and H(+) ions across the red blood cell membrane follows that of a Gibbs-Donnan equilibrium. The system of equations that results is solved numerically using constraints for mass balance and electroneutrality. The model reproduces the phenomena associated with CO2 carriage, including the magnitude of the Haldane effect, very well. The structural nature of the model allows various hypothetical scenarios to be explored. Here we examine the effects of 1) removing the ability of hemoglobin to form carbamino compounds; 2) allowing a degree of Cl(-) binding to deoxygenated hemoglobin; and 3) removing the chloride (Hamburger) shift. The insights gained could not have been obtained from empirical models.

  9. Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME

    PubMed Central

    Yang, Zhen; Kulkarni, Kaustubh; Zhu, Wei; Hu, Ming

    2014-01-01

    Genistein, one of the most active natural flavonoids, exerts various biological effects including chemoprevention, antioxidation, antiproliferation and anticancer. More than 30 clinical trials of genistein with various disease indications have been conducted to evaluate its clinical efficacy. Based on many animals and human pharmacokinetic studies, it is well known that the most challenge issue for developing genistein as a chemoprevention agent is the low oral bioavailability, which may be the major reason relating to its ambiguous therapeutic effects and large interindividual variations in clinical trials. In order to better correlate pharmacokinetic to pharmacodynamics results in animals and clinical studies, an in-depth understanding of pharmacokinetic behavior of genistein and its ADME properties are needed. Numerous in vitro/in vivo ADME studies had been conducted to reveal the main factors contributing to the low oral bioavailability of genistein. Therefore, this review focuses on summarizing the most recent progress on mechanistic studies of genistein ADME and provides a systemic view of these processes to explain genistein pharmacokinetic behaviors in vivo. The better understanding of genistein ADME property may lead to development of proper strategy to improve genistein oral bioavailability via mechanism-based approaches. PMID:22583407

  10. Mechanistic insight into sonochemical biodiesel synthesis using heterogeneous base catalyst.

    PubMed

    Choudhury, Hanif A; Chakma, Sankar; Moholkar, Vijayanand S

    2014-01-01

    The beneficial effect of ultrasound on transesterification reaction is well known. Heterogeneous (or solid) catalysts for biodiesel synthesis have merit that they do not contaminate the byproduct of glycerol. In this paper, we have attempted to identify the mechanistic features of ultrasound-enhanced biodiesel synthesis with the base-catalyst of CaO. A statistical design of experiments (Box-Behnken) was used to identify the influence of temperature, alcohol to oil molar ratio and catalyst loading on transesterification yield. The optimum values of these parameters for the highest yield were identified through Response Surface Method (with a quadratic model) and ANOVA. These values are: temperature=62 °C, molar ratio=10:1 and catalyst loading=6 wt.%. The activation energy was determined as 82.3 kJ/mol, which is higher than that for homogeneous catalyzed system (for both acidic and basic catalyst). The experimental results have been analyzed vis-à-vis simulations of cavitation bubble dynamics. Due to 3-phase heterogeneity of the system, the yield was dominated by intrinsic kinetics, and the optimum temperature for the highest yield was close to boiling point of methanol. At this temperature, the influence of cavitation bubbles (in terms of both sonochemical and sonophysical effect) is negligible, and ultrasonic micro-streaming provided necessary convection in the system. The influence of all parameters on the reaction system was found to be strongly inter-dependent.

  11. Refined pipe theory for mechanistic modeling of wood development.

    PubMed

    Deckmyn, Gaby; Evans, Sam P; Randle, Tim J

    2006-06-01

    We present a mechanistic model of wood tissue development in response to changes in competition, management and climate. The model is based on a refinement of the pipe theory, where the constant ratio between sapwood and leaf area (pipe theory) is replaced by a ratio between pipe conductivity and leaf area. Simulated pipe conductivity changes with age, stand density and climate in response to changes in allocation or pipe radius, or both. The central equation of the model, which calculates the ratio of carbon (C) allocated to leaves and pipes, can be parameterized to describe the contrasting stem conductivity behavior of different tree species: from constant stem conductivity (functional homeostasis hypothesis) to height-related reduction in stem conductivity with age (hydraulic limitation hypothesis). The model simulates the daily growth of pipes (vessels or tracheids), fibers and parenchyma as well as vessel size and simulates the wood density profile and the earlywood to latewood ratio from these data. Initial runs indicate the model yields realistic seasonal changes in pipe radius (decreasing pipe radius from spring to autumn) and wood density, as well as realistic differences associated with the competitive status of trees (denser wood in suppressed trees).

  12. MECHANISTIC AND BIOLOGICAL ASPECTS OF HELICASE ACTION ON DAMAGED DNA

    PubMed Central

    Suhasini, Avvaru N.; Brosh, Robert M.

    2010-01-01

    Helicases catalytically unwind structured nucleic acids in a nucleoside-triphosphate-dependent and directionally specific manner, and are essential for virtually all aspects of nucleic acid metabolism. ATPase-driven helicases which translocate along nucleic acids play a role in damage recognition or unwinding of a DNA tract containing the lesion. Although classical biochemical experiments provided evidence that bulky covalent adducts inhibit DNA unwinding catalyzed by certain DNA helicases in a strand-specific manner (i.e. , block to DNA unwinding restricted to adduct residence in the strand the helicase translocates), recent studies suggest more complex arrangements that may depend on the helicase under study, its assembly in a protein complex, and the type of structural DNA perturbation. Moreover, base and sugar phosphate backbone modifications exert effects on DNA helicases that suggest specialized tracking mechanisms. As a component of the replication stress response, the single-stranded DNA binding protein Replication Protein A (RPA) may serve to enable eukaryotic DNA helicases to overcome certain base lesions. Helicases play important roles in DNA damage signaling which also involve their partnership with RPA. In this review, we will discuss our current understanding of mechanistic and biological aspects of helicase action on damaged DNA. PMID:20574162

  13. Mechanistic solutions to the opening of the Gulf of Mexico

    USGS Publications Warehouse

    Schouten, Hans; Klitgord, Kim D.

    1994-01-01

    Two mechanistic models-which are unlike the traditional plate-tectonic landfill models used for most proposed Pangea reconstructions of the Yucatán block-relate the Mesozoic opening of the Gulf of Mexico directly to the movement of the North and South American plates: (1) a previous piggyback model in which Yucatán moves with South America out of the western gulf and (2) a new edge-driven model in which the motion of the Yucatán block is caused by forces applied to its margins by the movement of the North and South American plates. In the second model, Yucatán moves out of the northern Gulf of Mexico as a gear or roller bearing. On the basis of magnetic edge anomalies around the gulf, this edge-driven model predicts that from the Bathonian to Tithonian (~170 to ~50 Ma), Yucatán was rotated ~60° counterclockwise as a rigid block between North and South America with rift propagation and extension occurring simultaneously in the Gulf of Mexico and Yucatán Basin.

  14. Mechanistic modeling of aberrant energy metabolism in human disease

    PubMed Central

    Sangar, Vineet; Eddy, James A.; Simeonidis, Evangelos; Price, Nathan D.

    2012-01-01

    Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based (CB) models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell. PMID:23112774

  15. Neutron structure and mechanistic studies of diisopropyl fluorophosphatase (DFPase)

    SciTech Connect

    Chen, Julian C.-H.; Mustyakimov, Marat; Schoenborn, Benno P.; Langan, Paul; Blum, Marc-Michael

    2010-11-01

    The structure and mechanism of diisopropyl fluorophosphatase (DFPase) have been studied using a variety of methods, including isotopic labelling, X-ray crystallography and neutron crystallography. The neutron structure of DFPase, mechanistic studies and subsequent rational design efforts are described. Diisopropyl fluorophosphatase (DFPase) is a calcium-dependent phosphotriesterase that acts on a variety of highly toxic organophosphorus compounds that act as inhibitors of acetylcholinesterase. The mechanism of DFPase has been probed using a variety of methods, including isotopic labelling, which demonstrated the presence of a phosphoenzyme intermediate in the reaction mechanism. In order to further elucidate the mechanism of DFPase and to ascertain the protonation states of the residues and solvent molecules in the active site, the neutron structure of DFPase was solved at 2.2 Å resolution. The proposed nucleophile Asp229 is deprotonated, while the active-site solvent molecule W33 was identified as water and not hydroxide. These data support a mechanism involving direct nucleophilic attack by Asp229 on the substrate and rule out a mechanism involving metal-assisted water activation. These data also allowed for the re-engineering of DFPase through rational design to bind and productively orient the more toxic S{sub P} stereoisomers of the nerve agents sarin and cyclosarin, creating a modified enzyme with enhanced overall activity and significantly increased detoxification properties.

  16. Mechanistic modelling of the drying behaviour of single pharmaceutical granules.

    PubMed

    Mortier, Séverine Thérèse F C; De Beer, Thomas; Gernaey, Krist V; Vercruysse, Jurgen; Fonteyne, Margot; Remon, Jean Paul; Vervaet, Chris; Nopens, Ingmar

    2012-04-01

    The trend to move towards continuous production processes in pharmaceutical applications enhances the necessity to develop mechanistic models to understand and control these processes. This work focuses on the drying behaviour of a single wet granule before tabletting, using a six-segmented fluidised bed drying system, which is part of a fully continuous from-powder-to-tablet manufacturing line. The drying model is based on a model described by Mezhericher et al. and consists of two submodels. In the first drying phase (submodel 1), the surface water evaporates, while in the second drying phase (submodel 2), the water inside the granule evaporates. The second submodel contains an empirical power coefficient, β. A sensitivity analysis was performed to study the influence of parameters on the moisture content of single pharmaceutical granules, which clearly points towards the importance of β on the drying behaviour. Experimental data with the six-segmented fluidised bed dryer were collected to calibrate β. An exponential dependence on the drying air temperature was found. Independent experiments were done for the validation of the drying model.

  17. Mechanistic understanding of monosaccharide-air flow battery electrochemistry

    NASA Astrophysics Data System (ADS)

    Scott, Daniel M.; Tsang, Tsz Ho; Chetty, Leticia; Aloi, Sekotilani; Liaw, Bor Yann

    Recently, an inexpensive monosaccharide-air flow battery configuration has been demonstrated to utilize a strong base and a mediator redox dye to harness electrical power from the partial oxidation of glucose. Here the mechanistic understanding of glucose oxidation in this unique glucose-air power source is further explored by acid-base titration experiments, 13C NMR, and comparison of results from chemically different redox mediators (indigo carmine vs. methyl viologen) and sugars (fructose vs. glucose) via studies using electrochemical techniques. Titration results indicate that gluconic acid is the main product of the cell reaction, as supported by evidence in the 13C NMR spectra. Using indigo carmine as the mediator dye and fructose as the energy source, an abiotic cell configuration generates a power density of 1.66 mW cm -2, which is greater than that produced from glucose under similar conditions (ca. 1.28 mW cm -2). A faster transition from fructose into the ene-diol intermediate than from glucose likely contributed to this difference in power density.

  18. Mechanistic Enzymology of the Radical SAM Enzyme DesII.

    PubMed

    Ruszczycky, Mark W; Liu, Hung-Wen

    2015-04-01

    DesII is a member of the radical SAM family of enzymes that catalyzes radical-mediated transformations of TDP-4-amino-4,6-didexoy-D-glucose as well as other sugar nucleotide diphosphates. Like nearly all radical SAM enzymes, the reactions begin with the reductive homolysis of SAM to produce a 5'-deoxyadenosyl radical which is followed by regiospecific hydrogen atom abstraction from the substrate. What happens next, however, depends on the nature of the substrate radical so produced. In the case of the biosynthetically relevant substrate, a radical-mediated deamination ensues; however, when this amino group is replaced with a hydroxyl, one instead observes dehydrogenation. The factors that govern the fate of the initially generated substrate radical as well as the mechanistic details underlying these transformations have been a key focus of research into the chemistry of DesII. This review will discuss recent discoveries pertaining to the enzymology of DesII, how it may relate to understanding other radical-mediated lyases and dehydrogenases and the working hypotheses currently being investigated regarding the mechanism of DesII catalysis.

  19. A mechanistic stochastic framework for regulating bacterial cell division.

    PubMed

    Ghusinga, Khem Raj; Vargas-Garcia, Cesar A; Singh, Abhyudai

    2016-07-26

    How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells add a fixed size (volume) from birth to division, irrespective of their size at birth. To mechanistically explain the adder principle, we consider a timekeeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that the noise in division timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distribution of the added volume when scaled by its mean becomes invariant of the growth rate. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for controlling size.

  20. Anti-fibro-hepatocarcinogenic Chinese herbal medicines: A mechanistic overview

    PubMed Central

    Boye, Alex; Yang, Yan; Asenso, James; Wei, Wei

    2016-01-01

    Chinese herbal medicine (CHM) is an integral component of complementary/alternative medicine and it is increasingly becoming the preferred therapeutic modality for the treatment of liver fibrosis and hepatocellular carcinoma (HCC) worldwide. Accordingly, the World Health Organization (WHO) has attested to the popularity and efficacy of indigenous herbal therapies including CHM as a first line of treatment for some diseases including liver disorders. However, the WHO and drug discovery experts have always recommended that use of indigenous herbal remedies must go hand-in-hand with the requisite mechanistic elucidation so as to constitute a system of verification of efficacy within the ethnobotanical context of use. Although many CHM experts have advanced knowledge on CHM, nonetheless, more enlightenment is needed, particularly mechanisms of action of CHMs on fibro-hepato-carcinogenesis. We, herein, provide in-depth mechanisms of the action of CHMs which have demonstrated anti-fibro-hepatocarcinogenic effects, in pre-clinical and clinical studies as published in PubMed and other major scientific databases. Specifically, the review brings out the important signaling pathways, and their downstream targets which are modulated at multi-level by various anti-fibro-hepatocarcinogenic CHMs. PMID:27366355

  1. Mechanistic rationales for targeting interleukin-17A in spondyloarthritis.

    PubMed

    Raychaudhuri, Siba P; Raychaudhuri, Smriti K

    2017-03-08

    The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis. Clinical evidence for the efficacy of IL-17A inhibition by biologic agents was initially shown in patients with chronic plaque psoriasis, another autoimmune disease mediated by the IL-17 pathway. Subsequently, similar positive efficacy for inhibition of IL-17A was seen in patients with ankylosing spondylitis and psoriatic arthritis. Inhibition of IL-17A may also improve cardiovascular and metabolic comorbidities often found in patients with SpA because studies have linked these disorders to the IL-17 pathway. In this review, we will examine key preclinical studies that demonstrated the mechanistic role of IL-17A in the development SpA and discuss how these observations were translated into clinical practice.

  2. Mechanistic Investigation on ROS Resistance of Phosphorothioated DNA

    PubMed Central

    Wu, Tingting; Huang, Qiang; Wang, Xiao-Lei; Shi, Ting; Bai, Linquan; Liang, Jingdan; Wang, Zhijun; Deng, Zixin; Zhao, Yi-Lei

    2017-01-01

    Phosphorothioated DNA (PT-DNA) exhibits a mild anti-oxidant property both in vivo and in vitro. It was found that 8-OHdG and ROS levels were significantly lower in dnd+ (i.e. S+) E. coli., compared to a dnd− (i.e. S−) strain. Furthermore, different from traditional antioxidants, phosphorothioate compound presents an unexpectedly high capacity to quench hydroxyl radical. Oxidative product analysis by liquid chromatography-mass spectrometry and quantum mechanistic computation supported its unique anti-oxidant characteristic of the hydroxyl selectivity: phosphorothioate donates an electron to either hydroxyl radical or guanine radical derived from hydroxyl radical, leading to a PS• radical; a complex of PS• radical and OH− (i.e. the reductive product of hydroxyl radical) releases a highly reductive HS• radical, which scavenges more equivalents of oxidants in the way to high-covalent sulphur compounds such as sulphur, sulphite and sulphate. The PS-PO conversion (PS and PO denote phosphorus-sulphur and phosphorus-oxygen compounds, respectively) made a switch of extremely oxidative OH• to highly reductive HS• species, endowing PT-DNA with the observed high capacity in hydroxyl-radical neutralization. This plausible mechanism provides partial rationale as to why bacteria develop the resource-demanding PT modification on guanine-neighboring phosphates in genome. PMID:28216673

  3. Mechanistic modeling of broth temperature in outdoor photobioreactors.

    PubMed

    Béchet, Quentin; Shilton, Andy; Fringer, Oliver B; Muñoz, Raul; Guieysse, Benoit

    2010-03-15

    This study presents the first mechanistic model describing broth temperature in column photobioreactors as a function of static (location, reactor geometry) and dynamic (light irradiance, air temperature, wind velocity) parameters. Based on a heat balance on the liquid phase the model predicted temperature in a pneumatically agitated column photobioreactor (1 m(2) illuminated area, 0.19 m internal diameter, 50 L gas-free cultivation broth) operated outdoor in Singapore to an accuracy of 2.4 °C at the 95% confidence interval over the entire data set used (104 measurements from 7 different batches). Solar radiation (0 to 200 W) and air convection (-30 to 50 W)were the main contributors to broth temperature change. The model predicted broth temperature above 40 °C will be reached during summer months in the same photobioreactor operated in California, a value well over the maximum temperature tolerated by most commercial algae species. Accordingly, 18,000 and 5500 GJ year(-1) ha(-1) of heat energy must be removed to maintain broth temperature at or below 25 and 35 °C, respectively, assuming a reactor density of one reactor per square meter. Clearly, the significant issue of temperature control must be addressed when evaluating the technical feasibility, costs, and sustainability of large-scale algae production.

  4. Circadian rhythms and addiction: mechanistic insights and future directions.

    PubMed

    Logan, Ryan W; Williams, Wilbur P; McClung, Colleen A

    2014-06-01

    Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug-induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction.

  5. A brief review of exercise, bipolar disorder, and mechanistic pathways

    PubMed Central

    Thomson, Daniel; Turner, Alyna; Lauder, Sue; Gigler, Margaret E.; Berk, Lesley; Singh, Ajeet B.; Pasco, Julie A.; Berk, Michael; Sylvia, Louisa

    2015-01-01

    Despite evidence that exercise has been found to be effective in the treatment of depression, it is unclear whether these data can be extrapolated to bipolar disorder. Available evidence for bipolar disorder is scant, with no existing randomized controlled trials having tested the impact of exercise on depressive, manic or hypomanic symptomatology. Although exercise is often recommended in bipolar disorder, this is based on extrapolation from the unipolar literature, theory and clinical expertise and not empirical evidence. In addition, there are currently no available empirical data on program variables, with practical implications on frequency, intensity and type of exercise derived from unipolar depression studies. The aim of the current paper is to explore the relationship between exercise and bipolar disorder and potential mechanistic pathways. Given the high rate of medical co-morbidities experienced by people with bipolar disorder, it is possible that exercise is a potentially useful and important intervention with regard to general health benefits; however, further research is required to elucidate the impact of exercise on mood symptomology. PMID:25788889

  6. Early Mechanistic Events in Biotin Dissociation from Streptavidin

    SciTech Connect

    Hyre, D. E.

    2002-01-01

    The streptavidin-biotin system has provided a unique opportunity to investigate the molecular details of ligand dissociation pathways. An underlying mechanistic question is whether ligand dissociation proceeds with a relatively ordered process of bond breaking and ligand escape. Here we report a joint computational and crystallographic study of the earliest events in biotin dissociation. In molecular dynamics potential of mean force simulations, a water molecule from a defined access channel intercalated into the hydrogen bond between Asp 128 and biotin, bridging them and stabilizing an intermediate state. In forced biotin dissociation simulations, this event led to subsequent bond breaking steps and ligand escape. In equilibrium simulations, the water molecule was sometimes observed to move back to the access channel with re-formation of the biotin hydrogen bond. Analysis of streptavidin crystal structures revealed a close overlap of crystallographically defined and simulated waters in the water access channel. These results suggest that biotin dissociation is initiated by stochastic coupling of water entry with lengthening of a specific biotin hydrogen-bonding interaction.

  7. Warming will affect phytoplankton differently: evidence through a mechanistic approach.

    PubMed

    Huertas, I Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo

    2011-12-07

    Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario.

  8. Equation-free mechanistic ecosystem forecasting using empirical dynamic modeling

    PubMed Central

    Ye, Hao; Beamish, Richard J.; Glaser, Sarah M.; Grant, Sue C. H.; Hsieh, Chih-hao; Richards, Laura J.; Schnute, Jon T.; Sugihara, George

    2015-01-01

    It is well known that current equilibrium-based models fall short as predictive descriptions of natural ecosystems, and particularly of fisheries systems that exhibit nonlinear dynamics. For example, model parameters assumed to be fixed constants may actually vary in time, models may fit well to existing data but lack out-of-sample predictive skill, and key driving variables may be misidentified due to transient (mirage) correlations that are common in nonlinear systems. With these frailties, it is somewhat surprising that static equilibrium models continue to be widely used. Here, we examine empirical dynamic modeling (EDM) as an alternative to imposed model equations and that accommodates both nonequilibrium dynamics and nonlinearity. Using time series from nine stocks of sockeye salmon (Oncorhynchus nerka) from the Fraser River system in British Columbia, Canada, we perform, for the the first time to our knowledge, real-data comparison of contemporary fisheries models with equivalent EDM formulations that explicitly use spawning stock and environmental variables to forecast recruitment. We find that EDM models produce more accurate and precise forecasts, and unlike extensions of the classic Ricker spawner–recruit equation, they show significant improvements when environmental factors are included. Our analysis demonstrates the strategic utility of EDM for incorporating environmental influences into fisheries forecasts and, more generally, for providing insight into how environmental factors can operate in forecast models, thus paving the way for equation-free mechanistic forecasting to be applied in management contexts. PMID:25733874

  9. Mechanistic studies of malonic acid-mediated in situ acylation.

    PubMed

    Chandra, Koushik; Naoum, Johnny N; Roy, Tapta Kanchan; Gilon, Chaim; Gerber, R Benny; Friedler, Assaf

    2015-09-01

    We have previously introduced an easy to perform, cost-effective and highly efficient acetylation technique for solid phase synthesis (SPPS). Malonic acid is used as a precursor and the reaction proceeds via a reactive ketene that acetylates the target amine. Here we present a detailed mechanistic study of the malonic acid-mediated acylation. The influence of reaction conditions, peptide sequence and reagents was systematically studied. Our results show that the methodology can be successfully applied to different types of peptides and nonpeptidic molecules irrespective of their structure, sequence, or conformation. Using alkyl, phenyl, and benzyl malonic acid, we synthesized various acyl peptides with almost quantitative yields. The ketenes obtained from the different malonic acid derived precursors were characterized by in situ (1) H-NMR. The reaction proceeded in short reaction times and resulted in excellent yields when using uronium-based coupling agents, DIPEA as a base, DMF/DMSO/NMP as solvents, Rink amide/Wang/Merrifield resins, temperature of 20°C, pH 8-12 and 5 min preactivation at inert atmosphere. The reaction was unaffected by Lewis acids, transition metal ions, surfactants, or salt. DFT studies support the kinetically favorable concerted mechanism for CO2 and ketene formation that leads to the thermodynamically stable acylated products. We conclude that the malonic acid-mediated acylation is a general method applicable to various target molecules.

  10. A global scale mechanistic model of the photosynthetic capacity

    NASA Astrophysics Data System (ADS)

    Ali, A. A.; Xu, C.; Rogers, A.; Fisher, R. A.; Wullschleger, S. D.; McDowell, N. G.; Massoud, E. C.; Vrugt, J. A.; Muss, J. D.; Fisher, J. B.; Reich, P. B.; Wilson, C. J.

    2015-08-01

    Although plant photosynthetic capacity as determined by the maximum carboxylation rate (i.e., Vc, max25) and the maximum electron transport rate (i.e., Jmax25) at a reference temperature (generally 25 °C) is known to vary substantially in space and time in response to environmental conditions, it is typically parameterized in Earth system models (ESMs) with tabulated values associated to plant functional types. In this study, we developed a mechanistic model of leaf utilization of nitrogen for assimilation (LUNA V1.0) to predict the photosynthetic capacity at the global scale under different environmental conditions, based on the optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The LUNA model was able to reasonably well capture the observed patterns of photosynthetic capacity in view that it explained approximately 55 % of the variation in observed Vc, max25 and 65 % of the variation in observed Jmax25 across the globe. Our model simulations under current and future climate conditions indicated that Vc, max25 could be most affected in high-latitude regions under a warming climate and that ESMs using a fixed Vc, max25 or Jmax25 by plant functional types were likely to substantially overestimate future global photosynthesis.

  11. A global scale mechanistic model of the photosynthetic capacity

    NASA Astrophysics Data System (ADS)

    Xu, C.; Ali, A. A.; Fisher, R.; Wullschleger, S. D.; Rogers, A.; McDowell, N. G.; Wilson, C. J.

    2015-12-01

    Although plant photosynthetic capacity as determined by the maximum carboxylation rate (i.e., Vc,max25) and the maximum electron transport rate (i.e., Jmax25) at a reference temperature (generally 25oC) is known to vary substantially in space and time in response to environmental conditions, it is typically parameterized in Earth system models (ESMs) with tabulated values associated to plant functional types. In this study, we developed a mechanistic model of leaf utilization of nitrogen for assimilation (LUNA V1.0) to predict the photosynthetic capacity at the global scale under different environmental conditions, based on the optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The LUNA model was able to reasonably well capture the observed patterns of photosynthetic capacity in view that it explained approximately 55% of the variation in observed Vc,max25 and 65% of the variation in observed Jmax25 across the globe. Our model simulations under current and future climate conditions indicated that Vc,max25 could be most affected in high-latitude regions under a warming climate and that ESMs using a fixed Vc,max25 or Jmax25 by plant functional types were likely to substantially overestimate future global photosynthesis.

  12. A windows based mechanistic subsidence prediction model for longwall mining

    SciTech Connect

    Begley, R.; Beheler, P.; Khair, A.W.

    1996-12-31

    The previously developed Mechanistic Subsidence Prediction Model (MSPM) has been incorporated into the graphical interface environment of MS Windows. MSPM has the unique capability of predicting maximum subsidence, angle of draw and the subsidence profile of a longwall panel at various locations for both the transverse and longitudinal orientations. The resultant enhanced model can be operated by individuals with little knowledge of subsidence prediction theories or little computer programming experience. In addition, predictions of subsidence can be made in a matter of seconds without the need to develop input data files or use the keyboard in some cases. The predictions are based upon the following input parameters: panel width, mining height, overburden depth, rock quality designation, and percent hard rock in the immediate roof, main roof and the entire overburden. The recently developed enhanced model has the capability to compare predictions in a graphical format for one half of the predicted subsidence profile based upon changes in input parameters easily and instantly on the same screen. In addition another screen can be obtained from a pull down menu where the operator can compare predictions for the entire subsidence profiles. This paper presents the background of the subsidence prediction model and the methodology of the enhanced model development. The paper also presents comparisons of subsidence predictions for several different sets of input parameters in addition to comparisons of the subsidence predictions with actual field data.

  13. Mechanistic insights into acyclovir-polyethylene glycol 20000 binary dispersions

    PubMed Central

    Venkateskumar, Krishnamoorthy; Parasuraman, Subramani; Gunasunderi, Raju; Sureshkumar, Krishnan; Nayak, M. Muralidhar; Shah, Syed Adnan Ali; Kassen, Khoo; Kai, Heng Wei

    2016-01-01

    Objective: The objective of this study is to provide a mechanistic insight into solubility enhancement and dissolution of acyclovir (ACY) by polyethylene glycol20000 (PEG20000). Materials and Methods: Solid dispersions with differing ratios of drug (ACY) and carrier (PEG20000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was also done by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR) analysis and surface morphology was assessed by Polarizing Microscopic Image (PMI) analysis, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR) analysis. Results: Thermodynamic parameters proved the solubilization effect of carrier. The aqueous solubility and dissolution of ACY were increased in all samples. Formation of solid solution, crystallinity reduction, and absence of interaction between drug and carrier was proved by XRD, DSC, and FTIR analysis. The particle size reduction and change in surface morphology were confirmed by SEM and AFM and analysis. The permeation coefficient and amount of drug diffused was higher in samples as compared to ACY. The stability was high in dispersions, and it was proved by NMR analysis. Conclusion: The mechanical insights into the enhancement of solubility and dissolution could be used as a platform to improve the aqueous solubility for other poor water soluble drugs. PMID:28123988

  14. Mechanistic aspects of photooxidation of polyhydroxylated molecules on metal oxides.

    SciTech Connect

    Shkrob, I. A.; Marin, T. M.; Sevilla, M. D.; Chemerisov, S.

    2011-03-24

    Polyhydroxylated molecules, including natural carbohydrates, are known to undergo photooxidation on wide-gap transition-metal oxides irradiated by ultraviolet light. In this study, we examine mechanistic aspects of this photoreaction on aqueous TiO{sub 2}, {alpha}-FeOOH, and {alpha}-Fe{sub 2}O{sub 3} particles using electron paramagnetic resonance (EPR) spectroscopy and site-selective deuteration. We demonstrate that the carbohydrates are oxidized at sites involved in the formation of oxo bridges between the chemisorbed carbohydrate molecule and metal ions at the oxide surface. This bridging inhibits the loss of water (which is the typical reaction of the analogous free radicals in bulk solvent) promoting instead a rearrangement that leads to elimination of the formyl radical. For natural carbohydrates, the latter reaction mainly involves carbon-1, whereas the main radical products of the oxidation are radical arising from H atom loss centered on carbon-1, -2, and -3 sites. Photoexcited TiO{sub 2} oxidizes all of the carbohydrates and polyols, whereas {alpha}-FeOOH oxidizes some of the carbohydrates, and {alpha}-Fe{sub 2}O{sub 3} is unreactive. These results serve as a stepping stone for understanding the photochemistry on mineral surfaces of more complex biomolecules such as nucleic acids.

  15. Mechanistic Differences Leading to Infectious and Sterile Inflammation.

    PubMed

    Behnia, Faranak; Sheller, Samantha; Menon, Ramkumar

    2016-05-01

    Inflammation is a physiologic component of pregnancy and parturition. Overwhelming intrauterine inflammatory load promotes quiescent feto-maternal tissues into a contractile phenotype. Like inflammation, oxidative stress is an inevitable component of both pregnancy and parturition. Pathologic activation of host innate immune response to adverse pregnancy conditions can lead to premature activation of inflammatory and oxidative stress. Inflammation and oxidative stress markers seen with both sterile and infectious inflammation are often similar; therefore, it is difficult to understand causality of conditions like spontaneous preterm birth. This review demonstrates potential mechanistic pathways of activation of sterile and infectious inflammation. We demonstrate the activation of two unique pathways of inflammation by factors that are well-documented proxies for oxidative stress (cigarette smoke extract) and infection (lipopolysaccharide). Sterile inflammation seen after exposure to an oxidative stress inducer is due to cellular elemental damage resulting in p38 mitogen-activated protein kinase (MAPK) induced cellular senescence. Infectious inflammation is through activation of transcription factor NF-κB and independent of oxidative stress-associated damages and p38 MAPK-induced senescence. Understanding the differences in the inflammatory pathway activation by various risk factors is important to design better screening, diagnostic and intervention strategies to reduce the risks of adverse pregnancy outcomes.

  16. Physical activity and its mechanistic effects on prostate cancer.

    PubMed

    Wekesa, A; Harrison, M; Watson, R W

    2015-09-01

    Beneficial effects of physical activity have been illustrated in numerous aspects of health. With the increasing incidence of prostate cancer and changes in physical activity of men, understanding the link between the two has important implications for changing this cancer burden. Both positive and negative associations between physical activity and prostate cancer have been previously demonstrated in observational epidemiological studies. Elucidating the biological mechanisms would lead to a better understanding of how physical activity influences the progression of prostate cancer. This review was undertaken to: (1) identify evidence in literature that demonstrates the effects of physical activity on skeletal muscle secretomes, (2) indicate the plausible signaling pathways these proteins might activate, and (3) identify evidence in literature that demonstrates the roles of the signaling pathways in prostate cancer progression and regression. We also discuss proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer. We discuss proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity. We further identify future directions for research, including a better understanding of the biological mechanisms, the need to standardize physical activity and identify mechanistic end points of physical activity that can then be correlated with outcomes.

  17. Mechanistic modeling of destratification in cryogenic storage tanks using ultrasonics.

    PubMed

    Jagannathan, T K; Mohanan, Srijith; Nagarajan, R

    2014-01-01

    Stratification is one of the main causes for vaporization of cryogens and increase of tank pressure during cryogenic storage. This leads subsequent problems such as cavitation in cryo-pumps, reduced length of storage time. Hence, it is vital to prevent stratification to improve the cost efficiency of storage systems. If stratified layers exist inside the tank, they have to be removed by suitable methods without venting the vapor. Sonication is one such method capable of keeping fluid layers mixed. In the present work, a mechanistic model for ultrasonic destratification is proposed and validated with destratification experiments done in water. Then, the same model is used to predict the destratification characteristics of cryogenic liquids such as liquid nitrogen (LN₂), liquid hydrogen (LH₂) and liquid ammonia (LNH₃). The destratification parameters are analysed for different frequencies of ultrasound and storage pressures by considering continuous and pulsed modes of ultrasonic operation. From the results, it is determined that use of high frequency ultrasound (low-power/continuous; high-power/pulsing) or low frequency ultrasound (continuous operation with moderate power) can both be effective in removing stratification.

  18. Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse.

    PubMed

    Agarwal, Vinayak; Miles, Zachary D; Winter, Jaclyn M; Eustáquio, Alessandra S; El Gamal, Abrahim A; Moore, Bradley S

    2017-01-20

    Naturally produced halogenated compounds are ubiquitous across all domains of life where they perform a multitude of biological functions and adopt a diversity of chemical structures. Accordingly, a diverse collection of enzyme catalysts to install and remove halogens from organic scaffolds has evolved in nature. Accounting for the different chemical properties of the four halogen atoms (fluorine, chlorine, bromine, and iodine) and the diversity and chemical reactivity of their organic substrates, enzymes performing biosynthetic and degradative halogenation chemistry utilize numerous mechanistic strategies involving oxidation, reduction, and substitution. Biosynthetic halogenation reactions range from simple aromatic substitutions to stereoselective C-H functionalizations on remote carbon centers and can initiate the formation of simple to complex ring structures. Dehalogenating enzymes, on the other hand, are best known for removing halogen atoms from man-made organohalogens, yet also function naturally, albeit rarely, in metabolic pathways. This review details the scope and mechanism of nature's halogenation and dehalogenation enzymatic strategies, highlights gaps in our understanding, and posits where new advances in the field might arise in the near future.

  19. A Mechanistic Link between Olfaction and Autism Spectrum Disorder.

    PubMed

    Rozenkrantz, Liron; Zachor, Ditza; Heller, Iris; Plotkin, Anton; Weissbrod, Aharon; Snitz, Kobi; Secundo, Lavi; Sobel, Noam

    2015-07-20

    Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD). However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication, remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children--18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = -0.75, p < 0.001), specifically with social (r = -0.72, p < 0.001), but not motor (r < -0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities.

  20. Warming will affect phytoplankton differently: evidence through a mechanistic approach

    PubMed Central

    Huertas, I. Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo

    2011-01-01

    Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario. PMID:21508031

  1. Air pollution, inflammation and preterm birth: a potential mechanistic link.

    PubMed

    Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A; Sánchez, Brisa N; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G; O'Neill, Marie S

    2014-02-01

    Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth.

  2. Mechanistic investigation of beta-galactosidase-activated MR contrast agents.

    PubMed

    Urbanczyk-Pearson, Lauren M; Femia, Frank J; Smith, Jeffrey; Parigi, Giacomo; Duimstra, Joseph A; Eckermann, Amanda L; Luchinat, Claudio; Meade, Thomas J

    2008-01-07

    We report a mechanistic investigation of an isomeric series of beta-galactosidase-activated magnetic resonance contrast agents. Our strategy focuses on the synthesis of macrocyclic caged-complexes that coordinatively saturate a chelated lanthanide. Enzyme cleavage of the complex results in an open coordination site available for water that creates a detectable MR contrast agent. The complexes consist of a DO3A Gd(III) chelator modified with a galactopyranose at the N-10 position of the macrocycle. We observed significant differences in relaxometric properties and coordination geometry that can be correlated to subtle variations of the linker between the macrocycle and the galactopyranose. After synthesis and purification of the R, S, and racemic mixtures of complexes 1 and 3 and measurement of the hydration number, water residence lifetime, and longitudinal relaxation rates, we propose mechanisms for water exclusion from the lanthanide in the precleavage state. While the stereochemistry of the linker does not influence the agents' properties, the mechanism of water exclusion for each isomer is significantly influenced by the position of modification. Data for one series with a methyl group substituted on the sugar-macrocycle linker at the alpha-position suggests a steric mechanism where the galactopyranose sugar blocks water from the Gd(III) center. In contrast, our observations for a second series with methyl substitution at the beta position of the sugar-macrocycle linker are consistent with a mechanism in which a bidentate anion occupies two available coordination sites of Gd(III) in the precleavage state.

  3. Environmental perception and epigenetic memory: mechanistic insight through FLC

    PubMed Central

    Berry, Scott; Dean, Caroline

    2015-01-01

    Chromatin plays a central role in orchestrating gene regulation at the transcriptional level. However, our understanding of how chromatin states are altered in response to environmental and developmental cues, and then maintained epigenetically over many cell divisions, remains poor. The floral repressor gene FLOWERING LOCUS C (FLC) in Arabidopsis thaliana is a useful system to address these questions. FLC is transcriptionally repressed during exposure to cold temperatures, allowing studies of how environmental conditions alter expression states at the chromatin level. FLC repression is also epigenetically maintained during subsequent development in warm conditions, so that exposure to cold may be remembered. This memory depends on molecular complexes that are highly conserved among eukaryotes, making FLC not only interesting as a paradigm for understanding biological decision-making in plants, but also an important system for elucidating chromatin-based gene regulation more generally. In this review, we summarize our understanding of how cold temperature induces a switch in the FLC chromatin state, and how this state is epigenetically remembered. We also discuss how the epigenetic state of FLC is reprogrammed in the seed to ensure a requirement for cold exposure in the next generation. Significance Statement FLOWERING LOCUS C (FLC) regulation provides a paradigm for understanding how chromatin can be modulated to determine gene expression in a developmental context. This review describes our current mechanistic understanding of how FLC expression is genetically specified and epigenetically regulated throughout the plant life cycle, and how this determines plant life-history strategy. PMID:25929799

  4. 78 FR 56583 - Deposit Insurance Regulations; Definition of Insured Deposit

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ... Part 330 RIN 3064-AE00 Deposit Insurance Regulations; Definition of Insured Deposit AGENCY: Federal...)(1), 12 U.S.C. 1821(f)(1). A. Definition of ``Deposit'' The term ``deposit'' is defined in section 3... between domestic and foreign deposits. The current statutory definition of ``deposit'' under section...

  5. Airfoil deposition model

    NASA Technical Reports Server (NTRS)

    Kohl, F. J.

    1982-01-01

    The methodology to predict deposit evolution (deposition rate and subsequent flow of liquid deposits) as a function of fuel and air impurity content and relevant aerodynamic parameters for turbine airfoils is developed in this research. The spectrum of deposition conditions encountered in gas turbine operations includes the mechanisms of vapor deposition, small particle deposition with thermophoresis, and larger particle deposition with inertial effects. The focus is on using a simplified version of the comprehensive multicomponent vapor diffusion formalism to make deposition predictions for: (1) simple geometry collectors; and (2) gas turbine blade shapes, including both developing laminar and turbulent boundary layers. For the gas turbine blade the insights developed in previous programs are being combined with heat and mass transfer coefficient calculations using the STAN 5 boundary layer code to predict vapor deposition rates and corresponding liquid layer thicknesses on turbine blades. A computer program is being written which utilizes the local values of the calculated deposition rate and skin friction to calculate the increment in liquid condensate layer growth along a collector surface.

  6. Riparian seed dispersal: transport and depositional processes

    NASA Astrophysics Data System (ADS)

    Cunnings, A.; Johnson, E. A.; Martin, Y. E.

    2012-04-01

    Riparian tree population dynamics are linked to the physical processes controlled by the hydrogeomorphic setting. In particular, fluvial seed dispersal is influenced by a combination of factors including the hydrology, fluvial geomorphology, and seed dispersal traits. This study examines the influence of stream flow patterns on the transportation and deposition of buoyant seeds by applying a one dimensional transport model. Conceptually, the model separates the stream into two components: the main channel and transient storage /deposition zones. The hydrologic processes are governed by an advection-dispersion equation and numerically solved using the Crank-Nicolson method. Additional terms in the equation allow for model variation in the flow regime (lateral inflow and outflow) and the incorporation of a transient storage/deposition component where seeds may be detained. The model parameters are based on a bedrock-gravel bed river with pool-riffle morphology where we conducted field experimentation in Coastal Northern California. The riparian zone of the study reach is inhabited by White Alder (Alnus rhombifolia) which disperses buoyant seeds in late winter/early spring coinciding with the latter part of the wet, Mediterranean climate. Artificial seeds with similar characteristic traits of buoyancy, density and Bond Number to White Alder seeds were used to quantify transport times and identify storage areas. The model output captures a greater number of seeds during a receding hydrograph due to the increase in transient storage. Typically, this is found in shallow stream margins where the flow is divergent such as areas with back-eddies. In the field, this is associated with the ends of gravel bars or riffles where flow expansion causes secondary flows. The results demonstrate the importance of transient storage for seed transport and depositional processes and emphasize the need for improved measurement techniques, in lieu of empirical coefficients, to advance the

  7. Ionized cluster beam deposition

    NASA Technical Reports Server (NTRS)

    Kirkpatrick, A. R.

    1983-01-01

    Ionized Cluster Beam (ICB) deposition, a new technique originated by Takagi of Kyoto University in Japan, offers a number of unique capabilities for thin film metallization as well as for deposition of active semiconductor materials. ICB allows average energy per deposited atom to be controlled and involves impact kinetics which result in high diffusion energies of atoms on the growth surface. To a greater degree than in other techniques, ICB involves quantitative process parameters which can be utilized to strongly control the characteristics of films being deposited. In the ICB deposition process, material to be deposited is vaporized into a vacuum chamber from a confinement crucible at high temperature. Crucible nozzle configuration and operating temperature are such that emerging vapor undergoes supercondensation following adiabatic expansion through the nozzle.

  8. ElectroSpark Deposition

    DTIC Science & Technology

    2007-01-25

    ElectroSpark Deposition Hard Chrome Alternatives Team Joint Cadmium Alternatives Team Canadian Hard Chrome Alternatives Team Joint Group on Pollution...00-2007 to 00-00-2007 4. TITLE AND SUBTITLE ElectroSpark Deposition 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Processes, Inc. ElectroSpark Deposition (ESD) Results of Materials Testing and Technology Insertion January 25, 2007 Advanced Surfaces And Processes, Inc. 3

  9. Mechanistic Investigation of Toxaphene Induced Mouse Liver Tumors.

    PubMed

    Wang, Zemin; Neal, Barbara H; Lamb, James C; Klaunig, James E

    2015-10-01

    Chronic exposure to toxaphene resulted in an increase in liver tumors in B6C3F1 mice. This study was performed to investigate the mode of action of toxaphene induced mouse liver tumors. Following an initial 14 day dietary dose range-finding study in male mice, a mechanistic study (0, 3, 32, and 320 ppm toxaphene in diet for 7, 14, and 28 days of treatment) was performed to examine the potential mechanisms of toxaphene induced mouse liver tumors. Toxaphene induced a significant increase in expression of constitutive androstane receptor (CAR) target genes (Cyp2b10, Cyp3a11) at 32 and 320 ppm toxaphene. aryl hydrocarbon receptor (AhR) target genes (Cyp1a1 and Cyp1a2) were slightly increased in expression at the highest toxaphene dose (320 ppm). No increase in peroxisome proliferator-activated receptor alpha activity or related genes was seen following toxaphene treatment. Lipid peroxidation was seen following treatment with 320 ppm toxaphene. These changes correlated with increases in hepatic DNA synthesis. To confirm the role of CAR in this mode of action, CAR knockout mice (CAR(-/-)) treated with toxaphene confirmed that the induction of CAR responsive genes seen in wild-type mice was abolished following treatment with toxaphene for 14 days. These findings, taken together with previously reported studies, support the mode of action of toxaphene induced mouse liver tumors is through a nongenotoxic mechanism involving primarily a CAR-mediated processes that results in an increase in cell proliferation in the liver, promotes the clonal expansion of preneoplastic lesions leading to adenoma formation.

  10. Metabolic diseases and pro- and prebiotics: Mechanistic insights.

    PubMed

    Nakamura, Yukiko K; Omaye, Stanley T

    2012-06-19

    Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual's behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases.

  11. The ecological impacts of nighttime light pollution: a mechanistic appraisal.

    PubMed

    Gaston, Kevin J; Bennie, Jonathan; Davies, Thomas W; Hopkins, John

    2013-11-01

    The ecological impacts of nighttime light pollution have been a longstanding source of concern, accentuated by realized and projected growth in electrical lighting. As human communities and lighting technologies develop, artificial light increasingly modifies natural light regimes by encroaching on dark refuges in space, in time, and across wavelengths. A wide variety of ecological implications of artificial light have been identified. However, the primary research to date is largely focused on the disruptive influence of nighttime light on higher vertebrates, and while comprehensive reviews have been compiled along taxonomic lines and within specific research domains, the subject is in need of synthesis within a common mechanistic framework. Here we propose such a framework that focuses on the cross-factoring of the ways in which artificial lighting alters natural light regimes (spatially, temporally, and spectrally), and the ways in which light influences biological systems, particularly the distinction between light as a resource and light as an information source. We review the evidence for each of the combinations of this cross-factoring. As artificial lighting alters natural patterns of light in space, time and across wavelengths, natural patterns of resource use and information flows may be disrupted, with downstream effects to the structure and function of ecosystems. This review highlights: (i) the potential influence of nighttime lighting at all levels of biological organisation (from cell to ecosystem); (ii) the significant impact that even low levels of nighttime light pollution can have; and (iii) the existence of major research gaps, particularly in terms of the impacts of light at population and ecosystem levels, identification of intensity thresholds, and the spatial extent of impacts in the vicinity of artificial lights.

  12. Toward a mechanistic modeling of nitrogen limitation on vegetation dynamics

    SciTech Connect

    Xu, Chonggang; Fisher, Rosie; Wullschleger, Stan D; Wilson, Cathy; Cai, Michael; McDowell, Nathan

    2012-01-01

    Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO{sub 2} concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO{sub 2} concentration, temperature, and radiation when evaluated against published data of V{sub c,max} (maximum carboxylation rate) and J{sub max} (maximum electron transport rate). A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO{sub 2} concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions

  13. Metabolic diseases and pro- and prebiotics: Mechanistic insights

    PubMed Central

    2012-01-01

    Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual’s behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases. PMID:22713169

  14. Human endotoxemia: a model for mechanistic insight and therapeutic targeting.

    PubMed

    Lowry, Stephen F

    2005-12-01

    The diversity of phenotypic manifestations, comorbidities, and therapeutic algorithms in patients with severe inflammation have confounded efforts to translate mechanistic insights from the bench top to the bedside. This dilemma has negatively impacted upon many therapeutic interventions that exhibited seemingly well-reasoned preclinical portfolios. Prudence urges the assessment of potent immunoregulatory therapies, wherever possible, in models that replicate the clinical phenotype absent overt manifestations of genetically or environmentally modified processes. The healthy human model of endotoxin administration (systemic or endobronchial) provides such an opportunity and has been used to great advantage for gaining insight into mechanisms of disease and for determination of therapeutic signal strength. When thoughtfully interpreted, the model may provide proof of principle as well as lessen the unpredictability of clinical responses. Although the broad characteristics of this model are well described in the literature, it is recognized that this model does not fully replicate the magnitude of initial inflammatory stress nor the latent spectrum of inflammation/sepsis-inducible organ system pathologies. Nevertheless, the similarities between the early, transient clinical phenotype, inducible physiochemical change, and biochemical pathway activation of this model to the early hyperdynamic phase of resuscitated injury and infection are striking. Rational testing of a therapeutic mechanism requires a quantifiable and reproducibly altered marker of the hypothetical mechanism. Given the modest nature of endotoxin induced insult, interventions that demonstrate target specific efficacy in conjunction with attenuated phenotype responses are more likely to exhibit efficacy within lower risk patient populations. By contrast, the model cannot predict clinical efficacy among higher risk patients nor in those who have endured extended periods of inflammatory stress.

  15. Mechanistic kinetic models of enzymatic cellulose hydrolysis-a review.

    PubMed

    Jeoh, Tina; Cardona, Maria J; Karuna, Nardrapee; Mudinoor, Akshata R; Nill, Jennifer

    2017-02-28

    Bioconversion of lignocellulose forms the basis for renewable, advanced biofuels, and bioproducts. Mechanisms of hydrolysis of cellulose by cellulases have been actively studied for nearly 70 years with significant gains in understanding of the cellulolytic enzymes. Yet, a full mechanistic understanding of the hydrolysis reaction has been elusive. We present a review to highlight new insights gained since the most recent comprehensive review of cellulose hydrolysis kinetic models by Bansal et al. () Biotechnol Adv 27:833-848. Recent models have taken a two-pronged approach to tackle the challenge of modeling the complex heterogeneous reaction-an enzyme-centric modeling approach centered on the molecularity of the cellulase-cellulose interactions to examine rate limiting elementary steps and a substrate-centric modeling approach aimed at capturing the limiting property of the insoluble cellulose substrate. Collectively, modeling results suggest that at the molecular-scale, how rapidly cellulases can bind productively (complexation) and release from cellulose (decomplexation) is limiting, while the overall hydrolysis rate is largely insensitive to the catalytic rate constant. The surface area of the insoluble substrate and the degrees of polymerization of the cellulose molecules in the reaction both limit initial hydrolysis rates only. Neither enzyme-centric models nor substrate-centric models can consistently capture hydrolysis time course at extended reaction times. Thus, questions of the true reaction limiting factors at extended reaction times and the role of complexation and decomplexation in rate limitation remain unresolved. Biotechnol. Bioeng. 2017;9999: 1-16. © 2017 Wiley Periodicals, Inc.

  16. Mechanistic basis of infertility of mouse intersubspecific hybrids

    PubMed Central

    Bhattacharyya, Tanmoy; Gregorova, Sona; Mihola, Ondrej; Anger, Martin; Sebestova, Jaroslava; Denny, Paul; Simecek, Petr; Forejt, Jiri

    2013-01-01

    According to the Dobzhansky–Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than the rest of the genome. Here we propose that asynapsis of heterospecific chromosomes in meiotic prophase provides a recurrently evolving trigger for the meiotic arrest of interspecific F1 hybrids. We observed extensive asynapsis of chromosomes and disturbance of the sex body in >95% of pachynemas of Mus m. musculus × Mus m. domesticus sterile F1 males. Asynapsis was not preceded by a failure of double-strand break induction, and the rate of meiotic crossing over was not affected in synapsed chromosomes. DNA double-strand break repair was delayed or failed in unsynapsed autosomes, and misexpression of chromosome X and chromosome Y genes was detected in single pachynemas and by genome-wide expression profiling. Oocytes of F1 hybrid females showed the same kind of synaptic problems but with the incidence reduced to half. Most of the oocytes with pachytene asynapsis were eliminated before birth. We propose the heterospecific pairing of homologous chromosomes as a preexisting condition of asynapsis in interspecific hybrids. The asynapsis may represent a universal mechanistic basis of F1 hybrid sterility manifested by pachytene arrest. It is tempting to speculate that a fast-evolving subset of the noncoding genomic sequence important for chromosome pairing and synapsis may be the culprit. PMID:23329330

  17. Mechanistic Understanding of Microbial Plugging for Improved Sweep Efficiency

    SciTech Connect

    Steven Bryant; Larry Britton

    2008-09-30

    Microbial plugging has been proposed as an effective low cost method of permeability reduction. Yet there is a dearth of information on the fundamental processes of microbial growth in porous media, and there are no suitable data to model the process of microbial plugging as it relates to sweep efficiency. To optimize the field implementation, better mechanistic and volumetric understanding of biofilm growth within a porous medium is needed. In particular, the engineering design hinges upon a quantitative relationship between amount of nutrient consumption, amount of growth, and degree of permeability reduction. In this project experiments were conducted to obtain new data to elucidate this relationship. Experiments in heterogeneous (layered) beadpacks showed that microbes could grow preferentially in the high permeability layer. Ultimately this caused flow to be equally divided between high and low permeability layers, precisely the behavior needed for MEOR. Remarkably, classical models of microbial nutrient uptake in batch experiments do not explain the nutrient consumption by the same microbes in flow experiments. We propose a simple extension of classical kinetics to account for the self-limiting consumption of nutrient observed in our experiments, and we outline a modeling approach based on architecture and behavior of biofilms. Such a model would account for the changing trend of nutrient consumption by bacteria with the increasing biomass and the onset of biofilm formation. However no existing model can explain the microbial preference for growth in high permeability regions, nor is there any obvious extension of the model for this observation. An attractive conjecture is that quorum sensing is involved in the heterogeneous bead packs.

  18. The attention schema theory: a mechanistic account of subjective awareness.

    PubMed

    Graziano, Michael S A; Webb, Taylor W

    2015-01-01

    We recently proposed the attention schema theory, a novel way to explain the brain basis of subjective awareness in a mechanistic and scientifically testable manner. The theory begins with attention, the process by which signals compete for the brain's limited computing resources. This internal signal competition is partly under a bottom-up influence and partly under top-down control. We propose that the top-down control of attention is improved when the brain has access to a simplified model of attention itself. The brain therefore constructs a schematic model of the process of attention, the 'attention schema,' in much the same way that it constructs a schematic model of the body, the 'body schema.' The content of this internal model leads a brain to conclude that it has a subjective experience. One advantage of this theory is that it explains how awareness and attention can sometimes become dissociated; the brain's internal models are never perfect, and sometimes a model becomes dissociated from the object being modeled. A second advantage of this theory is that it explains how we can be aware of both internal and external events. The brain can apply attention to many types of information including external sensory information and internal information about emotions and cognitive states. If awareness is a model of attention, then this model should pertain to the same domains of information to which attention pertains. A third advantage of this theory is that it provides testable predictions. If awareness is the internal model of attention, used to help control attention, then without awareness, attention should still be possible but should suffer deficits in control. In this article, we review the existing literature on the relationship between attention and awareness, and suggest that at least some of the predictions of the theory are borne out by the evidence.

  19. Conceptualising population health: from mechanistic thinking to complexity science.

    PubMed

    Jayasinghe, Saroj

    2011-01-20

    The mechanistic interpretation of reality can be traced to the influential work by René Descartes and Sir Isaac Newton. Their theories were able to accurately predict most physical phenomena relating to motion, optics and gravity. This paradigm had at least three principles and approaches: reductionism, linearity and hierarchy. These ideas appear to have influenced social scientists and the discourse on population health. In contrast, Complexity Science takes a more holistic view of systems. It views natural systems as being 'open', with fuzzy borders, constantly adapting to cope with pressures from the environment. These are called Complex Adaptive Systems (CAS). The sub-systems within it lack stable hierarchies, and the roles of agency keep changing. The interactions with the environment and among sub-systems are non-linear interactions and lead to self-organisation and emergent properties. Theoretical frameworks such as epi+demos+cracy and the ecosocial approach to health have implicitly used some of these concepts of interacting dynamic sub-systems. Using Complexity Science we can view population health outcomes as an emergent property of CAS, which has numerous dynamic non-linear interactions among its interconnected sub-systems or agents. In order to appreciate these sub-systems and determinants, one should acquire a basic knowledge of diverse disciplines and interact with experts from different disciplines. Strategies to improve health should be multi-pronged, and take into account the diversity of actors, determinants and contexts. The dynamic nature of the system requires that the interventions are constantly monitored to provide early feedback to a flexible system that takes quick corrections.

  20. Mechanistic studies of ubiquitin C-terminal hydrolase L1.

    PubMed

    Case, April; Stein, Ross L

    2006-02-21

    Ubiquitin C-terminal hydrolases (UCHs) cleave Ub-X bonds (Ub is ubiquitin and X an alcohol, an amine, or a protein) through a thioester intermediate that is produced by nucleophilic attack of the Cys residue of a Cys-SH/His-Im catalytic diad. We are studying the mechanism of UCH-L1, a UCH that is implicated in Parkinson's disease, and now wish to report our initial findings. (i) Pre-steady-state kinetic studies for UCH-L1-catalyzed hydrolysis of Ub-AMC (AMC, 7-amido-4-methylcoumarin) indicate that k(cat) is rate-limited by acyl-enzyme formation. Thus, K(m) = K(s), the dissociation constant for the Michaelis complex, and k(cat) = k(2), the rate constant for acyl-enzyme formation. (ii) For K(assoc) (=K(s)(-)(1)), DeltaC(p) = -0.8 kcal mol(-)(1) deg(-)(1) and is consistent with coupling between substrate association and a conformational change of the enzyme. For k(2), DeltaS(++) = 0 and suggests that in the E-S, substrate and active site residues are precisely aligned for reaction. (iii) Solvent isotope effects are (D)K(assoc) = 0.5 and (D)k(2) = 0.9, suggesting that the substrate binds to a form of free enzyme in which the active site Cys exists as the thiol. In the resultant Michaelis complex, the diad has tautomerized to ion pair Cys-S(-)/His-ImH(+). Subsequent attack of thiolate produces the acyl-enzyme species. In contrast, isotope effects for association of UCH-L1 with transition-state analogue ubiquitin aldehyde suggest that an alternative mechanistic pathway can sometimes be available to UCH-L1 involving general base-catalyzed attack of Cys-SH by His-Im.

  1. Acyclovir-Polyethylene Glycol 6000 Binary Dispersions: Mechanistic Insights.

    PubMed

    Venkateskumar, Krishnamoorthy; Parasuraman, Subramani; Gunasunderi, Raju; Sureshkumar, Krishnan; Nayak, M Muralidhar; Shah, Syed Adnan Ali; Khoo, Khassen; Kai, Heng Wei

    2016-12-21

    The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development.

  2. Mechanistic Study of Plasma Damage of Low k Dielectric Surfaces

    SciTech Connect

    Bao Junjing; Shi Hualiang; Huang Huai; Ho, P. S.; Liu Junjun; Goodner, M. D.; Moinpour, M.; Kloster, G. M.

    2007-10-31

    Plasma damage to low k dielectric materials was investigated from a mechanistic point of view. Low k dielectric films were treated by plasma Ar, O{sub 2}, N{sub 2}/H{sub 2}, N{sub 2} and H{sub 2} in a standard RIE chamber and the damage was characterized by Angle Resolved X-ray Photoelectron Spectroscopy (ARXPS), X-Ray Reflectivity (XRR), Fourier Transform Infrared Spectroscopy (FTIR) and Contact Angle measurements. Both carbon depletion and surface densification were observed on the top surface of damaged low k materials while the bulk remained largely unaffected. Plasma damage was found to be a complicated phenomenon involving both chemical and physical effects, depending on chemical reactivity and the energy and mass of the plasma species. A downstream hybrid plasma source with separate ions and atomic radicals was employed to study their respective roles in the plasma damage process. Ions were found to play a more important role in the plasma damage process. The dielectric constant of low k materials can increase up to 20% due to plasma damage and we attributed this to the removal of the methyl group making the low k surface hydrophilic. Annealing was generally effective in mitigating moisture uptake to restore the k value but the recovery was less complete for higher energy plasmas. Quantum chemistry calculation confirmed that physisorbed water in low k materials induces the largest increase of dipole moments in comparison with changes of surface bonding configurations, and is primarily responsible for the dielectric constant increase.

  3. Mechanistic Insights into Homogeneous and Heterogeneous Asymmetric Iron Catalysis

    NASA Astrophysics Data System (ADS)

    Sonnenberg, Jessica

    Our group has been focused on replacing toxic and expensive precious metal catalysts with iron for the synthesis of enantiopure compounds for industrial applications. During an investigation into the mechanism of asymmetric transfer hydrogenation with our first generation iron-(P-N-N-P) catalysts we found substantial evidence for zero-valent iron nanoparticles coated in chiral ligand acting as the active site. Extensive experimental and computational experiments were undertaken which included NMR, DFT, reaction profile analysis, substoichiometric poisoning, electron microscope imaging, XPS and multiphasic analysis, all of which supported the fact that NPs were the active species in catalysis. Reversibility of this asymmetric reaction on the nanoparticle surface was then probed using oxidative kinetic resolution of racemic alcohols, yielding modest enantiopurity and high turnover frequencies (TOF) for a range of aromatic alcohols. Efficient dehydrogenation of ammonia-borane for hydrogen evolution and the formation of B-N oligomers was also shown using the NP system, yielding highly active systems, with a maximum TOF of 3.66 H2/s-1 . We have also begun to focus on the development of iron catalysts for asymmetric direct hydrogenation of ketones using hydrogen gas. New chiral iron-(P-N-P) catalysts were developed and shown to be quite active and selective for a wide range of substrates. Mechanistic investigations primarily using NMR and DFT indicated that a highly active trans-dihydride species was being formed during catalyst activation. Lastly, a new library of chiral P-N-P and P-NH-P ligands were developed, as well as their corresponding iron complexes, some of which show promise for the development of future generations of active asymmetric direct hydrogenation catalysts.

  4. Radionuclide deposition control

    DOEpatents

    Brehm, William F.; McGuire, Joseph C.

    1980-01-01

    The deposition of radionuclides manganese-54, cobalt-58 and cobalt-60 from liquid sodium coolant is controlled by providing surfaces of nickel or high nickel alloys to extract the radionuclides from the liquid sodium, and by providing surfaces of tungsten, molybdenum or tantalum to prevent or retard radionuclide deposition.

  5. Domestic phosphate deposits

    USGS Publications Warehouse

    McKelvey, V.E.; Cathcart, J.B.; Altschuler, Z.S.; Swanson, R.W.; Lutz, Katherine

    1953-01-01

    Most of the worlds phosphate deposits can be grouped into six types: 1) igneous apatite deposits; 2) marine phosphorites; 3) residual phosphorites; 4) river pebble deposits; 5) phosphatized rock; and 6) guano. The igneous apatites and marine phosphorites form deposits measurable in millions or billions of tons; the residual deposits are measurable in thousands or millions; and the other types generally only in thousands of tons. Igneous apatite deposits have been mined on a small scale in New York, New Jersey, and Virginia. Marine phosphorites have been mined in Montana, Idaho, Utah, Wyoming, Arkansas, Tennessee, North Carolina, South Carolina, Georgia, and Florida. Residual phosphorites have been mined in Tennessee, Pennsylvania, and Florida. River pebble has been produced in South Carolina and Florida; phosphatized rock in Tennessee and Florida; and guano in New Mexico and Texas. Present production is limited almost entirely to Florida, Tennessee, Montana, Idaho, and Wyoming. Incomplete but recently partly revised estimates indicate the presence of about 5 billion tons of phosphate deposits in the United States that is minable under present economic conditions. Deposits too lean in quality or thickness to compete with those in the western and southeastern fields probably contain tens of billions of tons.

  6. ASSESSING POPULATION EXPOSURES TO MULTIPLE AIR POLLUTANTS USING A MECHANISTIC SOURCE-TO-DOSE MODELING FRAMEWORK

    EPA Science Inventory

    The Modeling Environment for Total Risks studies (MENTOR) system, combined with an extension of the SHEDS (Stochastic Human Exposure and Dose Simulation) methodology, provide a mechanistically consistent framework for conducting source-to-dose exposure assessments of multiple pol...

  7. UTILITY OF MECHANISTIC MODELS FOR DIRECTING ADVANCED SEPARATIONS RESEARCH & DEVELOPMENT ACTIVITIES: Electrochemically Modulated Separation Example

    SciTech Connect

    Schwantes, Jon M.

    2009-06-01

    The objective for this work was to demonstrate the utility of mechanistic computer models designed to simulate actinide behavior for use in efficiently and effectively directing advanced laboratory R&D activities associated with developing advanced separations methods.

  8. Dose-response relationships and extrapolation in toxicology - Mechanistic and statistical considerations

    EPA Science Inventory

    Controversy on toxicological dose-response relationships and low-dose extrapolation of respective risks is often the consequence of misleading data presentation, lack of differentiation between types of response variables, and diverging mechanistic interpretation. In this chapter...

  9. Plasma deposition of tungsten

    SciTech Connect

    Greenberg, K.E.

    1986-12-01

    Tungsten films were plasma-deposited using an abnormal glow discharge through a mixture of tungsten hexafluoride, hydrogen, and argon. The films adhered well to silicon, silicon dioxide, gallium arsenide, and aluminum substrates placed directly on the discharge cathode. Typical deposition rates were on the order of 160 Angstroms/minute with as-deposited film resistivities of 40 to 70 microohm-cm. The tungsten was analyzed using a number of techniques including x-ray diffraction, scanning electron microscopy, and Auger spectroscopy. Low-resistivity (<10 microohm-cm) films that adhered well to silicon dioxide were obtained with a two-step process utilizing plasma deposition and conventional chemical vapor deposition.

  10. Stratiform chromite deposit model

    USGS Publications Warehouse

    Schulte, Ruth F.; Taylor, Ryan D.; Piatak, Nadine M.; Seal, Robert R., II

    2010-01-01

    Stratiform chromite deposits are of great economic importance, yet their origin and evolution remain highly debated. Layered igneous intrusions such as the Bushveld, Great Dyke, Kemi, and Stillwater Complexes, provide opportunities for studying magmatic differentiation processes and assimilation within the crust, as well as related ore-deposit formation. Chromite-rich seams within layered intrusions host the majority of the world's chromium reserves and may contain significant platinum-group-element (PGE) mineralization. This model of stratiform chromite deposits is part of an effort by the U.S. Geological Survey's Mineral Resources Program to update existing models and develop new descriptive mineral deposit models to supplement previously published models for use in mineral-resource and mineral-environmental assessments. The model focuses on features that may be common to all stratiform chromite deposits as a way to gain insight into the processes that gave rise to their emplacement and to the significant economic resources contained in them.

  11. Solution deposition assembly

    SciTech Connect

    Roussillon, Yann; Scholz, Jeremy H; Shelton, Addison; Green, Geoff T; Utthachoo, Piyaphant

    2014-01-21

    Methods and devices are provided for improved deposition systems. In one embodiment of the present invention, a deposition system is provided for use with a solution and a substrate. The system comprises of a solution deposition apparatus; at least one heating chamber, at least one assembly for holding a solution over the substrate; and a substrate curling apparatus for curling at least one edge of the substrate to define a zone capable of containing a volume of the solution over the substrate. In another embodiment of the present invention, a deposition system for use with a substrate, the system comprising a solution deposition apparatus; at heating chamber; and at least assembly for holding solution over the substrate to allow for a depth of at least about 0.5 microns to 10 mm.

  12. The regularity theory of mechanistic constitution and a methodology for constitutive inference.

    PubMed

    Harbecke, Jens

    2015-12-01

    This paper discusses a Boolean method for establishing constitutive regularity statements which, according to the regularity theory of mechanistic constitution, form the core of any mechanistic explanation in neuroscience. After presenting the regularity definition for the constitution relation, the paper develops a set of inference rules allowing one to establish constitutive hypotheses in light of certain kinds of empirical evidence. The general methodology consisting of these rules is characterized as having formed the basis of many successful explanatory projects in neuroscience.

  13. Mechanistic species distribution modelling as a link between physiology and conservation

    PubMed Central

    Evans, Tyler G.; Diamond, Sarah E.; Kelly, Morgan W.

    2015-01-01

    Climate change conservation planning relies heavily on correlative species distribution models that estimate future areas of occupancy based on environmental conditions encountered in present-day ranges. The approach benefits from rapid assessment of vulnerability over a large number of organisms, but can have poor predictive power when transposed to novel environments and reveals little in the way of causal mechanisms that define changes in species distribution or abundance. Having conservation planning rely largely on this single approach also increases the risk of policy failure. Mechanistic models that are parameterized with physiological information are expected to be more robust when extrapolating distributions to future environmental conditions and can identify physiological processes that set range boundaries. Implementation of mechanistic species distribution models requires knowledge of how environmental change influences physiological performance, and because this information is currently restricted to a comparatively small number of well-studied organisms, use of mechanistic modelling in the context of climate change conservation is limited. In this review, we propose that the need to develop mechanistic models that incorporate physiological data presents an opportunity for physiologists to contribute more directly to climate change conservation and advance the field of conservation physiology. We begin by describing the prevalence of species distribution modelling in climate change conservation, highlighting the benefits and drawbacks of both mechanistic and correlative approaches. Next, we emphasize the need to expand mechanistic models and discuss potential metrics of physiological performance suitable for integration into mechanistic models. We conclude by summarizing other factors, such as the need to consider demography, limiting broader application of mechanistic models in climate change conservation. Ideally, modellers, physiologists and

  14. Mechanistically Distinct Mouse Models for CRX-Associated Retinopathy

    PubMed Central

    Tran, Nicholas M.; Zhang, Alan; Zhang, Xiaodong; Huecker, Julie B.; Hennig, Anne K.; Chen, Shiming

    2014-01-01

    Cone-rod homeobox (CRX) protein is a “paired-like” homeodomain transcription factor that is essential for regulating rod and cone photoreceptor transcription. Mutations in human CRX are associated with the dominant retinopathies Retinitis Pigmentosa (RP), Cone-Rod Dystrophy (CoRD) and Leber Congenital Amaurosis (LCA), with variable severity. Heterozygous Crx Knock-Out (KO) mice (“+/−”) have normal vision as adults and fail to model the dominant human disease. To investigate how different mutant CRX proteins produce distinct disease pathologies, we generated two Crx Knock-IN (K-IN) mouse models: CrxE168d2 (“E168d2”) and CrxR90W (“R90W”). E168d2 mice carry a frameshift mutation in the CRX activation domain, Glu168del2, which is associated with severe dominant CoRD or LCA in humans. R90W mice carry a substitution mutation in the CRX homeodomain, Arg90Trp, which is associated with dominant mild late-onset CoRD and recessive LCA. As seen in human patients, heterozygous E168d2 (“E168d2/+”) but not R90W (“R90W/+”) mice show severely impaired retinal function, while mice homozygous for either mutation are blind and undergo rapid photoreceptor degeneration. E168d2/+ mice also display abnormal rod/cone morphology, greater impairment of CRX target gene expression than R90W/+ or +/− mice, and undergo progressive photoreceptor degeneration. Surprisingly, E168d2/+ mice express more mutant CRX protein than wild-type CRX. E168d2neo/+, a subline of E168d2 with reduced mutant allele expression, displays a much milder retinal phenotype, demonstrating the impact of Crx expression level on disease severity. Both CRX[E168d2] and CRX[R90W] proteins fail to activate transcription in vitro, but CRX[E168d2] interferes more strongly with the function of wild type (WT) CRX, supporting an antimorphic mechanism. E168d2 and R90W are mechanistically distinct mouse models for CRX-associated disease that will allow the elucidation of molecular mechanisms and testing of

  15. Toward a mechanistic modeling of nitrogen limitation for photosynthesis

    NASA Astrophysics Data System (ADS)

    Xu, C.; Fisher, R. A.; Travis, B. J.; Wilson, C. J.; McDowell, N. G.

    2011-12-01

    The nitrogen limitation is an important regulator for vegetation growth and global carbon cycle. Most current ecosystem process models simulate nitrogen effects on photosynthesis based on a prescribed relationship between leaf nitrogen and photosynthesis; however, there is a large amount of variability in this relationship with different light, temperature, nitrogen availability and CO2 conditions, which can affect the reliability of photosynthesis prediction under future climate conditions. To account for the variability in nitrogen-photosynthesis relationship under different environmental conditions, in this study, we developed a mechanistic model of nitrogen limitation for photosynthesis based on nitrogen trade-offs among light absorption, electron transport, carboxylization and carbon sink. Our model shows that strategies of nitrogen storage allocation as determined by tradeoff among growth and persistence is a key factor contributing to the variability in relationship between leaf nitrogen and photosynthesis. Nitrogen fertilization substantially increases the proportion of nitrogen in storage for coniferous trees but much less for deciduous trees, suggesting that coniferous trees allocate more nitrogen toward persistence compared to deciduous trees. The CO2 fertilization will cause lower nitrogen allocation for carboxylization but higher nitrogen allocation for storage, which leads to a weaker relationship between leaf nitrogen and maximum photosynthesis rate. Lower radiation will cause higher nitrogen allocation for light absorption and electron transport but less nitrogen allocation for carboxylyzation and storage, which also leads to weaker relationship between leaf nitrogen and maximum photosynthesis rate. At the same time, lower growing temperature will cause higher nitrogen allocation for carboxylyzation but lower allocation for light absorption, electron transport and storage, which leads to a stronger relationship between leaf nitrogen and maximum

  16. Mechanistic simulation of the vertical soil organic matter profile

    NASA Astrophysics Data System (ADS)

    Braakhekke, M.; Beer, C.; Reichstein, M.; Hoosbeek, M.; Kruijt, B.; Kabat, P.

    2013-12-01

    Soil organic matter (SOM) constitutes a large global pool of carbon that may play a considerable role for future climate. The vertical distribution of SOM in the profile may be important due to depth-dependence of physical, chemical, and biological conditions, and links to physical processes such as heat and moisture transport. The aim of this thesis is to develop a dynamic and mechanistic representation of the vertical SOM profile that can be applied for large scale simulations as a part of global ecosystem and earth system models. A model structure called SOMPROF was developed that dynamically simulates the SOM profile based on above and below ground litter input, decomposition, bioturbation, and liquid phase transport. Furthermore, three organic surface horizons are explicitly represented. Since the organic matter transport processes have been poorly quantified in the past and are difficult to observe directly, the model was calibrated with a Bayesian approach for two contrasting temperate forest sites in Europe. Different types of data were included in the parameter estimation, including: organic carbon stocks and concentrations, respiration rates, and excess lead-210 activity. The calibrations yielded good fits to the observations, and showed that the two sites differ considerably with respect to the relevance of the different processes. These differences agree well with expectations based on local conditions. However, the results also demonstrate the difficulties arising from convolution of the processes. Several parameters are poorly constrained and for one of the sites, several distinct regions in parameter space exist that yield acceptable fit. In a subsequent study it was found that radiocarbon observations can offer much additional constraint on several parameters, most importantly on the turnover rate of the slowest SOM fraction. Additionally, for one site, a prognostic simulation until 2100 was performed using the resulting a posteriori parameter

  17. Mechanistic aspects of hydration of guanine radical cations in DNA.

    PubMed

    Rokhlenko, Yekaterina; Cadet, Jean; Geacintov, Nicholas E; Shafirovich, Vladimir

    2014-04-23

    The mechanistic aspects of hydration of guanine radical cations, G(•+) in double- and single-stranded oligonucleotides were investigated by direct time-resolved spectroscopic monitoring methods. The G(•+) radical one-electron oxidation products were generated by SO4(•-) radical anions derived from the photolysis of S2O8(2-) anions by 308 nm laser pulses. In neutral aqueous solutions (pH 7.0), after the complete decay of SO4(•-) radicals (∼5 μs after the actinic laser flash) the transient absorbance of neutral guanine radicals, G(-H)(•) with maximum at 312 nm, is dominant. The kinetics of decay of G(-H)(•) radicals depend strongly on the DNA secondary structure. In double-stranded DNA, the G(-H)(•) decay is biphasic with one component decaying with a lifetime of ∼2.2 ms and the other with a lifetime of ∼0.18 s. By contrast, in single-stranded DNA the G(-H)(•) radicals decay monophasically with a ∼ 0.28 s lifetime. The ms decay component in double-stranded DNA is correlated with the enhancement of 8-oxo-7,8-dihydroguanine (8-oxoG) yields which are ∼7 greater than in single-stranded DNA. In double-stranded DNA, it is proposed that the G(-H)(•) radicals retain radical cation character by sharing the N1-proton with the N3-site of C in the [G(•+):C] base pair. This [G(-H)(•):H(+)C ⇆ G(•+):C] equilibrium allows for the hydration of G(•+) followed by formation of 8-oxoG. By contrast, in single-stranded DNA, deprotonation of G(•+) and the irreversible escape of the proton into the aqueous phase competes more effectively with the hydration mechanism, thus diminishing the yield of 8-oxoG, as observed experimentally.

  18. Clinical and Mechanistic Drivers of Acute Traumatic Coagulopathy

    PubMed Central

    Cohen, Mitchell Jay; Kutcher, Matt; Redick, Britt; Nelson, Mary; Call, Mariah; Knudson, M Margaret; Schreiber, Martin A; Bulger, Eileen M; Muskat, Peter; Alarcon, Louis H; Myers, John G; Rahbar, Mohammad H; Brasel, Karen J; Phelan, Herb A; del Junco, Deborah J; Fox, Erin E; Wade, Charles E; Holcomb, John B; Cotton, Bryan A; Matijevic, Nena

    2013-01-01

    Background Acute Traumatic Coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma. Methods Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data. Results There were 1198 patients with laboratory results of whom 41.6% were coagulopathic. Using International Normalized Ratio (INR)≥1.3, 41.6% (448) of patients were coagulopathic while 20.5% (214) were coagulopathic using partial thromboplastin time (PTT)≥35. Coagulopathy was primarily associated with a combination of an ISS>15 and a BD<−6 (P<.05). Regression modeling for INR-based coagulopathy shows that pre-hospital crystalloid (odds ratio (OR)=1.05), Injury Severity Score (ISS, OR=1.03), Glasgow Coma Scale (OR=0.93), heart rate (OR=1.08), systolic blood pressure (OR=0.96), base deficit (BD, OR=0.92) and temperature (OR=0.84) were significant predictors of coagulopathy (all P<.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all P<.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p<.04). Similar results were found for PTT-defined coagulopathy. Conclusions ATC is associated with depletion of factors I, II, V, VII, VIII, IX and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of

  19. Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

    SciTech Connect

    Feng, Lei; Wanninayake, Udayanga; Strom, Susan; Geiger, James; Walker, Kevin D.

    2014-10-02

    The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 {angstrom} resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-{alpha}-phenylalanine to the (R)-{beta}-isomer by exchange of the NH{sub 2}/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-{beta}-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition, the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-{beta}-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C{sub 1}-C{sub {alpha}} and C{sub ipso}-C{sub {beta}} bonds 180{sup o} in the active site prior to exchange and rebinding of the NH{sub 2}/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an 1.5-fold increase in k{sub cat} and a decrease in K{sub M} values for sterically demanding 3'-methyl-{alpha}-phenylalanine and styryl-{alpha}-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-{alpha}-phenylalanine compared to those for TcPAM.

  20. Mechanistic modeling of turkey growth response to genotype and nutrition.

    PubMed

    Rivera-Torres, V; Ferket, P R; Sauvant, D

    2011-10-01

    Along with the fast genetic improvement, nutritional and environmental effects on poultry growth performance have made it necessary to develop growth models that have the flexibility to adapt to different genotypes and growing conditions. A mechanistic simulation model of energy and nutrient utilization in growing turkeys is presented herein. The model consists of simulating the average homeorhetic and homeostatic regulations associated with the utilization of circulating glucose, fatty acid, AA, and acetyl-CoA for protein and lipid retention in carcass, viscera, and feathers in a turkey population. Homeorhesis plays a major role in the control of protein and lipid turnover for the definition of genetic potential and feed intake, whereas homeostasis adjusts growth rate through protein and lipid turnover rates and, therefore, BW gain and feed intake to the growing conditions. Also, homeostasis enables the maintenance of a dynamic balance state during all the growing period through the control of circulating nutrient concentration. The model was developed and calibrated with experimental data that described energy utilization in male and female growing turkeys. Then, the ability of the model to adapt to genotypes and to predict the average response of a turkey population to dietary energy was evaluated. Model calibration showed simulations of energy and nutrient utilization that fitted well with the experimental data because ME was satisfyingly partitioned into heat production and energy retention as protein and lipid, and nutrient intake accurately partitioned BW gain into carcass, viscera, and feathers. The evaluation of the model was also satisfactory because BW gain and feed-to-gain ratio were globally in accordance with the observations in different male and female genotypes, in spite of an overestimation of the feed-to-gain ratio during the first weeks of age. Model evaluation showed that the BW gain and feed intake response of growing turkeys to dietary energy

  1. Mechanistic model for the leaching of retorted rundle oil shale

    SciTech Connect

    Krol, A.A.; Bell, P.R.F.; Greenfield, P.F.

    1985-12-09

    The mechanisms involved in the leaching of inorganic components from oil shale mined at the Rundle deposit, Queensland, Australia, and retorted by the Lurgi-Ruhrgas process were examined. The phenomena of most significance were found to be solute dissolution, cation exchange, solution speciation and hydrodynamic and unsaturated flow effects. To check on the completeness of this characterization, a model was developed which describes the generation and transport of the major components (Ca, Mg, Na, K, Cl and SO/sub 4/) in the leachate as it infiltrates a column of dry retorted shale. Model predictions compare well with experimental results. It is concluded that the dominant mechanisms which control the rate of leaching have been recognized. 8 references, 11 figures.

  2. EDITORIAL: Atomic layer deposition Atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Godlewski, Marek

    2012-07-01

    The growth method of atomic layer deposition (ALD) was introduced in Finland by Suntola under the name of atomic layer epitaxy (ALE). The method was originally used for deposition of thin films of sulphides (ZnS, CaS, SrS) activated with manganese or rare-earth ions. Such films were grown for applications in thin-film electroluminescence (TFEL) displays. The ALE mode of growth was also tested in the case of molecular beam epitaxy. Films grown by ALD are commonly polycrystalline or even amorphous. Thus, the name ALE has been replaced by ALD. In the 80s ALD was developed mostly in Finland and neighboring Baltic countries. Deposition of a range of different materials was demonstrated at that time, including II-VI semiconductors (e.g. CdTe, CdS) and III-V (e.g. GaAs, GaN), with possible applications in e.g. photovoltaics. The number of publications on ALD was slowly increasing, approaching about 100 each year. A real boom in interest came with the development of deposition methods of thin films of high-k dielectrics. This research was motivated by a high leakage current in field-effect transistors with SiO2-based gate dielectrics. In 2007 Intel introduced a new generation of integrated circuits (ICs) with thin films of HfO2 used as gate isolating layers. In these and subsequent ICs, films of HfO2 are deposited by the ALD method. This is due to their unique properties. The introduction of ALD to the electronics industry led to a booming interest in the ALD growth method, with the number of publications increasing rapidly to well above 1000 each year. A number of new applications were proposed, as reflected in this special issue of Semiconductor Science and Technology. The included articles cover a wide range of possible applications—in microelectronics, transparent electronics, optoelectronics, photovoltaics and spintronics. Research papers and reviews on the basics of ALD growth are also included, reflecting a growing interest in precursor chemistry and growth

  3. Chemical vapor deposition growth

    NASA Technical Reports Server (NTRS)

    Ruth, R. P.; Manasevit, H. M.; Kenty, J. L.; Moudy, L. A.; Simpson, W. I.; Yang, J. J.

    1976-01-01

    A chemical vapor deposition (CVD) reactor system with a vertical deposition chamber was used for the growth of Si films on glass, glass-ceramic, and polycrystalline ceramic substrates. Silicon vapor was produced by pyrolysis of SiH4 in a H2 or He carrier gas. Preliminary deposition experiments with two of the available glasses were not encouraging. Moderately encouraging results, however, were obtained with fired polycrystalline alumina substrates, which were used for Si deposition at temperatures above 1,000 C. The surfaces of both the substrates and the films were characterized by X-ray diffraction, reflection electron diffraction, scanning electron microscopy optical microscopy, and surface profilometric techniques. Several experiments were conducted to establish baseline performance data for the reactor system, including temperature distributions on the sample pedestal, effects of carrier gas flow rate on temperature and film thickness, and Si film growth rate as a function of temperature.

  4. World oil shale deposits

    SciTech Connect

    Hook, C.O.; Russell, P.L.

    1982-01-01

    The article estimates resources in-place and their oil equivalent. The major deposits are described in the U.S., Australia, USSR, Peoples Republic of China, Morocco, Israel, Jordan, Syria, Europe and South America. 2 refs.

  5. Electrospark deposition coatings

    NASA Astrophysics Data System (ADS)

    Sheely, W. F.

    1986-11-01

    Hard surfacing for wear resistant and low-friction coatings has been improved by means of advances in the computer controls in electronic circuitry of the electrospark deposition (ESD) process. coatings of nearly any electrically conductive metal alloy or cermet can be deposited on conductive materials. Thickness is usually two mils or less, but can be as high as 10 mils. ESD coatings can quadrupole cutting tool life.

  6. Electrospark deposition coatings

    SciTech Connect

    Sheely, W.F.

    1986-11-19

    Hard surfacing for wear resistant and low-friction coatings has been improved by means of advances in the computer controls in electronic circuitry of the electrospark deposition (ESD) process. coatings of nearly any electrically conductive metal alloy or cermet can be deposited on conductive materials. Thickness is usually two mils or less, but can be as high as 10 mils. ESD coatings can quadrupole cutting tool life. (DLC)

  7. Gemstone deposits of Serbia

    NASA Astrophysics Data System (ADS)

    Miladinović, Zoran; Simić, Vladimir; Jelenković, Rade; Ilić, Miloje

    2016-06-01

    Gemstone minerals in Serbia have never been regarded as an interesting and significant resource. Nevertheless, more than 150 deposits and occurrences have been recorded and some of them preliminarily explored in the last 50 years. The majority of deposits and occurrences are located within the Serbo-Macedonian metallogenic province and the most significant metallogenic units at the existing level of knowledge are the Fruska Gora ore district, Cer ore district, Sumadija metallogenic zone, Kopaonik metallogenic zone and Lece-Halkidiki metallogenic zone. The most important genetic type of deposits is hydrothermal, particularly in case of serpentinite/peridotite as host/parent rock. Placer deposits are also economically important. The dominant gemstones are silica minerals: chalcedony (Chrysoprase, carnelian, bluish chalcedony etc.), jasper (picture, landscape, red etc.), common opal (dendritic, green, milky white etc.), silica masses (undivided), and quartz (rock crystal, amethyst etc.). Beside silica minerals significant gemstones in Serbia include also beryl (aquamarine), garnet (almandine and pyrope), tourmaline, fluorite, rhodochrosite, carbonate-silica breccia, carbonate-silica onyx, silicified wood, howlite, serpentinite, marble onyx, and kyanite. This paper aims to present an overview of Serbian gemstone deposits and occurrences and their position based on a simplified gemstone metallogenic map of Serbia, as well as genetic-industrial classification of gemstone deposits and gemstone varieties.

  8. 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

  9. DEPOSITION AND EMISSION OF GASEOUS MERCURY TO AND FROM LAKE MICHIGAN DURING THE LAKE MICHIGAN MASS BALANCE STUDY (JULY, 1994 - OCTOBER, 1995)

    EPA Science Inventory

    This paper presents measurements of dissolved gaseous mercury (DGM) concentrations in Lake Michigan and the application of a mechanistic approach to estimate deposition and emission fluxes of gaseous mercury (Hg2+ and Hg0) to and from Lake Michigan. Measurements of DGM concentr...

  10. Mechanistic platform knowledge of concomitant sugar uptake in Escherichia coli BL21(DE3) strains

    PubMed Central

    Wurm, David J.; Hausjell, Johanna; Ulonska, Sophia; Herwig, Christoph; Spadiut, Oliver

    2017-01-01

    When producing recombinant proteins, the use of Escherichia coli strain BL21(DE3) in combination with the T7-based pET-expression system is often the method of choice. In a recent study we introduced a mechanistic model describing the correlation of the specific glucose uptake rate (qs,glu) and the corresponding maximum specific lactose uptake rate (qs,lac,max) for a pET-based E. coli BL21(DE3) strain producing a single chain variable fragment (scFv). We showed the effect of qs,lac,max on productivity and product location underlining its importance for recombinant protein production. In the present study we investigated the mechanistic qs,glu/qs,lac,max correlation for four pET-based E. coli BL21(DE3) strains producing different recombinant products and thereby proved the mechanistic model to be platform knowledge for E. coli BL21(DE3). However, we found that the model parameters strongly depended on the recombinant product. Driven by this observation we tested different dynamic bioprocess strategies to allow a faster investigation of this mechanistic correlation. In fact, we succeeded and propose an experimental strategy comprising only one batch cultivation, one fed-batch cultivation as well as one dynamic experiment, to reliably determine the mechanistic model for qs,glu/qs,lac,max and get trustworthy model parameters for pET-based E. coli BL21(DE3) strains which are the basis for bioprocess development. PMID:28332595

  11. Putting the psychology back into psychological models: mechanistic versus rational approaches.

    PubMed

    Sakamoto, Yasuaki; Jones, Mattr; Love, Bradley C

    2008-09-01

    Two basic approaches to explaining the nature of the mind are the rational and the mechanistic approaches. Rational analyses attempt to characterize the environment and the behavioral outcomes that humans seek to optimize, whereas mechanistic models attempt to simulate human behavior using processes and representations analogous to those used by humans. We compared these approaches with regard to their accounts of how humans learn the variability of categories. The mechanistic model departs in subtle ways from rational principles. In particular, the mechanistic model incrementally updates its estimates of category means and variances through error-driven learning, based on discrepancies between new category members and the current representation of each category. The model yields a prediction, which we verify, regarding the effects of order manipulations that the rational approach does not anticipate. Although both rational and mechanistic models can successfully postdict known findings, we suggest that psychological advances are driven primarily by consideration of process and representation and that rational accounts trail these breakthroughs.

  12. Becquerel Crater Deposit

    NASA Technical Reports Server (NTRS)

    2002-01-01

    (Released 28 May 2002) The finely layered deposit in Becquerel crater, seen in the center of this THEMIS image, is slowly being eroded away by the action of windblown sand. Dark sand from a source north of the bright deposit is collecting along its northern edge, forming impressive barchan style dunes. These vaguely boomerang-shaped dunes form with their two points extending in the downwind direction, demonstrating that the winds capable of moving sand grains come from the north. Grains that leave the dunes climb the eroding stair-stepped layers, collecting along the cliff faces before reaching the crest of the deposit. Once there, the sand grains are unimpeded and continue down the south side of the deposit without any significant accumulation until they fall off the steep cliffs of the southern margin. The boat-hull shaped mounds and ridges of bright material called yardangs form in response to the scouring action of the migrating sand. To the west, the deposit has thinned enough that the barchan dunes extend well into the deeply eroded north-south trending canyons. Sand that reaches the south side collects and reforms barchan dunes with the same orientation as those on the north side of the deposit. Note the abrupt transition between the bright material and the dark crater floor on the southern margin. Steep cliffs are present with no indication of rubble from the obvious erosion that produced them. The lack of debris at the base of the cliffs is evidence that the bright material is readily broken up into particles that can be transported away by the wind. The geological processes that are destroying the Becquerel crater deposit appear active today. But it is also possible that they are dormant, awaiting a particular set of climatic conditions that produces the right winds and perhaps even temperatures to allow the erosion to continue.

  13. 78 FR 11604 - Deposit Insurance Regulations; Definition of Insured Deposit

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ...; Definition of Insured Deposit AGENCY: Federal Deposit Insurance Corporation (FDIC). SUMMARY: The FDIC is... FDI Act definition of the term ``deposit'' expressly excludes any obligation of a bank that is payable... purposes of national depositor preference. III. Statutory Framework A. Definition of ``Deposit'' The...

  14. 157 nm Pellicles (Thin Films) for Photolithography: Mechanistic Investigation of the VUV and UV-C Photolysis of Fluorocarbons

    SciTech Connect

    Lee, Kwangjoo; Jockusch, Steffen; Turro, Nicholas J.; French, Roger H.; Wheland, Robert C.; Lemon, M F.; Braun, Andre M.; Widerschpan, Tatjana; Dixon, David A.; Li, Jun; Ivan, Marius; Zimmerman, Paul

    2005-06-15

    The use of 157 nm as the next lower wavelength for photolithography for the production of semiconductors has created a need for transparent and radiation-durable polymers for use in soft pellicles, the polymer films which protect the chip from particle deposition. The most promising materials for pellicles are fluorinated polymers, but currently available fluorinated polymers undergo photodegradation and/or photodarkening upon long term exposure to 157 nm irradiation. To understand the mechanism of the photodegradation and photodarkening of fluorinated polymers, mechanistic studies on the photolysis of liquid model fluorocarbons, including perfluorobutylethyl ether and perfluoro-2 H-3-oxa-heptane, were performed employing UV, NMR, FTIR, GC, and GC/MS analyses. All hydrogen-containing compounds showed decreased photostability compared to the fully perfluorinated compounds. Irradiation in the presence of atmospheric oxygen showed reduced photostability compared to deoxygenated samples. Photolysis of the samples was performed at 157, 172, 185, and 254 nm and showed only minor wavelength dependence. Mechanisms for photodegradation of the fluorocarbons are proposed, which involve Rydberg excited states. Time-dependent density functional theory has been used to predict the excitation spectra of model compounds.

  15. Modelling airborne concentration and deposition rate of maize pollen

    NASA Astrophysics Data System (ADS)

    Jarosz, Nathalie; Loubet, Benjamin; Huber, Laurent

    2004-10-01

    The introduction of genetically modified (GM) crops has reinforced the need to quantify gene flow from crop to crop. This requires predictive tools which take into account meteorological conditions, canopy structure as well as pollen aerodynamic characteristics. A Lagrangian Stochastic (LS) model, called SMOP-2D (Stochastic Mechanistic model for Pollen dispersion and deposition in 2 Dimensions), is presented. It simulates wind dispersion of pollen by calculating individual pollen trajectories from their emission to their deposition. SMOP-2D was validated using two field experiments where airborne concentration and deposition rate of pollen were measured within and downwind from different sized maize (Zea mays) plots together with micrometeorological measurements. SMOP-2D correctly simulated the shapes of the concentration profiles but generally underestimated the deposition rates in the first 10 m downwind from the source. Potential explanations of this discrepancy are discussed. Incorrect parameterisation of turbulence in the transition from the crop to the surroundings is probably the most likely reason. This demonstrates that LS models for particle transfer need to be coupled with air-flow models under complex terrain conditions.

  16. Oxide Deposition By PECVD

    NASA Astrophysics Data System (ADS)

    Ibbotson, Dale E.; Hsieh, Julian J.; Flamm, Daniel L.; Mucha, J. A.

    1989-03-01

    We have studied the chemical and physical properties of silicon oxide films plasma deposited from TEOS (tetraethoxysilane), to gain an understanding of the origins of (1) step coverage and (2) film stability. TEOS was diluted in helium/oxygen mixtures and deposited as a function of discharge frequency (150 kHz and 14 MHz) and 02 flow in a parallel plate reactor. The typical deposition conditions were 1 torr total pressure, 320°C substrate temperature, 1 -9% TEOS, 1 -80% 02, and -0.1 W/cm2 discharge power. Films deposited at high frequency with excess oxygen were generally oxygen-rich, chemically unstable and hygroscopic, while films deposited at low frequency were stable to moisture and slightly deficient in oxygen. However, coverage profiles of high frequency films showed an unusual degree of directionality, which could be used to advantage for the coating of high aspect ratio features. We suggest that a judicious combination of high and low frequency discharges may improve film properties while maintaining directional step coverage. Isotopic labeling experiments were performed using 1802 to gain insight into the origins of the oxygen that is contained in these PECVD films. Complete isotopic scrambling was not observed. Film composition data suggest that there is one tenacious Si-0 bond which remains with the silicon from the original TEOS molecule during the reaction to form Si02.

  17. Applying math onto mechanisms: mechanistic knowledge is associated with the use of formal mathematical strategies.

    PubMed

    Liu, Allison S; Schunn, Christian D

    2017-01-01

    It is notoriously difficult for people to adaptively apply formal mathematical strategies learned in school to real-world contexts, even when they possess the required mathematical skills. The current study explores whether a problem context's mechanism can act as an "embodied analogy" onto which abstract mathematical concepts can be applied, leading to more frequent use of formal mathematical strategies. Participants were asked to program a robot to navigate a maze and to create a navigation strategy that would work for differently sized robots. We compared the strategy complexity of participants with high levels of mechanistic knowledge about the robot against participants with low levels of mechanistic knowledge about the robot. Mechanistic knowledge was significantly associated with the frequency and complexity of the mathematical strategies used by participants, suggesting that learning to recognize a problem context's mechanism may promote independent mathematical problem solving in applied contexts.

  18. Computer-assisted mechanistic structure-activity studies: application to diverse classes of chemical carcinogens.

    PubMed Central

    Loew, G H; Poulsen, M; Kirkjian, E; Ferrell, J; Sudhindra, B S; Rebagliati, M

    1985-01-01

    In the first part of this paper we have indicated how the techniques and capabilities of theoretical chemistry, together with experimental results, can be used in a mechanistic approach to structure-activity studies of toxicity. In the second part, we have illustrated how this computer-assisted approach has been used to identify and calculate causally related molecular indicators of relative carcinogenic activity in five classes of chemical carcinogens: polycyclic aromatic hydrocarbons and their methyl derivatives, aromatic amines, chloroethanes, chloroalkenes and dialkyl nitrosamines. In each class of chemicals studied, candidate molecular indicators have been identified that could be useful in predictive screening of unknown compounds. In addition, further insights into some mechanistic aspects of chemical carcinogenesis have been obtained. Finally, experiments have been suggested to both verify the usefulness of the indicators and test their mechanistic implications. PMID:3905382

  19. Real-time forecasting of infectious disease dynamics with a stochastic semi-mechanistic model.

    PubMed

    Funk, Sebastian; Camacho, Anton; Kucharski, Adam J; Eggo, Rosalind M; Edmunds, W John

    2016-12-16

    Real-time forecasts of infectious diseases can help public health planning, especially during outbreaks. If forecasts are generated from mechanistic models, they can be further used to target resources or to compare the impact of possible interventions. However, paremeterising such models is often difficult in real time, when information on behavioural changes, interventions and routes of transmission are not readily available. Here, we present a semi-mechanistic model of infectious disease dynamics that was used in real time during the 2013-2016 West African Ebola epidemic, and show fits to a Ebola Forecasting Challenge conducted in late 2015 with simulated data mimicking the true epidemic. We assess the performance of the model in different situations and identify strengths and shortcomings of our approach. Models such as the one presented here which combine the power of mechanistic models with the flexibility to include uncertainty about the precise outbreak dynamics may be an important tool in combating future outbreaks.

  20. Venus - Landslide Deposits

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The Magellan spacecraft has observed remnant landslide deposits apparently resulting from the collapse of volcanic structures. This image, centered at 45.2 degrees south latitude, 201.4 degrees east longitude, shows a collapse deposit 70 kilometers (43 miles) across. The bright, highly textured deposit near the center of the image probably consists of huge blocks of fractured volcanic rock, many as large as several hundred meters across. A remnant of the volcano itself, about 20 kilometers (12.4 miles) across, is seen at the center of the image. The distorted radar appearance of the volcano is a result of extremely steep slopes on the 'scars' from which the landslide material originated. A field of numerous small volcanic domes can be seen in the northern half of the image. The bright irregular lineaments trending to the north-northwest are ridges caused by regional tectonic deformation of the upper layers of the Venusian crust.

  1. Turbine Airfoil Deposition Models

    NASA Technical Reports Server (NTRS)

    Rosner, D. E.

    1984-01-01

    Gas turbine failures associated with sea-salt ingestion and sulfur-containing fuel impurities have directed attention to alkali sulfate deposition and the associated hot corrosion of gas turbine (GT) blades under some GT operating conditions. These salt deposits form thin, molten films which undermine the protective metal oxide coating normally found on GT blades. The prediction of molten salt deposition, flow and oxide dissolution, and their effects on the lifetime of turbine blades are examined. Goals include rationalizing and helping to predict corrosion patterns on operational GT rotor blades and stators, and ultimately providing some of the tools required to design laboratory simulators and future corrosion-resistant high-performance engines. Necessary background developments are reviewed first, and then recent results and tentative conclusions are presented along with a brief account of the present research plans.

  2. Laser assisted deposition

    NASA Technical Reports Server (NTRS)

    Dutta, S.

    1983-01-01

    Applications of laser-based processing techniques to solar cell metallization are discussed. Laser-assisted thermal or photolytic maskless deposition from organometallic vapors or solutions may provide a viable alternative to photovoltaic metallization systems currently in use. High power, defocused excimer lasers may be used in conjunction with masks as an alternative to direct laser writing to provide higher throughput. Repeated pulsing with excimer lasers may eliminate the need for secondary plating techniques for metal film buildup. A comparison between the thermal and photochemical deposition processes is made.

  3. "Total Deposition (TDEP) Maps"

    EPA Science Inventory

    The presentation provides an update on the use of a hybrid methodology that relies on measured values from national monitoring networks and modeled values from CMAQ to produce of maps of total deposition for use in critical loads and other ecological assessments. Additionally, c...

  4. Shaping by Deposition

    DTIC Science & Technology

    1991-01-01

    pasticprototypegreater design flexibility , rapid fabrication, and reduce cost.odels are built directly fronm liquid photopolymers by Shaping deposition processes build...ate on design models to help the designer create manufactura - ble designs on the basis of requirements and limitations of the This paper describes the

  5. Volcanogenic Massive Sulfide Deposit Density

    USGS Publications Warehouse

    Mosier, Dan L.; Singer, Donald A.; Berger, Vladimir I.

    2007-01-01

    A mineral-deposit density model for volcanogenic massive sulfide deposits was constructed from 38 well-explored control areas from around the world. Control areas contain at least one exposed volcanogenic massive sulfide deposit. The control areas used in this study contain 150 kuroko, 14 Urals, and 25 Cyprus massive sulfide subtypes of volcanogenic massive sulfide deposits. For each control area, extent of permissive rock, number of exposed volcanogenic massive sulfide deposits, map scale, deposit age, and deposit density were determined. The frequency distribution of deposit densities in these 38 control areas provides probabilistic estimates of the number of deposits for tracts that are permissive for volcanogenic massive sulfide deposits-90 percent of the control areas have densities of 100 or more deposits per 100,000 square kilometers, 50 percent of the control areas have densities of 700 or more deposits per 100,000 square kilometers, and 10 percent of the control areas have densities of 3,700 or more deposits per 100,000 square kilometers. Both map scale and the size of the control area are shown to be predictors of deposit density. Probabilistic estimates of the number of volcanogenic massive sulfide deposits can be made by conditioning the estimates on sizes of permissive area. The model constructed for this study provides a powerful tool for estimating the number of undiscovered volcanogenic massive sulfide deposits when conducting resource assessments. The value of these deposit densities is due to the consistency of these models with the grade and tonnage and the descriptive models. Mineral-deposit density models combined with grade and tonnage models allow reasonable estimates of the number, size, and grades of volcanogenic massive sulfide deposits to be made.

  6. Trouvelot Crater Deposit

    NASA Technical Reports Server (NTRS)

    2002-01-01

    [figure removed for brevity, see original site]

    Like many of the craters in the Oxia Palus region of Mars, Trouvelot Crater hosts an eroded, light-toned, sedimentary deposit on its floor. Compared with the much larger example in Becquerel Crater to the NE, the Trouvelot deposit has been so eroded by the scouring action of dark, wind-blown sand that very little of it remains. Tiny outliers of bright material separated from the main mass attest to the once, more really extensive coverage by the deposit. A similar observation can be made for White Rock, the best known example of a bright, crater interior deposit. The origin of the sediments in these deposits remains enigmatic but they are likely the result of fallout from ash or dust carried by the thin martian atmosphere.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  7. Mechanistic home range models capture spatial patterns and dynamics of coyote territories in Yellowstone

    PubMed Central

    Moorcroft, Paul R; Lewis, Mark A; Crabtree, Robert L

    2006-01-01

    Patterns of space-use by individuals are fundamental to the ecology of animal populations influencing their social organization, mating systems, demography and the spatial distribution of prey and competitors. To date, the principal method used to analyse the underlying determinants of animal home range patterns has been resource selection analysis (RSA), a spatially implicit approach that examines the relative frequencies of animal relocations in relation to landscape attributes. In this analysis, we adopt an alternative approach, using a series of mechanistic home range models to analyse observed patterns of territorial space-use by coyote packs in the heterogeneous landscape of Yellowstone National Park. Unlike RSAs, mechanistic home range models are derived from underlying correlated random walk models of individual movement behaviour, and yield spatially explicit predictions for patterns of space-use by individuals. As we show here, mechanistic home range models can be used to determine the underlying determinants of animal home range patterns, incorporating both movement responses to underlying landscape heterogeneities and the effects of behavioural interactions between individuals. Our analysis indicates that the spatial arrangement of coyote territories in Yellowstone is determined by the spatial distribution of prey resources and an avoidance response to the presence of neighbouring packs. We then show how the fitted mechanistic home range model can be used to correctly predict observed shifts in the patterns of coyote space-use in response to perturbation. PMID:16769637

  8. Territoriality and home-range dynamics in meerkats, Suricata suricatta: a mechanistic modelling approach.

    PubMed

    Bateman, Andrew W; Lewis, Mark A; Gall, Gabriella; Manser, Marta B; Clutton-Brock, Tim H

    2015-01-01

    Multiple approaches exist to model patterns of space use across species, among them resource selection analysis, statistical home-range modelling and mechanistic movement modelling. Mechanistic home-range models combine the benefits of these approaches, describing emergent territorial patterns based on fine-scale individual- or group-movement rules and incorporating interactions with neighbours and the environment. These models have not, to date, been extended to dynamic contexts. Using mechanistic home-range models, we explore meerkat (Suricata suricatta) territorial patterns, considering scent marking, direct group interactions and habitat selection. We also extend the models to accommodate dynamic aspects of meerkat territoriality (territory development and territory shift). We fit models, representing multiple working hypotheses, to data from a long-term meerkat study in South Africa, and we compare models using Akaike's and Bayesian Information Criteria. Our results identify important features of meerkat territorial patterns. Notably, larger groups do not seem to control larger territories, and groups apparently prefer dune edges along a dry river bed. Our model extensions capture instances in which 1) a newly formed group interacts more strongly with its parent groups over time and 2) a group moves its territory core out of aversive habitat. This extends our mechanistic modelling framework in previously unexplored directions.

  9. A mechanistic treatment of the dominant soil nitrogen cycling processes: Model development, testing, and application

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The development and initial application of a mechanistic model (TOUGHREACT-N) designed to characterize soil nitrogen (N) cycling and losses are described. The model couples advective and diffusive nutrient transport, multiple microbial biomass dynamics, and equilibrium and kinetic chemical reactions...

  10. Productivity of "Collisions Generate Heat" for Reconciling an Energy Model with Mechanistic Reasoning: A Case Study

    ERIC Educational Resources Information Center

    Scherr, Rachel E.; Robertson, Amy D.

    2015-01-01

    We observe teachers in professional development courses about energy constructing mechanistic accounts of energy transformations. We analyze a case in which teachers investigating adiabatic compression develop a model of the transformation of kinetic energy to thermal energy. Among their ideas is the idea that thermal energy is generated as a…

  11. DEVELOPING MECHANISTIC DATA FOR INCORPORATION INTO CANCER AND GENETIC RISK ASSESSMENTS: OLD PROBLEMS AND NEW APPROACHES

    EPA Science Inventory

    26th Lauriston S. Taylor Lecture
    DEVELOPING MECHANISTIC DATA FOR INCORPORATION INTO CANCER AND
    GENETIC RISK ASSESSMENTS: OLD PROBLEMS AND NEW APPROACHES
    R. Julian Preston, Environmental Carcinogenesis Division, U.S. Environmental Protection
    Agency, NHEERL, Research Tr...

  12. An Emphasis on Perception: Teaching Image Formation Using a Mechanistic Model of Vision.

    ERIC Educational Resources Information Center

    Allen, Sue; And Others

    An effective way to teach the concept of image is to give students a model of human vision which incorporates a simple mechanism of depth perception. In this study two almost identical versions of a curriculum in geometrical optics were created. One used a mechanistic, interpretive eye model, and in the other the eye was modeled as a passive,…

  13. Predictive mechanistic bioenergetics to model habitat suitability of shellfish culture in coastal lakes

    NASA Astrophysics Data System (ADS)

    Rinaldi, A.; Montalto, V.; Manganaro, A.; Mazzola, A.; Mirto, S.; Sanfilippo, M.; Sarà, G.

    2014-05-01

    Quantitative tools based on mechanistic modelling of functional traits able to enhance the sustainability of aquaculture and most other human activities (i.e. reducing the likelihood of detrimental impacts optimising productions), are especially important factors in the decision to site aquaculture facilities in coastal lakes, ponds and lagoons and, in the case of detrimental impact, to adopt mitigation measures. We tested the ability of mechanistic functional trait based models to predict life history traits of cultivable shellfish in shallow coastal lakes. Dynamic Energy Budget (DEB) models were run to generate spatially explicit predictions of Mytilus galloprovincialis life history (LH) traits (e.g. body size and fecundity). Using fortnightly data of food supply and hourly data of body temperatures, and exploiting the power of mechanistic rules, we estimated the amount of faeces ejected by a fixed quantity of organisms cultivated in two shallow Southern Mediterranean (Sicily) lakes. These differed in terms of temperature and food density, implying large differences in life history traits of mussels in the two study areas. This information could help facilitate the selection of sites where environmental conditions are more suitable for aquaculture and contextually compatible with sustainability. The validation exercise obtained by comparing the predicted and observed data was nearly consistent. Therefore, a mechanistic functional traits-based model seems able to capture the link between habitat characteristics and functional traits of organisms, delineating the fundamental portion of an ecological niche, the possibility of predicting LH traits and potential ecological applications in the management of natural coastal resources.

  14. Enhancing Critical Thinking through Creation of Learning Organizations within the Confines of an Overarching Mechanistic Organization

    DTIC Science & Technology

    2015-05-01

    standardized tasks – Centralized decision - making processes – Higher efficiencies through lessened variation and improved predictability – Restricted...responsive to changes in the environment – Learns from mistake – Adapts to new realities more readily – Better decision - making in non-problematic...Enhancing Critical Thinking through Creation of Learning Organizations within the Confines of an Overarching Mechanistic Organization David Riel

  15. New Simulation Methods to Facilitate Achieving a Mechanistic Understanding of Basic Pharmacology Principles in the Classroom

    ERIC Educational Resources Information Center

    Grover, Anita; Lam, Tai Ning; Hunt, C. Anthony

    2008-01-01

    We present a simulation tool to aid the study of basic pharmacology principles. By taking advantage of the properties of agent-based modeling, the tool facilitates taking a mechanistic approach to learning basic concepts, in contrast to the traditional empirical methods. Pharmacodynamics is a particular aspect of pharmacology that can benefit from…

  16. USE OF MECHANISTIC DATA TO HELP DEFINE DOSE-RESPONSE CURVES

    EPA Science Inventory

    Use of Mechanistic Data to Help Define Dose-Response Curves

    The cancer risk assessment process described by the U.S. EPA necessitates a description of the dose-response curve for tumors in humans at low (environmental) exposures. This description can either be a default l...

  17. INCORPORATION OF MECHANISTIC INFORMATION IN THE ARSENIC PBPK MODEL DEVELOPMENT PROCESS

    EPA Science Inventory

    INCORPORATING MECHANISTIC INSIGHTS IN A PBPK MODEL FOR ARSENIC

    Elaina M. Kenyon, Michael F. Hughes, Marina V. Evans, David J. Thomas, U.S. EPA; Miroslav Styblo, University of North Carolina; Michael Easterling, Analytical Sciences, Inc.

    A physiologically based phar...

  18. From Source to Sink: Mechanistic Reasoning Using the Electron-Pushing Formalism

    ERIC Educational Resources Information Center

    Bhattacharyya, Gautam

    2013-01-01

    Since the introduction of Morrison and Boyd's textbook in organic chemistry over 50 years ago, reaction mechanisms and mechanistic reasoning using the electron-pushing formalism (EPF) have become a mainstay of organic chemistry courses. In recent years there have even been several papers in this Journal and others detailing research on how…

  19. Combining correlative and mechanistic habitat suitability models to improve ecological compensation.

    PubMed

    Meineri, Eric; Deville, Anne-Sophie; Grémillet, David; Gauthier-Clerc, Michel; Béchet, Arnaud

    2015-02-01

    Only a few studies have shown positive impacts of ecological compensation on species dynamics affected by human activities. We argue that this is due to inappropriate methods used to forecast required compensation in environmental impact assessments. These assessments are mostly descriptive and only valid at limited spatial and temporal scales. However, habitat suitability models developed to predict the impacts of environmental changes on potential species' distributions should provide rigorous science-based tools for compensation planning. Here we describe the two main classes of predictive models: correlative models and individual-based mechanistic models. We show how these models can be used alone or synoptically to improve compensation planning. While correlative models are easier to implement, they tend to ignore underlying ecological processes and lack accuracy. On the contrary, individual-based mechanistic models can integrate biological interactions, dispersal ability and adaptation. Moreover, among mechanistic models, those considering animal energy balance are particularly efficient at predicting the impact of foraging habitat loss. However, mechanistic models require more field data compared to correlative models. Hence we present two approaches which combine both methods for compensation planning, especially in relation to the spatial scale considered. We show how the availability of biological databases and software enabling fast and accurate population projections could be advantageously used to assess ecological compensation requirement efficiently in environmental impact assessments.

  20. A Mechanistic Study of Arsenic (III) Rejection by Reverse Osmosis and Nanofiltration Membranes

    ERIC Educational Resources Information Center

    Suzuki, Tasuma

    2009-01-01

    Reverse osmosis/nanofiltration (RO/NF) membranes are capable to provide an effective barrier for a wide range of contaminants (including disinfection by-products precursors) in a single treatment step. However, solute rejection mechanisms by RO/NF membranes are not well understood. The lack of mechanistic information arises from experimental…

  1. Assessing Metal Levels in Children from the Mechanistic Indicators of Childhood Asthma(MICA) study

    EPA Science Inventory

    Toxic and essential metals levels can be used as health indicators. Here, we quantitatively compare and contrast toxic and essential metals levels in vacuum dust, urine, and fingernail samples of 109 children in Detroit, Michigan as part of The Mechanistic Indicators of Childhood...

  2. CHEMICAL MUTAGENESIS AND CARCINOGENESIS: INCORPORATION OF MECHANISTIC DATA INTO RISK ASSESSMENT

    EPA Science Inventory

    CHEMICAL MUTAGENESIS AND CARCINOGENESIS: INCORPORATION OF MECHANISTIC DATA INTO RISK ASSESSMENT

    The current understanding of cancer as a genetic disease, requiring a specific set of genomic alterations for a normal cell to form a metastatic tumor, has provided the oppor...

  3. Mechanistic modeling of pesticide exposure: The missing keystone of honey bee toxicology.

    PubMed

    Sponsler, Douglas B; Johnson, Reed M

    2017-04-01

    The role of pesticides in recent honey bee losses is controversial, partly because field studies often fail to detect effects predicted by laboratory studies. This dissonance highlights a critical gap in the field of honey bee toxicology: there exists little mechanistic understanding of the patterns and processes of exposure that link honey bees to pesticides in their environment. The authors submit that 2 key processes underlie honey bee pesticide exposure: 1) the acquisition of pesticide by foraging bees, and 2) the in-hive distribution of pesticide returned by foragers. The acquisition of pesticide by foraging bees must be understood as the spatiotemporal intersection between environmental contamination and honey bee foraging activity. This implies that exposure is distributional, not discrete, and that a subset of foragers may acquire harmful doses of pesticide while the mean colony exposure would appear safe. The in-hive distribution of pesticide is a complex process driven principally by food transfer interactions between colony members, and this process differs importantly between pollen and nectar. High priority should be placed on applying the extensive literature on honey bee biology to the development of more rigorously mechanistic models of honey bee pesticide exposure. In combination with mechanistic effects modeling, mechanistic exposure modeling has the potential to integrate the field of honey bee toxicology, advancing both risk assessment and basic research. Environ Toxicol Chem 2017;36:871-881. © 2016 SETAC.

  4. Mechanistic home range models capture spatial patterns and dynamics of coyote territories in Yellowstone.

    PubMed

    Moorcroft, Paul R; Lewis, Mark A; Crabtree, Robert L

    2006-07-07

    Patterns of space-use by individuals are fundamental to the ecology of animal populations influencing their social organization, mating systems, demography and the spatial distribution of prey and competitors. To date, the principal method used to analyse the underlying determinants of animal home range patterns has been resource selection analysis (RSA), a spatially implicit approach that examines the relative frequencies of animal relocations in relation to landscape attributes. In this analysis, we adopt an alternative approach, using a series of mechanistic home range models to analyse observed patterns of territorial space-use by coyote packs in the heterogeneous landscape of Yellowstone National Park. Unlike RSAs, mechanistic home range models are derived from underlying correlated random walk models of individual movement behaviour, and yield spatially explicit predictions for patterns of space-use by individuals. As we show here, mechanistic home range models can be used to determine the underlying determinants of animal home range patterns, incorporating both movement responses to underlying landscape heterogeneities and the effects of behavioural interactions between individuals. Our analysis indicates that the spatial arrangement of coyote territories in Yellowstone is determined by the spatial distribution of prey resources and an avoidance response to the presence of neighbouring packs. We then show how the fitted mechanistic home range model can be used to correctly predict observed shifts in the patterns of coyote space-use in response to perturbation.

  5. The Combined Use of Correlative and Mechanistic Species Distribution Models Benefits Low Conservation Status Species

    PubMed Central

    Rougier, Thibaud; Lassalle, Géraldine; Drouineau, Hilaire; Dumoulin, Nicolas; Faure, Thierry; Deffuant, Guillaume; Rochard, Eric; Lambert, Patrick

    2015-01-01

    Species can respond to climate change by tracking appropriate environmental conditions in space, resulting in a range shift. Species Distribution Models (SDMs) can help forecast such range shift responses. For few species, both correlative and mechanistic SDMs were built, but allis shad (Alosa alosa), an endangered anadromous fish species, is one of them. The main purpose of this study was to provide a framework for joint analyses of correlative and mechanistic SDMs projections in order to strengthen conservation measures for species of conservation concern. Guidelines for joint representation and subsequent interpretation of models outputs were defined and applied. The present joint analysis was based on the novel mechanistic model GR3D (Global Repositioning Dynamics of Diadromous fish Distribution) which was parameterized on allis shad and then used to predict its future distribution along the European Atlantic coast under different climate change scenarios (RCP 4.5 and RCP 8.5). We then used a correlative SDM for this species to forecast its distribution across the same geographic area and under the same climate change scenarios. First, projections from correlative and mechanistic models provided congruent trends in probability of habitat suitability and population dynamics. This agreement was preferentially interpreted as referring to the species vulnerability to climate change. Climate change could not be accordingly listed as a major threat for allis shad. The congruence in predicted range limits between SDMs projections was the next point of interest. The difference, when noticed, required to deepen our understanding of the niche modelled by each approach. In this respect, the relative position of the northern range limit between the two methods strongly suggested here that a key biological process related to intraspecific variability was potentially lacking in the mechanistic SDM. Based on our knowledge, we hypothesized that local adaptations to cold

  6. Are Mechanistic and Statistical QSAR Approaches Really Different? MLR Studies on 158 Cycloalkyl-Pyranones.

    PubMed

    Bhhatarai, Barun; Garg, Rajni; Gramatica, Paola

    2010-07-12

    Two parallel approaches for quantitative structure-activity relationships (QSAR) are predominant in literature, one guided by mechanistic methods (including read-across) and another by the use of statistical methods. To bridge the gap between these two approaches and to verify their main differences, a comparative study of mechanistically relevant and statistically relevant QSAR models, developed on a case study of 158 cycloalkyl-pyranones, biologically active on inhibition (Ki ) of HIV protease, was performed. Firstly, Multiple Linear Regression (MLR) based models were developed starting from a limited amount of molecular descriptors which were widely proven to have mechanistic interpretation. Then robust and predictive MLR models were developed on the same set using two different statistical approaches unbiased of input descriptors. Development of models based on Statistical I method was guided by stepwise addition of descriptors while Genetic Algorithm based selection of descriptors was used for the Statistical II. Internal validation, the standard error of the estimate, and Fisher's significance test were performed for both the statistical models. In addition, external validation was performed for Statistical II model, and Applicability Domain was verified as normally practiced in this approach. The relationships between the activity and the important descriptors selected in all the models were analyzed and compared. It is concluded that, despite the different type and number of input descriptors, and the applied descriptor selection tools or the algorithms used for developing the final model, the mechanistical and statistical approach are comparable to each other in terms of quality and also for mechanistic interpretability of modelling descriptors. Agreement can be observed between these two approaches and the better result could be a consensus prediction from both the models.

  7. Regulatory Technology Development Plan - Sodium Fast Reactor: Mechanistic Source Term – Trial Calculation

    SciTech Connect

    Grabaskas, David; Bucknor, Matthew; Jerden, James; Brunett, Acacia J.; Denman, Matthew; Clark, Andrew; Denning, Richard S.

    2016-10-01

    The potential release of radioactive material during a plant incident, referred to as the source term, is a vital design metric and will be a major focus of advanced reactor licensing. The U.S. Nuclear Regulatory Commission has stated an expectation for advanced reactor vendors to present a mechanistic assessment of the potential source term in their license applications. The mechanistic source term presents an opportunity for vendors to realistically assess the radiological consequences of an incident and may allow reduced emergency planning zones and smaller plant sites. However, the development of a mechanistic source term for advanced reactors is not without challenges, as there are often numerous phenomena impacting the transportation and retention of radionuclides. This project sought to evaluate U.S. capabilities regarding the mechanistic assessment of radionuclide release from core damage incidents at metal fueled, pool-type sodium fast reactors (SFRs). The purpose of the analysis was to identify, and prioritize, any gaps regarding computational tools or data necessary for the modeling of radionuclide transport and retention phenomena. To accomplish this task, a parallel-path analysis approach was utilized, as shown below. One path, led by Argonne and Sandia National Laboratories, sought to perform a mechanistic source term assessment using available codes, data, and models, with the goal to identify gaps in the current knowledge base. The second path, performed by an independent contractor, performed sensitivity analyses to determine the importance of particular radionuclides and transport phenomena in regards to offsite consequences. The results of the two pathways were combined to prioritize gaps in current capabilities.

  8. Hydroxyapatite Deposition Disease

    DTIC Science & Technology

    2006-11-01

    calcific tendinitis or calcific periarthritis, is characterized by the deposition of calcium phosphate crystals (predominantly hydroxyapatite) in...site of HADD is the hip, where calcifications are usually found in the gluteus medius tendon or along the femur at various sites of tendinous ...posterolateral femoral diaphysis, as well as in various other tendinous attachments to the femur. Computed tomography is also helpful in the demonstration

  9. Uranium deposits of Brazil

    SciTech Connect

    1991-09-01

    Brazil is a country of vast natural resources, including numerous uranium deposits. In support of the country`s nuclear power program, Brazil has developed the most active uranium industry in South America. Brazil has one operating reactor (Angra 1, a 626-MWe PWR), and two under construction. The country`s economic challenges have slowed the progress of its nuclear program. At present, the Pocos de Caldas district is the only active uranium production. In 1990, the Cercado open-pit mine produced approximately 45 metric tons (MT) U{sub 3}O{sub 8} (100 thousand pounds). Brazil`s state-owned uranium production and processing company, Uranio do Brasil, announced it has decided to begin shifting its production from the high-cost and nearly depleted deposits at Pocos de Caldas, to lower-cost reserves at Lagoa Real. Production at Lagoa Real is schedules to begin by 1993. In addition to these two districts, Brazil has many other known uranium deposits, and as a whole, it is estimated that Brazil has over 275,000 MT U{sub 3}O{sub 8} (600 million pounds U{sub 3}O{sub 8}) in reserves.

  10. Electrophoretic deposition of biomaterials

    PubMed Central

    Boccaccini, A. R.; Keim, S.; Ma, R.; Li, Y.; Zhitomirsky, I.

    2010-01-01

    Electrophoretic deposition (EPD) is attracting increasing attention as an effective technique for the processing of biomaterials, specifically bioactive coatings and biomedical nanostructures. The well-known advantages of EPD for the production of a wide range of microstructures and nanostructures as well as unique and complex material combinations are being exploited, starting from well-dispersed suspensions of biomaterials in particulate form (microsized and nanoscale particles, nanotubes, nanoplatelets). EPD of biological entities such as enzymes, bacteria and cells is also being investigated. The review presents a comprehensive summary and discussion of relevant recent work on EPD describing the specific application of the technique in the processing of several biomaterials, focusing on (i) conventional bioactive (inorganic) coatings, e.g. hydroxyapatite or bioactive glass coatings on orthopaedic implants, and (ii) biomedical nanostructures, including biopolymer–ceramic nanocomposites, carbon nanotube coatings, tissue engineering scaffolds, deposition of proteins and other biological entities for sensors and advanced functional coatings. It is the intention to inform the reader on how EPD has become an important tool in advanced biomaterials processing, as a convenient alternative to conventional methods, and to present the potential of the technique to manipulate and control the deposition of a range of nanomaterials of interest in the biomedical and biotechnology fields. PMID:20504802

  11. Inkjet deposited circuit components

    NASA Astrophysics Data System (ADS)

    Bidoki, S. M.; Nouri, J.; Heidari, A. A.

    2010-05-01

    All-printed electronics as a means of achieving ultra-low-cost electronic circuits has attracted great interest in recent years. Inkjet printing is one of the most promising techniques by which the circuit components can be ultimately drawn (i.e. printed) onto the substrate in one step. Here, the inkjet printing technique was used to chemically deposit silver nanoparticles (10-200 nm) simply by ejection of silver nitrate and reducing solutions onto different substrates such as paper, PET plastic film and textile fabrics. The silver patterns were tested for their functionality to work as circuit components like conductor, resistor, capacitor and inductor. Different levels of conductivity were achieved simply by changing the printing sequence, inks ratio and concentration. The highest level of conductivity achieved by an office thermal inkjet printer (300 dpi) was 5.54 × 105 S m-1 on paper. Inkjet deposited capacitors could exhibit a capacitance of more than 1.5 nF (parallel plate 45 × 45 mm2) and induction coils displayed an inductance of around 400 µH (planar coil 10 cm in diameter). Comparison of electronic performance of inkjet deposited components to the performance of conventionally etched items makes the technique highly promising for fabricating different printed electronic devices.

  12. Intricately Rippled Sand Deposits

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Click on the image for Intricately Rippled Sand Deposits (QTVR)

    NASA's Mars Exploration Rover Spirit welcomed the beginning of 2006 on Earth by taking this striking panorama of intricately rippled sand deposits in Gusev Crater on Mars. This is an approximate true-color rendering of the 'El Dorado' ripple field provided by Spirit over the New Year's holiday weekend. The view spans about 160 degrees in azimuth from left to right and consists of images acquired by Spirit's panoramic camera on Spirit's 708th and 710th Martian days, or sols, (Dec. 30, 2005 and Jan. 1, 2006). Spirit used the Pancam's 750-nanometer, 530-nanometer and 430-nanometer filters to capture the colors on Mars. Scientists have eliminated seams between individual frames in the sky portion of the mosaic to better simulate the vista a person standing on Mars would see. Spirit spent several days acquiring images, spectral data, and compositional and mineralogical information about these large sand deposits before continuing downhill toward 'Home Plate.'

  13. A Mechanistic Understanding of North American Monsoon and Microphysical Properties of Ice Particles

    NASA Astrophysics Data System (ADS)

    Erfani, Ehsan

    A mechanistic understanding of the North American Monsoon (NAM) is suggested by incorporating local- and synoptic-scale processes. The local-scale mechanism describes the effect sea surface temperature (SST) in Gulf of California (GC) and how it contributes to the low-level moisture during the 2004 NAM. Before NAM onset, the strong low-level temperature inversion exists over the GC, but this inversion weakens with increasing GC SST and generally disappears once SSTs exceed 29.5°C, allowing the moist air, trapped in the MBL, to mix with free tropospheric air. This leads to a deep, moist layer that can be transported toward the NAM regions to produce thunderstorms. The synoptic scale mechanism is based on climatologies from 1983 to 2010 and explains that the warmest SSTs moving up the coast contributes to NAM convection and atmospheric heating, and consequently advancing the position of the anticyclone and the region of descent northward. In order to improve microphysical properties of ice clouds, this study develops self-consistent second order polynomial mass- and projected area-dimension (m-D and A-D) expressions that are valid over a much larger size range, compared to traditional power laws. Such expressions can easily be reduced to power laws for the size range of interest, in order to use in cloud and climate models. This was done by combining field measurements of individual ice particle m and D with airborne optical probe measurements of D, A and estimates of m. The resulting m-D and A-D expressions are functions of temperature and cloud type (synoptic vs. anvil), and are in good agreement with m-D power laws developed from recent field studies. These expressions also appear representative for heavily rimed dendrites occurring over the Sierra Nevada Mountains. By using the m-D field measurements of rimed and unrimed particles, and by developing theoretical methods, an approach was suggested for calculating rimed m and A, which has the benefit of accounting

  14. Process and film characterization of chemical-bath-deposited ZnS thin films

    SciTech Connect

    Dona, J.M.; Herrero, J.

    1994-01-01

    Chemical-bath deposition of ZnS thin films from NH{sub 3}/NH{sub 2}-NH{sub 2}/SC(NH{sub 2}){sub 2}/ZnSO{sub 4} solutions has been studied. The effect of various process parameters on the growth and the film quality is presented. A first approach to a mechanistic interpretation of the chemical process is reported. The structural, optical, chemical, and electrical properties of the ZNS thin films deposited by this method have been studied. The electron diffraction (EDS) analysis shows that the films are microcrystalline with a cubic structure. EDS analysis has demonstrated that the films are highly stoichiometric. Scanning electron microscopy studies of the ZnS thin films deposited by this method show that the films are continuous and homogeneous. Electrical conductivity measurements have shown the highly resistivity nature of these films ({sigma} = 10{sup {minus}9} S/cm).

  15. Creep of chemically vapor deposited SiC fibers

    NASA Technical Reports Server (NTRS)

    Dicarlo, J. A.

    1984-01-01

    The creep, thermal expansion, and elastic modulus properties for chemically vapor deposited SiC fibers were measured between 1000 and 1500 C. Creep strain was observed to increase logarithmically with time, monotonically with temperature, and linearly with tensile stress up to 600 MPa. The controlling activation energy was 480 + or - 20 kJ/mole. Thermal pretreatments near 1200 and 1450 C were found to significantly reduce fiber creep. These results coupled with creep recovery observations indicate that below 1400 C fiber creep is anelastic with neglible plastic component. This allowed a simple predictive method to be developed for describing fiber total deformation as a function of time, temperature, and stress. Mechanistic analysis of the property data suggests that fiber creep is the result of beta-SiC grain boundary sliding controlled by a small percent of free silicon in the grain boundaries.

  16. Particle Deposition onto Enclosure Surfaces

    DTIC Science & Technology

    2009-08-20

    Rate, P 16 4.3 Comparison of vd and fi 16 5. Methods for Measurement of Particle Deposition 19 5.1 Measuring Particle Deposition Rate, p 19...deposition. 18 5. Methods for Measurement of Particle Deposition Owing to its importance for numerous engineering systems, the processes of particle...particle counter, time-of-flight aerosol spectrometer, electrical aerosol mobility analyzer, as well as aerosol generation methods , can be found in

  17. A Mechanistic study of Plasma Treatment Effects on Demineralized Dentin Surfaces for Improved Adhesive/Dentin Interface Bonding

    PubMed Central

    Dong, Xiaoqing; Chen, Meng; Wang, Yong; Yu, Qingsong

    2014-01-01

    Our previous work has shown that non-thermal plasma treatment of demineralized dentin significantly (p<0.05) improved adhesive/dentin bonding strength for dental composite restoration as compared with the untreated controls. This study is to achieve mechanistic understanding of the plasma treatment effects on dentin surface through investigating the plasma treated dentin surfaces and their interaction with adhesive monomer, 2-Hydroxyethyl methacrylate (HEMA). The plasma treated dentin surfaces from human third molars were evaluated by water contact angle measurements and scanning electron microscopy (SEM). It was found that plasma-treated dentin surface with subsequent HEMA immersion (Plasma/HEMA Treated) had much lower water contact angle compared with only plasma-treated (Plasma Treated) or only HEMA immersed (HEMA Treated) dentin surfaces. With prolong water droplet deposition time, water droplets spread out completely on the Plasma/HEMA Treated dentin surfaces. SEM images of Plasma/HEMA Treated dentin surfaces verified that dentin tubules were opened-up and filled with HEMA monomers. Extracted type I collagen fibrils, which was used as simulation of the exposed dentinal collagen fibrils after acid etching step, were plasma treated and analyzed with Fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) spectra. FT-IR spectra of the Plasma/HEMA Treated collage fibrils showed broadened amide I peak at 1660 cm−1 and amide II at 1550 cm−1, which indicate secondary structure changes of the collagen fibrils. CD spectra indicated that 67.4% collagen helix structures were denatured after plasma treatment. These experimental results demonstrate that non-thermal argon plasma treatment was very effective in loosing collagen structure and enhancing adhesive monomer penetration, which are beneficial to thicker hybrid layer and longer resin tag formation, and consequently enhance adhesive/dentin interface bonding. PMID:25267936

  18. A Mechanistic study of Plasma Treatment Effects on Demineralized Dentin Surfaces for Improved Adhesive/Dentin Interface Bonding.

    PubMed

    Dong, Xiaoqing; Chen, Meng; Wang, Yong; Yu, Qingsong

    2014-07-01

    Our previous work has shown that non-thermal plasma treatment of demineralized dentin significantly (p<0.05) improved adhesive/dentin bonding strength for dental composite restoration as compared with the untreated controls. This study is to achieve mechanistic understanding of the plasma treatment effects on dentin surface through investigating the plasma treated dentin surfaces and their interaction with adhesive monomer, 2-Hydroxyethyl methacrylate (HEMA). The plasma treated dentin surfaces from human third molars were evaluated by water contact angle measurements and scanning electron microscopy (SEM). It was found that plasma-treated dentin surface with subsequent HEMA immersion (Plasma/HEMA Treated) had much lower water contact angle compared with only plasma-treated (Plasma Treated) or only HEMA immersed (HEMA Treated) dentin surfaces. With prolong water droplet deposition time, water droplets spread out completely on the Plasma/HEMA Treated dentin surfaces. SEM images of Plasma/HEMA Treated dentin surfaces verified that dentin tubules were opened-up and filled with HEMA monomers. Extracted type I collagen fibrils, which was used as simulation of the exposed dentinal collagen fibrils after acid etching step, were plasma treated and analyzed with Fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) spectra. FT-IR spectra of the Plasma/HEMA Treated collage fibrils showed broadened amide I peak at 1660 cm(-1) and amide II at 1550 cm(-1), which indicate secondary structure changes of the collagen fibrils. CD spectra indicated that 67.4% collagen helix structures were denatured after plasma treatment. These experimental results demonstrate that non-thermal argon plasma treatment was very effective in loosing collagen structure and enhancing adhesive monomer penetration, which are beneficial to thicker hybrid layer and longer resin tag formation, and consequently enhance adhesive/dentin interface bonding.

  19. Deposition of SOCs in forests

    SciTech Connect

    Horstmann, M.; McLachlan, M.S.

    1995-12-31

    The bulk deposition, wet-only deposition, dry-only deposition and ambient air concentrations of PCDD/Fs, PCBs and PAHs were measured in an 80 year old spruce forest, an 80 year old mixed deciduous (beech and oak) forest, and in an adjacent clearing over a period of 1--2 years. The deposition of the less volatile compounds that are primarily particle bound in the atmosphere was similar at both sites. These compounds were deposited primarily through wet deposition, as shown by the measurements in the clearing. In contrast, the deposition of the more volatile compounds was much higher at the forest sites than in the clearing. For instance, the annual deposition of Cl{sub 4}DF was 5 times higher in the spruce forest and 8 times higher in the deciduous forest. The excess deposition in the deciduous forest was almost completely due to the leaf fall in October--December, while about half of the excess deposition in the spruce forest was the result of needle fall. A further, as yet unexplained deposition mechanism accounted for the remainder of the flux in the spruce forest. Other studies have shown that more volatile SOCs are deposited to vegetation primarily through dry gaseous deposition. Hence, while forests have little influence on the deposition of less volatile compounds like the higher chlorinated PCDD/Fs and the 5--6 ring PAHs, dry deposition to leaves/needles and their subsequent falling to the forest floor make forest soils an extremely important sink for more volatile SOC.

  20. Fluidized Crater Ejecta Deposit

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The Mars Orbiter Camera (MOC) onboard the Mars Global Surveyor (MGS) spacecraft continued to obtain high resolution images of the red planet into August 1998. At this time, each ground track (the portion of Mars available for MOC imaging on a given orbit) covers areas from about 40oN on the late afternoon side of the planet, up over the sunlit north polar cap, and down the early morning side of Mars to about 20oN latitude. Early morning and late afternoon views provide good shadowing to reveal subtle details on the martian surface. Views of Mars with such excellent lighting conditions will not be seen by MOC once MGS's Science Phasing Orbits end in mid-September 1998.

    The image shown here, MOC image 47903, was targeted on Friday afternoon (PDT), August 7, 1998. This picture of ejecta from a nameless 9.1 kilometer (5.7 mile)-diameter crater was designed to take full advantage of the present lighting conditions. When the image was taken (around 5:38 p.m. (PDT) on Saturday, August 8, 1998), the Sun had just risen and was only about 6o above the eastern horizon. With the Sun so low in the local sky, the contrast between sunlit and shadowed surfaces allowed new, subtle details to be revealed on the surface of the crater ejecta deposit.

    The crater shown here has ejecta of a type that was first identified in Mariner 9 and Viking Orbiter images as 'fluidized' ejecta. Ejecta is the material that is thrown out from the crater during the explosion that results when a meteor--piece of a comet or asteroid--collides with the planet. Fluidized ejecta is characterized by its lobate appearance, and sometimes by the presence of a ridge along the margin of the ejecta deposit. In the case of the crater shown here, there are two ridges that encircle the crater ejecta--this type of ejecta deposit is sometimes called a double-lobe rampart deposit. The MOC image shows that this particular crater also has 'normal' ejecta that occurs out on the plains, beyond the outermost ridge of

  1. Coffee ring deposition in bands

    NASA Astrophysics Data System (ADS)

    Mandre, Shreyas; Wu, Ning; Aizenberg, Joanna; Mahadevan, Lakshminarayanan

    2010-11-01

    Microscopic particles suspended in a liquid are transported and deposited at a contact line, as the contact line recedes due to evaporation. A particle layer of uniform thickness is deposited if the particle concentration is above a threshold; below this threshold the deposit forms periodic bands oriented parallel to the contact line. We present a model for the formation of these bands based on evaporation leading to the breakup of the thin liquid film near the contact line. The threshold results from a competition between evaporation speed and deposition speed. Using this model, we predict the thickness and length of the bands, making the control of patterned deposition possible.

  2. Database of recent tsunami deposits

    USGS Publications Warehouse

    Peters, Robert; Jaffe, Bruce E.

    2010-01-01

    This report describes a database of sedimentary characteristics of tsunami deposits derived from published accounts of tsunami deposit investigations conducted shortly after the occurrence of a tsunami. The database contains 228 entries, each entry containing data from up to 71 categories. It includes data from 51 publications covering 15 tsunamis distributed between 16 countries. The database encompasses a wide range of depositional settings including tropical islands, beaches, coastal plains, river banks, agricultural fields, and urban environments. It includes data from both local tsunamis and teletsunamis. The data are valuable for interpreting prehistorical, historical, and modern tsunami deposits, and for the development of criteria to identify tsunami deposits in the geologic record.

  3. Multi-chamber deposition system

    DOEpatents

    Jacobson, Richard L.; Jeffrey, Frank R.; Westerberg, Roger K.

    1989-10-17

    A system for the simultaneous deposition of different coatings onto a thin web within a large volume vacuum chamber is disclosed which chamber is provided with a plurality of deposition chambers in which the different layers are deposited onto the film as its moves from a supply roll to a finished take-up roll of coated web. The deposition chambers provided within the large vacuum chamber are provided with separate seals which minimize back diffusion of any dopant gas from adjacent deposition chambers.

  4. Multi-chamber deposition system

    DOEpatents

    Jacobson, Richard L.; Jeffrey, Frank R.; Westerberg, Roger K.

    1989-06-27

    A system for the simultaneous deposition of different coatings onto a thin web within a large volume vacuum chamber is disclosed which chamber is provided with a plurality of deposition chambers in which the different layers are deposited onto the film as its moves from a supply roll to a finished take-up roll of coated web. The deposition chambers provided within the large vacuum chamber are provided with separate seals which minimize back diffusion of any dopant gas from adjacent deposition chambers.

  5. Electrophoretic Deposition for Fabricating Microbatteries

    NASA Technical Reports Server (NTRS)

    West, William; Whitacre, Jay; Bugga, Ratnakumar

    2003-01-01

    An improved method of fabrication of cathodes of microbatteries is based on electrophoretic deposition. Heretofore, sputtering (for deposition) and the use of photoresist and liftoff (for patterning) have been the primary methods of fabricating components of microbatteries. The volume of active electrode material that can be deposited by sputtering is limited, and the discharge capacities of prior microbatteries have been limited accordingly. In addition, sputter deposition is slow. In contrast, electrophoretic deposition is much faster and has shown promise for increasing discharge capacities by a factor of 10, relative to those of microbatteries fabricated by prior methods.

  6. The Chilean nitrate deposits.

    USGS Publications Warehouse

    Ericksen, G.E.

    1983-01-01

    The nitrate deposits in the arid Atacama desert of northern Chile consist of saline-cemented surficial material, apparently formed in and near a playa lake that formerly covered the area. Many features of their distribution and chemical composition are unique. The author believes the principal sources of the saline constituents were the volcanic rocks of late Tertiary and Quaternary age in the Andes and that the nitrate is of organic origin. Possible sources of the nitrate, iodate, perchlorate and chromate are discussed. -J.J.Robertson

  7. TOPICAL REVIEW: Mechanistically based probability modelling, life prediction and reliability assessment

    NASA Astrophysics Data System (ADS)

    Wei, Robert P.; Harlow, D. Gary

    2005-01-01

    Life prediction and reliability assessment are essential components for the life-cycle engineering and management (LCEM) of modern engineered systems. These systems can range from microelectronic and bio-medical devices to large machinery and structures. To be effective, the underlying approach to LCEM must be transformed to embody mechanistically based probability modelling, vis-à-vis the more traditional experientially based statistical modelling, for predicting damage evolution and distribution. In this paper, the probability and statistical approaches are compared and differentiated. The process of model development on the basis of mechanistic understanding derived from critical experiments is illustrated through selected examples. The efficacy of this approach is illustrated through an example of the evolution and distribution of corrosion and corrosion fatigue damage in aluminium alloys in relation to aircraft that had been in long-term service.

  8. Formalising a mechanistic linkage between heterotrophic feeding and thermal bleaching resistance

    NASA Astrophysics Data System (ADS)

    Wooldridge, Scott A.

    2014-12-01

    In this paper, I utilise the CO2 (sink) limitation model of coral bleaching to propose a new biochemical framework that explains how certain (well-adapted) coral species can utilise heterotrophic carbon acquisition to combat the damaging algal photoinhibition response sequence that underpins thermal bleaching, thereby increasing thermal bleaching resistance. This mechanistic linkage helps to clarify a number of previously challenging experimental responses arising from feeding (versus starved) temperature stress experiments, and isotope labelling (tracer) experiments with heterotrophic carbon sources (e.g., zooplankton). In an era of rapidly warming surface ocean temperatures, the conferred fitness benefits arising from such a mechanistic linkage are considerable. Yet, various ecological constraints are outlined which caution against the ultimate benefit of the mechanism for raising bleaching thresholds at the coral community (reef) scale. Future experiments are suggested that can strengthen these proposed arguments.

  9. Tautomeric stabilities of 4-fluorohistidine shed new light on mechanistic experiments with labeled ribonuclease A

    NASA Astrophysics Data System (ADS)

    Kasireddy, Chandana; Ellis, Jonathan M.; Bann, James G.; Mitchell-Koch, Katie R.

    2016-12-01

    Ribonuclease A is the oldest model for studying enzymatic mechanisms, yet questions remain about proton transfer within the active site. Seminal work by Jackson et al. (1994) labeled Ribonuclease A with 4-fluorohistidine, concluding that active-site histidines act as general acids and bases. Calculations of 4-fluorohistidine indicate that the π-tautomer is predominant in all simulated environments (by ∼17 kJ/mol), strongly suggesting that fluoro-labeled ribonuclease A functions with His119 in π-tautomer. The tautomeric form of His119 during proton transfer and tautomerism as a putative mechanistic step in wild-type RNase A remain open questions and should be considered in future mechanistic studies.

  10. Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

    NASA Astrophysics Data System (ADS)

    Grossmann, Nina; Vakkasoglu, Ahmet S.; Hulpke, Sabine; Abele, Rupert; Gaudet, Rachelle; Tampé, Robert

    2014-11-01

    The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the conserved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. Our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.

  11. Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce; Chiang, Chun-Te; Mai, Zhiming; Goldschmidt, Ruth; Rizvi, Imran; Ebrahim-Zadeh, Neema; Hasan, Tayyaba

    2016-03-01

    It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.

  12. Mechanistic modelling of urania fuel evolution and fission product migration during irradiation and heating

    NASA Astrophysics Data System (ADS)

    Veshchunov, M. S.; Dubourg, R.; Ozrin, V. D.; Shestak, V. E.; Tarasov, V. I.

    2007-05-01

    The models of the mechanistic code MFPR (Module for Fission Product Release) developed by IBRAE in collaboration with IRSN are described briefly in the first part of the paper. The influence of microscopic defects in the UO2 crystal structure on fission-gas transport out of grains and release from fuel pellets is described. These defects include point defects such as vacancies, interstitials and fission atoms, and extended defects such as bubbles, pores and dislocations. The mechanistic description of chemically active elements behaviour (fission-induced) is based on complex association of diffusion-vaporisation mechanism involving multi-phase and multi-component thermo-chemical equilibrium at the grain boundary with accurate calculation of fuel oxidation. In the second part, results of the code applications are given to different situations: normal LWR reactor operation, high temperature annealing, loss of coolant accident (LOCA) and severe accidents conditions.

  13. A data-intensive approach to mechanistic elucidation applied to chiral anion catalysis

    PubMed Central

    Milo, Anat; Neel, Andrew J.; Toste, F. Dean; Sigman, Matthew S.

    2015-01-01

    Knowledge of chemical reaction mechanisms can facilitate catalyst optimization, but extracting that knowledge from a complex system is often challenging. Here we present a data-intensive method for deriving and then predictively applying a mechanistic model of an enantioselective organic reaction. As a validating case study, we selected an intramolecular dehydrogenative C-N coupling reaction, catalyzed by chiral phosphoric acid derivatives, in which catalyst-substrate association involves weak, non-covalent interactions. Little was previously understood regarding the structural origin of enantioselectivity in this system. Catalyst and substrate substituent effects were probed by systematic physical organic trend analysis. Plausible interactions between the substrate and catalyst that govern enantioselectivity were identified and supported experimentally, indicating that such an approach can afford an efficient means of leveraging mechanistic insight to optimize catalyst design. PMID:25678656

  14. Mechanistic modelling of cancer: some reflections from software engineering and philosophy of science.

    PubMed

    Cañete-Valdeón, José M; Wieringa, Roel; Smallbone, Kieran

    2012-12-01

    There is a growing interest in mathematical mechanistic modelling as a promising strategy for understanding tumour progression. This approach is accompanied by a methodological change of making research, in which models help to actively generate hypotheses instead of waiting for general principles to become apparent once sufficient data are accumulated. This paper applies recent research from philosophy of science to uncover three important problems of mechanistic modelling which may compromise its mainstream application, namely: the dilemma of formal and informal descriptions, the need to express degrees of confidence and the need of an argumentation framework. We report experience and research on similar problems from software engineering and provide evidence that the solutions adopted there can be transferred to the biological domain. We hope this paper can provoke new opportunities for further and profitable interdisciplinary research in the field.

  15. Mechanistic modelling of cancer: some reflections from software engineering and philosophy of science

    NASA Astrophysics Data System (ADS)

    Cañete-Valdeón, José M.; Wieringa, Roel; Smallbone, Kieran

    2012-12-01

    There is a growing interest in mathematical mechanistic modelling as a promising strategy for understanding tumour progression. This approach is accompanied by a methodological change of making research, in which models help to actively generate hypotheses instead of waiting for general principles to become apparent once sufficient data are accumulated. This paper applies recent research from philosophy of science to uncover three important problems of mechanistic modelling which may compromise its mainstream application, namely: the dilemma of formal and informal descriptions, the need to express degrees of confidence and the need of an argumentation framework. We report experience and research on similar problems from software engineering and provide evidence that the solutions adopted there can be transferred to the biological domain. We hope this paper can provoke new opportunities for further and profitable interdisciplinary research in the field.

  16. Synthesis, cytotoxicity and mechanistic evaluation of 4-oxoquinoline-3-carboxamide derivatives: finding new potential anticancer drugs.

    PubMed

    Forezi, Luana da S M; Tolentino, Nathalia M C; de Souza, Alessandra M T; Castro, Helena C; Montenegro, Raquel C; Dantas, Rafael F; Oliveira, Maria E I M; Silva, Floriano P; Barreto, Leilane H; Burbano, Rommel M R; Abrahim-Vieira, Bárbara; de Oliveira, Riethe; Ferreira, Vitor F; Cunha, Anna C; Boechat, Fernanda da C S; de Souza, Maria Cecília B V

    2014-05-22

    As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10-18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

  17. Exploiting the Imidazolium Effect in Base-free Ammonium Enolate Generation: Synthetic and Mechanistic Studies.

    PubMed

    Young, Claire M; Stark, Daniel G; West, Thomas H; Taylor, James E; Smith, Andrew D

    2016-11-07

    N-Acyl imidazoles and catalytic isothiourea hydrochloride salts function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition-cyclization reactions using different α,β-unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the "imidazolium" effect in ammonium enolate formation and have highlighted key differences with traditional base-mediated processes.

  18. Microstructural and Mechanistic Study of Primary Creep in Titanium Alloys at Lower Temperatures.

    DTIC Science & Technology

    2007-11-02

    98- ata sources, spect of this 15 Jefferson 503. 1. AGENCY USE ONLY (Leave blank) | 2. REPORT DATE 5 June 1998 3. REPORT TYPE AND DATES...COVERED Final Technical Report 1 Feb 95 to 31 Jan 98 4. TITLE AND SUBTITLE Microstructural and Mechanistic Study of Primary Creep in titanium...alloys at Lower Temperatures 6. AUTHOR(S) Professor Michael J. Mills 5 . FUNDING NUMBERS F49620-95-1-0153 7. PERFORMING ORGANIZATION NAME(S) AND

  19. N-Heterocyclic carbene-mediated oxidative esterification of aldehydes: ester formation and mechanistic studies.

    PubMed

    Maji, Biswajit; Vedachalan, Seenuvasan; Ge, Xin; Cai, Shuting; Liu, Xue-Wei

    2011-05-06

    An unexpected N-heterocyclic carbene-catalyzed esterification of α,β-unsaturated aldehydes including aromatic aldehydes with reactive cinnamyl bromides in the presence of air oxygen or MnO(2) as an oxidant is described. In the presence of oxygen, halogenated and electron-deficient aldehydes react smoothly to furnish esters in good yields. Great efforts have been made on mechanistic studies to deduce a plausible mechanism, based on the experimental results and isotopic labeling experiment.

  20. Solving Inverse Problems for Mechanistic Systems Biology Models with Unknown Inputs

    DTIC Science & Technology

    2014-10-16

    the therapy is extremely difficult [9]. Other drug therapies, including pain medicine, vasopressors and type 2 diabetes mellitus , basically suffer...interrelationships between tesaglitazar exposure and renal function in patients with type 2 diabetes mellitus ,” J. Clin. Pharmacol., vol. 52, pp. 1317–1327...including mechanistic modeling studies in cancer chemotherapy (e.g., [12, 13]), anti- diabetic drugs (e.g., [14]) and HIV (e.g., [15]). Figure 1

  1. Enhancing Critical Thinking Through Creation of Learning Organizations Within the Confines of an Overarching Mechanistic Organization

    DTIC Science & Technology

    2015-04-30

    the Department of Defense’s (DoD’s) acquisition workforce to apply critical thinking skills in executing acquisition programs. Quotes include “Like...p. 3). This has led to requests for greater education and training in critical thinking skills , including a recent article, which states...Functional specialization, another key characteristic of mechanistic organizations and the acquisition workforce, while providing the specific skills needed

  2. Canyon Floor Deposits

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Context image for PIA03598 Canyon Floor Deposits

    The layered and wind eroded deposits seen in this VIS image occur on the floor of Chandor Chasma.

    Image information: VIS instrument. Latitude 5.2S, Longitude 283.4E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  3. Radioactive deposits in California

    USGS Publications Warehouse

    Walker, George W.; Lovering, Tom G.

    1954-01-01

    Reconnaissance examination by Government geologists of many areas, mine properties, and prospects in California during the period between 1948 and 1953 has confirmed the presence of radioactive materials in place at more than 40 localities. Abnormal radioactivity at these localities is due to concentrations of primary and secondary uranium minerals, to radon gas, radium (?), and to thorium minerals. Of the known occurrences only three were thought to contain uranium oxide (uranitite or pitchblende), 4 contained uranium-bearing columbate, tantalate, or titanate minerals, 12 contained secondary uranium minerals, such as autunite, carnotite, and torbernite, one contained radon gas, 7 contained thorium minerals, and, at the remaining 16 localities, the source of the anomalous radiation was not positively determined. The occurrences in which uranium oxide has been tentatively identified include the Rathgeb mine (Calaveras County), the Yerih group of claims (San Bernardino County), and the Rainbow claim (Madera County). Occurrences of secondary uranium minerals are largely confined to the arid desert regions of south-eastern California including deposits in San Bernardino, Kern, Inyo, and Imperial Counties. Uranium-bearing columbate, tantalate, or titanate minerals have been reported from pegmatite and granitic rock in southeastern and eastern California. Thorium minerals have been found in vein deposits in eastern San Bernardino County and from pegmatites and granitic rocks in various parts of southeastern California; placer concentrations of thorium minerals are known from nearly all areas in the State that are underlain, in part, by plutonic crystalline rocks. The primary uranium minerals occur principally as minute accessory crystals in pegmatite or granitic rock, or with base-metal sulfide minerals in veins. Thorium minerals also occur as accessory crystals in pegmatite or granitic rock, in placer deposits derived from such rock, and, at Mountain Pass, in veins

  4. The mechanistic-holistic divide revisited: The case of the lac operon.

    PubMed

    Racine, Valérie

    2016-10-01

    In this paper, I revisit the development of the repression model of genetic regulation in the lac operon to challenge a common application of a conceptual framework in the history of biology. I take Allen's (1978) account of the changes in the life sciences during the early and mid-twentieth century as an example of a common application of a framework based on the dichotomy between a mechanistic, or reductionist, approach to science and a holistic one. From this conceptual framework, Allen infers two general claims about the process of science and its goals: (1) that "mechanistic materialism" has often presented a more practical way to begin the study of complex phenomena in the life sciences, and (2) that the approach described as "holistic materialism" provides a more complete or accurate description of the natural world. The development of the lac operon model does not fit Allen's generalizations about scientific developments, and it can be used to cast some doubt on the scope of application of that conceptual framework. I argue that a better framework to interpret particular episodes in the history of molecular biology is to consider the ways in which biologists prioritize and track different aspects of the phenomena under study, rather than to focus on whether certain scientific practices are best described as developing from mechanistic to more holistic approaches. I end with some implications for the historiography of science by considering the appropriateness of different conceptual frameworks for different grains of resolution in the history of biology.

  5. Mechanistic analytical models for long-distance seed dispersal by wind.

    PubMed

    Katul, G G; Porporato, A; Nathan, R; Siqueira, M; Soons, M B; Poggi, D; Horn, H S; Levin, S A

    2005-09-01

    We introduce an analytical model, the Wald analytical long-distance dispersal (WALD) model, for estimating dispersal kernels of wind-dispersed seeds and their escape probability from the canopy. The model is based on simplifications to well-established three-dimensional Lagrangian stochastic approaches for turbulent scalar transport resulting in a two-parameter Wald (or inverse Gaussian) distribution. Unlike commonly used phenomenological models, WALD's parameters can be estimated from the key factors affecting wind dispersal--wind statistics, seed release height, and seed terminal velocity--determined independently of dispersal data. WALD's asymptotic power-law tail has an exponent of -3/2, a limiting value verified by a meta-analysis for a wide variety of measured dispersal kernels and larger than the exponent of the bivariate Student t-test (2Dt). We tested WALD using three dispersal data sets on forest trees, heathland shrubs, and grassland forbs and compared WALD's performance with that of other analytical mechanistic models (revised versions of the tilted Gaussian Plume model and the advection-diffusion equation), revealing fairest agreement between WALD predictions and measurements. Analytical mechanistic models, such as WALD, combine the advantages of simplicity and mechanistic understanding and are valuable tools for modeling large-scale, long-term plant population dynamics.

  6. Comparative Evaluation of Statistical and Mechanistic Models of Escherichia coli at Beaches in Southern Lake Michigan.

    PubMed

    Safaie, Ammar; Wendzel, Aaron; Ge, Zhongfu; Nevers, Meredith B; Whitman, Richard L; Corsi, Steven R; Phanikumar, Mantha S

    2016-03-01

    Statistical and mechanistic models are popular tools for predicting the levels of indicator bacteria at recreational beaches. Researchers tend to use one class of model or the other, and it is difficult to generalize statements about their relative performance due to differences in how the models are developed, tested, and used. We describe a cooperative modeling approach for freshwater beaches impacted by point sources in which insights derived from mechanistic modeling were used to further improve the statistical models and vice versa. The statistical models provided a basis for assessing the mechanistic models which were further improved using probability distributions to generate high-resolution time series data at the source, long-term "tracer" transport modeling based on observed electrical conductivity, better assimilation of meteorological data, and the use of unstructured-grids to better resolve nearshore features. This approach resulted in improved models of comparable performance for both classes including a parsimonious statistical model suitable for real-time predictions based on an easily measurable environmental variable (turbidity). The modeling approach outlined here can be used at other sites impacted by point sources and has the potential to improve water quality predictions resulting in more accurate estimates of beach closures.

  7. Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model.

    PubMed

    Harfoot, Michael B J; Newbold, Tim; Tittensor, Derek P; Emmott, Stephen; Hutton, Jon; Lyutsarev, Vassily; Smith, Matthew J; Scharlemann, Jörn P W; Purves, Drew W

    2014-04-01

    Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures.

  8. Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage

    NASA Astrophysics Data System (ADS)

    McMahon, Stephen J.; Schuemann, Jan; Paganetti, Harald; Prise, Kevin M.

    2016-09-01

    Characterising and predicting the effects of ionising radiation on cells remains challenging, with the lack of robust models of the underlying mechanism of radiation responses providing a significant limitation to the development of personalised radiotherapy. In this paper we present a mechanistic model of cellular response to radiation that incorporates the kinetics of different DNA repair processes, the spatial distribution of double strand breaks and the resulting probability and severity of misrepair. This model enables predictions to be made of a range of key biological endpoints (DNA repair kinetics, chromosome aberration and mutation formation, survival) across a range of cell types based on a set of 11 mechanistic fitting parameters that are common across all cells. Applying this model to cellular survival showed its capacity to stratify the radiosensitivity of cells based on aspects of their phenotype and experimental conditions such as cell cycle phase and plating delay (correlation between modelled and observed Mean Inactivation Doses R2 > 0.9). By explicitly incorporating underlying mechanistic factors, this model can integrate knowledge from a wide range of biological studies to provide robust predictions and may act as a foundation for future calculations of individualised radiosensitivity.

  9. Emergent Global Patterns of Ecosystem Structure and Function from a Mechanistic General Ecosystem Model

    PubMed Central

    Emmott, Stephen; Hutton, Jon; Lyutsarev, Vassily; Smith, Matthew J.; Scharlemann, Jörn P. W.; Purves, Drew W.

    2014-01-01

    Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures. PMID:24756001

  10. Natural Variation of Plant Metabolism: Genetic Mechanisms, Interpretive Caveats, and Evolutionary and Mechanistic Insights1

    PubMed Central

    Soltis, Nicole E.; Kliebenstein, Daniel J.

    2015-01-01

    Combining quantitative genetics studies with metabolomics/metabolic profiling platforms, genomics, and transcriptomics is creating significant progress in identifying the causal genes controlling natural variation in metabolite accumulations and profiles. In this review, we discuss key mechanistic and evolutionary insights that are arising from these studies. This includes the potential role of transport and other processes in leading to a separation of the site of mechanistic causation and metabolic consequence. A reilluminated observation is the potential for genomic variation in the organelle to alter phenotypic variation alone and in epistatic interaction with the nuclear genetic variation. These studies are also highlighting new aspects of metabolic pleiotropy both in terms of the breadth of loci altering metabolic variation as well as the potential for broader effects on plant defense regulation of the metabolic variation than has previously been predicted. We also illustrate caveats that can be overlooked when translating quantitative genetics descriptors such as heritability and per-locus r2 to mechanistic or evolutionary interpretations. PMID:26272883

  11. Mechanistic models of animal migration behaviour--their diversity, structure and use.

    PubMed

    Bauer, Silke; Klaassen, Marcel

    2013-05-01

    1. Migration is a widespread phenomenon in the animal kingdom, including many taxonomic groups and modes of locomotion. Developing an understanding of the proximate and ultimate causes for this behaviour not only addresses fundamental ecological questions but has relevance to many other fields, for example in relation to the spread of emerging zoonotic diseases, the proliferation of invasive species, aeronautical safety as well as the conservation of migrants. 2. Theoretical methods can make important contributions to our understanding of migration, by allowing us to integrate findings on this complex behaviour, identify caveats in our understanding and to guide future empirical research efforts. Various mechanistic models exist to date, but their applications seem to be scattered and far from evenly distributed across taxonomic units. 3. Therefore, we provide an overview of the major mechanistic modelling approaches used in the study of migration behaviour and characterize their fundamental features, assumptions and limitations and discuss their typical data requirements both for model parameterization and for scrutinizing model predictions. 4. Furthermore, we review 155 studies that have used mechanistic models to study animal migration and analyse them with regard to the approaches used and the focal species, and also explore their contribution to advancing current knowledge within six broad migration ecology research themes. 5. This identifies important gaps in our present knowledge, which should be tackled in future research using existing and to-be developed theoretical approaches.

  12. Comparative evaluation of statistical and mechanistic models of Escherichia coli at beaches in southern Lake Michigan

    USGS Publications Warehouse

    Safaie, Ammar; Wendzel, Aaron; Ge, Zhongfu; Nevers, Meredith; Whitman, Richard L.; Corsi, Steven R.; Phanikumar, Mantha S.

    2016-01-01

    Statistical and mechanistic models are popular tools for predicting the levels of indicator bacteria at recreational beaches. Researchers tend to use one class of model or the other, and it is difficult to generalize statements about their relative performance due to differences in how the models are developed, tested, and used. We describe a cooperative modeling approach for freshwater beaches impacted by point sources in which insights derived from mechanistic modeling were used to further improve the statistical models and vice versa. The statistical models provided a basis for assessing the mechanistic models which were further improved using probability distributions to generate high-resolution time series data at the source, long-term “tracer” transport modeling based on observed electrical conductivity, better assimilation of meteorological data, and the use of unstructured-grids to better resolve nearshore features. This approach resulted in improved models of comparable performance for both classes including a parsimonious statistical model suitable for real-time predictions based on an easily measurable environmental variable (turbidity). The modeling approach outlined here can be used at other sites impacted by point sources and has the potential to improve water quality predictions resulting in more accurate estimates of beach closures.

  13. Exploiting Bioprocessing Fluctuations to Elicit the Mechanistics of De Novo Lipogenesis in Yarrowia lipolytica

    PubMed Central

    Silverman, Andrew M.; Stephanopoulos, Gregory

    2017-01-01

    Despite substantial achievements in elucidating the metabolic pathways of lipogenesis, a mechanistic representation of lipid accumulation and degradation has not been fully attained to-date. Recent evidence suggests that lipid accumulation can occur through increases of either the cytosolic copy-number of lipid droplets (LDs), or the LDs size. However, the prevailing phenotype, or how such mechanisms pertain to lipid degradation remain poorly understood. To address this shortcoming, we employed the–recently discovered–innate bioprocessing fluctuations in Yarrowia lipolytica, and performed single-cell fluctuation analysis using optical microscopy and microfluidics that generate a quasi-time invariant microenvironment. We report that lipid accumulation at early stationary phase in rich medium is substantially more likely to occur through variations in the LDs copy-number, rather than the LDs size. Critically, these mechanistics are also preserved during lipid degradation, as well as upon exposure to a protein translation inhibitor. The latter condition additionally induced a lipid accumulation phase, accompanied by the downregulation of lipid catabolism. Our results enable an in-depth mechanistic understanding of lipid biogenesis, and expand longitudinal single-cell fluctuation analyses from gene regulation to metabolism. PMID:28052085

  14. Model-free forecasting outperforms the correct mechanistic model for simulated and experimental data

    PubMed Central

    Perretti, Charles T.; Munch, Stephan B.; Sugihara, George

    2013-01-01

    Accurate predictions of species abundance remain one of the most vexing challenges in ecology. This observation is perhaps unsurprising, because population dynamics are often strongly forced and highly nonlinear. Recently, however, numerous statistical techniques have been proposed for fitting highly parameterized mechanistic models to complex time series, potentially providing the machinery necessary for generating useful predictions. Alternatively, there is a wide variety of comparatively simple model-free forecasting methods that could be used to predict abundance. Here we pose a rather conservative challenge and ask whether a correctly specified mechanistic model, fit with commonly used statistical techniques, can provide better forecasts than simple model-free methods for ecological systems with noisy nonlinear dynamics. Using four different control models and seven experimental time series of flour beetles, we found that Markov chain Monte Carlo procedures for fitting mechanistic models often converged on best-fit parameterizations far different from the known parameters. As a result, the correctly specified models provided inaccurate forecasts and incorrect inferences. In contrast, a model-free method based on state-space reconstruction gave the most accurate short-term forecasts, even while using only a single time series from the multivariate system. Considering the recent push for ecosystem-based management and the increasing call for ecological predictions, our results suggest that a flexible model-free approach may be the most promising way forward. PMID:23440207

  15. Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

    PubMed

    MacLeod, Miles; Nersessian, Nancy J

    2015-02-01

    In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding."

  16. Integration of QSAR and SAR methods for the mechanistic interpretation of predictive models for carcinogenicity

    PubMed Central

    Fjodorova, Natalja; Novič, Marjana

    2012-01-01

    The knowledge-based Toxtree expert system (SAR approach) was integrated with the statistically based counter propagation artificial neural network (CP ANN) model (QSAR approach) to contribute to a better mechanistic understanding of a carcinogenicity model for non-congeneric chemicals using Dragon descriptors and carcinogenic potency for rats as a response. The transparency of the CP ANN algorithm was demonstrated using intrinsic mapping technique specifically Kohonen maps. Chemical structures were represented by Dragon descriptors that express the structural and electronic features of molecules such as their shape and electronic surrounding related to reactivity of molecules. It was illustrated how the descriptors are correlated with particular structural alerts (SAs) for carcinogenicity with recognized mechanistic link to carcinogenic activity. Moreover, the Kohonen mapping technique enables one to examine the separation of carcinogens and non-carcinogens (for rats) within a family of chemicals with a particular SA for carcinogenicity. The mechanistic interpretation of models is important for the evaluation of safety of chemicals. PMID:24688639

  17. 20 CFR 703.306 - Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...' COMPENSATION ACT AND RELATED STATUTES INSURANCE REGULATIONS Authorization of Self-Insurers § 703.306 Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits. A self-insurer or... deposited; conditions of deposit; acceptance of deposits. 703.306 Section 703.306 Employees' Benefits...

  18. 20 CFR 703.306 - Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...' COMPENSATION ACT AND RELATED STATUTES INSURANCE REGULATIONS Authorization of Self-Insurers § 703.306 Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits. A self-insurer or... deposited; conditions of deposit; acceptance of deposits. 703.306 Section 703.306 Employees' Benefits...

  19. 20 CFR 703.306 - Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...' COMPENSATION ACT AND RELATED STATUTES INSURANCE REGULATIONS Authorization of Self-Insurers § 703.306 Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits. A self-insurer or... deposited; conditions of deposit; acceptance of deposits. 703.306 Section 703.306 Employees' Benefits...

  20. 20 CFR 703.306 - Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...' COMPENSATION ACT AND RELATED STATUTES INSURANCE REGULATIONS Authorization of Self-Insurers § 703.306 Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits. A self-insurer or... deposited; conditions of deposit; acceptance of deposits. 703.306 Section 703.306 Employees' Benefits...

  1. 20 CFR 703.306 - Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AND RELATED STATUTES INSURANCE REGULATIONS Authorization of Self-Insurers § 703.306 Kinds of negotiable securities that may be deposited; conditions of deposit; acceptance of deposits. A self-insurer or... deposited; conditions of deposit; acceptance of deposits. 703.306 Section 703.306 Employees'...

  2. Endogenous murine Aβ increases amyloid deposition in APP23 but not in APPPS1 transgenic mice.

    PubMed

    Mahler, Jasmin; Morales-Corraliza, Jose; Stolz, Julia; Skodras, Angelos; Radde, Rebecca; Duma, Carmen C; Eisele, Yvonne S; Mazzella, Matthew J; Wong, Harrison; Klunk, William E; Nilsson, K Peter R; Staufenbiel, Matthias; Mathews, Paul M; Jucker, Mathias; Wegenast-Braun, Bettina M

    2015-07-01

    Endogenous murine amyloid-β peptide (Aβ) is expressed in most Aβ precursor protein (APP) transgenic mouse models of Alzheimer's disease but its contribution to β-amyloidosis remains unclear. We demonstrate ∼ 35% increased cerebral Aβ load in APP23 transgenic mice compared with age-matched APP23 mice on an App-null background. No such difference was found for the much faster Aβ-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine Aβ, and immunoelectron microscopy revealed a tight association of murine Aβ with human Aβ fibrils. Deposition of murine Aβ was considerably less efficient compared with the deposition of human Aβ indicating a lower amyloidogenic potential of murine Aβ in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human Aβ and deposits of mixed human-murine Aβ. Our data demonstrate a differential effect of murine Aβ on human Aβ deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse Aβ may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.

  3. Acid deposition in Asia: Emissions, deposition, and ecosystem effects

    NASA Astrophysics Data System (ADS)

    Duan, Lei; Yu, Qian; Zhang, Qiang; Wang, Zifa; Pan, Yuepeng; Larssen, Thorjørn; Tang, Jie; Mulder, Jan

    2016-12-01

    We review and synthesize the current state of knowledge regarding acid deposition and its environmental effects across Asia. The extent and magnitude of acid deposition in Asia became apparent only about one decade after this issue was well described in Europe and North America. In addition to the temperate zone, much of eastern and southern Asia is situated in the tropics and subtropics, climate zones hitherto little studied with respect to the effects of high loads of acid deposition. Surface waters across Asia are generally not sensitive to the effects of acid deposition, whereas soils in some regions are sensitive to acidification due to low mineral weathering. However, soil acidification was largely neutralized by such processes as base cation deposition, nitrate (NO3-) denitrification, and sulfate (SO42-) adsorption. Accompanying the decrease in S deposition in recent years, N deposition is of increasing concern in Asia. The acidifying effect of N deposition may be more important than S deposition in well drained tropical/subtropical soils due to high SO42- adsorption. The risk of regional soil acidification is a major threat in Eastern Asia, indicated by critical load exceedance in large areas.

  4. Experimental reproduction of tsunami deposit

    NASA Astrophysics Data System (ADS)

    Yoshii, T.; Matsuyama, M.; Tanaka, S.

    2015-12-01

    Understanding the process of sediment transport and deposition under a tsunami inundation is essential to provide the credible information about potential tsunamis from tsunami deposits. Detections of tsunami deposit has contributed to reveal centuries-old record of tsunami incursions. However, our knowledge is still not enough for evaluating the scale of past tsunamis using deposits. In this study, a laboratory experiment was conducted to investigate the relationship between the hydraulic condition and sedimentological features of tsunami deposit. The large wave flume in CRIEPI, one of the largest wave flume in the world, which has 205 m length, 3.4 m width and 6 m depth was used. The sandy beach with uniform slope (1/50) were made in the flume. Sand dune of 0.2 high was placed near the shoreline. The tsunami was made by the wave generator which has 2.2 m stroke. The wave at the shore line has 0.6 m depth and the horizontal velocity reached up to 3.5 m/s. The incursion of the wave and its return flow completely washed out the dune and resulted in the deposition especially near the dune. The thickness of deposit shows landward thinning and fining, which has been widely confirmed by field observations. In addition, sedimentary structures of the deposit was investigated using the method similar to that used in geological survey such as core sampling and relief peel sampling. The obtained samples were investigated using a X-ray computed tomography. The obtained CT-images shows that most part of deposition consists two or more subsections divided by horizontal lamination although the deposition near the dune has drastic and complex change thickness and grain size. The subsections shows upward-fining and upward-coarsening which are been reported as common sedimentary structures of tsunami deposit from field surveys. Considering the similarity of sedimentary structures in the deposit reconstructed in this experiment and actual tsunami deposits, this experiment succeeded

  5. Chemical vapor deposition growth

    NASA Technical Reports Server (NTRS)

    Ruth, R. P.; Manasevit, H. M.; Kenty, J. L.; Moudy, L. A.; Simpson, W. I.; Yang, J. J.

    1976-01-01

    The chemical vapor deposition (CVD) method for the growth of Si sheet on inexpensive substrate materials is investigated. The objective is to develop CVD techniques for producing large areas of Si sheet on inexpensive substrate materials, with sheet properties suitable for fabricating solar cells meeting the technical goals of the Low Cost Silicon Solar Array Project. Specific areas covered include: (1) modification and test of existing CVD reactor system; (2) identification and/or development of suitable inexpensive substrate materials; (3) experimental investigation of CVD process parameters using various candidate substrate materials; (4) preparation of Si sheet samples for various special studies, including solar cell fabrication; (5) evaluation of the properties of the Si sheet material produced by the CVD process; and (6) fabrication and evaluation of experimental solar cell structures, using standard and near-standard processing techniques.

  6. Volcanology and mineral deposits

    USGS Publications Warehouse

    Lipman, P.W.

    1990-01-01

    In contrast, old volcanic regions, which host many of the world's major hydrothermal-vein, porphyry, and massive-sulfide ore deposits, have been studied mainly by economic geologists, regional stratigraphers, and structural geologists who have limited familiarity with the complexities of volcanic processes. Such "dead" volcanoes, ranging in age from a few million million years (tertiary) to a few billion years (Precambrian), are commonly incompletely and discontinuously preserved due to rapid erosion of originally high-standing volcanic edifices. They can be difficult to date reliably, especially in terms of the time scales of individual volcanic events, and are variably hydrothermally altered-impeding high-resolution petrologic and geochemical studies. Many volcanologists, geochemists, and geophysicists who work on active volcanoes accordingly have been reluctant to become involved in studies of such less tractable rocks. 

  7. The deposit size frequency method for estimating undiscovered uranium deposits

    USGS Publications Warehouse

    McCammon, R.B.; Finch, W.I.

    1993-01-01

    The deposit size frequency (DSF) method has been developed as a generalization of the method that was used in the National Uranium Resource Evaluation (NURE) program to estimate the uranium endowment of the United States. The DSF method overcomes difficulties encountered during the NURE program when geologists were asked to provide subjective estimates of (1) the endowed fraction of an area judged favorable (factor F) for the occurrence of undiscovered uranium deposits and (2) the tons of endowed rock per unit area (factor T) within the endowed fraction of the favorable area. Because the magnitudes of factors F and T were unfamiliar to nearly all of the geologists, most geologists responded by estimating the number of undiscovered deposits likely to occur within the favorable area and the average size of these deposits. The DSF method combines factors F and T into a single factor (F??T) that represents the tons of endowed rock per unit area of the undiscovered deposits within the favorable area. Factor F??T, provided by the geologist, is the estimated number of undiscovered deposits per unit area in each of a number of specified deposit-size classes. The number of deposit-size classes and the size interval of each class are based on the data collected from the deposits in known (control) areas. The DSF method affords greater latitude in making subjective estimates than the NURE method and emphasizes more of the everyday experience of exploration geologists. Using the DSF method, new assessments have been made for the "young, organic-rich" surficial uranium deposits in Washington and idaho and for the solution-collapse breccia pipe uranium deposits in the Grand Canyon region in Arizona and adjacent Utah. ?? 1993 Oxford University Press.

  8. Momentum Deposition in Curvilinear Coordinates

    SciTech Connect

    Cleveland, Mathew Allen; Lowrie, Robert Byron; Rockefeller, Gabriel M.; Thompson, Kelly Glen; Wollaber, Allan Benton

    2015-08-03

    The momentum imparted into a material by thermal radiation deposition is an important physical process in astrophysics and inertial confinement fusion (ICF) simulations. In recent work we presented a new method of evaluating momentum deposition that relies on the combination of a time-averaged approximation and a numerical integration scheme. This approach robustly and efficiently evaluates the momentum deposition in spherical geometry. Future work will look to extend this approach to 2D cylindrical geometries.

  9. Chirality-Controlled Growth of Single-Wall Carbon Nanotubes Using Vapor Phase Epitaxy: Mechanistic Understanding and Scalable Production

    DTIC Science & Technology

    2016-09-15

    period, that is, growth plus termination, we assume the average growth rate (R̅t) of a (n, m) SWCNT at time t follows exponential kinetics ?̅?...AFRL-AFOSR-VA-TR-2016-0319 Chirality-Controlled Growth of Single-Wall Carbon Nanotubes Using Vapor Phase Epitaxy: Mechanistic Understanding and...controlled growth of single-wall carbon nanotubes using vapor phase epitaxy: mechanistic understanding and scalable production FA9550-14-1-0115 Zhou

  10. Organophotocatalysis: Insights into the Mechanistic Aspects of Thiourea-Mediated Intermolecular [2+2] Photocycloadditions.

    PubMed

    Vallavoju, Nandini; Selvakumar, Sermadurai; Pemberton, Barry C; Jockusch, Steffen; Sibi, Mukund P; Sivaguru, Jayaraman

    2016-04-25

    Mechanistic investigations of the intermolecular [2+2] photocycloaddition of coumarin with tetramethylethylene mediated by thiourea catalysts reveal that the reaction is enabled by a combination of minimized aggregation, enhanced intersystem crossing, and altered excited-state lifetime(s). These results clarify how the excited-state reactivity can be manipulated through catalyst-substrate interactions and reveal a third mechanistic pathway for thiourea-mediated organo-photocatalysis.

  11. (Acidic deposition and the environment)

    SciTech Connect

    Garten, C.T.; Lindberg, S.E.; Van Miegroet, H.

    1990-10-24

    The travelers presented several papers at the Fourth International Conference on Acidic Deposition. These covered the following topics: atmospheric chemistry and deposition of airborne nitrogen compounds, soil solution chemistry in high-elevation spruce forests, and forest throughfall measurements for estimating total sulfur deposition to ecosystems. In addition, S. E. Lindberg was invited to organize and chair a conference session on Throughfall and Stemflow Experiments, and to present an invited lecture on Atmospheric Deposition and Canopy Interactions of Metals and Nitrogen in Forest Ecosystems: The Influence of Global Change'' at the 110th Anniversary Celebration of the Free University of Amsterdam.

  12. Geochemistry of sedimentary ore deposits

    SciTech Connect

    Maynard, J. B.

    1983-01-01

    A text providing a sedimentological treatment of a study on ore deposits, and especially as related to geochemistry. Excellently documented (about 5000 citations). Well indexed with the index of deposits and localities separated. Contents, Iron. Copper and silver. Aluminum and nickel. Manganese. Uranium. Lead and zinc. Volcanic-sedimentary ores. Appendix. Indexes.

  13. MODELING DEPOSITION OF INHALED PARTICLES

    EPA Science Inventory

    Modeling Deposition of Inhaled Particles: ABSTRACT

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeut...

  14. Particle Deposition in Granular Media

    SciTech Connect

    Tien, C.

    1992-01-01

    Objective is to understand aerosol deposition from gas streams flowing through granular media; this is important to the design of granular filtration systems. The following investigations were carried out: transient behavior of granular filtration of aerosols, and stochastic simulation of aerosol deposition in granular media.

  15. Variable temperature semiconductor film deposition

    DOEpatents

    Li, Xiaonan; Sheldon, Peter

    1998-01-01

    A method of depositing a semiconductor material on a substrate. The method sequentially comprises (a) providing the semiconductor material in a depositable state such as a vapor for deposition on the substrate; (b) depositing the semiconductor material on the substrate while heating the substrate to a first temperature sufficient to cause the semiconductor material to form a first film layer having a first grain size; (c) continually depositing the semiconductor material on the substrate while cooling the substrate to a second temperature sufficient to cause the semiconductor material to form a second film layer deposited on the first film layer and having a second grain size smaller than the first grain size; and (d) raising the substrate temperature, while either continuing or not continuing to deposit semiconductor material to form a third film layer, to thereby anneal the film layers into a single layer having favorable efficiency characteristics in photovoltaic applications. A preferred semiconductor material is cadmium telluride deposited on a glass/tin oxide substrate already having thereon a film layer of cadmium sulfide.

  16. Variable temperature semiconductor film deposition

    DOEpatents

    Li, X.; Sheldon, P.

    1998-01-27

    A method of depositing a semiconductor material on a substrate is disclosed. The method sequentially comprises (a) providing the semiconductor material in a depositable state such as a vapor for deposition on the substrate; (b) depositing the semiconductor material on the substrate while heating the substrate to a first temperature sufficient to cause the semiconductor material to form a first film layer having a first grain size; (c) continually depositing the semiconductor material on the substrate while cooling the substrate to a second temperature sufficient to cause the semiconductor material to form a second film layer deposited on the first film layer and having a second grain size smaller than the first grain size; and (d) raising the substrate temperature, while either continuing or not continuing to deposit semiconductor material to form a third film layer, to thereby anneal the film layers into a single layer having favorable efficiency characteristics in photovoltaic applications. A preferred semiconductor material is cadmium telluride deposited on a glass/tin oxide substrate already having thereon a film layer of cadmium sulfide.

  17. Deposited films with improved microstructures

    DOEpatents

    Patten, James W.; Moss, Ronald W.; McClanahan, Edwin D.

    1984-01-01

    Methods for improving microstructures of line-of-sight deposited films are described. Columnar growth defects ordinarily produced by geometrical shadowing during deposition of such films are eliminated without resorting to post-deposition thermal or mechanical treatments. The native, as-deposited coating qualities, including homogeneity, fine grain size, and high coating-to-substrate adherence, can thus be retained. The preferred method includes the steps of emitting material from a source toward a substrate to deposit a coating non-uniformly on the substrate surface, removing a portion of the coating uniformly over the surface, again depositing material onto the surface, but from a different direction, and repeating the foregoing steps. The quality of line-of-sight deposited films such as those produced by sputtering, progressively deteriorates as the angle of incidence between the flux and the surface becomes increasingly acute. Depositing non-uniformly, so that the coating becomes progressively thinner as quality deteriorates, followed by uniformly removing some of the coating, such as by resputtering, eliminates the poor quality portions, leaving only high quality portions of the coating. Subsequently sputtering from a different direction applies a high quality coating to other regions of the surface. Such steps can be performed either simultaneously or sequentially to apply coatings of a uniformly high quality, closed microstructure to three-dimensional or large planar surfaces.

  18. Chemical vapor deposition growth

    NASA Technical Reports Server (NTRS)

    Ruth, R. P.; Manasevit, H. M.; Campbell, A. G.; Johnson, R. E.; Kenty, J. L.; Moudy, L. A.; Shaw, G. L.; Simpson, W. I.; Yang, J. J.

    1978-01-01

    The objective was to investigate and develop chemical vapor deposition (CVD) techniques for the growth of large areas of Si sheet on inexpensive substrate materials, with resulting sheet properties suitable for fabricating solar cells that would meet the technical goals of the Low Cost Silicon Solar Array Project. The program involved six main technical tasks: (1) modification and test of an existing vertical-chamber CVD reactor system; (2) identification and/or development of suitable inexpensive substrate materials; (3) experimental investigation of CVD process parameters using various candidate substrate materials; (4) preparation of Si sheet samples for various special studies, including solar cell fabrication; (5) evaluation of the properties of the Si sheet material produced by the CVD process; and (6) fabrication and evaluation of experimental solar cell structures, using impurity diffusion and other standard and near-standard processing techniques supplemented late in the program by the in situ CVD growth of n(+)/p/p(+) sheet structures subsequently processed into experimental cells.

  19. Chemical vapor deposition growth

    NASA Technical Reports Server (NTRS)

    Ruth, R. P.; Manasevit, H. M.; Johnson, R. E.; Kenty, J. L.; Moudy, L. A.; Simpson, W. I.; Yang, J. J.

    1976-01-01

    A laboratory type CVD reactor system with a vertical deposition chamber and sample pedestal heated by an external RF coil has been extensively modified by installation of mass flow controllers, automatic process sequence timers, and special bellows-sealed air-operated valves for overall improved performance. Various film characterization procedures, including classical metallography, SEM analyses, X ray diffraction analyses, surface profilometry, and electrical measurements (resistivity, carrier concentration, mobility, spreading resistance profiles, and minority-carrier lifetime by the C-V-t method) area used to correlate Si sheet properties with CVD parameters and substrate properties. Evaluation procedures and measurements are given. Experimental solar cell structures were made both in epitaxial Si sheet (on sapphire substrates) and in polycrystalline material on alumina substrates, the former to provide an indication of what might be an upper limit on performance of the latter. Preliminary results are given, as obtained in cell structures not specially designed to allow for the unique properties of the sheet material, and fabricated in material known to be far from optimum for photovoltaic performance. Low power conversion efficiencies have been obtained in the epitaxial as well as the polycrystalline Si sheet.

  20. Radioactive deposits of Nevada

    USGS Publications Warehouse

    Lovering, T.G.

    1954-01-01

    Thirty-five occurrences of radioactive rocks had been reported from Nevada prior to 1952. Twenty-five of these had been investigated by personnel of the U. S. Geological Surveyor of the U. S. Atomic Energy Commission. Of those investigated, uranium minerals were identified at 13 sites; two sites contained a thorium mineral (monazite); the source of radioactivity on nine properties was not ascertained, and one showed no abnormal radioactivity. Of the other reported occurrences, one is said to contain uraniferous hydrocarbons and nine are placers containing thorian monazite. Pitchblende occurs at two localities, the East Walker River area, and the Stalin's Present prospect, where it is sparsely disseminated in tabular bodies cutting granitic rocks. Other uranium minerals found in the state include: carnotite, tyuyamunite, autunite, torbernite, gummite, uranophane, kasolite, and an unidentified mineral which may be dumontite. Monazite is the only thorium mineral of possible economic importance that has been reported. From an economic standpoint, only four of the properties examined showed reserves of uranium ore in 1952; these are: the Green Monster mine, which shipped 5 tons of ore to Marysvale, Utah, during 1951; the Majuba Hill mine; the Stalin's Present prospect; and the West Willys claim in the Washington district. No estimate has been made of thorium reserves and no commercial deposits of thorium are known.

  1. Radioactive deposits of Nevada

    USGS Publications Warehouse

    Lovering, T.G.

    1953-01-01

    Thirty-five occurrences of radioactive rocks had been reported from Nevada prior to 1952. Twenty-five of these had been investigated by the U. S. Geological Survey and the U. S. Atomic Energy Commission. Of those investigated, uranium minerals were identified in 13; two contained a thorium mineral (monazite); the source of radioactivity on 7 properties was not ascertained; and one showed no abnormal radioactivity. Of the other reported occurrences, one is said to contain uraniferous hydrocarbons and 9 are placers containing thorian monazite. Pitchblende occurs at two localities; the East Walker River area, and the Stalin's Present prospect, where it is sparsely disseminated in tabular bodies cutting granitic rocks. Other uranium minerals found in the state include: carnotite, tyuyamunite, autunite, torbernite, gummite, uranophane, kasolite, and an unidentified mineral which may be dumontit. Monazite is the only thorium mineral of possible economic importance that has been reported. From an economic standpoint 9 only 4 of the properties examined showed reserves of uranium ore in 1952; these are: the Green Monster mine, which shipped 5 tons of ore to Marysvale, Utah, during 1951, the Majuba Hill mine, the Stalin's Present prospect, and the West Willys claim in the Washington district. Reserves of ore grade are small on all of these properties and probably cannot be developed commercially unless an ore-buying station is set up nearby. No estimate has been made of thorium reserves and no commercial deposits of thorium are known.

  2. A dynamic and mechanistic model of PCB bioaccumulation in the European hake ( Merluccius merluccius)

    NASA Astrophysics Data System (ADS)

    Bodiguel, Xavier; Maury, Olivier; Mellon-Duval, Capucine; Roupsard, François; Le Guellec, Anne-Marie; Loizeau, Véronique

    2009-08-01

    Bioaccumulation is difficult to document because responses differ among chemical compounds, with environmental conditions, and physiological processes characteristic of each species. We use a mechanistic model, based on the Dynamic Energy Budget (DEB) theory, to take into account this complexity and study factors impacting accumulation of organic pollutants in fish through ontogeny. The bioaccumulation model proposed is a comprehensive approach that relates evolution of hake PCB contamination to physiological information about the fish, such as diet, metabolism, reserve and reproduction status. The species studied is the European hake ( Merluccius merluccius, L. 1758). The model is applied to study the total concentration and the lipid normalised concentration of 4 PCB congeners in male and female hakes from the Gulf of Lions (NW Mediterranean sea) and the Bay of Biscay (NE Atlantic ocean). Outputs of the model compare consistently to measurements over the life span of fish. Simulation results clearly demonstrate the relative effects of food contamination, growth and reproduction on the PCB bioaccumulation in hake. The same species living in different habitats and exposed to different PCB prey concentrations exhibit marked difference in the body accumulation of PCBs. At the adult stage, female hakes have a lower PCB concentration compared to males for a given length. We successfully simulated these sex-specific PCB concentrations by considering two mechanisms: a higher energy allocation to growth for females and a transfer of PCBs from the female to its eggs when allocating lipids from reserve to eggs. Finally, by its mechanistic description of physiological processes, the model is relevant for other species and sets the stage for a mechanistic understanding of toxicity and ecological effects of organic contaminants in marine organisms.

  3. A mechanistic model of ion-exchange chromatography on polymer fiber stationary phases.

    PubMed

    Winderl, Johannes; Hahn, Tobias; Hubbuch, Jürgen

    2016-12-02

    Fibers are prominent among novel stationary phase supports for preparative chromatography. Several recent studies have highlighted the potential of fiber-based adsorbents for high productivity downstream processing in both batch and continuous mode, but so far the development of these materials and of processes employing these materials has solely been based on experimental data. In this study we assessed whether mechanistic modeling can be performed on fiber-based adsorbents. With a column randomly filled with short cut hydrogel grafted anion exchange fibers, we tested whether tracer, linear gradient elution, and breakthrough data could be reproduced by mechanistic models. Successful modeling was achieved for all of the considered experiments, for both non-retained and retained molecules. For the fibers used in this study the best results were obtained with a transport-dispersive model in combination with a steric mass action isotherm. This approach accurately accounted for the convection and dispersion of non-retained tracers, and the breakthrough and elution behaviors of three different proteins with sizes ranging from 6 to 160kDa were accurately modeled, with simulation results closely resembling the experimental data. The estimated model parameters were plausible both from their physical meaning, and from an analysis of the underlying model assumptions. Parameters were determined within good confidence levels; the average confidence estimate was below 7% for confidence levels of 95%. This shows that fiber-based adsorbents can be modeled mechanistically, which will be valuable for the future design and evaluation of these novel materials and for the development of processes employing such materials.

  4. Inferring Mechanistic Parameters from Amyloid Formation Kinetics by Approximate Bayesian Computation.

    PubMed

    Nakatani-Webster, Eri; Nath, Abhinav

    2017-03-14

    Amyloid formation is implicated in a number of human diseases, and is thought to proceed via a nucleation-dependent polymerization mechanism. Experimenters often wish to relate changes in amyloid formation kinetics, for example, in response to small molecules to specific mechanistic steps along this pathway. However, fitting kinetic fibril formation data to a complex model including explicit rate constants results in an ill-posed problem with a vast number of potential solutions. The levels of uncertainty remaining in parameters calculated from these models, arising both from experimental noise and high levels of degeneracy or codependency in parameters, is often unclear. Here, we demonstrate that a combination of explicit mathematical models with an approximate Bayesian computation approach can be used to assign the mechanistic effects of modulators on amyloid fibril formation. We show that even when exact rate constants cannot be extracted, parameters derived from these rate constants can be recovered and used to assign mechanistic effects and their relative magnitudes with a great deal of confidence. Furthermore, approximate Bayesian computation provides a robust method for visualizing uncertainty remaining in the model parameters, regardless of its origin. We apply these methods to the problem of heparin-mediated tau polymerization, which displays complex kinetic behavior not amenable to analysis by more traditional methods. Our analysis indicates that the role of heparin cannot be explained by enhancement of nucleation alone, as has been previously proposed. The methods described here are applicable to a wide range of systems, as models can be easily adapted to account for new reactions and reversibility.

  5. A translational preclinical model of interstitial pulmonary fibrosis and pulmonary hypertension: mechanistic pathways driving disease pathophysiology

    PubMed Central

    Jarman, Elizabeth R.; Khambata, Valerie S.; Yun Ye, Li; Cheung, Kenneth; Thomas, Matthew; Duggan, Nicholas; Jarai, Gabor

    2014-01-01

    Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease, in which a decline in patient prognosis is frequently associated with the onset of pulmonary hypertension (PH). Animal models exhibiting principle pathophysiological features of IPF and PH could provide greater insight into mechanistic pathways underlying disease progression and a means for evaluating novel therapeutic approaches for intervention. Here, we describe an in vivo disease model, in which animals develop progressive interstitial pulmonary fibrosis and associated PH, as defined by the presence of fibrotic foci adjacent to areas of alveolar injury and remodeling of the pulmonary vasculature. Associated changes in physiological parameters included a decline in lung function and increase in mean pulmonary arterial pressure (mPAP) >25 mmHg. The early fibrotic pathology is associated with a profibrogenic microenvironment, elevated levels of the matrix metalloproteases, MMP‐2, MMP‐7, and MMP‐12, TIMP‐1, the chemoattractant and mitogen, PDGF‐β, and the chemokines CCL2 and CXCL12, that are associated with the recruitment of macrophages, mast cells, and fibrocytes. Principle mechanistic pathways associated with disease pathogenesis are upregulated in the lungs and pulmonary arteries, with sustained increases in gene transcripts for the profibrotic mediator TGF‐β1 and components of the TGF‐β signaling pathway; PAI‐1, Nox‐4, and HIF‐1α. Therapeutic treatment with the ALK‐5/TGF‐β RI inhibitor SB‐525334 reversed established pulmonary fibrosis and associated vascular remodeling, leading to normalization in clinically translatable physiological parameters including lung function and hemodynamic measurements of mPAP. These studies highlight the application of this model in validating potential approaches for targeting common mechanistic pathways driving disease pathogenesis. PMID:25214520

  6. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

    PubMed Central

    Allison, Beth J.; Kaandorp, Joepe J.; Kane, Andrew D.; Camm, Emily J.; Lusby, Ciara; Cross, Christine M.; Nevin-Dolan, Rhianon; Thakor, Avnesh S.; Derks, Jan B.; Tarry-Adkins, Jane L.; Ozanne, Susan E.; Giussani, Dino A.

    2016-01-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. PMID:26932929

  7. Mechanistic pathways of mindfulness meditation in combat veterans with posttraumatic stress disorder

    PubMed Central

    Wahbeh, Helané; Goodrich, Elena; Goy, Elizabeth; Oken, Barry S.

    2015-01-01

    Objective This study’s objective was to evaluate the effect of two common components of meditation (mindfulness and slow breathing) on potential mechanistic pathways. Methods 102 combat veterans with posttraumatic stress disorder (PTSD) were randomized to: 1) the body scan mindfulness meditation (MM), 2) slow breathing (SB) with a biofeedback device, 3) mindful awareness of the breath with an intention to slow the breath (MM+SB), or 4) sitting quietly (SQ). Participants had six weekly one-on-one sessions with 20 minutes of daily home practice. The mechanistic pathways and measures were: 1) Autonomic Nervous System: hyperarousal symptoms, heart-rate (HR), heart-rate variability (HRV); 2) Frontal Cortex Activity: Attentional Network Task (ANT) conflict effect and event-related negativity, and intrusive thoughts; and 3) Hypothalamic-pituitary-adrenal axis: awakening cortisol. PTSD measures were also evaluated. Results Meditation participants had significant but modest within-group improvement in PTSD and related symptoms although there were no between-group effects. Perceived impression of PTSD symptom improvement was greater in the meditation arms compared to controls. Resting respiration decreased in the meditation arms compared to SQ. For the mechanistic pathways 1) Subjective hyperarousal symptoms improved within-group (but not between-group) for MM, MM+SB, and SQ while HR and HRV did not; 2) Intrusive thoughts decreased in MM compared to MM+SB and SB while the ANT measures did not change; and 3) MM had lower awakening cortisol within-group but not between-group. Conclusion Treatment effects were mostly specific to self-report rather than physiological measures. Continued research is needed to further evaluate mindfulness meditation’s mechanism in people with PTSD. PMID:26797725

  8. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

    PubMed

    Allison, Beth J; Kaandorp, Joepe J; Kane, Andrew D; Camm, Emily J; Lusby, Ciara; Cross, Christine M; Nevin-Dolan, Rhianon; Thakor, Avnesh S; Derks, Jan B; Tarry-Adkins, Jane L; Ozanne, Susan E; Giussani, Dino A

    2016-05-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2-1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.-Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

  9. Validating Mechanistic Sorption Model Parameters and Processes for Reactive Transport in Alluvium

    SciTech Connect

    Zavarin, M; Roberts, S K; Rose, T P; Phinney, D L

    2002-05-02

    The laboratory batch and flow-through experiments presented in this report provide a basis for validating the mechanistic surface complexation and ion exchange model we use in our hydrologic source term (HST) simulations. Batch sorption experiments were used to examine the effect of solution composition on sorption. Flow-through experiments provided for an analysis of the transport behavior of sorbing elements and tracers which includes dispersion and fluid accessibility effects. Analysis of downstream flow-through column fluids allowed for evaluation of weakly-sorbing element transport. Secondary Ion Mass Spectrometry (SIMS) analysis of the core after completion of the flow-through experiments permitted the evaluation of transport of strongly sorbing elements. A comparison between these data and model predictions provides additional constraints to our model and improves our confidence in near-field HST model parameters. In general, cesium, strontium, samarium, europium, neptunium, and uranium behavior could be accurately predicted using our mechanistic approach but only after some adjustment was made to the model parameters. The required adjustments included a reduction in strontium affinity for smectite, an increase in cesium affinity for smectite and illite, a reduction in iron oxide and calcite reactive surface area, and a change in clinoptilolite reaction constants to reflect a more recently published set of data. In general, these adjustments are justifiable because they fall within a range consistent with our understanding of the parameter uncertainties. These modeling results suggest that the uncertainty in the sorption model parameters must be accounted for to validate the mechanistic approach. The uncertainties in predicting the sorptive behavior of U-1a and UE-5n alluvium also suggest that these uncertainties must be propagated to nearfield HST and large-scale corrective action unit (CAU) models.

  10. ReactionPredictor: prediction of complex chemical reactions at the mechanistic level using machine learning.

    PubMed

    Kayala, Matthew A; Baldi, Pierre

    2012-10-22

    Proposing reasonable mechanisms and predicting the course of chemical reactions is important to the practice of organic chemistry. Approaches to reaction prediction have historically used obfuscating representations and manually encoded patterns or rules. Here we present ReactionPredictor, a machine learning approach to reaction prediction that models elementary, mechanistic reactions as interactions between approximate molecular orbitals (MOs). A training data set of productive reactions known to occur at reasonable rates and yields and verified by inclusion in the literature or textbooks is derived from an existing rule-based system and expanded upon with manual curation from graduate level textbooks. Using this training data set of complex polar, hypervalent, radical, and pericyclic reactions, a two-stage machine learning prediction framework is trained and validated. In the first stage, filtering models trained at the level of individual MOs are used to reduce the space of possible reactions to consider. In the second stage, ranking models over the filtered space of possible reactions are used to order the reactions such that the productive reactions are the top ranked. The resulting model, ReactionPredictor, perfectly ranks polar reactions 78.1% of the time and recovers all productive reactions 95.7% of the time when allowing for small numbers of errors. Pericyclic and radical reactions are perfectly ranked 85.8% and 77.0% of the time, respectively, rising to >93% recovery for both reaction types with a small number of allowed errors. Decisions about which of the polar, pericyclic, or radical reaction type ranking models to use can be made with >99% accuracy. Finally, for multistep reaction pathways, we implement the first mechanistic pathway predictor using constrained tree-search to discover a set of reasonable mechanistic steps from given reactants to given products. Webserver implementations of both the single step and pathway versions of Reaction

  11. Molecular Signaling Network Motifs Provide a Mechanistic Basis for Cellular Threshold Responses

    PubMed Central

    Bhattacharya, Sudin; Conolly, Rory B.; Clewell, Harvey J.; Kaminski, Norbert E.; Andersen, Melvin E.

    2014-01-01

    Background: Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations. Objectives: Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data. Methods: Here we have examined dose–response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. Discussion and Conclusion: Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays. Citation: Zhang Q, Bhattacharya S, Conolly RB, Clewell HJ III, Kaminski NE, Andersen ME. 2014. Molecular signaling network motifs provide a

  12. Ni-Co laterite deposits

    USGS Publications Warehouse

    Marsh, Erin E.; Anderson, Eric D.

    2011-01-01

    Nickel-cobalt (Ni-Co) laterite deposits are an important source of nickel (Ni). Currently, there is a decline in magmatic Ni-bearing sulfide lode deposit resources. New efforts to develop an alternative source of Ni, particularly with improved metallurgy processes, make the Ni-Co laterites an important exploration target in anticipation of the future demand for Ni. This deposit model provides a general description of the geology and mineralogy of Ni-Co laterite deposits, and contains discussion of the influences of climate, geomorphology (relief), drainage, tectonism, structure, and protolith on the development of favorable weathering profiles. This model of Ni-Co laterite deposits represents part of the U.S. Geological Survey Mineral Resources Program's effort to update the existing models to be used for an upcoming national mineral resource assessment.

  13. The Cycloaddition of the Benzimidazolium Ylides with Alkynes: New Mechanistic Insights

    PubMed Central

    Moldoveanu, Costel; Zbancioc, Gheorghita; Mantu, Dorina; Maftei, Dan; Mangalagiu, Ionel

    2016-01-01

    New insights concerning the reaction mechanism in the cycloaddition reaction of benzimidazolium ylides to activated alkynes are presented. The proposed pathway leading both to 2-(1H-pyrrol-1-yl)anilines and to pyrrolo[1,2-a]quinoxalin-4(5H)-ones involves an opening of the imidazole ring from the cycloaddition product, followed by a nucleophilic attack of the aminic nitrogen to a proximal carbonyl group and the elimination of a leaving group. The mechanistic considerations are fully supported by experimental data, including the XRD resolved structure of the key reaction intermediate. PMID:27224656

  14. Diversity Takes Shape: Understanding the Mechanistic and Adaptive Basis of Bacterial Morphology

    PubMed Central

    2016-01-01

    The modern age of metagenomics has delivered unprecedented volumes of data describing the genetic and metabolic diversity of bacterial communities, but it has failed to provide information about coincident cellular morphologies. Much like metabolic and biosynthetic capabilities, morphology comprises a critical component of bacterial fitness, molded by natural selection into the many elaborate shapes observed across the bacterial domain. In this essay, we discuss the diversity of bacterial morphology and its implications for understanding both the mechanistic and the adaptive basis of morphogenesis. We consider how best to leverage genomic data and recent experimental developments in order to advance our understanding of bacterial shape and its functional importance. PMID:27695035

  15. Neuronal nicotinic receptors as novel targets for inflammation and neuroprotection: mechanistic considerations and clinical relevance

    PubMed Central

    Bencherif, Merouane

    2009-01-01

    A number of studies have confirmed the potential for neuronal nicotinic acetylcholine receptor (NNR)-mediated neuroprotection and, more recently, its anti-inflammatory effects. The mechanistic overlap between these pathways and the ubiquitous effects observed following diverse insults suggest that NNRs modulate fundamental pathways involved in cell survival. These results have wide-reaching implications for the design of experimental therapeutics that regulate inflammatory and anti-apoptotic responses through NNRs and represent an initial step toward understanding the benefits of novel therapeutic strategies for the management of central nervous system disorders that target neuronal survival and associated inflammatory processes. PMID:19498416

  16. Development of a mechanistically based computer simulation of nitrogen oxide absorption in packed towers

    SciTech Connect

    Counce, R.M.

    1981-01-01

    A computer simulation for nitrogen oxide (NO/sub x/) scrubbing in packed towers was developed for use in process design and process control. This simulation implements a mechanistically based mathematical model, which was formulated from (1) an exhaustive literature review; (2) previous NO/sub x/ scrubbing experience with sieve-plate towers; and (3) comparisons of sequential sets of experiments. Nitrogen oxide scrubbing is characterized by simultaneous absorption and desorption phenomena: the model development is based on experiments designed to feature these two phenomena. The model was then successfully tested in experiments designed to put it in jeopardy.

  17. A mechanistic study of the effects of nitrogen on the corrosion properties of stainless steels

    SciTech Connect

    Levey, P.R.; Bennekom, A. van

    1995-12-01

    The effects of nitrogen alloying on the corrosion properties of stainless steels (SS) is a matter of debate. A number of apparently contradictory results have been presented by various researchers. The actual mechanism by which nitrogen alloying influences the corrosion properties of SS has been the topic of even more controversy. The effects of nitrogen on the corrosion and mechanical properties of SS were reviewed. Various proposals relating to the mechanistic effect of nitrogen alloying on the corrosion properties of SS were evaluated critically by comparing the various theories.

  18. Prediction of Damage in Randomly Oriented Short-Fibre Composites by means of A Mechanistic Approach

    SciTech Connect

    Nguyen, Ba Nghiep; Khaleel, Mohammad A.

    2004-05-01

    A micro-macro mechanistic approach to damage in short-fiber composites is developed in this paper. At the micro-scale, the damage mechanisms such as matrix cracking, fiber/matrix debonding are analyzed to define the associated damage variables. The stiffness reduction law dependent on these variables is then established using micromechanical models and average orientation distributions of fibers and microcracks. The macroscopic response is obtained by means of thermodynamics of continuous media, continuum damage mechanics and a finite element formulation.

  19. New mechanistic insights in the NH3-SCR reactions at low temperature

    DOE PAGES

    Ruggeri, Maria Pia; Selleri, Tomasso; Nova, Isabella; ...

    2016-05-06

    The present study is focused on the investigation of the low temperature Standard SCR reaction mechanism over Fe- and Cu-promoted zeolites. Different techniques are employed, including in situ DRIFTS, transient reaction analysis and chemical trapping techniques. The results present strong evidence of nitrite formation in the oxidative activation of NO and of their role in SCR reactions. These elements lead to a deeper understanding of the standard SCR chemistry at low temperature and can potentially improve the consistency of mechanistic mathematical models. Furthermore, comprehension of the mechanism on a fundamental level can contribute to the development of improved SCR catalysts.

  20. Problems in mechanistic theoretical models for cell transformation by ionizing radiation

    SciTech Connect

    Chatterjee, A.; Holley, W.R.

    1991-10-01

    A mechanistic model based on yields of double strand breaks has been developed to determine the dose response curves for cell transformation frequencies. At its present stage the model is applicable to immortal cell lines and to various qualities (X-rays, Neon and Iron) of ionizing radiation. Presently, we have considered four types of processes which can lead to activation phenomena: (1) point mutation events on a regulatory segment of selected oncogenes, (2) inactivation of suppressor genes, through point mutation, (3) deletion of a suppressor gene by a single track, and (4) deletion of a suppressor gene by two tracks.

  1. Catalytic reactions of titanium alkoxides with Grignard reagents and imines: a mechanistic study.

    PubMed

    Kumar, Akshai; Samuelson, Ashoka G

    2010-08-02

    The reactivity of Grignard reagents towards imines in the presence of catalytic and stoichiometric amounts of titanium alkoxides is reported. Alkylation, reduction, and coupling of imines take place. Whereas reductive coupling is the major reaction in stoichiometric reactions, alkylation is favored in catalytic reactions. Mechanistic studies clearly indicate that intermediates involved in the two reactions are different. Catalytic reactions involve a metal-alkyl complex. This has been confirmed by reactions of deuterium-labeled substrates and different alkylating agents. Under the stoichiometric conditions, however, titanium olefin complexes are formed through reductive elimination, probably through a multinuclear intermediate.

  2. Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes

    NASA Astrophysics Data System (ADS)

    Niemeyer, Zachary L.; Milo, Anat; Hickey, David P.; Sigman, Matthew S.

    2016-06-01

    The mechanistic foundation behind the identity of a phosphine ligand that best promotes a desired reaction outcome is often non-intuitive, and thus has been addressed in numerous experimental and theoretical studies. In this work, multivariate correlations of reaction outcomes using 38 different phosphine ligands were combined with classic potentiometric analyses to study a Suzuki reaction, for which the site selectivity of oxidative addition is highly dependent on the nature of the phosphine. These studies shed light on the generality of hypotheses regarding the structural influence of different classes of phosphine ligands on the reaction mechanism(s), and deliver a methodology that should prove useful in future studies of phosphine ligands.

  3. Bird Migration Under Climate Change - A Mechanistic Approach Using Remote Sensing

    NASA Technical Reports Server (NTRS)

    Smith, James A.; Blattner, Tim; Messmer, Peter

    2010-01-01

    The broad-scale reductions and shifts that may be expected under climate change in the availability and quality of stopover habitat for long-distance migrants is an area of increasing concern for conservation biologists. Researchers generally have taken two broad approaches to the modeling of migration behaviour to understand the impact of these changes on migratory bird populations. These include models based on causal processes and their response to environmental stimulation, "mechanistic models", or models that primarily are based on observed animal distribution patterns and the correlation of these patterns with environmental variables, i.e. "data driven" models. Investigators have applied the latter technique to forecast changes in migration patterns with changes in the environment, for example, as might be expected under climate change, by forecasting how the underlying environmental data layers upon which the relationships are built will change over time. The learned geostatstical correlations are then applied to the modified data layers.. However, this is problematic. Even if the projections of how the underlying data layers will change are correct, it is not evident that the statistical relationships will remain the same, i.e. that the animal organism may not adapt its' behaviour to the changing conditions. Mechanistic models that explicitly take into account the physical, biological, and behaviour responses of an organism as well as the underlying changes in the landscape offer an alternative to address these shortcomings. The availability of satellite remote sensing observations at multiple spatial and temporal scales, coupled with advances in climate modeling and information technologies enable the application of the mechanistic models to predict how continental bird migration patterns may change in response to environmental change. In earlier work, we simulated the impact of effects of wetland loss and inter-annual variability on the fitness of

  4. New mechanistic insights in the NH3-SCR reactions at low temperature

    SciTech Connect

    Ruggeri, Maria Pia; Selleri, Tomasso; Nova, Isabella; Tronconi, Enrico; Pihl, Josh A.; Toops, Todd J.; Partridge, Jr., William P.

    2016-05-06

    The present study is focused on the investigation of the low temperature Standard SCR reaction mechanism over Fe- and Cu-promoted zeolites. Different techniques are employed, including in situ DRIFTS, transient reaction analysis and chemical trapping techniques. The results present strong evidence of nitrite formation in the oxidative activation of NO and of their role in SCR reactions. These elements lead to a deeper understanding of the standard SCR chemistry at low temperature and can potentially improve the consistency of mechanistic mathematical models. Furthermore, comprehension of the mechanism on a fundamental level can contribute to the development of improved SCR catalysts.

  5. Catalytic intermolecular amination of C-H bonds: method development and mechanistic insights.

    PubMed

    Fiori, Kristin Williams; Du Bois, J

    2007-01-24

    Reaction methodology for intermolecular C-H amination of benzylic and 3 degrees C-H bonds is described. This process uses the starting alkane as the limiting reagent, gives optically pure tetrasubstituted amines through stereospecific insertion into enantiomeric 3 degrees centers, displays high chemoselectivity for benzylic oxidation, and enables the facile preparation of isotopically enriched 15N-labeled compounds. Access to substituted amines, amino alcohols, and diamines is thereby made possible in a single transformation. Important information relevant to understanding the initial steps in the catalytic cycle, reaction chemoselectivity, the nature of the active oxidant, and pathways for catalyst inactivation has been gained through mechanistic analysis; these studies are also presented.

  6. Alcohol amination with ammonia catalyzed by an acridine-based ruthenium pincer complex: a mechanistic study.

    PubMed

    Ye, Xuan; Plessow, Philipp N; Brinks, Marion K; Schelwies, Mathias; Schaub, Thomas; Rominger, Frank; Paciello, Rocco; Limbach, Michael; Hofmann, Peter

    2014-04-23

    The mechanistic course of the amination of alcohols with ammonia catalyzed by a structurally modified congener of Milstein's well-defined acridine-based PNP-pincer Ru complex has been investigated both experimentally and by DFT calculations. Several key Ru intermediates have been isolated and characterized. The detailed analysis of a series of possible catalytic pathways (e.g., with and without metal-ligand cooperation, inner- and outer-sphere mechanisms) leads us to conclude that the most favorable pathway for this catalyst does not require metal-ligand cooperation.

  7. TULSA UNIVERSITY PARAFFIN DEPOSITION PROJECTS

    SciTech Connect

    Michael Volk; Cem Sarica

    2003-10-01

    As oil and gas production moves to deeper and colder water, subsea multiphase production systems become critical for economic feasibility. It will also become increasingly imperative to adequately identify the conditions for paraffin precipitation and predict paraffin deposition rates to optimize the design and operation of these multiphase production systems. Although several oil companies have paraffin deposition predictive capabilities for single-phase oil flow, these predictive capabilities are not suitable for the multiphase flow conditions encountered in most flowlines and wellbores. For deepwater applications in the Gulf of Mexico, it is likely that multiphase production streams consisting of crude oil, produced water and gas will be transported in a single multiphase pipeline to minimize capital cost and complexity at the mudline. Existing single-phase (crude oil) paraffin deposition predictive tools are clearly inadequate to accurately design these pipelines because they do not account for the second and third phases, namely, produced water and gas. The objective of this program is to utilize the current test facilities at The University of Tulsa, as well as member company expertise, to accomplish the following: enhance our understanding of paraffin deposition in single and two-phase (gas-oil) flows; conduct focused experiments to better understand various aspects of deposition physics; and, utilize knowledge gained from experimental modeling studies to enhance the computer programs developed in the previous JIP for predicting paraffin deposition in single and two-phase flow environments. These refined computer models will then be tested against field data from member company pipelines. The following deliverables are scheduled during the first three projects of the program: (1) Single-Phase Studies, with three different black oils, which will yield an enhanced computer code for predicting paraffin deposition in deepwater and surface pipelines. (2) Two

  8. South Polar Layered Deposits

    NASA Technical Reports Server (NTRS)

    2003-01-01

    [figure removed for brevity, see original site]

    Released 17 July 2003

    Similar to ice cores taken from Greenland and Antarctica, Mars also has fine-scale layered deposits in both the north and south polar regions. In this image from the south pole, alternating light and dark bands represent varying amounts of dust or sand mixed in with carbon dioxide ice. These layers are related in part to climate cycles caused by variations in the tilt of Mars' rotational axis, as well as other orbital variations that occur on geologic time scales (tens of thousands of years).

    Image information: VIS instrument. Latitude -80.1, Longitude 260.4 East (99.6 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  9. Deposition + Erosion = Textures

    NASA Technical Reports Server (NTRS)

    2003-01-01

    [figure removed for brevity, see original site]

    Released 7 May 2003

    Toward the westernmost extent of the Medusae Fossae Formation, a 5000+ km long belt of eroding sediments, the interleaving of erosional surfaces produces dramatic textural variations. In the lower third of this image, the cross-hatched MFF layer is being stripped back from a surface that was already heavily eroded before the MFF layer was deposited. Also, note the sinuous and, in places, dendritic ridges that are either linear dunes or inverted channels.

    Image information: VIS instrument. Latitude -3.9, Longitude 154.1East (205.9). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  10. Glacial atmospheric phosphorus deposition

    NASA Astrophysics Data System (ADS)

    Kjær, Helle Astrid; Dallmayr, Remi; Gabrieli, Jacopo; Goto-Azuma, Kumiko; Hirabayashi, Motohiro; Svensson, Anders; Vallelonga, Paul

    2016-04-01

    Phosphorus in the atmosphere is poorly studied and thus not much is known about atmospheric phosphorus and phosphate transport and deposition changes over time, though it is well known that phosphorus can be a source of long-range nutrient transport, e.g. Saharan dust transported to the tropical forests of Brazil. In glacial times it has been speculated that transport of phosphorus from exposed shelves would increase the ocean productivity by wash out. However whether the exposed shelf would also increase the atmospheric load to more remote places has not been investigated. Polar ice cores offer a unique opportunity to study the atmospheric transport of aerosols on various timescales, from glacial-interglacial periods to recent anthropogenic influences. We have for the first time determined the atmospheric transport of phosphorus to the Arctic by means of ice core analysis. Both total and dissolved reactive phosphorus were measured to investigate current and past atmospheric transport of phosphorus to the Arctic. Results show that glacial cold stadials had increased atmospheric total phosphorus mass loads of 70 times higher than in the past century, while DRP was only increased by a factor of 14. In the recent period we find evidence of a phosphorus increase over the past 50 yrs in ice cores close to human occupation likely correlated to forest fires. References: Kjær, Helle Astrid, et al. "Continuous flow analysis method for determination of dissolved reactive phosphorus in ice cores." Environmental science & technology 47.21 (2013): 12325-12332. Kjær, Helle Astrid, et al. "Greenland ice cores constrain glacial atmospheric fluxes of phosphorus." Journal of Geophysical Research: Atmospheres120.20 (2015).

  11. Sputter Deposition of Metallic Sponges

    SciTech Connect

    Jankowski, A F; Hayes, J P

    2002-01-18

    Metallic films are grown with a sponge-like morphology in the as-deposited condition using planar magnetron sputtering. The morphology of the deposit is characterized by metallic continuity in three dimensions with continuous porosity on the sub-micron scale. The stabilization of the metallic sponge is directly correlated with a limited range for the sputter deposition parameters of working gas pressure and substrate temperature. This sponge-like morphology augments the features as generally understood in the classic zone models of growth for physical vapor deposits. Nickel coatings are deposited with working gas pressures up to 4 Pa and for substrate temperatures up to 1100 K. The morphology of the deposits is examined in plan and in cross-section with scanning electron microscopy. The parametric range of gas pressure and substrate temperature (relative to absolute melt point) for the deposition processing under which the metallic sponges are produced appear universal for many metals, as for example, including gold, silver, and aluminum.

  12. Jet aircraft fuel system deposits

    SciTech Connect

    Hazlett, R.N.; Hall, J.M.

    1981-03-01

    Deposits samples were from the valve cavity of a fuel nozzle of a CF6-50A engine, from the fuel manifold adjacent to the combustor nozzles of a TR-30 engine, fuel test devices, and heat exchange tubes, operated in the laboratories of the Naval Air Propulsion Center and the Air Force Aero Propulsion Laboratory. Carbon, hydrogen, nitrogen and oxygen in the deposits were determined with a Perkin Elmer Elemental Analyzer. Sulfur was determined on a separate sample by modifying ASTM method D3120-75. The high amount of oxygen, nitrogen and sulfur found in the deposits is noteworthy. The data reported generally corroborates the information from the literature. All of the deposits from the engines and the test devices point to the importance of compounds containing hereto atoms. The importance of oxidation in triggering solids formation has been reviewed. It would appear that the trace primary oxidation reactions occurring in a fuel system would be insufficient to give the high concentration of oxygen in the deposit. However, if the compounds undergoing oxidation were oxygen-containing compounds rather than hydrocarbons the high oxygen concentrations in the deposit would be more reasonable. The high enhancement factors observed, causes one to conclude that some nitrogen and sulfur compounds found in fuels are very susceptible to oxidation and subsequent deposit formation. The high concentrations of hereto atoms implies that the deposits have highly polar characteristics. Since such material would have little attraction for the non-polar fuel, the insolubility of deposits may be due primarily to polarity differences rather than high molecular weight.

  13. Experimental and numerical studies on laser-based powder deposition of slurry erosion resistant materials

    NASA Astrophysics Data System (ADS)

    Balu, Prabu

    cracking issue, and 3) the effect of composition and composition gradient of Ni and WC on the slurry erosion resistance over a wide range of erosion conditions. This thesis presents a set of numerical and experimental methods in order to address the challenges mentioned above. A three-dimensional (3-D) computational fluid dynamics (CFD) based powder flow model and three vision based techniques were developed in order to visualize the process of feeding the Ni-WC powder in the LBPD process. The results provide the guidelines for efficiently feeding the Ni-WC composite powder into the laser-formed molten pool. The finite element (FE) based experimentally verified 3-D thermal and thermo-mechanical models are developed in order to understand the thermal and stress evolutions in Ni-WC composite material during the LBPD process. The models address the effect of the process variables, preheating temperature, and different mass fractions of WC in Ni on thermal cycles and stress distributions within the deposited material. The slurry erosion behavior of the single and multilayered deposits of Ni-WC composite material produced by the LBPD process is investigated using an accelerated slurry erosion testing machine and a 3-D FE dynamic model. The verified model is used to identify the appropriate composition and composition gradient of Ni-WC composite material required to achieve erosion resistance over a wide range of erosion conditions.

  14. Simulating the Risk of Liver Fluke Infection using a Mechanistic Hydro-epidemiological Model

    NASA Astrophysics Data System (ADS)

    Beltrame, Ludovica; Dunne, Toby; Rose, Hannah; Walker, Josephine; Morgan, Eric; Vickerman, Peter; Wagener, Thorsten

    2016-04-01

    Liver Fluke (Fasciola hepatica) is a common parasite found in livestock and responsible for considerable economic losses throughout the world. Risk of infection is strongly influenced by climatic and hydrological conditions, which characterise the host environment for parasite development and transmission. Despite on-going control efforts, increases in fluke outbreaks have been reported in recent years in the UK, and have been often attributed to climate change. Currently used fluke risk models are based on empirical relationships derived between historical climate and incidence data. However, hydro-climate conditions are becoming increasingly non-stationary due to climate change and direct anthropogenic impacts such as land use change, making empirical models unsuitable for simulating future risk. In this study we introduce a mechanistic hydro-epidemiological model for Liver Fluke, which explicitly simulates habitat suitability for disease development in space and time, representing the parasite life cycle in connection with key environmental conditions. The model is used to assess patterns of Liver Fluke risk for two catchments in the UK under current and potential future climate conditions. Comparisons are made with a widely used empirical model employing different datasets, including data from regional veterinary laboratories. Results suggest that mechanistic models can achieve adequate predictive ability and support adaptive fluke control strategies under climate change scenarios.

  15. Stoichiometry of proton translocation by respiratory complex I and its mechanistic implications

    PubMed Central

    Wikström, Mårten; Hummer, Gerhard

    2012-01-01

    Complex I (NADH-ubiquinone oxidoreductase) in the respiratory chain of mitochondria and several bacteria functions as a redox-driven proton pump that contributes to the generation of the protonmotive force across the inner mitochondrial or bacterial membrane and thus to the aerobic synthesis of ATP. The stoichiometry of proton translocation is thought to be 4 H+ per NADH oxidized (2 e-). Here we show that a H+/2 e- ratio of 3 appears more likely on the basis of the recently determined H+/ATP ratio of the mitochondrial F1Fo-ATP synthase of animal mitochondria and of a set of carefully determined ATP/2 e- ratios for different segments of the mitochondrial respiratory chain. This lower H+/2 e- ratio of 3 is independently supported by thermodynamic analyses of experiments with both mitochondria and submitochondrial particles. A reduced H+/2 e- stoichiometry of 3 has important mechanistic implications for this proton pump. In a rough mechanistic model, we suggest a concerted proton translocation mechanism in the three homologous and tightly packed antiporter-like subunits L, M, and N of the proton-translocating membrane domain of complex I. PMID:22392981

  16. From the exposome to mechanistic understanding of chemical-induced adverse effects.

    PubMed

    Escher, Beate I; Hackermüller, Jörg; Polte, Tobias; Scholz, Stefan; Aigner, Achim; Altenburger, Rolf; Böhme, Alexander; Bopp, Stephanie K; Brack, Werner; Busch, Wibke; Chadeau-Hyam, Marc; Covaci, Adrian; Eisenträger, Adolf; Galligan, James J; Garcia-Reyero, Natalia; Hartung, Thomas; Hein, Michaela; Herberth, Gunda; Jahnke, Annika; Kleinjans, Jos; Klüver, Nils; Krauss, Martin; Lamoree, Marja; Lehmann, Irina; Luckenbach, Till; Miller, Gary W; Müller, Andrea; Phillips, David H; Reemtsma, Thorsten; Rolle-Kampczyk, Ulrike; Schüürmann, Gerrit; Schwikowski, Benno; Tan, Yu-Mei; Trump, Saskia; Walter-Rohde, Susanne; Wambaugh, John F

    2017-02-01

    The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. Here, we explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health.

  17. Uncertainty analysis in a mechanistic model of bacterial regrowth in distribution systems.

    PubMed

    Digiano, Francis A; Zhang, Weidong

    2004-11-15

    The first generation of mechanistic models of bacterial regrowth in distribution systems (DS) provides insight into cause-and-effect relationships. However, the state of knowledge about the processes included in these models is insufficient to warrant deterministic predictions. Even if the process descriptions are reasonable, the uncertainty in values of key system constants limits predictions of bacterial growth. A new mechanistic model was developed to incorporate the accepted knowledge of physical, chemical, and biological processes with the hydraulic features in order to capture the unsteady state behavior of the DS. Sensitivitytesting showed that the extent of bacterial regrowth was affected mainly by the rate constants for chlorine decay reactions in bulk water and on the pipe wall and by the maximum growth rate constant of attached bacteria. A simple hypothetical network was used to evaluate the effects of uncertainty in these three system constants by running 100 Monte Carlo simulations. Cumulative probability plots showed a wide range of predictions for concentrations of bacteria and chlorine in bulk water at various nodes in the DS. The magnitude of these concentrations and the range of values were greatly affected by water residence time to each node. Once the chlorine residual is depleted, bacterial growth is mainly influenced by the amount of substrate available. However, high values of the coefficients for the maximum growth rate of attached bacteria, the chlorine decay in bulk water, and the chlorine decay by wall reaction did not necessarily lead to the maximum bacterial growth at a given location.

  18. Induced polarization dependence on pore space geometry: Empirical observations and mechanistic predictions

    NASA Astrophysics Data System (ADS)

    Weller, A.; Slater, L. D.

    2015-12-01

    We use an extensive database to compare empirical observations and previously proposed empirical models against recently developed mechanistic formulations for the induced polarization (IP) response in porous media as a function of pore space geometry and interfacial chemistry. These comparisons support the argument that the pore-volume normalized internal surface (Spor) is the most important geometric parameter influencing the polarization. The specific polarizability derived from the empirical relationship between imaginary conductivity σ″ and Spor is independent of the porosity. By contrast, equivalent specific polarizability terms in recently proposed mechanistic models are found to be significantly correlated with porosity, and thus do not appear to represent an interfacial chemistry factor independent of the pore space geometry. Furthermore, the database shows no evidence for a significant decrease in the counterion mobility of clayey materials relative to clay-free materials, as postulated in recent studies. On the contrary, a single value of cp is consistent with no significant differences in ionic mobility given that all samples were saturated with a NaCl solution close to a common salinity of about 100 mS/m.

  19. Mechanistic Insight and Management of Diabetic Nephropathy: Recent Progress and Future Perspective

    PubMed Central

    Xue, Rui; Gui, Dingkun; Zheng, Liyang; Zhai, Ruonan

    2017-01-01

    Diabetic nephropathy (DN) is the most serious microvascular complication of diabetes and the largest single cause of end-stage renal disease (ESRD) in many developed countries. DN is also associated with an increased cardiovascular mortality. It occurs as a result of interaction between both genetic and environmental factors. Hyperglycemia, hypertension, and genetic predisposition are the major risk factors. However, the exact mechanisms of DN are unclear. Despite the benefits derived from strict control of glucose and blood pressure, as well as inhibition of renin-angiotensin-aldosterone system, many patients continue to enter into ESRD. Thus, there is urgent need for improving mechanistic understanding of DN and then developing new and effective therapeutic approaches to delay the progression of DN. This review focuses on recent progress and future perspective about mechanistic insight and management of DN. Some preclinical relevant studies are highlighted and new perspectives of traditional Chinese medicine (TCM) for delaying DN progression are discussed in detail. These findings strengthen the therapeutic rationale for TCM in the treatment of DN and also provide new insights into the development of novel drugs for the prevention of DN. However, feasibility and safety of these therapeutic approaches and the clinical applicability of TCM in human DN need to be further investigated. PMID:28386567

  20. The autism puzzle: challenging a mechanistic model on conceptual and historical grounds

    PubMed Central

    2013-01-01

    Although clinicians and researchers working in the field of autism are generally not concerned with philosophical categories of kinds, a model for understanding the nature of autism is important for guiding research and clinical practice. Contemporary research in the field of autism is guided by the depiction of autism as a scientific object that can be identified with systematic neuroscientific investigation. This image of autism is compatible with a permissive account of natural kinds: the mechanistic property cluster (MPC) account of natural kinds, recently proposed as the model for understanding psychiatric disorders. Despite the heterogeneity, multicausality and fuzzy boundaries that complicate autism research, a permissive account of natural kinds (MPC kinds) provides prescriptive guidance for the investigation of objective causal mechanisms that should inform nosologists in their attempt to carve autism’s boundaries at its natural joints. However, this essay will argue that a mechanistic model of autism is limited since it disregards the way in which autism relates to ideas about what kind of behavior is abnormal. As historical studies and definitions of autism show, normative issues concerning disability, impairment and societal needs have been and still are inextricably linked to how we recognize and understand autism. The current search for autism’s unity in neurobiological mechanisms ignores the values, social norms and various perspectives on mental pathology that play a significant role in 'the thing called autism’. Autism research needs to engage with these issues in order to achieve more success in the effort to become clinically valuable. PMID:24207065

  1. Life at the Common Denominator: Mechanistic and Quantitative Biology for the Earth and Space Sciences

    NASA Technical Reports Server (NTRS)

    Hoehler, Tori M.

    2010-01-01

    The remarkable challenges and possibilities of the coming few decades will compel the biogeochemical and astrobiological sciences to characterize the interactions between biology and its environment in a fundamental, mechanistic, and quantitative fashion. The clear need for integrative and scalable biology-environment models is exemplified in the Earth sciences by the challenge of effectively addressing anthropogenic global change, and in the space sciences by the challenge of mounting a well-constrained yet sufficiently adaptive and inclusive search for life beyond Earth. Our understanding of the life-planet interaction is still, however, largely empirical. A variety of approaches seek to move from empirical to mechanistic descriptions. One approach focuses on the relationship between biology and energy, which is at once universal (all life requires energy), unique (life manages energy flow in a fashion not seen in abiotic systems), and amenable to characterization and quantification in thermodynamic terms. Simultaneously, a focus on energy flow addresses a critical point of interface between life and its geological, chemical, and physical environment. Characterizing and quantifying this relationship for life on Earth will support the development of integrative and predictive models for biology-environment dynamics. Understanding this relationship at its most fundamental level holds potential for developing concepts of habitability and biosignatures that can optimize astrobiological exploration strategies and are extensible to all life.

  2. Comparison of Two-Phase Pipe Flow in OpenFOAM with a Mechanistic Model

    NASA Astrophysics Data System (ADS)

    Shuard, Adrian M.; Mahmud, Hisham B.; King, Andrew J.

    2016-03-01

    Two-phase pipe flow is a common occurrence in many industrial applications such as power generation and oil and gas transportation. Accurate prediction of liquid holdup and pressure drop is of vast importance to ensure effective design and operation of fluid transport systems. In this paper, a Computational Fluid Dynamics (CFD) study of a two-phase flow of air and water is performed using OpenFOAM. The two-phase solver, interFoam is used to identify flow patterns and generate values of liquid holdup and pressure drop, which are compared to results obtained from a two-phase mechanistic model developed by Petalas and Aziz (2002). A total of 60 simulations have been performed at three separate pipe inclinations of 0°, +10° and -10° respectively. A three dimensional, 0.052m diameter pipe of 4m length is used with the Shear Stress Transport (SST) k - ɷ turbulence model to solve the turbulent mixtures of air and water. Results show that the flow pattern behaviour and numerical values of liquid holdup and pressure drop compare reasonably well to the mechanistic model.

  3. Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

    DOE PAGES

    Grossmann, Nina; Vakkasoglu, Ahmet S.; Hulpke, Sabine; ...

    2014-11-07

    The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the converved aspartate, whichmore » coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. As a result, our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.« less

  4. Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

    SciTech Connect

    Grossmann, Nina; Vakkasoglu, Ahmet S.; Hulpke, Sabine; Abele, Rupert; Gaudet, Rachelle; Tampé, Robert

    2014-11-07

    The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the converved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. As a result, our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.

  5. Mechanistic approach to multi-element isotope modeling of organic contaminant degradation.

    PubMed

    Jin, Biao; Rolle, Massimo

    2014-01-01

    We propose a multi-element isotope modeling approach to simultaneously predict the evolution of different isotopes during the transformation of organic contaminants. The isotopic trends of different elements are explicitly simulated by tracking position-specific isotopologues that contain the isotopes located at fractionating positions. Our approach is self-consistent and provides a mechanistic description of different degradation pathways that accounts for the influence of both primary and secondary isotope effects during contaminant degradation. The method is particularly suited to quantitatively describe the isotopic evolution of relatively large organic contaminant molecules. For such compounds, an integrated approach, simultaneously considering all possible isotopologues, would be impractical due to the large number of isotopologues. We apply the proposed modeling approach to the degradation of toluene, methyl tert-butyl ether (MTBE) and nitrobenzene observed in previous experimental studies. Our model successfully predicts the multi-element isotope data (both 2D and 3D), and accurately captures the distinct trends observed for different reaction pathways. The proposed approach provides an improved and mechanistic methodology to interpret multi-element isotope data and to predict the extent of multi-element isotope fractionation that goes beyond commonly applied modeling descriptions and simplified methods based on the ratio between bulk enrichment factors or on linear regression in dual-isotope plots.

  6. Use of mechanistic data in assessing human risks from exposure to particles.

    PubMed Central

    McClellan, R O

    1997-01-01

    The ultimate goal of toxicologic investigations of both natural and man-made fibrous and nonfibrous particles is to provide essential input for the assessment of potential human risks from exposure to these materials. The development of risk assessment procedures for airborne particles has evolved over the years. The earliest assessments for naturally occurring materials used direct human observations and incorporated safety factors to arrive at allowable human exposures. More recently, there has been a need to assess the potential risk associated with production and use of certain man-made materials for which human data are not available or are inadequate. For these materials, it has been necessary to assess human risks using data obtained from studies conducted in laboratory animals and with cells or tissues. During the last several decades, it has been suggested that data on the mechanisms by which particles cause disease could be used to reduce the uncertainty in estimates of human risks of particle exposures. This article provides comments on the use of mechanistic data in the risk assessment process and suggestions for increasing the successful development and use of mechanistic data in risk assessments conducted in the future. PMID:9400751

  7. Systems biology and the integration of mechanistic explanation and mathematical explanation.

    PubMed

    Brigandt, Ingo

    2013-12-01

    The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models-which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation (as the analysis of a whole in terms of its structural parts and their qualitative interactions) have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena (rather than the explanation of quantitative details), where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism's ability to respond to perturbations (beyond its actual operation). I offer general conclusions for philosophical accounts of explanation.

  8. Mechanistic investigation of the reaction of epoxides with heterocumulenes catalysed by a bimetallic aluminium salen complex.

    PubMed

    Beattie, Christopher; North, Michael

    2014-06-23

    The bimetallic aluminium(salen) complex [(Al(salen))2O] is known to catalyse the reaction between epoxides and heterocumulenes (carbon dioxide, carbon disulfide and isocyanates) leading to five-membered ring heterocycles. Despite their apparent similarities, these three reactions have very different mechanistic features, and a kinetic study of oxazolidinone synthesis combined with previous kinetic work on cyclic carbonate and cyclic dithiocarbonate synthesis showed that all three reactions follow different rate equations. An NMR study of [Al(salen)]2O and phenylisocyanate provided evidence for an interaction between them, consistent with the rate equation data. A variable-temperature kinetics study on all three reactions showed that cyclic carbonate synthesis had a lower enthalpy of activation and a more negative entropy of activation than the other two heterocycle syntheses. The kinetic study was extended to oxazolidinone synthesis catalysed by the monometallic complex Al(salen)Cl, and this reaction was found to have a much less negative entropy of activation than any reaction catalysed by [Al(salen)]2O, a result that can be explained by the partial dissociation of an oligomeric Al(salen)Cl complex. A mechanistic rationale for all of the results is presented in terms of [Al(salen)]2O being able to function as a Lewis acid and/or a Lewis base, depending upon the susceptibility of the heterocumulene to reaction with nucleophiles.

  9. A Framework and Mechanistically Focused, In Silico Method for Enabling Rational Translational Research

    PubMed Central

    Hunt, C. Anthony; Baranzini, Sergio; Matthay, Michael A.; Park, Sunwoo

    2008-01-01

    A precondition for understanding if-and-when observations on wet-lab research models can translate to patients (and vice versa) is to have a method that enables anticipating how each system at the mechanism level will respond to the same or similar new intervention. A new class of mechanistic, in silico analogues is described. We argue that, although abstract, they enable developing that method. Building an analogue of each system within a common framework allows exploration of how one analogue might undergo (automated) metamorphosis to become the other. When successful, a concrete mapping is achieved. We hypothesize that such a mapping is, itself, an analogue of a corresponding mapping between the two referent systems. The analogue mapping can help establish how targeted aspects of the two referent systems are similar and different, at the mechanistic level and, importantly, at the systemic, emergent property level. The vision is that the analogues along with the metamorphosis method can be improved iteratively as part of a rational approach to translational research. PMID:21347126

  10. Ecological Forecasting in Chesapeake Bay: Using a Mechanistic-Empirical Modelling Approach

    SciTech Connect

    Brown, C. W.; Hood, Raleigh R.; Long, Wen; Jacobs, John M.; Ramers, D. L.; Wazniak, C.; Wiggert, J. D.; Wood, R.; Xu, J.

    2013-09-01

    The Chesapeake Bay Ecological Prediction System (CBEPS) automatically generates daily nowcasts and three-day forecasts of several environmental variables, such as sea-surface temperature and salinity, the concentrations of chlorophyll, nitrate, and dissolved oxygen, and the likelihood of encountering several noxious species, including harmful algal blooms and water-borne pathogens, for the purpose of monitoring the Bay's ecosystem. While the physical and biogeochemical variables are forecast mechanistically using the Regional Ocean Modeling System configured for the Chesapeake Bay, the species predictions are generated using a novel mechanistic empirical approach, whereby real-time output from the coupled physical biogeochemical model drives multivariate empirical habitat models of the target species. The predictions, in the form of digital images, are available via the World Wide Web to interested groups to guide recreational, management, and research activities. Though full validation of the integrated forecasts for all species is still a work in progress, we argue that the mechanistic–empirical approach can be used to generate a wide variety of short-term ecological forecasts, and that it can be applied in any marine system where sufficient data exist to develop empirical habitat models. This paper provides an overview of this system, its predictions, and the approach taken.

  11. Mechanistic studies of protein arginine deiminase 2: evidence for a substrate-assisted mechanism.

    PubMed

    Dreyton, Christina J; Knuckley, Bryan; Jones, Justin E; Lewallen, Daniel M; Thompson, Paul R

    2014-07-15

    Citrullination, which is catalyzed by protein arginine deiminases (PADs 1-4 and 6), is a post-translational modification (PTM) that effectively neutralizes the positive charge of a guanidinium group by its replacement with a neutral urea. Given the sequence similarity of PAD2 across mammalian species and the genomic organization of the PAD2 gene, PAD2 is predicted to be the ancestral homologue of the PADs. Although PAD2 has long been known to play a role in myelination, it has only recently been linked to other cellular processes, including gene transcription and macrophage extracellular trap formation. For example, PAD2 deiminates histone H3 at R26, and this PTM leads to the increased transcription of more than 200 genes under the control of the estrogen receptor. Given that our understanding of PAD2 biology remains incomplete, we initiated mechanistic studies on this enzyme to aid the development of PAD2-specific inhibitors. Herein, we report that the substrate specificity and calcium dependence of PAD2 are similar to those of PADs 1, 3, and 4. However, unlike those isozymes, PAD2 appears to use a substrate-assisted mechanism of catalysis in which the positively charged substrate guanidinium depresses the pKa of the nucleophilic cysteine. By contrast, PADs 1, 3, and 4 use a reverse-protonation mechanism. These mechanistic differences will aid the development of isozyme-specific inhibitors.

  12. A mechanistic description of the formation and evolution of vegetation patterns

    NASA Astrophysics Data System (ADS)

    Foti, R.; Ramírez, J. A.

    2013-01-01

    Vegetation patterns are a common and well-defined characteristic of many landscapes. In this paper we explore some of the physical mechanisms responsible for the establishment of self-organized, non-random vegetation patterns that arise at the hillslope scale in many areas of the world, especially in arid and semi-arid regions. In doing so, we provide a fundamental mechanistic understanding of the dynamics of vegetation pattern formation and development. Reciprocal effects of vegetation on the hillslope thermodynamics, runoff production and run-on infiltration, root density, surface albedo and soil moisture content are analyzed. In particular, we: (1) present a physically based mechanistic description of processes leading to vegetation pattern formation; (2) quantify the relative impact of each process on pattern formation; and (3) describe the relationships between vegetation patterns and the climatic, hydraulic and topographic characteristics of the system. We validate the model by comparing simulations with observed natural patterns in the areas of Niger near Niamey and Somalia near Garoowe. Our analyses suggest that the phenomenon of pattern formation is primarily driven by run-on infiltration and mechanisms of facilitation/inhibition among adjacent vegetation groups, mediated by vegetation effects on soil properties and controls on soil moisture and albedo. Nonetheless, even in presence of those mechanisms, patterns arise only when the climatic conditions, particularly annual precipitation and net radiation, are favorable.

  13. On a novel mechanistic model for simultaneous enzymatic hydrolysis of cellulose and hemicellulose considering morphology.

    PubMed

    Zhang, Yang; Xu, Bingqian; Zhou, Wen

    2014-09-01

    We develop a novel and general modeling framework for enzymatic hydrolysis of cellulose and hemicellulose simultaneously. Our mechanistic model, for the first time, takes into consideration explicitly the time evolution of morphologies of intertwining cellulose and hemicelluloses within substrate during enzymatic hydrolysis. This morphology evolution is driven by hydrolytic chain fragmentation and solubilization, which is, in return, profoundly affected by the substrate morphology. We represent the substrate morphology as a randomly distributed smallest accessible compartments (SACs) which are described by geometric functions to track total volume and exposed surface substrate materials, including both cellulose and hemicelluloses. Our morphology-plus-kinetics approach then couple the time-dependent morphology with chain fragmentation and solubilization resulted from enzymatic reactions between various bonds in cellulose and hemicelluloses and a mixture (i.e., endo-, exo-, and oligomer- acting) of cellulases and hemicellulases. In addition, we propose an advanced and generalized site concentration formalism that considers different polysaccharide chain types and different monomer unit types on chains. The resulting ODE system has a substantially reduced size compared to conventional chain concentration formalism. We present numerical simulation results under real enzymatic hydrolysis experimental conditions from literature. The comparisons between the simulation results and the experiment measurements demonstrate effectiveness and wide applicability of the proposed mechanistic model.

  14. Productivity of "collisions generate heat" for reconciling an energy model with mechanistic reasoning: A case study

    NASA Astrophysics Data System (ADS)

    Scherr, Rachel E.; Robertson, Amy D.

    2015-06-01

    We observe teachers in professional development courses about energy constructing mechanistic accounts of energy transformations. We analyze a case in which teachers investigating adiabatic compression develop a model of the transformation of kinetic energy to thermal energy. Among their ideas is the idea that thermal energy is generated as a byproduct of individual particle collisions, which is represented in science education research literature as an obstacle to learning. We demonstrate that in this instructional context, the idea that individual particle collisions generate thermal energy is not an obstacle to learning, but instead is productive: it initiates intellectual progress. Specifically, this idea initiates the reconciliation of the teachers' energy model with mechanistic reasoning about adiabatic compression, and leads to a canonically correct model of the transformation of kinetic energy into thermal energy. We claim that the idea's productivity is influenced by features of our particular instructional context, including the instructional goals of the course, the culture of collaborative sense making, and the use of certain representations of energy.

  15. Particle deposition in ventilation ducts

    SciTech Connect

    Sippola, Mark Raymond

    2002-09-01

    Exposure to airborne particles is detrimental to human health and indoor exposures dominate total exposures for most people. The accidental or intentional release of aerosolized chemical and biological agents within or near a building can lead to exposures of building occupants to hazardous agents and costly building remediation. Particle deposition in heating, ventilation and air-conditioning (HVAC) systems may significantly influence exposures to particles indoors, diminish HVAC performance and lead to secondary pollutant release within buildings. This dissertation advances the understanding of particle behavior in HVAC systems and the fates of indoor particles by means of experiments and modeling. Laboratory experiments were conducted to quantify particle deposition rates in horizontal ventilation ducts using real HVAC materials. Particle deposition experiments were conducted in steel and internally insulated ducts at air speeds typically found in ventilation ducts, 2-9 m/s. Behaviors of monodisperse particles with diameters in the size range 1-16 μm were investigated. Deposition rates were measured in straight ducts with a fully developed turbulent flow profile, straight ducts with a developing turbulent flow profile, in duct bends and at S-connector pieces located at duct junctions. In straight ducts with fully developed turbulence, experiments showed deposition rates to be highest at duct floors, intermediate at duct walls, and lowest at duct ceilings. Deposition rates to a given surface increased with an increase in particle size or air speed. Deposition was much higher in internally insulated ducts than in uninsulated steel ducts. In most cases, deposition in straight ducts with developing turbulence, in duct bends and at S-connectors at duct junctions was higher than in straight ducts with fully developed turbulence. Measured deposition rates were generally higher than predicted by published models. A model incorporating empirical equations based on the

  16. Mechanistic insights on the cycloisomerization of polyunsaturated precursors catalyzed by platinum and gold complexes.

    PubMed

    Soriano, Elena; Marco-Contelles, José

    2009-08-18

    Organometallic chemistry provides powerful tools for the stereocontrolled synthesis of heterocycles and carbocycles. The electrophilic transition metals Pt(II) and Au(I, III) are efficient catalysts in these transitions and promote a variety of organic transformations of unsaturated precursors. These reactions produce functionalized cyclic and acyclic scaffolds for the synthesis of natural and non-natural products efficiently, under mild conditions, and with excellent chemoselectivity. Because these transformations are strongly substrate-dependent, they are versatile and may yield diverse molecular scaffolds. Therefore, synthetic chemists need a mechanistic interpretation to optimize this reaction process and design a new generation of catalysts. However, so far, no intermediate species has been isolated or characterized, so the formulated mechanistic hypotheses have been primarily based on labeling studies or trapping reactions. Recently, theoretical DFT studies have become a useful tool in our research, giving us insights into the key intermediates and into a variety of plausible reaction pathways. In this Account, we present a comprehensive mechanistic overview of transformations promoted by Pt and Au in a non-nucleophilic medium based on quantum-mechanical studies. The calculations are consistent with the experimental observations and provide fundamental insights into the versatility of these reaction processes. The reactivity of these metals results from their peculiar Lewis acid properties: the alkynophilic character of these soft metals and the pi-acid activation of unsaturated groups promotes the intra- or intermolecular attack of a nucleophile. 1,n-Enynes (n = 3-8) are particularly important precursors, and their transformation may yield a variety of cycloadducts depending on the molecular structure. However, the calculations suggest that these different cyclizations would have closely related reaction mechanisms, and we propose a unified mechanistic

  17. Mechanistic Studies at the Interface Between Organometallic Chemistry and Homogeneous Catalysis

    SciTech Connect

    Casey, Charles P

    2012-11-14

    Mechanistic Studies at the Interface Between Organometallic Chemistry and Homogeneous Catalysis Charles P. Casey, Principal Investigator Department of Chemistry, University of Wisconsin - Madison, Madison, Wisconsin 53706 Phone 608-262-0584 FAX: 608-262-7144 Email: casey@chem.wisc.edu http://www.chem.wisc.edu/main/people/faculty/casey.html Executive Summary. Our goal was to learn the intimate mechanistic details of reactions involved in homogeneous catalysis and to use the insight we gain to develop new and improved catalysts. Our work centered on the hydrogenation of polar functional groups such as aldehydes and ketones and on hydroformylation. Specifically, we concentrated on catalysts capable of simultaneously transferring hydride from a metal center and a proton from an acidic oxygen or nitrogen center to an aldehyde or ketone. An economical iron based catalyst was developed and patented. Better understanding of fundamental organometallic reactions and catalytic processes enabled design of energy and material efficient chemical processes. Our work contributed to the development of catalysts for the selective and mild hydrogenation of ketones and aldehydes; this will provide a modern green alternative to reductions by LiAlH4 and NaBH4, which require extensive work-up procedures and produce waste streams. (C5R4OH)Ru(CO)2H Hydrogenation Catalysts. Youval Shvo described a remarkable catalytic system in which the key intermediate (C5R4OH)Ru(CO)2H (1) has an electronically coupled acidic OH unit and a hydridic RuH unit. Our efforts centered on understanding and improving upon this important catalyst for reduction of aldehydes and ketones. Our mechanistic studies established that the reduction of aldehydes by 1 to produce alcohols and a diruthenium bridging hydride species occurs much more rapidly than regeneration of the ruthenium hydride from the diruthenium bridging hydride species. Our mechanistic studies require simultaneous transfer of hydride from ruthenium to

  18. A Top-Down Approach to Mechanistic Biological Modeling: Application to the Single-Chain Antibody Folding Pathway

    PubMed Central

    Hildebrandt, Scott; Raden, David; Petzold, Linda; Robinson, Anne Skaja; Doyle, Francis J.

    2008-01-01

    A top-down approach to mechanistic modeling of biological systems is presented and exemplified with the development of a hypothesis-driven mathematical model for single-chain antibody fragment (scFv) folding in Saccharomyces cerevisiae by mediators BiP and PDI. In this approach, model development starts with construction of the most basic mathematical model—typically consisting of predetermined or newly-elucidated biological behavior motifs—capable of reproducing desired biological behaviors. From this point, mechanistic detail is added incrementally and systematically, and the effects of each addition are evaluated. This approach follows the typical progression of experimental data availability in that higher-order, lumped measurements are often more prevalent initially than specific, mechanistic ones. It also necessarily provides the modeler with insight into the structural requirements and performance capabilities of the resulting detailed mechanistic model, which facilitates further analysis. The top-down approach to mechanistic modeling identified three such requirements and a branched dependency-degradation competition motif critical for the scFv folding model to reproduce experimentally observed scFv folding dependencies on BiP and PDI and increased production when both species are overexpressed and promoted straightforward prediction of parameter dependencies. It also prescribed modification of the guiding hypothesis to capture BiP and PDI synergy. PMID:18641066

  19. A Mechanistic Explanation of the Peculiar Amphiphobic Properties of Hybrid Organic-Inorganic Coatings by Combining XPS Characterization and DFT Modeling.

    PubMed

    Motta, Alessandro; Cannelli, Oliviero; Boccia, Alice; Zanoni, Robertino; Raimondo, Mariarosa; Caldarelli, Aurora; Veronesi, Federico

    2015-09-16

    We report a combined X-ray photoelectron spectroscopy and theoretical modeling analysis of hybrid functional coatings constituted by fluorinated alkylsilane monolayers covalently grafted on a nanostructured ceramic oxide (Al2O3) thin film deposited on aluminum alloy substrates. Such engineered surfaces, bearing hybrid coatings obtained via a classic sol-gel route, have been previously shown to possess amphiphobic behavior (superhydrophobicity plus oleophobicity) and excellent durability, even under simulated severe working environments. Starting from XPS, SEM, and contact angle results and analysis, and combining it with DFT results, the present investigation offers a first mechanistic explanation at a molecular level of the peculiar properties of the hybrid organic-inorganic coating in terms of composition and surface structural arrangements. Theoretical modeling shows that the active fluorinated moiety is strongly anchored on the alumina sites with single Si-O-Al bridges and that the residual valence of Si is saturated by Si-O-Si bonds which form a reticulation with two vicinal fluoroalkylsilanes. The resulting hybrid coating consists of stable rows of fluorinated alkyl chains in reciprocal contact, which form well-ordered and packed monolayers.

  20. The zeolite deposits of Greece

    USGS Publications Warehouse

    Stamatakis, M.G.; Hall, A.; Hein, J.R.

    1996-01-01

    Zeolites are present in altered pyroclastic rocks at many localities in Greece, and large deposits of potential economic interest are present in three areas: (1) the Evros region of the province of Thrace in the north-eastern part of the Greek mainland; (2) the islands of Kimolos and Poliegos in the western Aegean; and (3) the island of Samos in the eastern Aegean Sea. The deposits in Thrace are of Eocene-Oligocene age and are rich in heulandite and/or clinoptilolite. Those of Kimolos and Poliegos are mainly Quaternary and are rich in mordenite. Those of Samos are Miocene, and are rich in clinoptilolite and/or analcime. The deposits in Thrace are believed to have formed in an open hydrological system by the action of meteoric water, and those of the western Aegean islands in a similar way but under conditions of high heat flow, whereas the deposits in Samos were formed in a saline-alkaline lake.

  1. Modeling Deposition of Inhaled Particles

    EPA Science Inventory

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeutic dose delivered by inhaled pharmacological drugs. Howeve...

  2. Vapor deposition of hardened niobium

    DOEpatents

    Blocher, Jr., John M.; Veigel, Neil D.; Landrigan, Richard B.

    1983-04-19

    A method of coating ceramic nuclear fuel particles containing a major amount of an actinide ceramic in which the particles are placed in a fluidized bed maintained at ca. 800.degree. to ca. 900.degree. C., and niobium pentachloride vapor and carbon tetrachloride vapor are led into the bed, whereby niobium metal is deposited on the particles and carbon is deposited interstitially within the niobium. Coating apparatus used in the method is also disclosed.

  3. Chemical enhancement of surface deposition

    DOEpatents

    Patch, K.D.; Morgan, D.T.

    1997-07-29

    A method and apparatus are disclosed for increasing the deposition of ions onto a surface, such as the adsorption of uranium ions on the detecting surface of a radionuclide detector. The method includes the step of exposing the surface to a complexing agent, such as a phosphate ion solution, which has an affinity for the dissolved species to be deposited on the surface. This provides, for example, enhanced sensitivity of the radionuclide detector. 16 figs.

  4. Chemical enhancement of surface deposition

    DOEpatents

    Patch, Keith D.; Morgan, Dean T.

    1997-07-29

    A method and apparatus for increasing the deposition of ions onto a surface, such as the adsorption of uranium ions on the detecting surface of a radionuclide detector. The method includes the step of exposing the surface to a complexing agent, such as a phosphate ion solution, which has an affinity for the dissolved species to be deposited on the surface. This provides, for example, enhanced sensitivity of the radionuclide detector.

  5. Selective molybdenum deposition by LPCVD

    SciTech Connect

    Lifshitz, N.; Williams, D.S.; Capio, C.D.; Brown, J.M.

    1987-08-01

    Molybdenum films have been deposited by low pressure chemical vapor deposition (LPCVD) on silicon substrates by the reduction of molybdenum hexafluoride in hydrogen and argon atmospheres. The deposition is extremely selective, with no Mo observed on silicon dioxide surfaces over the temperature range of 200/sup 0/-400/sup 0/C. Reduction by both hydrogen and silicon contribute to the deposition, with approximately equal, extremely high deposition rates; no self-limiting thickness was observed. Extensive TEM and SEM studies were conducted in order to characterize the microstructure of the deposited films. The main feature of the films is their extreme porosity - about 30%, which can explain many unusual properties of the process and the films. On the basis of experiments the authors propose a model to explain the origin of the porosity in the films. Comparative studies of tungsten and molybdenum LPCVD reveal that the difference between the two processes lie in the self-limiting mechanism occurring during the silicon reduction of tungsten hexafluoride.

  6. A radon progeny deposition model

    SciTech Connect

    Rielage, Keith; Elliott, Steven R; Hime, Andrew; Guiseppe, Vincente E; Westerdale, S.

    2010-12-01

    The next generation low-background detectors operating underground aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly {sup 222}Rn) and its subsequent progeny present in an experiment are potential backgrounds, also problematic is the deposition of radon progeny on detector materials. Exposure to radon at any stage of assembly of an experiment can result in surface contamination by progeny supported by the long half life (22 y) of {sup 210}Pb on sensitive locations of a detector. An understanding of the potential surface contamination from deposition will enable requirements of radon-reduced air and clean room environments for the assembly of low background experiments. It is known that there are a number of environmental factors that govern the deposition of progeny onto surfaces. However, existing models have not explored the impact of some environmental factors important for low background experiments. A test stand has been constructed to deposit radon progeny on various surfaces under a controlled environment in order to develop a deposition model. Results from this test stand and the resulting deposition model are presented.

  7. A Radon Progeny Deposition Model

    SciTech Connect

    Guiseppe, V. E.; Elliott, S. R.; Hime, A.; Rielage, K.; Westerdale, S.

    2011-04-27

    The next generation low-background detectors operating underground aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly {sup 222}Rn) and its subsequent progeny present in an experiment are potential backgrounds, also problematic is the deposition of radon progeny on detector materials. Exposure to radon at any stage of assembly of an experiment can result in surface contamination by progeny supported by the long half life (22 y) of {sup 210}Pb on sensitive locations of a detector. An understanding of the potential surface contamination from deposition will enable requirements of radon-reduced air and clean room environments for the assembly of low background experiments. It is known that there are a number of environmental factors that govern the deposition of progeny onto surfaces. However, existing models have not explored the impact of some environmental factors important for low background experiments. A test stand has been constructed to deposit radon progeny on various surfaces under a controlled environment in order to develop a deposition model. Results from this test stand and the resulting deposition model are presented.

  8. Biophysical properties of presynaptic short-term plasticity in hippocampal neurons: insights from electrophysiology, imaging and mechanistic models

    PubMed Central

    Dutta Roy, Ranjita; Stefan, Melanie I.; Rosenmund, Christian

    2014-01-01

    Hippocampal neurons show different types of short-term plasticity (STP). Some exhibit facilitation of their synaptic responses and others depression. In this review we discuss presynaptic biophysical properties behind heterogeneity in STP in hippocampal neurons such as alterations in vesicle priming and docking, fusion, neurotransmitter filling and vesicle replenishment. We look into what types of information electrophysiology, imaging and mechanistic models have given about the time scales and relative impact of the different properties on STP with an emphasis on the use of mechanistic models as complementary tools to experimental procedures. Taken together this tells us that it is possible for a multitude of different mechanisms to underlie the same STP pattern, even though some are more important in specific cases, and that mechanistic models can be used to integrate the biophysical properties to see which mechanisms are more important in specific cases of STP. PMID:24904286

  9. Intermolecular hydroamination of vinylarenes by iminoanilide alkaline-earth catalysts: a computational scrutiny of mechanistic pathways.

    PubMed

    Tobisch, Sven

    2014-07-14

    A thorough computational exploration of the mechanistic intricacies of the intermolecular hydroamination (HA) of vinylarenes by a recently reported class of kinetically stabilised iminoanilide [{N^N}Ae{N(SiMe3)2}⋅(THF)n] alkaline-earth amido compounds (Ae = Ca, Sr, Ba) is presented. Two distinct mechanistic pathways for catalytic HA mediated by alkaline-earth and rare-earth compounds have emerged over the years that account equally well for the specific features of the process. On one hand, a concerted proton-assisted pathway to deliver the amine product in a single step can be invoked and, on the other, a stepwise σ-insertive pathway that comprises a rapid, reversible migratory olefin insertion step linked to a less facile, irreversible Ae-C alkyl bond aminolysis. The results of the study presented herein, which employed a heavily benchmarked and reliable DFT methodology, supports a stepwise σ-insertive pathway that involves fast and reversible migratory C=C bond insertion into the polar Ae-N pyrrolido σ bond. This proceeds with strict 2,1 regioselectivity via a highly polarised four-centre transition state (TS) structure, linked to irreversible intramolecular Ae-C bond aminolysis of the alkaline-earth alkyl intermediate as the energetically favourable mechanism. Turnover-limiting aminolysis is consistent with the significant KIE measured; the DFT-derived effective barrier matches the Eyring parameter empirically determined for the best-performing {N^N}Ba(NR2) catalyst gratifyingly well. It also predicts the observed trend in reactivity (Ca

  10. Mechanistic models of plant seed dispersal by wind in heterogeneous landscapes

    NASA Astrophysics Data System (ADS)

    Trakhtenbrot, A.; Katul, G. G.; Nathan, R.

    2010-12-01

    Seed dispersal, and especially long-distance dispersal (LDD), is a key process in plant population survival, colonization, and gene flow. Its importance is amplified by the man-induced habitat fragmentation, climate change and invasions of exotic species. Mechanistic seed dispersal models are central to quantitative prediction of dispersal patterns and understanding their underlying mechanisms. For wind dispersal, most current mechanistic models assume homogenous environment. Although both topography and sharp transitions in vegetation stature profoundly affect wind flow, accounting for these effects via simplified models remains a vexing research problem. Such simplified models are needed to inform ecosystem managers about consequences of landscape fragmentation. We modified the Coupled Eulerian-Lagrangian closure (CELC) mechanistic dispersal model to represent scenarios of wind flow over a sharp transition from short to tall vegetation or over forested hilly terrain, and predicted the resulting dispersal distances and direction. We parameterized the wind and vegetation factors using measurements taken on a hill with short height Mediterranean shrubland and pine forest vegetation at Mt. Pithulim, Israel. For the short-to-tall vegetation transition scenario, the main feature of the modeled wind field is an exponential decay of the mean horizontal wind velocity, assuming that the mean momentum equation simplifies to a balance between the advective acceleration and the drag force terms. As a consequence of the incompressibility condition, this exponential decay leads to strong upward mean vertical velocity component. We found that for seed release downwind of the edge, the simulated median (short) and 99-th percentile (long) distances were longer than those for the homogeneous tall vegetation scenario. For seed release upwind of the edge the effect on dispersal distance was more complex and depended on the release height and he seed terminal velocity of the seeds

  11. Determination of the upper and lower limits of the mechanistic stoichiometry of incompletely coupled fluxes. Stoichiometry of incompletely coupled reactions.

    PubMed

    Beavis, A D; Lehninger, A L

    1986-07-15

    A rationale is formulated for the design of experiments to determine the upper and lower limits of the mechanistic stoichiometry of any two incompletely coupled fluxes J1 and J2. Incomplete coupling results when there is a branch at some point in the sequence of reactions or processes coupling the two fluxes. The upper limit of the mechanistic stoichiometry is given by the minimum value of dJ2/dJ1 obtained when the fluxes are systematically varied by changes in steps after the branch point. The lower limit is given by the maximum value of dJ2/dJ1 obtained when the fluxes are varied by changes in steps prior to the branch point. The rationale for determining these limits is developed from both a simple kinetic model and from a linear nonequilibrium thermodynamic treatment of coupled fluxes, using the mechanistic approach [Westerhoff, H. V. & van Dam, K. (1979) Curr. Top. Bioenerg. 9, 1-62]. The phenomenological stoichiometry, the flux ratio at level flow and the affinity ratio at static head of incompletely coupled fluxes are defined in terms of mechanistic conductances and their relationship to the mechanistic stoichiometry is discussed. From the rationale developed, experimental approaches to determine the mechanistic stoichiometry of mitochondrial oxidative phosphorylation are outlined. The principles employed do not require knowledge of the pathway or the rate of transmembrane leaks or slippage and may also be applied to analysis of the stoichiometry of other incompletely coupled systems, including vectorial H+/O and K+/O translocation coupled to mitochondrial electron transport.

  12. Improving Predictive Modeling in Pediatric Drug Development: Pharmacokinetics, Pharmacodynamics, and Mechanistic Modeling

    SciTech Connect

    Slikker, William; Young, John F.; Corley, Rick A.; Dorman, David C.; Conolly, Rory B.; Knudsen, Thomas; Erstad, Brian L.; Luecke, Richard H.; Faustman, Elaine M.; Timchalk, Chuck; Mattison, Donald R.

    2005-07-26

    A workshop was conducted on November 18?19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. The goals of the meeting included a description of when, during development, infants/children become adultlike in handling drugs. The issue of incorporating the most recent advances into the predictive models was also addressed: both the use of imaging approaches and genomic information were considered. Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human.

  13. Selective Synthesis of Cyclic Carbonate by Salalen-Aluminum Complexes and Mechanistic Studies.

    PubMed

    Cozzolino, Mariachiara; Rosen, Tomer; Goldberg, Israel; Mazzeo, Mina; Lamberti, Marina

    2017-03-22

    Salalen-aluminum complexes were synthesized and used as catalysts in the reactions of CO2 with different epoxides. The reaction of cyclohexene oxide and CO2 was thoroughly investigated. In particular, the effect of the reaction conditions (nature and equivalents of the co-catalyst, CO2 pressure, and temperature) and of the ligands (substituents on the ancillary ligand, nature of the labile ligand, and nature of the nitrogen-donor atoms) on the results of this reaction was studied. The cycloaddition reaction of CO2 with terminal epoxides bearing different functional groups was realized. Moreover, NMR mechanistic studies provided information on the catalytic cycle. Interestingly, the characterization of an intermediate species in the mechanism of the reaction of cyclohexene oxide with CO2 , catalyzed by one of the salalen-aluminum complexes, was accomplished.

  14. Lipids, adiposity and tendinopathy: is there a mechanistic link? Critical review

    PubMed Central

    Scott, Alex; Zwerver, Johannes; Grewal, Navi; de Sa, Agnetha; Alktebi, Thuraya; Granville, David J; Hart, David A

    2015-01-01

    Being overweight or obese is associated with an elevated risk of tendon pathology. However, for sportspeople the epidemiological data linking weight or adiposity on one hand, and risk of tendon pathology on the other, are less consistent. Indeed, the mechanistic links between diet, adiposity and tendon pathology remain largely unexamined. Recent studies have begun to examine the effects of dietary interventions on outcomes such as tendon biomechanics or pain. Oxidised low-density lipoprotein has been shown to (A) accumulate in the tendon tissues of mice that eat a fatty diet and (B) induce a pathological phenotype in human tendon cells. This paper addresses the current debate: is excessive body mass index (causing increased load and strain on tendon tissue) per se the underlying mechanism? Or do local or systemic influences of fat on tendons predispose to tendon pathology? This narrative review argues that excessive blood lipids may be an important avenue for clinical investigations. PMID:25488953

  15. Lipids, adiposity and tendinopathy: is there a mechanistic link? Critical review.

    PubMed

    Scott, Alex; Zwerver, Johannes; Grewal, Navi; de Sa, Agnetha; Alktebi, Thuraya; Granville, David J; Hart, David A

    2015-08-01

    Being overweight or obese is associated with an elevated risk of tendon pathology. However, for sportspeople the epidemiological data linking weight or adiposity on one hand, and risk of tendon pathology on the other, are less consistent. Indeed, the mechanistic links between diet, adiposity and tendon pathology remain largely unexamined. Recent studies have begun to examine the effects of dietary interventions on outcomes such as tendon biomechanics or pain. Oxidised low-density lipoprotein has been shown to (A) accumulate in the tendon tissues of mice that eat a fatty diet and (B) induce a pathological phenotype in human tendon cells. This paper addresses the current debate: is excessive body mass index (causing increased load and strain on tendon tissue) per se the underlying mechanism? Or do local or systemic influences of fat on tendons predispose to tendon pathology? This narrative review argues that excessive blood lipids may be an important avenue for clinical investigations.

  16. Structural neurobiology: missing link to a mechanistic understanding of neural computation.

    PubMed

    Denk, Winfried; Briggman, Kevin L; Helmstaedter, Moritz

    2012-02-22

    High-resolution, comprehensive structural information is often the final arbiter between competing mechanistic models of biological processes, and can serve as inspiration for new hypotheses. In molecular biology, definitive structural data at atomic resolution are available for many macromolecules; however, information about the structure of the brain is much less complete, both in scope and resolution. Several technical developments over the past decade, such as serial block-face electron microscopy and trans-synaptic viral tracing, have made the structural biology of neural circuits conceivable: we may be able to obtain the structural information needed to reconstruct the network of cellular connections for large parts of, or even an entire, mouse brain within a decade or so. Given that the brain's algorithms are ultimately encoded by this network, knowing where all of these connections are should, at the very least, provide the data needed to distinguish between models of neural computation.

  17. Unification and mechanistic detail as drivers of model construction: models of networks in economics and sociology.

    PubMed

    Kuorikoski, Jaakko; Marchionni, Caterina

    2014-12-01

    We examine the diversity of strategies of modelling networks in (micro) economics and (analytical) sociology. Field-specific conceptions of what explaining (with) networks amounts to or systematic preference for certain kinds of explanatory factors are not sufficient to account for differences in modelling methodologies. We argue that network models in both sociology and economics are abstract models of network mechanisms and that differences in their modelling strategies derive to a large extent from field-specific conceptions of the way in which a good model should be a general one. Whereas the economics models aim at unification, the sociological models aim at a set of mechanism schemas that are extrapolatable to the extent that the underlying psychological mechanisms are general. These conceptions of generality induce specific biases in mechanistic explanation and are related to different views of when knowledge from different fields should be seen as relevant.

  18. How do animal territories form and change? Lessons from 20 years of mechanistic modelling

    PubMed Central

    Potts, Jonathan R.; Lewis, Mark A.

    2014-01-01

    Territory formation is ubiquitous throughout the animal kingdom. At the individual level, various behaviours attempt to exclude conspecifics from regions of space. At the population level, animals often segregate into distinct territorial areas. Consequently, it should be possible to derive territorial patterns from the underlying behavioural processes of animal movements and interactions. Such derivations are an important element in the development of an ecological theory that can predict the effects of changing conditions on territorial populations. Here, we review the approaches developed over the past 20 years or so, which go under the umbrella of ‘mechanistic territorial models’. We detail the two main strands to this research: partial differential equations and individual-based approaches, showing what each has offered to our understanding of territoriality and how they can be unified. We explain how they are related to other approaches to studying territories and home ranges, and point towards possible future directions. PMID:24741017

  19. Optimization of biopharmaceutical downstream processes supported by mechanistic models and artificial neural networks.

    PubMed

    Pirrung, Silvia M; van der Wielen, Luuk A M; van Beckhoven, Ruud F W C; van de Sandt, Emile J A X; Eppink, Michel H M; Ottens, Marcel

    2017-01-05

    Downstream process development is a major area of importance within the field of bioengineering. During the design of such a downstream process, important decisions have to be made regarding the type of unit operations as well as their sequence and their operating conditions. Current computational approaches addressing these issues either show a high level of simplification or struggle with computational speed. Therefore, this article presents a new approach that combines detailed mechanistic models and speed-enhancing artificial neural networks. This approach was able to simultaneously optimize a process with three different chromatographic columns toward yield with a minimum purity of 99.9%. The addition of artificial neural networks greatly accelerated this optimization. Due to high computational speed, the approach is easily extendable to include more unit operations. Therefore, it can be of great help in the acceleration of downstream process development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 2017.

  20. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    PubMed Central

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  1. Carbenic vs. ionic mechanistic pathway in reaction of cyclohexanone with bromoform.

    PubMed

    Vitnik, Vesna D; Vitnik, Zeljko J; Juranić, Ivan O

    2012-10-01

    The extensive computation study was done to elucidate the mechanism of formation dibromoepoxide from cyclohexanone and bromoform. In this reaction, the formation of dihaloepoxide 2 is postulated as a key step that determines the distribution and stereochemistry of products. Two mechanistic paths of reaction were investigated: the addition of dibromocarbene to carbonyl group of ketone, and the addition of tribromomethyl carbanion to the same (C=O) group. The mechanisms for the addition reactions of dibromocarbenes and tribromomethyl carbanions with cyclohexanone have been investigated using ab initio HF/6-311++G** and MP2/6-311+G* level of theory. Solvent effects on these reactions have been explored by calculations which included a continuum polarizable conductor model (CPCM) for the solvent (H₂O). The calculations showed that both mechanisms are possible and are exothermic, but have markedly different activation energies.

  2. Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality

    USGS Publications Warehouse

    Warnecke, Lisa; Turner, James M.; Bollinger, Trent K.; Misra, Vikram; Cryan, Paul M.; Blehert, David S.; Wibbelt, Gudrun; Willis, Craig K.R.

    2013-01-01

    White-nose syndrome is devastating North American bat populations but we lack basic information on disease mechanisms. Altered blood physiology owing to epidermal invasion by the fungal pathogen Geomyces destructans (Gd) has been hypothesized as a cause of disrupted torpor patterns of affected hibernating bats, leading to mortality. Here, we present data on blood electrolyte concentration, haematology and acid–base balance of hibernating little brown bats, Myotis lucifugus, following experimental inoculation with Gd. Compared with controls, infected bats showed electrolyte depletion (i.e. lower plasma sodium), changes in haematology (i.e. increased haematocrit and decreased glucose) and disrupted acid–base balance (i.e. lower CO2 partial pressure and bicarbonate). These findings indicate hypotonic dehydration, hypovolaemia and metabolic acidosis. We propose a mechanistic model linking tissue damage to altered homeostasis and morbidity/mortality.

  3. Mechanistic Basis for Plant Responses to Drought Stress : Regulatory Mechanism of Abscisic Acid Signaling

    NASA Astrophysics Data System (ADS)

    Miyakawa, Takuya; Tanokura, Masaru

    The phytohormone abscisic acid (ABA) plays a key role in the rapid adaptation of plants to environmental stresses such as drought and high salinity. Accumulated ABA in plant cells promotes stomatal closure in guard cells and transcription of stress-tolerant genes. Our understanding of ABA responses dramatically improved by the discovery of both PYR/PYL/RCAR as a soluble ABA receptor and inhibitory complex of a protein phospatase PP2C and a protein kinase SnRK2. Moreover, several structural analyses of PYR/PYL/RCAR revealed the mechanistic basis for the regulatory mechanism of ABA signaling, which provides a rational framework for the design of alternative agonists in future.

  4. Bacterial diterpene synthases: new opportunities for mechanistic enzymology and engineered biosynthesis.

    PubMed

    Smanski, Michael J; Peterson, Ryan M; Huang, Sheng-Xiong; Shen, Ben

    2012-04-01

    Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging. Bacteria are emerging as prolific producers of diterpenoid natural products, and bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis. Here we will first survey diterpenoid natural products of bacterial origin and briefly review their biosynthesis with emphasis on diterpene synthases (DTSs) that channel geranylgeranyl diphosphate to various diterpenoid scaffolds. We will then highlight differences of DTSs of bacterial and higher organism origins and discuss the challenges in discovering novel bacterial DTSs. We will conclude by discussing new opportunities for DTS mechanistic enzymology and applications of bacterial DTS in biocatalysis and metabolic pathway engineering.

  5. Desmosomes in the heart: a review of clinical and mechanistic analyses.

    PubMed

    Patel, Dipal M; Green, Kathleen J

    2014-06-01

    Desmosomes have long been appreciated as intercellular junctions that are vital for maintaining the structural integrity of stratified epithelia. More recent clinical investigations of patients with diseases such as arrhythmogenic cardiomyopathy have further highlighted the importance of desmosomes in cardiac tissue, where they help to maintain coordination of cardiac myocytes. Here, we review clinical and mechanistic studies that provide insight into the functions of desmosomal proteins in skin and heart during homeostasis and in disease. While intercellular junctions are organized differently in cardiac and epithelial tissues, studies conducted in epithelial systems may inform our understanding of cardiac desmosomes. We explore traditional and non-traditional roles of desmosomal proteins, ranging from adhesive capacities to nuclear functions. Finally, we discuss how these studies can guide future investigations focused on determining the molecular mechanisms by which desmosomal mutations promote the development of cardiac diseases.

  6. Inhibition of the mechanistic target of rapamycin (mTOR) - Rapamycin and beyond

    PubMed Central

    Lamming, Dudley W.

    2016-01-01

    Rapamycin is an FDA-approved immunosuppressant and anti-cancer agent discovered in the soil of Easter Island in the early 1970s. Rapamycin is a potent and selective inhibitor of the mTOR (mechanistic Target Of Rapamycin) protein kinase, which acts as a central integrator of nutrient signaling pathways. During the last decade, genetic and pharmaceutical inhibition of mTOR pathway signaling has been found to promote longevity in yeast, worms, flies and mice. In this chapter, we will discuss the molecular biology underlying the effects of rapamycin and its physiological effects; evidence for rapamycin as an anti-aging compound; mechanisms by which rapamycin may extend lifespan; and the potential limitations of rapamycin as an anti-aging molecule. Finally, we will discuss possible strategies that may allow us to inhibit mTOR signaling safely while minimizing side effects, and reap the health, social and economic benefits from slowing the aging process. PMID:27048303

  7. Synthetic and Mechanistic Studies of Strained Heterocycle Opening Reactions Mediated by Zirconium(IV) Imido Complexes

    PubMed Central

    Blum, Suzanne A.; Rivera, Vicki A.; Ruck, Rebecca T.; Michael, Forrest E.; Bergman, Robert G.

    2005-01-01

    The reactions of the bis(cyclopentadienyl)(tert-butylimido)zirconium complex (Cp2Zr=N-t-Bu)(THF) (1) with epoxides, aziridines, and episulfides were investigated. Heterocycles without accessible β-hydrogens undergo insertion/protonation of the C–X bond to produce 1,2-amino alcohols (X = O) and 1,2-diamines (X = NR), whereas heterocycles with accessible β-hydrogens undergo elimination/protonation to produce allylic alcohols (X = O) and allylic sulfides (X = S). Mechanistic investigations support a stepwise pathway with zwitterionic intermediates for the first reaction class and a concerted pathway for the second reaction class. Additionally, the feasibility of chirality transfer from the planar-chiral ebthi (ebthi = ethylenebis(tetrahydroindenyl)) ligand was demonstrated with a chiral analogue, (ebthi)-Zr=NAr(THF) (Ar = 2,6-dimethylphenyl), 2, through the diastereoselective ring opening of meso epoxides. PMID:16508693

  8. Organolanthanide-catalyzed imine hydrogenation. Scope, selectivity, mechanistic observations, and unusual byproducts

    SciTech Connect

    Obora, Yasushi; Ohta, Tetsuo; Stern, C.L.; Marks, T.J.

    1997-04-23

    This paper reports a catalytic, synthetic, and molecular structure study of the Cp{prime}{sub 2}Ln/Me{sub 2}SiCp{double_prime}{sub 2}Ln-catalyzed (Cp{prime} = {eta}{sup 5}-Me{sub 5}C{sub 5}; Cp{double_prime} = {eta}{sup 5}-Me{sub 4}C{sub 5}) hydrogenation of acyclic imines to yield the corresponding amines, using well-defined precatalysts and focusing on scope, selectivity, mechanistic observations, and the information nature of several unusual organolanthanide byproducts. The results demonstrate that the rates are modest and roughly comparable to those mediated by a chiral titanocene. 49 refs., 4 figs., 5 tabs.

  9. Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights.

    PubMed

    Ueda, Atsushi; Umeno, Tomohiro; Doi, Mitsunobu; Akagawa, Kengo; Kudo, Kazuaki; Tanaka, Masakazu

    2016-08-05

    Helical peptide foldamer catalyzed Michael addition reactions of nitroalkane or dialkyl malonate to α,β-unsaturated ketones are reported along with the mechanistic considerations of the enantio-induction. A wide variety of α,β-unsaturated ketones, including β-aryl, β-alkyl enones, and cyclic enones, were found to be catalyzed by the helical peptide to give Michael adducts with high enantioselectivities (up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide study, the amide protons, N(2)-H and N(3)-H, at the N terminus in the α-helical peptide catalyst were crucial for activating Michael donors, while the N-terminal primary amine activated Michael acceptors through the formation of iminium ion intermediates.

  10. Iodine-catalyzed aminosulfonation of hydrocarbons by imidoiodinanes. A synthetic and mechanistic investigation.

    PubMed

    Lamar, Angus A; Nicholas, Kenneth M

    2010-11-19

    The amino-functionalization of a range of benzylic and some aliphatic saturated and unsaturated hydrocarbons by reaction with imido-iodinanes (PhI═NSO2Ar) is catalyzed by I2 under operationally simple and mild conditions. The first examples of 1,2-functionalization of unactivated C-H bonds using imido-iodinanes as aminating agents are reported. Mechanistic investigations, including Hammett analysis, kinetic isotope effects, a cyclopropane clock experiment, and stereoselectivity tests, are indicative of a stepwise pathway in C-N bond formation. Investigation into the nature of the active aminating species has led to the isolation of a novel aminating agent formulated as (ArSO2N)(x)I(y) (x = 1, y = 2; or x = 3, y = 4).

  11. Continually emerging mechanistic complexity of the multi-enzyme cellulosome complex.

    PubMed

    Smith, Steven P; Bayer, Edward A; Czjzek, Mirjam

    2017-04-06

    The robust plant cell wall polysaccharide-degrading properties of anaerobic bacteria are harnessed within elegant, marcomolecular assemblages called cellulosomes, in which proteins of complementary activities amass on scaffold protein networks. Research efforts have focused and continue to focus on providing detailed mechanistic insights into cellulosomal complex assembly, topology, and function. The accumulated information is expanding our fundamental understanding of the lignocellulosic biomass decomposition process and enhancing the potential of engineered cellulosomal systems for biotechnological purposes. Ongoing biochemical studies continue to reveal unexpected functional diversity within traditional cellulase families. Genomic, proteomic, and functional analyses have uncovered unanticipated cellulosomal proteins that augment the function of the native and designer cellulosomes. In addition, complementary structural and computational methods are continuing to provide much needed insights on the influence of cellulosomal interdomain linker regions on cellulosomal assembly and activity.

  12. Combating Pathogenic Microorganisms Using Plant-Derived Antimicrobials: A Minireview of the Mechanistic Basis

    PubMed Central

    Upadhyaya, Indu; Kollanoor-Johny, Anup

    2014-01-01

    The emergence of antibiotic resistance in pathogenic bacteria has led to renewed interest in exploring the potential of plant-derived antimicrobials (PDAs) as an alternative therapeutic strategy to combat microbial infections. Historically, plant extracts have been used as a safe, effective, and natural remedy for ailments and diseases in traditional medicine. Extensive research in the last two decades has identified a plethora of PDAs with a wide spectrum of activity against a variety of fungal and bacterial pathogens causing infections in humans and animals. Active components of many plant extracts have been characterized and are commercially available; however, research delineating the mechanistic basis of their antimicrobial action is scanty. This review highlights the potential of various plant-derived compounds to control pathogenic bacteria, especially the diverse effects exerted by plant compounds on various virulence factors that are critical for pathogenicity inside the host. In addition, the potential effect of PDAs on gut microbiota is discussed. PMID:25298964

  13. Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis.

    PubMed

    Díaz Velázquez, Heriberto; Ruiz García, Yara; Vandichel, Matthias; Madder, Annemieke; Verpoort, Francis

    2014-12-14

    Copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chemistry. Here we report a new series of water-soluble catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are additionally functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the production of triazoles with different substitution patterns. Additionally, successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calculations.

  14. Determining environmental causes of biological effects: the need for a mechanistic physiological dimension in conservation biology.

    PubMed

    Seebacher, Frank; Franklin, Craig E

    2012-06-19

    The emerging field of Conservation Physiology links environmental change and ecological success by the application of physiological theory, approaches and tools to elucidate and address conservation problems. Human activity has changed the natural environment to a point where the viability of many ecosystems is now under threat. There are already many descriptions of how changes in biological patterns are correlated with environmental changes. The next important step is to determine the causative relationship between environmental variability and biological systems. Physiology provides the mechanistic link between environmental change and ecological patterns. Physiological research, therefore, should be integrated into conservation to predict the biological consequences of human activity, and to identify those species or populations that are most vulnerable.

  15. Estimating biofilm reaction kinetics using hybrid mechanistic-neural network rate function model.

    PubMed

    Kumar, B Shiva; Venkateswarlu, Ch

    2012-01-01

    This work describes an alternative method for estimation of reaction rate of a biofilm process without using a model equation. A first principles model of the biofilm process is integrated with artificial neural networks to derive a hybrid mechanistic-neural network rate function model (HMNNRFM), and this combined model structure is used to estimate the complex kinetics of the biofilm process as a consequence of the validation of its steady state solution. The performance of the proposed methodology is studied with the aid of the experimental data of an anaerobic fixed bed biofilm reactor. The statistical significance of the method is also analyzed by means of the coefficient of determination (R2) and model efficiency (ME). The results demonstrate the effectiveness of HMNNRFM for estimating the complex kinetics of the biofilm process involved in the treatment of industry wastewater.

  16. Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics.

    PubMed

    Haiser, Henry J; Seim, Kristen L; Balskus, Emily P; Turnbaugh, Peter J

    2014-01-01

    The human gut microbiota plays a key role in pharmacology, yet the mechanisms responsible remain unclear, impeding efforts toward personalized medicine. We recently identified a cytochrome-encoding operon in the common gut Actinobacterium Eggerthella lenta that is transcriptionally activated by the cardiac drug digoxin. These genes represent a predictive microbial biomarker for the inactivation of digoxin. Gnotobiotic mouse experiments revealed that increased protein intake can limit microbial drug inactivation. Here, we present a biochemical rationale for how the proteins encoded by this operon might inactivate digoxin through substrate promiscuity. We discuss digoxin signaling in eukaryotic systems, and consider the possibility that endogenous digoxin-like molecules may have selected for microbial digoxin inactivation. Finally, we highlight the diverse contributions of gut microbes to drug metabolism, present a generalized approach to studying microbe-drug interactions, and argue that mechanistic studies will pave the way for the clinical application of this work.

  17. Pollution and skin: from epidemiological and mechanistic studies to clinical implications.

    PubMed

    Krutmann, Jean; Liu, Wei; Li, Li; Pan, Xiaochuan; Crawford, Martha; Sore, Gabrielle; Seite, Sophie

    2014-12-01

    In recent years, the health effects associated with air pollution have been intensively studied. Most studies focus on air pollution effects on the lung and the cardiovascular system. More recently, however, epidemiological and mechanistic studies suggest that air pollution is also affecting skin integrity. This state-of-the-art review focuses on this latter aspect; it was developed with the collaboration of European and Chinese board of experts with specific interests in environmental health, clinical and basic research in dermatology and cosmetic dermatology. A literature review limited to pollution and health effects and (sensitive) skin was performed using PubMed. Review and original articles were chosen. We summarize the existing scientific evidence that air pollution exerts detrimental effects on human skin, discuss potential clinical implications and suggest specific and unspecific cosmetic protective measures.

  18. Eyespot colour pattern determination by serial induction in fish: Mechanistic convergence with butterfly eyespots.

    PubMed

    Ohno, Yoshikazu; Otaki, Joji M

    2012-01-01

    Vertebrate and invertebrate colour pattern determination mechanisms are considered distinct; recently, however, both fish and butterfly colour patterns have been partly explained by reaction-diffusion mechanisms. Here, we show that multi-coloured eyespots of the spotted mandarin fish, which are reminiscent of butterfly eyespots, are determined by the serial induction of colour patterns. The morphological characterisation of eyespots indicates a sequence of colour pattern development and dynamic interactions between eyespots. A substantial part of an eyespot can be surgically removed and is then reconstructed by regeneration. Strikingly, ectopic patterns are induced by damage at a background (eyespotless) area, but focal damage did not change the eyespot size. Early stages of damage repair were accompanied by calcium oscillations. These results demonstrate that fish eyespots are determined by serial induction, which is likely based on a reaction-diffusion mechanism. These findings suggest mechanistic similarities between the fish and butterfly systems.

  19. Determining environmental causes of biological effects: the need for a mechanistic physiological dimension in conservation biology

    PubMed Central

    Seebacher, Frank; Franklin, Craig E.

    2012-01-01

    The emerging field of Conservation Physiology links environmental change and ecological success by the application of physiological theory, approaches and tools to elucidate and address conservation problems. Human activity has changed the natural environment to a point where the viability of many ecosystems is now under threat. There are already many descriptions of how changes in biological patterns are correlated with environmental changes. The next important step is to determine the causative relationship between environmental variability and biological systems. Physiology provides the mechanistic link between environmental change and ecological patterns. Physiological research, therefore, should be integrated into conservation to predict the biological consequences of human activity, and to identify those species or populations that are most vulnerable. PMID:22566670

  20. A structural classification of carbohydrate epimerases: From mechanistic insights to practical applications.

    PubMed

    Van Overtveldt, Stevie; Verhaeghe, Tom; Joosten, Henk-Jan; van den Bergh, Tom; Beerens, Koen; Desmet, Tom

    2015-12-01

    In recent years, carbohydrate epimerases have attracted a lot of attention as efficient biocatalysts that can convert abundant sugars (e.g.d-fructose) directly into rare counterparts (e.g.d-psicose). Despite increased research activities, no review about these enzymes has been published in more than a decade, meaning that their full potential is hard to appreciate. Here, we present an overview of all known carbohydrate epimerases based on a classification in structural families, which links every substrate specificity to a well-defined reaction mechanism. The mechanism can even be predicted for enzymes that have not yet been characterized or that lack structural information. In this review, the different families are discussed in detail, both structurally and mechanistically, with special reference to recent examples in the literature. Furthermore, the value of understanding the reaction mechanism will be illustrated by making the link to possible application and engineering targets.

  1. Assessing first-order emulator inference for physical parameters in nonlinear mechanistic models

    USGS Publications Warehouse

    Hooten, Mevin B.; Leeds, William B.; Fiechter, Jerome; Wikle, Christopher K.

    2011-01-01

    We present an approach for estimating physical parameters in nonlinear models that relies on an approximation to the mechanistic model itself for computational efficiency. The proposed methodology is validated and applied in two different modeling scenarios: (a) Simulation and (b) lower trophic level ocean ecosystem model. The approach we develop relies on the ability to predict right singular vectors (resulting from a decomposition of computer model experimental output) based on the computer model input and an experimental set of parameters. Critically, we model the right singular vectors in terms of the model parameters via a nonlinear statistical model. Specifically, we focus our attention on first-order models of these right singular vectors rather than the second-order (covariance) structure.

  2. A Three-Stage Mechanistic Model for Ammonia Borane Dehydrogenation by Shvo’s Catalyst

    PubMed Central

    Lu, Zhiyao; Conley, Brian L.; Williams, Travis J.

    2012-01-01

    We propose a mechanistic model for three-stage dehydrogenation of ammonia borane (AB) catalyzed by Shvo’s cyclopentadienone-ligated ruthenium complex. We provide evidence for a plausible mechanism for catalyst deactivation, the transition from fast catalysis to slow catalysis, and relate those findings to the invention of a second-generation catalyst that does not suffer from the same deactivation chemistry. The primary mechanism of catalyst deactivation is borazine-mediated hydroboration of the ruthenium species that is the active oxidant in the fast catalysis case. This transition is characterized by a change in the rate law for the reaction and changes in the apparent resting state of the catalyst. Also, in this slow catalysis situation, we see an additional intermediate in the sequence of boron, nitrogen species, aminodiborane. This occurs with concurrent generation of NH3, which itself does not strongly affect the rate of AB dehydrogenation. PMID:23335832

  3. Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

    PubMed

    Ainsbury, Elizabeth A; Barnard, Stephen; Bright, Scott; Dalke, Claudia; Jarrin, Miguel; Kunze, Sarah; Tanner, Rick; Dynlacht, Joseph R; Quinlan, Roy A; Graw, Jochen; Kadhim, Munira; Hamada, Nobuyuki

    The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.

  4. Mechanistically compatible mixtures of bacterial antagonists improve biological control of fire blight of pear.

    PubMed

    Stockwell, V O; Johnson, K B; Sugar, D; Loper, J E

    2011-01-01

    Mixtures of biological control agents can be superior to individual agents in suppressing plant disease, providing enhanced efficacy and reliability from field to field relative to single biocontrol strains. Nonetheless, the efficacy of combinations of Pseudomonas fluorescens A506, a commercial biological control agent for fire blight of pear, and Pantoea vagans strain C9-1 or Pantoea agglomerans strain Eh252 rarely exceeds that of individual strains. A506 suppresses growth of the pathogen on floral colonization and infection sites through preemptive exclusion. C9-1 and Eh252 produce peptide antibiotics that contribute to disease control. In culture, A506 produces an extracellular protease that degrades the peptide antibiotics of C9-1 and Eh252. We hypothesized that strain A506 diminishes the biological control activity of C9-1 and Eh252, thereby reducing the efficacy of biocontrol mixtures. This hypothesis was tested in five replicated field trials comparing biological control of fire blight using strain A506 and A506 aprX::Tn5, an extracellular protease-deficient mutant, as individuals and combined with C9-1 or Eh252. On average, mixtures containing A506 aprX::Tn5 were superior to those containing the wild-type strain, confirming that the extracellular protease of A506 diminished the biological control activity of C9-1 and Eh252 in situ. Mixtures of A506 aprX::Tn5 and C9-1 or Eh252 were superior to oxytetracycline or single biocontrol strains in suppressing fire blight of pear. These experiments demonstrate that certain biological control agents are mechanistically incompatible, in that one strain interferes with the mechanism by which a second strain suppresses plant disease. Mixtures composed of mechanistically compatible strains of biological control agents can suppress disease more effectively than individual biological control agents.

  5. Revisiting sesquiterpene biosynthetic pathways leading to santalene and its analogues: a comprehensive mechanistic study.

    PubMed

    Jindal, Garima; Sunoj, Raghavan B

    2012-10-21

    Santalene and bergamotene are the major olefinic sesquiterpenes responsible for the fragrance of sandalwood oil. Herein we report the details of density functional theory investigations on the biosynthetic pathway of this important class of terpenes. The mechanistic study has been found to be effective toward gaining significant new insight into different possibilities for the formation of the key intermediates involved in santalene and bergamotene biosynthesis. The stereoelectronic features of the transition states and intermediates for (i) ring closure of the initial bisabolyl cation, and (ii) skeletal rearrangements in the ensuing bicyclic carbocationic intermediates leading to (-)-epi-β-santalene, (-)-β-santalene, (-)-α-santalene, (+)-epi-β-santalene, exo-β-bergamotene, endo-β-bergamotene, exo-α-bergamotene, and endo-α-bergamotene are presented. Interesting structural features pertaining to certain new carbocationic intermediates (such as b) resulting from the ring closure of bisabolyl cation are discussed. Extensive conformational sampling of all key intermediates along the biosynthetic pathway offered new insight into the role of the isoprenyl side chain conformation in the formation of santalene and its analogues. Although the major bicyclic products in Santalum album appear to arise from the right or left handed helical form of farnesyl pyrophosphate (FPP), different alternatives for their formation are found to be energetically feasible. The interconversion of the exo and endo isomers of bisabolyl cation and a likely epimerization, both with interesting mechanistic implications, are presented. The exo to endo conversion is identified to be energetically more favorable than another pathway emanating from the left handed helical FPP. The role of pyrophosphate (OPP(-)) in the penultimate deprotonation step leading to olefinic sesquiterpenes is also examined.

  6. Mechanistic Aspects in the Formation, Growth and Surface Functionalization of Metal Oxide Nanoparticles in Organic Solvents.

    PubMed

    Niederberger, Markus; Deshmukh, Rupali

    2017-04-04

    The synthesis of metal oxide nanoparticles in organic solvents, so-called nonaqueous (or nonhydrolytic) processes represent powerful alternatives to aqueous approaches and have become an independent research field. 10 years ago, when we published our first review on organic reaction pathways in nonaqueous sol-gel approaches,[1] the number of examples was relatively limited. Nowadays, it is almost impossible to provide an exhaustive overview. Here we review the development of the last few years, without neglecting pioneering examples, which help to follow the historical development. The importance of a profound understanding of mechanistic aspects of nanoparticle crystallization and formation mechanisms can't be overestimated, when it comes to the design of rational synthesis concepts under minimization of trial-and-error experiments. The main reason for the progress in mechanistic understanding lies in the availability of characterization tools that make it possible to monitor chemical reactions from the dissolution of the precursor to the nucleation and growth of the nanoparticles, by ex-situ methods involving sampling after different reaction times, but more and more also by in-situ studies. After a short introduction to experimental aspects of nonaqueous sol-gel routes to metal oxide nanoparticles, we provide an overview of the main and basic organic reaction pathways in these approaches. Afterwards, we summarize the main characterization methods to study formation mechanisms, and then we discuss in great depth the chemical formation mechanisms of many different types of metal oxide nanoparticles. The review concludes with a paragraph on selected crystallization mechanisms reported for nonaqueous systems and a few illustrative examples of nonaqueous sol-gel concepts applied to surface chemistry.

  7. Advancements in the mechanistic understanding of the copper-catalyzed azide-alkyne cycloaddition.

    PubMed

    Berg, Regina; Straub, Bernd F

    2013-12-02

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC's catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates.

  8. Regulatory Technology Development Plan - Sodium Fast Reactor. Mechanistic Source Term - Metal Fuel Radionuclide Release

    SciTech Connect

    Grabaskas, David; Bucknor, Matthew; Jerden, James

    2016-02-01

    The development of an accurate and defensible mechanistic source term will be vital for the future licensing efforts of metal fuel, pool-type sodium fast reactors. To assist in the creation of a comprehensive mechanistic source term, the current effort sought to estimate the release fraction of radionuclides from metal fuel pins to the primary sodium coolant during fuel pin failures at a variety of temperature conditions. These release estimates were based on the findings of an extensive literature search, which reviewed past experimentation and reactor fuel damage accidents. Data sources for each radionuclide of interest were reviewed to establish release fractions, along with possible release dependencies, and the corresponding uncertainty levels. Although the current knowledge base is substantial, and radionuclide release fractions were established for the elements deemed important for the determination of offsite consequences following a reactor accident, gaps were found pertaining to several radionuclides. First, there is uncertainty regarding the transport behavior of several radionuclides (iodine, barium, strontium, tellurium, and europium) during metal fuel irradiation to high burnup levels. The migration of these radionuclides within the fuel matrix and bond sodium region can greatly affect their release during pin failure incidents. Post-irradiation examination of existing high burnup metal fuel can likely resolve this knowledge gap. Second, data regarding the radionuclide release from molten high burnup metal fuel in sodium is sparse, which makes the assessment of radionuclide release from fuel melting accidents at high fuel burnup levels difficult. This gap could be addressed through fuel melting experimentation with samples from the existing high burnup metal fuel inventory.

  9. A Mechanistic Beta-Binomial Probability Model for mRNA Sequencing Data.

    PubMed

    Smith, Gregory R; Birtwistle, Marc R

    2016-01-01

    A main application for mRNA sequencing (mRNAseq) is determining lists of differentially-expressed genes (DEGs) between two or more conditions. Several software packages exist to produce DEGs from mRNAseq data, but they typically yield different DEGs, sometimes markedly so. The underlying probability model used to describe mRNAseq data is central to deriving DEGs, and not surprisingly most softwares use different models and assumptions to analyze mRNAseq data. Here, we propose a mechanistic justification to model mRNAseq as a binomial process, with data from technical replicates given by a binomial distribution, and data from biological replicates well-described by a beta-binomial distribution. We demonstrate good agreement of this model with two large datasets. We show that an emergent feature of the beta-binomial distribution, given parameter regimes typical for mRNAseq experiments, is the well-known quadratic polynomial scaling of variance with the mean. The so-called dispersion parameter controls this scaling, and our analysis suggests that the dispersion parameter is a continually decreasing function of the mean, as opposed to current approaches that impose an asymptotic value to the dispersion parameter at moderate mean read counts. We show how this leads to current approaches overestimating variance for moderately to highly expressed genes, which inflates false negative rates. Describing mRNAseq data with a beta-binomial distribution thus may be preferred since its parameters are relatable to the mechanistic underpinnings of the technique and may improve the consistency of DEG analysis across softwares, particularly for moderately to highly expressed genes.

  10. Reduction of Carbon Dioxide by a Molybdenum-Containing Formate Dehydrogenase: A Kinetic and Mechanistic Study.

    PubMed

    Maia, Luisa B; Fonseca, Luis; Moura, Isabel; Moura, José J G

    2016-07-20

    Carbon dioxide accumulation is a major concern for the ecosystems, but its abundance and low cost make it an interesting source for the production of chemical feedstocks and fuels. However, the thermodynamic and kinetic stability of the carbon dioxide molecule makes its activation a challenging task. Studying the chemistry used by nature to functionalize carbon dioxide should be helpful for the development of new efficient (bio)catalysts for atmospheric carbon dioxide utilization. In this work, the ability of Desulfovibrio desulfuricans formate dehydrogenase (Dd FDH) to reduce carbon dioxide was kinetically and mechanistically characterized. The Dd FDH is suggested to be purified in an inactive form that has to be activated through a reduction-dependent mechanism. A kinetic model of a hysteretic enzyme is proposed to interpret and predict the progress curves of the Dd FDH-catalyzed reactions (initial lag phase and subsequent faster phase). Once activated, Dd FDH is able to efficiently catalyze, not only the formate oxidation (kcat of 543 s(-1), Km of 57.1 μM), but also the carbon dioxide reduction (kcat of 46.6 s(-1), Km of 15.7 μM), in an overall reaction that is thermodynamically and kinetically reversible. Noteworthy, both Dd FDH-catalyzed formate oxidation and carbon dioxide reduction are completely inactivated by cyanide. Current FDH reaction mechanistic proposals are discussed and a different mechanism is here suggested: formate oxidation and carbon dioxide reduction are proposed to proceed through hydride transfer and the sulfo group of the oxidized and reduced molybdenum center, Mo(6+)═S and Mo(4+)-SH, are suggested to be the direct hydride acceptor and donor, respectively.

  11. Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily.

    PubMed

    Sunden, Fanny; AlSadhan, Ishraq; Lyubimov, Artem Y; Ressl, Susanne; Wiersma-Koch, Helen; Borland, Jamar; Brown, Clayton L; Johnson, Tory A; Singh, Zorawar; Herschlag, Daniel

    2016-11-02

    Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP). We carried out a series of experiments to map out and learn from the differences and similarities between these enzymes. First, we asked why there would be independent instances of monoesterases in the AP superfamily? PafA has a much weaker product inhibition and slightly higher activity relative to EcAP, suggesting that different metabolic evolutionary pressures favored distinct active-site architectures. Next, we addressed the preferential phosphate monoester and diester catalysis of PafA and NPP, respectively. We asked whether the >80% sequence differences throughout these scaffolds provide functional specialization for each enzyme's cognate reaction. In contrast to expectations from this model, PafA and NPP mutants with the common subset of active-site groups embedded in each native scaffold had the same monoesterase:diesterase specificities; thus, the >10(7)-fold difference in native specificities appears to arise from distinct interactions at a single phosphoryl substituent. We also uncovered striking mechanistic similarities between the PafA and EcAP monoesterases, including evidence for ground-state destabilization and functional active-site networks that involve different active-site groups but may play analogous catalytic roles. Discovering common network functions may reveal active-site architectural connections that are critical for function, and identifying regions of functional modularity may facilitate the design of new enzymes

  12. Differential Site Accessibility Mechanistically Explains Subcellular-Specific N-Glycosylation Determinants

    PubMed Central

    Lee, Ling Yen; Lin, Chi-Hung; Fanayan, Susan; Packer, Nicolle H.; Thaysen-Andersen, Morten

    2014-01-01

    Glycoproteins perform extra- and intracellular functions in innate and adaptive immunity by lectin-based interactions to exposed glyco-determinants. Herein, we document and mechanistically explain the formation of subcellular-specific N-glycosylation determinants on glycoproteins trafficking through the shared biosynthetic machinery of human cells. LC-MS/MS-based quantitative glycomics showed that the secreted glycoproteins of eight human breast epithelial cells displaying diverse geno- and phenotypes consistently displayed more processed, primarily complex type, N-glycans than the high-mannose-rich microsomal glycoproteins. Detailed subcellular glycome profiling of proteins derived from three breast cell lines (MCF7/MDA468/MCF10A) demonstrated that secreted glycoproteins displayed significantly more α-sialylation and α1,6-fucosylation, but less α-mannosylation, than both the intermediately glycan-processed cell-surface glycoproteomes and the under-processed microsomal glycoproteomes. Subcellular proteomics and gene ontology revealed substantial presence of endoplasmic reticulum resident glycoproteins in the microsomes and confirmed significant enrichment of secreted and cell-surface glycoproteins in the respective subcellular fractions. The solvent accessibility of the glycosylation sites on maturely folded proteins of the 100 most abundant putative N-glycoproteins observed uniquely in the three subcellular glycoproteomes correlated with the glycan type processing thereby mechanistically explaining the formation of subcellular-specific N-glycosylation. In conclusion, human cells have developed mechanisms to simultaneously and reproducibly generate subcellular-specific N-glycosylation using a shared biosynthetic machinery. This aspect of protein-specific glycosylation is important for structural and functional glycobiology and discussed here in the context of the spatio-temporal interaction of glyco-determinants with lectins central to infection and immunity

  13. Mechanistic Modeling of Genetic Circuits for ArsR Arsenic Regulation.

    PubMed

    Berset, Yves; Merulla, Davide; Joublin, Aurélie; Hatzimanikatis, Vassily; van der Meer, Jan R

    2017-02-24

    Bioreporters are living cells that generate an easily measurable signal in the presence of a chemical compound. They acquire their functionality from synthetic gene circuits, the configuration of which defines the response signal and signal-to-noise ratio. Bioreporters based on the Escherichia coli ArsR system have raised significant interest for quantifying arsenic pollution, but they need to be carefully optimized to accurately work in the required low concentration range (1-10 μg arsenite L(-1)). To better understand the general functioning of ArsR-based genetic circuits, we developed a comprehensive mechanistic model that was empirically tested and validated in E. coli carrying different circuit configurations. The model accounts for the different elements in the circuits (proteins, DNA, chemical species), and their detailed affinities and interactions, and predicts the (fluorescent) output from the bioreporter cell as a function of arsenite concentration. The model was parametrized using existing ArsR biochemical data, and then complemented by parameter estimations from the accompanying experimental data using a scatter search algorithm. Model predictions and experimental data were largely coherent for feedback and uncoupled circuit configurations, different ArsR alleles, promoter strengths, and presence or absence of arsenic efflux in the bioreporters. Interestingly, the model predicted a particular useful circuit variant having steeper response at low arsenite concentrations, which was experimentally confirmed and may be useful as arsenic bioreporter in the field. From the extensive validation we expect the mechanistic model to further be a useful framework for detailed modeling of other synthetic circuits.

  14. A mechanistic model for electricity consumption on dairy farms: definition, validation, and demonstration.

    PubMed

    Upton, J; Murphy, M; Shalloo, L; Groot Koerkamp, P W G; De Boer, I J M

    2014-01-01

    Our objective was to define and demonstrate a mechanistic model that enables dairy farmers to explore the impact of a technical or managerial innovation on electricity consumption, associated CO2 emissions, and electricity costs. We, therefore, (1) defined a model for electricity consumption on dairy farms (MECD) capable of simulating total electricity consumption along with related CO2 emissions and electricity costs on dairy farms on a monthly basis; (2) validated the MECD using empirical data of 1yr on commercial spring calving, grass-based dairy farms with 45, 88, and 195 milking cows; and (3) demonstrated the functionality of the model by applying 2 electricity tariffs to the electricity consumption data and examining the effect on total dairy farm electricity costs. The MECD was developed using a mechanistic modeling approach and required the key inputs of milk production, cow number, and details relating to the milk-cooling system, milking machine system, water-heating system, lighting systems, water pump systems, and the winter housing facilities as well as details relating to the management of the farm (e.g., season of calving). Model validation showed an overall relative prediction error (RPE) of less than 10% for total electricity consumption. More than 87% of the mean square prediction error of total electricity consumption was accounted for by random variation. The RPE values of the milk-cooling systems, water-heating systems, and milking machine systems were less than 20%. The RPE values for automatic scraper systems, lighting systems, and water pump systems varied from 18 to 113%, indicating a poor prediction for these metrics. However, automatic scrapers, lighting, and water pumps made up only 14% of total electricity consumption across all farms, reducing the overall impact of these poor predictions. Demonstration of the model showed that total farm electricity costs increased by between 29 and 38% by moving from a day and night tariff to a flat

  15. Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

    PubMed Central

    2013-01-01

    Summary The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

  16. Beneficial effects of melatonin on bovine oocytes maturation: a mechanistic approach.

    PubMed

    Tian, XiuZhi; Wang, Feng; He, ChangJiu; Zhang, Lu; Tan, DunXian; Reiter, Russel J; Xu, Jing; Ji, PengYun; Liu, GuoShi

    2014-10-01

    This study was performed to investigate the effect of melatonin on bovine oocyte maturation and subsequent embryonic development in vitro. The endogenous melatonin concentration in bovine follicular fluid is approximately 10(-11) M. To examine the potential beneficial effects of melatonin on bovine oocyte maturation in vitro, germinal vesicle (GV) oocytes were incubated with different concentrations of melatonin (10(-11), 10(-9), 10(-7), 10(-5), 10(-3) M). Melatonin supplementation at suitable concentrations significantly promoted oocyte maturation. The development of embryos and the mean cell number/blastocyst produced after in vitro fertilization were remarkably improved. The most effective melatonin concentrations obtained from the studies ranged from 10(-9) to 10(-7) M. The expression of melatonin receptor MT1 and MT2 genes was identified in cumulus cells, granulosa cells, and oocytes using reverse transcription PCR, immunofluorescence, and Western blot. The mechanistic studies show that the beneficial effects of melatonin on bovine oocyte maturation are mediated via melatonin membrane receptors as the melatonin receptor agonist (IIK7) promotes this effect while the melatonin receptor antagonist (luzindole) blocks this action. Mechanistic explorations revealed that melatonin supplementation during bovine oocyte maturation significantly up-regulated the expressions of oocyte maturation-associated genes (GDF9, MARF1, and DNMT1a) and cumulus cells expansion-related gene (PTX3, HAS1/2) and that LHR1/2, EGFR are involved in signal transduction and epigenetic reprogramming. The results obtained from the studies provide new information regarding the mechanisms by which melatonin promotes bovine oocyte maturation in vitro and provide an important reference for in vitro embryo production of bovine and the human-assisted reproductive technology.

  17. Mechanistic models for the spatial spread of species under climate change.

    PubMed

    Leroux, Shawn J; Larrivée, Maxim; Boucher-Lalonde, Véronique; Hurford, Amy; Zuloaga, Juan; Kerr, Jeremy T; Lutscher, Frithjof

    2013-06-01

    Global climate change is a major threat to biodiversity. The most common methods for predicting the response of biodiversity to changing climate do not explicitly incorporate fundamental evolutionary and ecological processes that determine species responses to changing climate, such as reproduction, dispersal, and adaptation. We provide an overview of an emerging mechanistic spatial theory of species range shifts under climate change. This theoretical framework explicitly defines the ecological processes that contribute to species range shifts via biologically meaningful dispersal, reproductive, and climate envelope parameters. We present methods for estimating the parameters of the model with widely available species occurrence and abundance data and then apply these methods to empirical data for 12 North American butterfly species to illustrate the potential use of the theory for global change biology. The model predicts species persistence in light of current climate change and habitat loss. On average, we estimate that the climate envelopes of our study species are shifting north at a rate of 3.25 +/- 1.36 km/yr (mean +/- SD) and that our study species produce 3.46 +/- 1.39 (mean +/- SD) viable offspring per individual per year. Based on our parameter estimates, we are able to predict the relative risk of our 12 study species for lagging behind changing climate. This theoretical framework improves predictions of global change outcomes by facilitating the development and testing of hypotheses, providing mechanistic predictions of current and future range dynamics, and encouraging the adaptive integration of theory and data. The theory is ripe for future developments such as the incorporation of biotic interactions and evolution of adaptations to novel climatic conditions, and it has the potential to be a catalyst for the development of more effective conservation strategies to mitigate losses of biodiversity from global climate change.

  18. Fetal programming of CVD and renal disease: animal models and mechanistic considerations.

    PubMed

    Langley-Evans, Simon C

    2013-08-01

    The developmental origins of health and disease hypothesis postulates that exposure to a less than optimal maternal environment during fetal development programmes physiological function, and determines risk of disease in adult life. Much evidence of such programming comes from retrospective epidemiological cohorts, which demonstrate associations between birth anthropometry and non-communicable diseases of adulthood. The assertion that variation in maternal nutrition drives these associations is supported by studies using animal models, which demonstrate that maternal under- or over-nutrition during pregnancy can programme offspring development. Typically, the offspring of animals that are undernourished in pregnancy exhibit a relatively narrow range of physiological phenotypes that includes higher blood pressure, glucose intolerance, renal insufficiency and increased adiposity. The observation that common phenotypes arise from very diverse maternal nutritional insults has led to the proposal that programming is driven by a small number of mechanistic processes. The remodelling of tissues during development as a consequence of maternal nutritional status being signalled by endocrine imbalance or key nutrients limiting processes in the fetus may lead to organs having irreversibly altered structures that may limit their function with ageing. It has been proposed that the maternal diet may impact upon epigenetic marks that determine gene expression in fetal tissues, and this may be an important mechanism connecting maternal nutrient intakes to long-term programming of offspring phenotype. The objective for this review is to provide an overview of the mechanistic basis of fetal programming, demonstrating the critical role of animal models as tools for the investigation of programming phenomena.

  19. Mechanistic Variants in Gas-Phase Metal-Oxide Mediated Activation of Methane at Ambient Conditions.

    PubMed

    Li, Jilai; Zhou, Shaodong; Zhang, Jun; Schlangen, Maria; Usharani, Dandamudi; Shaik, Sason; Schwarz, Helmut

    2016-09-07

    The C-H bond activation of methane mediated by a prototypical heteronuclear metal-oxide cluster, [Al2Mg2O5](•+), was investigated by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) in conjunction with high-level quantum mechanical calculations. Experimentally, hydrogen-atom abstraction from methane by the cluster ion [Al2Mg2O5](•+) takes place at ambient conditions. As to the mechanism, according to our computational findings, both the proton-coupled electron transfer (PCET) and the conventional hydrogen-atom transfer (HAT) are feasible and compete with each other. This is in distinct contrast to the [XYO2](+) (X, Y = Mg, Al, Si) cluster oxide ions which activate methane exclusively via the PCET route (Li, J.; Zhou, S.; Zhang, J.; Schlangen, M.; Weiske, T.; Usharani, D.; Shaik, S.; Schwarz, H. J. Am. Chem. Soc. 2016, 138, 7973-7981). The electronic origins of the mechanistically rather complex reactivity scenarios of the [Al2Mg2O5](•+)/CH4 couple were elucidated. For the PCET mechanism, in which the Lewis acid-base pair [Al(+)-O(-)] of the cluster acts as the active site, a clear correlation has been established between the nature of the transition state, the corresponding barrier height, the Lewis acidity-basicity of the [M(+)-O(-)] unit, as well as the bond order of the M(+)-O(-) bond. Also addressed is the role of the spin and charge distributions of a terminal oxygen radical site in the direct HAT route. The knowledge of the factors that control the reactivity of PCET and HAT pathways not only deepens our mechanistic understanding of metal-oxide mediated C-H bond activation but may also provide guidance for the rational design of catalysts.

  20. Explicit kinetic heterogeneity: mechanistic models for interpretation of labeling data in heterogeneous populations

    SciTech Connect

    Ganusov, Vitaly V

    2008-01-01

    Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system. Deuterium, in the form of deuterated glucose or heavy water, can be used to measure rates of proliferation and death of lymphocytes in vivo. Inferring these rates from labeling and delabeling curves has been subject to considerable debate with different groups suggesting different mathematical models for that purpose. We show that the three models that are most commonly used are in fact mathematically identical and differ only in their interpretation of the estimated parameters. By extending these previous models, we here propose a more mechanistic approach for the analysis of data from deuterium labeling experiments. We construct a model of 'kinetic heterogeneity' in which the total cell population consists of many sub-populations with different rates of cell turnover. In this model, for a given distribution of the rates of turnover, the predicted fraction of labeled DNA accumulated and lost can be calculated. Our model reproduces several previously made experimental observations, such as a negative correlation between the length of the labeling period and the rate at which labeled DNA is lost after label cessation. We demonstrate the reliability of the new explicit kinetic heterogeneity model by applying it to artificially generated datasets, and illustrate its usefulness by fitting experimental data. In contrast to previous models, the explicit kinetic heterogeneity model (1) provides a mechanistic way of interpreting labeling data; (2) allows for a non-exponential loss of labeled cells during delabeling, and (3) can be used to describe data with variable labeling length.

  1. Descriptive vs. mechanistic network models in plant development in the post-genomic era.

    PubMed

    Davila-Velderrain, J; Martinez-Garcia, J C; Alvarez-Buylla, E R

    2015-01-01

    Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.

  2. Mechanistic insight into the ribosome biogenesis functions of the ancient protein KsgA

    PubMed Central

    Connolly, Keith; Rife, Jason P.; Culver, Gloria

    2009-01-01

    Summary While the general blueprint of ribosome biogenesis is evolutionarily conserved, most details have diverged considerably. A striking exception to this divergence is the universally conserved KsgA/Dim1p enzyme family, which modifies two adjacent adenosines in the terminal helix of small subunit ribosomal RNA (rRNA). While localization of KsgA on 30S subunits (SSUs) and genetic interaction data have suggested that KsgA acts as a ribosome biogenesis factor, mechanistic details and a rationale for its extreme conservation are still lacking. To begin to address these questions we have characterized the function of E. coli KsgA in vivo using both a ksgA deletion strain and a methyltransferase deficient form of this protein. Our data reveals cold sensitivity and altered ribosomal profiles are associated with a ΔksgA genotype in E. coli. Our work also indicates that loss of KsgA alters 16S rRNA processing. These findings allow KsgAs role in SSU biogenesis to be integrated into the network of other identified factors. Moreover, a methyltransferase-inactive form of KsgA, which we show to be deleterious to cell growth, profoundly impairs ribosome biogenesis prompting discussion of KsgA as a possible anti-microbial drug target. These unexpected data suggest that methylation is a second layer of function for KsgA and that its critical role is as a supervisor of biogenesis of SSUs in vivo. These new findings and this proposed regulatory role offer a mechanistic explanation for the extreme conservation of the KsgA/Dim1p enzyme family. PMID:18990185

  3. Metal film deposition by laser breakdown chemical vapor deposition

    SciTech Connect

    Jervis, T.R.

    1985-01-01

    Dielectric breakdown of gas mixtures can be used to deposit homogeneous thin films by chemical vapor deposition with appropriate control of flow and pressure conditions to suppress gas phase nucleation and particle formation. Using a pulsed CO/sub 2/ laser operating at 10.6 microns where there is no significant resonant absorption in any of the source gases, we have succeeded in depositing homogeneous films from several gas phase precursors by gas phase laser pyrolysis. Nickel and molybdenum from the respective carbonyls and tungsten from the hexafluoride have been examined to date. In each case the gas precursor is buffered to reduce the partial pressure of the reactants and to induce breakdown. The films are spectrally reflective and uniform over a large area. Films have been characterized by Auger electron spectroscopy, x-ray diffraction, pull tests, and resistivity measurements. The highest quality films have resulted from the nickel depositions. Detailed x-ray diffraction analysis of these films yields a very small domain size (approx. 50 A) consistent with rapid quenching from the gas phase reaction zone. This analysis also shows nickel carbide formation consistent with the temperature of the reaction zone and the Auger electron spectroscopy results which show some carbon and oxygen incorporation (8% and 1% respectively). Gas phase transport and condensation of the molybdenum carbonyl results in substantial carbon and oxygen contamination of the molybdenum films requiring heated substrates, a requirement not consistent with the goals of the program to maximize the quench rate of the deposition. Results from tungsten deposition experiments representing a reduction chemistry instead of the decomposition chemistry involved in the carbonyl experiments are also reported.

  4. Metal film deposition by laser breakdown chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Jervis, T. R.

    1985-01-01

    Dielectric breakdown of gas mixtures can be used to deposit homogeneous thin films by chemical vapor deposition with appropriate control of flow and pressure conditions to suppress gas phase nucleation and particle formation. Using a pulsed CO2 laser operating at 10.6 microns where there is no significant resonant absorption in any of the source gases, we have succeeded in depositing homogeneous films from several gas phase precursors by gas phase laser pyrolysis. Nickel and molybdenum from the respective carbonyls and tungsten from the hexafluoride have been examined to date. In each case the gas precursor is buffered to reduce the partial pressure of the reactants and to induce breakdown. The films are spectrally reflective and uniform over a large area. Films have been characterized by Auger electron spectroscopy, X-ray diffraction, pull tests, and resistivity measurements. The highest quality films have resulted from the nickel depositions. Detailed X-ray diffraction analysis of these films yields a very small domain size (approx. 50 A) consistent with rapid quenching from the gas phase reaction zone. This analysis also shows nickel carbide formation consistent with the temperature of the reaction zone and the Auger electron spectroscopy results which show some carbon and oxygen incorporation (8% and 1% respectively). Gas phase transport and condensation of the molybdenum carbonyl results in substantial carbon and oxygen contamination of the molybdenum films requiring heated substrates, a requirement not consistent with the goals of the program to maximize the quench rate of the deposition. Results from tungsten deposition experiments representing a reduction chemistry instead of the decomposition chemistry involved in the carbonyl experiments are also reported.

  5. Deposition of ozone to tundra

    SciTech Connect

    Jacob, D.J.; Fan, S.M.; Wofsy, S.C.; Spiro, P.A.; Bakwin, P.S.; Ritter, J.A.; Browell, E.V.; Gregory, G.L.; Fitzjarrald, D.R.; Moore, K.E. NASA, Langley Research Center, Hampton, VA New York State Univ., Albany )

    1992-10-01

    Eddy correlation measurements of O3 deposition fluxes to tundra during the Arctic Boundary Layer Expedition (ABLE 3A) are reported. The mean O[sub 3] deposition velocity was 0.24 cm/s in the daytime and 0.12 cm/s at night. The day-to-day difference in deposition velocity was driven by both atmospheric stability and surface reactivity. The mean surface resistance to O[sub 3] deposition was 2.6 s/cm in the daytime and 3.4 s/cm at night. The relatively low surface resistance at night is attributed to light-insensitive uptake of O[sub 3] at dry upland tundra surfaces. The small day-tonight difference in surface resistance is attributed to additional stomatal uptake by wet meadow tundra plants in the daytime. The mean O[sub 3] deposition flux to the world north of 60 deg N in July-August is estimated at 8.2 x 10 exp 10 molecules/sq cm/s. Suppression of photochemical loss by small anthropogenic inputs of nitrogen oxides could have a major effect on O[sub 3] concentrations in the summertime Arctic troposphere. 34 refs.

  6. Deposition of ozone to tundra

    NASA Technical Reports Server (NTRS)

    Jacob, D. J.; Fan, S.-M.; Wofsy, S. C.; Spiro, P. A.; Bakwin, P. S.; Ritter, J. A.; Browell, E. V.; Gregory, G. L.; Fitzjarrald, D. R.; Moore, K. E.

    1992-01-01

    Eddy correlation measurements of O3 deposition fluxes to tundra during the Arctic Boundary Layer Expedition (ABLE 3A) are reported. The mean O3 deposition velocity was 0.24 cm/s in the daytime and 0.12 cm/s at night. The day-to-day difference in deposition velocity was driven by both atmospheric stability and surface reactivity. The mean surface resistance to O3 deposition was 2.6 s/cm in the daytime and 3.4 s/cm at night. The relatively low surface resistance at night is attributed to light-insensitive uptake of O3 at dry upland tundra surfaces. The small day-tonight difference in surface resistance is attributed to additional stomatal uptake by wet meadow tundra plants in the daytime. The mean O3 deposition flux to the world north of 60 deg N in July-August is estimated at 8.2 x 10 exp 10 molecules/sq cm/s. Suppression of photochemical loss by small anthropogenic inputs of nitrogen oxides could have a major effect on O3 concentrations in the summertime Arctic troposphere.

  7. 46 CFR 287.11 - Time deposits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Time deposits. 287.11 Section 287.11 Shipping MARITIME... OF CONSTRUCTION RESERVE FUNDS § 287.11 Time deposits. Deposits in the construction reserve fund not invested in securities may be placed in time deposits when, in the judgment of the taxpayer, it...

  8. 24 CFR 891.635 - Security deposits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Security deposits. 891.635 Section... Assistance § 891.635 Security deposits. The general requirements for security deposits on assisted units are... a security deposit equal to one month's rent payable by the family. (b) The Borrower shall...

  9. 24 CFR 891.635 - Security deposits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Security deposits. 891.635 Section... Assistance § 891.635 Security deposits. The general requirements for security deposits on assisted units are... a security deposit equal to one month's rent payable by the family. (b) The Borrower shall...

  10. 46 CFR 287.11 - Time deposits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Time deposits. 287.11 Section 287.11 Shipping MARITIME... OF CONSTRUCTION RESERVE FUNDS § 287.11 Time deposits. Deposits in the construction reserve fund not invested in securities may be placed in time deposits when, in the judgment of the taxpayer, it...

  11. 46 CFR 287.11 - Time deposits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Time deposits. 287.11 Section 287.11 Shipping MARITIME... OF CONSTRUCTION RESERVE FUNDS § 287.11 Time deposits. Deposits in the construction reserve fund not invested in securities may be placed in time deposits when, in the judgment of the taxpayer, it...

  12. 46 CFR 287.11 - Time deposits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Time deposits. 287.11 Section 287.11 Shipping MARITIME... OF CONSTRUCTION RESERVE FUNDS § 287.11 Time deposits. Deposits in the construction reserve fund not invested in securities may be placed in time deposits when, in the judgment of the taxpayer, it...

  13. 46 CFR 287.11 - Time deposits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false Time deposits. 287.11 Section 287.11 Shipping MARITIME... OF CONSTRUCTION RESERVE FUNDS § 287.11 Time deposits. Deposits in the construction reserve fund not invested in securities may be placed in time deposits when, in the judgment of the taxpayer, it...

  14. TULSA UNIVERSITY PARAFFIN DEPOSITION PROJECTS

    SciTech Connect

    Cem Sarica; Michael Volk

    2004-06-01

    As oil and gas production moves to deeper and colder water, subsea multiphase production systems become critical for economic feasibility. It will also become increasingly imperative to adequately identify the conditions for paraffin precipitation and predict paraffin deposition rates to optimize the design and operation of these multi-phase production systems. Although several oil companies have paraffin deposition predictive capabilities for single-phase oil flow, these predictive capabilities are not suitable for the multiphase flow conditions encountered in most flowlines and wellbores. For deepwater applications in the Gulf of Mexico, it is likely that multiphase production streams consisting of crude oil, produced water and gas will be transported in a single multiphase pipeline to minimize capital cost and complexity at the mudline. Existing single-phase (crude oil) paraffin deposition predictive tools are clearly inadequate to accurately design these pipelines, because they do not account for the second and third phases, namely, produced water and gas. The objective of this program is to utilize the current test facilities at The University of Tulsa, as well as member company expertise, to accomplish the following: enhance our understanding of paraffin deposition in single and two-phase (gas-oil) flows; conduct focused experiments to better understand various aspects of deposition physics; and, utilize knowledge gained from experimental modeling studies to enhance the computer programs developed in the previous JIP for predicting paraffin deposition in single and two-phase flow environments. These refined computer models will then be tested against field data from member company pipelines.

  15. Metal film deposition by laser breakdown chemical vapor deposition

    SciTech Connect

    Jervis, T. R.; Newkirk, L. R.

    1986-06-01

    Dielectric breakdown of gas mixtures can be used to deposit thin films by chemical vapor deposition with appropriate control of flow and pressure conditions to suppress gas-phase nucleation and particle formation. Using a pulsed CO/sub 2/ laser operating at 10.6 ..mu.. where there is no significant resonant absorption in any of the source gases, homogeneous films from several gas-phase precursors have been sucessfully deposited by gas-phase laser pyrolysis. Nickel and molybdenum from the respective carbonyls representing decomposition chemistry and tungsten from the hexafluoride representing reduction chemistry have been demonstrated. In each case the gas precursor is buffered with argon to reduce the partial pressure of the reactants and to induce breakdown. Films have been characterized by Auger electron spectroscopy, x-ray diffraction, transmission electron microscopy, pull tests, and resistivity measurements. The highest quality films have resulted from the nickel depositions. Detailed x-ray diffraction analysis of these films yields a very small domain size consistent with the low temperature of the substrate and the formation of metastable nickel carbide. Transmission electron microscopy supports this analysis.

  16. 76 FR 41392 - Interest on Deposits; Deposit Insurance Coverage

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... marginal rates of return. Increased deposits might also mean added pressure for depository institutions to... institutions with heightened risk due to repeal of the statutory prohibition; (c) stress tests should be... the meaning of the relevant sections of the Small Business Regulatory Enforcement Act of 1996...

  17. Atmospheric deposition to high-elevation forests

    SciTech Connect

    Lovett, G.M.; Weathers, K.C.; Lindberg, S.E. Oak Ridge National Lab., TN )

    1994-06-01

    Three important phenomena characterize atmospheric deposition to high-elevation forests: (1) multiple deposition mechanisms (wet, dry, and cloud deposition), (2) high rates of deposition, and (3) high spatial variability. The high rates of deposition are caused by changes in meteorological conditions with elevation, especially increasing wind speed and cloud immersion frequency. The high spatial variability of deposition is a result of the regulation of cloud and dry deposition rates by microclimatic and canopy structure conditions, which can be extremely heterogeneous in mountain landscapes. Spruce-fir forests are often [open quotes]hot spots[close quotes] of deposition when viewed in a landscape or regional context because of their elevation, exposure, and evergreen canopy. In this talk we will consider atmospheric depositions to high-elevation forests in both the northeastern and southeastern U.S., using field data and geographic information systems to illustrate deposition patterns.

  18. Fluidized bed deposition of diamond

    DOEpatents

    Laia, Jr., Joseph R.; Carroll, David W.; Trkula, Mitchell; Anderson, Wallace E.; Valone, Steven M.

    1998-01-01

    A process for coating a substrate with diamond or diamond-like material including maintaining a substrate within a bed of particles capable of being fluidized, the particles having substantially uniform dimensions and the substrate characterized as having different dimensions than the bed particles, fluidizing the bed of particles, and depositing a coating of diamond or diamond-like material upon the substrate by chemical vapor deposition of a carbon-containing precursor gas mixture, the precursor gas mixture introduced into the fluidized bed under conditions resulting in excitation mechanisms sufficient to form the diamond coating.

  19. Deposition of diamondlike carbon films

    NASA Technical Reports Server (NTRS)

    Mirtich, M. J.; Sovey, J. S.; Banks, B. A. (Inventor)

    1984-01-01

    A diamondlike carbon film is deposited in the surface of a substrate by exposing the surface to an argon ion beam containing a hydrocarbon. The current density in the ion beam is low during initial deposition of the film. Subsequent to this initial low current condition, the ion beam is increased to full power. At the same time, a second argon ion beam is directed toward the surface of the substrate. The second ion beam has an energy level much greater than that of the ion beam containing the hydrocarbon. This addition of energy to the system increases mobility of the condensing atoms and serves to remove lesser bound atoms.

  20. Vapor deposition of thin films

    DOEpatents

    Smith, David C.; Pattillo, Stevan G.; Laia, Jr., Joseph R.; Sattelberger, Alfred P.

    1992-01-01

    A highly pure thin metal film having a nanocrystalline structure and a process of preparing such highly pure thin metal films of, e.g., rhodium, iridium, molybdenum, tungsten, rhenium, platinum, or palladium by plasma assisted chemical vapor deposition of, e.g., rhodium(allyl).sub.3, iridium(allyl).sub.3, molybdenum(allyl).sub.4, tungsten(allyl).sub.4, rhenium(allyl).sub.4, platinum(allyl).sub.2, or palladium(allyl).sub.2 are disclosed. Additionally, a general process of reducing the carbon content of a metallic film prepared from one or more organometallic precursor compounds by plasma assisted chemical vapor deposition is disclosed.

  1. Metalliferous lode deposits of Alaska

    USGS Publications Warehouse

    Berg, Henry C.; Cobb, Edward Huntington

    1967-01-01

    This report summarizes from repoAs of Federal and State agencies published before August 31, 1965, the geology of Alaska's metal-bearing lodes, including their structural or stratigraphic control, host rock, mode of origin, kinds of .Q minerals, grade, past production, and extent of exploration. In addition, the lists of mineral occurrences that accompany the 35 mineral-deposit location maps constitute an inventory of the State's known lodes. A total of 692 localities where m&alliferous deposits have been found are shown on the maps. The localities include 1,739 mines, prospects, and reported occurrences, of which 821 are described individually or otherwise cited in the text.

  2. Non-directed aromatic C–H amination: catalytic and mechanistic studies enabled by Pd catalyst and reagent design†

    PubMed Central

    Bandara, H. M. D.; Jin, D.; Mantell, M. A.; Field, K. D.; Wang, A.; Narayanan, R. P.; Deskins, N. A.; Emmert, M. H.

    2016-01-01

    This manuscript describes the systematic development of pyridine-type ligands, which promote the Pd catalyzed, non-directed amination of benzene in combination with novel, hydroxylamine-based electrophilic amination reagents. DFT calculations and mechanistic experiments provide insights into the factors influencing the arene C–H amination protocol. PMID:28066540

  3. GENE ARRAYS FOR ELUCIDATING MECHANISTIC DATA FROM MODELS OF MALE INFERTILITY AND CHEMICAL EXPOSURE IN MICE, RATS AND HUMANS

    EPA Science Inventory

    Gene arrays for elucidating mechanistic data from models of male infertility and chemical exposure in mice, rats and humans
    John C. Rockett and David J. Dix
    Gamete and Early Embryo Biology Branch, Reproductive Toxicology Division, National Health and Environmental Effects ...

  4. At the Intersection of Attention and Memory: The Mechanistic Role of the Posterior Parietal Lobe in Working Memory

    ERIC Educational Resources Information Center

    Berryhill, Marian E.; Chein, Jason; Olson, Ingrid R.

    2011-01-01

    Portions of the posterior parietal cortex (PPC) play a role in working memory (WM) yet the precise mechanistic function of this region remains poorly understood. The "pure storage" hypothesis proposes that this region functions as a short-lived modality-specific memory store. Alternatively, the "internal attention" hypothesis proposes that the PPC…

  5. Mechanistic models as a transferable framework for projecting effects of habitat change on production and delivery of ecosystem services

    EPA Science Inventory

    Drawing a link between habitat change and the production and delivery of ecosystem services is a priority in coastal estuarine ecosystems. Mechanistic modeling tools are highly functional for exploring this link because they allow for the synthesis of multiple ecological and beh...

  6. A MECHANISTIC MODEL FOR MERCURY CAPTURE WITH IN-SITU GENERATED TITANIA PARTICLES: ROLE OF WATER VAPOR

    EPA Science Inventory

    A mechanistic model to predict the capture of gas phase mercury species using in-situ generated titania nanosize particles activated by UV irradiation is developed. The model is an extension of a recently reported model1 for photochemical reactions that accounts for the rates of...

  7. Correlation of mechanistic data and histopathology in the evaluation of selected toxic endpoints of the endocrine system.

    PubMed

    Capen, C C

    1998-12-28

    The objective of this review is to correlate endocrinologic data from mechanistic studies with quantitative histopathology in selected examples of toxic endpoints of the endocrine system in laboratory animals. Mechanistic data can aid in the interpretation of animal toxicology findings and help clarify their significance in risk assessment. Endocrine organs of rodents frequently undergo proliferative changes with advancing age and following chronic exposure to large doses of xenobiotic chemicals, and the sensitivity of rodent endocrine tissues appears to be increasing. Many xenobiotic chemicals in large doses disrupt thyroid function in rodents either by a direct effect on the thyroid influencing synthesis of thyroid hormones or by adversely influencing their peripheral metabolism. A number of chemicals disrupt thyroid function by inhibiting the important enzyme, thyroperoxidase (TPO). A contemporary example of a chemical acting as TPO-inhibitor is sulfamethazine. In short-term mechanistic studies in rats there was a log-dose response relationship in circulating levels of thyroid and pituitary hormones plus a similar non-linear dose-response in morphologic changes in thyroid follicular cells. Endocrinologic data from mechanistic studies and histopathologic/ultrastructural findings will also be presented for the effects of the food color, FDC Red No. 3 (Erythrosine), on the thyroid gland in rats and parathyroid hormone-related protein (a major causative factor in cancer-associated hypercalcemia) on parathyroid chief cells in mice.

  8. An Oligocene subaqueous PDC deposit: inferences on its depositional mechanisms

    NASA Astrophysics Data System (ADS)

    Di Capua, A.; Groppelli, G.

    2014-12-01

    We studied and discussed the depositional mechanisms of a PDC deposit recognized in the Oligocene turbite system of the Val d'Aveto Formation (Northern Italian Apennines). The deposit is characterized by a sandy-sized base (4 m-thick), overlain by a massive conglomerate (46 m-thick), whose gravel-sized detritus is overall represented by substrate-derived clasts (~80%), rather than volcaniclastic ones. Optical, diffractometric (XRD) and minero-chemical (SEM-EDS) analyses on matrix samples reveal a welded volcanic felty texture, rich in plagioclase and horneblende, with accidental metamorphic rock fragments and loose crystals that tend to upward increase along the deposit. Lithological association and roundness of gravel-sized detritus, together with the accidental lithics and loose crystals in the matrix fraction, suggest that this PDC ran channelized in a continental (mountain?) drainage before entering the basin. Channelization in this type of setting 1) enhanced the PDC erosion capacity during the motion and 2) partially cooled it. Flow reached the water at temperatures which triggered the formation of a trapped gas carapace, able to inhibit the water-flow mixing (Sparks et al. (1980-Journal of Volcanology and Geothermal Research). This preserved the current from a shocking water mix and favored its welding. Thus, we suggest that this model can be generally applied when PDC temperatures trigger a stable heat transfer between the flow and the water, which allows the generation of trapped gas carapace and preservation from phreatomagmatic explosions. In contrast, depositional mechanisms inferred by Whitman (1989-Marine Geology) and the ones proposed through the direct observation and sampling of a hot PDC at Montserrat Volcano (Trofimovs et al., 2006-Geology) are developed when fundamental role is played by phreatomagmatic explosions and violent water-flow mix.

  9. Atomic-layer-deposition oxide nanoglue for sodium ion batteries.

    PubMed

    Han, Xiaogang; Liu, Yang; Jia, Zheng; Chen, Yu-Chen; Wan, Jiayu; Weadock, Nicholas; Gaskell, Karen J; Li, Teng; Hu, Liangbing

    2014-01-08

    Atomic-layer-deposition (ALD) coatings have been increasingly used to improve battery performance. However, the electrochemical and mechanistic roles remain largely unclear, especially for ALD coatings on electrodes that undergo significant volume changes (up to 100%) during charging/discharging. Here we investigate an anode consisting of tin nanoparticles (SnNPs) with an ALD-Al2O3 coating. For the first time, in situ transmission electron microscopy unveiled the dynamic mechanical protection of the ALD-Al2O3 coating by coherently deforming with the SnNPs under the huge volume changes during charging/discharging. Battery tests in coin-cells further showed the ALD-Al2O3 coating remarkably boosts the cycling performance of the Sn anodes, comparing with those made of bare SnNPs. Chemomechanical simulations clearly revealed that a bare SnNP debonds and falls off the underlying substrate upon charging, and by contrast the ALD-Al2O3 coating, like ion-conductive nanoglue, robustly anchors the SnNP anode to the substrate during charging/discharging, a key to improving battery cycle performance.

  10. Drop Coating Deposition Raman Spectroscopy of Fluorescein Isothiocyanate Labeled Protein

    PubMed Central

    Vangala, Karthikeshwar; Jiang, Dongping; Zou, Sige; Pechan, Tibor

    2011-01-01

    Using bovine serum albumin (BSA) as the model protein normal Raman spectra of Fluorescein isothiocyanate (FITC) -conjugated protein was systematically studied for the first time using both solution and the drop coating deposition Raman (DCDR) sampling techniques. The FITC-BSA Raman spectra are dominated by the FITC Raman features that are strongly pH dependent. Current DCDR detection sensitivity obtained with a 10:1 FITC-BSA conjugate is 45 fmol in terms of total protein consumption and ~15 attomol at laser probed volume. Unlike the FITC-BSA solution Raman spectra where the FITC Raman features are photostable, concurrent FITC fluorescence and Raman photobleaching is observed in the DCDR spectra of FITC-BSA. While the FITC Raman photobleaching follows a single exponential decay function with a time constant independent of the FITC labeling ratio, the fluorescence background photobleaching is much more complicated and it depends strongly on the FITC labeling ratio and sample conditions. Mechanistically, the FITC Raman photobleaching is believed to be due to photochemical reaction of the FITC molecules in the electronically excited state. The FITC fluorescence photobleaching involves both concentration quenching and photochemical quenching, and the latter may involve a photochemical intermediate that is fluorescence inactive but Raman active. PMID:20925976

  11. Phenological controls on inter-annual variability in ozone dry deposition velocity

    NASA Astrophysics Data System (ADS)

    Clifton, Olivia; Fiore, Arlene; Munger, J. William; Shevliakova, Elena; Horowitz, Larry; Malyshev, Sergey; Griffin, Kevin

    2016-04-01

    Our understanding of ozone removal by northern mid-latitude temperate deciduous forests is largely based on short-term observational studies, and thus year-to-year variations of this sink have received little attention. The specific pathways for ozone dry deposition include stomatal uptake and other non-stomatal processes that are poorly understood. Given the importance of ozone dry deposition to model accurately the tropospheric ozone budget and regional air quality, an improved mechanistic understanding of this ozone sink is needed. We investigate here the physical and biological controls on inter-annual variations in seasonal and diurnal cycles of ozone dry deposition velocity using nine years of hourly observations of eddy covariance ozone flux and concentration measurements at Harvard Forest, a northern mid-latitude temperate deciduous forest. We also use coincident eddy covariance water vapor flux and sensible heat flux and other micrometeorological measurements to infer stomatal conductance in order to separate the impacts of stomatal versus non-stomatal pathways on ozone deposition. There is a difference of approximately a factor of two between minimum and maximum monthly daytime mean ozone dry deposition velocities at Harvard Forest. The highest summertime mean ozone dry deposition velocities occur during 1998 and 1999 (0.72 cm/s), and similar seasonal and diurnal cycles occur in both years. The similar dry deposition velocities during these two years, however, may reflect compensation between different processes as mean daytime summertime stomatal conductance during 1998 is roughly 1.5 times higher than for 1999, suggesting large year-to-year variations in non-stomatal as well as stomatal uptake of ozone. We partition the onset and decline of the growing season each year into different periods using spring and fall phenology observations at Harvard Forest. Combining the dry deposition velocities across years during each phenological period, we find that

  12. Mechanistic variables can enhance predictive models of endotherm distributions: The American pika under current, past, and future climates

    USGS Publications Warehouse

    Mathewson, Paul; Moyer-Horner, Lucas; Beever, Erik; Briscoe, Natalie; Kearney, Michael T; Yahn, Jeremiah; Porter, Warren P.

    2017-01-01

    How climate constrains species’ distributions through time and space is an important question in the context of conservation planning for climate change. Despite increasing awareness of the need to incorporate mechanism into species distribution models (SDMs), mechanistic modeling of endotherm distributions remains limited in this literature. Using the American pika (Ochotona princeps) as an example, we present a framework whereby mechanism can be incorporated into endotherm SDMs. Pika distribution has repeatedly been found to be constrained by warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to convert macroclimate data to pika-specific surface activity time in summer across the western United States. We then explored the difference between using a macroclimate predictor (summer temperature) and using a mechanistic predictor (predicted surface activity time) in SDMs. Both approaches accurately predicted pika presences in current and past climate regimes. However, the activity models predicted 8–19% less habitat loss in response to annual temperature increases of ~3–5 °C predicted in the region by 2070, suggesting that pikas may be able to buffer some climate change effects through behavioral thermoregulation that can be captured by mechanistic modeling. Incorporating mechanism added value to the modeling by providing increased confidence in areas where different modeling approaches agreed and providing a range of outcomes in areas of disagreement. It also provided a more proximate variable relating animal distribution to climate, allowing investigations into how unique habitat characteristics and intraspecific phenotypic variation may allow pikas to exist in areas outside those predicted by generic SDMs. Only a small number of easily obtainable data are required to parameterize this mechanistic model for any endotherm, and its use can improve SDM predictions by explicitly modeling a widely applicable direct physiological effect

  13. Mechanistic variables can enhance predictive models of endotherm distributions: the American pika under current, past, and future climates.

    PubMed

    Mathewson, Paul D; Moyer-Horner, Lucas; Beever, Erik A; Briscoe, Natalie J; Kearney, Michael; Yahn, Jeremiah M; Porter, Warren P

    2017-03-01

    How climate constrains species' distributions through time and space is an important question in the context of conservation planning for climate change. Despite increasing awareness of the need to incorporate mechanism into species distribution models (SDMs), mechanistic modeling of endotherm distributions remains limited in this literature. Using the American pika (Ochotona princeps) as an example, we present a framework whereby mechanism can be incorporated into endotherm SDMs. Pika distribution has repeatedly been found to be constrained by warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to convert macroclimate data to pika-specific surface activity time in summer across the western United States. We then explored the difference between using a macroclimate predictor (summer temperature) and using a mechanistic predictor (predicted surface activity time) in SDMs. Both approaches accurately predicted pika presences in current and past climate regimes. However, the activity models predicted 8-19% less habitat loss in response to annual temperature increases of ~3-5 °C predicted in the region by 2070, suggesting that pikas may be able to buffer some climate change effects through behavioral thermoregulation that can be captured by mechanistic modeling. Incorporating mechanism added value to the modeling by providing increased confidence in areas where different modeling approaches agreed and providing a range of outcomes in areas of disagreement. It also provided a more proximate variable relating animal distribution to climate, allowing investigations into how unique habitat characteristics and intraspecific phenotypic variation may allow pikas to exist in areas outside those predicted by generic SDMs. Only a small number of easily obtainable data are required to parameterize this mechanistic model for any endotherm, and its use can improve SDM predictions by explicitly modeling a widely applicable direct physiological effect

  14. The upper and lower limits of the mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Stoichiometry of oxidative phosphorylation.

    PubMed

    Beavis, A D; Lehninger, A L

    1986-07-15

    Determination of the intrinsic or mechanistic P/O ratio of oxidative phosphorylation is difficult because of the unknown magnitude of leak fluxes. Applying a new approach developed to overcome this problem (see our preceding paper in this journal), the relationships between the rate of O2 uptake [( Jo)3], the net rate of phosphorylation (Jp), the P/O ratio, and the respiratory control ratio (RCR) have been determined in rat liver mitochondria when the rate of phosphorylation was systematically varied by three specific means. (a) When phosphorylation is titrated with carboxyatractyloside, linear relationships are observed between Jp and (Jo)3. These data indicate that the upper limit of the mechanistic P/O ratio is 1.80 for succinate and 2.90 for 3-hydroxybutyrate oxidation. (b) Titration with malonate or antimycin yields linear relationships between Jp and (Jo)3. These data give the lower limit of the mechanistic P/O ratio of 1.63 for succinate and 2.66 for 3-hydroxybutyrate oxidation. (c) Titration with a protonophore yields linear relationships between Jp, (Jo)3, and (Jo)4 and between P/O and 1/RCR. Extrapolation of the P/O ratio to 1/RCR = 0 yields P/O ratios of 1.75 for succinate and 2.73 for 3-hydroxybutyrate oxidation which must be equal to or greater than the mechanistic stoichiometry. When published values for the H+/O and H+/ATP ejection ratios are taken into consideration, these measurements suggest that the mechanistic P/O ratio is 1.75 for succinate oxidation and 2.75 for NADH oxidation.

  15. Advanced deposition model for thermal activated chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Cai, Dang

    Thermal Activated Chemical Vapor Deposition (TACVD) is defined as the formation of a stable solid product on a heated substrate surface from chemical reactions and/or dissociation of gaseous reactants in an activated environment. It has become an essential process for producing solid film, bulk material, coating, fibers, powders and monolithic components. Global market of CVD products has reached multi billions dollars for each year. In the recent years CVD process has been extensively used to manufacture semiconductors and other electronic components such as polysilicon, AlN and GaN. Extensive research effort has been directed to improve deposition quality and throughput. To obtain fast and high quality deposition, operational conditions such as temperature, pressure, fluid velocity and species concentration and geometry conditions such as source-substrate distance need to be well controlled in a CVD system. This thesis will focus on design of CVD processes through understanding the transport and reaction phenomena in the growth reactor. Since the in situ monitor is almost impossible for CVD reactor, many industrial resources have been expended to determine the optimum design by semi-empirical methods and trial-and-error procedures. This approach has allowed the achievement of improvements in the deposition sequence, but begins to show its limitations, as this method cannot always fulfill the more and more stringent specifications of the industry. To resolve this problem, numerical simulation is widely used in studying the growth techniques. The difficulty of numerical simulation of TACVD crystal growth process lies in the simulation of gas phase and surface reactions, especially the latter one, due to the fact that very limited kinetic information is available in the open literature. In this thesis, an advanced deposition model was developed to study the multi-component fluid flow, homogeneous gas phase reactions inside the reactor chamber, heterogeneous surface

  16. Vacuum vapor deposition gun assembly

    DOEpatents

    Zeren, Joseph D.

    1985-01-01

    A vapor deposition gun assembly includes a hollow body having a cylindrical outer surface and an end plate for holding an adjustable heat sink, a hot hollow cathode gun, two magnets for steering the plasma from the gun into a crucible on the heat sink, and a shutter for selectively covering and uncovering the crucible.

  17. Grow Your Own Copper Deposit

    ERIC Educational Resources Information Center

    Corcoran, Timothy John

    2009-01-01

    Crystals are beautiful structures--yet they occur naturally in dirty and remote places. In the inquiry-based activity described here, students will enjoy the process of creating their own crystals and using microscopes to examine them. It demonstrates the process of mineral concentration and deposition. Upon completing this activity, students…

  18. Modeling of heavy organic deposition

    SciTech Connect

    Chung, F.T.H.

    1992-01-01

    Organic deposition is often a major problem in petroleum production and processing. This problem is manifested by current activities in gas flooding and heavy oil production. The need for understanding the nature of asphaltenes and asphaltics and developing solutions to the deposition problem is well recognized. Prediction technique is crucial to solution development. In the past 5 years, some progress in modeling organic deposition has been made. A state-of-the-art review of methods for modeling organic deposition is presented in this report. Two new models were developed in this work; one based on a thermodynamic equilibrium principle and the other on the colloidal stability theory. These two models are more general and realistic than others previously reported. Because experimental results on the characteristics of asphaltene are inconclusive, it is still not well known whether the asphaltenes is crude oil exist as a true solution or as a colloidal suspension. Further laboratory work which is designed to study the solubility properties of asphaltenes and to provide additional information for model development is proposed. Some experimental tests have been conducted to study the mechanisms of CO{sub 2}-induced asphaltene precipitation. Coreflooding experiments show that asphaltene precipitation occurs after gas breakthrough. The mechanism of CO{sub 2}-induced asphaltene precipitation is believed to occur by hydrocarbon extraction which causes change in oil composition. Oil swelling due to CO{sub 2} solubilization does not induce asphaltene precipitation.

  19. OXALATE DEPOSITION ON ASBESTOS BODIES

    EPA Science Inventory

    The clinical and histopathologic findings in three patients with a deposition of calcium oxalate crystals on ferruginous bodies after occupational exposure to asbestos are provided. In addition, we test the hypothesis that this oxalate can be generated through a nonenzymatic o...

  20. Subconjunctival and episcleral lipid deposits.

    PubMed Central

    Fraunfelder, F. T.; Garner, A.; Barras, T. C.

    1976-01-01

    Biomicroscopical examination of the bulbar conjunctiva and anterior episclera of 1000 randomly selected outpatients showed the presence of multiple discrete lipid globules in 30 per cent. The lipid deposits were asymptomatic. Their prevalence was age-related, while their distribution and composition were consistent with origin from the conjunctival blood vessels. Images PMID:952830