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. A MECHANISTIC MODEL FOR PARTICLE DEPOSITION IN DIESEL PARTICLUATE FILTERS USING THE LATTICE-BOLTZMANN TECHNIQUE

    SciTech Connect

    Stewart, Mark L.; Rector, David R.; Muntean, George G.; Maupin, Gary D.

    2004-08-01

    Cordierite diesel particulate filters (DPFs) offer one of the most promising aftertreatment technologies to meet the quickly approaching EPA 2007 heavy-duty emissions regulations. A critical, yet poorly understood, component of particulate filter modeling is the representation of soot deposition. The structure and distribution of soot deposits upon and within the ceramic substrate directly influence many of the macroscopic phenomenon of interest, including filtration efficiency, back pressure, and filter regeneration. Intrinsic soot cake properties such as packing density and permeability coefficients remain inadequately characterized. The work reported in this paper involves subgrid modeling techniques which may prove useful in resolving these inadequacies. The technique involves the use of a lattice Boltzmann modeling approach. This approach resolves length scales which are orders of magnitude below those typical of a standard computational fluid dynamics (CFD) representation of an aftertreatment device. Individual soot particles are introduced and tracked as they move through the flow field and are deposited on the filter substrate or previously deposited particles. Electron micrographs of actual soot deposits were taken and compared to the model predictions. Descriptions of the modeling technique and the development of the computational domain are provided. Preliminary results are presented, along with some comparisons with experimental observations.

  3. Disintegration of nano-embedded microparticles after deposition on mucus: A mechanistic study.

    PubMed

    Ruge, Christian A; Bohr, Adam; Beck-Broichsitter, Moritz; Nicolas, Valérie; Tsapis, Nicolas; Fattal, Elias

    2016-03-01

    The conversion of colloidal drug carriers/polymeric nanoparticles into dry microparticulate powders (e.g., by spray-drying) is a prominent approach to overcome the aerodynamic limitations of these formulations for delivery via inhalation. However, to what extent such nano-embedded microparticles disintegrate into individual/intact nanoparticles after contacting relevant physiological media has so far not been addressed. Polymeric nanoparticles were spray-dried into nano-embedded microparticles (NEMs) using different amounts of trehalose as embedding matrix excipient. Formulations were characterized and then evaluated for their disintegration behavior after aerosolization onto model mucus. Although a rapid and complete aqueous redispersion was observed for specific excipient/nanoparticle weight ratios (i.e., greater than 1/1), the same formulations revealed no disintegration after deposition onto a static mucus layer. Double-labeled NEMs powders (i.e., dual color staining of polymeric nanoparticles and trehalose) demonstrated rapid matrix dissolution, while the nanoparticle aggregates persisted. When deposited onto agitated mucus, however, sufficient disintegration of NEMs into individual polymeric nanoparticles was observed. These findings indicate that mechanical forces are necessary to overcome the attraction between individual nanoparticles found within the NEMs. Thus, it remains questionable whether the lung mechanics (e.g., breathing, mucociliary clearance) acting on these formulations will contribute to the overall disintegration process.

  4. Atomic layer deposition, characterization, and growth mechanistic studies of TiO2 thin films.

    PubMed

    Kaipio, Mikko; Blanquart, Timothee; Tomczak, Yoann; Niinistö, Jaakko; Gavagnin, Marco; Longo, Valentino; Wanzenböck, Heinz D; Pallem, Venkateswara R; Dussarrat, Christian; Puukilainen, Esa; Ritala, Mikko; Leskelä, Markku

    2014-07-01

    Two heteroleptic titanium precursors were investigated for the atomic layer deposition (ALD) of titanium dioxide using ozone as the oxygen source. The precursors, titanium (N,N'-diisopropylacetamidinate)tris(isopropoxide) (Ti(O(i)Pr)3(N(i)Pr-Me-amd)) and titanium bis(dimethylamide)bis(isopropoxide) (Ti(NMe2)2(O(i)Pr)2), exhibit self-limiting growth behavior up to a maximum temperature of 325 °C. Ti(NMe2)2(O(i)Pr)2 displays an excellent growth rate of 0.9 Å/cycle at 325 °C while the growth rate of Ti(O(i)Pr)3(N(i)Pr-Me-amd) is 0.3 Å/cycle at the same temperature. In the temperature range of 275-325 °C, both precursors deposit titanium dioxide in the anatase phase. In the case of Ti(NMe2)2(O(i)Pr)2, high-temperature X-ray diffraction (HTXRD) studies reveal a thickness-dependent phase change from anatase to rutile at 875-975 °C. X-ray photoelectron spectroscopy (XPS) indicates that the films have high purity and are close to the stoichiometric composition. Reaction mechanisms taking place during the ALD process were studied in situ with quadrupole mass spectrometry (QMS) and quartz crystal microbalance (QCM).

  5. Electrophoretic deposition and mechanistic studies of nano-Al/CuO thermites

    NASA Astrophysics Data System (ADS)

    Sullivan, K. T.; Kuntz, J. D.; Gash, A. E.

    2012-07-01

    Electrophoretic deposition was used to deposit thin films (˜10-200 μm) of nano-aluminum/copper oxide thermites, with a density of 29% the theoretical maximum. The reaction propagation velocity was examined using fine-patterned electrodes (0.25 × 20 mm), and the optimum velocity was found to correspond to a fuel-rich equivalence ratio of 1.7. This value did not correlate with the calculated maximum in gas production or temperature, and it is suggested that it is a result of enhanced condensed-phase transport, which is speculated to increase for fuel-rich conditions. A ˜25% drop in propagation velocity occurred above an equivalence ratio of 2.0, where Al2O3 is predicted to undergo a phase change from liquid to solid. This is expected to hinder the kinetics by decreasing the mobility of condensed-phase reacting species. The effect of film thickness on propagation velocity was investigated, using the optimum equivalence ratio. The velocity was seen to exhibit a two-plateau behavior, with one plateau between 13 and 50 μm film thickness, and the other above ˜120 μm. The latter had nearly an order of magnitude faster velocity than the former, 36 m/s vs. 4 m/s, respectively. For film thicknesses in the 50-120 μm range, a linear transitional regime was observed. Images from the combustion studies showed an increase in forward-transported particles as the film thickness increased, along with more turbulent behavior of the flame. It was suggested that the two-plateau behavior indicated a shift in the energy transport mechanism. While nanocomposite thermites have been traditionally thought to exhibit convective energy transport, we find in this work that particle advection may also be important. The velocity of particles ejected through a thin slit mounted above a thermite strip was measured, and was found to be even faster (˜2-3×) than the flame propagation velocity. The morphology of captured particles was examined with an electron microscope, and indicated that

  6. 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. PMID:26937889

  7. 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.

  8. 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.

  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. An asynchronous metamodel-assisted memetic algorithm for CFD-based shape optimization

    NASA Astrophysics Data System (ADS)

    Kontoleontos, Evgenia A.; Asouti, Varvara G.; Giannakoglou, Kyriakos C.

    2012-02-01

    This article presents an asynchronous metamodel-assisted memetic algorithm for the solution of CFD-based optimization problems. This algorithm is appropriate for use on multiprocessor platforms and may solve computationally expensive optimization problems in reduced wall-clock time, compared to conventional evolutionary or memetic algorithms. It is, in fact, a hybridization of non-generation-based (asynchronous) evolutionary algorithms, assisted by surrogate evaluation models, a local search method and the Lamarckian learning process. For the objective function gradient computation, in CFD applications, the adjoint method is used. Issues concerning the 'smart' implementation of local search in multi-objective problems are discussed. In this respect, an algorithmic scheme for reducing the number of calls to the adjoint equations to just one, irrespective of the number of objectives, is proposed. The algorithm is applied to the CFD-based shape optimization of the tubes of a heat exchanger and of a turbomachinery cascade.

  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. 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.

  14. 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

    2016-07-01

    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.

  15. 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.

  16. Advanced process engineering co-simulation using CFD-based reduced order models

    SciTech Connect

    Lang, Y.-D.; Biegler, L.T.; Munteanu, S.; Madsen, J.I.; Zitney, S.E.

    2007-11-04

    The process and energy industries face the challenge of designing the next generation of plants to operate with unprecedented efficiency and near-zero emissions, while performing profitably amid fluctuations in costs for raw materials, finished products, and energy. To achieve these targets, the designers of future plants are increasingly relying upon modeling and simulation to create virtual plants that allow them to evaluate design concepts without the expense of pilot-scale and demonstration facilities. Two of the more commonly used simulation tools include process simulators for describing the entire plant as a network of simplified equipment models and computational fluid dynamic (CFD) packages for modeling an isolated equipment item in great detail by accounting for complex thermal and fluid flow phenomena. The Advanced Process Engineering Co-Simulator (APECS) sponsored by the U.S. Department of Energy’s (DOE) National Energy Technology Laboratory (NETL) has been developed to combine process simulation software with CFD-based equipment simulation software so that design engineers can analyze and optimize the coupled fluid flow, heat and mass transfer, and chemical reactions that drive overall plant performance (Zitney et al., 2006). The process/CFD software integration was accomplished using the process-industry standard CAPE-OPEN interfaces.

  17. 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.

  18. An automatic CFD-based flow diverter optimization principle for patient-specific intracranial aneurysms.

    PubMed

    Janiga, Gábor; Daróczy, László; Berg, Philipp; Thévenin, Dominique; Skalej, Martin; Beuing, Oliver

    2015-11-01

    The optimal treatment of intracranial aneurysms using flow diverting devices is a fundamental issue for neuroradiologists as well as neurosurgeons. Due to highly irregular manifold aneurysm shapes and locations, the choice of the stent and the patient-specific deployment strategy can be a very difficult decision. To support the therapy planning, a new method is introduced that combines a three-dimensional CFD-based optimization with a realistic deployment of a virtual flow diverting stent for a given aneurysm. To demonstrate the feasibility of this method, it was applied to a patient-specific intracranial giant aneurysm that was successfully treated using a commercial flow diverter. Eight treatment scenarios with different local compressions were considered in a fully automated simulation loop. The impact on the corresponding blood flow behavior was evaluated qualitatively as well as quantitatively, and the optimal configuration for this specific case was identified. The virtual deployment of an uncompressed flow diverter reduced the inflow into the aneurysm by 24.4% compared to the untreated case. Depending on the positioning of the local stent compression below the ostium, blood flow reduction could vary between 27.3% and 33.4%. Therefore, a broad range of potential treatment outcomes was identified, illustrating the variability of a given flow diverter deployment in general. This method represents a proof of concept to automatically identify the optimal treatment for a patient in a virtual study under certain assumptions. Hence, it contributes to the improvement of virtual stenting for intracranial aneurysms and can support physicians during therapy planning in the future.

  19. 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.

  20. On the Accuracy of CFD-Based Pressure Drop Predictions for Right-Angle Ducts

    NASA Technical Reports Server (NTRS)

    Brankovic, Andreja

    1993-01-01

    The predictive capability of computational fluid dynamics (CFD) codes for turbulent flow through curved ducts is of significant importance to the design and performance analysis of modern rocket engine flowpaths. Code calibration and validation studies for this class of flow are desireable to estimate the performance margin and operating range of components designed using Navier-Stokes methods. Parametric experimental studies such as that of Weske (NACA ARR W-39) provided a wealth of performance data for the design of single- and compound elbow configurations with various cross-sections, curvature and aspect ratios at varying Reynolds numbers. In that work, the majority of data is presented in the form of loss coefficients, characterizing pressure losses due to duct curvature, and including losses due to wall friction. Using measured friction coefficients, losses of equivalent straight lengths of duct are subtracted, resulting in performance curves useful for design computations. These data are currently used in a CFD-based parametric study covering a broad range of operating conditions. Of particular interest for the accuracy of CFD predictions are the effects on pressure loss due to inlet boundary layer thickness (dependent on upstream development length), and the wall treatment for the turbulence equations (conventional wall functions vs. wall integration using a two-layer model). The experimental data are reassessed in the form of an error analysis, and are compared with CFD predictions for 18 computational cases. Grid-independence, grid spacing, and convergence requirements of the cases are discussed. Conclusions regarding the relative importance of the parametric variables will be presented.

  1. Mechanistic study of atomic layer deposition of Al{sub x}Si{sub y}O thin film via in-situ FTIR spectroscopy

    SciTech Connect

    Cho, Jea; Kim, Taeseung; Seegmiller, Trevor; Chang, Jane P.

    2015-09-15

    A study of surface reaction mechanism on atomic layer deposition (ALD) of aluminum silicate (Al{sub x}Si{sub y}O) was conducted with trimethylaluminum (TMA) and tetraethoxysilane (TEOS) as precursors and H{sub 2}O as the oxidant. In-situ Fourier transform infrared spectroscopy (FTIR) was utilized to elucidate the underlying surface mechanism that enables the deposition of Al{sub x}Si{sub y}O by ALD. In-situ FTIR study revealed that ineffective hydroxylation of the surface ethoxy (–OCH{sub 2}CH{sub 3}) groups prohibits ALD of SiO{sub 2} by TEOS/H{sub 2}O. In contrast, effective desorption of the surface ethoxy group was observed in TEOS/H{sub 2}O/TMA/H{sub 2}O chemistry. The presence of Al-OH* group in vicinity of partially hydroxylated ethoxy (–OCH{sub 2}CH{sub 3}) group was found to propagate disproportionation reaction, which results in ALD of Al{sub x}Si{sub y}O. The maximum thickness from incorporation of SiO{sub x} from alternating exposures of TEOS/H{sub 2}O chemistry in Al{sub x}Si{sub y}O was found to be ∼2 Å, confirmed by high resolution transmission electron microscopy measurements.

  2. 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.

  3. CFD-based model for melt flow in laser beam welding of aluminium with coaxial magnetic field

    NASA Astrophysics Data System (ADS)

    Gatzen, M.; Tang, Z.

    The use of magnetic fields to influence weld bead shape and dilution in laser welding of aluminium alloys was recently suggested. For the case of laser welding of hot-cracking sensitive aluminium alloys with silicon-containing filler wire it was already demonstrated that applying alternating magnetic fields has an impact on the dilution of silicon in the melt pool, yielding sufficient silicon content throughout the weld to suppress hot-cracking. This is due to the changed melt flow condition resulting from induced magnetic volume forces. In this paper, a CFD-based model will be presented that was used to numerically calculate the resulting velocity field for laser beam welding of aluminium with external applied magnetic fields. The model includes temperaturedepending material properties, surface tension and buoyancy. The inhomogeneous magnetic flux density distribution implemented in this model has been derived from Hall sensor probes of a welding head prototype used for experimental investigations. It is shown that a steady magnetic field applied coaxially to the laser beam will affect the direction of melt flow and can be described as an inhomogeneous electromagnetic break.

  4. 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.

  5. 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.

  6. 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.

  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. Electron transfer with self-assembled copper ions at Au-deposited biomimetic films: mechanistic ‘anomalies’ disclosed by temperature- and pressure-assisted fast-scan voltammetry

    NASA Astrophysics Data System (ADS)

    Khoshtariya, Dimitri E.; Dolidze, Tinatin D.; Tretyakova, Tatyana; van Eldik, Rudi

    2015-06-01

    It has been suggested that electron transfer (ET) processes occurring in complex environments capable of glass transitions, specifically in biomolecules, under certain conditions may experience the medium’s nonlinear response and nonergodic kinetic patterns. The interiors of self-assembled organic films (SAMs) deposited on solid conducting platforms (electrodes) are known to undergo glassy dynamics as well, hence they may also exhibit the abovementioned ‘irregularities’. We took advantage of Cu2+ ions as redox-active probes trapped in the Au-deposited  -COOH-terminated SAMs, either L-cysteine, or 3-mercaptopropionic acid diluted by the inert 2-mercaptoethanol, to systematically study the impact of glassy dynamics on ET using the fast-scan voltammetry technique and its temperature and high-pressure extensions. We found that respective kinetic data can be rationalized within the extended Marcus theory, taking into account the frictionally controlled (adiabatic) mechanism for short-range ET, and complications due to the medium’s nonlinear response and broken ergodicity. This combination shows up in essential deviations from the conventional energy gap (overpotential) dependence and in essentially nonlinear temperature (Arrhenius) and high-pressure patterns, respectively. Biomimetic aspects for these systems are also discussed in the context of recently published results for interfacial ET involving self-assembled blue copper protein (azurin) placed in contact with a glassy environment.

  10. 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

  11. Conceptualization and analysis of mechanistic studies.

    PubMed

    Aickin, Mikel

    2007-01-01

    Much recent attention has been given to the priority for doing "mechanistic studies" of complementary and alternative medicine (CAM) modalities. A preference for such studes has been clearly indicated by the National Center for Complementary and Alternative Medicine program of funding for CAM research. It is, however, difficult to find canons by which "mechanistic" studies should be analyzed, and even harder to find a good definition of "mechanism." Social scientists have well-developed ways of approaching these issues, but their methods suffer from a fatal flaw, the ecologic mechanistic fallacy. Basic scientists fare even worse, often conducting mechanistic studies that may have no plausible mechanistic content, and that also commit the ecologic mechanistic fallacy. More methodological work on the concept of mechanism is needed at a fundamental level.

  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. PMID:26597869

  15. 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.

  16. The Substitution-Elimination Mechanistic Disc Method

    ERIC Educational Resources Information Center

    Buonora, Paul T.; Yu Jin Lim

    2004-01-01

    A method designed to facilitate prediction of mechanism and products by developing critical thinking skills and reducing memorization is presented. The mechanistic disc method requiring students to utilize their understanding of charge stabilization, structural organic chemistry, and the fundamental mechanisms of aliphatic substitution and…

  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. 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.

  19. Evolving biosynthetic tangos negotiate mechanistic landscapes.

    PubMed

    Austin, Michael B; O'Maille, Paul E; Noel, Joseph P

    2008-04-01

    The dependence of polyketide synthase and terpene cyclase mechanistic adaptation on the chemistry of their oligomeric substrates illuminates a convergent evolutionary strategy for shaping cyclization in these otherwise disparate reactions. Evolution of these enzyme families relies on rhythmic tangos, in which the enzymes and substrates together determine product outcome by negotiating decision networks governing intrinsic and induced chemical reactivities. PMID:18347585

  20. 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.

  1. Mechanistic analysis of challenge-response experiments.

    PubMed

    Shotwell, M S; Drake, K J; Sidorov, V Y; Wikswo, J P

    2013-09-01

    We present an application of mechanistic modeling and nonlinear longitudinal regression in the context of biomedical response-to-challenge experiments, a field where these methods are underutilized. In this type of experiment, a system is studied by imposing an experimental challenge, and then observing its response. The combination of mechanistic modeling and nonlinear longitudinal regression has brought new insight, and revealed an unexpected opportunity for optimal design. Specifically, the mechanistic aspect of our approach enables the optimal design of experimental challenge characteristics (e.g., intensity, duration). This article lays some groundwork for this approach. We consider a series of experiments wherein an isolated rabbit heart is challenged with intermittent anoxia. The heart responds to the challenge onset, and recovers when the challenge ends. The mean response is modeled by a system of differential equations that describe a candidate mechanism for cardiac response to anoxia challenge. The cardiac system behaves more variably when challenged than when at rest. Hence, observations arising from this experiment exhibit complex heteroscedasticity and sharp changes in central tendency. We present evidence that an asymptotic statistical inference strategy may fail to adequately account for statistical uncertainty. Two alternative methods are critiqued qualitatively (i.e., for utility in the current context), and quantitatively using an innovative Monte-Carlo method. We conclude with a discussion of the exciting opportunities in optimal design of response-to-challenge experiments. PMID:23859366

  2. A mechanistic analysis of the Birch Reduction.

    PubMed

    Zimmerman, Howard E

    2012-02-21

    The Birch Reduction is one of the main reactions of organic chemistry. The reaction involves the reaction of dissolving metals in ammonia with aromatic compounds to produce 1,4-cyclohexadienes. Discovered by Arthur Birch in 1944, the reaction occupies 300 pages in Organic Reactions to describe its synthetic versatility. Thus, it is remarkable that the reaction mechanism has been so very controversial and only relatively recently has been firmly established. Perhaps this is not that surprising, since the reaction also has many unusual and esoteric mechanistic facets. Here, I provide a description of how I have applied ever-evolving levels of quantum mechanics and a novel experimental test to understand details of the mechanism and the origins of the selectivities observed in the Birch reduction. The reaction involves an initial radical anion resulting from introduction of an electron from the blue liquid ammonia solution of free electrons formed by the dissolution of Li or related metals. This radical anion is protonated by an alcohol and then further reduced to a carbanion. Finally, the carbanion is protonated using a second proton to afford a nonconjugated cyclohexadiene. The regiochemistry depends on substituents present. With 18 resonance structures in the case of anisole radical anion, prediction of the initial protonation site would seem difficult. Nevertheless, computational methods from Hückel theory through modern density functional calculations do correctly predict the site of protonation. An esoteric test established this mechanism experimentally. The nature of the carbanion also is of mechanistic interest, and the preponderance of the resonance structure shown was revealed from Hückel calculations involving variable bond orders. For the trianion from benzoic acid, parallel questions about structure are apparent, and have been answered. Some mechanistic questions are answered experimentally and some by modern computations. Recently, our mechanistic

  3. 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.

  4. 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.

  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. 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)

  7. 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.

  8. Reaction Coordinates and Mechanistic Hypothesis Tests.

    PubMed

    Peters, Baron

    2016-05-27

    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.

  9. 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.

  10. 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

  11. Mechanistic insights into type III restriction enzymes.

    PubMed

    Raghavendra, Nidhanapati K; Bheemanaik, Shivakumara; Rao, Desirazu N

    2012-01-01

    Type III restriction-modification (R-M) enzymes need to interact with two separate unmethylated DNA sequences in indirectly repeated, head-to-head orientations for efficient cleavage to occur at a defined location next to only one of the two sites. However, cleavage of sites that are not in head-to-head orientation have been observed to occur under certain reaction conditions in vitro. ATP hydrolysis is required for the long-distance communication between the sites prior to cleavage. Type III R-M enzymes comprise two subunits, Res and Mod that form a homodimeric Mod2 and a heterotetrameric Res2Mod2 complex. The Mod subunit in M2 or R2M2 complex recognizes and methylates DNA while the Res subunit in R2M2 complex is responsible for ATP hydrolysis, DNA translocation and cleavage. A vast majority of biochemical studies on Type III R-M enzymes have been undertaken using two closely related enzymes, EcoP1I and EcoP15I. Divergent opinions about how the long-distance interaction between the recognition sites exist and at least three mechanistic models based on 1D- diffusion and/or 3D- DNA looping have been proposed.

  12. Structural and mechanistic insights on nitrate reductases.

    PubMed

    Coelho, Catarina; Romão, Maria João

    2015-12-01

    Nitrate reductases (NR) belong to the DMSO reductase family of Mo-containing enzymes and perform key roles in the metabolism of the nitrogen cycle, reducing nitrate to nitrite. Due to variable cell location, structure and function, they have been divided into periplasmic (Nap), cytoplasmic, and membrane-bound (Nar) nitrate reductases. The first crystal structure obtained for a NR was that of the monomeric NapA from Desulfovibrio desulfuricans in 1999. Since then several new crystal structures were solved providing novel insights that led to the revision of the commonly accepted reaction mechanism for periplasmic nitrate reductases. The two crystal structures available for the NarGHI protein are from the same organism (Escherichia coli) and the combination with electrochemical and spectroscopic studies also lead to the proposal of a reaction mechanism for this group of enzymes. Here we present an overview on the current advances in structural and functional aspects of bacterial nitrate reductases, focusing on the mechanistic implications drawn from the crystallographic data. PMID:26362109

  13. Mechanistically based mapping of human cardiac fibrillation.

    PubMed

    Narayan, Sanjiv M; Zaman, Junaid A B

    2016-05-01

    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

  14. 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

  15. Somatodendritic dopamine release: recent mechanistic insights

    PubMed Central

    Rice, Margaret E.; Patel, Jyoti C.

    2015-01-01

    Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

  16. Polymyxin B hemoperfusion: a mechanistic perspective.

    PubMed

    Ronco, Claudio; Klein, David J

    2014-06-09

    Direct hemoperfusion therapy with polymyxin B immobilized fiber cartridge (PMX-DHP) is an established strategy in the treatment of septic shock in Japan and parts of Western Europe. PMX-DHP is currently the subject of a pivotal North American randomized controlled trial (EUPHRATES) in patients with septic shock and confirmed endotoxemia, as measured by the endotoxin activity assay. The major mechanism of action of this therapy is the removal of circulating endotoxin. High affinity binding of circulating endotoxin by the PMX-DHP column may decrease circulating endotoxin levels by up to 90% after two standard treatments. Basic research has shown reductions in circulating cytokine levels and in renal tubular apoptosis. Clinical research has shown that PMX-DHP therapy results in hemodynamic improvements, improvements in oxygenation, renal function, and reductions in mortality. Further research is needed to further define additional patient populations with endotoxemia that may benefit from PMX-DHP therapy as well as to further elucidate dosing, timing, and additional information on mechanisms of action. This review will present the mechanistic rationale for this targeted strategy of endotoxin removal using PMX-DHP in endotoxemic septic patients, highlighting both the specific effects of the therapy and the evidence accumulated so far of clinical improvement following this therapy in terms of recovery of organ function.

  17. Black tea polyphenols: a mechanistic treatise.

    PubMed

    Butt, M S; Imran, A; Sharif, M K; Ahmad, Rabia Shabir; Xiao, Hang; Imran, M; Rsool, H A

    2014-01-01

    Dietary interventions are among the emerging trends to curtail physiological malfunctioning like cancer, diabetes, cardiac complications, etc. The essence of phytonutrients has developed the concept of nutraceuticals at the junction of diet health linkages. In this context, theaflavin & thearubigins are the oxidized derivatives of black tea catechins during fermentation having nutraceutical potential owing to esterification of hydroxyl ring with digallate esters. Theaflavin may influence activation of transcription factors such as NFnB or AP-1 that ultimately hinder the formation of nitric oxide expression gene. Likewise, black tea contains a unique amino acid theanine acts as neurotransmitter owing to its ability to cross the blood-brain barrier. Moreover, it boasts immunity by enhancing the disease-fighting ability of gamma delta T cells. Theaflavin & thearubigins act as safeguard against oxidative stress thereby effective in the cardiac functioning. The mechanistic approach of these antioxidants is likely to be associated with inhibition of redox sensitive transcription factors & pro-oxidant enzymes such as xanthine oxidase or nitric oxide synthase. However, their involvement in antioxidative enzyme induction as in glutathione-S-transferases is also well documented. They act as curative agent against numerous pathological disorders by disrupting the electron chain thus inhibiting the progression of certain ailments. Black tea polyphenols established themselves as strong antioxidants due to their standard one-electron potential, and their vitality is dependent on the concentration of polyphenols and pH for their inclusive execution. Present review is an attempt to enrich the readers regarding the health promoting aspects of black tea polyphenols. Concomitantly, it needs core attention of researchers for the exploitations of black tea flavanols as an important dietary constituent for the vulnerable segment.

  18. 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...

  19. Mechanistic, kinetic, and processing aspects of tungsten chemical mechanical polishing

    NASA Astrophysics Data System (ADS)

    Stein, David

    This dissertation presents an investigation into tungsten chemical mechanical polishing (CMP). CMP is the industrially predominant unit operation that removes excess tungsten after non-selective chemical vapor deposition (CVD) during sub-micron integrated circuit (IC) manufacture. This work explores the CMP process from process engineering and fundamental mechanistic perspectives. The process engineering study optimized an existing CMP process to address issues of polish pad and wafer carrier life. Polish rates, post-CMP metrology of patterned wafers, electrical test data, and synergy with a thermal endpoint technique were used to determine the optimal process. The oxidation rate of tungsten during CMP is significantly lower than the removal rate under identical conditions. Tungsten polished without inhibition during cathodic potentiostatic control. Hertzian indenter model calculations preclude colloids of the size used in tungsten CMP slurries from indenting the tungsten surface. AFM surface topography maps and TEM images of post-CMP tungsten do not show evidence of plow marks or intergranular fracture. Polish rate is dependent on potassium iodate concentration; process temperature is not. The colloid species significantly affects the polish rate and process temperature. Process temperature is not a predictor of polish rate. A process energy balance indicates that the process temperature is predominantly due to shaft work, and that any heat of reaction evolved during the CMP process is negligible. Friction and adhesion between alumina and tungsten were studied using modified AFM techniques. Friction was constant with potassium iodate concentration, but varied with applied pressure. This corroborates the results from the energy balance. Adhesion between the alumina and the tungsten was proportional to the potassium iodate concentration. A heuristic mechanism, which captures the relationship between polish rate, pressure, velocity, and slurry chemistry, is presented

  20. How Much Atmospheric Deposition Across the US: Comparison of N and S Deposition Estimates

    NASA Astrophysics Data System (ADS)

    Weathers, K. C.; Lynch, J. A.

    2008-12-01

    Despite decades of research and monitoring efforts, generating accurate measurements of total (wet + dry) atmospheric deposition across heterogeneous landscapes is still a challenge. In addition, there have been two major, national scale approaches used for generating nitrogen (N) and sulfur (S) deposition across the US. There are two monitoring sources that, when combined with deposition models, result in S and N input estimates. Here we compare N and S total deposition as modeled using the (1) Community Multiscale Air Quality (CMAQ) modeling system, which uses air emissions data combined with chemical transformations, meterologic, and land cover data in a mechanistic model, and (2) the sum of the Clean Air Status and Trends (CASTNET) air chemistry and modeling program data for dry deposition and wet deposition estimates from the National Atmospheric Deposition Program (NADP). Here we examine wet, dry and total deposition estimates based on these two approaches. Overall, estimates of wet deposition of S and N comparisons showed close agreement (r2 = 0.79 to 0.83) while estimates of dry deposition based on the two approaches varied considerably (r2 = 0.25 to 0.67). Relative to deposition measured at NADP sites, CMAQ values slightly over represented wet sulfate deposition, but slightly underrepresented wet nitrate and ammonium input. However, CMAQ-estimated dry deposition of nitric acid was much higher than CASTNET-estimated deposition, while dry ammonium and nitrate were much lower using the CMAQ model. When compared spatially, regions that showed large differences in total N and S deposition included the Midwest and west central Appalachian mountains, showing differences of up to 6kgN or S/ha/yr.

  1. 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.

  2. Managing mechanistic and organic structure in health care organizations.

    PubMed

    Olden, Peter C

    2012-01-01

    Managers at all levels in a health care organization must organize work to achieve the organization's mission and goals. This requires managers to decide the organization structure, which involves dividing the work among jobs and departments and then coordinating them all toward the common purpose. Organization structure, which is reflected in an organization chart, may range on a continuum from very mechanistic to very organic. Managers must decide how mechanistic versus how organic to make the entire organization and each of its departments. To do this, managers should carefully consider 5 factors for the organization and for each individual department: external environment, goals, work production, size, and culture. Some factors may push toward more mechanistic structure, whereas others may push in the opposite direction toward more organic structure. Practical advice can help managers at all levels design appropriate structure for their departments and organization.

  3. Cognitive science as an interface between rational and mechanistic explanation.

    PubMed

    Chater, Nick

    2014-04-01

    Cognitive science views thought as computation; and computation, by its very nature, can be understood in both rational and mechanistic terms. In rational terms, a computation solves some information processing problem (e.g., mapping sensory information into a description of the external world; parsing a sentence; selecting among a set of possible actions). In mechanistic terms, a computation corresponds to causal chain of events in a physical device (in engineering context, a silicon chip; in biological context, the nervous system). The discipline is thus at the interface between two very different styles of explanation--as the papers in the current special issue well illustrate, it explores the interplay of rational and mechanistic forces.

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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…

  9. 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

  10. 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...

  11. 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 ...

  12. 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

  13. Answering evolutionary questions: A guide for mechanistic biologists.

    PubMed

    Masel, Joanna; Promislow, Daniel E L

    2016-07-01

    The questions and methods of molecular biology and evolutionary biology are clearly distinct, yet a unified approach can lead to deep insights. Unfortunately, attempts to unify these approaches are fraught with pitfalls. In this informal series of questions and answers, we offer the mechanistically oriented biologist a set of steps to come up with evolutionarily reasonable and meaningful hypotheses. We emphasize the critical power and importance of carefully constructed null hypotheses, and we illustrate our ideas with examples representing a range of topics, from the biology of aging, to protein structure, to speciation, and more. We also stress the importance of mathematics as the lingua franca for biologists of all stripes, and encourage mechanistic biologists to seek out quantitative collaborators to build explicit mathematical models, making their assumptions explicit, and their logic clear and testable. Biologists in all realms of inquiry stand to gain from strong bridges between our disciplines. PMID:27151396

  14. 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.

  15. 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

  16. Underreliance on mechanistic models: Comment on Ferguson (2015).

    PubMed

    Tryon, Warren W

    2016-09-01

    Ferguson (see record ) proposed that our overreliance on mechanistic models is responsible for the public's negative view of psychology. On the contrary, I claim that our explanations do not actually explain because they lack mechanism information and that is why the public has a negative view of psychology. Some of the mechanism information required to move from interpretations to explanations can be found in parallel distributed processing connectionist neural network models of psychology and behavior. (PsycINFO Database Record PMID:27571530

  17. Millifluidics for chemical synthesis and time-resolved mechanistic studies.

    PubMed

    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

  18. Home range analysis using a mechanistic home range model

    SciTech Connect

    Moorcroft, P.R. . Dept. of Ecology and Evolutionary Biology); Lewis, M.A. . Dept. of Mathematics) Crabtree, R.L. . Dept. of Fish and Wildlife Resources)

    1999-07-01

    The traditional models used to characterize animal home ranges have no mechanistic basis underlying their descriptions of space use, and as a result, the analysis of animal home ranges has primarily been a descriptive endeavor. In this paper, the authors characterize coyote (Canis latrans) home range patterns using partial differential equations for expected space use that are formally derived from underlying descriptions of individual movement behavior. To the authors' knowledge, this is the first time that mechanistic models have been used to characterize animal home ranges. The results provide empirical support for a model formulation of movement response to scent marks, and suggest that having relocation data for individuals in adjacent groups is necessary to capture the spatial arrangement of home range boundaries. The authors then show how the model fits can be used to obtain predictions for individual movement and scent marking behavior and to predict changes in home range patterns. More generally, the findings illustrate how mechanistic models permit the development of a predictive theory for the relationship between movement behavior and animal spatial distribution.

  19. Mechanistic modelling and mechanistic monitoring: simulation and shadowgraph imaging of particulate dissolution in the flow-through apparatus.

    PubMed

    D'arcy, Deirdre M; Persoons, Tim

    2011-03-01

    Accurate mechanistic modelling of a complex system requires insight into the process being simulated, in addition to a theoretical 'first-principles' approach. The current work uses a numerical mechanistic model to simulate dissolution of a particulate system in the flow-through dissolution apparatus. A shadowgraph imaging method is also used to monitor the dissolution process, providing real-time estimates of particle motion, number and total dissolution time. Experimental dissolution studies of ibuprofen particles are used to assess the accuracy of the model. The numerical model adequately predicts the ibuprofen particle dissolution rate at 16 mL min(-1) . Parameter sensitivity analysis identified dissolution test circumstances requiring more, or less, accuracy in the particle size and density calculations. The shadowgraph imaging method successfully determined the total dissolution time and decreasing particle numbers over time. The images confirmed the pulsing particle motion of the numerical model but revealed some more complex velocity patterns, assisting numerical model development. Further optimisation of the sampling window is required to capture all relevant particle motion and changing particle size distribution. A mechanistic model can successfully simulate particulate dissolution in the flow-through apparatus, and when used along with shadowgraph imaging, can give valuable insight into the dissolution process mechanisms and environment. PMID:20848646

  20. Advanced Reach Tool (ART): development of the mechanistic model.

    PubMed

    Fransman, Wouter; Van Tongeren, Martie; Cherrie, John W; Tischer, Martin; Schneider, Thomas; Schinkel, Jody; Kromhout, Hans; Warren, Nick; Goede, Henk; Tielemans, Erik

    2011-11-01

    This paper describes the development of the mechanistic model within a collaborative project, referred to as the Advanced REACH Tool (ART) project, to develop a tool to model inhalation exposure for workers sharing similar operational conditions across different industries and locations in Europe. The ART mechanistic model is based on a conceptual framework that adopts a source receptor approach, which describes the transport of a contaminant from the source to the receptor and defines seven independent principal modifying factors: substance emission potential, activity emission potential, localized controls, segregation, personal enclosure, surface contamination, and dispersion. ART currently differentiates between three different exposure types: vapours, mists, and dust (fumes, fibres, and gases are presently excluded). Various sources were used to assign numerical values to the multipliers to each modifying factor. The evidence used to underpin this assessment procedure was based on chemical and physical laws. In addition, empirical data obtained from literature were used. Where this was not possible, expert elicitation was applied for the assessment procedure. Multipliers for all modifying factors were peer reviewed by leading experts from industry, research institutes, and public authorities across the globe. In addition, several workshops with experts were organized to discuss the proposed exposure multipliers. The mechanistic model is a central part of the ART tool and with advancing knowledge on exposure, determinants will require updates and refinements on a continuous basis, such as the effect of worker behaviour on personal exposure, 'best practice' values that describe the maximum achievable effectiveness of control measures, the intrinsic emission potential of various solid objects (e.g. metal, glass, plastics, etc.), and extending the applicability domain to certain types of exposures (e.g. gas, fume, and fibre exposure).

  1. 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.

  2. [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.

  3. A mechanistic, stochastic, population model of egg production.

    PubMed

    Johnston, S A; Gous, R M

    2007-04-01

    1. A mechanistic, stochastic egg production model is presented. Mean age at first egg may be predicted from the lighting programme applied during rearing, using the Bristol-Reading model (Lewis et al., 2002). 2. Rate of ovulation is determined by an amended version of the mathematical model of the ovulatory cycle, originally proposed by Etches and Schoch (1984). 3. Oviposition times are estimated from ovulation times. 4. Yolk, albumen and shell weights are calculated using allometric functions. 5. The model predicts egg production of a theoretical flock of laying hens for a full laying year, including random occurrences of double-yolked and soft-shelled eggs and internal ovulations.

  4. Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.

    PubMed

    Cotton, Travis B; Nguyen, Hien H; Said, Joseph I; Ouyang, Zhengyu; Zhang, Jinfa; Song, Mingzhou

    2015-01-01

    Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in differentiating rewired chaotic systems, whose dynamics are notoriously difficult to predict. Applying the Q-method on transcriptome data of four yeasts, we show that pathway interaction heterogeneity for known metabolic and signaling pathways is indeed a predictor of interspecies genetic rewiring due to unbalanced TATA box-containing genes among the yeasts. The demonstrated effectiveness of the Q-method paves the way to understanding network evolution at the resolution of functional biological pathways. PMID:25921728

  5. New web-based applications for mechanistic case diagramming

    PubMed Central

    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. PMID:25059836

  6. Mechanistic study of a diazo dye degradation by Soybean Peroxidase

    PubMed Central

    2013-01-01

    Background Enzyme based remediation of wastewater is emerging as a novel, efficient and environmentally-friendlier approach. However, studies showing detailed mechanisms of enzyme mediated degradation of organic pollutants are not widely published. Results The present report describes a detailed study on the use of Soybean Peroxidase to efficiently degrade Trypan Blue, a diazo dye. In addition to examining various parameters that can affect the dye degradation ability of the enzyme, such as enzyme and H2O2 concentration, reaction pH and temperature, we carried out a detailed mechanistic study of Trypan Blue degradation. HPLC-DAD and LC-MS/MS studies were carried out to confirm dye degradation and analyze the intermediate metabolites and develop a detailed mechanistic dye degradation pathway. Conclusion We report that Soybean peroxidase causes Trypan Blue degradation via symmetrical azo bond cleavage and subsequent radical-initiated ring opening of the metabolites. Interestingly, our results also show that no high molecular weight polymers were produced during the peroxidase-H2O2 mediated degradation of the phenolic Trypan Blue. PMID:23711110

  7. 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.

  8. Grignard Reaction of an Epoxide: A Mechanistic Study

    NASA Astrophysics Data System (ADS)

    Ciaccio, James A.; Volpi, Sabrina; Clarke, Ransford

    1996-12-01

    Addition of PhMgBr to styrene oxide (1) affords a mixture of 2,2-diphenylethanol (3) and 1,2-diphenylethanol (6) (3:6 = 1:3); reversing the order of addition inverts the ratio of 3 to 6 formed (3:6 = 2:1). Students identify 3 and 6 by TLC comparison with authentic samples which they prepare by independent synthesis (hydride reduction of the corresponding carbonyl compounds), and establish the ratios of 3 to 6 by a combination of 1H and 13C NMR spectroscopies. This undergraduate experiment serves as an interesting alternative to more traditional Grignard experiments and is an excellent vehicle for a "discovery-based" experiment in which students are introduced to epoxide chemistry, share their laboratory data and make mechanistic conclusions from their experimental results. Unlike most undergraduate Grignard experiments which are performed merely for the sake of illustrating a textbook reaction, this Grignard synthesis is performed to probe the reactivity of styrene oxide. Students are required to analyze their products by TLC and NMR spectroscopy (instead of just submitting them for a grade) in order to obtain the data necessary for making mechanistic conclusions.

  9. 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.

  10. 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

  11. 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

  12. Water on hydrophobic surfaces: Mechanistic modeling of hydrophobic interaction chromatography.

    PubMed

    Wang, Gang; Hahn, Tobias; Hubbuch, Jürgen

    2016-09-23

    Mechanistic models are successfully used for protein purification process development as shown for ion-exchange column chromatography (IEX). Modeling and simulation of hydrophobic interaction chromatography (HIC) in the column mode has been seldom reported. As a combination of these two techniques is often encountered in biopharmaceutical purification steps, accurate modeling of protein adsorption in HIC is a core issue for applying holistic model-based process development, especially in the light of the Quality by Design (QbD) approach. In this work, a new mechanistic isotherm model for HIC is derived by consideration of an equilibrium between well-ordered water molecules and bulk-like ordered water molecules on the hydrophobic surfaces of protein and ligand. The model's capability of describing column chromatography experiments is demonstrated with glucose oxidase, bovine serum albumin (BSA), and lysozyme on Capto™ Phenyl (high sub) as model system. After model calibration from chromatograms of bind-and-elute experiments, results were validated with batch isotherms and prediction of further gradient elution chromatograms. PMID:27575919

  13. 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.

  14. 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

  15. A mechanistic model of global soil nitric oxide emissions: Predictions and Evaluation

    NASA Astrophysics Data System (ADS)

    Cohen, R. C.; Hudman, R. C.

    2011-12-01

    We describe a mechanistic global model of soil nitric oxide emissions (SNOx) as implemented in a chemical transport model (GEOS-Chem) and evaluated using tropospheric NO2 column measurements from the Ozone Monitoring Instrument (OMI). The model has a continuous dependence on soil moisture, pulsed emissions, and an improved N-fertilizer and manure representation, and includes effects associated with N-deposition to natural soils. Global above-canopy SNOx estimates are 7.6 Tg N yr-1, with 1.4 Tg N yr-1 from fertilizer/manure N input (0.62% of applied N) and 0.5 Tg N yr-1 from atmospheric N-deposition. Relative to previous models, the largest enhancements are predicted over the African Sahel during the monsoon onset (April -June). We show that OMI mean (median) NO2 on the overpass following first rainfall are 50% (20%) higher than in the five days preceding. The NO2 on the day after rainfall is still 20% (5%) higher, suggesting pulses last on average 1-2 days, consistent with the pulsing representation used here and shorter than 5-14 days used in current models. Over the United States Great Plains, SNOx is predicted to contribute 15-40% of NOx emissions and to increase variability by a factor of 2-4. We find the model is able to reproduce the observed pulsed-N induced interannual variability over the region giving us confidence in the soil moisture/temperature relationship used as well as the magnitude of the fertilizer response.

  16. Emerging Mechanistic Targets in Lung Injury Induced by Combustion-Generated Particles

    PubMed Central

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

    2013-01-01

    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. PMID:23322347

  17. Respiratory cancer risks associated with low-level nickel exposure: an integrated assessment based on animal, epidemiological, and mechanistic data.

    PubMed

    Seilkop, Steven K; Oller, Adriana R

    2003-04-01

    Increased lung and nasal cancer risks have been reported in several cohorts of nickel refinery workers, but in more than 90% of the nickel-exposed workers that have been studied there is little, if any evidence of excess risk. This investigation utilizes human exposure measurements, animal data from cancer bioassays of three nickel compounds, and a mechanistic theory of nickel carcinogenesis to reconcile the disparities in lung cancer risk among nickel-exposed workers. Animal data and mechanistic theory suggest that the apparent absence of risk in workers with low nickel exposures is due to threshold-like responses in lung tumor incidence (oxidic nickel), tumor promotion (soluble nickel), and genetic damage (sulfidic nickel). When animal-based lung cancer dose-response functions for these compounds are extrapolated to humans, taking into account interspecies differences in deposition and clearance, differences in particle size distributions, and human work activity patterns, the predicted risks at occupational exposures are remarkably similar to those observed in nickel-exposed workers. This provides support for using the animal-based dose-response functions to estimate occupational exposure limits, which are found to be comparable to those in current use. PMID:12726752

  18. 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.

  19. 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

  20. 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

  1. 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.

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

    PubMed Central

    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. PMID:27057292

  3. Mechanistic insights into selective autophagy pathways: lessons from yeast.

    PubMed

    Farré, Jean-Claude; Subramani, Suresh

    2016-09-01

    Autophagy has burgeoned rapidly as a field of study because of its evolutionary conservation, the diversity of intracellular cargoes degraded and recycled by this machinery, the mechanisms involved, as well as its physiological relevance to human health and disease. This self-eating process was initially viewed as a non-selective mechanism used by eukaryotic cells to degrade and recycle macromolecules in response to stress; we now know that various cellular constituents, as well as pathogens, can also undergo selective autophagy. In contrast to non-selective autophagy, selective autophagy pathways rely on a plethora of selective autophagy receptors (SARs) that recognize and direct intracellular protein aggregates, organelles and pathogens for specific degradation. Although SARs themselves are not highly conserved, their modes of action and the signalling cascades that activate and regulate them are. Recent yeast studies have provided novel mechanistic insights into selective autophagy pathways, revealing principles of how various cargoes can be marked and targeted for selective degradation. PMID:27381245

  4. 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.

  5. Mechanistic issues concerning cancer prevention by tea catechins.

    PubMed

    Yang, Chung S; Wang, Hong

    2011-06-01

    The cancer preventive activities of tea (Camellia sinensis, Theaceae) have been demonstrated in animal models for cancers at different organ sites and suggested by some epidemiological studies. Many mechanisms for cancer prevention have been proposed based on studies in cell lines, which demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events may result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, it is not known whether these are the molecular mechanisms of inhibition of carcinogenesis in animals and humans. This article discusses the key issues involved in extrapolating results from cell line studies to mechanistic information in vivo and in translating animal studies to human cancer prevention. PMID:21538856

  6. Synthetic and mechanistic aspects of titanium-mediated carbonyl olefinations

    SciTech Connect

    Petasis, N.A.; Staszewski, J.P.; Hu, Yong-Han; Lu, Shao-Po

    1995-12-31

    A new method for the olefination of carbonyl compounds with dimethyl titanocene, and other related bishydrocarbyl titanocene derivatives has been recently developed in the author`s laboratories. This process is experimentally convenient and works with various types of carbonyl compounds, including aldehydes, ketones, esters, lactones, carbonates, anhydrides, amides, imides, lactams, thioesters, selenoesters, and acylsilanes. More recent studies have focused on the scope and utility of this reaction, including mechanistic studies and synthetic applications. In addition to varying the reaction conditions, the authors have examined several mixed titanocene derivatives and have found ways for carrying out this type of olefination at room temperature, such as the use of tris(trimethylsilyl) titanacyclobutene. The authors have also employed this reaction in the modification of carbohydrates and cyclobutenediones. This olefination was also followed-up with subsequent transformations to produce carbocycles and heterocycles, including tetrahydrofurans and tetrahydropyrans.

  7. 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. PMID:27057292

  8. 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.

  9. Mechanistic model for void distribution in flashing flow

    NASA Astrophysics Data System (ADS)

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

    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.

  10. 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

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

    PubMed

    Phair, Robert D

    2014-11-01

    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.

  12. Mechanistic failure mode investigation and resolution of parvovirus retentive filters.

    PubMed

    LaCasse, Daniel; Lute, Scott; Fiadeiro, Marcus; Basha, Jonida; Stork, Matthew; Brorson, Kurt; Godavarti, Ranga; Gallo, Chris

    2016-07-01

    Virus retentive filters are a key product safety measure for biopharmaceuticals. A simplistic perception is that they function solely based on a size-based particle removal mechanism of mechanical sieving and retention of particles based on their hydrodynamic size. Recent observations have revealed a more nuanced picture, indicating that changes in viral particle retention can result from process pressure and/or flow interruptions. In this study, a mechanistic investigation was performed to help identify a potential mechanism leading to the reported reduced particle retention in small virus filters. Permeate flow rate or permeate driving force were varied and analyzed for their impact on particle retention in three commercially available small virus retentive filters. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:959-970, 2016.

  13. Obesity, energy balance, and cancer: a mechanistic perspective.

    PubMed

    Hursting, Stephen D

    2014-01-01

    Nearly 36 % of adults and 20 % of children in the USA are obese, defined as a body mass index (BMI) ≥30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and/or progression. This chapter synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes, as well as obesity-dependent microenvironmental perturbations, including the epithelial-to-mesenchymal transition. These interrelated pathways represent possible mechanistic targets for disrupting the obesity-cancer link.

  14. Mechanistic modeling confronts the complexity of molecular cell biology

    PubMed Central

    Phair, Robert D.

    2014-01-01

    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. PMID:25368428

  15. 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.

  16. Mechanistic models of biofilm growth in porous media

    NASA Astrophysics Data System (ADS)

    Jaiswal, Priyank; Al-Hadrami, Fathiya; Atekwana, Estella A.; Atekwana, Eliot A.

    2014-07-01

    Nondestructive acoustics methods can be used to monitor in situ biofilm growth in porous media. In practice, however, acoustic methods remain underutilized due to the lack of models that can translate acoustic data into rock properties in the context of biofilm. In this paper we present mechanistic models of biofilm growth in porous media. The models are used to quantitatively interpret arrival times and amplitudes recorded in the 29 day long Davis et al. (2010) physical scale biostimulation experiment in terms of biofilm morphologies and saturation. The model pivots on addressing the sediment elastic behavior using the lower Hashin-Shtrikman bounds for grain mixing and Gassmann substitution for fluid saturation. The time-lapse P wave velocity (VP; a function of arrival times) is explained by a combination of two rock models (morphologies); "load bearing" which assumes the biofilm as an additional mineral in the rock matrix and "pore filling" which assumes the biofilm as an additional fluid phase in the pores. The time-lapse attenuation (QP-1; a function of amplitudes), on the other hand, can be explained adequately in two ways; first, through squirt flow where energy is lost from relative motion between rock matrix and pore fluid, and second, through an empirical function of porosity (φ), permeability (κ), and grain size. The squirt flow model-fitting results in higher internal φ (7% versus 5%) and more oblate pores (0.33 versus 0.67 aspect ratio) for the load-bearing morphology versus the pore-filling morphology. The empirical model-fitting results in up to 10% increase in κ at the initial stages of the load-bearing morphology. The two morphologies which exhibit distinct mechanical and hydraulic behavior could be a function of pore throat size. The biofilm mechanistic models developed in this study can be used for the interpretation of seismic data critical for the evaluation of biobarriers in bioremediation, microbial enhanced oil recovery, and CO2

  17. Antiproliferative naphthopyrans: biological activity, mechanistic studies and therapeutic potential.

    PubMed

    Dell, C P

    1998-06-01

    This article will firstly briefly review the newer generation of immunosuppressant drugs, focusing mainly on tacrolimus (FK-506), sirolimus (rapamycin), mycophenolate mofetil (RS-61443) and leflunomide (HWA 486) and then describe work carried out at the Lilly Research Centre on analogues of leflunomide and subsequent diversion into a structurally distinct series of compounds, the naphthopyrans. A clear structure activity relationship exists within this series and selected data from a Concanavalin A stimulated T-cell proliferation assay are presented to illustrate this. Although the compounds proved to possess little in vivo activity in our rheumatoid arthritis program, examination of the compounds in in vitro and in vivo models within the diabetic complications group showed the compounds behaved as would be anticipated for inhibitors of protein kinase C, although this direct mode of action was clearly not correct. Mechanistic investigations revealed that the favoured compound 290181 blocks phorbol 12,13-dibutyrate-induced binding of transcription factor proteins to the PEA3/TRE sequence of the promoter region of the urokinase plasminogen activator gene. The compounds also showed antiproliferative effects on vascular smooth muscle cells, an in vitro activity that translated into in vivo efficacy in a rat model of restenosis. Mechanistic studies here demonstrated that 290181 blocks proliferation in the G2/M phase of the cell cycle by binding directly to a novel site on tubulin. Finally the compounds were shown to inhibit the release of neutral proteases from interleukin-1 stimulated articular chondrocytes, this activity having implications in the degenerative aspects of osteoarthritis. PMID:9562601

  18. 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

  19. 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.

  20. Toxic neuropathies: Mechanistic insights based on a chemical perspective.

    PubMed

    LoPachin, Richard M; Gavin, Terrence

    2015-06-01

    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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

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

    NASA Astrophysics Data System (ADS)

    Ogee, J.; Sauze, J.; Kesselmeier, J.; Genty, B.; Whelan, M.; Launois, T.; Wingate, L.

    2015-12-01

    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 sulphide (OCS) has been proposed as a new tracer of gross photosynthesis (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. But 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 or anoxic soils. To date no mechanistic framework exists to describe this exchange of OCS between soils and the atmosphere but empirical results, once up-scaled to the global scale, indicate that OCS consumption by soils dominates over production and its contribution to the atmospheric budget is large, at about one third of the OCS uptake by vegetation, with also 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 emissions. 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. In order to simulate the exact OCS uptake rates and patterns observed on several soils collected from a range of biomes, different CA activities

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

    NASA Astrophysics Data System (ADS)

    Ogée, J.; Sauze, J.; Kesselmeier, J.; Genty, B.; Van Diest, H.; Launois, T.; Wingate, L.

    2015-09-01

    Estimates of photosynthetic and respiratory fluxes at large scales is needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulphide (OCS) is the most abundant sulphur gas in the atmosphere and has been proposed as a new tracer of photosynthesis (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. But 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 over production and its contribution to the atmospheric budget is large, at about one third of the OCS uptake by vegetation, with also 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 emissions. 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 depth observed previously. In

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Cascadia Tsunami Deposit Database

    USGS Publications Warehouse

    Peters, Robert; Jaffe, Bruce; Gelfenbaum, Guy; Peterson, Curt

    2003-01-01

    The Cascadia Tsunami Deposit Database contains data on the location and sedimentological properties of tsunami deposits found along the Cascadia margin. Data have been compiled from 52 studies, documenting 59 sites from northern California to Vancouver Island, British Columbia that contain known or potential tsunami deposits. Bibliographical references are provided for all sites included in the database. Cascadia tsunami deposits are usually seen as anomalous sand layers in coastal marsh or lake sediments. The studies cited in the database use numerous criteria based on sedimentary characteristics to distinguish tsunami deposits from sand layers deposited by other processes, such as river flooding and storm surges. Several studies cited in the database contain evidence for more than one tsunami at a site. Data categories include age, thickness, layering, grainsize, and other sedimentological characteristics of Cascadia tsunami deposits. The database documents the variability observed in tsunami deposits found along the Cascadia margin.

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

    NASA Astrophysics Data System (ADS)

    Schouten, Hans; Klitgord, Kim D.

    1994-06-01

    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 ˜150 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 Yucatan Basin.

  15. Mechanistic Features of Nanodiamonds in the Lapping of Magnetic Heads

    PubMed Central

    Jiang, Xionghua; Chen, Zhenxing; Wolfram, Joy; Yang, Zhizhou

    2014-01-01

    Nanodiamonds, which are the main components of slurry in the precision lapping process of magnetic heads, play an important role in surface quality. This paper studies the mechanistic features of nanodiamond embedment into a Sn plate in the lapping process. This is the first study to develop mathematical models for nanodiamond embedment. Such models can predict the optimum parameters for particle embedment. From the modeling calculations, the embedded pressure satisfies p0 = (3/2)·(W/πa2) and the indentation depth satisfies δ=k1P/HV. Calculation results reveal that the largest embedded pressure is 731.48 GPa and the critical indentation depth δ is 7 nm. Atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger electron spectroscopy (AES) were used to carry out surface quality detection and analysis of the disk head. Both the formation of black spots on the surface and the removal rate have an important correlation with the size of nanodiamonds. The results demonstrate that an improved removal rate (21 nm·min−1) can be obtained with 100 nm diamonds embedded in the plate. PMID:25045730

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

    PubMed

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

    2015-03-31

    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.

  17. 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

  18. Thermal hydrogen-atom transfer from methane: A mechanistic exercise

    NASA Astrophysics Data System (ADS)

    Schwarz, Helmut

    2015-06-01

    Hydrogen-atom transfer (HAT) constitutes a key process in a broad range of chemical transformations as it covers heterogeneous, homogeneous, and enzymatic reactions. While open-shell metal oxo species [MO]rad are no longer regarded as being involved in the heterogeneously catalyzed oxidative coupling of methane (2CH4 + → C2H6 + H2O), these reagents are rather versatile in bringing about (gas-phase) hydrogen-atom transfer, even from methane at ambient conditions. In this mini-review, various mechanistic scenarios will be presented, and it will be demonstrated how these are affected by the composition of the metal-oxide cluster ions. Examples will be discussed, how 'doping' the clusters permits the control of the charge and spin situation at the active site and, thus, the course of the reaction. Also, the interplay between supposedly inert support material and the active site - the so-called 'aristocratic atoms' - of the gas-phase catalyst will be addressed. Finally, gas-phase HAT from methane will be analyzed in the broader context of thermal activation of inert Csbnd H bonds by metal-oxo species.

  19. Spectroscopic and Mechanistic Investigations of Dehaloperoxidase B from Amphitrite ornata†

    PubMed Central

    D’Antonio, Jennifer; D’Antonio, Edward L.; Thompson, Matthew K.; Bowden, Edmond F.; Franzen, Stefan; Smirnova, Tatyana; Ghiladi, Reza A.

    2010-01-01

    Dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a bifunctional enzyme that possesses both hemoglobin and peroxidase activities. Of the two DHP isoenzymes identified to date, much of the recent focus has been on DHP A, whereas very little is known pertaining to the activity, substrate specificity, mechanism of function, or spectroscopic properties of DHP B. Herein, we report the recombinant expression and purification of DHP B, as well as the details of our investigations into its catalytic cycle using biochemical assays, stopped-flow UV-visible, resonance Raman and rapid-freeze-quench electron paramagnetic resonance spectroscopies, and spectroelectrochemistry. Our experimental design reveals mechanistic insights and kinetic descriptions of the dehaloperoxidase mechanism which have not been previously reported for isoenzyme A. Namely, we demonstrate a novel reaction pathway in which the products of the oxidative dehalogenation of trihalophenols (dihaloquinones) are themselves capable of inducing formation of oxyferrous DHP B, and an updated catalytic cycle for DHP is proposed. We further demonstrate that unlike the traditional monofunctional peroxidases, the oxyferrous state in DHP is a peroxidase competent starting species, which suggests that the ferric oxidation state may not be an obligatory starting point for the enzyme. The data presented herein provide a link between the peroxidase and oxygen transport activities which furthers our understanding of how this bifunctional enzyme is able to unite its two inherent functions in one system. PMID:20545299

  20. 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

  1. 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.

  2. 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. PMID:23810463

  3. Mechanistic basis of infertility of mouse intersubspecific hybrids.

    PubMed

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

    2013-02-01

    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.

  4. 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

  5. A mechanistic compartmental model for total antibody uptake in tumors.

    PubMed

    Thurber, Greg M; Dane Wittrup, K

    2012-12-01

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. PMID:22974563

  6. A mechanistic compartmental model for total antibody uptake in tumors

    PubMed Central

    Thurber, Greg M.; Dane Wittrup, K.

    2012-01-01

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. PMID:22974563

  7. Mechanistic modelling of toxicokinetic processes within Myriophyllum spicatum.

    PubMed

    Heine, S; Schmitt, W; Schäffer, A; Görlitz, G; Buresová, H; Arts, G; Preuss, T G

    2015-02-01

    Effects of chemicals are, in most cases, caused by internal concentrations within organisms which rely on uptake and elimination kinetics. These processes might be key components for assessing the effects of time-variable exposure of chemicals which regularly occur in aquatic systems. However, the knowledge of toxicokinetic patterns caused by time-variable exposure is limited, and gaining such information is complex. In this work, a previously developed mechanistic growth model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic part, providing a model that is able to predict uptake and elimination of chemicals, as well as distribution processes between plant compartments (leaves, stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least for most of the investigated chemicals, can be calculated in agreement with experimental observations, by only calibrating two chemical- specific parameters, the cuticular permeability and a plant/water partition coefficient. Through the model-based determination of the cuticular permeabilities of Isoproturon, Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern can be described with the model approach. For the use of the model for predicting toxicokinetics of other chemicals, where experimental data is not available, equations are presented that are based on the log (P oct/wat) of a chemical and estimate parameters that are necessary to run the model. In general, a method is presented to analyze time-variable exposure of chemicals more in detail without conducting time and labour intensive experiments. PMID:25129053

  8. 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

  9. 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.

  10. 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. PMID:24382337

  11. 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. PMID:25846609

  12. A Mechanistic Stochastic Ricker Model: Analytical and Numerical Investigations

    NASA Astrophysics Data System (ADS)

    Gadrich, Tamar; Katriel, Guy

    The Ricker model is one of the simplest and most widely-used ecological models displaying complex nonlinear dynamics. We study a discrete-time population model, which is derived from simple assumptions concerning individual organisms’ behavior, using the “site-based” approach, developed by Brännström, Broomhead, Johansson and Sumpter. In the large-population limit the model converges to the Ricker model, and can thus be considered a mechanistic version of the Ricker model, derived from basic ecological principles, and taking into account the demographic stochasticity inherent to finite populations. We employ several analytical and precise numerical methods to study the model, showing how each approach contributes to understanding the model’s dynamics. Expressing the model as a Markov chain, we employ the concept of quasi-stationary distributions, which are computed numerically, and used to examine the interaction between complex deterministic dynamics and demographic stochasticity, as well as to calculate mean times to extinction. A Gaussian Markov chain approximation is used to obtain quantitative asymptotic approximations for the size of fluctuations of the stochastic model’s time series around the deterministic trajectory, and for the correlations between successive fluctuations. Results of these approximations are compared to results obtained from quasi-stationary distributions and from direct simulations, and are shown to be in good agreement.

  13. 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

  14. 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

  15. 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.

  16. 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. PMID:23742888

  17. 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.

  18. 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.

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

    PubMed

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

    2011-12-01

    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.

  20. Mechanistic Enzymology of the Radical SAM Enzyme DesII

    PubMed Central

    2016-01-01

    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.

  1. 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.

  2. Mechanistic overview of immune modulatory effects of environmental toxicants.

    PubMed

    Bahadar, Haji; Abdollahi, Mohammad; Maqbool, Faheem; Baeeri, Maryam; Niaz, Kamal

    2015-01-01

    The immune system is an integrated organization, comprising of specific organs, cells and molecules playing a crucial role in the maintenance of health. The purpose of this paper is to give a mechanistic overview of toxic effects of various chemicals and pharmacological agents, and their interaction with the various components of the immune system that leads to modulation of the immune responses. Studies suggest that many chemical agents present in the environment like; heavy metals, agrochemicals, and various types of hydrocarbons possess immune toxicity and cause either structural, functional or compositional changes in various components of the immune system that alters immune response. There is present a complex bidirectional relationship between central nervous system (CNS) and the immune system. And receptors for neuropeptides, neurotransmitters, and hormones are located on lymphoid organs. Therefore, we are of the opinion that Endocrine Disrupting Chemicals (EDCs) present in our environment may be indirectly involved in causing immune toxicity via neuroendocrine channels, and vice versa many neurological disorders may be associated with environmental pollutants utilizing immuno-neuroendocrine pathways.

  3. Functional and mechanistic diversity of distal transcription enhancers

    PubMed Central

    Bulger, Michael; Groudine, Mark

    2013-01-01

    Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. PMID:21295696

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

    PubMed

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

    2015-03-31

    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

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

    PubMed

    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

  6. Ancient Chinese medicine and mechanistic evidence of acupuncture physiology.

    PubMed

    Yang, Edward S; Li, Pei-Wen; Nilius, Bernd; Li, Geng

    2011-11-01

    Acupuncture has been widely used in China for three millennia as an art of healing. Yet, its physiology is not yet understood. The current interest in acupuncture started in 1971. Soon afterward, extensive research led to the concept of neural signaling with possible involvement of opioid peptides, glutamate, adenosine and identifying responsive parts in the central nervous system. In the last decade scientists began investigating the subject with anatomical and molecular imaging. It was found that mechanical movements of the needle, ignored in the past, appear to be central to the method and intracellular calcium ions may play a pivotal role. In this review, we trace the technique of clinical treatment from the first written record about 2,200 years ago to the modern time. The ancient texts have been used to introduce the concepts of yin, yang, qi, de qi, and meridians, the traditional foundation of acupuncture. We explore the sequence of the physiological process, from the turning of the needle, the mechanical wave activation of calcium ion channel to beta-endorphin secretion. By using modern terminology to re-interpret the ancient texts, we have found that the 2nd century B.C.: physiologists were meticulous investigators and their explanation fits well with the mechanistic model derived from magnetic resonance imaging (MRI) and confocal microscopy. In conclusion, the ancient model appears to have withstood the test of time surprisingly well confirming the popular axiom that the old wine is better than the new.

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

    PubMed Central

    Shkrob, Ilya A.; Marin, Timothy M.; Chemerisov, Sergey D.; Sevilla, Michael D.

    2011-01-01

    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 TiO2, α-FeOOH, and α-Fe2O3 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 TiO2 oxidizes all of the carbohydrates and polyols, whereas α-FeOOH oxidizes some of the carbohydrates, and α-Fe2O3 is unreactive. These results serve as a stepping stone for understanding the photochemistry on mineral surfaces of more complex biomolecules such as nucleic acids. PMID:21532934

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

    PubMed

    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

  9. Mechanistic insight into the photosensory versatility of DXCF cyanobacteriochromes.

    PubMed

    Rockwell, Nathan C; Martin, Shelley S; Lagarias, J Clark

    2012-05-01

    Cyanobacteriochromes (CBCRs) are photosensory proteins related to the red/far-red phytochromes. Like phytochromes, CBCRs use linear tetrapyrrole (bilin) chromophores covalently attached via a thioether linkage to a conserved Cys residue also found in plant and cyanobacterial phytochromes. Unlike almost all phytochromes, CBCRs require only an isolated GAF domain to undergo efficient, reversible photocycles that are responsible for their broad light sensing range, spanning the visible to the near ultraviolet (UV). Sensing of blue, violet, and near-UV light by CBCRs requires another Cys residue proposed to form a second linkage to the bilin precursor. Light triggers 15,16-double bond isomerization as in phytochromes. After photoisomerization, elimination of the second linkage frequently occurs, thus yielding a large red shift of the stable photoproducts. Here we examine this process for representative DXCF CBCRs, a large subfamily named for the conserved Asp-Xaa-Cys-Phe motif that contains their second Cys residue. DXCF CBCRs with such dual-Cys photocycles yield a wide diversity of photoproducts absorbing teal, green, or orange light. Using a combination of CD spectroscopy, chemical modification, and bilin substitution experiments with recombinant CBCRs from Thermosynechococcus elongatus and Nostoc punctiforme expressed in Escherichia coli, we establish that second-linkage elimination is required for all of these photocycles. We also identify deconjugation of the D-ring as the mechanism for specific detection of teal light, at approximately 500 nm. Our studies thus provide new mechanistic insight into the photosensory versatility of this important family of photosensory proteins.

  10. 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

  11. 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

  12. 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.

  13. 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. PMID:25847385

  14. 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

  15. 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

  16. The road to advanced glycation end products: a mechanistic perspective.

    PubMed

    Cho, S-J; Roman, G; Yeboah, F; Konishi, Y

    2007-01-01

    Protein glycation is a slow natural process involving the chemical modification of the reactive amino and guanidine functions in amino acids by sugars and carbohydrates-derived reactive carbonyls. Its deleterious consequences are obvious in the case of long-lived proteins in aged people and are exacerbated by the high blood concentration of sugars in diabetic patients. The non-enzymatic glycation of proteins occurs through a wide range of concurrent processes comprising condensation, rearrangement, fragmentation, and oxidation reactions. Using a few well established intermediates such as Schiff base, Amadori product and reactive a-dicarbonyls as milestones and the results of in vitro glycation investigations, an overall detailed mechanistic analysis of protein glycation is presented for the first time. The pathways leading to several advanced glycation end products (AGEs) such as (carboxymethyl)lysine, pentosidine, and glucosepane are outlined, whereas other AGEs useful as potential biomarkers of glycation are only briefly mentioned. The current stage of the development of glycation inhibitors has been reviewed with an emphasis on their mechanism of action.

  17. 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.

  18. 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.

  19. 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.

  20. A mechanistic model for permeability evolution in fractured sorbing media

    NASA Astrophysics Data System (ADS)

    Wang, Shugang; Elsworth, Derek; Liu, Jishan

    2012-06-01

    A mechanistic model is presented to represent the evolution of permeability in fractured sorbing media such as coal beds and organic-rich shales. This model accommodates key competing processes of poromechanical dilation and sorption-induced swelling. We show that the significant difference in stiffness between fracture and matrix transforms the composite system from globally unconstrained to locally constrained by the development of a virtual "stiff shell" that envelops the perimeter of a representative elementary volume containing a fracture. It is this transformation that results in swelling-induced permeability reduction at low (sorbing) gas pressures and self consistently allows competitive dilation of the fracture as gas pressures are increased. Importantly, net dilation is shown to require a mismatch in the Biot coefficients of fracture and matrix with the coefficient for the fracture exceeding that for the matrix—a condition that is logically met. Permeability evolution is cast in terms of series and parallel models with the series model better replicating observational data. The model may be cast in terms of nondimensional parameters representing sorptive and poromechanical effects and modulated by the sensitivity of the fracture network to dilation or compaction of the individual fractures. This latter parameter encapsulates the effects of fracture spacing and initial permeability and scale changes in permeability driven by either sorption or poromechanical effects. This model is applied to well-controlled observational data for different ranks of coals and different gases (He, CO2) and satisfactory agreement is obtained.

  1. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems.

    PubMed

    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

  2. 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.

  3. 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.

  4. Deposition of Atmospheric Pollutants

    NASA Astrophysics Data System (ADS)

    Malet, L. M.

    Deposition of Atmospheric Pollutants, containing the proceedings of a colloquium held at Oberursel/Taunus, FRG, November 9-11, 1981, is divided into three main parts: dry deposition; wet deposition; and deposition on plants and vegetation.The 20 articles in the volume permit a fair survey of present-day knowledge and will be a useful tool to all working on the topic. Pollution by deposition of either the dry or wet sort is very insidious; its importance only appears in the long range, when its effects are or are almost irreversible. That is why concern was so long in emerging from decision makers.

  5. A mechanistic model of global soil nitric oxide emissions: implementation and space based-constraints

    NASA Astrophysics Data System (ADS)

    Hudman, R. C.; Moore, N. E.; Martin, R. V.; Russell, A. R.; Mebust, A. K.; Valin, L. C.; Cohen, R. C.

    2012-02-01

    Soil emissions have been identified as a major source (~15%) of global nitrogen oxide (NOx) emissions. Parameterizations of soil NOx emissions (SNOx) for use in the current generation of chemical transport models were designed to capture mean seasonal behaviour. These parameterizations do not, however, respond quantitatively to the meteorological triggers that result in pulsed SNOx as are widely observed. Here we present a new mechanistic parameterization of SNOx implemented into a global chemical transport model (GEOS-Chem). The parameterization represents available nitrogen (N) in soils using biome specific emission factors, online wet- and dry-deposition of N as well as fertilizer and manure N derived from a spatially explicit dataset distributed using seasonality derived from data obtained by the Moderate Resolution Imaging Spectrometer. Moreover, it represents the functional form of emissions derived from point measurements and ecosystem scale experiments including pulsing following soil wetting by rain or irrigation, and emissions that are a smooth function of soil moisture. This parameterization yields global above-soil SNOx of 10.7 Tg N yr-1, including 1.8 Tg N yr-1 from fertilizer N input (0.68% of applied N) and 0.5 Tg N yr-1 from atmospheric N deposition. Over the United States Great Plains, SNOx are predicted to comprise 15-40% of the tropospheric NO2 column and increase column variability by a factor of 2-4 during the summer months due to chemical fertilizer application and warm temperatures. SNOx enhancements of 50-80% of the simulated NO2 column are predicted over the African Sahel during the monsoon onset (April-June). In this region the day-to-day variability of column NO2 is increased by a factor of 5 due to pulsed-N emissions. We evaluate the model by comparison to observations of the NO2 column from the OMI instrument. We find the model is able to reproduce observations of pulsed-N induced interannual variability over the US Great Plains. We

  6. 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. PMID:25954242

  7. Mechanistic analysis of cavitation assisted transesterification on biodiesel characteristics.

    PubMed

    Sajjadi, Baharak; Abdul Aziz, A R; Ibrahim, Shaliza

    2015-01-01

    The influence of sonoluminescence transesterification on biodiesel physicochemical properties was investigated and the results were compared to those of traditional mechanical stirring. This study was conducted to identify the mechanistic features of ultrasonication by coupling statistical analysis of the experiments into the simulation of cavitation bubble. Different combinations of operational variables were employed for alkali-catalysis transesterification of palm oil. The experimental results showed that transesterification with ultrasound irradiation could change the biodiesel density by about 0.3kg/m(3); the viscosity by 0.12mm(2)/s; the pour point by about 1-2°C and the flash point by 5°C compared to the traditional method. Furthermore, 93.84% of yield with alcohol to oil molar ratio of 6:1 could be achieved through ultrasound assisted transesterification within only 20min. However, only 89.09% of reaction yield was obtained by traditional macro mixing/heating under the same condition. Based on the simulated oscillation velocity value, the cavitation phenomenon significantly contributed to generation of fine micro emulsion and was able to overcome mass transfer restriction. It was found that the sonoluminescence bubbles reached the temperature of 758-713K, pressure of 235.5-159.55bar, oscillation velocity of 3.5-6.5cm/s, and equilibrium radius of 17.9-13.7 times greater than its initial size under the ambient temperature of 50-64°C at the moment of collapse. This showed that the sonoluminescence bubbles were in the condition in which the decomposition phenomena were activated and the reaction rate was accelerated together with a change in the biodiesel properties.

  8. 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

  9. 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.

  10. Common Mechanistic Themes for the Powerstroke of Kinesin-14 motors

    PubMed Central

    Gonzalez, Miguel A.; Cope, Julia; Rank, Katherine C.; Chen, Chun Ju; Tittmann, Peter; Rayment, Ivan; Gilbert, Susan P.; Hoenger, Andreas

    2013-01-01

    Kar3Cik1 is a heterodimeric kinesin-14 from Saccharomyces cerevisiae involved in spindle formation during mitosis and karyogamy in mating cells. Kar3 represents a canonical kinesin motor domain that interacts with microtubules under the control of ATP-hydrolysis. In vivo, the localization and function of Kar3 is differentially regulated by its interacting stoichiometrically with either Cik1 or Vik1, two closely related motor homology domains that lack the nucleotide-binding site. Indeed, Vik1 structurally resembles the core of a kinesin head. Despite being closely related, Kar3Cik1 and Kar3Vik1 are each responsible for a distinct set of functions in vivo and also display different biochemical behavior in vitro. To determine a structural basis for their distinct functional abilities, we used cryo-electron microscopy and helical reconstruction to investigate the 3-D structure of Kar3Cik1 complexed to microtubules in various nucleotide states and compared our 3-D data of Kar3Cik1 with that of Kar3Vik1 and the homodimeric kinesin-14 Ncd from Drosophila melanogaster. Due to the lack of an X-ray crystal structure of the Cik1 motor homology domain, we predicted the structure of this Cik1 domain based on sequence similarity to its relatives Vik1, Kar3 and Ncd. By molecular docking into our 3-D maps, we produced a detailed near-atomic model of Kar3Cik1 complexed to microtubules in two distinct nucleotide states, a nucleotide-free state and an ATP-bound state. Our data show that despite their functional differences, heterodimeric Kar3Cik1 and Kar3Vik1 and homodimeric Ncd, all share striking structural similarities at distinct nucleotide states indicating a common mechanistic theme within the kinesin-14 family. PMID:24099757

  11. 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

  12. Vitamins C and E: Beneficial effects from a mechanistic perspective

    PubMed Central

    Traber, Maret G.; Stevens, Jan F.

    2011-01-01

    The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid soluble antioxidant, scavenging hydroperoxyl radicals in lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C plays also a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review. PMID:21664268

  13. Toward a mechanistic understanding and prediction of biotic homogenization.

    PubMed

    Olden, Julian D; Poff, N LeRoy

    2003-10-01

    The widespread replacement of native species with cosmopolitan, nonnative species is homogenizing the global fauna and flora. While the empirical study of biotic homogenization is substantial and growing, theoretical aspects have yet to be explored. Consequently, the breadth of possible ecological mechanisms that can shape current and future patterns and rates of homogenization remain largely unknown. Here, we develop a conceptual model that describes 14 potential scenarios by which species invasions and/or extinctions can lead to various trajectories of biotic homogenization (increased community similarity) or differentiation (decreased community similarity); we then use a simulation approach to explore the model's predictions. We found changes in community similarity to vary with the type and number of nonnative and native species, the historical degree of similarity among the communities, and, to a lesser degree, the richness of the recipient communities. Homogenization is greatest when similar species invade communities, causing either no extinction or differential extinction of native species. The model predictions are consistent with current empirical data for fish, bird, and plant communities and therefore may represent the dominant mechanisms of contemporary homogenization. We present a unifying model illustrating how the balance between invading and extinct species dictates the outcome of biotic homogenization. We conclude by discussing a number of critical but largely unrecognized issues that bear on the empirical study of biotic homogenization, including the importance of spatial scale, temporal scale, and data resolution. We argue that the study of biotic homogenization needs to be placed in a more mechanistic and predictive framework in order for studies to provide adequate guidance in conservation efforts to maintain regional distinctness of the global biota. PMID:14582007

  14. Mechanistic analysis of cavitation assisted transesterification on biodiesel characteristics.

    PubMed

    Sajjadi, Baharak; Abdul Aziz, A R; Ibrahim, Shaliza

    2015-01-01

    The influence of sonoluminescence transesterification on biodiesel physicochemical properties was investigated and the results were compared to those of traditional mechanical stirring. This study was conducted to identify the mechanistic features of ultrasonication by coupling statistical analysis of the experiments into the simulation of cavitation bubble. Different combinations of operational variables were employed for alkali-catalysis transesterification of palm oil. The experimental results showed that transesterification with ultrasound irradiation could change the biodiesel density by about 0.3kg/m(3); the viscosity by 0.12mm(2)/s; the pour point by about 1-2°C and the flash point by 5°C compared to the traditional method. Furthermore, 93.84% of yield with alcohol to oil molar ratio of 6:1 could be achieved through ultrasound assisted transesterification within only 20min. However, only 89.09% of reaction yield was obtained by traditional macro mixing/heating under the same condition. Based on the simulated oscillation velocity value, the cavitation phenomenon significantly contributed to generation of fine micro emulsion and was able to overcome mass transfer restriction. It was found that the sonoluminescence bubbles reached the temperature of 758-713K, pressure of 235.5-159.55bar, oscillation velocity of 3.5-6.5cm/s, and equilibrium radius of 17.9-13.7 times greater than its initial size under the ambient temperature of 50-64°C at the moment of collapse. This showed that the sonoluminescence bubbles were in the condition in which the decomposition phenomena were activated and the reaction rate was accelerated together with a change in the biodiesel properties. PMID:24981808

  15. Mechanistic basis for overcoming platinum resistance using copper chelating agents.

    PubMed

    Liang, Zheng D; Long, Yan; Tsai, Wen-Bin; Fu, Siqing; Kurzrock, Razelle; Gagea-Iurascu, Mihai; Zhang, Fan; Chen, Helen H W; Hennessy, Bryan T; Mills, Gordon B; Savaraj, Niramol; Kuo, Macus Tien

    2012-11-01

    Platinum-based antitumor agents are widely used in cancer chemotherapy. Drug resistance is a major obstacle to the successful use of these agents because once drug resistance develops, other effective treatment options are limited. Recently, we conducted a clinical trial using a copper-lowering agent to overcome platinum drug resistance in ovarian cancer patients and the preliminary results are encouraging. In supporting this clinical study, using three pairs of cisplatin (cDDP)-resistant cell lines and two ovarian cancer cell lines derived from patients who had failed in platinum-based chemotherapy, we showed that cDDP resistance associated with reduced expression of the high-affinity copper transporter (hCtr1), which is also a cDDP transporter, can be preferentially resensitized by copper-lowering agents because of enhanced hCtr1 expression, as compared with their drug-sensitive counterparts. Such a preferential induction of hCtr1 expression in cDDP-resistant variants by copper chelation can be explained by the mammalian copper homeostasis regulatory mechanism. Enhanced cell-killing efficacy by a copper-lowering agent was also observed in animal xenografts bearing cDDP-resistant cells. Finally, by analyzing a public gene expression dataset, we found that ovarian cancer patients with elevated levels of hCtr1 in their tumors, but not ATP7A and ATP7B, had more favorable outcomes after platinum drug treatment than those expressing low hCtr1 levels. This study reveals the mechanistic basis for using copper chelation to overcome cDDP resistance in clinical investigations.

  16. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    PubMed Central

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  17. 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.

  18. 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.

  19. A partial mechanistic understanding of the North American monsoon

    NASA Astrophysics Data System (ADS)

    Erfani, Ehsan; Mitchell, David

    2014-12-01

    An understanding of the major governing processes of North American monsoon (NAM) is necessary to guide improvement in global and regional climate modeling of the NAM, as well as NAM's impacts on the summer circulation, precipitation, and drought over North America. A mechanistic understanding of the NAM is suggested by incorporating local- and synoptic-scale processes. The local-scale mechanism describes the effect of the temperature inversion over the Gulf of California (GC) on controlling low-level moisture during the 2004 NAM. The strong low-level inversion inhibits the exchange between the moist air in the marine boundary layer (MBL) and the overlying dry air. This inversion weakens with increasing sea surface temperatures (SSTs) in GC 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 by across-gulf (along-gulf) flow toward the NAM core region (southwestern U.S.) to form thunderstorms. On the synoptic scale, climatologies from 1983 to 2010 exhibit a temporal correspondence between coastal warm tropical surface water, NAM deep convection, NAM anticyclone center, and NAM-induced strong descent. A hypothesis is proposed to explain this correspondence, based on limited soundings at the GC entrance (suggesting this local mechanism may also be active in that region), the climatologies, and the relevant literature. The warmest SSTs moving up the coast may initiate NAM convection and atmospheric heating, advancing the position of the anticyclone and the region of descent northward.

  20. 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.

  1. 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

  2. Mechanistic Insight into DNA-Guided Control of Nanoparticle Morphologies.

    PubMed

    Tan, Li Huey; Yue, Yuan; Satyavolu, Nitya Sai Reddy; Ali, Arzeena Sultana; Wang, Zidong; Wu, Yuqing; Lu, Yi

    2015-11-18

    Although shapes and surface characteristics of nanoparticles are known to play important roles in defining their properties, it remains challenging to fine-tune the morphologies systematically and predictably. Recently, we have shown that DNA molecules can serve as programmable ligands to fine-tune the morphologies of nanomaterials. Despite this discovery, the mechanism of how the morphology can be controlled and the roles of the DNA molecules in contributing to such control are not understood. We herein report mechanistic investigation of DNA-mediated morphological evolution of gold nanoprism seeds into nonagon, hexagon, and six-pointed stars, some of which display rough surfaces, in the presence of homo-oligomeric T30, G20, C30, and A30. The growth, elucidated through various analytical methods including UV-vis, SEM, TEM, zeta potential, fluorescence, and cyclic voltammetry, is found to occur in two stages: control of shape, followed by control of thickness. A careful analysis of diffraction patterns of the nanoprism seeds as well as the resulting intermediate shapes by TEM allowed us to deduce the exact sequence of shape evolution. Through systematic comparison of the nanoparticle growth process, the DNA molecules were found to play important roles by influencing diffusion of the Au precursor to the seed and modulating the growth through differences in DNA desorption, density, and mobility on the seed surface. These insights into the mechanism of DNA-guided control of nanomaterial morphologies provide deeper understanding of the interactions between the DNA and nanomaterials and will allow better control of the shapes and surface properties of many nanomaterials. PMID:26492515

  3. Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Bennett, Charles L.; Kim, Benjamin; Zakarija, Anaadriana; Bandarenko, Nicholas; Pandey, Dilip K.; Buffie, Charlie G.; McKoy, June M.; Tevar, Amul D.; Cursio, John F.; Yarnold, Paul R.; Kwaan, Hau C.; De Masi, Davide; Sarode, Ravindra; Raife, Thomas J.; Kiss, Joseph E.; Raisch, Dennis W.; Davidson, Charles; Sadler, J. Evan; Ortel, Thomas L.; Zheng, X. Long; Kato, Seiji; Matsumoto, Masanori; Uemura, Masahito; Fujimura, Yoshihiro

    2011-01-01

    Objectives We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. PMID:17868804

  4. 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.

  5. A mechanistic accounting of SOM speciation and kinetics in soils

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    The nature and dynamics of soil organic matter (SOM) are arguably far from being understood and accurately represented in current site, regional, and global land use and climate models. Whereas consolidated models make use of aggregated pools describing SOM with characteristic turnover times such as inert, passive, slow cycling, and fast cycling, or linking the turnover time to the molecular weight of the compound, recent analyses of SOM below the top soil suggest that those approaches only partially capture SOM dynamics, and that SOM stability may largely be determined by biological and chemical protection as well as other environmental factors rather than the molecular structure of the compound and its molecular weight. We introduce here a new paradigm of SOM speciation and kinetics that explicitly decouples the assumed recalcitrance and turnover time from the SOM molecular density and structure in favour of a mechanistic accounting of microbially mediated processes and chemo-physical interactions among the various SOM species and soil environment. These processes include microbial assimilation, respiration and C recycling; depolymerization of solid litter, root exudates, and dead cells into various decomposed SOM groups; and incorporation of soluble SOM species into a protected phase not available to chemical and biological agents. SOM was described by means of functional compounds including mono- and polysaccharides, lignin, amino compounds, organic acids, nucleic acids, lipids, and phenols, each being accounted for by one or more representative species in the model. Fungal and bacterial microbial functional groups were used to characterize depolymerization and respiration rates. The SOM reaction network and characteristics, its mathematical inclusion within the TOUGHREACT framework, and some preliminary results of modeling grasslands and forested ecosystems are presented here. Biogeochemical reaction network of SOC pathways. Steady state vertical contentration

  6. 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.

  7. 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...

  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. Use of Gene Expression Changes in Blood to Elucidate Mechanistic Indicators of Childhood Asthma (MICA)

    EPA Science Inventory

    Risk assessment increasingly relies more heavily on mode of action, thus the identification of human bioindicators of disease becomes all the more important. Genomic methods represent a tool for both mode of action determination and bioindicator identification. The Mechanistic In...

  10. 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.

  11. 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

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

    PubMed

    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

  13. Ionized cluster beam deposition

    NASA Astrophysics Data System (ADS)

    Kirkpatrick, A. R.

    1983-11-01

    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.

  14. 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.

  15. 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.

  16. 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

  17. Mechanistic study of silver nanoparticle formation on conducting polymer surfaces.

    PubMed

    Mack, Nathan H; Bailey, James A; Doorn, Stephen K; Chen, Chien-An; Gau, Han-Mou; Xu, Ping; Williams, Darrick J; Akhadov, Elshan A; Wang, Hsing-Lin

    2011-04-19

    Conducting polymer (polyaniline) sheets are shown to be active substrates to promote the growth of nanostructured silver thin films with highly tunable morphologies. Using the spontaneous electroless deposition of silver, we show that a range of nanostructured metallic features can be controllably and reproducibly formed over large surface areas. The structural morphology of the resulting metal-polymer nanocomposite is demonstrated to be sensitive to experimental parameters such as ion concentration, temperature, and polymer processing and can range from densely packed oblate nanosheets to bulk crystalline metals. The deposition mechanisms are explained using a diffusion-limited aggregation (DLA) model to describe the semi-fractal-like growth of the metal nanostructures. We find these composite films to exhibit strong surface-enhanced Raman (SERS) activity, and the nanostructured features are optimized with respect to SERS activity using a self-assembled monolayer of mercapto-benzoic acid as a model Raman reporter. SERS enhancements are estimated to be on the order of 10(7). Through micro-Raman SERS mapping, these materials are shown to exhibit uniform SERS responses over macroscopic areas. These metal-polymer nanocomposites benefit from the underlying polymer's processability to yield SERS-active materials of almost limitless shape and size and show significant promise for future SERS-based sensing and detection schemes. PMID:21434643

  18. 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.

  19. 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.

  20. Impact of Surface Chemistry on Copper Deposition in Mesoporous Silicon.

    PubMed

    Darwich, Walid; Garron, Anthony; Bockowski, Piotr; Santini, Catherine; Gaillard, Frédéric; Haumesser, Paul-Henri

    2016-08-01

    An easy, efficient, and safe process is developed to metallize mesoporous silicon (PSi) with Cu from the decomposition of a solution of mesitylcopper (CuMes) in an imidazolium-based ionic liquid (IL), [C1C4Im][NTf2]. The impregnation of a solution of CuMes in IL affords the deposition of metallic islands not only on the surface but also deep within the pores of a mesoporous Si layer with small pores below 10 nm. Therefore, this process is well suited to efficiently and completely metallize PSi layers. An in-depth mechanistic study shows that metal deposition is due to the reduction of CuMes by surface silane groups rather than by Si oxidation as observed in aqueous or water-containing media. This could open a new route to the chemical metallization of PSi by less-noble metals difficult to attain by a conventional displacement reaction.

  1. Impact of Surface Chemistry on Copper Deposition in Mesoporous Silicon.

    PubMed

    Darwich, Walid; Garron, Anthony; Bockowski, Piotr; Santini, Catherine; Gaillard, Frédéric; Haumesser, Paul-Henri

    2016-08-01

    An easy, efficient, and safe process is developed to metallize mesoporous silicon (PSi) with Cu from the decomposition of a solution of mesitylcopper (CuMes) in an imidazolium-based ionic liquid (IL), [C1C4Im][NTf2]. The impregnation of a solution of CuMes in IL affords the deposition of metallic islands not only on the surface but also deep within the pores of a mesoporous Si layer with small pores below 10 nm. Therefore, this process is well suited to efficiently and completely metallize PSi layers. An in-depth mechanistic study shows that metal deposition is due to the reduction of CuMes by surface silane groups rather than by Si oxidation as observed in aqueous or water-containing media. This could open a new route to the chemical metallization of PSi by less-noble metals difficult to attain by a conventional displacement reaction. PMID:27368422

  2. Biomimetic thin film deposition

    SciTech Connect

    Rieke, P.R.; Graff, G.E.; Campbell, A.A.; Bunker, B.C.; Baskaran, S.; Song, L.; Tarasevich, B.J.; Fryxell, G.E.

    1995-09-01

    Biological mineral deposition for the formation of bone, mollusk shell and other hard tissues provides materials scientists with illustrative materials processing strategies. This presentation will review the key features of biomineralization and how these features can be of technical importance. We have adapted existing knowledge of biomineralization to develop a unique method of depositing inorganic thin films and coating. Our approach to thin film deposition is to modify substrate surfaces to imitate the proteins found in nature that are responsible for controlling mineral deposition. These biomimetic surfaces control the nucleation and growth of the mineral from a supersaturated aqueous solution. This has many processing advantages including simple processing equipment, environmentally benign reagents, uniform coating of highly complex shapes, and enhanced adherence of coating. Many different types of metal oxide, hydroxide, sulfide and phosphate materials with useful mechanical, optical, electronic and biomedical properties can be deposited.

  3. 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.

  4. 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.

  5. Tsunami Deposit Data Base

    NASA Astrophysics Data System (ADS)

    Keating, B. H.; Wanink, M.

    2007-05-01

    A digital database has been established describing tsunami deposits around the world (3 phases; 15 months). The projects involved the review and tabulation of data derived from books, catalogs, journals, preprints, citations and abstracts (currently 1000 references), into a database designed to provide a comprehensive review of the types of tsunami deposits, their geographic distribution and location, sedimentary characteristics, fossil content, age, preservation, run-up, wave height and inundation observations, etc. (34 parameters). The tsunami occurrences can be divided into many subjects, e.g., Volcanogenic (N=375), Seismites (N=49), Co-seismic (N=258), K/T Boundary Impact-triggered debris flows (N=97), Landslides (N=43), etc. Numerous publications compare tsunami deposits to storm deposits (N=38), or analyze the origin of megaboulders (N=22). Tsunami deposits occur throughout geologic time (Pre-Cambrian to present day), and because of plate tectonics, they occur along plate margins (primarily subduction zones) as well as interior to plates. In addition, they occur in epi-continental seas, fjords, etc. Few publications describe depositional processes. Deposits generated by tsunamis occur in multiple environments such as the marine, fresh water, and subaerial. Common characteristics of tsunami deposits include: 1) Deposition of thin sand sheets (can be normal, massive, inversely graded, chaotic or bimodal). 2) Erosional: basal uncomformity, mud balls, rip-up clasts, reworked fossils produced by scouring. 3) Lithology: Stacks of couplets reflecting marine incursions (often sands) into fresh water or subaerial environments (mud, soil, peat). 4) Fossil: Couplets reflects marine fossils, fresh water fossils or a mixed assemblage. 5) Geomorphology: The sand sheets taper landward and can rise in elevation. 6) Deformation: syn-depositional (soft sediments) and intraformational (stiff sediments).

  6. A mechanistic examination of redox cycling activity in carbonaceous particulate matter

    NASA Astrophysics Data System (ADS)

    McWhinney, Robert David

    Mechanistic aspects of carbonaceous aerosol toxicity were examined with respect to the ability of particles to catalyse reactive oxygen species-generating redox cycling reactions. To investigate the role of secondary organic material, we examined two systems. In the first, two-stroke engine exhaust particles were found to increase their ability to catalyse redox cycling in the presence of a reducing agent, dithiothreitol (DTT), when the exhaust was exposed to ozone. This occurred through deposition of redox-active secondary organic aerosol (SOA) onto the particle that was ten times more redox active per microgram than the primary engine particle. In the second system, naphthalene SOA formed highly redox active particles. Activity was strongly correlated to the amount of the 1,4- and 1,2-naphthoquinone measured in the particle phase. However, these species and the newly quantified naphthalene oxidation product 5-hydroxy-1,4-naphthoquinone accounted for only 30% of the observed DTT decay from the particles. Gas-particle partitioning coefficients suggest 1,4- and 1,2- naphthoquinone are not strong contributors to ambient particle redox activity at 25 °C. However, a large number of redox active species are unidentified. Some of these may be highly oxidised products of sufficiently low vapour pressure to be atmospherically relevant. DTT activity of diesel particles was found to be high per unit mass. The activity was found to be associated with the insoluble fraction as filtration of the particles nearly eliminated DTT decay. Neither methanol nor dichloromethane extracts of diesel particles exhibited redox activity, indicating that the redox active species are associated with the black carbon portion of the particles. Examination of particle concentration techniques found that use of water condensation to grow and concentrate particles introduced a large organic artefact to the particles. Experiments with concentrated inorganic particles suggest that the source of this

  7. 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

  8. Mechanistic controls on diverse fates of terrestrial organic components in the East China Sea

    NASA Astrophysics Data System (ADS)

    Zhu, Chun; Wagner, Thomas; Talbot, Helen M.; Weijers, Johan W. H.; Pan, Jian-Ming; Pancost, Richard D.

    2013-09-01

    Terrestrial carbon transferred from the land to sea is a critical component of the global carbon cycle. A range of geochemical proxies has been developed to fingerprint the fate of terrestrial organic matter (TOM) in marine sediments. However, discrepancies among different proxies limit our ability to quantify and interpret the terrestrial signals in marine sediments, with consequences for the investigation of both the modern carbon cycle and past environmental change. To mechanistically understand these discrepancies, we examined the distributions of a range of terrestrial proxies and their aquatic counterparts (i.e. marine proxies) in the Yangtze river-East China Sea (YR-ECS) shelf system, where TOM experiences extensive modification during transport and burial. TOM proxies in the YR-ECS system collectively fit a power-law model but with distinct attenuation rates (the a∗ values) for individual molecular proxy groups. Among a range of TOM proxies, the modeled a∗ values decrease in the order: soil-marker BHPs > triterpenols > lignin > HMW n-alkanols > branched GDGTs > HMW n-alkanes for biomarkers; and Rsoil > BIT > %TOMiso for proxies tracing %TOM. Rapid loss of TOM components through dissociation in the narrow estuary, followed by oxidation over the wide open shelf, are best described by power curves. Inherent chemical reactivity (i.e. the number of functional groups), responses to hydraulic sorting, and in situ production regulate the individual attenuation rates. Of them, chemical reactivity plays the most important role on proxy behavior, supported by a strong correlation between a∗ values and standard molal Gibbs energies. Both, physical protection and chemical reactivity fundamentally control the overall behavior of TOM components, with the relative importance being setting-dependant: The former is relatively important in the estuary, whereas the later is the primary control over the open shelf. Moreover, regional variation of different marine

  9. Mechanistic study and modeling of precipitation scale inhibitor squeeze processes

    SciTech Connect

    Malandrino, A.; Yuan, M.D.; Sorbie, K.S.; Jordan, M.M.

    1995-11-01

    A scale inhibitor precipitation squeeze is one of the two main types of treatment for preventing downhole scale deposition; the other type is an adsorption squeeze. However, unlike for the adsorption squeeze process, the mechanism for inhibitor retention within the formation through precipitation/re-dissolution is not fully understood and it is this issue that is considered in this work. Here, the central objective is to consider a range of possible models of the precipitation squeeze process and to determine which of these are consistent with the available laboratory core flood and field data. Such models range from pure precipitation through to more complex models which couple the precipitation process with an adsorption process or with a mechanical transport phenomenon. The various models are explained in terms of the chemical processes which are observed. Results from two inhibitor precipitation core floods and one field squeeze treatment are presented along with the modeled inhibitor return curves. Based on certain model assumptions, the authors understanding of the process allows them to optimize the squeeze design of both inhibitor solution and operational parameters for extending the precipitation squeeze life time.

  10. 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.

  11. 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.

  12. 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.

  13. Automatic Payroll Deposit System.

    ERIC Educational Resources Information Center

    Davidson, D. B.

    1979-01-01

    The Automatic Payroll Deposit System in Yakima, Washington's Public School District No. 7, directly transmits each employee's salary amount for each pay period to a bank or other financial institution. (Author/MLF)

  14. A review of lithium deposition in lithium-ion and lithium metal secondary batteries

    NASA Astrophysics Data System (ADS)

    Li, Zhe; Huang, Jun; Yann Liaw, Bor; Metzler, Viktor; Zhang, Jianbo

    2014-05-01

    Major aspects related to lithium deposition in lithium-ion and lithium metal secondary batteries are reviewed. For lithium-ion batteries with carbonaceous anode, lithium deposition may occur under harsh charging conditions such as overcharging or charging at low temperatures. The major technical solutions include: (1) applying electrochemical models to predict the critical conditions for deposition initiation; (2) preventions by improved battery design and material modification; (3) applying adequate charging protocols to inhibit lithium deposition. For lithium metal secondary batteries, the lithium deposition is the inherent reaction during charging. The major technical solutions include: (1) the use of mechanistic models to elucidate and control dendrite initiation and growth; (2) engineering surface morphology of the lithium deposition to avoid dendrite formation via adjusting the composition and concentration of the electrolyte; (3) controlling battery working conditions. From a survey of the literature, the areas that require further study are proposed; e.g., refining the lithium deposition criteria, developing an effective AC self pre-heating method for low-temperature charging of lithium-ion batteries, and clarifying the role the solid electrolyte interphase (SEI) plays in determining the deposition morphology; to facilitate a refined control of the lithium deposition.

  15. 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...

  16. The use of mechanistic descriptions of algal growth and zooplankton grazing in an estuarine eutrophication model

    NASA Astrophysics Data System (ADS)

    Baird, M. E.; Walker, S. J.; Wallace, B. B.; Webster, I. T.; Parslow, J. S.

    2003-03-01

    A simple model of estuarine eutrophication is built on biomechanical (or mechanistic) descriptions of a number of the key ecological processes in estuaries. Mechanistically described processes include the nutrient uptake and light capture of planktonic and benthic autotrophs, and the encounter rates of planktonic predators and prey. Other more complex processes, such as sediment biogeochemistry, detrital processes and phosphate dynamics, are modelled using empirical descriptions from the Port Phillip Bay Environmental Study (PPBES) ecological model. A comparison is made between the mechanistically determined rates of ecological processes and the analogous empirically determined rates in the PPBES ecological model. The rates generally agree, with a few significant exceptions. Model simulations were run at a range of estuarine depths and nutrient loads, with outputs presented as the annually averaged biomass of autotrophs. The simulations followed a simple conceptual model of eutrophication, suggesting a simple biomechanical understanding of estuarine processes can provide a predictive tool for ecological processes in a wide range of estuarine ecosystems.

  17. 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.

  18. Deposited atmospheric chemicals

    SciTech Connect

    Schell, W.R.

    1986-09-01

    A mountaintop bog in western Pennsylvania serves as a reservoir for materials deposited from the atmosphere. Biological activity in the bog decomposes plant matter, which becomes humified and mineralized at increasing depths. Little or no mixing of elements occurs below the active root zone. Radionuclides produced by natural means and by nuclear weapons have been used to measure the ages of the layers deposited during the growing season of each year. The upper layers of the bog indicate that the deposition of total sulfur is at least 20 times and that of nitrogen is 45 times the value estimated prior to cutting the forest, with a doubling time for each of 25-35 yr. Bromine deposition also doubles every 35 yr. The pattern of mass and element deposition illustrates the changes in land use and industrial effluents that were sources for the material deposited on the bog. The decrease in atmospheric particle removal shows up in the 1960 and later layers. Compared with terrestrial abundances, the relative enrichments over time for chlorine, nitrogen, sulfur, and bromine are more than 100 times those calculated for 1817; lead, calcium, and antimony are 10 to 40 times greater.

  19. Convective microsphere monolayer deposition

    NASA Astrophysics Data System (ADS)

    Gilchrist, James

    2011-03-01

    There is perhaps no simpler way of modifying surface chemistry and morphology than surface deposition of particles. Micron-sized microspheres were deposited into thin films via rapid convective deposition, similar to the `coffee ring effect' using a similar method to that studied by Prevo and Velev, Langmuir, 2003. By varying deposition rate and blade angle, the optimal operating ranges in which 2D close-packed arrays of microspheres existed were obtained. Self-assembly of colloidal particles through a balance of electrostatic and capillary forces during solvent evaporation was revealed. These interactions were explored through a model comparing the residence time of a particle in the thin film and the characteristic time of capillary-driven crystallization to describe the morphology and microstructure of deposited particles. Co-deposition of binary suspensions of micron and nanoscale particles was tailored to generate higher-quality surface coatings and a simple theory describes the immergence of instabilities that result in formation of stripes. Optical and biomedical applications that utilize the described nanoscale control over surface morphology will also be discussed.

  20. Integrating mechanistic organism--environment interactions into the basic theory of community and evolutionary ecology.

    PubMed

    Baskett, Marissa L

    2012-03-15

    This paper presents an overview of how mechanistic knowledge of organism-environment interactions, including biomechanical interactions of heat, mass and momentum transfer, can be integrated into basic theoretical population biology through mechanistic functional responses that quantitatively describe how organisms respond to their physical environment. Integrating such functional responses into simple community and microevolutionary models allows scaling up of the organism-level understanding from biomechanics both ecologically and temporally. For community models, Holling-type functional responses for predator-prey interactions provide a classic example of the functional response affecting qualitative model dynamics, and recent efforts are expanding analogous models to incorporate environmental influences such as temperature. For evolutionary models, mechanistic functional responses dependent on the environment can serve as fitness functions in both quantitative genetic and game theoretic frameworks, especially those concerning function-valued traits. I present a novel comparison of a mechanistic fitness function based on thermal performance curves to a commonly used generic fitness function, which quantitatively differ in their predictions for response to environmental change. A variety of examples illustrate how mechanistic functional responses enhance model connections to biologically relevant traits and processes as well as environmental conditions and therefore have the potential to link theoretical and empirical studies. Sensitivity analysis of such models can provide biologically relevant insight into which parameters and processes are important to community and evolutionary responses to environmental change such as climate change, which can inform conservation management aimed at protecting response capacity. Overall, the distillation of detailed knowledge or organism-environment interactions into mechanistic functional responses in simple population

  1. Mechanistic insights into nickamine-catalyzed alkyl-alkyl cross-coupling reactions.

    PubMed

    Breitenfeld, Jan; Hu, Xile

    2014-01-01

    Within the last decades the transition metal-catalyzed cross-coupling of non-activated alkyl halides has significantly progressed. Within the context of alkyl-alkyl cross-coupling, first row transition metals spanning from iron, over cobalt, nickel, to copper have been successfully applied to catalyze this difficult reaction. The mechanistic understanding of these reactions is still in its infancy. Herein we outline our latest mechanistic studies that explain the efficiency of nickel, in particular nickamine-catalyzed alkyl-alkyl cross-coupling reactions.

  2. Enantioselective and Regiodivergent Functionalization of N-Allylcarbamates by Mechanistically Divergent Multicatalysis.

    PubMed

    Richmond, Edward; Khan, Ismat Ullah; Moran, Joseph

    2016-08-22

    A pair of mechanistically divergent multicatalytic reaction sequences has been developed consisting of nickel-catalyzed isomerization of N-allylcarbamates and subsequent phosphoric-acid-catalyzed enantioselective functionalization of the resulting intermediates. By appropriate selection of reaction partners, in situ generated imines and ene-carbamates are mechanistically partitioned to yield opposing functionalized products. Formal α-functionalization to give protected α-arylamines is achieved upon enantioselective Friedel-Crafts reaction with arene nucleophiles, whereas formal β-functionalization is achieved upon reaction with diarylimine electrophiles in an enantioselective Povarov-[4+2] cycloaddition. PMID:27461524

  3. Enantioselective and Regiodivergent Functionalization of N-Allylcarbamates by Mechanistically Divergent Multicatalysis.

    PubMed

    Richmond, Edward; Khan, Ismat Ullah; Moran, Joseph

    2016-08-22

    A pair of mechanistically divergent multicatalytic reaction sequences has been developed consisting of nickel-catalyzed isomerization of N-allylcarbamates and subsequent phosphoric-acid-catalyzed enantioselective functionalization of the resulting intermediates. By appropriate selection of reaction partners, in situ generated imines and ene-carbamates are mechanistically partitioned to yield opposing functionalized products. Formal α-functionalization to give protected α-arylamines is achieved upon enantioselective Friedel-Crafts reaction with arene nucleophiles, whereas formal β-functionalization is achieved upon reaction with diarylimine electrophiles in an enantioselective Povarov-[4+2] cycloaddition.

  4. 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.

  5. 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.

  6. 76 FR 41392 - Interest on Deposits; Deposit Insurance Coverage

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... From the Federal Register Online via the Government Publishing Office FEDERAL DEPOSIT INSURANCE CORPORATION 12 CFR Parts 329 and 330 RIN 3064-AD78 Interest on Deposits; Deposit Insurance Coverage AGENCY: Federal Deposit Insurance Corporation (FDIC). ACTION: Final rule. SUMMARY: The FDIC is issuing a...

  7. 76 FR 21265 - Interest on Deposits; Deposit Insurance Coverage

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... From the Federal Register Online via the Government Publishing Office FEDERAL DEPOSIT INSURANCE CORPORATION 12 CFR Parts 329 and 330 RIN 3064-AD78 Interest on Deposits; Deposit Insurance Coverage AGENCY: Federal Deposit Insurance Corporation (FDIC). ACTION: Notice of proposed rulemaking (NPR) and request...

  8. Vacuum arc deposition devices

    NASA Astrophysics Data System (ADS)

    Boxman, R. L.; Zhitomirsky, V. N.

    2006-02-01

    The vacuum arc is a high-current, low-voltage electrical discharge which produces a plasma consisting of vaporized and ionized electrode material. In the most common cathodic arc deposition systems, the arc concentrates at minute cathode spots on the cathode surface and the plasma is emitted as a hypersonic jet, with some degree of contamination by molten droplets [known as macroparticles (MPs)] of the cathode material. In vacuum arc deposition systems, the location and motion of the cathode spots are confined to desired surfaces by an applied magnetic field and shields around undesired surfaces. Substrates are mounted on a holder so that they intercept some portion of the plasma jet. The substrate often provides for negative bias to control the energy of depositing ions and heating or cooling to control the substrate temperature. In some systems, a magnetic field is used to guide the plasma around an obstacle which blocks the MPs. These elements are integrated with a deposition chamber, cooling, vacuum gauges and pumps, and power supplies to produce a vacuum arc deposition system.

  9. Vacuum arc deposition devices

    SciTech Connect

    Boxman, R.L.; Zhitomirsky, V.N.

    2006-02-15

    The vacuum arc is a high-current, low-voltage electrical discharge which produces a plasma consisting of vaporized and ionized electrode material. In the most common cathodic arc deposition systems, the arc concentrates at minute cathode spots on the cathode surface and the plasma is emitted as a hypersonic jet, with some degree of contamination by molten droplets [known as macroparticles (MPs)] of the cathode material. In vacuum arc deposition systems, the location and motion of the cathode spots are confined to desired surfaces by an applied magnetic field and shields around undesired surfaces. Substrates are mounted on a holder so that they intercept some portion of the plasma jet. The substrate often provides for negative bias to control the energy of depositing ions and heating or cooling to control the substrate temperature. In some systems, a magnetic field is used to guide the plasma around an obstacle which blocks the MPs. These elements are integrated with a deposition chamber, cooling, vacuum gauges and pumps, and power supplies to produce a vacuum arc deposition system.

  10. Metallogeny of gold deposits

    SciTech Connect

    Hutchinson, R.W.

    1985-01-01

    The metallogeny of various gold deposits, particularly their broad temporal and spatial relations, and their relations to other metallic ores, is significant to genetic understanding and also useful in exploration. Archean gold deposits co-exist, both regionally and locally, with certain iron formations, massive base metal and nickel sulfide ores, but these occur generally in differing parts of the host stratigraphic sequences. Gold deposits in marine-eugeosynclinal environments are most important and numerous in Archean rocks. They become increasingly rare in successively younger strata where epithermal deposits in subaerial-continental rocks become important. The hydrothermal systems that formed both were apparently similar; one active in submarine tectonic settings, the other in sub-volcanic continental ones. Gold was apparently first introduced extensively into supracrustal rocks by sub-sea floor hydrothermal processes in Archean time, forming gold-enriched exhalites. These were reworked by metamorphic processes forming epithermal veins in many lode districts, and by sedimentary processes in the Witwatersrand. Epithermal gold deposits were generated where these older, auriferous basement source rocks were affected by younger, plutonic-volcanic-hydrothermal activity.

  11. Pulsed laser deposition: Prospects for commercial deposition of epitaxial films

    SciTech Connect

    Muenchausen, R.E.

    1999-03-01

    Pulsed laser deposition (PLD) is a physical vapor deposition (PVD) technique for the deposition of thin films. The vapor source is induced by the flash evaporation that occurs when a laser pulse of sufficient intensity (about 100 MW/cm{sup 2}) is absorbed by a target. In this paper the author briefly defines pulsed laser deposition, current applications, research directed at gaining a better understanding of the pulsed laser deposition process, and suggests some future directions to enable commercial applications.

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

    PubMed

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

    2006-07-01

    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.

  13. 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…

  14. 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...

  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. 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...

  17. 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…

  18. 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...

  19. 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...

  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. 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...

  2. 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.

  3. 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.

  4. 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...

  5. 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,…

  6. 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. PMID:24995457

  7. MECHANISTIC DATA & CANCER RISK ASSESSMENT: THE NEED FOR QUANTITATIVE MOLECULAR ENDPOINTS

    EPA Science Inventory

    The cancer risk assessment process as currently proposed by the U.S. Environmental Protection Agency allows for the use of mechanistic data to inform the low dose tumor response in humans and in laboratory animals. The aim is to reduce the reliance on defaults that introduce a re...

  8. 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.

  9. Electroless Deposition Processes and Tools

    NASA Astrophysics Data System (ADS)

    Hu, Z.; Ritzdorf, T.

    Electroless deposition, which was introduced in 1946 by Brenner and Riddell [1], is a type of electrochemical deposition that is gaining interest in semiconductor and related applications. Electroless deposition utilizes complementary electrochemical reactions to cause metal deposition. The oxidation of a reducing agent supplies the electrons needed for reducing metal ions to their metallic state [2]. This encompasses both immersion (displacement) deposition reactions and autocatalytic reactions. One should use electroless deposition in cases where it is desirable to deposit metal on non-conducting surfaces or to deposit metal selectively to certain underlying materials, especially if there is no possibility to have a continuous conductive underlayer. Current applications of interest in the microelectronics industry include copper deposition for seed layer and interconnect metallization, nickel and gold depositions for contact metallurgy in microelectronics packaging and related applications, and cobalt-tungsten alloys as diffusion barrier for copper interconnects.

  10. 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.

  11. 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.

  12. 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

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

    PubMed

    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

  14. Mathematical modeling of G protein-coupled receptor function: what can we learn from empirical and mechanistic models?

    PubMed

    Roche, David; Gil, Debora; Giraldo, Jesús

    2014-01-01

    Empirical and mechanistic models differ in their approaches to the analysis of pharmacological effect. Whereas the parameters of the former are not physical constants those of the latter embody the nature, often complex, of biology. Empirical models are exclusively used for curve fitting, merely to characterize the shape of the E/[A] curves. Mechanistic models, on the contrary, enable the examination of mechanistic hypotheses by parameter simulation. Regretfully, the many parameters that mechanistic models may include can represent a great difficulty for curve fitting, representing, thus, a challenge for computational method development. In the present study some empirical and mechanistic models are shown and the connections, which may appear in a number of cases between them, are analyzed from the curves they yield. It may be concluded that systematic and careful curve shape analysis can be extremely useful for the understanding of receptor function, ligand classification and drug discovery, thus providing a common language for the communication between pharmacologists and medicinal chemists.

  15. "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...

  16. 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.

  17. 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.

  18. 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

  19. Mechanistic Evaluation of LixOy Formation on δ-MnO2 in Nonaqueous Li-Air Batteries.

    PubMed

    Liu, Zhixiao; De Jesus, Luis R; Banerjee, Sarbajit; Mukherjee, Partha P

    2016-09-01

    Transition metal oxides are usually used as catalysts in the air cathode of lithium-air (Li-air) batteries. This study elucidates the mechanistic origin of the oxygen reduction reaction catalyzed by δ-MnO2 monolayers and maps the conditions for Li2O2 growth using a combination of first-principles calculations and mesoscale modeling. The MnO2 monolayer, in the absence of an applied potential, preferentially reacts with a Li atom instead of an O2 molecule to initiate the formation of LiO2. The oxygen reduction products (LiO2, Li2O2, and Li2O molecules) strongly interact with the MnO2 monolayer via the stabilization of Li-O chemical bonds with lattice oxygen atoms. As compared to the disproportionation reaction, direct lithiation reactions are the primary contributors to the stabilization of Li2O2 on the MnO2 monolayer. The energy profiles of (Li2O2)2 and (Li2O)2 nucleation on δ-MnO2 monolayer during the discharge process demonstrate that Li2O2 is the predominant discharge product and that further reduction to Li2O is inhibited by the high overpotential of 1.21 V. Interface structures have been examined to study the interaction between the Li2O2 and MnO2 layers. This study demonstrates that a Li2O2 film can be homogeneously deposited onto δ-MnO2 and that the Li2O2/MnO2 interface acts as an electrical conductor. A mesoscale model, developed based on findings from the first-principles calculations, further shows that Li2O2 is the primary product of electrochemical reactions when the applied potential is smaller than 2.4 V. PMID:27532334

  20. 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.

  1. Electrochemically Deposited Ceria Structures for Advanced Solid Oxide Fuel Cells

    NASA Astrophysics Data System (ADS)

    Brown, Evan C.

    As the pursuit towards emissions reduction intensifies with growing interest and nascent technologies, solid oxide fuel cells (SOFCs) remain an illustrious candidate for achieving our goals. Despite myriad advantages, SOFCs are still too costly for widespread deployment, even as unprecedented materials developments have recently emerged. This suggests that, in addition to informed materials selection, the necessary power output--and, thereby, cost-savings--gains must come from the fuel cell architecture. The work presented in this manuscript primarily investigates cathodic electrochemical deposition (CELD) as a scalable micro-/nanoscale fabrication tool for engineering ceria-based components in a SOFC assembly. Also, polymer sphere lithography was utilized to deposit fully connected, yet fully porous anti-dot metal films on yttira-stabilized zirconia (YSZ) with specific and knowable geometries, useful for mechanistic studies. Particular attention was given to anode structures, for which anti-dot metal films on YSZ served as composite substrates for subsequent CELD of doped ceria. By tuning the applied potential, a wide range of microstructures from high surface area coatings to planar, thin films was possible. In addition, definitive deposition was shown to occur on the electronically insulating YSZ surfaces, producing quality YSZ|ceria interfaces. These CELD ceria deposits exhibited promising electrochemical activity, as probed by A.C. Impedance Spectroscopy. In an effort to extend its usefulness as a SOFC fabrication tool, the CELD of ceria directly onto common SOFC cathode materials without a metallic phase was developed, as well as templated deposition schemes producing ceria nanowires and inverse opals.

  2. 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.

  3. 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.'

  4. Electrophoretic deposition of biomaterials.

    PubMed

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

    2010-10-01

    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.

  5. 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.

  6. 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

  7. Mechanistic Basis of Resistance to PCBs in Atlantic Tomcod from the Hudson River

    PubMed Central

    Wirgin, Isaac; Roy, Nirmal K.; Loftus, Matthew; Chambers, R. Christopher; Franks, Diana G.; Hahn, Mark E.

    2011-01-01

    The mechanistic basis of resistance of vertebrate populations to contaminants, including Atlantic tomcod from the Hudson River (HR) to polychlorinated biphenyls (PCBs), is unknown. HR tomcod exhibited variants in the aryl hydrocarbon receptor 2 (AHR2) that were nearly absent elsewhere. In ligand-binding assays, AHR2-1 protein (common in the HR) was impaired as compared to widespread AHR2-2 in binding TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and in driving expression in reporter gene assays in AHR-deficient cells treated with TCDD or PCB126. We identified a six-base deletion in AHR2 as the basis of resistance and suggest that the HR population has undergone rapid evolution, probably due to contaminant exposure. This mechanistic basis of resistance in a vertebrate population provides evidence of evolutionary change due to selective pressure at a single locus. PMID:21330491

  8. 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.

  9. Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis.

    PubMed

    Brown, Gordon T; Murray, Graeme I

    2015-11-01

    The purpose of this review is to highlight the recent mechanistic developments elucidating the role of matrix metalloproteinases (MMPs) in tumour invasion and metastasis. The ability of tumour cells to invade, migrate, and subsequently metastasize is a fundamental characteristic of cancer. Tumour invasion and metastasis are increasingly being characterized by the dynamic relationship between cancer cells and their microenvironment and developing a greater understanding of these basic pathological mechanisms is crucial. While MMPs have been strongly implicated in these processes as a result of extensive circumstantial evidence--for example, increased expression of individual MMPs in tumours and association of specific MMPs with prognosis--the underpinning mechanisms are only now being elucidated. Recent studies are now providing a mechanistic basis, highlighting and reinforcing the catalytic and non-catalytic roles of specific MMPs as key players in tumour invasion and metastasis.

  10. 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.

  11. Conceptual models for waste tank mechanistic analysis. Status report, January 1991

    SciTech Connect

    Allemann, R. T.; Antoniak, Z. I.; Eyler, L. L.; Liljegren, L. M.; Roberts, J. S.

    1992-02-01

    Pacific Northwest Laboratory (PNL) is conducting a study for Westinghouse Hanford Company (Westinghouse Hanford), a contractor for the US Department of Energy (DOE). The purpose of the work is to study possible mechanisms and fluid dynamics contributing to the periodic release of gases from double-shell waste storage tanks at the Hanford Site in Richland, Washington. This interim report emphasizing the modeling work follows two other interim reports, Mechanistic Analysis of Double-Shell Tank Gas Release Progress Report -- November 1990 and Collection and Analysis of Existing Data for Waste Tank Mechanistic Analysis Progress Report -- December 1990, that emphasized data correlation and mechanisms. The approach in this study has been to assemble and compile data that are pertinent to the mechanisms, analyze the data, evaluate physical properties and parameters, evaluate hypothetical mechanisms, and develop mathematical models of mechanisms.

  12. 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.

  13. 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.

  14. 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

    2014-01-01

    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. PMID:24858098

  15. 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.

  16. Silicon source for vacuum deposition

    NASA Technical Reports Server (NTRS)

    Racette, G. W.; Rutecki, D. J.

    1979-01-01

    Device using two independent silicon sources for ultra-high-vacuum deposition on large substrates can deposit P and N types of silicon simultaneously. Efficient water cooled copper shield supports and cools structure and isolates two filaments.

  17. Data-driven mechanistic analysis method to reveal dynamically evolving regulatory networks

    PubMed Central

    Intosalmi, Jukka; Nousiainen, Kari; Ahlfors, Helena; Lähdesmäki, Harri

    2016-01-01

    Motivation: Mechanistic models based on ordinary differential equations provide powerful and accurate means to describe the dynamics of molecular machinery which orchestrates gene regulation. When combined with appropriate statistical techniques, mechanistic models can be calibrated using experimental data and, in many cases, also the model structure can be inferred from time–course measurements. However, existing mechanistic models are limited in the sense that they rely on the assumption of static network structure and cannot be applied when transient phenomena affect, or rewire, the network structure. In the context of gene regulatory network inference, network rewiring results from the net impact of possible unobserved transient phenomena such as changes in signaling pathway activities or epigenome, which are generally difficult, but important, to account for. Results: We introduce a novel method that can be used to infer dynamically evolving regulatory networks from time–course data. Our method is based on the notion that all mechanistic ordinary differential equation models can be coupled with a latent process that approximates the network structure rewiring process. We illustrate the performance of the method using simulated data and, further, we apply the method to study the regulatory interactions during T helper 17 (Th17) cell differentiation using time–course RNA sequencing data. The computational experiments with the real data show that our method is capable of capturing the experimentally verified rewiring effects of the core Th17 regulatory network. We predict Th17 lineage specific subnetworks that are activated sequentially and control the differentiation process in an overlapping manner. Availability and Implementation: An implementation of the method is available at http://research.ics.aalto.fi/csb/software/lem/. Contacts: jukka.intosalmi@aalto.fi or harri.lahdesmaki@aalto.fi PMID:27307629

  18. Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

    PubMed Central

    Ghashghaei, Ouldouz; Manna, Consiglia Annamaria; Vicente-García, Esther; Revés, Marc

    2014-01-01

    Summary The interaction of imines with isocyanides has been studied. The main product results from a sequential process involving the attack of two units of isocyanide, under Lewis acid catalysis, upon the carbon–nitrogen double bond of the imine to form the 4-membered ring system. The scope of the reaction regarding the imine and isocyanide ranges has been determined, and also some mechanistic variations and structural features have been described. PMID:24454559

  19. Pulse plating of nickel deposits

    SciTech Connect

    Stimetz, C.J.; Stevenson, M.F.

    1980-02-01

    Pulse plated and conventional nickel deposits have been compared for differences in morphology, mechanical properties, and microstructure. The deposits were obtained from nickel sulfamate, nickel chloride, and Watts nickel plating solutions. No significant differences were found in the direct and pulse current deposits from the sulfamate and chloride solutions; however, significant differences in microstructure, yield strength, and microhardness were observed in deposits from the Watts nickel solution.

  20. 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.

  1. Mechanistic models of animal migration behaviour – their diversity, structure and use

    PubMed Central

    Bauer, Silke; Klaassen, Marcel

    2013-01-01

    Migration is a wide-spread 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, e.g. in relation to the spread of emerging zoonotic diseases, the proliferation of invasive species, aeronautical safety as well as the conservation of migrants.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 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.Therefore, we provide an overview of the major mechanistic modelling approaches used in the study of migration behaviour and characterise their fundamental features, assumptions and limitations, and discuss their typical data requirements both for model parameterisation and for scrutinizing model predictions.Furthermore, we review 155 studies that have used mechanistic models to study animal migration and analyse them with regard to the approaches used, focal species and also explore their contribution of advancing current knowledge within six broad migration ecology research themes.This identifies important gaps in our present knowledge, which should be tackled in future research using existing and to-be developed theoretical approaches. PMID:23373515

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

    PubMed Central

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

    2016-01-01

    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. PMID:27624453

  3. 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.

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

    PubMed

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

    2016-01-01

    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 R(2) > 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. PMID:27624453

  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. PMID:16224691

  6. Ecological forecasting in Chesapeake Bay: Using a mechanistic-empirical modeling approach

    NASA Astrophysics Data System (ADS)

    Brown, C. W.; Hood, R. R.; Long, W.; Jacobs, J.; 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.

  7. 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.

  8. 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.

  9. Model discrimination and mechanistic interpretation of kinetic data in protein aggregation studies.

    PubMed

    Bernacki, Joseph P; Murphy, Regina M

    2009-04-01

    Given the importance of protein aggregation in amyloid diseases and in the manufacture of protein pharmaceuticals, there has been increased interest in measuring and modeling the kinetics of protein aggregation. Several groups have analyzed aggregation data quantitatively, typically measuring aggregation kinetics by following the loss of protein monomer over time and invoking a nucleated growth mechanism. Such analysis has led to mechanistic conclusions about the size and nature of the nucleus, the aggregation pathway, and/or the physicochemical properties of aggregation-prone proteins. We have examined some of the difficulties that arise when extracting mechanistic meaning from monomer-loss kinetic data. Using literature data on the aggregation of polyglutamine, a mutant beta-clam protein, and protein L, we determined parameter values for 18 different kinetic models. We developed a statistical model discrimination method to analyze protein aggregation data in light of competing mechanisms; a key feature of the method is that it penalizes overparameterization. We show that, for typical monomer-loss kinetic data, multiple models provide equivalent fits, making mechanistic determination impossible. We also define the type and quality of experimental data needed to make more definitive conclusions about the mechanism of aggregation. Specifically, we demonstrate how direct measurement of fibril size provides robust discrimination. PMID:19348769

  10. 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.

  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. 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."

  13. Left ventricular partitioning in systolic heart failure subjects: addressing a mechanistic void with current therapies.

    PubMed

    Schäfer, Ulrich

    2016-05-17

    ICD patients with narrow QRS, CRT non-responders, and functional MR patients all have one mechanistic failure mode that is left untreated - the scar left behind following an MI. ICDs, CRTs, and MitraClip implantation are all well-proven therapies, but the Parachute device may address the mechanistic void that remains after each of these therapies has been used and may further improve patients' outcomes. A pooled analysis of 134 subjects was conducted using the first three clinical trials which included subjects with symptomatic ischaemic HF with LV wall motion abnormalities secondary to MI, and an LV ejection fraction less than 40%. The two-year cumulative mortality rate was 12.9%, with 8.7% in the first year and an increment of 4.2% in the second, which is a 53% reduction as compared to the first year. There is a significant proportion of patients with ischaemic heart failure being excluded from cardiac rhythm management (CRT, etc.), leaving a large treatment gap until mechanical support devices (LVAD) or heart transplantation in progressive heart failure are indicated. Along with other heart failure devices, Parachute may be a useful treatment modality, addressing a mechanistic void in the treatment of this disease. Current data support improvements in haemodynamics, functional capacity, six-minute walk distance, quality of life and a promising decline in mortality two years after Parachute implantation. PMID:27174122

  14. 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. PMID:26825142

  15. 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

  16. Mechanistic insight into gramicidin-based detection of protein-ligand interactions via sensitized photoinactivation.

    PubMed

    Rokitskaya, Tatyana I; Macrae, Michael X; Blake, Steven; Egorova, Natalya S; Kotova, Elena A; Yang, Jerry; Antonenko, Yuri N

    2010-11-17

    Among the many challenges for the development of ion channel-based sensors is the poor understanding of how to engineer modified transmembrane pores with tailored functionality that can respond to external stimuli. Here, we use the method of sensitized photoinactivation of gramicidin A (gA) channels in planar bilayer lipid membranes to help elucidate the underlying mechanistic details for changes in macroscopic transmembrane ionic current observed upon interaction of C-terminally attached gA ligands with specific proteins in solution. Three different systems were studied: (i) carbonic anhydrase (CA) and gA-sulfonamide, (ii) PSD-95 protein (belonging to the 'PDZ domain-containing protein') and a gA analog carrying the KGGHRRSARYLESSV peptide sequence at the C-terminus, and (iii) an anti-biotin antibody and gA-biotin. The results challenge a previously proposed mechanistic hypothesis suggesting that protein-induced current suppression is due to steric blockage of the ion passage through gA channels, while they reveal new insight for consideration in alternative mechanistic models. Additionally, we demonstrate that the length of a linker between the ligand and the gA channel may be less important for gramicidin-based detection of monovalent compared to multivalent protein-ligand interactions. These studies collectively shed new light on the mechanism of protein-induced current alterations in bilayer recordings of gA derivatives, which may be important in the design of new gramicidin-based sensors.

  17. Mechanistic insight into gramicidin-based detection of protein-ligand interactions via sensitized photoinactivation

    NASA Astrophysics Data System (ADS)

    Rokitskaya, Tatyana I.; Macrae, Michael X.; Blake, Steven; Egorova, Natalya S.; Kotova, Elena A.; Yang, Jerry; Antonenko, Yuri N.

    2010-11-01

    Among the many challenges for the development of ion channel-based sensors is the poor understanding of how to engineer modified transmembrane pores with tailored functionality that can respond to external stimuli. Here, we use the method of sensitized photoinactivation of gramicidin A (gA) channels in planar bilayer lipid membranes to help elucidate the underlying mechanistic details for changes in macroscopic transmembrane ionic current observed upon interaction of C-terminally attached gA ligands with specific proteins in solution. Three different systems were studied: (i) carbonic anhydrase (CA) and gA-sulfonamide, (ii) PSD-95 protein (belonging to the 'PDZ domain-containing protein') and a gA analog carrying the KGGHRRSARYLESSV peptide sequence at the C-terminus, and (iii) an anti-biotin antibody and gA-biotin. The results challenge a previously proposed mechanistic hypothesis suggesting that protein-induced current suppression is due to steric blockage of the ion passage through gA channels, while they reveal new insight for consideration in alternative mechanistic models. Additionally, we demonstrate that the length of a linker between the ligand and the gA channel may be less important for gramicidin-based detection of monovalent compared to multivalent protein-ligand interactions. These studies collectively shed new light on the mechanism of protein-induced current alterations in bilayer recordings of gA derivatives, which may be important in the design of new gramicidin-based sensors.

  18. Mechanistic models

    SciTech Connect

    Curtis, S.B.

    1990-09-01

    Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (1) interaction'' of lesions produced by statistically independent particle tracks; (2) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (3) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the RMR and LPL models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.

  19. Mechanistic models

    SciTech Connect

    Curtis, S.B.

    1990-09-01

    Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (1) ``interaction`` of lesions produced by statistically independent particle tracks; (2) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (3) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the RMR and LPL models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Chemical vapor deposition sciences

    SciTech Connect

    1992-12-31

    Chemical vapor deposition (CVD) is a widely used method for depositing thin films of a variety of materials. Applications of CVD range from the fabrication of microelectronic devices to the deposition of protective coatings. New CVD processes are increasingly complex, with stringent requirements that make it more difficult to commercialize them in a timely fashion. However, a clear understanding of the fundamental science underlying a CVD process, as expressed through computer models, can substantially shorten the time required for reactor and process development. Research scientists at Sandia use a wide range of experimental and theoretical techniques for investigating the science of CVD. Experimental tools include optical probes for gas-phase and surface processes, a range of surface analytic techniques, molecular beam methods for gas/surface kinetics, flow visualization techniques and state-of-the-art crystal growth reactors. The theoretical strategy uses a structured approach to describe the coupled gas-phase and gas-surface chemistry, fluid dynamics, heat and mass transfer of a CVD process. The software used to describe chemical reaction mechanisms is easily adapted to codes that model a variety of reactor geometries. Carefully chosen experiments provide critical information on the chemical species, gas temperatures and flows that are necessary for model development and validation. This brochure provides basic information on Sandia`s capabilities in the physical and chemical sciences of CVD and related materials processing technologies. It contains a brief description of the major scientific and technical capabilities of the CVD staff and facilities, and a brief discussion of the approach that the staff uses to advance the scientific understanding of CVD processes.

  5. [Triglyceride deposit cardiomyovasculopathy].

    PubMed

    Hirano, Ken-Ichi

    2013-09-01

    Cholesterol is a vital causal factor and focus of research into heart diseases, however the involvement of triglycerides remains unclear. We recently reported a patient suffering from severe congestive heart failure and needing cardiac transplantation. Massive accumulation of triglycerides was noted in coronary atherosclerotic lesions as well as in the myocardium. We named this phenotype"triglyceride deposit cardiomyovasculopathy (TGCV)". The patient was identified as homozygous for a genetic mutation in the adipose triglyceride lipase (ATGL), an essential molecule for hydrolysis of intracellular triglycerides. In this paper, we describe clinical characteristics of ATGL deficiency and discuss what we can learn from this disorder.

  6. Deposition System Controller

    2005-10-01

    This software is a complete thin film deposition controller. The software takes as its input a script file that dictates enablinig/disabling of sputtering power supplies, pause times, velocities and distances to move a substrate. An emulator has been created and built into the software package that can debug in advance any deposition script and decide if there is an overrun condition, accidental infinite look, and can estimate a time for completion. All necessary process variablesmore » are data logged and recorded for later inspection. This emulator currently interfaces to a Parker-Compumotor SX6 stepper moror indexer, but the software is written in such a way that it is easily modifiable for interface to othe brand and models of motor drivers. Other process I/O variables may be easily added. The software uses any multifunction DAQ card from National Instruments via their free NIDAQ API package, but again, the software is written such that othe brand DAQ cards may be used.« less

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. A Parsimonious Modular Approach to Building a Mechanistic Belowground C and N Model

    NASA Astrophysics Data System (ADS)

    Abramoff, R. Z.; Davidson, E. A.; Finzi, A.

    2014-12-01

    Ecosystem models simulate belowground processes of element cycling, such as soil carbon dynamics, through numerical representations of our mechanistic understanding of these processes. This poses a great challenge, because many mechanistic models are so highly parameterized and complex that the reasons for their behavior are often difficult to understand, while others are so simplistic that they are unlikely to capture potentially important complexities, such as C-N interactions. Here we propose a mechanistic, but parsimonious modular approach to building a belowground C and N model, with a core processes-level representation of microbial and exoenzymatic activity. We have merged the Dual-Arrhenius Michaelis Menten (DAMM) model of Davidson et al. (2012) with the Microbial Carbon and Nitrogen Physiology (MCNiP) model of Drake et al. (2013). DAMM explicitly simulates the effects of temperature, soil moisture and substrate supply on the kinetics of soil organic matter (SOM) depolymerization. MCNiP is a stoichiometrically constrained model of microbial maintenance and growth respiration, exoenzyme production, and C and N uptake and mineralization. Here we present the results of this model merger, focusing on how temperature, soil moisture, substrate limitation, and the stoichiometry of microbial processes individually and interactively regulate gains or losses of C and N from SOM at the Harvard Forest. We compare model performance running DAMM-MCNiP with and without C-N linkages. We find that substrate limitation is a major constraint over SOM decomposition and that N availability can be a strong regulator of decomposition. The C-only formulation of DAMM-MCNiP generally results in greater losses of SOC than the coupled C-N formulation. Future data-model assimilation and parameter estimation will help determine which aspects of the merged model can be well constrained and which aspects will need further refinement through new data collection or meta-analysis.

  13. 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

  14. 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

  15. Mechanistic Explanations for Restricted Evolutionary Paths That Emerge from Gene Regulatory Networks

    PubMed Central

    Cotterell, James; Sharpe, James

    2013-01-01

    The extent and the nature of the constraints to evolutionary trajectories are central issues in biology. Constraints can be the result of systems dynamics causing a non-linear mapping between genotype and phenotype. How prevalent are these developmental constraints and what is their mechanistic basis? Although this has been extensively explored at the level of epistatic interactions between nucleotides within a gene, or amino acids within a protein, selection acts at the level of the whole organism, and therefore epistasis between disparate genes in the genome is expected due to their functional interactions within gene regulatory networks (GRNs) which are responsible for many aspects of organismal phenotype. Here we explore epistasis within GRNs capable of performing a common developmental function – converting a continuous morphogen input into discrete spatial domains. By exploring the full complement of GRN wiring designs that are able to perform this function, we analyzed all possible mutational routes between functional GRNs. Through this study we demonstrate that mechanistic constraints are common for GRNs that perform even a simple function. We demonstrate a common mechanistic cause for such a constraint involving complementation between counter-balanced gene-gene interactions. Furthermore we show how such constraints can be bypassed by means of “permissive” mutations that buffer changes in a direct route between two GRN topologies that would normally be unviable. We show that such bypasses are common and thus we suggest that unlike what was observed in protein sequence-function relationships, the “tape of life” is less reproducible when one considers higher levels of biological organization. PMID:23613807

  16. Global deposition of airborne dioxin.

    PubMed

    Booth, Shawn; Hui, Joe; Alojado, Zoraida; Lam, Vicky; Cheung, William; Zeller, Dirk; Steyn, Douw; Pauly, Daniel

    2013-10-15

    We present a global dioxin model that simulates one year of atmospheric emissions, transport processes, and depositions to the earth's terrestrial and marine habitats. We map starting emission levels for each land area, and we also map the resulting deposits to terrestrial and marine environments. This model confirms that 'hot spots' of deposition are likely to be in northern Europe, eastern North America, and in parts of Asia with the highest marine dioxin depositions being the northeast and northwest Atlantic, western Pacific, northern Indian Ocean and the Mediterranean. It also reveals that approximately 40% of airborne dioxin emissions are deposited to marine environments and that many countries in Africa receive more dioxin than they produce, which results in these countries being disproportionately impacted. Since human exposure to dioxin is largely through diet, this work highlights food producing areas that receive higher atmospheric deposits of dioxin than others.

  17. Lunar western limb pyroclastic deposits

    NASA Technical Reports Server (NTRS)

    Coombs, Cassandra R.; Hawke, B. Ray

    1991-01-01

    It has become increasingly evident that the lunar pyroclastic volcanism played an important role in the formation and resurfacing of many areas of the Moon. On-going analysis of lunar Orbiter and Apollo photographs continues to locate and identify pyroclastic deposits and suggests that they just may be more ubiquitous than once thought. Located near mare/highland boundaries, many of these deposits formed contemporaneously with effusive mare volcanism. The mantling deposits formed as products of fire-fountaining. Probable source vents for these deposits include irregular depressions at the head of associated sinuous rilles and/or along irregular fractures in the floors of ancient craters. Here, researchers provide a brief synopsis of the nature of the dark mantling deposits and briefly discuss several newly identified deposits on the western limb.

  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. 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.

  20. 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.

  1. Copper/TEMPO-Catalyzed Aerobic Alcohol Oxidation: Mechanistic Assessment of Different Catalyst Systems

    PubMed Central

    Hoover, Jessica M.; Ryland, Bradford L.; Stahl, Shannon S.

    2013-01-01

    Combinations of homogeneous Cu salts and TEMPO have emerged as practical and efficient catalysts for the aerobic oxidation of alcohols. Several closely related catalyst systems have been reported, which differ in the identity of the solvent, the presence of 2,2′-bipyridine as a ligand, the identity of basic additives, and the oxidation state of the Cu source. These changes have a significant influence on the reaction rates, yields, and substrate scope. In this report, we probe the mechanistic basis for differences among four different Cu/TEMPO catalyst systems and elucidate the features that contribute to efficient oxidation of aliphatic alcohols. PMID:24558634

  2. 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.

  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. 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

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

    DOE PAGES

    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.

  6. Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging.

    PubMed

    Kiecolt-Glaser, Janice K; Wilson, Stephanie J

    2016-09-01

    A meta-analysis published in this issue of Psychosomatic Medicine provides convincing evidence that certain psychiatric populations have shorter telomeres than nonpsychiatric controls, in accord with the strong evidence linking psychiatric disorders with premature mortality. After addressing the clinical significance of shorter telomeres, this editorial describes mechanistic pathways that lead to telomere shortening. Additionally, two other novel methods for measuring biological markers of accelerated aging are briefly discussed: DNA methylation and cellular senescence based on p16. These innovative approaches could be used to confirm and extend our understanding of psychiatric patients' increased health and mortality risks.

  7. 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

  8. Cross-Coupling Synthesis of Methylallyl Alkenes: Scope Extension and Mechanistic Study.

    PubMed

    Tabélé, Clémence; Curti, Christophe; Kabri, Youssef; Primas, Nicolas; Vanelle, Patrice

    2015-12-21

    Cross-coupling reactions between 2-methyl-2-propen-1-ol and various boronic acids are used to obtain aromatic-(2-methylallyl) derivatives. However, deboronation or isomerization side reactions may occur for several boronic acids. We describe herein the synthesis of original alkenes with good yields under mild reaction conditions that decrease these side reactions. The scope of this environmentally benign reaction is thereby extended to a wide variety of boronic acids. A mechanistic study was conducted and suggested a plausible catalytic cycle mechanism, pointing to the importance of the Lewis acidity of the boronic acid used.

  9. Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

    PubMed

    Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

    2016-08-01

    Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed. PMID:27444495

  10. Copper/TEMPO-Catalyzed Aerobic Alcohol Oxidation: Mechanistic Assessment of Different Catalyst Systems.

    PubMed

    Hoover, Jessica M; Ryland, Bradford L; Stahl, Shannon S

    2013-11-01

    Combinations of homogeneous Cu salts and TEMPO have emerged as practical and efficient catalysts for the aerobic oxidation of alcohols. Several closely related catalyst systems have been reported, which differ in the identity of the solvent, the presence of 2,2'-bipyridine as a ligand, the identity of basic additives, and the oxidation state of the Cu source. These changes have a significant influence on the reaction rates, yields, and substrate scope. In this report, we probe the mechanistic basis for differences among four different Cu/TEMPO catalyst systems and elucidate the features that contribute to efficient oxidation of aliphatic alcohols. PMID:24558634

  11. 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.

  12. 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.

  13. (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.

  14. Electron beam deposition for nanofabrication: Insights from surface science

    NASA Astrophysics Data System (ADS)

    Wnuk, J. D.; Rosenberg, S. G.; Gorham, J. M.; van Dorp, W. F.; Hagen, C. W.; Fairbrother, D. H.

    2011-02-01

    Electron beam induced deposition (EBID) is a direct-write lithographic technique that utilizes the dissociation of volatile precursors by a focused electron beam in a low vacuum environment to create nanostructures. Notable advantages of EBID over competing lithographic techniques are that it is a single step process that allows three-dimensional free-standing structures to be created, including features with single-nanometer scale dimensions. However, despite the inherent advantages of EBID, scientific and technological issues are impeding its development as an industrial nanofabrication tool. Perhaps the greatest single limitation of EBID is that metal-containing nanostructures deposited from organometallic precursors typically possess unacceptable levels of organic contamination which adversely affects the material's properties. In addition to the issue of purity, there is also a lack of understanding and quantitative information on the fundamental surface reactions and reaction cross-sections that are responsible for EBID. In this prospective, we describe how surface analytical techniques have begun to provide mechanistic and kinetic insights into the molecular level processes associated with EBID. This has been achieved by observing the effect of electron irradiation on nanometer thick films of organometallic precursors adsorbed onto solid substrates at low temperatures (< 200 K) under ultra-high vacuum conditions. Experimental observations include probing changes in surface composition, metal oxidation state, and the evolution of volatile species. Insights into surface reactions associated with purification strategies are also detailed. We also discuss unresolved scientific challenges and opportunities for future EBID research.

  15. Methodology for estimating crop loss from acidic deposition

    SciTech Connect

    Irving, P.M.

    1982-01-01

    Crop losses affect the production, availability and cost of food, and therefore have important economic, social, and political implications especially during this period of rapid world population growth. The fact that air-borne pollutants affect vegetative growth has been known for more than a century. Recently, the acidic deposition phenomenon has gained increasing attention, especially when implicated as a factor potentially responsible for crop yield losses. Experimental approaches utilized in traditional pollution effects research include: field surveys, sensitivity classification, dose-response studies, and regional-impact evaluation. Acid rain is a unique pollutant having special problems associated with researching its effects. For example, the description of dose for this pollutant should include rain chemistry (not just pH), rainfall rate, duration of event, total deposition, droplet size, etc. These parameters must also be considered when simulating rain in controlled studies. Due to the potential for interactions with biotic and abiotic entities, factorial research designs and multivariate analyses may be necessary for investigations of acid-rain impacts on crops. Results from well-planned mechanistic studies and dose-response experiments may be used to predict effects (both positive and negative), assess economic impacts, and establish tolerance thresholds for this form of pollution.

  16. Multiphysics modeling of porous CRUD deposits in nuclear reactors

    NASA Astrophysics Data System (ADS)

    Short, M. P.; Hussey, D.; Kendrick, B. K.; Besmann, T. M.; Stanek, C. R.; Yip, S.

    2013-11-01

    The formation of porous CRUD deposits on nuclear reactor fuel rods, a longstanding problem in the operation of pressurized water reactors (PWRs), is a significant challenge to science-based multiscale modeling and simulation. While existing, published studies have focused on individual or loosely coupled processes, such as heat transfer, fluid flow, and compound dissolution/precipitation, none have addressed their coupled effects sufficiently to enable a comprehensive, scientific understanding of CRUD. Here we present the formulation and results of a model, MAMBA-BDM, which begins to incorporate mechanistic details in describing CRUD in PWRs. CRUD is treated as a chemical deposition process in an environment of variable concentration, an arbitrary level of heating, and a complex fractal-based flow geometry. We present results on spatial distributions of temperature, pressure, velocity, and concentration that give insight into the interplay between these physical properties and geometrical parameters. We show the role of heat convection which has not been discussed previously. Furthermore, we suggest that the assumption of liquid saturation in the CRUD deserves scrutiny, as a result of our attempt to determine an effective CRUD thermal conductivity.

  17. 78 FR 11604 - Deposit Insurance Regulations; Definition of Insured Deposit

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ... face as a global deposit insurer. Should a United States bank make its foreign deposits dually payable... will be protected from potential global liability. The proposed rule would not affect the ability of a... faces potential liability that could be global in scope, a risk that could extend to the United...

  18. Enhanced nitrogen deposition over China.

    PubMed

    Liu, Xuejun; Zhang, Ying; Han, Wenxuan; Tang, Aohan; Shen, Jianlin; Cui, Zhenling; Vitousek, Peter; Erisman, Jan Willem; Goulding, Keith; Christie, Peter; Fangmeier, Andreas; Zhang, Fusuo

    2013-02-28

    China is experiencing intense air pollution caused in large part by anthropogenic emissions of reactive nitrogen. These emissions result in the deposition of atmospheric nitrogen (N) in terrestrial and aquatic ecosystems, with implications for human and ecosystem health, greenhouse gas balances and biological diversity. However, information on the magnitude and environmental impact of N deposition in China is limited. Here we use nationwide data sets on bulk N deposition, plant foliar N and crop N uptake (from long-term unfertilized soils) to evaluate N deposition dynamics and their effect on ecosystems across China between 1980 and 2010. We find that the average annual bulk deposition of N increased by approximately 8 kilograms of nitrogen per hectare (P < 0.001) between the 1980s (13.2 kilograms of nitrogen per hectare) and the 2000s (21.1 kilograms of nitrogen per hectare). Nitrogen deposition rates in the industrialized and agriculturally intensified regions of China are as high as the peak levels of deposition in northwestern Europe in the 1980s, before the introduction of mitigation measures. Nitrogen from ammonium (NH4(+)) is the dominant form of N in bulk deposition, but the rate of increase is largest for deposition of N from nitrate (NO3(-)), in agreement with decreased ratios of NH3 to NOx emissions since 1980. We also find that the impact of N deposition on Chinese ecosystems includes significantly increased plant foliar N concentrations in natural and semi-natural (that is, non-agricultural) ecosystems and increased crop N uptake from long-term-unfertilized croplands. China and other economies are facing a continuing challenge to reduce emissions of reactive nitrogen, N deposition and their negative effects on human health and the environment. PMID:23426264

  19. Enhanced nitrogen deposition over China.

    PubMed

    Liu, Xuejun; Zhang, Ying; Han, Wenxuan; Tang, Aohan; Shen, Jianlin; Cui, Zhenling; Vitousek, Peter; Erisman, Jan Willem; Goulding, Keith; Christie, Peter; Fangmeier, Andreas; Zhang, Fusuo

    2013-02-28

    China is experiencing intense air pollution caused in large part by anthropogenic emissions of reactive nitrogen. These emissions result in the deposition of atmospheric nitrogen (N) in terrestrial and aquatic ecosystems, with implications for human and ecosystem health, greenhouse gas balances and biological diversity. However, information on the magnitude and environmental impact of N deposition in China is limited. Here we use nationwide data sets on bulk N deposition, plant foliar N and crop N uptake (from long-term unfertilized soils) to evaluate N deposition dynamics and their effect on ecosystems across China between 1980 and 2010. We find that the average annual bulk deposition of N increased by approximately 8 kilograms of nitrogen per hectare (P < 0.001) between the 1980s (13.2 kilograms of nitrogen per hectare) and the 2000s (21.1 kilograms of nitrogen per hectare). Nitrogen deposition rates in the industrialized and agriculturally intensified regions of China are as high as the peak levels of deposition in northwestern Europe in the 1980s, before the introduction of mitigation measures. Nitrogen from ammonium (NH4(+)) is the dominant form of N in bulk deposition, but the rate of increase is largest for deposition of N from nitrate (NO3(-)), in agreement with decreased ratios of NH3 to NOx emissions since 1980. We also find that the impact of N deposition on Chinese ecosystems includes significantly increased plant foliar N concentrations in natural and semi-natural (that is, non-agricultural) ecosystems and increased crop N uptake from long-term-unfertilized croplands. China and other economies are facing a continuing challenge to reduce emissions of reactive nitrogen, N deposition and their negative effects on human health and the environment.

  20. Computational mechanistic study of the Julia-Kocieński reaction.

    PubMed

    Legnani, Laura; Porta, Alessio; Caramella, Pierluigi; Toma, Lucio; Zanoni, Giuseppe; Vidari, Giovanni

    2015-03-20

    This paper describes the first detailed computational mechanistic study of the Julia-Kocieński olefination between acetaldehyde (1) and ethyl 1-phenyl-1H-tetrazol-5-yl sulfone (2), considered a paradigmatic example of the reaction between unsubstituted alkyl PT sulfones and linear aliphatic aldehydes. The theoretical study was performed within the density functional approach through calculations at the B3LYP/6-311+G(d,p) level for all atoms except sulfur for which the 6-311+G(2df,p) basis set was used. All the different intermediates and transition states encountered along the reaction pathways leading to final E and Z olefins have been located and the relative energies calculated, both for the reactions with potassium- and lithium-metalated sulfones, in THF and toluene, respectively. We have essentially confirmed the complex multistep mechanistic manifold proposed by others; however, the formation of a spirocyclic intermediate in the Smiles rearrangement was excluded. Instead, we found that this step involves a concerted, though asynchronous, mechanism. Moreover, our calculations nicely fit with the diastereoselectivities observed experimentally for potassium- and lithium-metalated sulfones, in THF and toluene, respectively.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25377891

  2. Mechanistic determination of fission product releases for a Mark III BWR plant

    SciTech Connect

    Ludewig, H.; Yu, W.S.; Jaung, R.; Pratt, W.T.

    1986-01-01

    During the review of the GESSAR-II PRA by the Nuclear Regulatory Commission (NRC) and their contractors at Brookhaven National Laboratory (BNL) it was necessary to reanalyze potential fission product releases to the environment for several core meltdown accident sequences. The reanalysis was performed at BNL in two stages. The first stage was carried out prior to detailed mechanistic models were available at BNL and consisted of a sensitivity analysis using the MARCH and CORRAL computer codes. The effects of uncertainties in primary system retention, suppression pool scrubbing and core/concrete interactions on fission product release were handled by varying inputs to the MARCH/CORRAL codes. In this paper we outline the second stage of fission product release calculations, which was based on a system of codes developed under sponsorship of the Accident Source Term Program Office (ASTPO), USNRC. A comparison will be made between the range of source terms calculated by the first approach and the point estimate calculations provided by the more mechanistic codes. 8 refs., 2 tabs.

  3. 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

  4. 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.

  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. 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.

  7. Unravelling the Relationship between Body Mass Index and Polychlorinated Biphenyl Concentrations Using a Mechanistic Model.

    PubMed

    Wood, Stephen A; Xu, Feng; Armitage, James M; Wania, Frank

    2016-09-20

    Human biomonitoring (HBM) often reveals statistical associations between persistent organic pollutant (POP) concentrations and body mass index (BMI). Both negative and positive associations have been observed, which has been hypothesized to reflect variable toxicokinetics in lean and obese individuals during times of increasing and decreasing exposure. We examined this hypothesis and assessed the influence of the obesity epidemic on time trends in human exposure to polychlorinated biphenyls (PCB) at the population level using a mechanistic modeling approach and data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Using model results for PCB-153, we simulated cross-sectional body burden versus BMI trends (CBBTs), as well as population level body burden versus time trends. Negative associations between PCB-153 concentrations and BMI are predicted for all birth cohorts in HBM studies conducted in the 1990s, while for future cross-sectional studies, we predict negative or positive relationships depending on the age group sampled. At the population level, demographic changes such as the obesity epidemic and population aging had only marginal influence on the simulated rate of decline in PCB-153 concentrations between 1980 and 2010. Mechanistic bioaccumulation models can help unravel relationships between age, BMI, and POP concentrations, informing efforts to understand potential obesogenic effects of POPs. PMID:27616073

  8. 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.

  9. Ultrasound and Microbubble Guided Drug Delivery: Mechanistic Understanding and Clinical Implications

    PubMed Central

    Wang, Tzu-Yin; Wilson, Katheryne E.; Machtaler, Steven; Willmann, Jürgen K.

    2014-01-01

    Ultrasound mediated drug delivery using microbubbles is a safe and noninvasive approach for spatially localized drug administration. This approach can create temporary and reversible openings on cellular membranes and vessel walls (a process called “sonoporation”), allowing for enhanced transport of therapeutic agents across these natural barriers. It is generally believed that the sonoporation process is highly associated with the energetic cavitation activities (volumetric expansion, contraction, fragmentation, and collapse) of the microbubble. However, a thorough understanding of the process was unavailable until recently. Important progress on the mechanistic understanding of sonoporation and the corresponding physiological responses in vitro and in vivo has been made. Specifically, recent research shed light on the cavitation process of microbubbles and fluid motion during insonation of ultrasound, on the spatio-temporal interactions between microbubbles and cells or vessel walls, as well as on the temporal course of the subsequent biological effects. These findings have significant clinical implications on the development of optimal treatment strategies for effective drug delivery. In this article, current progress in the mechanistic understanding of ultrasound and microbubble mediated drug delivery and its implications for clinical translation is discussed. PMID:24372231

  10. 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.

  11. 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.

  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. Physiologically induced color-pattern changes in butterfly wings: mechanistic and evolutionary implications.

    PubMed

    Otaki, Joji M

    2008-07-01

    A mechanistic understanding of the butterfly wing color-pattern determination can be facilitated by experimental pattern changes. Here I review physiologically induced color-pattern changes in nymphalid butterflies and their mechanistic and evolutionary implications. A type of color-pattern change can be elicited by elemental changes in size and position throughout the wing, as suggested by the nymphalid groundplan. These changes of pattern elements are bi-directional and bi-sided dislocation toward or away from eyespot foci and in both proximal and distal sides of the foci. The peripheral elements are dislocated even in the eyespot-less compartments. Anterior spots are more severely modified, suggesting the existence of an anterior-posterior gradient. In one species, eyespots are transformed into white spots with remnant-like orange scales, and such patterns emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to heterochronic uncoupling between the signaling and reception steps. The conventional gradient model can be revised to account for these observed color-pattern changes. PMID:18638480

  14. A mechanistic description of the formation and evolution of vegetation patterns

    NASA Astrophysics Data System (ADS)

    Foti, R.; Ramírez, J. A.

    2012-07-01

    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.

  15. 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.

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

    DOE PAGES

    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, 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

  17. Prediction of Phospholipid-Water Partition Coefficients of Ionic Organic Chemicals Using the Mechanistic Model COSMOmic.

    PubMed

    Bittermann, Kai; Spycher, Simon; Endo, Satoshi; Pohler, Larissa; Huniar, Uwe; Goss, Kai-Uwe; Klamt, Andreas

    2014-12-26

    The partition coefficient of chemicals from water to phospholipid membrane, K(lipw), is of central importance for various fields. For neutral organic molecules, log K(lipw) correlates with the log of bulk solvent-water partition coefficients such as the octanol-water partition coefficient. However, this is not the case for charged compounds, for which a mechanistic modeling approach is highly necessary. In this work, we extend the model COSMOmic, which adapts the COSMO-RS theory for anisotropic phases and has been shown to reliably predict K(lipw) for neutral compounds, to the use of ionic compounds. To make the COSMOmic model applicable for ionic solutes, we implemented the internal membrane dipole potential in COSMOmic. We empirically optimized the potential with experimental K(lipw) data of 161 neutral and 75 ionic compounds, yielding potential shapes that agree well with experimentally determined potentials from the literature. This model refinement has no negative effect on the prediction accuracy of neutral compounds (root-mean-square error, RMSE = 0.62 log units), while it highly improves the prediction of ions (RMSE = 0.70 log units). The refined COSMOmic is, to our knowledge, the first mechanistic model that predicts K(lipw) of both ionic and neutral species with accuracies better than 1 log unit.

  18. Mechanistic sediment quality guidelines based on contaminant bioavailability: equilibrium partitioning sediment benchmarks.

    PubMed

    Burgess, Robert M; Berry, Walter J; Mount, David R; Di Toro, Dominic M

    2013-01-01

    Globally, estimated costs to manage (i.e., remediate and monitor) contaminated sediments are in the billions of U.S. dollars. Biologically based approaches for assessing the contaminated sediments which pose the greatest ecological risk range from toxicity testing to benthic community analysis. In addition, chemically based sediment quality guidelines (SQGs) provide a relatively inexpensive line of evidence for supporting these assessments. The present study summarizes a mechanistic SQG based on equilibrium partitioning (EqP), which uses the dissolved concentrations of contaminants in sediment interstitial waters as a surrogate for bioavailable contaminant concentrations. The EqP-based mechanistic SQGs are called equilibrium partitioning sediment benchmarks (ESBs). Sediment concentrations less than or equal to the ESB values are not expected to result in adverse effects and benthic organisms should be protected, while sediment concentrations above the ESB values may result in adverse effects to benthic organisms. In the present study, ESB values are reported for 34 polycyclic aromatic hydrocarbon, 32 other organic contaminants, and seven metals (cadmium, chromium, copper, nickel, lead, silver, zinc). Also included is an overview of EqP theory, ESB derivation, examples of applying ESB values, and considerations when using ESBs. The ESBs are intended as a complement to existing sediment-assessment tools, to assist in determining the extent of sediment contamination, to help identify chemicals causing toxicity, and to serve as targets for pollutant loading control measures.

  19. Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

    PubMed Central

    Carver, Scott; Mills, James N.; Parmenter, Cheryl A.; Parmenter, Robert R.; Richardson, Kyle S.; Harris, Rachel L.; Douglass, Richard J.; Kuenzi, Amy J.; Luis, Angela D.

    2015-01-01

    Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses. PMID:26955081

  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. Biomimetic and Live Medusae Reveal the Mechanistic Advantages of a Flexible Bell Margin

    PubMed Central

    Colin, Sean P.; Costello, John H.; Dabiri, John O.; Villanueva, Alex; Blottman, John B.; Gemmell, Brad J.; Priya, Shashank

    2012-01-01

    Flexible bell margins are characteristic components of rowing medusan morphologies and are expected to contribute towards their high propulsive efficiency. However, the mechanistic basis of thrust augmentation by flexible propulsors remained unresolved, so the impact of bell margin flexibility on medusan swimming has also remained unresolved. We used biomimetic robotic jellyfish vehicles to elucidate that propulsive thrust enhancement by flexible medusan bell margins relies upon fluid dynamic interactions between entrained flows at the inflexion point of the exumbrella and flows expelled from under the bell. Coalescence of flows from these two regions resulted in enhanced fluid circulation and, therefore, thrust augmentation for flexible margins of both medusan vehicles and living medusae. Using particle image velocimetry (PIV) data we estimated pressure fields to demonstrate a mechanistic basis of enhanced flows associated with the flexible bell margin. Performance of vehicles with flexible margins was further enhanced by vortex interactions that occur during bell expansion. Hydrodynamic and performance similarities between robotic vehicles and live animals demonstrated that the propulsive advantages of flexible margins found in nature can be emulated by human-engineered propulsors. Although medusae are simple animal models for description of this process, these results may contribute towards understanding the performance of flexible margins among other animal lineages. PMID:23145016

  2. Physiologically induced color-pattern changes in butterfly wings: mechanistic and evolutionary implications.

    PubMed

    Otaki, Joji M

    2008-07-01

    A mechanistic understanding of the butterfly wing color-pattern determination can be facilitated by experimental pattern changes. Here I review physiologically induced color-pattern changes in nymphalid butterflies and their mechanistic and evolutionary implications. A type of color-pattern change can be elicited by elemental changes in size and position throughout the wing, as suggested by the nymphalid groundplan. These changes of pattern elements are bi-directional and bi-sided dislocation toward or away from eyespot foci and in both proximal and distal sides of the foci. The peripheral elements are dislocated even in the eyespot-less compartments. Anterior spots are more severely modified, suggesting the existence of an anterior-posterior gradient. In one species, eyespots are transformed into white spots with remnant-like orange scales, and such patterns emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to heterochronic uncoupling between the signaling and reception steps. The conventional gradient model can be revised to account for these observed color-pattern changes.

  3. 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.

  4. A tissue-engineered gastric cancer model for mechanistic study of anti-tumor drugs.

    PubMed

    Gao, Ming; Cai, Yiting; Wu, Wei; Shi, Yazhou; Fei, Zhewei

    2013-08-01

    The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24(+) and CD44(+) cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44(+) subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells. PMID:23715169

  5. Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link.

    PubMed

    Hursting, Stephen D; Lashinger, Laura M; Wheatley, Karrie W; Rogers, Connie J; Colbert, Lisa H; Nunez, Nomeli P; Perkins, Susan N

    2008-08-01

    The prevalence of obesity, an established epidemiologic risk factor for many cancers, has risen steadily for the past several decades in the US. The increasing rates of obesity among children are especially alarming and suggest continuing increases in the rates of obesity-related cancers for many years to come. Unfortunately, the mechanisms underlying the association between obesity and cancer are not well understood. In particular, the effects on the carcinogenesis process and mechanistic targets of interventions that modulate energy balance, such as reduced-calorie diets and physical activity, have not been well characterized. The purpose of this review is to provide a strong foundation for the translation of mechanism-based research in this area by describing key animal and human studies of energy balance modulations involving diet or physical activity and by focusing on the interrelated pathways affected by alterations in energy balance. Particular attention is placed on signaling through the insulin and insulin-like growth factor-1 receptors, including components of the Akt and mammalian target of rapamycin (mTOR) signaling pathways downstream of these growth factor receptors. These pathways have emerged as potential targets for disrupting the obesity-cancer link. The ultimate goal of this work is to provide the missing mechanistic information necessary to identify targets for the prevention and control of cancers related to or caused by excess body weight.

  6. A Mechanistic Explanation Linking Adaptive Mutation, Niche Change, and Fitness Advantage for the Wrinkly Spreader

    PubMed Central

    Spiers, Andrew J.

    2014-01-01

    Experimental evolution studies have investigated adaptive radiation in static liquid microcosms using the environmental bacterium Pseudomonas fluorescens SBW25. In evolving populations a novel adaptive mutant known as the Wrinkly Spreader arises within days having significant fitness advantage over the ancestral strain. A molecular investigation of the Wrinkly Spreader has provided a mechanistic explanation linking mutation with fitness improvement through the production of a cellulose-based biofilm at the air-liquid interface. Colonisation of this niche provides greater access to oxygen, allowing faster growth than that possible for non-biofilm—forming competitors located in the lower anoxic region of the microcosm. Cellulose is probably normally used for attachment to plant and soil aggregate surfaces and to provide protection in dehydrating conditions. However, the evolutionary innovation of the Wrinkly Spreader in static microcosms is the use of cellulose as the matrix of a robust biofilm, and is achieved through mutations that deregulate multiple diguanylate cyclases leading to the over-production of cyclic-di-GMP and the stimulation of cellulose expression. The mechanistic explanation of the Wrinkly Spreader success is an exemplar of the modern evolutionary synthesis, linking molecular biology with evolutionary ecology, and provides an insight into the phenomenal ability of bacteria to adapt to novel environments. PMID:24551477

  7. 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

  8. 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.

  9. Vacuum vapor deposition

    NASA Technical Reports Server (NTRS)

    Poorman, Richard M. (Inventor); Weeks, Jack L. (Inventor)

    1995-01-01

    A method and apparatus is described for vapor deposition of a thin metallic film utilizing an ionized gas arc directed onto a source material spaced from a substrate to be coated in a substantial vacuum while providing a pressure differential between the source and the substrate so that, as a portion of the source is vaporized, the vapors are carried to the substrate. The apparatus includes a modified tungsten arc welding torch having a hollow electrode through which a gas, preferably inert, flows and an arc is struck between the electrode and the source. The torch, source, and substrate are confined within a chamber within which a vacuum is drawn. When the arc is struck, a portion of the source is vaporized and the vapors flow rapidly toward the substrate. A reflecting shield is positioned about the torch above the electrode and the source to ensure that the arc is struck between the electrode and the source at startup. The electrode and the source may be confined within a vapor guide housing having a duct opening toward the substrate for directing the vapors onto the substrate.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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.

  18. 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.

  19. Mechanistic aspects of the ethanol steam reforming reaction for hydrogen production on Pt, Ni, and PtNi catalysts supported on gamma-Al2O3.

    PubMed

    Sanchez-Sanchez, Maria Cruz; Navarro Yerga, Rufino M; Kondarides, Dimitris I; Verykios, Xenophon E; Fierro, Jose Luis G

    2010-03-25

    Mechanistic aspects of ethanol steam reforming on Pt, Ni, and PtNi catalysts supported on gamma-Al(2)O(3) are investigated from the analysis of adsorbed species and gas phase products formed on catalysts during temperature-programmed desorption of ethanol and during ethanol steam reforming reaction. DRIFTS-MS analyses of ethanol decomposition and ethanol steam reforming reactions show that PtNi and Ni catalysts are more stable than the Pt monometallic counterpart. Ethanol TPD results on Ni, Pt, and NiPt catalysts point to ethanol dehydrogenation and acetaldehyde decomposition as the first reaction pathways of ethanol steam reforming over the studied catalysts. The active sites responsible for the acetaldehyde decomposition are easily deactivated in the first minutes on-stream by carbon deposits. For Ni and PtNi catalysts, a second reaction pathway, consisting in the decomposition of acetate intermediates formed over the surface of alumina support, becomes the main reaction pathway operating in steam reforming of ethanol once the acetaldehyde decomposition pathway is deactivated. Taking into account the differences observed in the mechanism of ethanol decomposition, the better stability observed for PtNi catalyst is proposed to be related with a cooperative effect between Pt and Ni activities together with the enhanced ability of Ni to gasify the methyl groups formed by decomposition of acetate species. On the contrary, monometallic catalysts are believed to dehydrogenate these methyl groups forming coke that leads to deactivation of metal particles. PMID:19824680

  20. 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.

  1. 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).

  2. 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

  3. 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

  4. Bridging the gap between empirical and mechanistic models for nitrate in groundwater

    NASA Astrophysics Data System (ADS)

    Nolan, B. T.; Malone, R. W.; Gronberg, J.; Thorp, K.; Ma, L.

    2011-12-01

    Water-quality models are useful tools for predicting the vulnerability of groundwater to nitrate contamination, and include both empirical and mechanistic approaches. Empirical models commonly are used at regional and national scales. Such models are data-driven and have comparatively few parameters, but their capability to simulate processes is limited. In contrast, mechanistic models are physically based, simulate controlling processes, and can have many parameters. The GroundWAter Vulnerability Assessment model (GWAVA), an example of the first approach, is a national-scale nonlinear regression model (R2=0.80) that predicts areally averaged nitrate concentration in groundwater based on mid-1990s land use. The Root Zone Water Quality Model (RZWQM2) is an example of the second approach and simulates N cycling processes, crop growth, and the fate and transport of agricultural chemicals at the field-scale for daily time steps. Thorough accounting by RZWQM2 of key processes can yield more accurate predictions, but application at large spatial scales is difficult because of the numerous parameters. To bridge the gap between these contrasting scales and approaches, we developed metamodels (MMs) to predict nitrate concentrations and N fluxes in the Corn Belt. Metamodels are simplified representations of mechanistic models which map outputs from the latter onto the inputs. Our MMs consisted of artificial neural networks (ANNs), which are inherently flexible and do not require linearity or normally distributed data. The MMs were based on RZWQM2 models previously calibrated to data from field sites in Nebraska, Iowa, and Maryland. The three sites are in corn-soybean rotation and reflect diverse soil types and climatic conditions as well as different management practices. We calibrated the MMs to RZWQM2 predictions of N in tile drainage and leachate below the root zone of crops. Therefore the MMs represent an integrated approach to vulnerability assessment-nitrate leaching

  5. A reductionist mechanistic model for bioconcentration of neutral and weakly polar organic compounds in fish.

    PubMed

    Kuo, Dave T F; Di Toro, Dominic M

    2013-09-01

    The bioconcentration factor (BCF) of neutral and weakly polar organic chemicals in fish is modeled using independently calibrated models of chemical partitioning (freely dissolved fraction of chemical in the aqueous phase [φsys ] and wet-weight fish-water partition coefficient [KFW ]), respiratory exchange (respiratory update rate constant [k1 ], and respiratory elimination rate constant [k2  = k1 /KFW ]), and biotransformation (whole-body biotransformation rate constant [kM ]) as BCF = φsys KFW /(1 + kM /k2 ). Existing k1 models tend to overestimate for chemicals with log KOW  < 3.5, which constituted 30% to 50% of the examined chemicals. A revised k1 model covering a wider log KOW range (0-8.5) is presented k1  = (5.46 × 10(-6) MW + 0.261/KOW )(-1) , where MW is the molecular weight. The biotransformation rate constant kM is modeled using biota internal partitioning and Abraham parameters as reactivity descriptors. The reductionist model was tested using 3 different BCF data sets (US Environmental Protection Agency's Estimation Programs Interface [EPI], n = 548; Hertfordshire, n = 210; Arnot-Gobas, n = 1855) and compared with the following 3 state-of-the-art models: 1) the EPI Suite BCFBAF module, 2) the European Commision's Computer Assisted Evaluation of industrial chemical Substances According to Regulations (CAESAR), and 3) the EPI/Arnot mechanistic kinetic model. The reductionist model performed comparably with the alternative models (root mean square errors [RMSEs] = 0.72-0.77), with only 5 fitting parameters and no training against experimental BCFs. Respiratory elimination and biotransformation dominate the total depuration (i.e., [k2  + kM ]/kT  ≥ 0.8) for approximately 98% of the data entries, thus validating the reductionist approximation. Mechanistic models provide greater insights into bioaccumulation and are more sensitive to biological variation. All three BCF data sets and relevant

  6. A mechanistic code for intact and defective nuclear fuel element performance

    NASA Astrophysics Data System (ADS)

    Shaheen, Khaled

    During reactor operation, nuclear fuel elements experience an environment featuring high radiation, temperature, and pressure. Predicting in-reactor performance of nuclear fuel elements constitutes a complex multi-physics problem, one that requires numerical codes to be solved. Fuel element performance codes have been developed for different reactor and fuel designs. Most of these codes simulate fuel elements using one-or quasi-two-dimensional geometries, and some codes are only applicable to steady state but not transient behaviour and vice versa. Moreover, while many conceptual and empirical separate-effects models exist for defective fuel behaviour, wherein the sheath is breached allowing coolant ingress and fission gas escape, there have been few attempts to predict defective fuel behaviour in the context of a mechanistic fuel performance code. Therefore, a mechanistic fuel performance code, called FORCE (Fuel Operational peRformance Computations in an Element) is proposed for the time-dependent behaviour of intact and defective CANDU nuclear fuel elements. The code, which is implemented in the COMSOL Multiphysics commercial software package, simulates the fuel, sheath, and fuel-to-sheath gap in a radial-axial geometry. For intact fuel performance, the code couples models for heat transport, fission gas production and diffusion, and structural deformation of the fuel and sheath. The code is extended to defective fuel performance by integrating an adapted version of a previously developed fuel oxidation model, and a model for the release of radioactive fission product gases from the fuel to the coolant. The FORCE code has been verified against the ELESTRES-IST and ELESIM industrial code for its predictions of intact fuel performance. For defective fuel behaviour, the code has been validated against coulometric titration data for oxygen-to-metal ratio in defective fuel elements from commercial reactors, while also being compared to a conceptual oxidation model

  7. 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.

  8. 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.

  9. Particle deposition in ventilation ducts

    SciTech Connect

    Sippola, Mark R.

    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 {micro}m 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

  10. Can mechanistic explanation be reconciled with scale-free constitution and dynamics?

    PubMed

    Bechtel, William

    2015-10-01

    This paper considers two objections to explanations that appeal to mechanisms to explain biological phenomena. Marom argues that the time-scale on which many phenomena occur is scale-free. There is also reason to suspect that the network of interacting entities is scale-free. The result is that mechanisms do not have well-delineated boundaries in nature. I argue that bounded mechanisms should be viewed as entities scientists posit in advancing scientific hypotheses. In positing such entities, scientists idealize. Such idealizations can be highly productive in developing and improving scientific explanations even if the hypothesized mechanisms never precisely correspond to bounded entities in nature. Mechanistic explanations can be reconciled with scale-free constitution and dynamics even if mechanisms as bounded entities don't exist. PMID:25977254

  11. 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.

  12. 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.

  13. Activity restriction and the mechanistic basis for extinctions under climate warming.

    PubMed

    R Kearney, Michael

    2013-12-01

    Correlative analyses predict that anthropogenic climate warming will cause widespread extinction but the nature and generality of the underlying mechanisms is unclear. Warming-induced activity restriction has been proposed as a general explanatory mechanism for recent population extinctions in lizards, and has been used to forecast future extinction. Here, I test this hypothesis using globally applied biophysical calculations of the effects of warming and shade reduction on potential activity time and whole-life-cycle energy budgets. These 'thermodynamic niche' analyses show that activity restriction from climate warming is unlikely to provide a general explanation of recent extinctions, and that loss of shade is viable alternative explanation. Climate warming could cause population declines, even under increased activity potential, through joint impacts on fecundity and mortality rates. However, such responses depend strongly on behaviour, habitat (shade, food) and life history, all of which should be explicitly incorporated in mechanistic forecasts of extinction risk under climate change.

  14. 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

  15. 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). PMID:20977281

  16. LiDAR improves fire behaviour predictions using a biophysical, mechanistic model

    NASA Astrophysics Data System (ADS)

    Zylstra, Philip; Horsey, Bronwyn; Yebra, Marta; Marselis, Suzanne

    2016-04-01

    Numerous studies have attempted to address the utility of LiDAR as a tool for measuring fuel inputs to fire behaviour models, however the direct effect of this approach on fire behaviour prediction requires quantification. We used a biophysical, mechanistic model validated for eucalypt forest in SE Australia to assess the improvement in prediction accuracy afforded using LiDAR-derived inputs. The accuracy of modelling with these inputs was compared to modelling using detailed site-specific field surveys of a dry sclerophyll forest to represent the highest standard of inputs, and values derived from desktop-available community-wide descriptors to represent baseline inputs. Use of LiDAR significantly improved on baseline predictions and enabled site-specific decision making across the study area. When used with an appropriate model, LiDAR can facilitate improved decision-making in regard to forest fire behaviour.

  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. PMID:25278222

  18. 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

  19. A Three-Stage Mechanistic Model for Ammonia Borane Dehydrogenation by Shvo's Catalyst.

    PubMed

    Lu, Zhiyao; Conley, Brian L; Williams, Travis J

    2012-10-01

    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 NH(3), which itself does not strongly affect the rate of AB dehydrogenation. PMID:23335832

  20. Bacterial Diterpene Synthases: New Opportunities for Mechanistic Enzymology and Engineered Biosynthesis

    PubMed Central

    Smanski, Michael J.; Peterson, Ryan M.; Huang, Sheng-Xiong; Shen, Ben

    2012-01-01

    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. PMID:22445175

  1. 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.

  2. Evaluation and verification of two systems for mechanistic structural design of asphalt concrete pavements in Nebraska

    NASA Astrophysics Data System (ADS)

    Sneddon, R. V.

    1982-07-01

    The VESY-3-A mechanistic design system for asphalt pavements was field verified for three pavement sections at two test sites in Nebraska. PSI predictions from VESYS were in good agreement with field measurements for a 20 year old 3 layer pavement located near Elmwood, Nebraska. Field measured PSI values for an 8 in. full depth pavement also agreed with VESYS predictions for the study period. Rut depth estimates from the model were small and were in general agreement with field measurements. Cracking estimates were poor and tended to underestimate the time required to develop observable fatigue cracking in the field. Asphalt, base course and subgrade materials were tested in a 4.0 in. diameter modified triaxial cell. Test procedures used dynamic conditioning and rest periods to simulate service conditions.

  3. 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

  4. Inhibition of the Mechanistic Target of Rapamycin (mTOR)-Rapamycin and Beyond.

    PubMed

    Lamming, Dudley W

    2016-01-01

    Rapamycin is a Food and Drug Administration (FDA)-approved immunosuppressant and anticancer agent discovered in the soil of Easter Island in the early 1970s. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) 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 article, we will discuss the molecular biology underlying the effects of rapamycin and its physiological effects, evidence for rapamycin as an antiaging compound, mechanisms by which rapamycin may extend life span, and the potential limitations of rapamycin as an antiaging 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

  5. Glucosamine condensation catalyzed by 1-ethyl-3-methylimidazolium acetate: mechanistic insight from NMR spectroscopy.

    PubMed

    Jia, Lingyu; Pedersen, Christian Marcus; Qiao, Yan; Deng, Tiansheng; Zuo, Pingping; Ge, Wenzhi; Qin, Zhangfeng; Hou, Xianglin; Wang, Yingxiong

    2015-09-21

    The basic ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) could efficiently catalyze the conversion of 2-amino-2-deoxy-d-glucose (GlcNH2) into deoxyfructosazine (DOF) and fructosazine (FZ). Mechanistic investigation by NMR studies disclosed that [C2C1Im][OAc], exhibiting strong hydrogen bonding basicity, could coordinate with the hydroxyl and amino groups of GlcNH2via the promotion of hydrogen bonding in bifunctional activation of substrates and further catalyzing product formation, based on which a plausible reaction pathway involved in this homogeneous base-catalyzed reaction was proposed. Hydrogen bonding as an activation force, therefore, is responsible for the remarkable selectivity and rate enhancement observed. PMID:26278065

  6. How do animal territories form and change? Lessons from 20 years of mechanistic modelling.

    PubMed

    Potts, Jonathan R; Lewis, Mark A

    2014-06-01

    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

  7. Mechanistic studies related to the safety of Li/SOCl2 cells

    NASA Technical Reports Server (NTRS)

    Carter, B. J.; Williams, R. M.; Tsay, F. D.; Rodriguez, A.; Kim, S.; Evans, M. M.; Frank, H.

    1985-01-01

    Mechanistic studies of the reactions in Li-SOCl2 cells have been undertaken to improve understanding of the safety problems of these cells. The electrochemical reduction of 1.5M LiAlCl4/SOCl2 has been investigated using gas chromatography, electron spin resonance spectroscopy, and infrared spectroscopy. Cl2 and S2Cl2 have been identified as intermediates in the reduction of SOCl2, along with a radical species (g/xx/ = 2.004, g/yy/ = 2.016, g/zz/ = 2.008) and the proposed triplet ground-state dimer of this radical. SO2 and sulfur have been identified as products. Based upon these findings, a mechanism for the electrochemical reduction of 1.5M LiAlCl4/SOCl2 has been proposed, and its implications for safety of Li-SOCl2 cells during discharge to +0.5V at 25-30 C are discussed.

  8. Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality.

    PubMed

    Warnecke, Lisa; Turner, James M; Bollinger, Trent K; Misra, Vikram; Cryan, Paul M; Blehert, David S; Wibbelt, Gudrun; Willis, Craig K R

    2013-08-23

    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. PMID:23720520

  9. Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight.

    PubMed

    Scior, Thomas; Lozano-Aponte, Jorge; Ajmani, Subhash; Hernández-Montero, Eduardo; Chávez-Silva, Fabiola; Hernández-Núñez, Emanuel; Moo-Puc, Rosa; Fraguela-Collar, Andres; Navarrete-Vázquez, Gabriel

    2015-01-01

    In view of the serious health problems concerning infectious diseases in heavily populated areas, we followed the strategy of lead compound diversification to evaluate the near-by chemical space for new organic compounds. To this end, twenty derivatives of nitazoxanide (NTZ) were synthesized and tested for activity against Entamoeba histolytica parasites. To ensure drug-likeliness and activity relatedness of the new compounds, the synthetic work was assisted by a quantitative structure-activity relationships study (QSAR). Many of the inherent downsides - well-known to QSAR practitioners - we circumvented thanks to workarounds which we proposed in prior QSAR publication. To gain further mechanistic insight on a molecular level, ligand-enzyme docking simulations were carried out since NTZ is known to inhibit the protozoal pyruvate ferredoxin oxidoreductase (PFOR) enzyme as its biomolecular target. PMID:25872791

  10. 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

  11. 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. PMID:22375251

  12. A mechanistic breast cancer survival modelling through the axillary lymph node chain.

    PubMed

    Cobre, Juliana; Castro Perdoná, Gleici S; Peria, Fernanda M; Louzada, Francisco

    2013-04-30

    In this paper, we proposed a mechanistic breast cancer survival model based on the axillary lymph node chain structure, considering lymph nodes as a potential dissemination arrangement. We assume a naive breast cancer treatment protocol consisting of exposing patients first to a chemotherapy treatment on r intervals at k-cycles separated by equal time intervals, and then they proceed to surgery. Our model, different from former ones, accommodates a quantity of contaminated lymph nodes, which is observed during surgery. We assume a generalised negative binomial survival distribution for the unknown number of contaminated lymph nodes after surgery, which, during an unknown period, may potentially propagate the disease. Estimation is based on a maximum likelihood approach. A simulation study assesses the coverage probability of asymptotic confidence intervals when small or moderate samples are considered. A Brazilian breast cancer data illustrate the applicability of our modelling.

  13. 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

  14. Correlation between mechanistic biotransformation and biochemical toxicology of some antihypertensive drugs.

    PubMed

    Akintonwa, D A

    1986-11-01

    Mechanistic biochemistry (consideration of metabolism in the context of knowledge of contemporary biochemistry) was applied to propanolol (1), hydrochlorothiazide (2), hydralazine (3), and triamterene (4), representative of the main types of anti-hypertensive drugs in common use. Three routes of metabolism, that is, acetylation, generation of free radicals (leading to peroxidation of lipids), and osazone formation were considered in relation to the structures of these drugs. The possibility that acetylation can lead to hepatic toxicity, lipid peroxidation to membrane lesion, and osazone formation to glucose and energy depletion was highlighted. Hydralazine, with its potential for osazone formation and great susceptibility to acetylation and free radical formation, was judged most capable of giving rise to these side effects, in agreement with reported toxicity. Triamterene was judged less susceptible than hydralazine to acetylation and free radical formation, and hydrochlorothiazide even less so. Propanolol is immune to any of these consequences. PMID:3509327

  15. Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy.

    PubMed

    Singh, Natalia N; Lee, Brian M; DiDonato, Christine J; Singh, Ravindra N

    2015-01-01

    Spinal muscular atrophy (SMA) is a major neurodegenerative disorder of children and infants. SMA is primarily caused by low levels of SMN protein owing to deletions or mutations of the SMN1 gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of the production of the functional SMN protein due to predominant skipping of exon 7. Several compounds, including antisense oligonucleotides (ASOs) that elevate SMN protein from SMN2 hold the promise for treatment. An ASO-based drug currently under Phase III clinical trial employs intronic splicing silencer N1 (ISS-N1) as its target. Cumulative studies on ISS-N1 reveal a wealth of information with significance to the overall therapeutic development for SMA. Here, the authors summarize the mechanistic principles behind various antisense targets currently available for SMA therapy.

  16. Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth.

    PubMed

    Zhu, Yi; Pires, Karla M P; Whitehead, Kevin J; Olsen, Curtis D; Wayment, Benjamin; Zhang, Yi Cheng; Bugger, Heiko; Ilkun, Olesya; Litwin, Sheldon E; Thomas, George; Kozma, Sara C; Abel, E Dale

    2013-01-01

    Mechanistic target of rapamycin (Mtor) is required for embryonic inner cell mass proliferation during early development. However, Mtor expression levels are very low in the mouse heart during embryogenesis. To determine if Mtor plays a role during mouse cardiac development, cardiomyocyte specific Mtor deletion was achieved using α myosin heavy chain (α-MHC) driven Cre recombinase. Initial mosaic expression of Cre between embryonic day (E) 10.5 and E11.5 eliminated a subset of cardiomyocytes with high Cre activity by apoptosis and reduced overall cardiac proliferative capacity. The remaining cardiomyocytes proliferated and expanded normally. However loss of 50% of cardiomyocytes defined a threshold that impairs the ability of the embryonic heart to sustain the embryo's circulatory requirements. As a result 92% of embryos with cardiomyocyte Mtor deficiency died by the end of gestation. Thus Mtor is required for survival and proliferation of cardiomyocytes in the developing heart.

  17. Mechanistic principles of antisense targets for the treatment of Spinal Muscular Atrophy

    PubMed Central

    Singh, Natalia N.; Lee, Brian M.; DiDonato, Christine J.; Singh, Ravindra N.

    2015-01-01

    Spinal muscular atrophy (SMA) is a major neurodegenerative disorder of children and infants. SMA is primarily caused by low levels of SMN protein owing to deletions or mutations of the survival motor neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of the production of the functional SMN protein due to predominant skipping of exon 7. Several compounds, including antisense oligonucleotides (ASOs) that elevate SMN protein from SMN2 hold the promise for treatment. An ASO-based drug currently under phase 3 clinical trial employs intronic splicing silencer N1 (ISS-N1) as its target. Cumulative studies on the ISS-N1 reveal a wealth of information with significance to the overall therapeutic development for SMA. Here we summarize the mechanistic principles behind various antisense targets currently available for SMA therapy. PMID:26381381

  18. The Role of Mechanistic Target of Rapamycin (mTOR) Complexes Signaling in the Immune Responses

    PubMed Central

    Soliman, Ghada A.

    2013-01-01

    The mechanistic Target of Rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase which is a member of the PI3K related kinase (PIKK) family. mTOR emerged as a central node in cellular metabolism, cell growth, and differentiation, as well as cancer metabolism. mTOR senses the nutrients, energy, insulin, growth factors, and environmental cues and transmits signals to downstream targets to effectuate the cellular and metabolic response. Recently, mTOR was also implicated in the regulation of both the innate and adaptive immune responses. This paper will summarize the current knowledge of mTOR, as related to the immune microenvironment and immune responses. PMID:23783557

  19. Mechanistic causality and counterfactual-manipulative causality: recent insights from philosophy of science.

    PubMed

    Campaner, Raffaella

    2011-12-01

    Current epidemiological and statistical theory about research methods and how to elicit causation from epidemiological studies is strongly influenced by counterfactual-manipulative thinking. However, thinking about how disease states develop is rooted in mechanistic 'webs of causes'. After a tremendous growth of research in molecular biology, biochemistry and genetics, attention has increasingly been paid to environmental and socioeconomic factors as determinants of diseases. This led to conceiving of most pathologies as caused by multilevel mechanical systems. The nature of 'mechanisms' has been the subject of extensive philosophical reflection over the past couple of decades. The present paper will first present some of today's philosophical insights in what are called biologic or other 'mechanisms' and thereafter show how these concepts can be linked to counterfactual-manipulative views.

  20. Mechanistic insights into the interactions of magnetic nanoparticles with bovine serum albumin in presence of surfactants.

    PubMed

    Joseph, Delina; Sachar, Shilpee; Kishore, Nand; Chandra, Sudeshna

    2015-11-01

    This work reports the physicochemical parameters and the nature of association between magnetic nanoparticles and bovine serum albumin (BSA) in presence of cationic and anionic surfactants. Magnetic iron oxide nanoparticles (MNPs) are first synthesized using chemical co-precipitation method and subsequently characterized by FTIR, XRD, DLS, TEM and Zeta potential. The bare nanoparticles are then coated with BSA and their interactions studied using fluorescence spectroscopy, dynamic light scattering and circular dichroism techniques. The spectroscopic investigation sheds light into various aspects of binding and size variation during the molecular association of BSA with the MNPs in absence and presence of cationic and anionic surfactants. Isothermal titration calorimetry was used to probe the thermodynamic parameters of the systems. MNPs-BSA system was found to be more stable in presence of cationic surfactant. This study provides valuable mechanistic insights into the interactions taking place at the interface of the nanoparticles which further helps in designing a stable colloidal MNPs systems.

  1. 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.

  2. Reactions of Co(III)–Nitrosyl Complexes with Superoxide and Their Mechanistic Insights

    PubMed Central

    Kumar, Pankaj; Lee, Yong-Min; Park, Young Jun; Siegler, Maxime A.; Karlin, Kenneth D.; Nam, Wonwoo

    2015-01-01

    New CoIII-nitrosyl complexes bearing N-tetramethylated cyclam (TMC) ligands, [(12-TMC)CoIII(NO)]2+ (1) and [(13-TMC)CoIII(NO)]2+ (2), were synthesized via [(TMC)CoII(CH3CN)]2+ plus NO(g) reactions. Spectroscopic and structural characterization shows that these compounds bind the nitrosyl moiety in a bent end-on fashion. The CoIII-nitrosyl complexes, (1) and (2), reacted with KO2/2.2.2-Cryptand and produced [(12-TMC)CoII(NO2)]+ (3) and [(13-TMC)CoII(NO2)]+ (4), respectively; these possess O,O’-chelated nitrito ligands. Mechanistic studies using 18O-labeled superoxide (18O2•−) demonstrate that one oxygen atom in the nitrito ligand derives from superoxide and dioxygen produced comes from the other superoxide oxygen atom. Evidence supporting the formation of a Co-peroxynitrite intermediate is also presented. PMID:25793706

  3. Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights.

    PubMed

    Ueda, Atsushi; Umeno, Tomohiro; Doi, Mitsunobu; Akagawa, Kengo; Kudo, Kazuaki; Tanaka, Masakazu

    2016-08-01

    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.

  4. Accessing N-Stereogenicity through a Double Aza-Michael Reaction: Mechanistic Insights.

    PubMed

    Kohrt, Sonja; Santschi, Nico; Cvengroš, Ján

    2016-01-01

    Further development of the chemistry and applications of chiral compounds that possess configurationally stable stereogenic nitrogen atoms is hampered by the lack of efficient strategies to access such compounds in an enantiomerically pure form. Esters of propiolic acid and chiral alcohols were evaluated as cheap and readily available Michael acceptors in a diastereoselective synthesis of N-stereogenic compounds by means of a double aza-Michael conjugate addition. Diastereomeric ratios of up to 74:26 and high yields were achieved with (-)-menthyl propiolate as a substrate. Furthermore, a detailed mechanistic investigation was undertaken to shed some light on the course of this domino transformation. Kinetic studies revealed that the protic-solvent additive acts as a Brønsted acid and activates the ester toward the initial attack of the tetrahydrodiazocine partner. Conversely, acidic conditions proved unfavorable during the final cyclization step that provides the product.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Mechanistic study of synthesis of gold nanoparticles using multi-functional polymer

    NASA Astrophysics Data System (ADS)

    Yu, Taekyung; Kim, Rayoung; Park, Hoseok; Yi, Jonghyup; Kim, Woo-Sik

    2014-01-01

    This Letter presents a mechanistic study of the large-scale synthesis of Au nanoparticles when using branched polyethyleneimine (BPEI) as a multi-functional reducing agent, capping agent, and stabilizer. During the synthesis, the molar ratio of BPEI/HAuCl4, reaction temperature, and pH of the reacting solution were all found to be important factors in the formation, size control, and stabilization of the Au nanoparticles. The proposed synthetic route provided a highly concentrated product of Au nanoparticles (above 40 g/L), at least 10- to 200-fold more than previous methods, and can be readily applied to a large-scale process due to its simple and mild reaction conditions.

  10. 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.

  11. 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

  12. Dual effect of red wine on liver redox status: a concise and mechanistic review.

    PubMed

    Silva, Paula; Fernandes, Eduarda; Carvalho, Félix

    2015-10-01

    Chronic ethanol consumption is a strong risk factor for the development of liver disease. Multiple mechanisms are involved in ethanol-mediated liver injury; oxidative stress being pointed has an important factor. However, it should be noted that moderate consumption of red wine has been associated with hepatoprotective effects, mainly due to the antioxidant effect of resveratrol, one of its polyphenolic compounds. In this paper, the potential molecular mechanisms through which the protective effects of resveratrol counteract the oxidative effect of ethanol and the way as this dual effect impacts liver oxidative stress are reviewed. Mechanistic evaluation of modulation of oxidative signaling pathways by ethanol and resveratrol may explain the pathogenesis of various liver diseases and ultimately to disclose possible pharmacological therapies.

  13. Joint modeling of the clinical progression and of the biomarkers' dynamics using a mechanistic model.

    PubMed

    Guedj, Jeremie; Thiébaut, Rodolphe; Commenges, Daniel

    2011-03-01

    Joint models are used to rigorously explore the relationship between the dynamics of biomarkers and clinical events. In the context of HIV infection, where the multivariate dynamics of HIV-RNA and CD4 are complex, a mechanistic approach based on a system of nonlinear differential equations naturally takes into account the correlation between the biomarkers. Using data from a randomized clinical trial comparing dual antiretroviral therapy to a single drug regimen, a full maximum likelihood approach is proposed to explore the relationship between the evolution of the biomarkers and the time to a clinical event. The role of each marker as an independent predictor of disease progression is assessed. We show that the joint dynamics of HIV-RNA and CD4 captures the effect of antiretroviral treatment; the CD4 dynamics alone is found to capture most but not all of the treatment effect. PMID:20377577

  14. Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer.

    PubMed

    Hursting, Stephen D; Hursting, Marcie J

    2012-08-01

    Nearly 35% of adults and 20% of children in the United States are obese, defined as a body mass index ≥ 30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and progression. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent possible mechanistic targets for disrupting the obesity-cancer link.

  15. Detailed Mechanistic Investigation of Preferential Flow and Transport in Variably- Saturated Fractured Clayey Till

    NASA Astrophysics Data System (ADS)

    Rosenbom, A. E.; Refsgaard, J.; Jensen, K. H.; Fluehler, H.; Ernstsen, V.; Klint, K. S.; Therrien, R.

    2008-12-01

    By applying fluorescence imaging with high spatial resolution (1mm2) to tracer distribution in variably saturated fractured clayey till, a mechanistic study of preferential flow and transport were performed. Tracer experiments with two fluorescent tracers, Acid Yellow (AY7) and Sulforhodamine (SB), were conducted for three different rain events under dry and wet conditions, respectively. Two-dimensional vertical apparent concentration distribution profiles of both tracers to depths of 2.8 m were delineated simultaneously using an imaging device. The profiles showed that: i) biopores formed the primarily migration paths in the upper 1.4 meters, ii) only fractures connected to hydraulically active biopores contributed to tracer migration, (iii) dead- end biopores were not active under wet conditions, (iv) under dry conditions, AY7 was displaced piston-flow like down to 20 cm below irrigation level, which was not observed for SB, (v) the highest apparent tracer pixel concentrations (per pixel) are often found in macropores particularly under dry conditions, and (vi) the maximum migration depths observed for SB and AY7 were 1.7 and 3 m below surface, respectively. To achieve a better mechanistic understanding of the different tracer migration pathways for various initial water content, rain intensities, tracer characteristics, geometry of the structural discontinuity setting, and domain properties, a detailed numerical analysis of the tracer experiments using the three-dimensional discrete fracture model HydroGeoSphere was performed. Detailed data on the geometry and hydraulic properties of the different domains of the till (two matrix units, fractures, and biopores), and tracer characteristics were incorporated in the model. Overall, the analysis showed that discontinuities control tracer migration even at high matrix suction values. Hence, the study revealed that, for any risk assessment analysis of these complex media, it is necessary to account for fast flow

  16. 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. PMID:25757787

  17. 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.

  18. Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury

    PubMed Central

    Woodhead, Jeffrey L.; Yang, Kyunghee; Siler, Scott Q.; Watkins, Paul B.; Brouwer, Kim L. R.; Barton, Hugh A.; Howell, Brett A.

    2014-01-01

    Inhibition of the bile salt export pump (BSEP) has been linked to incidence of drug-induced liver injury (DILI), presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors bosentan and CP-724,714 and the non-hepatotoxic BSEP inhibitor telmisartan in humans in order to explore whether we can predict that hepatotoxic BSEP inhibitors can cause bile acid accumulation to reach toxic levels. We also simulate bosentan in rats in order to illuminate potential reasons behind the lack of toxicity in rats compared to the toxicity observed in humans. DILIsym® predicts that bosentan, but not telmisartan, will cause mild hepatocellular ATP decline and serum ALT elevation in a simulated population of humans. The difference in hepatotoxic potential between bosentan and telmisartan is consistent with clinical observations. However, DILIsym® underpredicts the incidence of bosentan toxicity. DILIsym® also predicts that bosentan will not cause toxicity in a simulated population of rats, and that the difference between the response to bosentan in rats and in humans is primarily due to the less toxic bile acid pool in rats. Our simulations also suggest a potential synergistic role for bile acid accumulation and mitochondrial electron transport chain (ETC) inhibition in producing the observed toxicity in CP-724,714, and suggest that CP-724,714 metabolites may also play a role in the observed toxicity. Our work also compares the impact of competitive and noncompetitive BSEP inhibition for CP-724,714 and demonstrates that noncompetitive inhibition leads to much greater bile acid accumulation and potential toxicity. Our research demonstrates the potential for mechanistic modeling to contribute to the understanding of how bile acid transport inhibitors cause DILI

  19. A minimal mechanistic model for temporal signal processing in the lateral geniculate nucleus.

    PubMed

    Norheim, Eivind S; Wyller, John; Nordlie, Eilen; Einevoll, Gaute T

    2012-06-01

    The receptive fields of cells in the lateral geniculate nucleus (LGN) are shaped by their diverse set of impinging inputs: feedforward synaptic inputs stemming from retina, and feedback inputs stemming from the visual cortex and the thalamic reticular nucleus. To probe the possible roles of these feedforward and feedback inputs in shaping the temporal receptive-field structure of LGN relay cells, we here present and investigate a minimal mechanistic firing-rate model tailored to elucidate their disparate features. The model for LGN relay ON cells includes feedforward excitation and inhibition (via interneurons) from retinal ON cells and excitatory and inhibitory (via thalamic reticular nucleus cells and interneurons) feedback from cortical ON and OFF cells. From a general firing-rate model formulated in terms of Volterra integral equations, we derive a single delay differential equation with absolute delay governing the dynamics of the system. A freely available and easy-to-use GUI-based MATLAB version of this minimal mechanistic LGN circuit model is provided. We particularly investigate the LGN relay-cell impulse response and find through thorough explorations of the model's parameter space that both purely feedforward models and feedback models with feedforward excitation only, can account quantitatively for previously reported experimental results. We find, however, that the purely feedforward model predicts two impulse response measures, the time to first peak and the biphasic index (measuring the relative weight of the rebound phase) to be anticorrelated. In contrast, the models with feedback predict different correlations between these two measures. This suggests an experimental test assessing the relative importance of feedforward and feedback connections in shaping the impulse response of LGN relay cells.

  20. 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

    2016-09-01

    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. PMID:27518766

  1. 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

  2. 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.

  3. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    PubMed

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition.

  4. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    PubMed

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition. PMID:25956735

  5. A Mechanistic Beta-Binomial Probability Model for mRNA Sequencing Data

    PubMed Central

    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. PMID:27326762

  6. 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. PMID:27326762

  7. 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

    2016-09-01

    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.

  8. 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

  9. Mechanistic modelling of fluidized bed drying processes of wet porous granules: a review.

    PubMed

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

    2011-10-01

    Fluidized bed dryers are frequently used in industrial applications and also in the pharmaceutical industry. The general incentives to develop mechanistic models for pharmaceutical processes are listed, and our vision on how this can particularly be done for fluidized bed drying processes of wet granules is given. This review provides a basis for future mechanistic model development for the drying process of wet granules in pharmaceutical processes. It is intended for a broad audience with a varying level of knowledge on pharmaceutical processes and mathematical modelling. Mathematical models are powerful tools to gain process insight and eventually develop well-controlled processes. The level of detail embedded in such a model depends on the goal of the model. Several models have therefore been proposed in the literature and are reviewed here. The drying behaviour of one single granule, a porous particle, can be described using the continuum approach, the pore network modelling method and the shrinkage of the diameter of the wet core approach. As several granules dry at a drying rate dependent on the gas temperature, gas velocity, porosity, etc., the moisture content of a batch of granules will reside in a certain interval. Population Balance Model (ling) (PBM) offers a tool to describe the distribution of particle properties which can be of interest for the application. PBM formulation and solution methods are therefore reviewed. In a fluidized bed, the granules show a fluidization pattern depending on the geometry of the gas inlet, the gas velocity, characteristics of the particles, the dryer design, etc. Computational Fluid Dynamics (CFD) allows to model this behaviour. Moreover, turbulence can be modelled using several approaches: Reynolds-averaged Navier-Stokes Equations (RANS) or Large Eddy Simulation (LES). Another important aspect of CFD is the choice between the Eulerian-Lagrangian and the Eulerian-Eulerian approach. Finally, the PBM and CFD frameworks

  10. 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

  11. 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

  12. Advancements in the mechanistic understanding of the copper-catalyzed azide-alkyne cycloaddition.

    PubMed

    Berg, Regina; Straub, Bernd F

    2013-01-01

    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

  13. 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. PMID:27348246

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Tracking colloid transport in porous media using discrete flow fields and sensitivity of simulated colloid deposition to space discretization.

    PubMed

    Li, Zhelong; Zhang, Dongxiao; Li, Xiqing

    2010-02-15

    Advances in pore structure characterization and lattice-Boltzmann (LB) simulations of flow fields in pore spaces are making mechanistic simulations of colloid transport in real porous media a realistic goal. The primary challenge to reach this goal may be the computational demand of LB flow simulations in discretized porous medium domains at an assemblage scale. In this work, flow fields in simple cubic and dense packing systems were simulated at different discretization resolutions using the LB method. The simulated flow fields were incorporated into to a three-dimensional particle tracking model to simulate colloid transport in the two systems. The simulated colloid deposition tended to become asymptotic at a critical discretization resolution (voxel-grain size ratio = 0.01) at groundwater flow regimes for colloids down to submicrometer level under favorable conditions and down to around 1 microm under unfavorable conditions. The average simulated fluid velocities near grain surfaces were extracted to explain the sensitivities of simulated depositions to space discretization under both conditions. At the critical discretization resolution, current computation capacity would allow flow simulations and particle tracking in assemblage porous medium domains. In addition, particle tracking simulations revealed that colloids may be retained in flow vortices under conditions both favorable and unfavorable for deposition. Colloid retention in flow vortices has been proposed only very recently. Here we provide a mechanistic confirmation to this novel retention process. PMID:20088544

  20. 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.

  1. A Radon Progeny Deposition Model

    NASA Astrophysics Data System (ADS)

    Guiseppe, V. E.; Elliott, S. R.; Hime, A.; Rielage, K.; Westerdale, S.

    2011-04-01

    The next generation low-background detectors operating underground aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly 222Rn) 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 210Pb 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.

  2. 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.

  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. 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...

  5. Recognizing Mechanistic Reasoning in Student Scientific Inquiry: A Framework for Discourse Analysis Developed from Philosophy of Science

    ERIC Educational Resources Information Center

    Russ, Rosemary S.; Scherr, Rachel E.; Hammer, David; Mikeska, Jamie

    2008-01-01

    Science education reform has long focused on assessing student inquiry, and there has been progress in developing tools specifically with respect to experimentation and argumentation. We suggest the need for attention to another aspect of inquiry, namely "mechanistic reasoning." Scientific inquiry focuses largely on understanding causal…

  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. 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…

  8. Energy deposition of thermal tides

    NASA Astrophysics Data System (ADS)

    Becker, E.

    2015-12-01

    The main role of vertically propagating waves in the general circulation is to transfer pseudo momentum from the region of generation to the region of wave breaking. The most prominent examples in atmospheric dynamics are planetary Rossby waves forced in the troposphere, which drive a poleward residual circulation in the winter stratosphere, and mesoscale gravity waves with tropospheric origin, which drive a summer-to-winter-pole circulation in the mesopasue region. In addition, the role of energy deposition by gravity waves has long been recognized to contribute substantially to the energy budget above the stratopause. In atmospheric circulation models, gravity waves are usually parameterized. Their energy deposition can be computed along with the momentum deposition and the turbulent diffusivity associated with wave breaking. In particular, the energy deposition is expressed in terms of secondary moments of the parameterized waves. Therefore, one is tempted to assume that the energy deposition of waves that are resolved in circulation models, e.g., Rossby waves and thermal tides, is automatically taken into account. This assumption is, however, flawed. We show that the energy deposition by resolved waves corresponds to the shear production (frictional heating) of the subgrid-scale turbulence model by which these waves are damped. Computational results from an atmospheric circulation model with energetically consistent treatment of momentum diffusion and frictional heating show that the energy deposition of thermal tides is substantial above the mesopause. This effect is either incomplete or even ignored in conventional atmospheric models that resolve the mesopause region. An idealized sensitivity experiment furthermore shows that thermal tides lead to a significant downward shift of gravity-wave breaking in the upper mesosphere.

  9. ZnO layers deposited by Atomic Layer Deposition

    NASA Astrophysics Data System (ADS)

    Pécz, B.; Baji, Zs; Lábadi, Z.; Kovács, A.

    2013-11-01

    The structure of 40 nm thick epitaxial ZnO layers grown on single crystalline sapphire and GaN substrates by atomic layer deposition has been studied using transmission electron microscopy. The growth is carried out between 150°C and 300°C without any buffer layer using di-ethyl zinc and water precursors. The ZnO layer on sapphire is found to be polycrystalline, which is probably due to the large misfit (~15 %) and the relatively low deposition temperature. However, the small misfit (~1.8 %) between the ZnO layer that is deposited on GaN at 300°C resulted in a high quality single crystalline layer.

  10. 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.

    2016-01-01

    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

  11. 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.

  12. 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.

  13. 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.

  14. Prediction of episodic acidification in North-eastern USA: An empirical/mechanistic approach

    USGS Publications Warehouse

    Davies, T.D.; Tranter, M.; Wigington, P.J.; Eshleman, K.N.; Peters, N.E.; Van Sickle, J.; DeWalle, David R.; Murdoch, Peter S.

    1999-01-01

    Observations from the US Environmental Protection Agency's Episodic Response Project (ERP) in the North-eastern United States are used to develop an empirical/mechanistic scheme for prediction of the minimum values of acid neutralizing capacity (ANC) during episodes. An acidification episode is defined as a hydrological event during which ANC decreases. The pre-episode ANC is used to index the antecedent condition, and the stream flow increase reflects how much the relative contributions of sources of waters change during the episode. As much as 92% of the total variation in the minimum ANC in individual catchments can be explained (with levels of explanation >70% for nine of the 13 streams) by a multiple linear regression model that includes pre-episode ANC and change in discharge as independent variable. The predictive scheme is demonstrated to be regionally robust, with the regional variance explained ranging from 77 to 83%. The scheme is not successful for each ERP stream, and reasons are suggested for the individual failures. The potential for applying the predictive scheme to other watersheds is demonstrated by testing the model with data from the Panola Mountain Research Watershed in the South-eastern United States, where the variance explained by the model was 74%. The model can also be utilized to assess 'chemically new' and 'chemically old' water sources during acidification episodes.Observations from the US Environmental Protection Agency's Episodic Response Project (ERP) in the Northeastern United States are used to develop an empirical/mechanistic scheme for prediction of the minimum values of acid neutralizing capacity (ANC) during episodes. An acidification episode is defined as a hydrological event during which ANC decreases. The pre-episode ANC is used to index the antecedent condition, and the stream flow increase reflects how much the relative contributions of sources of waters change during the episode. As much as 92% of the total variation in

  15. Solar Arctic Connection on Multidecadal to Centennial Timescales: Empirical Evidence and Mechanistic Explanation

    NASA Astrophysics Data System (ADS)

    Soon, W.

    2006-12-01

    In Soon (2005), the variable total solar irradiance series of Hoyt and Schatten (1993) has been shown to be able to explain, rather surprisingly, well over 75% of the variance for the decadally-smoothed Arctic-wide surface air temperature of Polyakov et al. (2003) over the past 130 years or so. Detailed examination and reconstruction of the seasonal pattern of Arctic temperature records, based on inverse wavelet transform, support a solar-Arctic physical connection. In this paper, I will provide additional empirical evidence for this physical connection both through several newly published, high-resolution paleo-proxy records and through reliable climate modeling outputs, and sketch a mechanistic explanation, involving the variable strength of the Atlantic meridional overturning circulation, the shift and modulation of the Inter-tropical Convergence Zone (ITCZ) rainbelt, and perhaps the intensity of the wind-driven subtropical and subpolar gyre circulation, while taking full advantage of the decomposition of solar insolation forcing into its symmetric and antisymmetric components proposed earlier by Bin Wang (1994), in order to better spell out the physical reality of this connection. The latter unique perspective is to offer a better interpretation and synthesis framework that would allow, in dynamical systems theory, a more natural correspondence with the decomposition of multidecadal and centennial climate variability into wind-driven and the thermohaline circulation modes with large-scale zonal (east-west) and meridional (north-south) symmetries or asymmetries (Dijkstra 2006). The ultimate goal of my scientific research, though, is to gain sufficient mechanistic details so that the proposed solar Arctic climate connection on multidecadal to centennial timescales can be confirmed or falsified. A differentiation of this total solar irradiance forcing proposal on the focused timescale from the related decadal-scale solar UV irradiance forcing will also be

  16. Mechanistic modeling of ion-exchange process chromatography of charge variants of monoclonal antibody products.

    PubMed

    Kumar, Vijesh; Leweke, Samuel; von Lieres, Eric; Rathore, Anurag S

    2015-12-24

    Ion-exchange chromatography (IEX) is universally accepted as the optimal method for achieving process scale separation of charge variants of a monoclonal antibody (mAb) therapeutic. These variants are closely related to the product and a baseline separation is rarely achieved. The general practice is to fractionate the eluate from the IEX column, analyze the fractions and then pool the desired fractions to obtain the targeted composition of variants. This is, however, a very cumbersome and time consuming exercise. A mechanistic model that is capable of simulating the peak profile will be a much more elegant and effective way to make a decision on the pooling strategy. This paper proposes a mechanistic model, based on the general rate model, to predict elution peak profile for separation of the main product from its variants. The proposed approach uses inverse fit of process scale chromatogram for estimation of model parameters using the initial values that are obtained from theoretical correlations. The packed bed column has been modeled along with the chromatographic system consisting of the mixer, tubing and detectors as a series of dispersed plug flow and continuous stirred tank reactors. The model uses loading ranges starting at 25% to a maximum of 70% of the loading capacity and hence is applicable to process scale separations. Langmuir model has been extended to include the effects of salt concentration and temperature on the model parameters. The extended Langmuir model that has been proposed uses one less parameter than the SMA model and this results in a significant ease of estimating the model parameters from inverse fitting. The proposed model has been validated with experimental data and has been shown to successfully predict peak profile for a range of load capacities (15-28mg/mL), gradient lengths (10-30CV), bed heights (6-20cm), and for three different resins with good accuracy (as measured by estimation of residuals). The model has been also

  17. Annual cycle of the global-mean energy budget in a mechanistic middle atmosphere GCM

    NASA Astrophysics Data System (ADS)

    Becker, Erich; Knoepfel, Rahel

    2014-05-01

    A new mechanistic climate model from the surface to the lower thermosphere is presented. The model is based on a standard spectral dynamical core and includes an idealized radiation scheme with continuous computation of energy fluxes. The surface energy budget is fully taken into account by means of a slap ocean with prescribed lateral oceanic heat-flux convergence. The moisture budget is based on a new transport scheme and simple parameterizations of condensation and convection. Subgrid-scale parameterizations include gravity waves and turbulent diffusion. Each parameterized process is formulated in an energy conserving fashion such that the resulting numerical error of the net radiation at the top of the atmosphere (RTOA) is about 0.2 W/m/m. The model shows a pronounced annual cycle of the RTOA of several W/m/m, with the minimum occurring in late NH winter. On a seasonal timescale this variation is synchronous with an equally strong imbalance at the surface. The annual cycle of the RTOA results from the hemispheric differences in the distribution of land and ocean surfaces, which are characterized by different heat capacities and albedos. While the absorbed solar radiation (ASR) is dominated by a semi-annual component associated with maximum absorption at the surface during the equinoxes, the global-mean surface temperature is governed by an annual component with a minimum during late NH winter. The reason is a smaller surface heat capacity in the NH, giving rise to global-mean cooling particularly during early NH winter. The annual cycle in the surface temperature then implies a corresponding behavior in the outgoing long-wave radiation (OLR), which gives the main contribution to the annual component of the RTOA. These mechanistic model results are supported by existing observational analyses. Analysing the global-mean energy budget as a function of height, the residual circulation is found to account for a downward dynamical energy flux from the stratosphere

  18. Hydroxyl radical induced oxidation of theophylline in water: a kinetic and mechanistic study.

    PubMed

    Sunil Paul, M M; Aravind, U K; Pramod, G; Saha, A; Aravindakumar, C T

    2014-08-14

    Oxidative destruction and mineralization of emerging organic pollutants by hydroxyl radicals (˙OH) is a well established area of research. The possibility of generating hazardous by-products in the case of ˙OH reaction demands extensive investigations on the degradation mechanism. A combination of pulse radiolysis and steady state photolysis (H2O2/UV photolysis) followed by high resolution mass spectrometric (HRMS) analysis have been employed to explicate the kinetic and mechanistic features of the destruction of theophylline, a model pharmaceutical compound and an identified pollutant, by ˙OH in the present study. The oxidative destruction of this molecule, for intermediate product studies, was initially achieved by H2O2/UV photolysis. The transient absorption spectrum corresponding to the reaction of ˙OH with theophylline at pH 6, primarily caused by the generation of (T8-OH)˙, was characterised by an absorption band at 330 nm (k2 = (8.22 ± 0.03) × 10(9) dm(3) mol(-1) s(-1)). A significantly different spectrum (λmax: 340 nm) was observed at highly alkaline pH (10.2) due to the deprotonation of this radical (pKa∼ 10.0). Specific one electron oxidants such as sulphate radical anions (SO4˙(-)) and azide radicals (N3˙) produce the deprotonated form (T(-H)˙) of the radical cation (T˙(+)) of theophylline (pKa 3.1) with k2 values of (7.51 ± 0.04) × 10(9) dm(3) mol(-1) s(-1) and (7.61 ± 0.02) × 10(9) dm(3) mol(-1) s(-1) respectively. Conversely, oxide radicals (O˙(-)) react with theophylline via a hydrogen abstraction protocol with a rather slow k2 value of (1.95 ± 0.02) × 10(9) dm(3) mol(-1) s(-1). The transient spectral studies were complemented by the end product profile acquired by HRMS analysis. Various transformation products of theophylline induced by ˙OH were identified by this technique which include derivatives of uric acids (i, iv & v) and xanthines (ii, iii & vi). Further breakdown of the early formed product due to ˙OH attack leads to

  19. Mechanistic modeling of ion-exchange process chromatography of charge variants of monoclonal antibody products.

    PubMed

    Kumar, Vijesh; Leweke, Samuel; von Lieres, Eric; Rathore, Anurag S

    2015-12-24

    Ion-exchange chromatography (IEX) is universally accepted as the optimal method for achieving process scale separation of charge variants of a monoclonal antibody (mAb) therapeutic. These variants are closely related to the product and a baseline separation is rarely achieved. The general practice is to fractionate the eluate from the IEX column, analyze the fractions and then pool the desired fractions to obtain the targeted composition of variants. This is, however, a very cumbersome and time consuming exercise. A mechanistic model that is capable of simulating the peak profile will be a much more elegant and effective way to make a decision on the pooling strategy. This paper proposes a mechanistic model, based on the general rate model, to predict elution peak profile for separation of the main product from its variants. The proposed approach uses inverse fit of process scale chromatogram for estimation of model parameters using the initial values that are obtained from theoretical correlations. The packed bed column has been modeled along with the chromatographic system consisting of the mixer, tubing and detectors as a series of dispersed plug flow and continuous stirred tank reactors. The model uses loading ranges starting at 25% to a maximum of 70% of the loading capacity and hence is applicable to process scale separations. Langmuir model has been extended to include the effects of salt concentration and temperature on the model parameters. The extended Langmuir model that has been proposed uses one less parameter than the SMA model and this results in a significant ease of estimating the model parameters from inverse fitting. The proposed model has been validated with experimental data and has been shown to successfully predict peak profile for a range of load capacities (15-28mg/mL), gradient lengths (10-30CV), bed heights (6-20cm), and for three different resins with good accuracy (as measured by estimation of residuals). The model has been also

  20. Higher plant modelling for life support applications: first results of a simple mechanistic model

    NASA Astrophysics Data System (ADS)

    Hezard, Pauline; Dussap, Claude-Gilles; Sasidharan L, Swathy

    2012-07-01

    In the case of closed ecological life support systems, the air and water regeneration and food production are performed using microorganisms and higher plants. Wheat, rice, soybean, lettuce, tomato or other types of eatable annual plants produce fresh food while recycling CO2 into breathable oxygen. Additionally, they evaporate a large quantity of water, which can be condensed and used as potable water. This shows that recycling functions of air revitalization and food production are completely linked. Consequently, the control of a growth chamber for higher plant production has to be performed with efficient mechanistic models, in order to ensure a realistic prediction of plant behaviour, water and gas recycling whatever the environmental conditions. Purely mechanistic models of plant production in controlled environments are not available yet. This is the reason why new models must be developed and validated. This work concerns the design and test of a simplified version of a mathematical model coupling plant architecture and mass balance purposes in order to compare its results with available data of lettuce grown in closed and controlled chambers. The carbon exchange rate, water absorption and evaporation rate, biomass fresh weight as well as leaf surface are modelled and compared with available data. The model consists of four modules. The first one evaluates plant architecture, like total leaf surface, leaf area index and stem length data. The second one calculates the rate of matter and energy exchange depending on architectural and environmental data: light absorption in the canopy, CO2 uptake or release, water uptake and evapotranspiration. The third module evaluates which of the previous rates is limiting overall biomass growth; and the last one calculates biomass growth rate depending on matter exchange rates, using a global stoichiometric equation. All these rates are a set of differential equations, which are integrated with time in order to provide