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Sample records for flow dynamics binding

  1. Sequential memory: Binding dynamics

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  2. Effects of flow changes on radiotracer binding: Simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation.

    Sander, Christin Y; Mandeville, Joseph B; Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Rosen, Bruce R

    2017-01-01

    The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO 2 ) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D 2 /D 3 receptor binding of [ 11 C]raclopride or [ 18 F]fallypride was monitored with dynamic PET. Experiments showed that neither time activity curves nor quantification of binding through binding potentials ( BP ND ) were measurably affected by CBF increases, which were larger than two-fold. Simulations of experimental procedures showed that even large changes in CBF should have little effect on the time activity curves of radiotracers, given a set of realistic assumptions. The proposed method can be applied to experimentally assess the flow sensitivity of other radiotracers. Results demonstrate that CBF changes, which often occur due to behavioral tasks or pharmacological challenges, do not affect PET [ 11 C]raclopride or [ 18 F]fallypride binding studies and their quantification. The results from this study suggest flow effects may have limited impact on many PET neuroreceptor tracers with similar properties.

  3. Radial flow gas dynamic laser

    Damm, F.C.

    1975-01-01

    The unique gas dynamic laser provides outward radial supersonic flow from a toroidal shaped stacked array of a plurality of nozzles, through a diffuser having ring shaped and/or linear shaped vanes, and through a cavity which is cylindrical and concentric with the stacked array, with the resultant laser beam passing through the housing parallel to the central axis of the diffuser which is coincident with the axis of the gas dynamic laser. Therefore, greater beam extraction flexibility is attainable, because of fewer flow shock disturbances, as compared to the conventional unidirectional flow gas dynamic laser in which unidirectional supersonic flow sweeps through a rectangular cavity and is exhausted through a two-dimensional diffuser. (auth)

  4. Multiphase Flow Dynamics 1 Fundamentals

    Kolev, Nikolay Ivanov

    2012-01-01

    Multi-phase flows are part of our natural environment such as tornadoes, typhoons, air and water pollution and volcanic activities as well as part of industrial technology such as power plants, combustion engines, propulsion systems, or chemical and biological industry. The industrial use of multi-phase systems requires analytical and numerical strategies for predicting their behavior. In its fourth extended edition the successful monograph package “Multiphase Flow Dynmics” contains theory, methods and practical experience for describing complex transient multi-phase processes in arbitrary geometrical configurations, providing a systematic presentation of the theory and practice of numerical multi-phase fluid dynamics. In the present first volume the local volume and time averaging is used to derive a complete set of conservation equations for three fluids each of them having multi components as constituents. Large parts of the book are devoted on the design of successful numerical methods for solving the...

  5. Multiphase flow dynamics 1 fundamentals

    Kolev, Nikolay Ivanov

    2015-01-01

    In its fifth extended edition the successful monograph package “Multiphase Flow Dynamics” contains theory, methods and practical experience for describing complex transient multi-phase processes in arbitrary geometrical configurations, providing a systematic presentation of the theory and practice of numerical multi-phase fluid dynamics. In the present first volume the local volume and time averaging is used to derive a complete set of conservation equations for three fluids each of them having multi components as constituents. Large parts of the book are devoted on the design of successful numerical methods for solving the obtained system of partial differential equations. Finally the analysis is repeated for boundary fitted curvilinear coordinate systems designing methods applicable for interconnected multi-blocks. This fifth edition includes various updates, extensions, improvements and corrections, as well as  a completely new chapter containing the basic physics describing the multi-phase flow in tu...

  6. Multiphase flow dynamics 1 fundamentals

    Kolev, Nikolay Ivanov

    2004-01-01

    Multi-phase flows are part of our natural environment such as tornadoes, typhoons, air and water pollution and volcanic activities as well as part of industrial technology such as power plants, combustion engines, propulsion systems, or chemical and biological industry. The industrial use of multi-phase systems requires analytical and numerical strategies for predicting their behavior. In its third extended edition this monograph contains theory, methods and practical experience for describing complex transient multi-phase processes in arbitrary geometrical configurations, providing a systematic presentation of the theory and practice of numerical multi-phase fluid dynamics. In the present first volume the fundamentals of multiphase dynamics are provided. This third edition includes various updates, extensions and improvements in all book chapters.

  7. Reconstruction of dynamical equations for traffic flow

    Kriso, S.; Friedrich, R.; Peinke, J.; Wagner, P.

    2001-01-01

    Traffic flow data collected by an induction loop detector on the highway close to Koeln-Nord are investigated with respect to their dynamics including the stochastic content. In particular we present a new method, with which the flow dynamics can be extracted directly from the measured data. As a result a Langevin equation for the traffic flow is obtained. From the deterministic part of the flow dynamics, stable fixed points are extracted and set into relation with common features of the fund...

  8. Autogenic dynamics of debris-flow fans

    van den Berg, Wilco; de Haas, Tjalling; Braat, Lisanne; Kleinhans, Maarten

    2015-04-01

    Alluvial fans develop their semi-conical shape by cyclic avulsion of their geomorphologically active sector from a fixed fan apex. These cyclic avulsions have been attributed to both allogenic and autogenic forcings and processes. Autogenic dynamics have been extensively studied on fluvial fans through physical scale experiments, and are governed by cyclic alternations of aggradation by unconfined sheet flow, fanhead incision leading to channelized flow, channel backfilling and avulsion. On debris-flow fans, however, autogenic dynamics have not yet been directly observed. We experimentally created debris-flow fans under constant extrinsic forcings, and show that autogenic dynamics are a fundamental intrinsic process on debris-flow fans. We found that autogenic cycles on debris-flow fans are driven by sequences of backfilling, avulsion and channelization, similar to the cycles on fluvial fans. However, the processes that govern these sequences are unique for debris-flow fans, and differ fundamentally from the processes that govern autogenic dynamics on fluvial fans. We experimentally observed that backfilling commenced after the debris flows reached their maximum possible extent. The next debris flows then progressively became shorter, driven by feedbacks on fan morphology and flow-dynamics. The progressively decreasing debris-flow length caused in-channel sedimentation, which led to increasing channel overflow and wider debris flows. This reduced the impulse of the liquefied flow body to the flow front, which then further reduced flow velocity and runout length, and induced further in-channel sedimentation. This commenced a positive feedback wherein debris flows became increasingly short and wide, until the channel was completely filled and the apex cross-profile was plano-convex. At this point, there was no preferential transport direction by channelization, and the debris flows progressively avulsed towards the steepest, preferential, flow path. Simultaneously

  9. Online traffic flow model applying dynamic flow-density relation

    Kim, Y.

    2002-01-01

    This dissertation describes a new approach of the online traffic flow modelling based on the hydrodynamic traffic flow model and an online process to adapt the flow-density relation dynamically. The new modelling approach was tested based on the real traffic situations in various homogeneous motorway sections and a motorway section with ramps and gave encouraging simulation results. This work is composed of two parts: first the analysis of traffic flow characteristics and second the development of a new online traffic flow model applying these characteristics. For homogeneous motorway sections traffic flow is classified into six different traffic states with different characteristics. Delimitation criteria were developed to separate these states. The hysteresis phenomena were analysed during the transitions between these traffic states. The traffic states and the transitions are represented on a states diagram with the flow axis and the density axis. For motorway sections with ramps the complicated traffic flow is simplified and classified into three traffic states depending on the propagation of congestion. The traffic states are represented on a phase diagram with the upstream demand axis and the interaction strength axis which was defined in this research. The states diagram and the phase diagram provide a basis for the development of the dynamic flow-density relation. The first-order hydrodynamic traffic flow model was programmed according to the cell-transmission scheme extended by the modification of flow dependent sending/receiving functions, the classification of cells and the determination strategy for the flow-density relation in the cells. The unreasonable results of macroscopic traffic flow models, which may occur in the first and last cells in certain conditions are alleviated by applying buffer cells between the traffic data and the model. The sending/receiving functions of the cells are determined dynamically based on the classification of the

  10. Instantaneous aerosol dynamics in a turbulent flow

    Zhou, Kun

    2012-01-01

    Dibutyl phthalate aerosol particles evolution dynamics in a turbulent mixing layer is simulated by means of direct numerical simulation for the flow field and the direct quadrature method of moments for the aerosol evolution. Most par

  11. [Dynamic Attending Binds Time and Rhythm Perception].

    Kuroda, Tsuyoshi; Ono, Fuminori; Kadota, Hiroshi

    2017-11-01

    Relations between time and rhythm perception are discussed in this review of psychophysical research relevant to the multiple-look effect and dynamic-attending theory. Discrimination of two neighboring intervals that are marked by three successive sounds is improved when the presentation of the first (standard, S) interval is repeated before that of the second (comparison, C), as SSSSC. This improvement in sensitivity, called the multiple-look effect, occurs because listeners (1) perceive regular rhythm during the repetition of the standard interval, (2) predict the timing of subsequent sounds, and (3) detect sounds that are deviated from the predicted timing. The dynamic-attending theory attributes such predictions to the entrainment of attentional rhythms. An endogenous attentional rhythm is synchronized with the periodic succession of sounds marking the repeated standard. The standard and the comparison are discriminated on the basis of whether the ending marker of the comparison appears at the peak of the entrained attentional rhythm. This theory is compatible with the findings of recent neurophysiological studies that relate temporal prediction to neural oscillations.

  12. AN OVERVIEW ON PULSATILE FLOW DYNAMICS

    Çarpinlioğlu, Melda Özdinç

    2015-01-01

    Pulsatile flow dynamics in reference to the relevant experimental research on the manner between the time periods of 1997- 2015 is presented in this paper. The flow field under discussion is generated through a rigid circular cross-sectional pipe as an axial slightly- compressible and sinusoidal one in a controlled range of the oscillation parameters. Laminar and turbulent flow regimes are considered with a particular emphasis devoted to the transitional characteristics of laminar pulsatile f...

  13. Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

    Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

    2012-01-01

    The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

  14. Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

    Ji-Long Zhang

    Full Text Available The research on the binding process of ligand to pyrazinamidase (PncA is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD simulation methods were performed to investigate the unbinding process of nicotinamide (NAM from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF based on the steered molecular dynamics (SMD simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

  15. Fluid dynamics of bubbly flows

    Ziegenhein, Thomas

    2016-01-01

    Bubbly flows can be found in many applications in chemical, biological and power engineering. Reliable simulation tools of such flows that allow the design of new processes and optimization of existing one are therefore highly desirable. CFD-simulations applying the multi-fluid approach are very promising to provide such a design tool for complete facilities. In the multi-fluid approach, however, closure models have to be formulated to model the interaction between the continuous and dispersed phase. Due to the complex nature of bubbly flows, different phenomena have to be taken into account and for every phenomenon different closure models exist. Therefore, reliable predictions of unknown bubbly flows are not yet possible with the multi-fluid approach. A strategy to overcome this problem is to define a baseline model in which the closure models including the model constants are fixed so that the limitations of the modeling can be evaluated by validating it on different experiments. Afterwards, the shortcomings are identified so that the baseline model can be stepwise improved without losing the validity for the already validated cases. This development of a baseline model is done in the present work by validating the baseline model developed at the Helmholtz-Zentrum Dresden-Rossendorf mainly basing on experimental data for bubbly pipe flows to bubble columns, bubble plumes and air-lift reactors that are relevant in chemical and biological engineering applications. In the present work, a large variety of such setups is used for validation. The buoyancy driven bubbly flows showed thereby a transient behavior on the scale of the facility. Since such large scales are characterized by the geometry of the facility, turbulence models cannot describe them. Therefore, the transient simulation of bubbly flows with two equation models based on the unsteady Reynolds-averaged Navier-Stokes equations is investigated. In combination with the before mentioned baseline model these

  16. Fluid dynamics of bubbly flows

    Ziegenhein, Thomas

    2016-07-08

    Bubbly flows can be found in many applications in chemical, biological and power engineering. Reliable simulation tools of such flows that allow the design of new processes and optimization of existing one are therefore highly desirable. CFD-simulations applying the multi-fluid approach are very promising to provide such a design tool for complete facilities. In the multi-fluid approach, however, closure models have to be formulated to model the interaction between the continuous and dispersed phase. Due to the complex nature of bubbly flows, different phenomena have to be taken into account and for every phenomenon different closure models exist. Therefore, reliable predictions of unknown bubbly flows are not yet possible with the multi-fluid approach. A strategy to overcome this problem is to define a baseline model in which the closure models including the model constants are fixed so that the limitations of the modeling can be evaluated by validating it on different experiments. Afterwards, the shortcomings are identified so that the baseline model can be stepwise improved without losing the validity for the already validated cases. This development of a baseline model is done in the present work by validating the baseline model developed at the Helmholtz-Zentrum Dresden-Rossendorf mainly basing on experimental data for bubbly pipe flows to bubble columns, bubble plumes and air-lift reactors that are relevant in chemical and biological engineering applications. In the present work, a large variety of such setups is used for validation. The buoyancy driven bubbly flows showed thereby a transient behavior on the scale of the facility. Since such large scales are characterized by the geometry of the facility, turbulence models cannot describe them. Therefore, the transient simulation of bubbly flows with two equation models based on the unsteady Reynolds-averaged Navier-Stokes equations is investigated. In combination with the before mentioned baseline model these

  17. Information flow dynamics in the brain

    Rabinovich, Mikhail I.; Afraimovich, Valentin S.; Bick, Christian; Varona, Pablo

    2012-03-01

    Timing and dynamics of information in the brain is a hot field in modern neuroscience. The analysis of the temporal evolution of brain information is crucially important for the understanding of higher cognitive mechanisms in normal and pathological states. From the perspective of information dynamics, in this review we discuss working memory capacity, language dynamics, goal-dependent behavior programming and other functions of brain activity. In contrast with the classical description of information theory, which is mostly algebraic, brain flow information dynamics deals with problems such as the stability/instability of information flows, their quality, the timing of sequential processing, the top-down cognitive control of perceptual information, and information creation. In this framework, different types of information flow instabilities correspond to different cognitive disorders. On the other hand, the robustness of cognitive activity is related to the control of the information flow stability. We discuss these problems using both experimental and theoretical approaches, and we argue that brain activity is better understood considering information flows in the phase space of the corresponding dynamical model. In particular, we show how theory helps to understand intriguing experimental results in this matter, and how recent knowledge inspires new theoretical formalisms that can be tested with modern experimental techniques.

  18. Dynamic binding of visual features by neuronal/stimulus synchrony.

    Iwabuchi, A

    1998-05-01

    When people see a visual scene, certain parts of the visual scene are treated as belonging together and we regard them as a perceptual unit, which is called a "figure". People focus on figures, and the remaining parts of the scene are disregarded as "ground". In Gestalt psychology this process is called "figure-ground segregation". According to current perceptual psychology, a figure is formed by binding various visual features in a scene, and developments in neuroscience have revealed that there are many feature-encoding neurons, which respond to such features specifically. It is not known, however, how the brain binds different features of an object into a coherent visual object representation. Recently, the theory of binding by neuronal synchrony, which argues that feature binding is dynamically mediated by neuronal synchrony of feature-encoding neurons, has been proposed. This review article portrays the problem of figure-ground segregation and features binding, summarizes neurophysiological and psychophysical experiments and theory relevant to feature binding by neuronal/stimulus synchrony, and suggests possible directions for future research on this topic.

  19. Dynamics of assembly production flow

    Ezaki, Takahiro; Yanagisawa, Daichi; Nishinari, Katsuhiro

    2015-06-01

    Despite recent developments in management theory, maintaining a manufacturing schedule remains difficult because of production delays and fluctuations in demand and supply of materials. The response of manufacturing systems to such disruptions to dynamic behavior has been rarely studied. To capture these responses, we investigate a process that models the assembly of parts into end products. The complete assembly process is represented by a directed tree, where the smallest parts are injected at leaves and the end products are removed at the root. A discrete assembly process, represented by a node on the network, integrates parts, which are then sent to the next downstream node as a single part. The model exhibits some intriguing phenomena, including overstock cascade, phase transition in terms of demand and supply fluctuations, nonmonotonic distribution of stockout in the network, and the formation of a stockout path and stockout chains. Surprisingly, these rich phenomena result from only the nature of distributed assembly processes. From a physical perspective, these phenomena provide insight into delay dynamics and inventory distributions in large-scale manufacturing systems.

  20. Particle algorithms for population dynamics in flows

    Perlekar, Prasad; Toschi, Federico; Benzi, Roberto; Pigolotti, Simone

    2011-01-01

    We present and discuss particle based algorithms to numerically study the dynamics of population subjected to an advecting flow condition. We discuss few possible variants of the algorithms and compare them in a model compressible flow. A comparison against appropriate versions of the continuum stochastic Fisher equation (sFKPP) is also presented and discussed. The algorithms can be used to study populations genetics in fluid environments.

  1. Vesicle dynamics in shear and capillary flows

    Noguchi, Hiroshi; Gompper, Gerhard

    2005-01-01

    The deformation of vesicles in flow is studied by a mesoscopic simulation technique, which combines multi-particle collision dynamics for the solvent with a dynamically triangulated surface model for the membrane. Shape transitions are investigated both in simple shear flows and in cylindrical capillary flows. We focus on reduced volumes, where the discocyte shape of fluid vesicles is stable, and the prolate shape is metastable. In simple shear flow at low membrane viscosity, the shear induces a transformation from discocyte to prolate with increasing shear rate, while at high membrane viscosity, the shear induces a transformation from prolate to discocyte, or tumbling motion accompanied by oscillations between these two morphologies. In capillary flow, at small flow velocities the symmetry axis of the discocyte is found not to be oriented perpendicular to the cylinder axis. With increasing flow velocity, a transition to a prolate shape occurs for fluid vesicles, while vesicles with shear-elastic membranes (like red blood cells) transform into a coaxial parachute-like shape

  2. Dynamics of TBP binding to the TATA box

    Schluesche, Peter; Heiss, Gregor; Meisterernst, Michael; Lamb, Don C.

    2008-02-01

    Gene expression is highly controlled and regulated in living cells. One of the first steps in gene transcription is recognition of the promoter site by the TATA box Binding Protein (TBP). TBP recruits other transcriptions factors and eventually the RNA polymerase II to transcribe the DNA in mRNA. We developed a single pair Förster Resonance Energy Transfer (spFRET) assay to investigate the mechanism of gene regulation. Here, we apply this assay to investigate the initial binding process of TBP to the adenovirus major late (AdML) promoter site. From the spFRET measurements, we were able to identify two conformations of the TBP-DNA complex that correspond to TBP bound in the correct and the opposite orientation. Increased incubation times or the presence of the transcription factor TFIIA improved the alignment of TBP on the promoter site. Binding of TBP to the TATA box shows a rich dynamics with abrupt transitions between multiple FRET states. A frame-wise histogram analysis revealed the presence of at least six discrete states, showing that TBP binding is more complicated than previously thought. Hence, the spFRET assay is very sensitive to the conformation of the TBP-DNA complex and is very promising tool for investigating the pathway of TBP binding in detail.

  3. Nonlinear dynamics of two-phase flow

    Rizwan-uddin

    1986-01-01

    Unstable flow conditions can occur in a wide variety of laboratory and industry equipment that involve two-phase flow. Instabilities in industrial equipment, which include boiling water reactor (BWR) cores, steam generators, heated channels, cryogenic fluid heaters, heat exchangers, etc., are related to their nonlinear dynamics. These instabilities can be of static (Ledinegg instability) or dynamic (density wave oscillations) type. Determination of regions in parameters space where these instabilities can occur and knowledge of system dynamics in or near these regions is essential for the safe operation of such equipment. Many two-phase flow engineering components can be modeled as heated channels. The set of partial differential equations that describes the dynamics of single- and two-phase flow, for the special case of uniform heat flux along the length of the channel, can be reduced to a set of two coupled ordinary differential equations [in inlet velocity v/sub i/(t) and two-phase residence time tau(t)] involving history integrals: a nonlinear ordinary functional differential equation and an integral equation. Hence, to solve these equations, the dependent variables must be specified for -(nu + tau) ≤ t ≤ 0, where nu is the single-phase residence time. This system of nonlinear equations has been solved analytically using asymptotic expansion series for finite but small perturbations and numerically using finite difference techniques

  4. Dynamic membrane filtration in tangential flow

    Anon.

    1993-01-01

    Oil-containing waste water is produced in many cleaning processes and also on production of compressed air. Dynamic membrane filtration in the tangential flow mode has proved effective in the treatment of these stable emulsions. The possible applications of ceramic membrane filters are illustrated for a variety of examples. (orig.) [de

  5. Multiphase Flow Dynamics 2 Mechanical Interactions

    Kolev, Nikolay Ivanov

    2012-01-01

    Multi-phase flows are part of our natural environment such as tornadoes, typhoons, air and water pollution and volcanic activities as well as part of industrial technology such as power plants, combustion engines, propulsion systems, or chemical and biological industry. The industrial use of multi-phase systems requires analytical and numerical strategies for predicting their behavior. .In its fourth extended edition the successful monograph package “Multiphase Flow Daynmics” contains theory, methods and practical experience for describing complex transient multi-phase processes in arbitrary geometrical configurations, providing a systematic presentation of the theory and practice of numerical multi-phase fluid dynamics. In the present second volume the methods for describing the mechanical interactions in multiphase dynamics are provided. This fourth edition includes various updates, extensions, improvements and corrections.   "The literature in the field of multiphase flows is numerous. Therefore, it i...

  6. Multiphase Flow Dynamics 5 Nuclear Thermal Hydraulics

    Kolev, Nikolay Ivanov

    2012-01-01

    The present Volume 5 of the successful book package "Multiphase Flow Dynamics" is devoted to nuclear thermal hydraulics which is a substantial part of nuclear reactor safety. It provides knowledge and mathematical tools for adequate description of the process of transferring the fission heat released in materials due to nuclear reactions into its environment. It step by step introduces into the heat release inside the fuel, temperature fields in the fuels, the "simple" boiling flow in a pipe described using ideas of different complexity like equilibrium, non equilibrium, homogeneity, non homogeneity. Then the "simple" three-fluid boiling flow in a pipe is described by gradually involving the mechanisms like entrainment and deposition, dynamic fragmentation, collisions, coalescence, turbulence. All heat transfer mechanisms are introduced gradually discussing their uncertainty. Different techniques are introduced like boundary layer treatments or integral methods. Comparisons with experimental data at each step...

  7. Multiphase flow dynamics 5 nuclear thermal hydraulics

    Kolev, Nikolay Ivanov

    2015-01-01

    This Volume 5 of the successful book package "Multiphase Flow Dynamics" is devoted to nuclear thermal hydraulics which is a substantial part of nuclear reactor safety. It provides knowledge and mathematical tools for adequate description of the process of transferring the fission heat released in materials due to nuclear reactions into its environment. It step by step introduces into the heat release inside the fuel, temperature fields in the fuels, the "simple" boiling flow in a pipe described using ideas of different complexity like equilibrium, non equilibrium, homogeneity, non homogeneity. Then the "simple" three-fluid boiling flow in a pipe is described by gradually involving the mechanisms like entrainment and deposition, dynamic fragmentation, collisions, coalescence, turbulence. All heat transfer mechanisms are introduced gradually discussing their uncertainty. Different techniques are introduced like boundary layer treatments or integral methods. Comparisons with experimental data at each step demons...

  8. Topological fluid dynamics of interfacial flows

    Brøns, Morten

    1994-01-01

    The topological description of flows in the vicinity of a solid boundary, that is familiar from the aerodynamics literature, has recently been extended to the case of flow at a liquid–gas interface or a free surface by Lugt [Phys. Fluids 30, 3647 (1987)]. Lugt's work is revisited in a more general...... setting, including nonconstant curvature of the interface and gradients of surface tension, using tools of modern nonlinear dynamics. Bifurcations of the flow pattern occur at degenerate configurations. Using the theory of unfolding, this paper gives a complete description of the bifurcations that depend...... on terms up to the second order. The general theory of this paper is applied to the topology of streamlines during the breaking of a wave and to the flow below a stagnant surface film. Physics of Fluids is copyrighted by The American Institute of Physics....

  9. Edge Sheared Flows and Blob Dynamics

    Myra, J.; D' Ippolito, D.; Russell, D., E-mail: jrmyra@lodestar.com [Lodestar Research Corporation, Boulder (United States); Davis, W. M.; Zweben, S. [Princeton Plasma Physics Laboratory, Princeton (United States); Terry, J.; LaBombard, B. [Massachusetts Institute of Technology, Cambridge (United States)

    2012-09-15

    Full text: A study of sheared flows in the edge and scrape-off layer (SOL) and their interaction with blob-filaments is presented. Edge sheared flows are believed to be important for the L-H, and H-L transitions. Blob generation and dynamics impacts both the (near-separatrix) scrape-off-layer (SOL) width critical for power handling in the divertor, and the interaction of plasma in the far SOL with plasma-facing components. These topics are critical for ITER and future devices. A fluid-based 2D curvature-interchange model embedded in the SOLT code is employed to study these issues. Sheared binormal flows both regulate the power flux crossing the separatrix and control the character of emitted turbulence structures such as blob-filaments. At a critical power level (depending on parameters) the laminar flows containing intermittent, but bound, structures give way to full-blown blob emissions signifying a transition from quasi-diffusive to convective transport. In order to diagnose sheared flows in experiments and assess their interaction with blobs, a blob-tracking algorithm has been developed and applied to both NSTX and Alcator C-Mod data. Blob motion and ellipticity can be affected by sheared flows, and are diagnosed and compared with seeded blob simulations. A picture of the interaction of blobs and sheared flows is emerging from advances in the theory and simulation of edge turbulence, combined with ever-improving capabilities for edge diagnostics and their analysis. (author)

  10. Global workspace dynamics: Cortical "binding and propagation enables conscious contents.

    Bernard J Baars

    2013-05-01

    Full Text Available A global workspace is a hub of binding and propagation in a population of loosely coupled signaling elements. Global workspace (GW architectures recruit many distributed, specialized agents to help resolve focal ambiguities. In the brain, conscious experiences may reflect a global workspace function. For animals the natural world is full of fitness-related ambiguities, suggesting a general adaptive pressure for brains to resolve focal ambiguities quickly and accurately. In humans and related species the cortico-thalamic (C-T core is believed to underlie conscious aspects of perception, thinking, learning, feelings of knowing, emotions, imagery, working memory and executive control. The C-T core has many anatomical hubs, but conscious percepts are unitary and internally consistent at any given moment. The repertoire of conscious contents is a large, open set. These points suggest that a brain-based GW capacity cannot be localized in a single anatomical hub. Rather, it should be sought in a dynamic capacity for adaptive binding and propagation of neural signals over multi-hub networks. We refer to this as dynamic global workspace theory (dGW. In this view, conscious contents can arise in any region of the C-T core when multiple signal streams settle on a winner-take-all equilibrium. The resulting bound gestalt may ignite an any-to-many broadcast, lasting ~100-200 ms, and trigger widespread adaptation in established networks. Binding and broadcasting may involve theta/gamma or alpha/gamma phase coupling. Conscious contents (qualia may reflect their sources in cortex. Sensory percepts may bind and broadcast from posterior regions, while non-sensory feelings of knowing (FOKs may be frontotemporal. The small focal capacity of conscious contents may be the biological price to pay for global access. We propose that in the intact brain the hippocampal/rhinal complex may support conscious event organization as well as episodic memory coding.

  11. Multiphase Flow Dynamics 3 Thermal Interactions

    Kolev, Nikolay Ivanov

    2012-01-01

    Multi-phase flows are part of our natural environment such as tornadoes, typhoons, air and water pollution and volcanic activities as well as part of industrial technology such as power plants, combustion engines, propulsion systems, or chemical and biological industry. The industrial use of multi-phase systems requires analytical and numerical strategies for predicting their behavior. .In its fourth extended edition the successful monograph package “Multiphase Flow Daynmics” contains theory, methods and practical experience for describing complex transient multi-phase processes in arbitrary geometrical configurations, providing a systematic presentation of the theory and practice of numerical multi-phase fluid dynamics. In the present third volume methods for describing of the thermal interactions in multiphase dynamics are provided. In addition a large number of valuable experiments is collected and predicted using the methods introduced in this monograph. In this way the accuracy of the methods is reve...

  12. Traffic flow dynamics data, models and simulation

    Treiber, Martin

    2013-01-01

    This textbook provides a comprehensive and instructive coverage of vehicular traffic flow dynamics and modeling. It makes this fascinating interdisciplinary topic, which to date was only documented in parts by specialized monographs, accessible to a broad readership. Numerous figures and problems with solutions help the reader to quickly understand and practice the presented concepts. This book is targeted at students of physics and traffic engineering and, more generally, also at students and professionals in computer science, mathematics, and interdisciplinary topics. It also offers material for project work in programming and simulation at college and university level. The main part, after presenting different categories of traffic data, is devoted to a mathematical description of the dynamics of traffic flow, covering macroscopic models which describe traffic in terms of density, as well as microscopic many-particle models in which each particle corresponds to a vehicle and its driver. Focus chapters on ...

  13. Minimum cost dynamic flows: The series-parallel case

    Klinz, Bettina; Woeginger, Gerhard

    2004-01-01

    A dynamic network consists of a directed graph with capacities, costs, and integral transit times on the arcs. In the minimum-cost dynamic flow problem (MCDFP), the goal is to compute, for a given dynamic network with source s, sink t, and two integers v and T, a feasible dynamic flow from s to t of

  14. Flow dynamics around downwelling submarine canyons

    J. M. Spurgin

    2014-10-01

    Full Text Available Flow dynamics around a downwelling submarine canyon were analysed with the Massachusetts Institute of Technology general circulation model. Blanes Canyon (northwestern Mediterranean was used for topographic and initial forcing conditions. Fourteen scenarios were modelled with varying forcing conditions. Rossby and Burger numbers were used to determine the significance of Coriolis acceleration and stratification (respectively and their impacts on flow dynamics. A new non-dimensional parameter (χ was introduced to determine the significance of vertical variations in stratification. Some simulations do see brief periods of upwards displacement of water during the 10-day model period; however, the presence of the submarine canyon is found to enhance downwards advection of density in all model scenarios. High Burger numbers lead to negative vorticity and a trapped anticyclonic eddy within the canyon, as well as an increased density anomaly. Low Burger numbers lead to positive vorticity, cyclonic circulation, and weaker density anomalies. Vertical variations in stratification affect zonal jet placement. Under the same forcing conditions, the zonal jet is pushed offshore in more uniformly stratified domains. The offshore jet location generates upwards density advection away from the canyon, while onshore jets generate downwards density advection everywhere within the model domain. Increasing Rossby values across the canyon axis, as well as decreasing Burger values, increase negative vertical flux at shelf break depth (150 m. Increasing Rossby numbers lead to stronger downwards advection of a passive tracer (nitrate, as well as stronger vorticity within the canyon. Results from previous studies are explained within this new dynamic framework.

  15. Dynamic methods of air traffic flow management

    Jacek SKORUPSKI

    2011-01-01

    Full Text Available Air traffic management is a complex hierarchical system. Hierarchy levels can be defined according to decision making time horizon or to analyze area volume. For medium time horizon and wide analysis area, the air traffic flow management services were established. Their main task is to properly co-ordinate air traffic in European airspace, so as to minimize delays arising in congested sectors. Those services have to assure high safety level at the same time. Thus it is a very complex task, with many goals, many decision variables and many constraints.In the paper review of the methods developed for aiding air traffic flow management services is presented. More detailed description of a dynamic method is given. This method is based on stochastic capacity and scenario analysis. Some problems in utilization of presented methods are also pointed out, so are the next research possibilities.

  16. Instantaneous aerosol dynamics in a turbulent flow

    Zhou, Kun

    2012-01-01

    Dibutyl phthalate aerosol particles evolution dynamics in a turbulent mixing layer is simulated by means of direct numerical simulation for the flow field and the direct quadrature method of moments for the aerosol evolution. Most par-ticles are nucleated in a thin layer region corresponding to a specific narrow temperature range near the cool stream side. However, particles undergo high growth rate on the hot stream side due to condensation. Coagulation decreases the total particle number density at a rate which is highly correlated to the in-stantaneous number density.

  17. Dynamic Flow Management Problems in Air Transportation

    Patterson, Sarah Stock

    1997-01-01

    In 1995, over six hundred thousand licensed pilots flew nearly thirty-five million flights into over eighteen thousand U.S. airports, logging more than 519 billion passenger miles. Since demand for air travel has increased by more than 50% in the last decade while capacity has stagnated, congestion is a problem of undeniable practical significance. In this thesis, we will develop optimization techniques that reduce the impact of congestion on the national airspace. We start by determining the optimal release times for flights into the airspace and the optimal speed adjustment while airborne taking into account the capacitated airspace. This is called the Air Traffic Flow Management Problem (TFMP). We address the complexity, showing that it is NP-hard. We build an integer programming formulation that is quite strong as some of the proposed inequalities are facet defining for the convex hull of solutions. For practical problems, the solutions of the LP relaxation of the TFMP are very often integral. In essence, we reduce the problem to efficiently solving large scale linear programming problems. Thus, the computation times are reasonably small for large scale, practical problems involving thousands of flights. Next, we address the problem of determining how to reroute aircraft in the airspace system when faced with dynamically changing weather conditions. This is called the Air Traffic Flow Management Rerouting Problem (TFMRP) We present an integrated mathematical programming approach for the TFMRP, which utilizes several methodologies, in order to minimize delay costs. In order to address the high dimensionality, we present an aggregate model, in which we formulate the TFMRP as a multicommodity, integer, dynamic network flow problem with certain side constraints. Using Lagrangian relaxation, we generate aggregate flows that are decomposed into a collection of flight paths using a randomized rounding heuristic. This collection of paths is used in a packing integer

  18. Traffic flow dynamics. Data, models and simulation

    Treiber, Martin [Technische Univ. Dresden (Germany). Inst. fuer Wirtschaft und Verkehr; Kesting, Arne [TomTom Development Germany GmbH, Berlin (Germany)

    2013-07-01

    First comprehensive textbook of this fascinating interdisciplinary topic which explains advances in a way that it is easily accessible to engineering, physics and math students. Presents practical applications of traffic theory such as driving behavior, stability analysis, stop-and-go waves, and travel time estimation. Presents the topic in a novel and systematic way by addressing both microscopic and macroscopic models with a focus on traffic instabilities. Revised and extended edition of the German textbook ''Verkehrsdynamik und -simulation''. This textbook provides a comprehensive and instructive coverage of vehicular traffic flow dynamics and modeling. It makes this fascinating interdisciplinary topic, which to date was only documented in parts by specialized monographs, accessible to a broad readership. Numerous figures and problems with solutions help the reader to quickly understand and practice the presented concepts. This book is targeted at students of physics and traffic engineering and, more generally, also at students and professionals in computer science, mathematics, and interdisciplinary topics. It also offers material for project work in programming and simulation at college and university level. The main part, after presenting different categories of traffic data, is devoted to a mathematical description of the dynamics of traffic flow, covering macroscopic models which describe traffic in terms of density, as well as microscopic many-particle models in which each particle corresponds to a vehicle and its driver. Focus chapters on traffic instabilities and model calibration/validation present these topics in a novel and systematic way. Finally, the theoretical framework is shown at work in selected applications such as traffic-state and travel-time estimation, intelligent transportation systems, traffic operations management, and a detailed physics-based model for fuel consumption and emissions.

  19. Irreversible energy flow in forced Vlasov dynamics

    Plunk, Gabriel G.

    2014-10-01

    © EDP Sciences, Società Italiana di Fisica, Springer-Verlag. The recent paper of Plunk [G.G. Plunk, Phys. Plasmas 20, 032304 (2013)] considered the forced linear Vlasov equation as a model for the quasi-steady state of a single stable plasma wavenumber interacting with a bath of turbulent fluctuations. This approach gives some insight into possible energy flows without solving for nonlinear dynamics. The central result of the present work is that the forced linear Vlasov equation exhibits asymptotically zero (irreversible) dissipation to all orders under a detuning of the forcing frequency and the characteristic frequency associated with particle streaming. We first prove this by direct calculation, tracking energy flow in terms of certain exact conservation laws of the linear (collisionless) Vlasov equation. Then we analyze the steady-state solutions in detail using a weakly collisional Hermite-moment formulation, and compare with numerical solution. This leads to a detailed description of the Hermite energy spectrum, and a proof of no dissipation at all orders, complementing the collisionless Vlasov result.

  20. Irreversible energy flow in forced Vlasov dynamics

    Plunk, Gabriel G.; Parker, Joseph T.

    2014-01-01

    © EDP Sciences, Società Italiana di Fisica, Springer-Verlag. The recent paper of Plunk [G.G. Plunk, Phys. Plasmas 20, 032304 (2013)] considered the forced linear Vlasov equation as a model for the quasi-steady state of a single stable plasma wavenumber interacting with a bath of turbulent fluctuations. This approach gives some insight into possible energy flows without solving for nonlinear dynamics. The central result of the present work is that the forced linear Vlasov equation exhibits asymptotically zero (irreversible) dissipation to all orders under a detuning of the forcing frequency and the characteristic frequency associated with particle streaming. We first prove this by direct calculation, tracking energy flow in terms of certain exact conservation laws of the linear (collisionless) Vlasov equation. Then we analyze the steady-state solutions in detail using a weakly collisional Hermite-moment formulation, and compare with numerical solution. This leads to a detailed description of the Hermite energy spectrum, and a proof of no dissipation at all orders, complementing the collisionless Vlasov result.

  1. Fluid flow dynamics in MAS systems

    Wilhelm, Dirk; Purea, Armin; Engelke, Frank

    2015-08-01

    The turbine system and the radial bearing of a high performance magic angle spinning (MAS) probe with 1.3 mm-rotor diameter has been analyzed for spinning rates up to 67 kHz. We focused mainly on the fluid flow properties of the MAS system. Therefore, computational fluid dynamics (CFD) simulations and fluid measurements of the turbine and the radial bearings have been performed. CFD simulation and measurement results of the 1.3 mm-MAS rotor system show relatively low efficiency (about 25%) compared to standard turbo machines outside the realm of MAS. However, in particular, MAS turbines are mainly optimized for speed and stability instead of efficiency. We have compared MAS systems for rotor diameter of 1.3-7 mm converted to dimensionless values with classical turbomachinery systems showing that the operation parameters (rotor diameter, inlet mass flow, spinning rate) are in the favorable range. This dimensionless analysis also supports radial turbines for low speed MAS probes and diagonal turbines for high speed MAS probes. Consequently, a change from Pelton type MAS turbines to diagonal turbines might be worth considering for high speed applications. CFD simulations of the radial bearings have been compared with basic theoretical values proposing considerably smaller frictional loss values. The discrepancies might be due to the simple linear flow profile employed for the theoretical model. Frictional losses generated inside the radial bearings result in undesired heat-up of the rotor. The rotor surface temperature distribution computed by CFD simulations show a large temperature gradient over the rotor.

  2. Endothelial cell capture of heparin-binding growth factors under flow.

    Bing Zhao

    2010-10-01

    Full Text Available Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2 was used for both the experiments and simulations. Our computational model was composed of three parts: (1 media flow equations, (2 mass transport equations and (3 cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that

  3. RECOGNITION DYNAMICS OF ESCHERICHIA COLI THIOREDOXIN PROBED USING MOLECULAR DYNAMICS AND BINDING FREE ENERGY CALCULATIONS

    M. S. Shahul Hameed

    2016-03-01

    Full Text Available E. coli thioredoxin has been regarded as a hub protein as it interacts with, and regulates, numerous target proteins involved in a wide variety of cellular processes. Thioredoxin can form complexes with a variety of target proteins with a wide range of affinity, using a consensus binding surface. In this study an attempt to deduce the molecular basis for the observed multispecificity of E. coli thioredoxin has been made. In this manuscript it has been shown that structural plasticity, adaptable and exposed hydrophobic binding surface, surface electrostatics, closely clustered multiple hot spot residues and conformational changes brought about by the redox status of the protein have been shown to account for the observed multispecificity and molecular recognition of thioredoxin. Dynamical differences between the two redox forms of the enzyme have also been studied to account for their differing interactions with some target proteins.

  4. Dynamic exercise enhances regional cerebral artery mean flow velocity

    Linkis, P; Jørgensen, L G; Olesen, H L

    1995-01-01

    Dynamic exercise enhances regional cerebral artery mean flow velocity. J. Appl. Physiol. 78(1): 12-16, 1995.--Anterior (ACA) and middle (MCA) cerebral artery mean flow velocities (Vmean) and pulsatility indexes were determined using transcranial Doppler in 14 subjects during dynamic exercise afte...

  5. Modelling flow dynamics in water distribution networks using ...

    One such approach is the Artificial Neural Networks (ANNs) technique. The advantage of ANNs is that they are robust and can be used to model complex linear and non-linear systems without making implicit assumptions. ANNs can be trained to forecast flow dynamics in a water distribution network. Such flow dynamics ...

  6. Crystal Structures and Binding Dynamics of Odorant-Binding Protein 3 from two aphid species Megoura viciae and Nasonovia ribisnigri.

    Northey, Tom; Venthur, Herbert; De Biasio, Filomena; Chauviac, Francois-Xavier; Cole, Ambrose; Ribeiro, Karlos Antonio Lisboa; Grossi, Gerarda; Falabella, Patrizia; Field, Linda M; Keep, Nicholas H; Zhou, Jing-Jiang

    2016-04-22

    Aphids use chemical cues to locate hosts and find mates. The vetch aphid Megoura viciae feeds exclusively on the Fabaceae, whereas the currant-lettuce aphid Nasonovia ribisnigri alternates hosts between the Grossulariaceae and Asteraceae. Both species use alarm pheromones to warn of dangers. For N. ribisnigri this pheromone is a single component (E)-β-farnesene but M. viciae uses a mixture of (E)-β-farnesene, (-)-α-pinene, β-pinene, and limonene. Odorant-binding proteins (OBP) are believed to capture and transport such semiochemicals to their receptors. Here, we report the first aphid OBP crystal structures and examine their molecular interactions with the alarm pheromone components. Our study reveals some unique structural features: 1) the lack of an internal ligand binding site; 2) a striking groove in the surface of the proteins as a putative binding site; 3) the N-terminus rather than the C-terminus occupies the site closing off the conventional OBP pocket. The results from fluorescent binding assays, molecular docking and dynamics demonstrate that OBP3 from M. viciae can bind to all four alarm pheromone components and the differential ligand binding between these very similar OBP3s from the two aphid species is determined mainly by the direct π-π interactions between ligands and the aromatic residues of OBP3s in the binding pocket.

  7. Analyzing machupo virus-receptor binding by molecular dynamics simulations

    Austin G. Meyer

    2014-02-01

    Full Text Available In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein–protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host–virus protein–protein interface. We use steered molecular dynamics (SMD to computationally pull the machupo virus (MACV spike glycoprotein (GP1 away from the human transferrin receptor (hTfR1. We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein–protein interactions.

  8. Analyzing machupo virus-receptor binding by molecular dynamics simulations

    Sawyer, Sara L.; Ellington, Andrew D.; Wilke, Claus O.

    2014-01-01

    In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein–protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host–virus protein–protein interface. We use steered molecular dynamics (SMD) to computationally pull the machupo virus (MACV) spike glycoprotein (GP1) away from the human transferrin receptor (hTfR1). We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein–protein interactions. PMID:24624315

  9. A network-flow based valve-switching aware binding algorithm for flow-based microfluidic biochips

    Tseng, Kai-Han; You, Sheng-Chi; Minhass, Wajid Hassan

    2013-01-01

    -flow based resource binding algorithm based on breadth-first search (BFS) and minimum cost maximum flow (MCMF) in architectural-level synthesis. The experimental results show that our methodology not only makes significant reduction of valve-switching activities but also diminishes the application completion......Designs of flow-based microfluidic biochips are receiving much attention recently because they replace conventional biological automation paradigm and are able to integrate different biochemical analysis functions on a chip. However, as the design complexity increases, a flow-based microfluidic...... biochip needs more chip-integrated micro-valves, i.e., the basic unit of fluid-handling functionality, to manipulate the fluid flow for biochemical applications. Moreover, frequent switching of micro-valves results in decreased reliability. To minimize the valve-switching activities, we develop a network...

  10. Dynamic self-organization in particle-laden channel flow

    Geurts, Bernardus J.; Vreman, A.W.

    2006-01-01

    We study dynamic flow-structuring and mean-flow properties of turbulent particle-laden riser-flow at significant particle volume fractions of about 1.5%. We include particle–particle as well as particle–fluid interactions through inelastic collisions and drag forces, in a so-called four-way coupled

  11. Computational fluid dynamics incompressible turbulent flows

    Kajishima, Takeo

    2017-01-01

    This textbook presents numerical solution techniques for incompressible turbulent flows that occur in a variety of scientific and engineering settings including aerodynamics of ground-based vehicles and low-speed aircraft, fluid flows in energy systems, atmospheric flows, and biological flows. This book encompasses fluid mechanics, partial differential equations, numerical methods, and turbulence models, and emphasizes the foundation on how the governing partial differential equations for incompressible fluid flow can be solved numerically in an accurate and efficient manner. Extensive discussions on incompressible flow solvers and turbulence modeling are also offered. This text is an ideal instructional resource and reference for students, research scientists, and professional engineers interested in analyzing fluid flows using numerical simulations for fundamental research and industrial applications. • Introduces CFD techniques for incompressible flow and turbulence with a comprehensive approach; • Enr...

  12. Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an AAAAA DNA binding site

    Dolenc, Jožica; Oostenbrink, Chris; Koller, Jože; van Gunsteren, Wilfred F.

    2005-01-01

    Molecular dynamics simulations have been performed on netropsin in two different charge states and on distamycin binding to the minor groove of the DNA duplex d(CGCGAAAAACGCG)·d(CGCGTTTTTCGCG). The relative free energy of binding of the two non-covalently interacting ligands was calculated using the thermodynamic integration method and reflects the experimental result. From 2 ns simulations of the ligands free in solution and when bound to DNA, the mobility and the hydrogen-bonding patterns of the ligands were studied, as well as their hydration. It is shown that even though distamycin is less hydrated than netropsin, the loss of ligand–solvent interactions is very similar for both ligands. The relative mobilities of the ligands in their bound and free forms indicate a larger entropic penalty for distamycin when binding to the minor groove compared with netropsin, partially explaining the lower binding affinity of the distamycin molecule. The detailed structural and energetic insights obtained from the molecular dynamics simulations allow for a better understanding of the factors determining ligand–DNA binding. PMID:15687382

  13. Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an AAAAA DNA binding site.

    Dolenc, Jozica; Oostenbrink, Chris; Koller, Joze; van Gunsteren, Wilfred F

    2005-01-01

    Molecular dynamics simulations have been performed on netropsin in two different charge states and on distamycin binding to the minor groove of the DNA duplex d(CGCGAAAAACGCG).d(CGCGTTTTTCGCG). The relative free energy of binding of the two non-covalently interacting ligands was calculated using the thermodynamic integration method and reflects the experimental result. From 2 ns simulations of the ligands free in solution and when bound to DNA, the mobility and the hydrogen-bonding patterns of the ligands were studied, as well as their hydration. It is shown that even though distamycin is less hydrated than netropsin, the loss of ligand-solvent interactions is very similar for both ligands. The relative mobilities of the ligands in their bound and free forms indicate a larger entropic penalty for distamycin when binding to the minor groove compared with netropsin, partially explaining the lower binding affinity of the distamycin molecule. The detailed structural and energetic insights obtained from the molecular dynamics simulations allow for a better understanding of the factors determining ligand-DNA binding.

  14. Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

    Song, Wei; Guo, Jun-Tao

    2015-01-01

    Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

  15. Change of conformation and internal dynamics of supercoiled DNA upon binding of Escherichia coli single-strand binding protein

    Langowski, J.; Benight, A.S.; Fujimoto, B.S.; Schurr, J.M.; Schomburg, U.

    1985-01-01

    The influence of Escherichia coli single-strand binding (SSB) protein on the conformation and internal dynamics of pBR322 and pUC8 supercoiled DNAs has been investigated by using dynamic light scattering at 632.8 and 351.1 nm and time-resolved fluorescence polarization anisotropy of intercalated ethidium. SSB protein binds to both DNAs up to a stoichiometry that is sufficient to almost completely relax the superhelical turns. Upon saturation binding, the translational diffusion coefficients (D 0 ) of both DNAs decrease by approximately 20%. Apparent diffusion coefficients (D/sub app/) obtained from dynamic light scattering display the well-known increase with K 2 (K = scattering vector), leveling off toward a plateau value (D/sub plat/) at high K 2 . For both DNAs, the difference D/sub plat/ - D 0 increases upon relaxation of supercoils by SSB protein, which indicates a corresponding enhancement of the subunit mobilities in internal motions. Fluorescence polarization anisotropy measurements on free and complexed pBR322 DNA indicate a (predominantly) uniform torsional rigidity for the saturated DNA/SSB protein complex that is significantly reduced compared to the free DNA. These observations are all consistent with the notion that binding of SSB protein is accompanied by a gradual loss of supercoils and saturates when the superhelical twist is largely removed

  16. Dynamic measurements of flowing cells labeled by gold nanoparticles using full-field photothermal interferometric imaging

    Turko, Nir A.; Roitshtain, Darina; Blum, Omry; Kemper, Björn; Shaked, Natan T.

    2017-06-01

    We present highly dynamic photothermal interferometric phase microscopy for quantitative, selective contrast imaging of live cells during flow. Gold nanoparticles can be biofunctionalized to bind to specific cells, and stimulated for local temperature increase due to plasmon resonance, causing a rapid change of the optical phase. These phase changes can be recorded by interferometric phase microscopy and analyzed to form an image of the binding sites of the nanoparticles in the cells, gaining molecular specificity. Since the nanoparticle excitation frequency might overlap with the sample dynamics frequencies, photothermal phase imaging was performed on stationary or slowly dynamic samples. Furthermore, the computational analysis of the photothermal signals is time consuming. This makes photothermal imaging unsuitable for applications requiring dynamic imaging or real-time analysis, such as analyzing and sorting cells during fast flow. To overcome these drawbacks, we utilized an external interferometric module and developed new algorithms, based on discrete Fourier transform variants, enabling fast analysis of photothermal signals in highly dynamic live cells. Due to the self-interference module, the cells are imaged with and without excitation in video-rate, effectively increasing signal-to-noise ratio. Our approach holds potential for using photothermal cell imaging and depletion in flow cytometry.

  17. Energy flow theory of nonlinear dynamical systems with applications

    Xing, Jing Tang

    2015-01-01

    This monograph develops a generalised energy flow theory to investigate non-linear dynamical systems governed by ordinary differential equations in phase space and often met in various science and engineering fields. Important nonlinear phenomena such as, stabilities, periodical orbits, bifurcations and chaos are tack-led and the corresponding energy flow behaviors are revealed using the proposed energy flow approach. As examples, the common interested nonlinear dynamical systems, such as, Duffing’s oscillator, Van der Pol’s equation, Lorenz attractor, Rössler one and SD oscillator, etc, are discussed. This monograph lights a new energy flow research direction for nonlinear dynamics. A generalised Matlab code with User Manuel is provided for readers to conduct the energy flow analysis of their nonlinear dynamical systems. Throughout the monograph the author continuously returns to some examples in each chapter to illustrate the applications of the discussed theory and approaches. The book can be used as ...

  18. Flow-cytometric determination of high-density-lipoprotein binding sites on human leukocytes

    Schmitz, G.; Wulf, G.; Bruening, T.A.; Assmann, G.

    1987-01-01

    In this method, leukocytes were isolated from 6 mL of EDTA-blood by density-gradient centrifugation and subsequently incubated with rhodamine isothiocyanate (RITC)-conjugated high-density lipoproteins (HDL). The receptor-bound conjugate particles were determined by fluorescent flow cytometry and compared with 125 I-labeled HDL binding data for the same cells. Human granulocytes express the highest number of HDL binding sites (9.4 x 10(4)/cell), followed by monocytes (7.3 x 10(4)/cell) and lymphocytes (4.0 x 10(4)/cell). Compared with conventional analysis of binding of 125 I-labeled HDL in tissue-culture dishes, the present determination revealed significantly lower values for nonspecific binding. In competition studies, the conjugate competes for the same binding sites as 125 I-labeled HDL. With the use of tetranitromethane-treated HDL3, which fails to compete for the HDL receptor sites while nonspecific binding is not affected, we could clearly distinguish between 37 degrees C surface binding and specific 37 degrees C uptake of RITC-HDL3, confirming that the HDL receptor leads bound HDL particles into an intracellular pathway rather than acting as a docking type of receptor. Patients with familial dysbetalipoproteinemia showed a significantly higher number of HDL binding sites in the granulocyte population but normal in lymphocytes and monocytes, indicating increased uptake of cholesterol-containing lipoproteins. In patients with familial hypercholesterolemia, HDL binding was increased in all three cell types, indicating increased cholesterol uptake and increased cholesterol synthesis. The present method allows rapid determination of HDL binding sites in leukocytes from patients with various forms of hyper- and dyslipoproteinemias

  19. Thermo-Fluid Dynamics of Two-Phase Flow

    Ishii, Mamrou

    2011-01-01

    "Thermo-fluid Dynamics of Two-Phase Flow, Second Edition" is focused on the fundamental physics of two-phase flow. The authors present the detailed theoretical foundation of multi-phase flow thermo-fluid dynamics as they apply to: Nuclear reactor transient and accident analysis; Energy systems; Power generation systems; Chemical reactors and process systems; Space propulsion; Transport processes. This edition features updates on two-phase flow formulation and constitutive equations and CFD simulation codes such as FLUENT and CFX, new coverage of the lift force model, which is of part

  20. Dynamic Modeling Strategy for Flow Regime Transition in Gas-Liquid Two-Phase Flows

    Xia Wang

    2012-12-01

    Full Text Available In modeling gas-liquid two-phase flows, the concept of flow regimes has been widely used to characterize the global interfacial structure of the flows. Nearly all constitutive relations that provide closures to the interfacial transfers in two-phase flow models, such as the two-fluid model, are flow regime dependent. Current nuclear reactor safety analysis codes, such as RELAP5, classify flow regimes using flow regime maps or transition criteria that were developed for steady-state, fully-developed flows. As two-phase flows are dynamic in nature, it is important to model the flow regime transitions dynamically to more accurately predict the two-phase flows. The present work aims to develop a dynamic modeling strategy to determine flow regimes in gas-liquid two-phase flows through introduction of interfacial area transport equations (IATEs within the framework of a two-fluid model. The IATE is a transport equation that models the interfacial area concentration by considering the creation of the interfacial area, fluid particle (bubble or liquid droplet disintegration, boiling and evaporation, and the destruction of the interfacial area, fluid particle coalescence and condensation. For flow regimes beyond bubbly flows, a two-group IATE has been proposed, in which bubbles are divided into two groups based on their size and shapes, namely group-1 and group-2 bubbles. A preliminary approach to dynamically identify the flow regimes is discussed, in which discriminators are based on the predicted information, such as the void fraction and interfacial area concentration. The flow regime predicted with this method shows good agreement with the experimental observations.

  1. ON THE ANALYSIS OF IMPEDANCE-DRIVEN REVERSE FLOW DYNAMICS

    LEE V. C.-C.

    2017-02-01

    Full Text Available Impedance pump is a simple valve-less pumping mechanism, where an elastic tube is joined to a more rigid tube, at both ends. By inducing a periodic asymmetrical compression on the elastic tube will produce a unidirectional flow within the system. This pumping concept offers a low energy, low noise alternative, which makes it an effective driving mechanism, especially for micro-fluidic systems. In addition, the wave-based mechanism through which pumping occurs infers many benefits in terms of simplicity of design and manufacturing. Adjustment of simple parameters such as the excitation frequencies or compression locations will reverse the direction of flow, providing a very versatile range of flow outputs. This paper describes the experimental analysis of such impedance-driven flow with emphasis on the dynamical study of the reverse flow in open-loop environment. In this study, tapered section with converging steps is introduced at both ends of the elastic tube to amplify the magnitude of reverse flow. Study conducted shows that the reverse peak flow is rather significant with estimate of 23% lower than the forward peak flow. The flow dynamics on the other hand has shown to exhibit different characteristics as per the forward peak flow. The flow characteristics is then studied and showed that the tapered sections altered the impedance within the system and hence induce a higher flow in the reverse direction.

  2. A Dynamic Growth Model for Flows of Foreign Direct Investment

    Yi-Hui Chiang; Yiming Li; Chih-Young Hung

    2007-01-01

    In this work, we for the first time study the dynamic flows of the foreign direct investment (FDI) with a dynamic growth theory. We define the FDI flow as a process which transmits throughout a given social system by way of diverse communication channels. In model formulation, seven assumptions are thus proposed and the foreign capital policy of the host country is considered as an external influence; in addition, the investment policy of the investing country is modeled as an internal influe...

  3. Dynamics of zonal flows in helical systems.

    Sugama, H; Watanabe, T-H

    2005-03-25

    A theory for describing collisionless long-time behavior of zonal flows in helical systems is presented and its validity is verified by gyrokinetic-Vlasov simulation. It is shown that, under the influence of particles trapped in helical ripples, the response of zonal flows to a given source becomes weaker for lower radial wave numbers and deeper helical ripples while a high-level zonal-flow response, which is not affected by helical-ripple-trapped particles, can be maintained for a longer time by reducing their bounce-averaged radial drift velocity. This implies a possibility that helical configurations optimized for reducing neoclassical ripple transport can simultaneously enhance zonal flows which lower anomalous transport.

  4. Dynamical eigenfunction decomposition of turbulent channel flow

    Ball, K. S.; Sirovich, L.; Keefe, L. R.

    1991-01-01

    The results of an analysis of low-Reynolds-number turbulent channel flow based on the Karhunen-Loeve (K-L) expansion are presented. The turbulent flow field is generated by a direct numerical simulation of the Navier-Stokes equations at a Reynolds number Re(tau) = 80 (based on the wall shear velocity and channel half-width). The K-L procedure is then applied to determine the eigenvalues and eigenfunctions for this flow. The random coefficients of the K-L expansion are subsequently found by projecting the numerical flow field onto these eigenfunctions. The resulting expansion captures 90 percent of the turbulent energy with significantly fewer modes than the original trigonometric expansion. The eigenfunctions, which appear either as rolls or shearing motions, possess viscous boundary layers at the walls and are much richer in harmonics than the original basis functions.

  5. Flow cytometric analysis of lectin binding to in vitro-cultured Perkinsus marinus surface carbohydrates

    Gauthier, J.D.; Jenkins, J.A.; La Peyre, Jerome F.

    2004-01-01

    Parasite surface glycoconjugates are frequently involved in cellular recognition and colonization of the host. This study reports on the identification of Perkinsus marinus surface carbohydrates by flow cytometric analyses of fluorescein isothiocyanate-conjugated lectin binding. Lectin-binding specificity was confirmed by sugar inhibition and Kolmogorov-Smirnov statistics. Clear, measurable fluorescence peaks were discriminated, and no parasite autofluorescence was observed. Parasites (GTLA-5 and Perkinsus-1 strains) harvested during log and stationary phases of growth in a protein-free medium reacted strongly with concanavalin A and wheat germ agglutinin, which bind to glucose-mannose and N-acetyl-D-glucosamine (GlcNAc) moieties, respectively. Both P. marinus strains bound with lower intensity to Maclura pomifera agglutinin, Bauhinia purpurea agglutinin, soybean agglutinin (N-acetyl-D-galactosamine-specific lectins), peanut agglutinin (PNA) (terminal galactose specific), and Griffonia simplicifolia II (GlcNAc specific). Only background fluorescence levels were detected with Ulex europaeus agglutinin I (L-fucose specific) and Limulus polyphemus agglutinin (sialic acid specific). The lectin-binding profiles were similar for the 2 strains except for a greater relative binding intensity of PNA for Perkinsus-1 and an overall greater lectin-binding capacity of Perkinsus-1 compared with GTLA-5. Growth stage comparisons revealed increased lectin-binding intensities during stationary phase compared with log phase of growth. This is the first report of the identification of surface glycoconjugates on a Perkinsus spp. by flow cytometry and the first to demonstrate that differential surface sugar expression is growth phase and strain dependent. ?? American Society of Parasitologists 2004.

  6. Dangerous connections : on binding site models of infectious disease dynamics

    Leung, Ka Yin; Diekmann, Odo

    2017-01-01

    We formulate models for the spread of infection on networks that are amenable to analysis in the large population limit. We distinguish three different levels: (1) binding sites, (2) individuals, and (3) the population. In the tradition of physiologically structured population models, the

  7. Computational fluid dynamics (CFD) simulation of hot air flow ...

    Computational Fluid Dynamics simulation of air flow distribution, air velocity and pressure field pattern as it will affect moisture transient in a cabinet tray dryer is performed using SolidWorks Flow Simulation (SWFS) 2014 SP 4.0 program. The model used for the drying process in this experiment was designed with Solid ...

  8. Dynamics and statistics of heavy particles in turbulent flows

    Cencini, M.; Bec, J.; Biferale, L.; Boffetta, G.; Celani, A.; Lanotte, A.; Musacchio, S.; Toschi, F.

    2006-01-01

    We present the results of direct numerical simulations (DNS) of turbulent flows seeded with millions of passive inertial particles. The maximum Reynolds number is Re¿~ 200. We consider particles much heavier than the carrier flow in the limit when the Stokes drag force dominates their dynamical

  9. Are international fund flows related to exchange rate dynamics?

    Li, Suxiao; de Haan, Jakob; Scholtens, Bert

    2018-01-01

    Employing monthly data for 53 countries between 1996 and 2015, we investigate the relationship between international fund flows and exchange rate dynamics. We find strong co-movement between funds flows (as measured with the EPFR Global data base) and bilateral real exchange rates vis-à-vis the USD.

  10. Amendment to Validated dynamic flow model

    Knudsen, Torben

    2011-01-01

    The purpose of WP2 is to establish flow models relating the wind speed at turbines in a farm. Until now, active control of power reference has not been included in these models as only data with standard operation has been available. In this report the first data series with power reference excit...... turbine in undisturbed flow. For this data set both the multiplicative model and in particular the simple first order transfer function model can predict the down wind wind speed from upwind wind speed and loading.......The purpose of WP2 is to establish flow models relating the wind speed at turbines in a farm. Until now, active control of power reference has not been included in these models as only data with standard operation has been available. In this report the first data series with power reference...

  11. Turbomachinery Flow Physics and Dynamic Performance

    Schobeiri, Meinhard T

    2012-01-01

    With this second revised and extended edition, the readers have a solid source of information for designing state-of-the art turbomachinery components and systems at hand.   Based on fundamental principles of turbomachinery thermo-fluid mechanics, numerous CFD based calculation methods are being developed to simulate the complex 3-dimensional, highly unsteady turbulent flow within turbine or compressor stages. The objective of this book is to present the fundamental principles of turbomachinery fluid-thermodynamic design process of turbine and compressor components, power generation and aircraft gas turbines in a unified and compact manner. The book provides senior undergraduate students, graduate students and engineers in the turbomachinery industry with a solid background of turbomachinery flow physics and performance fundamentals that are essential for understanding turbomachinery performance and flow complexes.   While maintaining the unifying character of the book structure in this second revised and e...

  12. Calculation of the dynamic air flow resistivity of fibre materials

    Tarnow, Viggo

    1997-01-01

    The acoustic attenuation of acoustic fiber materials is mainly determined by the dynamic resistivity to an oscillating air flow. The dynamic resistance is calculated for a model with geometry close to the geometry of real fibre material. The model constists of parallel cylinders placed randomly.......The second procedure is an extension to oscillating air flow of the Brinkman self-consistent procedure for dc flow. The procedures are valid for volume concentrations of cylinders less than 0.1. The calculations show that for the density of fibers of interest for acoustic fibre materials the simple self...

  13. Flow dynamics of volume-heated boiling pools

    Ginsberg, T.; Jones, O.C.; Chen, J.C.

    1979-01-01

    Safety analyses of fast breeder reactors require understanding of the two-phase fluid dynamic and heat transfer characteristics of volume-heated boiling pool systems. Design of direct contact three-phase boilers, of practical interest in the chemical industries also requires understanding of the fundamental two-phase flow and heat transfer behavior of volume boiling systems. Several experiments have been recently reported relevant to the boundary heat-loss mechanisms of boiling pool systems. Considerably less is known about the two-phase fluid dynamic behavior of such systems. This paper describes an experimental investigation of the steady-state flow dynamics of volume-heated boiling pool systems

  14. Shear Layer Dynamics in Resonating Cavity Flows

    Ukeiley, Lawrence

    2004-01-01

    .... The PIV data was also combined with the surface pressure measurements through the application of the Quadratic Stochastic Estimation procedure to provide time resolved snapshots of the flow field. Examination of these results indicate the strong pumping action of the cavity regardless of whether resonance existed and was used to visualize the large scale structures interacting with the aft wall.

  15. A dynamic model of renal blood flow autoregulation

    Holstein-Rathlou, N H; Marsh, D J

    1994-01-01

    To test whether a mathematical model combining dynamic models of the tubuloglomerular feedback (TGF) mechanism and the myogenic mechanism was sufficient to explain dynamic autoregulation of renal blood flow, we compared model simulations with experimental data. To assess the dynamic characteristics...... of renal autoregulation, a broad band perturbation of the arterial pressure was employed in both the simulations and the experiments. Renal blood flow and tubular pressure were used as response variables in the comparison. To better approximate the situation in vivo where a large number of individual...... data, which shows a unimodal curve for the admittance phase. The ability of the model to reproduce the experimental data supports the hypothesis that dynamic autoregulation of renal blood flow is due to the combined action of TGF and the myogenic response....

  16. Highly Specific Binding on Antifouling Zwitterionic Polymer-Coated Microbeads as Measured by Flow Cytometry.

    van Andel, Esther; de Bus, Ian; Tijhaar, Edwin J; Smulders, Maarten M J; Savelkoul, Huub F J; Zuilhof, Han

    2017-11-08

    Micron- and nano-sized particles are extensively used in various biomedical applications. However, their performance is often drastically hampered by the nonspecific adsorption of biomolecules, a process called biofouling, which can cause false-positive and false-negative outcomes in diagnostic tests. Although antifouling coatings have been extensively studied on flat surfaces, their use on micro- and nanoparticles remains largely unexplored, despite the widespread experimental (specifically, clinical) uncertainties that arise because of biofouling. Here, we describe the preparation of magnetic micron-sized beads coated with zwitterionic sulfobetaine polymer brushes that display strong antifouling characteristics. These coated beads can then be equipped with recognition elements of choice, to enable the specific binding of target molecules. First, we present a proof of principle with biotin-functionalized beads that are able to specifically bind fluorescently labeled streptavidin from a complex mixture of serum proteins. Moreover, we show the versatility of the method by demonstrating that it is also possible to functionalize the beads with mannose moieties to specifically bind the carbohydrate-binding protein concanavalin A. Flow cytometry was used to show that thus-modified beads only bind specifically targeted proteins, with minimal/near-zero nonspecific protein adsorption from other proteins that are present. These antifouling zwitterionic polymer-coated beads, therefore, provide a significant advancement for the many bead-based diagnostic and other biosensing applications that require stringent antifouling conditions.

  17. Comparison of cerebral blood flow and metabolism to flumazenil binding potential in patients with hemodynamic ischemia

    Yukawa, Hirotsugu; Ogasawara, Kuniaki

    2003-01-01

    Because benzodiazepine receptors (BZR) are abundant in the cortex, an accumulation of 11 C-flumazenil which selectively bind to BZR may be useful as markers of neuron density. The aims of this study were to clarify the relationship between neuron density and cerebral oxygen metabolism and to investigate the usefulness of 11 C-flumazenil PET for detecting misery perfusion. The subjects were 16 patients with either internal carotid or middle cerebral arterial occlusive disease who underwent PET. Regional cerebral blood flow (CBF), regional cerebral oxygen extraction fraction (OEF), regional cerebral metabolic rate for oxygen (CMRO 2 ) and regional cerebrovascular reserve capacity (CVRC) to acetazolamide were calculated. After CBF study, flumazenil binding potential was measured using the [ 11 C] flumazenil bolus injection method. Forty-eight regions of interests (ROIs) were obtained in 16 patients. Flumazenil binding potential was correlated to CMRO 2 (r=0.337, p=0.0069), but in 7 of 48 ROIs, CMRO 2 decreased, whereas flumazenil binding potential did not change. Seventeen of 29 ROIs with decreased CVRC showed high OEF and the remaining 12 showed normal OEF. Flumazenil binding potential in ROIs with normal OEF was significantly lower than in those with high OEF (p=0.0003). This study demonstrated that 11 C-flumazenil PET is useful for detecting misery perfusion in patients with hemodynamic ischemia. (author)

  18. Modeling axisymmetric flows dynamics of films, jets, and drops

    Middleman, Stanley

    1995-01-01

    This concise book is intended to fulfill two purposes: to provide an important supplement to classic texts by carrying fluid dynamics students on into the realm of free boundary flows; and to demonstrate the art of mathematical modeling based on knowledge, intuition, and observation. In the authors words, the overall goal is make the complex simple, without losing the essence--the virtue--of the complexity.Modeling Axisymmetric Flows: Dynamics of Films, Jets, and Drops is the first book to cover the topics of axisymmetric laminar flows; free-boundary flows; and dynamics of drops, jets, and films. The text also features comparisons of models to experiments, and it includes a large selection of problems at the end of each chapter.Key Features* Contains problems at the end of each chapter* Compares real-world experimental data to theory* Provides one of the first comprehensive examinations of axisymmetric laminar flows, free-boundary flows, and dynamics of drops, jets, and films* Includes development of basic eq...

  19. Molecular dynamics simulations suggest that electrostatic funnel directs binding of Tamiflu to influenza N1 neuraminidases.

    Ly Le

    2010-09-01

    Full Text Available Oseltamivir (Tamiflu is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD and steered molecular dynamics (SMD simulations, as well as graphics processing unit (GPU-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 "avian" and H1N1pdm "swine" flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumvent the resistance mechanisms.

  20. Photocatalytic oxidation dynamics of acetone on TiO2: tight-binding quantum chemical molecular dynamics study

    Lv Chen; Wang Xiaojing; Agalya, Govindasamy; Koyama, Michihisa; Kubo, Momoji; Miyamoto, Akira

    2005-01-01

    The clarification of the excited states dynamics on TiO 2 surface is important subject for the design of the highly active photocatalysts. In the present study, we applied our novel tight-binding quantum chemical molecular dynamics method to the investigation on the photocatalytic oxidation dynamics of acetone by photogenerated OH radicals on the hydrated anatase TiO 2 surface. The elucidated photocatalytic reaction mechanism strongly supports the previous experimental proposal and finally the effectiveness of our new approach for the clarification of the photocatalytic reaction dynamics employing the large simulation model was confirmed

  1. Reservoir resistivity characterization incorporating flow dynamics

    Arango, Santiago; Sun, Shuyu; Hoteit, Ibrahim; Katterbauer, Klemens

    2016-01-01

    Systems and methods for reservoir resistivity characterization are provided, in various aspects, an integrated framework for the estimation of Archie's parameters for a strongly heterogeneous reservoir utilizing the dynamics of the reservoir are provided. The framework can encompass a Bayesian estimation/inversion method for estimating the reservoir parameters, integrating production and time lapse formation conductivity data to achieve a better understanding of the subsurface rock conductivity properties and hence improve water saturation imaging.

  2. Reservoir resistivity characterization incorporating flow dynamics

    Arango, Santiago

    2016-04-07

    Systems and methods for reservoir resistivity characterization are provided, in various aspects, an integrated framework for the estimation of Archie\\'s parameters for a strongly heterogeneous reservoir utilizing the dynamics of the reservoir are provided. The framework can encompass a Bayesian estimation/inversion method for estimating the reservoir parameters, integrating production and time lapse formation conductivity data to achieve a better understanding of the subsurface rock conductivity properties and hence improve water saturation imaging.

  3. Discrete event dynamic system (DES)-based modeling for dynamic material flow in the pyroprocess

    Lee, Hyo Jik; Kim, Kiho; Kim, Ho Dong; Lee, Han Soo

    2011-01-01

    A modeling and simulation methodology was proposed in order to implement the dynamic material flow of the pyroprocess. Since the static mass balance provides the limited information on the material flow, it is hard to predict dynamic behavior according to event. Therefore, a discrete event system (DES)-based model named, PyroFlow, was developed at the Korea Atomic Energy Research Institute (KAERI). PyroFlow is able to calculate dynamic mass balance and also show various dynamic operational results in real time. By using PyroFlow, it is easy to rapidly predict unforeseeable results, such as throughput in unit process, accumulated product in buffer and operation status. As preliminary simulations, bottleneck analyses in the pyroprocess were carried out and consequently it was presented that operation strategy had influence on the productivity of the pyroprocess.

  4. An evaluation of Dynamic TOPMODEL for low flow simulation

    Coxon, G.; Freer, J. E.; Quinn, N.; Woods, R. A.; Wagener, T.; Howden, N. J. K.

    2015-12-01

    Hydrological models are essential tools for drought risk management, often providing input to water resource system models, aiding our understanding of low flow processes within catchments and providing low flow predictions. However, simulating low flows and droughts is challenging as hydrological systems often demonstrate threshold effects in connectivity, non-linear groundwater contributions and a greater influence of water resource system elements during low flow periods. These dynamic processes are typically not well represented in commonly used hydrological models due to data and model limitations. Furthermore, calibrated or behavioural models may not be effectively evaluated during more extreme drought periods. A better understanding of the processes that occur during low flows and how these are represented within models is thus required if we want to be able to provide robust and reliable predictions of future drought events. In this study, we assess the performance of dynamic TOPMODEL for low flow simulation. Dynamic TOPMODEL was applied to a number of UK catchments in the Thames region using time series of observed rainfall and potential evapotranspiration data that captured multiple historic droughts over a period of several years. The model performance was assessed against the observed discharge time series using a limits of acceptability framework, which included uncertainty in the discharge time series. We evaluate the models against multiple signatures of catchment low-flow behaviour and investigate differences in model performance between catchments, model diagnostics and for different low flow periods. We also considered the impact of surface water and groundwater abstractions and discharges on the observed discharge time series and how this affected the model evaluation. From analysing the model performance, we suggest future improvements to Dynamic TOPMODEL to improve the representation of low flow processes within the model structure.

  5. Flow injection on-line oxidizing fluorometry coupled to dialysis sampling for the study of carbamazepine-protein binding

    Zhang Zhiqi [School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)]. E-mail: zqzhang@snnu.edu.cn; Liang Guoxi [School of Chemistry and Materials Science, Shaanxi Normal University, Xi' an 710062 (China)

    2005-04-22

    The mechanism of binding of carbamazepine (CBZ) with bovine serum albumin (BSA) has been investigated in vitro based on a new flow injection fluorometry coupled to the technique of dialysis sampling. The CBZ and BSA were mixed in different molar ratios in 0.050 mol L{sup -1} phosphate buffer (containing 0.9% NaCl), pH 7.4, and incubated at 37 {+-} 0.5 deg. C in a water bath. The dialysis sampler was utilized to sample free CBZ from mixed solution with a relative dialytic efficiency of 7.6%. Then the CBZ in dialysis solution was injected into carrier and on-line oxidized by lead dioxide solid-phase reactor into fluorescent product with a maximum excitation wavelength of 355 nm and a maximum emission wavelength of 478 nm. The fluorescence intensity measured was linear proportional with the concentration of free CBZ in mixed solution over the range of 1 x 10{sup -5} to 2 x 10{sup -4} mol L{sup -1} with the detection limit of 6 x 10{sup -6} mol L{sup -1}. According to the fluorescence measurement results from mixed solution, the association constant (K) estimated for CBZ-BSA binding and the number of the binding site (n) with Scatchard analysis were 1.08 x 10{sup 4} L mol{sup -1} and 0.94, respectively. Stern-Volmer plots indicated the presence of dynamic component in the quenching mechanism. The acting force was suggested to be mainly hydrophobic and the distance between the acceptor and donor was 3.12 nm. The estimated binding parameters agreed well with literature values.

  6. Alveolar Thin Layer Flows and Surfactant Dynamics

    Roumie, Ahmad; Jbaily, Abdulrahman; Szeri, Andrew J.

    2017-11-01

    Pulmonary surfactants play a vital role in everyday respiration. They regulate surface tension in the lungs by diffusing through the hypophase, a liquid layer that lines the interior surface of the alveoli, and adsorbing to the existing air-fluid interface. This decreases the equilibrium surface tension value by as much as a factor of 3, minimizing breathing effort and preventing lung collapse at the end of exhalation. Given that the hypophase thickness h lies within the range 0.1 μm < h <0.5 μm , and that the average alveolar radius R is 100 μm , for some purposes the hypophase may usefully be modeled as a fluid layer on a flat sheet representing the alveolar wall. Moreover, because of the large aspect ratio, the lubrication approximation can be applied. The aim of the present work is to study the interaction between the straining of the alveolar wall and the fluid flow in the hypophase. The analysis is governed by the relative magnitudes of the time scales of surfactant diffusion, adsorption, desorption, viscous dissipation and sheet straining. Cases of particular interest include non-uniform surfactant concentration at the interface, leading to Marangoni flows and a non-uniform hypophase thickness profile. The analytical formulation and numerical simulations are presented. This work is motivated by a need to understand alveolar deformation during breathing, and to do so in a way that derives from improved understanding of the fluid mechanics of the problem.

  7. Binding mechanism and dynamic conformational change of C subunit of PKA with different pathways.

    Chu, Wen-Ting; Chu, Xiakun; Wang, Jin

    2017-09-19

    The catalytic subunit of PKA (PKAc) exhibits three major conformational states (open, intermediate, and closed) during the biocatalysis process. Both ATP and substrate/inhibitor can effectively induce the conformational changes of PKAc from open to closed states. Aiming to explore the mechanism of this allosteric regulation, we developed a coarse-grained model and analyzed the dynamics of conformational changes of PKAc during binding by performing molecular dynamics simulations for apo PKAc, binary PKAc (PKAc with ATP, PKAc with PKI), and ternary PKAc (PKAc with ATP and PKI). Our results suggest a mixed binding mechanism of induced fit and conformational selection, with the induced fit dominant. The ligands can drive the movements of Gly-rich loop as well as some regions distal to the active site in PKAc and stabilize them at complex state. In addition, there are two parallel pathways (pathway with PKAc-ATP as an intermediate and pathway PKAc-PKI as an intermediate) during the transition from open to closed states. By molecular dynamics simulations and rate constant analyses, we find that the pathway through PKAc-ATP intermediate is the main binding route from open to closed state because of the fact that the bound PKI will hamper ATP from successful binding and significantly increase the barrier for the second binding subprocess. These findings will provide fundamental insights of the mechanisms of PKAc conformational change upon binding.

  8. Dynamic flow control strategies of vehicle SCR Urea Dosing System

    Lin, Wei; Zhang, Youtong; Asif, Malik

    2015-03-01

    Selective Catalyst Reduction(SCR) Urea Dosing System(UDS) directly affects the system accuracy and the dynamic response performance of a vehicle. However, the UDS dynamic response is hard to keep up with the changes of the engine's operating conditions. That will lead to low NO X conversion efficiency or NH3 slip. In order to optimize the injection accuracy and the response speed of the UDS in dynamic conditions, an advanced control strategy based on an air-assisted volumetric UDS is presented. It covers the methods of flow compensation and switching working conditions. The strategy is authenticated on an UDS and tested in different dynamic conditions. The result shows that the control strategy discussed results in higher dynamic accuracy and faster dynamic response speed of UDS. The inject deviation range is improved from being between -8% and 10% to -4% and 2% and became more stable than before, and the dynamic response time was shortened from 200 ms to 150 ms. The ETC cycle result shows that after using the new strategy the NH3 emission is reduced by 60%, and the NO X emission remains almost unchanged. The trade-off between NO X conversion efficiency and NH3 slip is mitigated. The studied flow compensation and switching working conditions can improve the dynamic performance of the UDS significantly and make the UDS dynamic response keep up with the changes of the engine's operating conditions quickly.

  9. Binding stability of peptides on major histocompatibility complex class I proteins: role of entropy and dynamics

    Gul, Ahmet; Erman, Burak

    2018-03-01

    Prediction of peptide binding on specific human leukocyte antigens (HLA) has long been studied with successful results. We herein describe the effects of entropy and dynamics by investigating the binding stabilities of 10 nanopeptides on various HLA Class I alleles using a theoretical model based on molecular dynamics simulations. The fluctuational entropies of the peptides are estimated over a temperature range of 310-460 K. The estimated entropies correlate well with experimental binding affinities of the peptides: peptides that have higher binding affinities have lower entropies compared to non-binders, which have significantly larger entropies. The computation of the entropies is based on a simple model that requires short molecular dynamics trajectories and allows for approximate but rapid determination. The paper draws attention to the long neglected dynamic aspects of peptide binding, and provides a fast computation scheme that allows for rapid scanning of large numbers of peptides on selected HLA antigens, which may be useful in defining the right peptides for personal immunotherapy.

  10. Visual Analysis of Inclusion Dynamics in Two-Phase Flow.

    Karch, Grzegorz Karol; Beck, Fabian; Ertl, Moritz; Meister, Christian; Schulte, Kathrin; Weigand, Bernhard; Ertl, Thomas; Sadlo, Filip

    2018-05-01

    In single-phase flow visualization, research focuses on the analysis of vector field properties. In two-phase flow, in contrast, analysis of the phase components is typically of major interest. So far, visualization research of two-phase flow concentrated on proper interface reconstruction and the analysis thereof. In this paper, we present a novel visualization technique that enables the investigation of complex two-phase flow phenomena with respect to the physics of breakup and coalescence of inclusions. On the one hand, we adapt dimensionless quantities for a localized analysis of phase instability and breakup, and provide detailed inspection of breakup dynamics with emphasis on oscillation and its interplay with rotational motion. On the other hand, we present a parametric tightly linked space-time visualization approach for an effective interactive representation of the overall dynamics. We demonstrate the utility of our approach using several two-phase CFD datasets.

  11. Lattice fluid dynamics from perfect discretizations of continuum flows

    Katz, E.; Wiese, U.

    1998-01-01

    We use renormalization group methods to derive equations of motion for large scale variables in fluid dynamics. The large scale variables are averages of the underlying continuum variables over cubic volumes and naturally exist on a lattice. The resulting lattice dynamics represents a perfect discretization of continuum physics, i.e., grid artifacts are completely eliminated. Perfect equations of motion are derived for static, slow flows of incompressible, viscous fluids. For Hagen-Poiseuille flow in a channel with a square cross section the equations reduce to a perfect discretization of the Poisson equation for the velocity field with Dirichlet boundary conditions. The perfect large scale Poisson equation is used in a numerical simulation and is shown to represent the continuum flow exactly. For nonsquare cross sections one can use a numerical iterative procedure to derive flow equations that are approximately perfect. copyright 1998 The American Physical Society

  12. Elucidating the evolutionary conserved DNA-binding specificities of WRKY transcription factors by molecular dynamics and in vitro binding assays

    Brand, Luise H.; Fischer, Nina M.; Harter, Klaus; Kohlbacher, Oliver; Wanke, Dierk

    2013-01-01

    WRKY transcription factors constitute a large protein family in plants that is involved in the regulation of developmental processes and responses to biotic or abiotic stimuli. The question arises how stimulus-specific responses are mediated given that the highly conserved WRKY DNA-binding domain (DBD) exclusively recognizes the ‘TTGACY’ W-box consensus. We speculated that the W-box consensus might be more degenerate and yet undetected differences in the W-box consensus of WRKYs of different evolutionary descent exist. The phylogenetic analysis of WRKY DBDs suggests that they evolved from an ancestral group IIc-like WRKY early in the eukaryote lineage. A direct descent of group IIc WRKYs supports a monophyletic origin of all other group II and III WRKYs from group I by loss of an N-terminal DBD. Group I WRKYs are of paraphyletic descent and evolved multiple times independently. By homology modeling, molecular dynamics simulations and in vitro DNA–protein interaction-enzyme-linked immunosorbent assay with AtWRKY50 (IIc), AtWRKY33 (I) and AtWRKY11 (IId) DBDs, we revealed differences in DNA-binding specificities. Our data imply that other components are essentially required besides the W-box-specific binding to DNA to facilitate a stimulus-specific WRKY function. PMID:23975197

  13. PASTA in Penicillin Binding Proteins and Serine/Threonine Kinases: A Recipe of Structural, Dynamic and Binding Properties.

    Calvanese, Luisa; Falcigno, Lucia; Squeglia, Flavia; D'Auria, Gabriella; Berisio, Rita

    2017-11-24

    Penicillin binding proteins (PBPs) and Serine Threonine kinases (STPKs) are two classes of bacterial enzymes whose involvement in a series of vital processes in bacterial growth and division is well assessed. Many PBPs and STPKs show linked an ancillary domain named PASTA, whose functional role is not completely deciphered so far. It has been proposed that PASTAs are sensor modules that by binding opportune ligands (i.e. muropeptides) activate the cognate proteins to their functions. However, based on recent data, the sensor annotation sounds true for PASTA from STPKs, and false for PASTA from PBPs. Different PASTA domains, belonging or not to different protein classes, sharing or not appreciable sequence identities, always show identical folds. This survey of the structural, binding and dynamic properties of PASTA domains pursues the reasons why identical topologies may turn in different roles. Amino acid compositions, total charges and distribution of the hydrophobic/hydrophilic patches on the surface, significantly vary among PASTAs from STPKs and PBPs and appear to correlate with different functions. A possible criterion to discriminate between PASTA modules of STPKs or PBPs solely based on their sequences is proposed. Possibly reflecting different species as well as functional roles and evolutionary profile, our routine represents a fast even though approximate method to distinguish between PASTA belonging to different classes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Dynamic MLD analysis with flow graphs

    Jenab, K.; Sarfaraz, A.; Dhillon, B.S.; Seyed Hosseini, S.M.

    2012-01-01

    Master Logic Diagram (MLD) depicts the interrelationships among the independent functions and dependent support functions. Using MLD, the manner in which all functions, sub-functions interact to achieve the overall system objective can be investigated. This paper reports a probabilistic model to analyze an MLD by translating the interrelationships to a graph model. The proposed model uses the flow-graph concept and Moment Generating Function (MGF) to analyze the dependency matrix representing the MLD with embedded self-healing function/sub-functions. The functions/sub-functions are featured by failure detection and recovery mechanisms. The newly developed model provides the probability of the system failure, and system mean and standard deviation time to failure in the MLD. An illustrative example is demonstrated to present the application of the model.

  15. Dynamics and Instabilities of Free Surface and Vortex Flows

    Tophøj, Laust Emil Hjerrild

    2012-01-01

    This PhD thesis consists of two main parts. The first part describes the dynamics of an ideal fluid on a stationary free surface of a given shape. It turns out that one can formulate a set of self-contained equations of momentum conservation for the tangential flow, with no reference to the flow ......)]. Finally, an experimental work on elastic collisions of wet spheres is briefly discussed....

  16. Deterministic chaotic dynamics of Raba River flow (Polish Carpathian Mountains)

    Kędra, Mariola

    2014-02-01

    Is the underlying dynamics of river flow random or deterministic? If it is deterministic, is it deterministic chaotic? This issue is still controversial. The application of several independent methods, techniques and tools for studying daily river flow data gives consistent, reliable and clear-cut results to the question. The outcomes point out that the investigated discharge dynamics is not random but deterministic. Moreover, the results completely confirm the nonlinear deterministic chaotic nature of the studied process. The research was conducted on daily discharge from two selected gauging stations of the mountain river in southern Poland, the Raba River.

  17. Development of dynamic PIV for droplet jet flow

    Okamoto, K.; Hong, S. D.; Bi, W. T.; Sugii, Y.; Madarame, H.; Hayami, H.

    2003-01-01

    The Particle Image Velocimetry (PIV) can capture velocity vector fields with high spatial resolution. In this study, the Dynamic PIV system up to 10kHz temporal resolution was developed with combining the High-speed camera and high speed Laser with Double pulse option. The 1024 x 1024 pixel images with frame straddling were captured in 2kHz. Also, PIV data were measured in 512 x 256 pixel in 10kHz. The system had been applied to capture the water droplet flow. The transient characteristics of the droplet flow can be clearly captured using the developed Dynamic PIV System

  18. Mapping the structural and dynamical features of multiple p53 DNA binding domains: insights into loop 1 intrinsic dynamics.

    Suryani Lukman

    Full Text Available The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD. In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs. Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3. Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart. Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1 a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2 possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site.

  19. QM/MM Molecular Dynamics Studies of Metal Binding Proteins

    Pietro Vidossich

    2014-07-01

    Full Text Available Mixed quantum-classical (quantum mechanical/molecular mechanical (QM/MM simulations have strongly contributed to providing insights into the understanding of several structural and mechanistic aspects of biological molecules. They played a particularly important role in metal binding proteins, where the electronic effects of transition metals have to be explicitly taken into account for the correct representation of the underlying biochemical process. In this review, after a brief description of the basic concepts of the QM/MM method, we provide an overview of its capabilities using selected examples taken from our work. Specifically, we will focus on heme peroxidases, metallo-β-lactamases, α-synuclein and ligase ribozymes to show how this approach is capable of describing the catalytic and/or structural role played by transition (Fe, Zn or Cu and main group (Mg metals. Applications will reveal how metal ions influence the formation and reduction of high redox intermediates in catalytic cycles and enhance drug metabolism, amyloidogenic aggregate formation and nucleic acid synthesis. In turn, it will become manifest that the protein frame directs and modulates the properties and reactivity of the metal ions.

  20. Dynamics of nuclear fuel assemblies in vertical flow channels

    Mason, V.A.

    1988-01-01

    DYNMOD is a computer program designed to predict the dynamic behaviour of nuclear fuel assemblies in axial flow. The calculations performed by DYNMOD and the input data required by the program are described in this report. Examples of DYNMOD usage and a brief assessment of the accuracy of the dynamic model are also presented. It is intended that the report will be used as a reference manual by users of DYNMOD

  1. Rarefield gas dynamics fundamentals, simulations and micro flows

    Shen, Ching

    2006-01-01

    This book elucidates the methods of molecular gas dynamics or rarefied gas dynamics which treat the problems of gas flows when the discrete molecular effects of the gas prevail under the circumstances of low density, the emphasis being on the basis of the methods, the direct simulation Monte Carlo method applied to the simulation of non-equilibrium effects and the frontier subjects related to low speed microscale rarefied gas flows. It provides a solid basis for the study of molecular gas dynamics for senior students and graduates in the aerospace and mechanical engineering departments of universities and colleges. It gives a general acquaintance of modern developments of rarefied gas dynamics in various regimes and leads to the frontier topics of non-equilibrium rarefied gas dynamics and low speed microscale gas dynamics. It will be also of benefit to the scientific and technical researchers engaged in aerospace high altitude aerodynamic force and heating design and in the research on gas flow in MEMS.

  2. Modeling of the Bosphorus exchange flow dynamics

    Sözer, Adil; Özsoy, Emin

    2017-04-01

    The fundamental hydrodynamic behavior of the Bosphorus Strait is investigated through a numerical modeling study using alternative configurations of idealized or realistic geometry. Strait geometry and basin stratification conditions allow for hydraulic controls and are ideally suited to support the maximal-exchange regime, which determines the rate of exchange of waters originating from the adjacent Black and Mediterranean Seas for a given net transport. Steady-state hydraulic controls are demonstrated by densimetric Froude number calculations under layered flow approximations when corrections are applied to account for high velocity shears typically observed in the Bosphorus. Analyses of the model results reveal many observed features of the strait, including critical transitions at hydraulic controls and dissipation by turbulence and hydraulic jumps. It is found that the solution depends on initialization, especially with respect to the basin initial conditions. Significant differences between the controlled maximal-exchange and drowned solutions suggest that a detailed modeling implementation involving coupling with adjacent basins needs to take full account of the Bosphorus Strait in terms of the physical processes to be resolved.

  3. Characterization of Flow Dynamics and Reduced-Order Description of Experimental Two-Phase Pipe Flow

    Viggiano, Bianca; SkjæRaasen, Olaf; Tutkun, Murat; Cal, Raul Bayoan

    2017-11-01

    Multiphase pipe flow is investigated using proper orthogonal decomposition for tomographic X-ray data, where holdup, cross sectional phase distributions and phase interface characteristics are obtained. Instantaneous phase fractions of dispersed flow and slug flow are analyzed and a reduced order dynamical description is generated. The dispersed flow displays coherent structures in the first few modes near the horizontal center of the pipe, representing the liquid-liquid interface location while the slug flow case shows coherent structures that correspond to the cyclical formation and breakup of the slug in the first 10 modes. The reconstruction of the fields indicate that main features are observed in the low order dynamical descriptions utilizing less than 1 % of the full order model. POD temporal coefficients a1, a2 and a3 show interdependence for the slug flow case. The coefficients also describe the phase fraction holdup as a function of time for both dispersed and slug flow. These flows are highly applicable to petroleum transport pipelines, hydroelectric power and heat exchanger tubes to name a few. The mathematical representations obtained via proper orthogonal decomposition will deepen the understanding of fundamental multiphase flow characteristics.

  4. Improving flow distribution in influent channels using computational fluid dynamics.

    Park, No-Suk; Yoon, Sukmin; Jeong, Woochang; Lee, Seungjae

    2016-10-01

    Although the flow distribution in an influent channel where the inflow is split into each treatment process in a wastewater treatment plant greatly affects the efficiency of the process, and a weir is the typical structure for the flow distribution, to the authors' knowledge, there is a paucity of research on the flow distribution in an open channel with a weir. In this study, the influent channel of a real-scale wastewater treatment plant was used, installing a suppressed rectangular weir that has a horizontal crest to cross the full channel width. The flow distribution in the influent channel was analyzed using a validated computational fluid dynamics model to investigate (1) the comparison of single-phase and two-phase simulation, (2) the improved procedure of the prototype channel, and (3) the effect of the inflow rate on flow distribution. The results show that two-phase simulation is more reliable due to the description of the free-surface fluctuations. It should first be considered for improving flow distribution to prevent a short-circuit flow, and the difference in the kinetic energy with the inflow rate makes flow distribution trends different. The authors believe that this case study is helpful for improving flow distribution in an influent channel.

  5. Molecular Dynamics Simulations Suggest Ligand’s Binding to Nicotinamidase/Pyrazinamidase

    Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

    2012-01-01

    The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA’s activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM’s unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand’s binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs. PMID:22761821

  6. Dynamics of renal blood flow autoregulation in rats

    Holstein-Rathlou, N H; Wagner, A J; Marsh, D J

    1991-01-01

    Two separate components could be resolved in tests of the dynamic autoregulation of renal blood flow. The slow component corresponds to the frequency at which spontaneous proximal tubular pressure oscillations are found, and are most likely due to the operation of the TGF. The high frequency...

  7. Particle hopping vs. fluid-dynamical models for traffic flow

    Nagel, K.

    1995-12-31

    Although particle hopping models have been introduced into traffic science in the 19509, their systematic use has only started recently. Two reasons for this are, that they are advantageous on modem computers, and that recent theoretical developments allow analytical understanding of their properties and therefore more confidence for their use. In principle, particle hopping models fit between microscopic models for driving and fluiddynamical models for traffic flow. In this sense, they also help closing the conceptual gap between these two. This paper shows connections between particle hopping models and traffic flow theory. It shows that the hydrodynamical limits of certain particle hopping models correspond to the Lighthill-Whitham theory for traffic flow, and that only slightly more complex particle hopping models produce already the correct traffic jam dynamics, consistent with recent fluid-dynamical models for traffic flow. By doing so, this paper establishes that, on the macroscopic level, particle hopping models are at least as good as fluid-dynamical models. Yet, particle hopping models have at least two advantages over fluid-dynamical models: they straightforwardly allow microscopic simulations, and they include stochasticity.

  8. Coupling-constant flows and dynamical symmetry breaking

    Yamagishi, H.

    1981-01-01

    The Coleman-Weinberg theory is reformulated in terms of flows in coupling-constant space. It is shown that the existence of dynamical symmetry breaking is governed essentially by the b functions. An application is made to the massless Weinberg-Salam model

  9. Translanguaging as Dynamic Activity Flows in CLIL Classrooms

    Lin, Angel M. Y.; He, Peichang

    2017-01-01

    In this article, the role of translanguaging in facilitating content and language integrated learning (CLIL) is examined in connection with the notion of academic language across the curriculum in multilingual contexts. Ethnographic naturalistic observations and interviews were conducted to analyse translanguaging in the dynamic flow of…

  10. Instabilities and vortex dynamics in shear flow of magnetized plasmas

    Tajima, T.; Horton, W.; Morrison, P.J.; Schutkeker, J.; Kamimura, T.; Mima, K.; Abe, Y.

    1990-03-01

    Gradient-driven instabilities and the subsequent nonlinear evolution of generated vortices in sheared E x B flows are investigated for magnetized plasmas with and without gravity (magnetic curvature) and magnetic shear by using theory and implicit particle simulations. In the linear eigenmode analysis, the instabilities considered are the Kelvin-Helmholtz (K-H) instability and the resistive interchange instability. The presence of the shear flow can stabilize these instabilities. The dynamics of the K-H instability and the vortex dynamics can be uniformly described by the initial flow pattern with a vorticity localization parameter ε. The observed growth of the K-H modes is exponential in time for linearly unstable modes, secular for marginal mode, and absent until driven nonlinearly for linearly stable modes. The distance between two vortex centers experiences rapid merging while the angle θ between the axis of vortices and the external shear flow increases. These vortices proceed toward their overall coalescence, while shedding small-scale vortices and waves. The main features of vortex dynamics of the nonlinear coalescence and the tilt or the rotational instabilities of vortices are shown to be given by using a low dimension Hamiltonian representation for interacting vortex cores in the shear flow. 24 refs., 19 figs., 1 tab

  11. Development of Methods for Obtaining Position Image and Chemical Binding Information from Flow Experiments of Porous Media

    Haugan, Are

    1998-12-01

    Existing oil reservoirs might be more fully exploited if the properties of the flow of oil and water in porous media were better known. In laboratory experiments it is important to collect as much information as possible to make a descriptive model of the system, including position imaging and chemical binding information. This thesis develops nuclear methods for obtaining position image and chemical binding information from flow experiments of porous media. A combined positron emission tomography and single photon emission computed tomography system to obtain position images, and a time-differential perturbed angular correlation system to obtain chemical binding information, have been built and thoroughly tested. 68 refs., 123 figs., 14 tabs.

  12. Dynamic ADMM for Real-time Optimal Power Flow: Preprint

    Dall-Anese, Emiliano [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-02-23

    This paper considers distribution networks featuring distributed energy resources (DERs), and develops a dynamic optimization method to maximize given operational objectives in real time while adhering to relevant network constraints. The design of the dynamic algorithm is based on suitable linearizations of the AC power flow equations, and it leverages the so-called alternating direction method of multipliers (ADMM). The steps of the ADMM, however, are suitably modified to accommodate appropriate measurements from the distribution network and the DERs. With the aid of these measurements, the resultant algorithm can enforce given operational constraints in spite of inaccuracies in the representation of the AC power flows, and it avoids ubiquitous metering to gather the state of non-controllable resources. Optimality and convergence of the propose algorithm are established in terms of tracking of the solution of a convex surrogate of the AC optimal power flow problem.

  13. Nephron blood flow dynamics measured by laser speckle contrast imaging

    von Holstein-Rathlou, Niels-Henrik; Sosnovtseva, Olga V; Pavlov, Alexey N

    2011-01-01

    Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular...... simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50-100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic...... pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons...

  14. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    Aradi, Balint; Frauenheim, Thomas

    2015-01-01

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born-Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materials science, chemistry, and biology

  15. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids.

    Aradi, Bálint; Niklasson, Anders M N; Frauenheim, Thomas

    2015-07-14

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born-Oppenheimer molecular dynamics. For systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can be applied to a broad range of problems in materials science, chemistry, and biology.

  16. Emerging insights into the dynamics of submarine debris flows

    A. Elverhøi

    2005-01-01

    Full Text Available Recent experimental and theoretical work on the dynamics of submarine debris flows is summarized. Hydroplaning was first discovered in laboratory flows and later shown to likely occur in natural debris flows as well. It is a prime mechanism for explaining the extremely long runout distances observed in some natural debris flows even of over-consolidated clay materials. Moreover, the accelerations and high velocities reached by the flow head in a short time appear to fit well with the required initial conditions of observed tsunamis as obtained from back-calculations. Investigations of high-speed video recordings of laboratory debris flows were combined with measurements of total and pore pressure. The results are pointing towards yet another important role of ambient water: Water that intrudes from the water cushion underneath the hydroplaning head and through cracks in the upper surface of the debris flow may drastically soften initially stiff clayey material in the 'neck' of the flow, where significant stretching occurs due to the reduced friction at the bottom of the hydroplaning head. This self-reinforcing process may lead to the head separating from the main body and becoming an 'outrunner' block as clearly observed in several natural debris flows. Comparison of laboratory flows with different material composition indicates a gradual transition from hydroplaning plug flows of stiff clay-rich material, with a very low suspension rate, to the strongly agitated flow of sandy materials that develop a pronounced turbidity current. Statistical analysis of the great number of distinguishable lobes in the Storegga slide complex reveals power-law scaling behavior of the runout distance with the release mass over many orders of magnitude. Mathematical flow models based on viscoplastic material behavior (e.g. BING successfully reproduce the observed scaling behavior only for relatively small clay-rich debris flows while granular (frictional models

  17. Comparative study of incompressible and isothermal compressible flow solvers for cavitating flow dynamics

    Park, Sun Ho [Korea Maritime and Ocean University, Busan (Korea, Republic of); Rhee, Shin Hyung [Seoul National University, Seoul (Korea, Republic of)

    2015-08-15

    Incompressible flow solvers are generally used for numerical analysis of cavitating flows, but with limitations in handling compressibility effects on vapor phase. To study compressibility effects on vapor phase and cavity interface, pressure-based incompressible and isothermal compressible flow solvers based on a cell-centered finite volume method were developed using the OpenFOAM libraries. To validate the solvers, cavitating flow around a hemispherical head-form body was simulated and validated against the experimental data. The cavity shedding behavior, length of a re-entrant jet, drag history, and the Strouhal number were compared between the two solvers. The results confirmed that computations of the cavitating flow including compressibility effects improved the reproduction of cavitation dynamics.

  18. Dynamic behaviors of cavitation bubble for the steady cavitating flow

    Cai, Jun; Huai, Xiulan; Li, Xunfeng

    2009-12-01

    In this paper, by introducing the flow velocity item into the classical Rayleigh-Plesset dynamic equation, a new equation, which does not involve the time term and can describe the motion of cavitation bubble in the steady cavitating flow, has been obtained. By solving the new motion equation using Runge-Kutta fourth order method with adaptive step size control, the dynamic behaviors of cavitation bubble driven by the varying pressure field downstream of a venturi cavitation reactor are numerically simulated. The effects of liquid temperature (corresponding to the saturated vapor pressure of liquid), cavitation number and inlet pressure of venturi on radial motion of bubble and pressure pulse due to the radial motion are analyzed and discussed in detail. Some dynamic behaviors of bubble different from those in previous papers are displayed. In addition, the internal relationship between bubble dynamics and process intensification is also discussed. The simulation results reported in this work reveal the variation laws of cavitation intensity with the flow conditions of liquid, and will lay a foundation for the practical application of hydrodynamic cavitation technology.

  19. Water Flow in Karst Aquifer Considering Dynamically Variable Saturation Conduit

    Tan, Chaoqun; Hu, Bill X.

    2017-04-01

    The karst system is generally conceptualized as dual-porosity system, which is characterized by low conductivity and high storage continuum matrix and high conductivity and quick flow conduit networks. And so far, a common numerical model for simulating flow in karst aquifer is MODFLOW2005-CFP, which is released by USGS in 2008. However, the steady-state approach for conduit flow in CFP is physically impractical when simulating very dynamic hydraulics with variable saturation conduit. So, we adopt the method proposed by Reimann et al. (2011) to improve current model, in which Saint-Venant equations are used to model the flow in conduit. Considering the actual background that the conduit is very big and varies along flow path and the Dirichlet boundary varies with rainfall in our study area in Southwest China, we further investigate the influence of conduit diameter and outflow boundary on numerical model. And we also analyze the hydraulic process in multi-precipitation events. We find that the numerical model here corresponds well with CFP for saturated conduit, and it could depict the interaction between matrix and conduit during very dynamic hydraulics pretty well compare with CFP.

  20. Computational fluid dynamics simulations of light water reactor flows

    Tzanos, C.P.; Weber, D.P.

    1999-01-01

    Advances in computational fluid dynamics (CFD), turbulence simulation, and parallel computing have made feasible the development of three-dimensional (3-D) single-phase and two-phase flow CFD codes that can simulate fluid flow and heat transfer in realistic reactor geometries with significantly reduced reliance, especially in single phase, on empirical correlations. The objective of this work was to assess the predictive power and computational efficiency of a CFD code in the analysis of a challenging single-phase light water reactor problem, as well as to identify areas where further improvements are needed

  1. Analysis of liver blood flow by dynamic hepatic scintigraphy

    Xie Tianhao; Jia Shiquan

    1996-01-01

    Liver blood flow was studied in 45 patients with solitary malignant liver cancer, 17 patients with multiple liver metastases, 18 patients with benign liver tumor and 20 control subjects by dynamic hepatic scintigraphy. The hepatic perfusion index (HPI) in control subjects, patients with liver malignant cancer and benign tumor was 0.33 +- 0.069, 0.589 +- 0.084, 0.384 +-0.046 respectively, and the mesenteric fraction (MF) was 0.56 +- 0.054, 0.246 +- 0.064, 0.524 +- 0.086 respectively. In conclusion, flow scintigraphy is a non-invasive, sensitive and repeatable method for detection of liver tumor

  2. Approaching multiphase flows from the perspective of computational fluid dynamics

    Banas, A.O.

    1992-01-01

    Thermalhydraulic simulation methodologies based on subchannel and porous-medium concepts are briefly reviewed and contrasted with the general approach of Computational Fluid Dynamics (CFD). An outline of the advanced CFD methods for single-phase turbulent flows is followed by a short discussion of the unified formulation of averaged equations for turbulent and multiphase flows. Some of the recent applications of CFD at Chalk River Laboratories are discussed, and the complementary role of CFD with regard to the established thermalhydraulic methods of analysis is indicated. (author). 8 refs

  3. Measurements of granular flow dynamics with high speed digital images

    Lee, Jingeol [Univ. of Florida, Gainesville, FL (United States)

    1994-01-01

    The flow of granular materials is common to many industrial processes. This dissertation suggests and validates image processing algorithms applied to high speed digital images to measure the dynamics (velocity, temperature and volume fraction) of dry granular solids flowing down an inclined chute under the action of gravity. Glass and acrylic particles have been used as granular solids in the experiment. One technique utilizes block matching for spatially averaged velocity measurements of the glass particles. This technique is compared with the velocity measurement using an optic probe which is a conventional granular flow velocity measurement device. The other technique for measuring the velocities of individual acrylic particles is developed with correspondence using a Hopfield network. This technique first locates the positions of particles with pattern recognition techniques, followed by a clustering technique, which produces point patterns. Also, several techniques are compared for particle recognition: synthetic discriminant function (SDF), minimum average correlation energy (MACE) filter, modified minimum average correlation energy (MMACE) filter and variance normalized correlation. The author proposes an MMACE filter which improves generalization of the MACE filter by adjusting the amount of averaged spectrum of training images in the spectrum whitening stages of the MACE filter. Variance normalized correlation is applied to measure the velocity and temperature of flowing glass particles down the inclined chute. The measurements are taken for the steady and wavy flow and qualitatively compared with a theoretical model of granular flow.

  4. A simple delay model for two-phase flow dynamics

    Clausse, A.; Delmastro, D.F.; Juanico`, L.E. [Centro Atomico Bariloche (Argentina)

    1995-09-01

    A model based in delay equations for density-wave oscillations is presented. High Froude numbers and moderate ones were considered. The equations were numerically analyzed and compared with more sophisticated models. The influence of the gravity term was studied. Different kinds of behavior were found, particularly sub-critical and super-critical Hopf bifurcations. Moreover the present approach can be used to better understand the complicated dynamics of boiling flows systems.

  5. Binding sites for luminescent amyloid biomarkers from non-biased molecular dynamics simulations.

    König, Carolin; Skånberg, Robin; Hotz, Ingrid; Ynnerman, Anders; Norman, Patrick; Linares, Mathieu

    2018-03-25

    A very stable binding site for the interaction between a pentameric oligothiophene and an amyloid-β(1-42) fibril has been identified by means of non-biased molecular dynamics simulations. In this site, the probe is locked in an all-trans conformation with a Coulombic binding energy of 1200 kJ mol -1 due to the interactions between the anionic carboxyl groups of the probe and the cationic ε-amino groups in the lysine side chain. Upon binding, the conformationally restricted probes show a pronounced increase in molecular planarity. This is in line with the observed changes in luminescence properties that serve as the foundation for their use as biomarkers.

  6. A dynamically coupled allosteric network underlies binding cooperativity in Src kinase.

    Foda, Zachariah H; Shan, Yibing; Kim, Eric T; Shaw, David E; Seeliger, Markus A

    2015-01-20

    Protein tyrosine kinases are attractive drug targets because many human diseases are associated with the deregulation of kinase activity. However, how the catalytic kinase domain integrates different signals and switches from an active to an inactive conformation remains incompletely understood. Here we identify an allosteric network of dynamically coupled amino acids in Src kinase that connects regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants (ATP and peptide substrates) bind with negative cooperativity to Src kinase while products (ADP and phosphopeptide) bind with positive cooperativity. We confirm the molecular details of the signal relay through the allosteric network by biochemical studies. Experiments on two additional protein tyrosine kinases indicate that the allosteric network may be largely conserved among these enzymes. Our work provides new insights into the regulation of protein tyrosine kinases and establishes a potential conduit by which resistance mutations to ATP-competitive kinase inhibitors can affect their activity.

  7. Hydro-dynamic damping theory in flowing water

    Monette, C.; Nennemann, B.; Seeley, C.; Coutu, A.; Marmont, H.

    2014-03-01

    Fluid-structure interaction (FSI) has a major impact on the dynamic response of the structural components of hydroelectric turbines. On mid-head to high-head Francis runners, the rotor-stator interaction (RSI) phenomenon always has to be considered carefully during the design phase to avoid operational issues later on. The RSI dynamic response amplitudes are driven by three main factors: (1) pressure forcing amplitudes, (2) excitation frequencies in relation to natural frequencies and (3) damping. The prediction of the two first factors has been largely documented in the literature. However, the prediction of fluid damping has received less attention in spite of being critical when the runner is close to resonance. Experimental damping measurements in flowing water on hydrofoils were presented previously. Those results showed that the hydro-dynamic damping increased linearly with the flow. This paper presents development and validation of a mathematical model, based on momentum exchange, to predict damping due to fluid structure interaction in flowing water. The model is implemented as an analytical procedure for simple structures, such as cantilever beams, but is also implemented in more general ways using three different approaches for more complex structures such as runner blades: a finite element procedure, a CFD modal work based approach and a CFD 1DOF approach. The mathematical model and all three implementation approaches are shown to agree well with experimental results.

  8. A note on the theory of fast money flow dynamics

    Sokolov, A.; Kieu, T.; Melatos, A.

    2010-08-01

    The gauge theory of arbitrage was introduced by Ilinski in [K. Ilinski, preprint arXiv:hep-th/9710148 (1997)] and applied to fast money flows in [A. Ilinskaia, K. Ilinski, preprint arXiv:cond-mat/9902044 (1999); K. Ilinski, Physics of finance: gauge modelling in non-equilibrium pricing (Wiley, 2001)]. The theory of fast money flow dynamics attempts to model the evolution of currency exchange rates and stock prices on short, e.g. intra-day, time scales. It has been used to explain some of the heuristic trading rules, known as technical analysis, that are used by professional traders in the equity and foreign exchange markets. A critique of some of the underlying assumptions of the gauge theory of arbitrage was presented by Sornette in [D. Sornette, Int. J. Mod. Phys. C 9, 505 (1998)]. In this paper, we present a critique of the theory of fast money flow dynamics, which was not examined by Sornette. We demonstrate that the choice of the input parameters used in [K. Ilinski, Physics of finance: gauge modelling in non-equilibrium pricing (Wiley, 2001)] results in sinusoidal oscillations of the exchange rate, in conflict with the results presented in [K. Ilinski, Physics of finance: gauge modelling in non-equilibrium pricing (Wiley, 2001)]. We also find that the dynamics predicted by the theory are generally unstable in most realistic situations, with the exchange rate tending to zero or infinity exponentially.

  9. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J.

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  10. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  11. Accessing a hidden conformation of the maltose binding protein using accelerated molecular dynamics.

    Denis Bucher

    2011-04-01

    Full Text Available Periplasmic binding proteins (PBPs are a large family of molecular transporters that play a key role in nutrient uptake and chemotaxis in Gram-negative bacteria. All PBPs have characteristic two-domain architecture with a central interdomain ligand-binding cleft. Upon binding to their respective ligands, PBPs undergo a large conformational change that effectively closes the binding cleft. This conformational change is traditionally viewed as a ligand induced-fit process; however, the intrinsic dynamics of the protein may also be crucial for ligand recognition. Recent NMR paramagnetic relaxation enhancement (PRE experiments have shown that the maltose binding protein (MBP - a prototypical member of the PBP superfamily - exists in a rapidly exchanging (ns to µs regime mixture comprising an open state (approx 95%, and a minor partially closed state (approx 5%. Here we describe accelerated MD simulations that provide a detailed picture of the transition between the open and partially closed states, and confirm the existence of a dynamical equilibrium between these two states in apo MBP. We find that a flexible part of the protein called the balancing interface motif (residues 175-184 is displaced during the transformation. Continuum electrostatic calculations indicate that the repacking of non-polar residues near the hinge region plays an important role in driving the conformational change. Oscillations between open and partially closed states create variations in the shape and size of the binding site. The study provides a detailed description of the conformational space available to ligand-free MBP, and has implications for understanding ligand recognition and allostery in related proteins.

  12. Molecular determinants of epidermal growth factor binding: a molecular dynamics study.

    Jeffrey M Sanders

    Full Text Available The epidermal growth factor receptor (EGFR is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both low affinity and high affinity EGFR ligands. While these studies have identified functional effects of ligand binding, high-resolution structural data are lacking. To gain a better understanding of the molecular basis of EGFR binding affinities, we docked each EGFR ligand to the putative active state extracellular domain dimer and 25.0 ns molecular dynamics simulations were performed. MM-PBSA/GBSA are efficient computational approaches to approximate free energies of protein-protein interactions and decompose the free energy at the amino acid level. We applied these methods to the last 6.0 ns of each ligand-receptor simulation. MM-PBSA calculations were able to successfully rank all seven of the EGFR ligands based on the two affinity classes: EGF>HB-EGF>TGF-α>BTC>EPR>EPG>AR. Results from energy decomposition identified several interactions that are common among binding ligands. These findings reveal that while several residues are conserved among the EGFR ligand family, no single set of residues determines the affinity class. Instead we found heterogeneous sets of interactions that were driven primarily by electrostatic and Van der Waals forces. These results not only illustrate the complexity of EGFR dynamics but also pave the way for structure-based design of

  13. Coarse-grained debris flow dynamics on erodible beds

    Lanzoni, Stefano; Gregoretti, Carlo; Stancanelli, Laura Maria

    2017-03-01

    A systematic set of flume experiments is used to investigate the features of velocity profiles within the body of coarse-grained debris flows and the dependence of the transport sediment concentration on the relevant parameters (runoff discharge, bed slope, grain size, and form). The flows are generated in a 10 m long laboratory flume, initially filled with a layer consisting of loose debris. After saturation, a prescribed water discharge is suddenly supplied over the granular bed, and the runoff triggers a debris flow wave that reaches nearly steady conditions. Three types of material have been used in the tests: gravel with mean grain size of 3 and 5 mm, and 3 mm glass spheres. Measured parameters included: triggering water discharge, volumetric sediment discharge, sediment concentration, flow depth, and velocity profiles. The dynamic similarity with full-sized debris flows is discussed on the basis of the relevant dimensionless parameters. Concentration data highlight the dependence on the slope angle and the importance of the quasi-static friction angle. The effects of flow rheology on the shape of velocity profiles are analyzed with attention to the role of different stress-generating mechanisms. A remarkable collapse of the dimensionless profiles is obtained by scaling the debris flow velocity with the runoff velocity, and a power law characterization is proposed following a heuristic approach. The shape of the profiles suggests a smooth transition between the different rheological regimes (collisional and frictional) that establish in the upper and lower regions of the flow and is compatible with the presence of multiple length scales dictated by the type of contacts (instantaneous or long lasting) between grains.

  14. Dynamics of a fluid flow on Mars: Lava or mud?

    Wilson, Lionel; Mouginis-Mark, Peter J.

    2014-05-01

    A distinctive flow deposit southwest of Cerberus Fossae on Mars is analyzed. The flow source is a ∼20 m deep, ∼12 × 1.5 km wide depression within a yardang associated with the Medusae Fossae Formation. The flow traveled for ∼40 km following topographic lows to leave a deposit on average 3-4 km wide. The surface morphology of the deposit suggests that it was produced by the emplacement of a fluid flowing in a laminar fashion and possessing a finite yield strength. We use topographic data from a digital elevation model (DEM) to model the dynamics of the motion and infer that the fluid had a Bingham rheology with a plastic viscosity of ∼1 Pa s and a yield strength of ∼185 Pa. Although the low viscosity is consistent with the properties of komatiite-like lava, the combination of values of viscosity and yield strength, as well as the surface morphology of the flow, suggests that this was a mud flow. Comparison with published experimental data implies a solids content close to 60% by volume and a grain size dominated by silt-size particles. Comparison of the ∼1.5 km3 deposit volume with the ∼0.03 km3 volume of the source depression implies that ∼98% of the flow material was derived from depth in the crust. There are similarities between the deposit studied here, which we infer to be mud, and other flow deposits on Mars currently widely held to be lavas. This suggests that a re-appraisal of many of these deposits is now in order.

  15. Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

    Anastasios Papaioannou

    Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

  16. Dynamics of flexible fibers transported in confined viscous flows

    Cappello, Jean; Duprat, Camille; Du Roure, Olivia; Nagel, Mathias; Gallaire, François; Lindner, Anke

    2017-11-01

    The dynamics of elongated objects has been extensively studied in unbounded media as for example the sedimentation of fibers at low Reynolds numbers. It has recently been shown that these transport dynamics are strongly modified by bounding walls. Here we focus on the dynamics of flexible fibers confined by the top and bottom walls of a microchannel and transported in pressure-driven flows. We combine well-controlled microfluidic experiments and simulations using modified Brinkmann equations. We control shape, orientation, and mechanical properties of our fibers using micro-fabrication techniques and in-situ characterization methods. These elastic fibers can be deformed by viscous and pressure forces leading to very rich transport dynamics coupling lateral drift with shape evolution. We show that the bending of a perpendicular fiber is proportional to an elasto-viscous number and we fully characterize the influence of the confinement on the deformation of the fiber. Experiments on parallel flexible fibers reveal the existence of a buckling threshold. The European Research Council is acknowledged for funding the work through a consolidator Grant (ERC PaDyFlow 682367).

  17. Mimicking the Interfacial Dynamics of Flowing White Blood Cells

    Santore, Maria

    2015-03-01

    The rolling of particles on surfaces, facilitated by hydrodynamic forces combined with localized surface interactions of the appropriate strengths, spatial arrangements, and ranges, is a technologically useful means of transporting and manipulating particles. One's intuition for the rolling of a marble or a car tire cannot be extrapolated down to microparticle length scales because the microparticle interactions are dominated by electrostatic, van der Waals, and hydrogen bonding interactions rather than a friction that depends on an imposed normal force. Indeed, our microparticle rolling systems are inspired by the rolling of white blood cells on the inner walls of venules as part of the innate immune response: Selectin molecules engage with their counterparts on the opposing surfaces to slow cell motion relative to that for freely flowing cells. In the resulting rolling signature, ligand-receptor binding and crack closing on the front of the cell are balanced with molecular dis-bonding and crack opening at the rear. The contact region is relatively static, allowing other interactions (for instance signaling) to occur for a finite duration. Thus, achieving particle rolling in synthetic systems is important because it facilitates particle-surface interactions in a continuous nonfouling fashion where the contact surface is continually renewed. In developing a synthetic model for this system, we employ polymers to modify flowing particles and /or planar collectors, producing heterogeneous interfaces which can support rolling or produce other motion signatures such as skipping, arrest, or free flow. We identify, in the synthetic system, combinations of variables that produce rolling and demonstrate how the distinction between rolling and arrest is not a simple matter of the adhesion strength between the particles and the collector. Rolling is a cooperative process and the coordination of binding in one location with dis-bonding in another requires appropriate length

  18. DYNAM, Once Through Boiling Flow with Steam Superheat, Laplace Transformation

    Schlueter, G.; Efferding, L.E.

    1973-01-01

    1 - Description of problem or function: DYNAM performs a dynamic analysis of once-through boiling flow oscillations with steam superheat. The model describing the superheat regime (single- phase, variable density fluid) for subcritical pressure operation is also applicable to the study of once-through operation using supercritical pressure water. 2 - Method of solution: Linearized partial differential conservation equations are solved using Laplace transformation of the temporal terms and integration of the spatial variations. DYNAM is written in complex variable notation. 3 - Restrictions on the complexity of the problem - Maxima of: 30 intervals used to describe the power distribution in the non-boiling and boiling regions, 29 boiling nodes, 7 intervals and corresponding friction multipliers read in per case, 14 exit qualities read in per case, 40 superheat nodes, 10 coefficients read in for the phi 2 vs, x-polynomial fit, 48 frequencies at which open-loop frequency response is desired, 48 frequencies at which signal output is desired

  19. Flow dynamics and energy efficiency of flow in the left ventricle during myocardial infarction.

    Vasudevan, Vivek; Low, Adriel Jia Jun; Annamalai, Sarayu Parimal; Sampath, Smita; Poh, Kian Keong; Totman, Teresa; Mazlan, Muhammad; Croft, Grace; Richards, A Mark; de Kleijn, Dominique P V; Chin, Chih-Liang; Yap, Choon Hwai

    2017-10-01

    Cardiovascular disease is a leading cause of death worldwide, where myocardial infarction (MI) is a major category. After infarction, the heart has difficulty providing sufficient energy for circulation, and thus, understanding the heart's energy efficiency is important. We induced MI in a porcine animal model via circumflex ligation and acquired multiple-slice cine magnetic resonance (MR) images in a longitudinal manner-before infarction, and 1 week (acute) and 4 weeks (chronic) after infarction. Computational fluid dynamic simulations were performed based on MR images to obtain detailed fluid dynamics and energy dynamics of the left ventricles. Results showed that energy efficiency flow through the heart decreased at the acute time point. Since the heart was observed to experience changes in heart rate, stroke volume and chamber size over the two post-infarction time points, simulations were performed to test the effect of each of the three parameters. Increasing heart rate and stroke volume were found to significantly decrease flow energy efficiency, but the effect of chamber size was inconsistent. Strong complex interplay was observed between the three parameters, necessitating the use of non-dimensional parameterization to characterize flow energy efficiency. The ratio of Reynolds to Strouhal number, which is a form of Womersley number, was found to be the most effective non-dimensional parameter to represent energy efficiency of flow in the heart. We believe that this non-dimensional number can be computed for clinical cases via ultrasound and hypothesize that it can serve as a biomarker for clinical evaluations.

  20. Extended Lagrangian formulation of charge-constrained tight-binding molecular dynamics.

    Cawkwell, M J; Coe, J D; Yadav, S K; Liu, X-Y; Niklasson, A M N

    2015-06-09

    The extended Lagrangian Born-Oppenheimer molecular dynamics formalism [Niklasson, Phys. Rev. Lett., 2008, 100, 123004] has been applied to a tight-binding model under the constraint of local charge neutrality to yield microcanonical trajectories with both precise, long-term energy conservation and a reduced number of self-consistent field optimizations at each time step. The extended Lagrangian molecular dynamics formalism restores time reversal symmetry in the propagation of the electronic degrees of freedom, and it enables the efficient and accurate self-consistent optimization of the chemical potential and atomwise potential energy shifts in the on-site elements of the tight-binding Hamiltonian that are required when enforcing local charge neutrality. These capabilities are illustrated with microcanonical molecular dynamics simulations of a small metallic cluster using an sd-valent tight-binding model for titanium. The effects of weak dissipation on the propagation of the auxiliary degrees of freedom for the chemical potential and on-site Hamiltonian matrix elements that is used to counteract the accumulation of numerical noise during trajectories was also investigated.

  1. Droplet sizes, dynamics and deposition in vertical annular flow

    Lopes, J.C.B.; Dukler, A.E.

    1985-10-01

    The role of droplets in vertical upwards annular flow is investigated, focusing on the droplet size distributions, dynamics, and deposition phenomena. An experimental program was performed based on a new laser optical technique developed in these laboratories and implemented here for annular flow. This permitted the simultaneous measurement of droplet size, axial and radial velocity. The dependence of droplet size distributions on flow conditions is analyzed. The Upper-Log Normal function proves to be a good model for the size distribution. The mechanism controlling the maximum stable drop size was found to result from the interaction of the pressure fluctuations of the turbulent flow of the gas core with the droplet. The average axial droplet velocity showed a weak dependence on gas rates. This can be explained once the droplet size distribution and droplet size-velocity relationship are analyzed simultaneously. The surprising result from the droplet conditional analysis is that larger droplet travel faster than smaller ones. This dependence cannot be explained if the drag curves used do not take into account the high levels of turbulence present in the gas core in annular flow. If these are considered, then interesting new situations of multiplicity and stability of droplet terminal velocities are encountered. Also, the observed size-velocity relationship can be explained. A droplet deposition is formulated based on the particle inertia control. This permitted the calculation of rates of drop deposition directly from the droplet size and velocities data

  2. Fluid dynamics following flow shut-off in bottle filling

    Thete, Sumeet; Appathurai, Santosh; Gao, Haijing; Basaran, Osman

    2012-11-01

    Bottle filling is ubiquitous in industry. Examples include filling of bottles with shampoos and cleaners, engine oil and pharmaceuticals. In these examples, fluid flows out of a nozzle to fill bottles in an assembly line. Once the required volume of fluid has flowed out of the nozzle, the flow is shut off. However, an evolving fluid thread or string may remain suspended from the nozzle following flow shut-off and persist. This stringing phenomenon can be detrimental to a bottle filling operation because it can adversely affect line speed and filling accuracy by causing uncertainty in fill volume, product loss and undesirable marring of the bottles' exterior surfaces. The dynamics of stringing are studied numerically primarily by using the 1D, slender-jet approximation of the flow equations. A novel feature entails development and use of a new boundary condition downstream of the nozzle exit to expedite the computations. While the emphasis is on stringing of Newtonian fluids and use of 1D approximations, results will also be presented for situations where (a) the fluids are non-Newtonian and (b) the full set of equations are solved without invoking the 1D approximation. Phase diagrams will be presented that identify conditions for which stringing can be problematic.

  3. Quantitative flow analysis of swimming dynamics with coherent Lagrangian vortices.

    Huhn, F; van Rees, W M; Gazzola, M; Rossinelli, D; Haller, G; Koumoutsakos, P

    2015-08-01

    Undulatory swimmers flex their bodies to displace water, and in turn, the flow feeds back into the dynamics of the swimmer. At moderate Reynolds number, the resulting flow structures are characterized by unsteady separation and alternating vortices in the wake. We use the flow field from simulations of a two-dimensional, incompressible viscous flow of an undulatory, self-propelled swimmer and detect the coherent Lagrangian vortices in the wake to dissect the driving momentum transfer mechanisms. The detected material vortex boundary encloses a Lagrangian control volume that serves to track back the vortex fluid and record its circulation and momentum history. We consider two swimming modes: the C-start escape and steady anguilliform swimming. The backward advection of the coherent Lagrangian vortices elucidates the geometry of the vorticity field and allows for monitoring the gain and decay of circulation and momentum transfer in the flow field. For steady swimming, momentum oscillations of the fish can largely be attributed to the momentum exchange with the vortex fluid. For the C-start, an additionally defined jet fluid region turns out to balance the high momentum change of the fish during the rapid start.

  4. A new algorithm for extended nonequilibrium molecular dynamics simulations of mixed flow

    Hunt, T.A.; Hunt, Thomas A.; Bernardi, Stefano; Todd, B.D.

    2010-01-01

    In this work, we develop a new algorithm for nonequilibrium molecular dynamics of fluids under planar mixed flow, a linear combination of planar elongational flow and planar Couette flow. To date, the only way of simulating mixed flow using nonequilibrium molecular dynamics techniques was to impose

  5. Muscle blood flow at onset of dynamic exercise in humans.

    Rådegran, G; Saltin, B

    1998-01-01

    To evaluate the temporal relationship between blood flow, blood pressure, and muscle contractions, we continuously measured femoral arterial inflow with ultrasound Doppler at onset of passive exercise and voluntary, one-legged, dynamic knee-extensor exercise in humans. Blood velocity and inflow increased (P dicrotic and diastolic blood pressure notches, respectively. Mechanical hindrance occurred (P dicrotic notch. The increase in blood flow (Q) was characterized by a one-component (approximately 15% of peak power output), two-component (approximately 40-70% of peak power output), or three-component exponential model (> or = 75% of peak power output), where Q(t) = Qpassive + delta Q1.[1 - e-(t - TD1/tau 1)]+ delta Q2.[1 - e-(t - TD2/tau 2)]+ delta Q3.[1 - e-(t - TD3/tau 3)]; Qpassive, the blood flow during passive leg movement, equals 1.17 +/- 0.11 l/min; TD is the onset latency; tau is the time constant; delta Q is the magnitude of blood flow rise; and subscripts 1-3 refer to the first, second, and third components of the exponential model, respectively. The time to reach 50% of the difference between passive and voluntary asymptotic blood flow was approximately 2.2-8.9 s. The blood flow leveled off after approximately 10-150 s, related to the power outputs. It is concluded that the elevation in blood flow with the first duty cycle(s) is due to muscle mechanical factors, but vasodilators initiate a more potent amplification within the second to fourth contraction.

  6. How does huperzine A enter and leave the binding gorge of acetylcholinesterase? Steered molecular dynamics simulations.

    Xu, Yechun; Shen, Jianhua; Luo, Xiaomin; Silman, Israel; Sussman, Joel L; Chen, Kaixian; Jiang, Hualiang

    2003-09-17

    The entering and leaving processes of Huperzine A (HupA) binding with the long active-site gorge of Torpedo californica acetylcholinesterase (TcAChE) have been investigated by using steered molecular dynamics simulations. The analysis of the force required along the pathway shows that it is easier for HupA to bind to the active site of AChE than to disassociate from it, which for the first time interprets at the atomic level the previous experimental result that unbinding process of HupA is much slower than its binding process to AChE. The direct hydrogen bonds, water bridges, and hydrophobic interactions were analyzed during two steered molecular dynamics (SMD) simulations. Break of the direct hydrogen bond needs a great pulling force. The steric hindrance of bottleneck might be the most important factor to produce the maximal rupture force for HupA to leave the binding site but it has a little effect on the binding process of HupA with AChE. Residue Asp72 forms a lot of water bridges with HupA leaving and entering the AChE binding gorge, acting as a clamp to take out HupA from or put HupA into the active site. The flip of the peptide bond between Gly117 and Gly118 has been detected during both the conventional MD and SMD simulations. The simulation results indicate that this flip phenomenon could be an intrinsic property of AChE and the Gly117-Gly118 peptide bond in both HupA bound and unbound AChE structures tends to adopt the native enzyme structure. At last, in a vacuum the rupture force is increased up to 1500 pN while in water solution the greatest rupture force is about 800 pN, which means water molecules in the binding gorge act as lubricant to facilitate HupA entering or leaving the binding gorge.

  7. Evaluation of flow accelerated corrosion by coupled analysis of corrosion and flow dynamics (2), flow dynamics calculations for determining mixing factors and mass transfer coefficients

    Uehara, Yasushi; Uchida, Shunsuke; Naitoh, Masanori; Okada, Hidetoshi; Koshizuka, Seiichi

    2009-01-01

    In order to predict and mitigate flow accelerated corrosion (FAC) of carbon steel piping in PWR and BWR secondary systems, computer program packages for evaluating FAC have been developed by coupling one through three dimensional (1-3D) computational flow dynamics (CFD) models and corrosion models. To evaluate corrosive conditions, e.g., oxygen concentration and electrochemical corrosion potential (ECP) along the flow path, flow pattern and temperature in each elemental volume were obtained with 1D computational flow dynamics (CFD) codes. Precise flow turbulence and mass transfer coefficients at the structure surface were calculated with 3D CFD codes to determine wall thinning rates. One of the engineering options is application of k-ε calculation as a 3D CFD code, which has limitation of detail evaluation of flow distribution at very surface of large scale piping. A combination of k-ε calculation and wall function was proposed to evaluate precise distribution of mass transfer coefficients with reasonable CPU volume and computing time and, at the same time, reasonable accuracy. (author)

  8. Molecular Dynamics Insights into Polyamine-DNA Binding Modes: Implications for Cross-Link Selectivity.

    Bignon, Emmanuelle; Chan, Chen-Hui; Morell, Christophe; Monari, Antonio; Ravanat, Jean-Luc; Dumont, Elise

    2017-09-18

    Biogenic polyamines, which play a role in DNA condensation and stabilization, are ubiquitous and are found at millimolar concentration in the nucleus of eukaryotic cells. The interaction modes of three polyamines-putrescine (Put), spermine (Spm), and spermidine (Spd)-with a self-complementary 16 base pair (bp) duplex, are investigated by all-atom explicit-solvent molecular dynamics. The length of the amine aliphatic chain leads to a change of the interaction mode from minor groove binding to major groove binding. Through all-atom dynamics, noncovalent interactions that stabilize the polyamine-DNA complex and prefigure the reactivity, leading to the low-barrier formation of deleterious DNA-polyamine cross-links, after one-electron oxidation of a guanine nucleobase, are unraveled. The binding strength is quantified from the obtained trajectories by molecular mechanics generalized Born surface area post-processing (MM-GBSA). The values of binding free energies provide the same affinity order, Putbinding modes and carbon-nitrogen distances along the series of polyamines illustrate the selectivity towards deleterious DNA-polyamine cross-link formation through the extraction of average approaching distances between the C8 atom of guanines and the ammonium group. These results imply that the formation of DNA-polyamine cross-links involves deprotonation of the guanine radical cation to attack the polyamines, which must be positively charged to lie in the vicinity of the B-helix. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Flow vibrations and dynamic instability of heat exchanger tube bundles

    Granger, S.; Langre, E. de

    1995-01-01

    This paper presents a review of external-flow-induced vibration of heat exchanger tube bundles. Attention is focused on a dynamic instability, known as ''fluidelastic instability'', which can develop when flow is transverse to the tube axis. The main physical models proposed in the literature are successively reviewed in a critical way. As a consequence, some concepts are clarified, some a priori plausible misinterpretations are rejected and finally, certain basic mechanisms, induced by the flow-structure interaction and responsible for the ultimate onset of fluidelastic instability, are elucidated. Design tools and methods for predictive analysis of industrial cases are then presented. The usual design tool is the ''stability map'', i.e. an empirical correlation which must be interpreted in a conservative way. Of course, when using this approach, the designer must also consider reasonable safety margins. In the area of predictive analysis, the ''unsteady semi-analytical models'' seem to be a promising and efficient methodology. A modern implementation of these ideas mix an original experimental approach for taking fluid dynamic forces into account, together with non-classical numerical methods of mechanical vibration. (authors). 20 refs., 9 figs

  10. Wake flow control using a dynamically controlled wind turbine

    Castillo, Ricardo; Wang, Yeqin; Pol, Suhas; Swift, Andy; Hussain, Fazle; Westergaard, Carsten; Texas Tech University Team

    2016-11-01

    A wind tunnel based "Hyper Accelerated Wind Farm Kinematic-Control Simulator" (HAWKS) is being built at Texas Tech University to emulate controlled wind turbine flow physics. The HAWKS model turbine has pitch, yaw and speed control which is operated in real model time, similar to that of an equivalent full scale turbine. Also, similar to that of a full scale wind turbine, the controls are developed in a Matlab Simulink environment. The current diagnostic system consists of power, rotor position, rotor speed measurements and PIV wake characterization with four cameras. The setup allows up to 7D downstream of the rotor to be mapped. The purpose of HAWKS is to simulate control strategies at turnaround times much faster than CFD and full scale testing. The fundamental building blocks of the simulator have been tested, and demonstrate wake steering for both static and dynamic turbine actuation. Parameters which have been studied are yaw, rotor speed and combinations hereof. The measured wake deflections for static yaw cases are in agreement with previously reported research implying general applicability of the HAWKS platform for the purpose of manipulating the wake. In this presentation the general results will be introduced followed by an analysis of the wake turbulence and coherent structures when comparing static and dynamic flow cases. The outcome of such studies could ultimately support effective wind farm wake flow control strategies. Texas Emerging Technology Fund (ETF).

  11. Development of tight-binding, chemical-reaction-dynamics simulator for combinatorial computational chemistry

    Kubo, Momoji; Ando, Minako; Sakahara, Satoshi; Jung, Changho; Seki, Kotaro; Kusagaya, Tomonori; Endou, Akira; Takami, Seiichi; Imamura, Akira; Miyamoto, Akira

    2004-01-01

    Recently, we have proposed a new concept called 'combinatorial computational chemistry' to realize a theoretical, high-throughput screening of catalysts and materials. We have already applied our combinatorial, computational-chemistry approach, mainly based on static first-principles calculations, to various catalysts and materials systems and its applicability to the catalysts and materials design was strongly confirmed. In order to realize more effective and efficient combinatorial, computational-chemistry screening, a high-speed, chemical-reaction-dynamics simulator based on quantum-chemical, molecular-dynamics method is essential. However, to the best of our knowledge, there is no chemical-reaction-dynamics simulator, which has an enough high-speed ability to perform a high-throughput screening. In the present study, we have succeeded in the development of a chemical-reaction-dynamics simulator based on our original, tight-binding, quantum-chemical, molecular-dynamics method, which is more than 5000 times faster than the regular first-principles, molecular-dynamics method. Moreover, its applicability and effectiveness to the atomistic clarification of the methanol-synthesis dynamics at reaction temperature were demonstrated

  12. Structure, dynamics and RNA binding of the multi-domain splicing factor TIA-1

    Wang, Iren; Hennig, Janosch; Jagtap, Pravin Kumar Ankush; Sonntag, Miriam; Valcárcel, Juan; Sattler, Michael

    2014-01-01

    Alternative pre-messenger ribonucleic acid (pre-mRNA) splicing is an essential process in eukaryotic gene regulation. The T-cell intracellular antigen-1 (TIA-1) is an apoptosis-promoting factor that modulates alternative splicing of transcripts, including the pre-mRNA encoding the membrane receptor Fas. TIA-1 is a multi-domain ribonucleic acid (RNA) binding protein that recognizes poly-uridine tract RNA sequences to facilitate 5′ splice site recognition by the U1 small nuclear ribonucleoprotein (snRNP). Here, we characterize the RNA interaction and conformational dynamics of TIA-1 by nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC) and small angle X-ray scattering (SAXS). Our NMR-derived solution structure of TIA-1 RRM2–RRM3 (RRM2,3) reveals that RRM2 adopts a canonical RNA recognition motif (RRM) fold, while RRM3 is preceded by an non-canonical helix α0. NMR and SAXS data show that all three RRMs are largely independent structural modules in the absence of RNA, while RNA binding induces a compact arrangement. RRM2,3 binds to pyrimidine-rich FAS pre-mRNA or poly-uridine (U9) RNA with nanomolar affinities. RRM1 has little intrinsic RNA binding affinity and does not strongly contribute to RNA binding in the context of RRM1,2,3. Our data unravel the role of binding avidity and the contributions of the TIA-1 RRMs for recognition of pyrimidine-rich RNAs. PMID:24682828

  13. Dynamically Partitionable Autoassociative Networks as a Solution to the Neural Binding Problem

    Kenneth Jeffrey Hayworth

    2012-09-01

    Full Text Available An outstanding question in theoretical neuroscience is how the brain solves the neural binding problem. In vision, binding can be summarized as the ability to represent that certain properties belong to one object while other properties belong to a different object. I review the binding problem in visual and other domains, and review its simplest proposed solution – the anatomical binding hypothesis. This hypothesis has traditionally been rejected as a true solution because it seems to require a type of one-to-one wiring of neurons that would be impossible in a biological system (as opposed to an engineered system like a computer. I show that this requirement for one-to-one wiring can be loosened by carefully considering how the neural representation is actually put to use by the rest of the brain. This leads to a solution where a symbol is represented not as a particular pattern of neural activation but instead as a piece of a global stable attractor state. I introduce the Dynamically Partitionable AutoAssociative Network (DPAAN as an implementation of this solution and show how DPANNs can be used in systems which perform perceptual binding and in systems that implement syntax-sensitive rules. Finally I show how the core parts of the cognitive architecture ACT-R can be neurally implemented using a DPAAN as ACT-R’s global workspace. Because the DPAAN solution to the binding problem requires only ‘flat’ neural representations (as opposed to the phase encoded representation hypothesized in neural synchrony solutions it is directly compatible with the most well developed neural models of learning, memory, and pattern recognition.

  14. Dynamic factors affecting gaseous ligand binding in an artificial oxygen transport protein.

    Zhang, Lei; Andersen, Eskil M E; Khajo, Abdelahad; Magliozzo, Richard S; Koder, Ronald L

    2013-01-22

    We report the functional analysis of an artificial hexacoordinate oxygen transport protein, HP7, which operates via a mechanism similar to that of human neuroglobin and cytoglobin: the destabilization of one of two heme-ligating histidine residues. In the case of HP7, this is the result of the coupling of histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Here we compare gaseous ligand binding, including rates, affinities, and oxyferrous state lifetimes, of both heme binding sites in HP7. We find that despite the identical sequence of helices in both binding sites, there are differences in oxygen affinity and oxyferrous state lifetime that may be the result of differences in the freedom of motion imposed by the candelabra fold on the two sites of the protein. We further examine the effect of mutational removal of the buried glutamates on function. Heme iron in the ferrous state of this mutant is rapidly oxidized when exposed to oxygen. Compared to that of HP7, the distal histidine affinity is increased by a 22-fold decrease in the histidine ligand off rate. Electron paramagnetic resonance comparison of these ferric hemoproteins demonstrates that the mutation increases the level of disorder at the heme binding site. Nuclear magnetic resonance-detected deuterium exchange demonstrates that the mutation greatly increases the degree of penetration of water into the protein core. The inability of the mutant protein to bind oxygen may be due to an increased level of water penetration, the large decrease in binding rate caused by the increase in distal histidine affinity, or a combination of the two factors. Together, these data underline the importance of the control of protein dynamics in the design of functional artificial proteins.

  15. Dynamic Factors Affecting Gaseous Ligand Binding in an Artificial Oxygen Transport Protein‡

    Zhang, Lei; Andersen, Eskil M.E.; Khajo, Abdelahad; Magliozzo, Richard S.; Koder, Ronald L.

    2013-01-01

    We report the functional analysis of an artificial hexacoordinate oxygen transport protein, HP7, which operates via a mechanism similar to that of human neuroglobin and cytoglobin: the destabilization of one of two heme-ligating histidine residues. In the case of HP7 this is the result of the coupling of histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Here we compare gaseous ligand binding, including rates, affinities and oxyferrous state lifetimes, of both heme binding sites in HP7. We find that despite the identical sequence of helices in both binding sites, there are differences in oxygen affinity and oxyferrous state lifetime which may be the result of differences in the freedom of motion imposed by the candelabra fold on the two sites of the protein. We further examine the effect of mutational removal of the buried glutamates on function. Heme iron in the ferrous state of this mutant is rapidly oxidized when when exposed to oxygen. Compared to HP7, distal histidine affinity is increased by a 22-fold decrease in the histidine ligand off-rate. EPR comparison of these ferric hemoproteins demonstrates that the mutation increases disorder at the heme binding site. NMR-detected deuterium exchange demonstrates that the mutation greatly increases water penetration into the protein core. The inability of the mutant protein to bind oxygen may be due to increased water penetration, the large decrease in binding rate caused by the increase in distal histidine affinity, or a combination of the two factors. Together these data underline the importance of the control of protein dynamics in the design of functional artificial proteins. PMID:23249163

  16. A numerical model for dynamic crustal-scale fluid flow

    Sachau, Till; Bons, Paul; Gomez-Rivas, Enrique; Koehn, Daniel

    2015-04-01

    Fluid flow in the crust is often envisaged and modeled as continuous, yet minimal flow, which occurs over large geological times. This is a suitable approximation for flow as long as it is solely controlled by the matrix permeability of rocks, which in turn is controlled by viscous compaction of the pore space. However, strong evidence (hydrothermal veins and ore deposits) exists that a significant part of fluid flow in the crust occurs strongly localized in both space and time, controlled by the opening and sealing of hydrofractures. We developed, tested and applied a novel computer code, which considers this dynamic behavior and couples it with steady, Darcian flow controlled by the matrix permeability. In this dual-porosity model, fractures open depending on the fluid pressure relative to the solid pressure. Fractures form when matrix permeability is insufficient to accommodate fluid flow resulting from compaction, decompression (Staude et al. 2009) or metamorphic dehydration reactions (Weisheit et al. 2013). Open fractures can close when the contained fluid either seeps into the matrix or escapes by fracture propagation: mobile hydrofractures (Bons, 2001). In the model, closing and sealing of fractures is controlled by a time-dependent viscous law, which is based on the effective stress and on either Newtonian or non-Newtonian viscosity. Our simulations indicate that the bulk of crustal fluid flow in the middle to lower upper crust is intermittent, highly self-organized, and occurs as mobile hydrofractures. This is due to the low matrix porosity and permeability, combined with a low matrix viscosity and, hence, fast sealing of fractures. Stable fracture networks, generated by fluid overpressure, are restricted to the uppermost crust. Semi-stable fracture networks can develop in an intermediate zone, if a critical overpressure is reached. Flow rates in mobile hydrofractures exceed those in the matrix porosity and fracture networks by orders of magnitude

  17. Statistical dynamical subgrid-scale parameterizations for geophysical flows

    O'Kane, T J; Frederiksen, J S

    2008-01-01

    Simulations of both atmospheric and oceanic circulations at given finite resolutions are strongly dependent on the form and strengths of the dynamical subgrid-scale parameterizations (SSPs) and in particular are sensitive to subgrid-scale transient eddies interacting with the retained scale topography and the mean flow. In this paper, we present numerical results for SSPs of the eddy-topographic force, stochastic backscatter, eddy viscosity and eddy-mean field interaction using an inhomogeneous statistical turbulence model based on a quasi-diagonal direct interaction approximation (QDIA). Although the theoretical description on which our model is based is for general barotropic flows, we specifically focus on global atmospheric flows where large-scale Rossby waves are present. We compare and contrast the closure-based results with an important earlier heuristic SSP of the eddy-topographic force, based on maximum entropy or statistical canonical equilibrium arguments, developed specifically for general ocean circulation models (Holloway 1992 J. Phys. Oceanogr. 22 1033-46). Our results demonstrate that where strong zonal flows and Rossby waves are present, such as in the atmosphere, maximum entropy arguments are insufficient to accurately parameterize the subgrid contributions due to eddy-eddy, eddy-topographic and eddy-mean field interactions. We contrast our atmospheric results with findings for the oceans. Our study identifies subgrid-scale interactions that are currently not parameterized in numerical atmospheric climate models, which may lead to systematic defects in the simulated circulations.

  18. Energy and ancillary service dispatch through dynamic optimal power flow

    Costa, A.L.; Costa, A. Simoes

    2007-01-01

    This paper presents an approach based on dynamic optimal power flow (DOPF) to clear both energy and spinning reserve day-ahead markets. A competitive environment is assumed, where agents can offer active power for both demand supply and ancillary services. The DOPF jointly determines the optimal solutions for both energy dispatch and reserve allocation. A non-linear representation for the electrical network is employed, which is able to take transmission losses and power flow limits into account. An attractive feature of the proposed approach is that the final optimal solution will automatically meet physical constraints such as generating limits and ramp rate restrictions. In addition, the proposed framework allows the definition of multiple zones in the network for each time interval, in order to ensure a more adequate distribution of reserves throughout the power system. (author)

  19. Mapping flow distortion on oceanographic platforms using computational fluid dynamics

    N. O'Sullivan

    2013-10-01

    Full Text Available Wind speed measurements over the ocean on ships or buoys are affected by flow distortion from the platform and by the anemometer itself. This can lead to errors in direct measurements and the derived parametrisations. Here we computational fluid dynamics (CFD to simulate the errors in wind speed measurements caused by flow distortion on the RV Celtic Explorer. Numerical measurements were obtained from the finite-volume CFD code OpenFOAM, which was used to simulate the velocity fields. This was done over a range of orientations in the test domain from −60 to +60° in increments of 10°. The simulation was also set up for a range of velocities, ranging from 5 to 25 m s−1 in increments of 0.5 m s−1. The numerical analysis showed close agreement to experimental measurements.

  20. Integrin activation dynamics between the RGD-binding site and the headpiece hinge.

    Puklin-Faucher, Eileen; Vogel, Viola

    2009-12-25

    Integrins form mechanical links between the extracellular matrix and the cytoskeleton. Although integrin activation is known to be regulated by an allosteric conformational change, which can be induced from the extracellular or intracellular end of the molecule, little is known regarding the sequence of structural events by which signals propagate between distant sites. Here, we reveal with molecular dynamics simulations of the FnIII(10)-bound alpha(V)beta(3) integrin headpiece how the binding pocket and interdomain betaA/hybrid domain hinge on the distal end of the betaA domain are allosterically linked via a hydrophobic T-junction between the middle of the alpha1 helix and top of the alpha7 helix. The key results of this study are: 1) that this T-junction is induced by ligand binding and hinge opening, and thus displays bidirectionality; 2) that formation of this junction can be accelerated by ligand-mediated force; and 3) how formation of this junction is inhibited by Ca(2+) in place of Mg(2+) at the site adjacent to the metal ion-dependent adhesion site ("ADMIDAS"). Together with recent experimental evidence that integrin complexes can form catch bonds (i.e. become strengthened under force), as well as earlier evidence that Ca(2+) at the ADMIDAS results in lower binding affinity, these simulations provide a common structural model for the dynamic process by which integrins become activated.

  1. Integrin Activation Dynamics between the RGD-binding Site and the Headpiece Hinge*

    Puklin-Faucher, Eileen; Vogel, Viola

    2009-01-01

    Integrins form mechanical links between the extracellular matrix and the cytoskeleton. Although integrin activation is known to be regulated by an allosteric conformational change, which can be induced from the extracellular or intracellular end of the molecule, little is known regarding the sequence of structural events by which signals propagate between distant sites. Here, we reveal with molecular dynamics simulations of the FnIII10-bound αVβ3 integrin headpiece how the binding pocket and interdomain βA/hybrid domain hinge on the distal end of the βA domain are allosterically linked via a hydrophobic T-junction between the middle of the α1 helix and top of the α7 helix. The key results of this study are: 1) that this T-junction is induced by ligand binding and hinge opening, and thus displays bidirectionality; 2) that formation of this junction can be accelerated by ligand-mediated force; and 3) how formation of this junction is inhibited by Ca2+ in place of Mg2+ at the site adjacent to the metal ion-dependent adhesion site (“ADMIDAS”). Together with recent experimental evidence that integrin complexes can form catch bonds (i.e. become strengthened under force), as well as earlier evidence that Ca2+ at the ADMIDAS results in lower binding affinity, these simulations provide a common structural model for the dynamic process by which integrins become activated. PMID:19762919

  2. Preferential binding effects on protein structure and dynamics revealed by coarse-grained Monte Carlo simulation

    Pandey, R. B.; Jacobs, D. J.; Farmer, B. L.

    2017-05-01

    The effect of preferential binding of solute molecules within an aqueous solution on the structure and dynamics of the histone H3.1 protein is examined by a coarse-grained Monte Carlo simulation. The knowledge-based residue-residue and hydropathy-index-based residue-solvent interactions are used as input to analyze a number of local and global physical quantities as a function of the residue-solvent interaction strength (f). Results from simulations that treat the aqueous solution as a homogeneous effective solvent medium are compared to when positional fluctuations of the solute molecules are explicitly considered. While the radius of gyration (Rg) of the protein exhibits a non-monotonic dependence on solvent interaction over a wide range of f within an effective medium, an abrupt collapse in Rg occurs in a narrow range of f when solute molecules rapidly bind to a preferential set of sites on the protein. The structure factor S(q) of the protein with wave vector (q) becomes oscillatory in the collapsed state, which reflects segmental correlations caused by spatial fluctuations in solute-protein binding. Spatial fluctuations in solute binding also modify the effective dimension (D) of the protein in fibrous (D ˜ 1.3), random-coil (D ˜ 1.75), and globular (D ˜ 3) conformational ensembles as the interaction strength increases, which differ from an effective medium with respect to the magnitude of D and the length scale.

  3. Comparative molecular dynamics study of neuromyelitis optica-immunoglobulin G binding to aquaporin-4 extracellular domains.

    Alberga, Domenico; Trisciuzzi, Daniela; Lattanzi, Gianluca; Bennett, Jeffrey L; Verkman, Alan S; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio

    2017-08-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system in which most patients have serum autoantibodies (called NMO-IgG) that bind to astrocyte water channel aquaporin-4 (AQP4). A potential therapeutic strategy in NMO is to block the interaction of NMO-IgG with AQP4. Building on recent observation that some single-point and compound mutations of the AQP4 extracellular loop C prevent NMO-IgG binding, we carried out comparative Molecular Dynamics (MD) investigations on three AQP4 mutants, TP 137-138 AA, N 153 Q and V 150 G, whose 295-ns long trajectories were compared to that of wild type human AQP4. A robust conclusion of our modeling is that loop C mutations affect the conformation of neighboring extracellular loop A, thereby interfering with NMO-IgG binding. Analysis of individual mutations suggested specific hydrogen bonding and other molecular interactions involved in AQP4-IgG binding to AQP4. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. DNA-magnetic Particle Binding Analysis by Dynamic and Electrophoretic Light Scattering.

    Haddad, Yazan; Dostalova, Simona; Kudr, Jiri; Zitka, Ondrej; Heger, Zbynek; Adam, Vojtech

    2017-11-09

    Isolation of DNA using magnetic particles is a field of high importance in biotechnology and molecular biology research. This protocol describes the evaluation of DNA-magnetic particles binding via dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Analysis by DLS provides valuable information on the physicochemical properties of particles including particle size, polydispersity, and zeta potential. The latter describes the surface charge of the particle which plays major role in electrostatic binding of materials such as DNA. Here, a comparative analysis exploits three chemical modifications of nanoparticles and microparticles and their effects on DNA binding and elution. Chemical modifications by branched polyethylenimine, tetraethyl orthosilicate and (3-aminopropyl)triethoxysilane are investigated. Since DNA exhibits a negative charge, it is expected that zeta potential of particle surface will decrease upon binding of DNA. Forming of clusters should also affect particle size. In order to investigate the efficiency of these particles in isolation and elution of DNA, the particles are mixed with DNA in low pH (~6), high ionic strength and dehydration environment. Particles are washed on magnet and then DNA is eluted by Tris-HCl buffer (pH = 8). DNA copy number is estimated using quantitative polymerase chain reaction (PCR). Zeta potential, particle size, polydispersity and quantitative PCR data are evaluated and compared. DLS is an insightful and supporting method of analysis that adds a new perspective to the process of screening of particles for DNA isolation.

  5. Improved Low Power FPGA Binding of Datapaths from Data Flow Graphs with NSGA II -based Schedule Selection

    BHUVANESWARI, M. C.

    2013-11-01

    Full Text Available FPGAs are increasingly being used to implement data path intensive algorithms for signal processing and image processing applications. In High Level Synthesis of Data Flow Graphs targeted at FPGAs, the effect of interconnect resources such as multiplexers must be considered since they contribute significantly to the area and switching power. We propose a binding framework for behavioral synthesis of Data Flow Graphs (DFGs onto FPGA targets with power reduction as the main criterion. The technique uses a multi-objective GA, NSGA II for design space exploration to identify schedules that have the potential to yield low-power bindings from a population of non-dominated solutions. A greedy constructive binding technique reported in the literature is adapted for interconnect minimization. The binding is further subjected to a perturbation process by altering the register and multiplexer assignments. Results obtained on standard DFG benchmarks indicate that our technique yields better power aware bindings than the constructive binding approach with little or no area overhead.

  6. Improved dynamic CT angiography visualization by flow territory masking

    Søren Christensen

    2015-01-01

    Full Text Available Backgound and Purpose: Computerized tomography (CT perfusion (or CTP source images from CT scanners with small detector widths can be used to create a dynamic CT angiogram (CTA similar to digital subtraction angiography (DSA. Because CTP studies use a single intravenous injection, all arterial territories enhance simultaneously, and individual arterial territories [i.e., anterior cerebral artery (ACA, middle cerebral artery (MCA, and posterior cerebral artery (PCA] cannot be delineated. This limits the ability to assess collateral flow patterns on dynamic CTAs. The aim of this study was to devise and test a postprocessing method to selectively color-label the major arterial territories on dynamic CTA. Materials and Methods: We identified 22 acute-stroke patients who underwent CTP on a 320-slice CT scanner within 6 h from symptom onset. For each case, two investigators independently generated an arterial territory map from CTP bolus arrival maps using a semiautomated method. The volumes of the arterial territories were calculated for each map and the average relative difference between these volumes was calculated for each case as a measure of interrater agreement. Arterial territory maps were superimposed on the dynamic CTA to create a vessel-selective dynamic CTA with color-coding of the main arterial territories. Two experts rated the arterial territory maps and the color-coded CTAs for consistency with expected arterial territories on a 3-point scale (excellent, moderate, poor. Results: Arterial territory maps were generated for all 22 patients. The median difference in arterial territory volumes between investigators was 2.2% [interquartile range (IQR 0.6-8.5%]. Based on expert review, the arterial territory maps and the vessel-selective dynamic CTAs showed excellent consistency with the expected arterial territories in 18 of 22 patients, moderate consistency in 2 patients, and poor consistency in another 2 patients. Conclusion: Using a

  7. In-Vivo High Dynamic Range Vector Flow Imaging

    Villagómez Hoyos, Carlos Armando; Stuart, Matthias Bo; Jensen, Jørgen Arendt

    2015-01-01

    example with a high dynamic velocity range. Velocities with an order of magnitude apart are detected on the femoral artery of a 41 years old healthy individual. Three distinct heart cycles are captured during a 3 secs acquisition. The estimated vector velocities are compared against each other within...... the heart cycle. The relative standard deviation of the measured velocity magnitude between the three peak systoles was found to be 5.11% with a standard deviation on the detected angle of 1.06◦ . In the diastole, it was 1.46% and 6.18◦ , respectively. Results proves that the method is able to estimate flow...

  8. Molecular dynamics simulations of oscillatory flows in microfluidic channels

    Hansen, J.S.; Ottesen, Johnny T.

    2006-01-01

    In this paper we apply the direct non-equilibrium molecular dynamics technique to oscillatory flows of fluids in microscopic channels. Initially, we show that the microscopic simulations resemble the macroscopic predictions based on the Navier–Stokes equation very well for large channel width, high...... density and low temperature. Further simulations for high temperature and low density show that the non-slip boundary condition traditionally used in the macroscopic equation is greatly compromised when the fluid–wall interactions are the same as the fluid–fluid interactions. Simulations of a system...

  9. Increasing the Dynamic Range of Synthetic Aperture Vector Flow Imaging

    Villagómez Hoyos, Carlos Armando; Stuart, Matthias Bo; Jensen, Jørgen Arendt

    2014-01-01

    images. The emissions for the two imaging modes are interleaved 1-to-1 ratio, providing a high frame rate equal to the effective pulse repetition frequency of each imaging mode. The direction of the flow is estimated, and the velocity is then determined in that direction. This method Works for all angles...... standard deviations are 1.59% and 6.12%, respectively. The presented method can improve the estimates by synthesizing a lower pulse repetition frequency, thereby increasing the dynamic range of the vector velocity imaging....

  10. Transverse flow reactor studies of the dynamics of radical reactions

    Macdonald, R.G. [Argonne National Laboratory, IL (United States)

    1993-12-01

    Radical reactions are in important in combustion chemistry; however, little state-specific information is available for these reactions. A new apparatus has been constructed to measure the dynamics of radical reactions. The unique feature of this apparatus is a transverse flow reactor in which an atom or radical of known concentration will be produced by pulsed laser photolysis of an appropriate precursor molecule. The time dependence of individual quantum states or products and/or reactants will be followed by rapid infrared laser absorption spectroscopy. The reaction H + O{sub 2} {yields} OH + O will be studied.

  11. Constrained dynamics of an inertial particle in a turbulent flow

    Obligado, M; Baudet, C; Gagne, Y; Bourgoin, M

    2011-01-01

    Most of theoretical and numerical works for free advected particles in a turbulent flow, which only consider the drag force acting on the particles, fails to predict recent experimental results for the transport of finite size particles. These questions have motivated a series of experiments trying to emphasize the actual role of the drag force by imposing this one as an unambiguous leading forcing term acting on a particle in a turbulent background. This is achieved by considering the constrained dynamics of towed particles in a turbulent environment. In the present work, we focus on the influence of particles inertia on its velocity and acceleration Lagrangian statistics and energy spectral density. Our results are consistent with a filtering scenario resulting from the viscous response time of an inertial particle whose dynamics is coupled to the surrounding fluid via strong contribution of drag.

  12. Channel Geometry and Flood Flows: Quantifying over-bank flow dynamics during high-flow events in North Carolina's floodplains

    Lovette, J. P.; Duncan, J. M.; Vimal, S.; Band, L. E.

    2015-12-01

    Natural riparian areas play numerous roles in the maintenance and improvement of stream water quality. Both restoration of riparian areas and improvement of hydrologic connectivity to the stream are often key goals of river restoration projects. These management actions are designed to improve nutrient removal by slowing and treating overland flow delivered from uplands and by storing, treating, and slowly releasing streamwater from overbank inundation during flood events. A major question is how effective this storage of overbank flow is at treating streamwater based on the cumulative time stream discharge at a downstream location has spent in shallower, slower overbank flow. The North Carolina Floodplain Mapping Program maintains a detailed statewide Flood Risk Information System (FRIS) using HEC-RAS modeling, lidar, and detailed surveyed river cross-sections. FRIS provides extensive information regarding channel geometry on approximately 39,000 stream reaches (a slightly coarser spatial resolution than the NHD+v2 dataset) with tens of cross-sections for each reach. We use this FRIS data to calculate volume and discharge from floodplain riparian areas separately from in-channel flow during overbank events. Preliminary results suggest that a small percentage of total annual discharge interacts with the full floodplain extent along a stream reach due to the infrequency of overbank flow events. However, with the significantly different physical characteristics of the riparian area when compared to the channel itself, this overbank flow can provide unique services to water quality. Our project aims to use this information in conjunction with data from the USGS SPARROW program to target non-point source hotspots of Nitrogen and Phosphorus addition and removal. By better understanding the flow dynamics within riparian areas during high flow events, riparian restoration projects can be carried out with improved efficacy.

  13. Understanding binding affinity : A combined isothermal titration calorimetry/molecular dynamics study of the binding of a series of hydrophobically modified benzamidinium chloride inhibitors to trypsin

    Talhout, Reinskje; Villa, Alessandra; Mark, AE; Engberts, JBFN

    2003-01-01

    The binding of a series of p-alkylbenzamidinium chloride inhibitors to the serine proteinase trypsin over a range of temperatures has been studied using isothermal titration (micro)calorimetry and molecular dynamics simulation techniques. The inhibitors have small structural variations at the para

  14. Characterization of binding and mobility of metals and xenobiotics in continuous flow and soil biosystems

    Sunovska, A.

    2016-01-01

    The main aim of the dissertation thesis was to contribute to development of analytical tools and approaches application in characterization of binding and mobility of heavy metals and organic compounds (xenobiotics) in continuous flow and soil biosystems. Within the solution of this aim, a wide range of analytical methods (gamma-spectrometry, UV-VIS spectrophotometry, AAS, X-ray fluorescence spectrometry, ion chromatography, and stripping volt-amperometry) and approaches (mathematical modelling - methods of nonlinear regression and in silico prediction modelling; chemometrics and statistical analysis of the data; single-step extraction methods, and lysimetry) were applied. In the first step of thesis solution, alternative sorbents of biological origin (biomass of microalgae, freshwater mosses, and waste biomass of hop) were obtained and physico-chemically characterized mainly in order to prediction of sorption capacities of Cd and synthetic dyes thioflavine T (TT), malachite green (MG) or methylene blue (MB) removal from single component or binary aqueous solutions and under conditions of batch or continuous flow systems. For these purposes, mathematical models of adsorption isotherms and models originated from chromatographic separation methods by application of methods of nonlinear regression analysis were used. In the second part of the work, methods of multivariate analysis in the evaluation of processes of synthetic dyes TT and MB binding in terms of the finding of relationships between sorption-desorption variables describing the stability of the bond and parameters defining the physic-chemical properties of river sediments and the environment of real or model waters were applied. In the last part of the work, a special laboratory lysimeter system was designed and applied within the soil biosystem defined by: soil additive (SA) derived from sewage sludge representing the source of microelements Zn and Cu <-> agriculturally used soil <-> soil solution <-> root

  15. Characterization of binding and mobility of metals and xenobiotics in continuous flow and soil biosystems

    Sunovska, A.

    2016-01-01

    The main aim of the dissertation thesis was to contribute to development of analytical tools and approaches application in characterization of binding and mobility of heavy metals and organic compounds (xenobiotics) in continuous flow and soil biosystems. Within the solution of this aim, a wide range of analytical methods (gamma-spectrometry, UV-VIS spectrophotometry, AAS, X-ray fluorescence spectrometry, ion chromatography, and stripping volt-amperometry) and approaches (mathematical modelling - methods of nonlinear regression and in silico prediction modelling; chemometrics and statistical analysis of the data; single-step extraction methods, and lysimetry) were applied. In the first step of thesis solution, alternative sorbents of biological origin (biomass of microalgae, freshwater mosses, and waste biomass of hop) were obtained and physico-chemically characterized mainly in order to prediction of sorption capacities of Cd and synthetic dyes thioflavine T (TT), malachite green (MG) or methylene blue (MB) removal from single component or binary aqueous solutions and under conditions of batch or continuous flow systems. For these purposes, mathematical models of adsorption isotherms and models originated from chromatographic separation methods by application of methods of nonlinear regression analysis were used. In the second part of the work, methods of multivariate analysis in the evaluation of processes of synthetic dyes TT and MB binding in terms of the finding of relationships between sorption-desorption variables describing the stability of the bond and parameters defining the physic-chemical properties of river sediments and the environment of real or model waters were applied. In the last part of the work, a special laboratory lysimeter system was designed and applied within the soil biosystem defined by: soil additive (SA) derived from sewage sludge representing the source of microelements Zn and Cu agriculturally used soil soil solution root system of

  16. Dynamics of GATA1 binding and expression response in a GATA1-induced erythroid differentiation system

    Deepti Jain

    2015-06-01

    Full Text Available During the maturation phase of mammalian erythroid differentiation, highly proliferative cells committed to the erythroid lineage undergo dramatic changes in morphology and function to produce circulating, enucleated erythrocytes. These changes are caused by equally dramatic alterations in gene expression, which in turn are driven by changes in the abundance and binding patterns of transcription factors such as GATA1. We have studied the dynamics of GATA1 binding by ChIP-seq and the global expression responses by RNA-seq in a GATA1-dependent mouse cell line model for erythroid maturation, in both cases examining seven progressive stages during differentiation. Analyses of these data should provide insights both into mechanisms of regulation (early versus late targets and the consequences in cell physiology (e.g., distinctive categories of genes regulated at progressive stages of differentiation. The data are deposited in the Gene Expression Omnibus, series GSE36029, GSE40522, GSE49847, and GSE51338.

  17. Dynamic Multi-Component Covalent Assembly for the Reversible Binding of Secondary Alcohols and Chirality Sensing

    You, Lei; Berman, Jeffrey S.; Anslyn, Eric V.

    2011-01-01

    Reversible covalent bonding is often employed for the creation of novel supramolecular structures, multi-component assemblies, and sensing ensembles. In spite of remarkable success of dynamic covalent systems, the reversible binding of a mono-alcohol with high strength is challenging. Here we show that a strategy of carbonyl activation and hemiaminal ether stabilization can be embodied in a four-component reversible assembly that creates a tetradentate ligand and incorporates secondary alcohols with exceptionally high affinity. Evidence is presented that the intermediate leading to binding and exchange of alcohols is an iminium ion. Further, to demonstrate the use of this assembly process we explored chirality sensing and enantiomeric excess determinations. An induced twist in the ligand by a chiral mono-ol results in large Cotton effects in the circular dichroism spectra indicative of the alcohol’s handedness. The strategy revealed in this study should prove broadly applicable for the incorporation of alcohols into supramolecular architecture construction. PMID:22109274

  18. Particle and Blood Cell Dynamics in Oscillatory Flows Final Report

    Restrepo, Juan M.

    2008-01-01

    Our aim has been to uncover fundamental aspects of the suspension and dislodgement of particles in wall-bounded oscillatory flows, in flows characterized by Reynolds numbers encompassing the situation found in rivers and near shores (and perhaps in some industrial processes). Our research tools are computational and our coverage of parameter space fairly broad. Computational means circumvent many complications that make the measurement of the dynamics of particles in a laboratory setting an impractical task, especially on the broad range of parameter space we plan to report upon. The impact of this work on the geophysical problem of sedimentation is boosted considerably by the fact that the proposed calculations can be considered ab-initio, in the sense that little to no modeling is done in generating dynamics of the particles and of the moving fluid: we use a three-dimensional Navier Stokes solver along with straightforward boundary conditions. Hence, to the extent that Navier Stokes is a model for an ideal incompressible isotropic Newtonian fluid, the calculations yield benchmark values for such things as the drag, buoyancy, and lift of particles, in a highly controlled environment. Our approach will be to make measurements of the lift, drag, and buoyancy of particles, by considering progressively more complex physical configurations and physics.

  19. Conformational dynamics and ligand binding in the multi-domain protein PDC109.

    Hyun Jin Kim

    2010-02-01

    Full Text Available PDC109 is a modular multi-domain protein with two fibronectin type II (Fn2 repeats joined by a linker. It plays a major role in bull sperm binding to the oviductal epithelium through its interactions with phosphorylcholines (PhCs, a head group of sperm cell membrane lipids. The crystal structure of the PDC109-PhC complex shows that each PhC binds to the corresponding Fn2 domain, while the two domains are on the same face of the protein. Long timescale explicit solvent molecular dynamics (MD simulations of PDC109, in the presence and absence of PhC, suggest that PhC binding strongly correlates with the relative orientation of choline-phospholipid binding sites of the two Fn2 domains; unless the two domains tightly bind PhCs, they tend to change their relative orientation by deforming the flexible linker. The effective PDC109-PhC association constant of 28 M(-1, estimated from their potential of mean force is consistent with the experimental result. Principal component analysis of the long timescale MD simulations was compared to the significantly less expensive normal mode analysis of minimized structures. The comparison indicates that difference between relative domain motions of PDC109 with bound and unbound PhC is captured by the first principal component in the principal component analysis as well as the three lowest normal modes in the normal mode analysis. The present study illustrates the use of detailed MD simulations to clarify the energetics of specific ligand-domain interactions revealed by a static crystallographic model, as well as their influence on relative domain motions in a multi-domain protein.

  20. POD- Mapping and analysis of hydroturbine exit flow dynamics

    Kjeldsen, Morten; Finstad, Pal Henrik

    2012-11-01

    Pairwise radial dynamic measurements of the swirling draft tube flow have been made at the 25 MW Svorka power plant in Surnadal operating at 48% load at 6 radial and 7 angular positions. The data is analyzed with traditional methods as well as with POD. The measurements were made in the turbine draft tube/exit flow in an axial measurement plane about 1200mm downstream the turbine runner. The draft tube diameter in the measurement plane is about 1300mm. The flow rate during measurements was close to 5.8m3/s. Two probes were used; both of length Le=700 mm and made of stainless steel with an outer diameter of Do=20 mm and inner diameter Di=4mm. At the end of each probe a full bridge cylindrical KULITE xcl152, 0-3.5, was mounted. 90 seconds samples at 10 kS/s were taken. The POD analysis largely follows that of Tutkun et al. (see e.g. AIAA J., 45,5,2008). The analysis shows that 26% of the pressure pulsation energy can be addressed to azimuthal mode 1. The work has been supported by Energy Norway.

  1. Stochastic Rotation Dynamics simulations of wetting multi-phase flows

    Hiller, Thomas; Sanchez de La Lama, Marta; Brinkmann, Martin

    2016-06-01

    Multi-color Stochastic Rotation Dynamics (SRDmc) has been introduced by Inoue et al. [1,2] as a particle based simulation method to study the flow of emulsion droplets in non-wetting microchannels. In this work, we extend the multi-color method to also account for different wetting conditions. This is achieved by assigning the color information not only to fluid particles but also to virtual wall particles that are required to enforce proper no-slip boundary conditions. To extend the scope of the original SRDmc algorithm to e.g. immiscible two-phase flow with viscosity contrast we implement an angular momentum conserving scheme (SRD+mc). We perform extensive benchmark simulations to show that a mono-phase SRDmc fluid exhibits bulk properties identical to a standard SRD fluid and that SRDmc fluids are applicable to a wide range of immiscible two-phase flows. To quantify the adhesion of a SRD+mc fluid in contact to the walls we measure the apparent contact angle from sessile droplets in mechanical equilibrium. For a further verification of our wettability implementation we compare the dewetting of a liquid film from a wetting stripe to experimental and numerical studies of interfacial morphologies on chemically structured surfaces.

  2. Free energy calculations on Transthyretin dissociation and ligand binding from Molecular Dynamics Simulations

    Sørensen, Jesper; Hamelberg, Donald; McCammon, J. Andrew

    experimental results have helped to explain this aberrant behavior of TTR, however, structural insights of the amyloidgenic process are still lacking. Therefore, we have used all-atom molecular dynamics simulation and free energy calculations to study the initial phase of this process. We have calculated......Many questions about the nature of aggregation and the proteins that are involved in these events are still left unanswered. One of the proteins that is known to form amyloids is Transthyretine (TTR), the secondary transporter of thyroxine and transporter of retinol-binding-protein. Several...

  3. Dynamics of the cross flow heat exchanger for heating purposes

    Mueller, K [Karlsruhe Univ. (TH) (Germany, F.R.). Inst. fuer Mess- und Regelungstechnik mit Maschinenlaboratorium

    1980-09-01

    A series of publications is available on the dynamic behaviour of heat exchangers (or heat transmitters, respectively), the subject of which is to deal with direct methods or with refined starting models for this general theme. The bridging between both these manners of advance remained as a problem. The author tried in his own investigation to solve the problem, and indeed by the selection of the correct starting model. He succeeded in this way, in that he removed conceptually a finned pipe from an arbitrary place of a heat exchanger and, furthermore, cut out from this particular pipe an arbitrary section. This section now does not stand alone for itself because the processes, which occur upstream of this section at the air-side and the water-side, are the input quantities of the section, which changes them due to its static and dynamic behaviour and emits them again as output quantities. The author, therefore, treats at first the dynamic behaviour of the section, which is represented in a signal flow diagram and which is used to derive approximate solutions from it. Furthermore, the author discusses the evident derivation of the total behaviour of heat exchangers.

  4. Dynamics of blood flow: twenty years of achievement

    Rosendorff, C.

    1988-01-01

    The physiology of blood circulation has evolved from the descriptive phenomenology of William Harvey's time to an interdisciplinary science, involving elements of fluid dynamics, vessel wall mechanics, electrophysiology, cell biology, biochemistry and molecular biology. Most of these new developments have occured during the lifetime of the South African Medical Research Council. Highlights of the research undertaken by the Council regarding circulatory physiology are given. In the 1960s the use of xenon-133 to study the flow of blood to the brain resulted in the first systematic description of cerebral blood flow and its control by sympathetic nerves. During the 1970s this technique was refined and the use of radioactive microspheres for the measurement of tissue blood flow was developed. Research concerning the control of blood vessels in the kidney was also carried out, and this showed that the sympathetic nerves control renal blood flow by releasing a local hormone called renin. The renal release of renin was later recognised as being important in the control of blood pressure. Another development was the discovery that vascular sensitivity to noradrenaline was increased in certain types of liver diseases. An analysis of the blood of patients with obstructive jaundice showed that the substance responsible for this noradrenaline effect was a combination of cholesterol and lipo-protein. This led to the theory that excessive cholesterol in the blood may be dangerous. In the late 1970s a shift in research emphasis to coronary artery physiology occurred and the 1980s saw research move into the area of cell biology

  5. Gas flow characteristics of a time modulated APPJ: the effect of gas heating on flow dynamics

    Zhang, S; Sobota, A; Van Veldhuizen, E M; Bruggeman, P J

    2015-01-01

    This work investigates the flow dynamics of a radio-frequency (RF) non-equilibrium argon atmospheric pressure plasma jet. The RF power is at a frequency of 50 Hz or 20 kHz. Combined flow pattern visualizations (obtained by shadowgraphy) and gas temperature distributions (obtained by Rayleigh scattering) are used to study the formation of transient vortex structures in initial flow field shortly after the plasma is switched on and off in the case of 50 Hz modulation. The transient vortex structures correlate well with observed temperature differences. Experimental results of the fast modulated (20 kHz) plasma jet that does not induce changes of the gas temperature are also presented. The latter result suggests that momentum transfer by ions does not have dominant effect on the flow pattern close to the tube. It is argued that the increased gas temperature and corresponding gas velocity increase at the tube exit due to the plasma heating increases the admixing of surrounding air and reduces the effective potential core length. With increasing plasma power a reduction of the effective potential core length is observed with a minimum length for 5.6 W after which the length extends again. Possible mechanisms related to viscosity effects and ionic momentum transfer are discussed. (paper)

  6. Membrane dynamics of γ-secretase provides a molecular basis for Aβ binding and processing

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2017-01-01

    and explicit dynamics relevant to substrate processing remain unknown. We report a modeled structure utilizing the optimal multi-template information available, including loops and missing side chains, account of maturation cleavage, and explicit all-atom molecular dynamics in the membrane. We observe three...... interactions and induces shorter residence time and by inference releases Aβ peptides of longer lengths. Our simulations thus provide a molecular basis for substrate processing and changes in the Aβ42/Aβ40 ratio. Accordingly, selective binding to protect the semi-open “innocent” conformation provides......γ-secretase produces β-amyloid (Aβ) within its presenilin (PS1) subunit, mutations in which cause Alzheimer’s disease, and current therapies thus seek to modulate its activity. While the general structure is known from recent electron microscopy studies, direct loop- and membrane-interactions...

  7. A molecular dynamics investigation of CDK8/CycC and ligand binding: conformational flexibility and implication in drug discovery

    Cholko, Timothy; Chen, Wei; Tang, Zhiye; Chang, Chia-en A.

    2018-05-01

    Abnormal activity of cyclin-dependent kinase 8 (CDK8) along with its partner protein cyclin C (CycC) is a common feature of many diseases including colorectal cancer. Using molecular dynamics (MD) simulations, this study determined the dynamics of the CDK8-CycC system and we obtained detailed breakdowns of binding energy contributions for four type-I and five type-II CDK8 inhibitors. We revealed system motions and conformational changes that will affect ligand binding, confirmed the essentialness of CycC for inclusion in future computational studies, and provide guidance in development of CDK8 binders. We employed unbiased all-atom MD simulations for 500 ns on twelve CDK8-CycC systems, including apoproteins and protein-ligand complexes, then performed principal component analysis (PCA) and measured the RMSF of key regions to identify protein dynamics. Binding pocket volume analysis identified conformational changes that accompany ligand binding. Next, H-bond analysis, residue-wise interaction calculations, and MM/PBSA were performed to characterize protein-ligand interactions and find the binding energy. We discovered that CycC is vital for maintaining a proper conformation of CDK8 to facilitate ligand binding and that the system exhibits motion that should be carefully considered in future computational work. Surprisingly, we found that motion of the activation loop did not affect ligand binding. Type-I and type-II ligand binding is driven by van der Waals interactions, but electrostatic energy and entropic penalties affect type-II binding as well. Binding of both ligand types affects protein flexibility. Based on this we provide suggestions for development of tighter-binding CDK8 inhibitors and offer insight that can aid future computational studies.

  8. Field flow fractionation for assessing neonatal Fc receptor and Fcγ receptor binding to monoclonal antibodies in solution.

    Pollastrini, Joey; Dillon, Thomas M; Bondarenko, Pavel; Chou, Robert Y-T

    2011-07-01

    Analysis of the strength and stoichiometry of immunoglobulin G (IgG) binding to neonatal Fc receptor (FcRn) and Fcγ receptor (FcγR) is important for evaluating the pharmacokinetics and effector functions of therapeutic monoclonal antibody (mAb) products, respectively. The current standard for assessing FcγR and FcRn binding is composed of cell-based and surface plasmon resonance (SPR) assays. In this work, asymmetrical flow field flow fractionation (AF4) was evaluated to establish the true stoichiometry of IgG binding in solution. AF4 and liquid chromatography-mass spectrometry (LC-MS) were applied to directly observe IgG/FcγR and IgG/FcRn complexes, which were not observed using nonequilibrium size exclusion chromatography (SEC) analysis. Human serum albumin (HSA), an abundant component of human blood and capable of binding FcRn, was studied in combination with FcRn and IgG. AF4 demonstrated that the majority of large complexes of IgG/FcRn/HSA were at an approximate 1:2:1 molar ratio. In addition, affinity measurements of the complex were performed in the sub-micromolar affinity range. A significant decrease in binding was detected for IgG molecules with increased oxidation in the Fc region. AF4 was useful in detecting weak binding between full-length IgG/Fc fragments and Fc receptors and the effect of chemical modifications on binding. AF4 is a useful technique in the assessment of mAb product quality attributes. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Molecular Dynamics Pinpoint the Global Fluorine Effect in Balanoid Binding to PKCε and PKA.

    Hardianto, Ari; Liu, Fei; Ranganathan, Shoba

    2018-02-26

    (-)-Balanol is an adenosine triphosphate mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is known as a tumor promoter, PKC isozymes can be tumor promoters or suppressors. In particular, PKCε is frequently involved in tumorigenesis and a potential target for anticancer drugs. We recently reported that stereospecific fluorination of balanol yielded a balanoid with enhanced selectivity for PKCε over other PKC isozymes and PKA, although the global fluorine effect behind the selectivity enhancement is not fully understood. Interestingly, in contrast to PKA, PKCε is more sensitive to this fluorine effect. Here we investigate the global fluorine effect on the different binding responses of PKCε and PKA to balanoids using molecular dynamics (MD) simulations. For the first time to the best of our knowledge, we found that a structurally equivalent residue in each kinase, Thr184 in PKA and Ala549 in PKCε, is essential for the different binding responses. Furthermore, the study revealed that the invariant Lys, Lys73 in PKA and Lys437 in PKCε, already known to have a crucial role in the catalytic activity of kinases, serves as the main anchor for balanol binding. Overall, while Thr184 in PKA attenuates the effect of fluorination, Ala549 permits remote response of PKCε to fluorine substitution, with implications for rational design of future balanol-based PKCε inhibitors.

  10. Preliminary Molecular Dynamic Simulations of the Estrogen Receptor Alpha Ligand Binding Domain from Antagonist to Apo

    Adrian E. Roitberg

    2008-06-01

    Full Text Available Estrogen receptors (ER are known as nuclear receptors. They exist in the cytoplasm of human cells and serves as a DNA binding transcription factor that regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding. The human estrogen receptor comes in two forms, alpha and beta. This work focuses on the alpha form of the estrogen receptor. The ERα is found in breast cancer cells, ovarian stroma cells, endometrium, and the hypothalamus. It has been suggested that exposure to DDE, a metabolite of DDT, and other pesticides causes conformational changes in the estrogen receptor. Before examining these factors, this work examines the protein unfolding from the antagonist form found in the 3ERT PDB crystal structure. The 3ERT PDB crystal structure has the estrogen receptor bound to the cancer drug 4-hydroxytamoxifen. The 4-hydroxytamoxifen ligand was extracted before the simulation, resulting in new conformational freedom due to absence of van der Waals contacts between the ligand and the receptor. The conformational changes that result expose the binding clef of the co peptide beside Helix 12 of the receptor forming an apo conformation. Two key conformations in the loops at either end of the H12 are produced resulting in the antagonist to apo conformation transformation. The results were produced over a 42ns Molecular Dynamics simulation using the AMBER FF99SB force field.

  11. Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells.

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

    2015-10-28

    Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies suggested that fisetin binds to β-tubulin with superior affinity compared to paclitaxel. Fisetin treatment of human prostate cancer cells resulted in robust up-regulation of microtubule associated proteins (MAP)-2 and -4. In addition, fisetin treated cells were enriched in α-tubulin acetylation, an indication of stabilization of microtubules. Fisetin significantly inhibited PCa cell proliferation, migration, and invasion. Nudc, a protein associated with microtubule motor dynein/dynactin complex that regulates microtubule dynamics, was inhibited with fisetin treatment. Further, fisetin treatment of a P-glycoprotein overexpressing multidrug-resistant cancer cell line NCI/ADR-RES inhibited the viability and colony formation. Our results offer in vitro proof-of-concept for fisetin as a microtubule targeting agent. We suggest that fisetin could be developed as an adjuvant for treatment of prostate and other cancer types. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Unique structure and dynamics of the EphA5 ligand binding domain mediate its binding specificity as revealed by X-ray crystallography, NMR and MD simulations.

    Xuelu Huan

    Full Text Available The 16 EphA and EphB receptors represent the largest family of receptor tyrosine kinases, and their interactions with 9 ephrin-A and ephrin-B ligands initiate bidirectional signals controlling many physiological and pathological processes. Most interactions occur between receptor and ephrins of the same class, and only EphA4 can bind all A and B ephrins. To understand the structural and dynamic principles that enable Eph receptors to utilize the same jellyroll β-sandwich fold to bind ephrins, the VAPB-MSP domain, peptides and small molecules, we have used crystallography, NMR and molecular dynamics (MD simulations to determine the first structure and dynamics of the EphA5 ligand-binding domain (LBD, which only binds ephrin-A ligands. Unexpectedly, despite being unbound, the high affinity ephrin-binding pocket of EphA5 resembles that of other Eph receptors bound to ephrins, with a helical conformation over the J-K loop and an open pocket. The openness of the pocket is further supported by NMR hydrogen/deuterium exchange data and MD simulations. Additionally, the EphA5 LBD undergoes significant picosecond-nanosecond conformational exchanges over the loops, as revealed by NMR and MD simulations, but lacks global conformational exchanges on the microsecond-millisecond time scale. This is markedly different from the EphA4 LBD, which shares 74% sequence identity and 87% homology. Consequently, the unbound EphA5 LBD appears to comprise an ensemble of open conformations that have only small variations over the loops and appear ready to bind ephrin-A ligands. These findings show how two proteins with high sequence homology and structural similarity are still able to achieve distinctive binding specificities through different dynamics, which may represent a general mechanism whereby the same protein fold can serve for different functions. Our findings also suggest that a promising strategy to design agonists/antagonists with high affinity and selectivity

  13. Nuclear receptor ligand-binding domains: reduction of helix H12 dynamics to favour crystallization

    Nahoum, Virginie; Lipski, Alexandra; Quillard, Fabien; Guichou, Jean-François [INSERM, U554, 34090 Montpellier (France); Université de Montpellier, CNRS, UMR5048, Centre de Biochimie Structurale (CBS), 34090 Montpellier (France); Boublik, Yvan [CNRS, UMR5237, Centre de Recherche de Biochimie Macromoléculaire (CRBM), 34293 Montpellier (France); Pérez, Efrèn [Universidade de Vigo, Departamento de Quimica Organica, Facultad de Química, 36310 Vigo (Spain); Germain, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), BP 10142, 67404 Illkirch CEDEX (France); Lera, Angel R. de [Universidade de Vigo, Departamento de Quimica Organica, Facultad de Química, 36310 Vigo (Spain); Bourguet, William, E-mail: bourguet@cbs.cnrs.fr [INSERM, U554, 34090 Montpellier (France); Université de Montpellier, CNRS, UMR5048, Centre de Biochimie Structurale (CBS), 34090 Montpellier (France)

    2008-07-01

    Attempts have been made to crystallize the ligand-binding domain of the human retinoid X receptor in complex with a variety of newly synthesized ligands. An inverse correlation was observed between the ‘crystallizability’ and the structural dynamics of the various receptor–ligand complexes. Crystallization trials of the human retinoid X receptor α ligand-binding domain (RXRα LBD) in complex with various ligands have been carried out. Using fluorescence anisotropy, it has been found that when compared with agonists these small-molecule effectors enhance the dynamics of the RXRα LBD C-terminal helix H12. In some cases, the mobility of this helix could be dramatically reduced by the addition of a 13-residue co-activator fragment (CoA). In keeping with these observations, crystals have been obtained of the corresponding ternary RXRα LBD–ligand–CoA complexes. In contrast, attempts to crystallize complexes with a highly mobile H12 remained unsuccessful. These experimental observations substantiate the previously recognized role of co-regulator fragments in facilitating the crystallization of nuclear receptor LBDs.

  14. Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.

    Zeynab Mohammad Hosseini Naveh

    Full Text Available Despite the large number of studies available on nicotinic acetylcholine receptors, a complete account of the mechanistic aspects of their gating transition in response to ligand binding still remains elusive. As a first step toward dissecting the transition mechanism by accelerated sampling techniques, we study the ligand-induced conformational changes of the acetylcholine binding protein (AChBP, a widely accepted model for the full receptor extracellular domain. Using unbiased Molecular Dynamics (MD and Temperature Accelerated Molecular Dynamics (TAMD simulations we investigate the AChBP transition between the apo and the agonist-bound state. In long standard MD simulations, both conformations of the native protein are stable, while the agonist-bound structure evolves toward the apo one if the orientation of few key sidechains in the orthosteric cavity is modified. Conversely, TAMD simulations initiated from the native conformations are able to produce the spontaneous transition. With respect to the modified conformations, TAMD accelerates the transition by at least a factor 10. The analysis of some specific residue-residue interactions points out that the transition mechanism is based on the disruption/formation of few key hydrogen bonds. Finally, while early events of ligand dissociation are observed already in standard MD, TAMD accelerates the ligand detachment and, at the highest TAMD effective temperature, it is able to produce a complete dissociation path in one AChBP subunit.

  15. Development of a dynamic flow imaging phantom for dynamic contrast-enhanced CT

    Driscoll, B.; Keller, H.; Coolens, C.

    2011-01-01

    Purpose: Dynamic contrast enhanced CT (DCE-CT) studies with modeling of blood flow and tissue perfusion are becoming more prevalent in the clinic, with advances in wide volume CT scanners allowing the imaging of an entire organ with sub-second image frequency and sub-millimeter accuracy. Wide-spread implementation of perfusion DCE-CT, however, is pending fundamental validation of the quantitative parameters that result from dynamic contrast imaging and perfusion modeling. Therefore, the goal of this work was to design and construct a novel dynamic flow imaging phantom capable of producing typical clinical time-attenuation curves (TACs) with the purpose of developing a framework for the quantification and validation of DCE-CT measurements and kinetic modeling under realistic flow conditions. Methods: The phantom is based on a simple two-compartment model and was printed using a 3D printer. Initial analysis of the phantom involved simple flow measurements and progressed to DCE-CT experiments in order to test the phantoms range and reproducibility. The phantom was then utilized to generate realistic input TACs. A phantom prediction model was developed to compute the input and output TACs based on a given set of five experimental (control) parameters: pump flow rate, injection pump flow rate, injection contrast concentration, and both control valve positions. The prediction model is then inversely applied to determine the control parameters necessary to generate a set of desired input and output TACs. A protocol was developed and performed using the phantom to investigate image noise, partial volume effects and CT number accuracy under realistic flow conditionsResults: This phantom and its surrounding flow system are capable of creating a wide range of physiologically relevant TACs, which are reproducible with minimal error between experiments (σ/μ 2 ) for the input function between 0.95 and 0.98, while the maximum enhancement differed by no more than 3.3%. The

  16. New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

    Hugo de Almeida

    Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

  17. Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding

    Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka, E-mail: kinjo@sci.hokudai.ac.jp

    2015-07-31

    Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS{sup SV40}) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS{sup SV40} in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS{sup SV40} formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS{sup SV40} likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS{sup SV40} can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. - Highlights: • Nuclear localization signal-tagged GFP (GFP-NLS) showed clear nuclear localization. • The GFP-NLS dynamically localized not only in the nucleoplasm, but also to the nucleolus. • The nuclear localization of GFP-NLS results from transient oligomerization mediated via RNA binding. • Our NLS-tagging procedure is ideal for use in artificial sequestration of proteins in the nucleus.

  18. Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding

    Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka

    2015-01-01

    Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS SV40 ) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS SV40 in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS SV40 formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS SV40 likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS SV40 can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. - Highlights: • Nuclear localization signal-tagged GFP (GFP-NLS) showed clear nuclear localization. • The GFP-NLS dynamically localized not only in the nucleoplasm, but also to the nucleolus. • The nuclear localization of GFP-NLS results from transient oligomerization mediated via RNA binding. • Our NLS-tagging procedure is ideal for use in artificial sequestration of proteins in the nucleus

  19. Dynamics of vortex interactions in two-dimensional flows

    Juul Rasmussen, J.; Nielsen, A.H.; Naulin, V.

    2002-01-01

    The dynamics and interaction of like-signed vortex structures in two dimensional flows are investigated by means of direct numerical solutions of the two-dimensional Navier-Stokes equations. Two vortices with distributed vorticity merge when their distance relative to their radius, d/R-0l. is below...... a critical value, a(c). Using the Weiss-field, a(c) is estimated for vortex patches. Introducing an effective radius for vortices with distributed vorticity, we find that 3.3 ... is effectively producing small scale structures and the relation to the enstrophy "cascade" in developed 2D turbulence is discussed. The influence of finite viscosity on the merging is also investigated. Additionally, we examine vortex interactions on a finite domain, and discuss the results in connection...

  20. The unsaturated flow in porous media with dynamic capillary pressure

    Milišić, Josipa-Pina

    2018-05-01

    In this paper we consider a degenerate pseudoparabolic equation for the wetting saturation of an unsaturated two-phase flow in porous media with dynamic capillary pressure-saturation relationship where the relaxation parameter depends on the saturation. Following the approach given in [13] the existence of a weak solution is proved using Galerkin approximation and regularization techniques. A priori estimates needed for passing to the limit when the regularization parameter goes to zero are obtained by using appropriate test-functions, motivated by the fact that considered PDE allows a natural generalization of the classical Kullback entropy. Finally, a special care was given in obtaining an estimate of the mixed-derivative term by combining the information from the capillary pressure with the obtained a priori estimates on the saturation.

  1. The Dynamics of the Impact of Past Performance on Mutual Fund Flows

    Goriaev, A.P.; Nijman, T.E.; Werker, B.J.M.

    2002-01-01

    This study reconsiders the determinants of flows into US growth funds, focusing in particular on the dynamics of the impact of past performance on flows.We model the flow-performance relationship at the monthly frequency, allowing for dependence of the sensitivity of flows to past performance on

  2. A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

    Polireddy, Kishore; Khan, Mohiuddin Md Taimur; Chavan, Hemantkumar; Young, Susan; Ma, Xiaochao; Waller, Anna; Garcia, Matthew; Perez, Dominique; Chavez, Stephanie; Strouse, Jacob J; Haynes, Mark K; Bologa, Cristian G; Oprea, Tudor I; Tegos, George P; Sklar, Larry A; Krishnamurthy, Partha

    2012-01-01

    ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

  3. A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

    Kishore Polireddy

    Full Text Available ABCB6 is a member of the adenosine triphosphate (ATP-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS, can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

  4. Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X.

    Okuwaki, Mitsuru; Abe, Mayumi; Hisaoka, Miharu; Nagata, Kyosuke

    2016-11-01

    Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Dynamic response of piping system subject to flow acoustic excitation

    Wang, T.; Sun, Y.S.

    1988-01-01

    Through the use of a theoretically derived and test data-calibrated forcing function, the dynamic response of a piping system subject to flow-acoustic induced vibration is analyzed. It is shown that the piping behavior can be predicted when consideration is given to both the wall flexural vibration and the piping system vibration. Piping responded as a system to the transversal excitation due to the swirling motion of the fluid flow, as well as flexurally to the high-frequency acoustic excitations. The transverse piping system response was calculated using a lumped mass piping model. The piping model has more stringent requirements than its counterpart for waterhammer and seismic modeling due to the shorter spiral wavelength and higher frequency of the forcing function. Proper modeling ensured that both the moment stress caused by system excitation and the local stress induced by the support reaction load were properly accounted for. Flexural vibration not only poses a threat to nipples and branch connections, but also contributes substantially to the resultant total stress experienced by the pipe. The forcing function approach has the advantage that the critical locations on the piping system can be identified by means of analysis, facilitating surveillance and inspection, as well as fatigue evaluation

  6. Dynamic interaction between myocardial contraction and coronary flow.

    Beyar, R; Sideman, S

    1997-01-01

    Phasic coronary flow is determined by the dynamic interaction between central hemodynamics and myocardial and ventricular mechanics. Various models, including the waterfall, intramyocardial pump and myocardial structural models, have been proposed for the coronary circulation. Concepts such as intramyocardial pressure, local elastance and others have been proposed to help explain the coronary compression by the myocardium. Yet some questions remain unresolved, and a new model has recently been proposed, linking a muscle collagen fibrous model to a physiologically based coronary model, and accounting for transport of fluids across the capillaries and lymphatic flow between the interstitial space and the venous system. One of the unique features of this model is that the intramyocardial pressure (IMP) in the interstitial space is calculated from the balance of forces and fluid transport in the system, and is therefore dependent on the coronary pressure conditions, the myocardial function and the transport properties of the system. The model predicts a wide range of experimentally observed phenomena associated with coronary compression.

  7. Dynamic evolution process of turbulent channel flow after opposition control

    Ge, Mingwei; Tian, De; Yongqian, Liu, E-mail: gmwncepu@163.com [State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources (North China Electric Power University), Beijing102206 (China)

    2017-02-15

    Dynamic evolution of turbulent channel flow after application of opposition control (OC), together with the mechanism of drag reduction, is studied through direct numerical simulation (DNS). In the simulation, the pressure gradient is kept constant, and the flow rate increases due to drag reduction. In the transport of mean kinetic energy (MKE), one part of the energy from the external pressure is dissipated by the mean shear, and the other part is transported to the turbulent kinetic energy (TKE) through a TKE production term (TKP). It is found that the increase of MKE is mainly induced by the reduction of TKP that is directly affected by OC. Further analysis shows that the suppression of the redistribution term of TKE in the wall normal direction plays a key role in drag reduction, which represses the wall normal velocity fluctuation and then reduces TKP through the attenuation of its main production term. When OC is suddenly applied, an acute imbalance of energy in space is induced by the wall blowing and suction. Both the skin-friction and TKP terms exhibit a transient growth in the initial phase of OC, which can be attributed to the local effect of 〈 v ′ v ′〉 and 〈− u ′ v ′〉 in the viscous sublayer. (paper)

  8. Neural network modeling of chaotic dynamics in nuclear reactor flows

    Welstead, S.T.

    1992-01-01

    Neural networks have many scientific applications in areas such as pattern classification and time series prediction. The universal approximation property of these networks, however, can also be exploited to provide researchers with tool for modeling observed nonlinear phenomena. It has been shown that multilayer feed forward networks can capture important global nonlinear properties, such as chaotic dynamics, merely by training the network on a finite set of observed data. The network itself then provides a model of the process that generated the data. Characterizations such as the existence and general shape of a strange attractor and the sign of the largest Lyapunov exponent can then be extracted from the neural network model. In this paper, the author applies this idea to data generated from a nonlinear process that is representative of convective flows that can arise in nuclear reactor applications. Such flows play a role in forced convection heat removal from pressurized water reactors and boiling water reactors, and decay heat removal from liquid-metal-cooled reactors, either by natural convection or by thermosyphons

  9. Pulsatility role in cylinder flow dynamics at low Reynolds number

    Qamar, Adnan

    2012-01-01

    We present dynamics of pulsatile flow past a stationary cylinder characterized by three non-dimensional parameters: the Reynolds number (Re), non-dimensional amplitude (A) of the pulsatile flow velocity, and Keulegan-Carpenter number (KC = Uo/Dωc). This work is motivated by the development of total artificial lungs (TAL) device, which is envisioned to provide ambulatory support to patients. Results are presented for 0.2 ≤ A ≤ 0.6 and 0.57 ≤ KC ≤ 2 at Re = 5 and 10, which correspond to the operating range of TAL. Two distinct fluid regimes are identified. In both regimes, the size of the separated zone is much greater than the uniform flow case, the onset of separation is function of KC, and the separation vortex collapses rapidly during the last fraction of the pulsatile cycle. The vortex size is independent of KC, but with an exponential dependency on A. In regime I, the separation point remains attached to the cylinder surface. In regime II, the separation point migrates upstream of the cylinder. Two distinct vortex collapse mechanisms are observed. For A < 0.4 and all KC and Re values, collapse occurs on the cylinder surface, whereas for A > 0.4 the separation vortex detaches from the cylinder surface and collapses at a certain distance downstream of the cylinder. The average drag coefficient is found to be independent of A and KC, and depends only on Re. However, for A > 0.4, for a fraction of the pulsatile cycle, the instantaneous drag coefficient is negative indicating a thrust production. © 2012 American Institute of Physics.

  10. Dynamic cycling in atrial size and flow during obstructive apnoea.

    Pressman, Gregg S; Cepeda-Valery, Beatriz; Codolosa, Nicolas; Orban, Marek; Samuel, Solomon P; Somers, Virend K

    2016-01-01

    Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease. However, acute cardiovascular effects of repetitive airway obstruction are poorly understood. While past research used a sustained Mueller manoeuver to simulate OSA we employed a series of gasping efforts to better simulate true obstructive apnoeas. This report describes acute changes in cardiac anatomy and flow related to sudden changes in intrathoracic pressure. 26 healthy, normal weight participants performed 5-6 gasping efforts (target intrathoracic pressure -40 mm Hg) while undergoing Doppler echocardiography. 14 participants had sufficient echocardiographic images to allow comparison of atrial areas during the manoeuver with baseline measurements. Mitral and tricuspid E-wave and A-wave velocities postmanoeuver were compared with baseline in all participants. Average atrial areas changed little during the manoeuver, but variance in both atrial areas was significantly greater than baseline. Further, an inverse relationship was noted with left atrial collapse and right atrial enlargement at onset of inspiratory effort. Significant inverse changes were noted in Doppler flow when comparing the first beat postmanoeuver (pMM1) with baseline. Mitral E-wave velocity increased 9.1 cm/s while tricuspid E-wave velocity decreased 7.0 cm/s; by the eighth beat postmanoeuver (pMM8) values were not different from baseline. Mitral and tricuspid A-wave velocities were not different from baseline at pMM1, but both were significantly higher by pMM8. Repetitive obstructive apnoeas produce dynamic, inverse changes in atrial size and Doppler flow across the atrioventricular valves. These observations have important implications for understanding the pathophysiology of OSA.

  11. Modeling self-consistent multi-class dynamic traffic flow

    Cho, Hsun-Jung; Lo, Shih-Ching

    2002-09-01

    In this study, we present a systematic self-consistent multiclass multilane traffic model derived from the vehicular Boltzmann equation and the traffic dispersion model. The multilane domain is considered as a two-dimensional space and the interaction among vehicles in the domain is described by a dispersion model. The reason we consider a multilane domain as a two-dimensional space is that the driving behavior of road users may not be restricted by lanes, especially motorcyclists. The dispersion model, which is a nonlinear Poisson equation, is derived from the car-following theory and the equilibrium assumption. Under the concept that all kinds of users share the finite section, the density is distributed on a road by the dispersion model. In addition, the dynamic evolution of the traffic flow is determined by the systematic gas-kinetic model derived from the Boltzmann equation. Multiplying Boltzmann equation by the zeroth, first- and second-order moment functions, integrating both side of the equation and using chain rules, we can derive continuity, motion and variance equation, respectively. However, the second-order moment function, which is the square of the individual velocity, is employed by previous researches does not have physical meaning in traffic flow. Although the second-order expansion results in the velocity variance equation, additional terms may be generated. The velocity variance equation we propose is derived from multiplying Boltzmann equation by the individual velocity variance. It modifies the previous model and presents a new gas-kinetic traffic flow model. By coupling the gas-kinetic model and the dispersion model, a self-consistent system is presented.

  12. Flow Equation Approach to the Statistics of Nonlinear Dynamical Systems

    Marston, J. B.; Hastings, M. B.

    2005-03-01

    The probability distribution function of non-linear dynamical systems is governed by a linear framework that resembles quantum many-body theory, in which stochastic forcing and/or averaging over initial conditions play the role of non-zero . Besides the well-known Fokker-Planck approach, there is a related Hopf functional methodootnotetextUriel Frisch, Turbulence: The Legacy of A. N. Kolmogorov (Cambridge University Press, 1995) chapter 9.5.; in both formalisms, zero modes of linear operators describe the stationary non-equilibrium statistics. To access the statistics, we investigate the method of continuous unitary transformationsootnotetextS. D. Glazek and K. G. Wilson, Phys. Rev. D 48, 5863 (1993); Phys. Rev. D 49, 4214 (1994). (also known as the flow equation approachootnotetextF. Wegner, Ann. Phys. 3, 77 (1994).), suitably generalized to the diagonalization of non-Hermitian matrices. Comparison to the more traditional cumulant expansion method is illustrated with low-dimensional attractors. The treatment of high-dimensional dynamical systems is also discussed.

  13. Modeling the Structure and Effectiveness of Intelligence Organizations: Dynamic Information Flow Simulation

    Behrman, Robert; Carley, Kathleen

    2003-01-01

    This paper describes the Dynamic Information Flow Simulation (DIFS), an abstract model for analyzing the structure and function of intelligence support organizations and the activities of entities within...

  14. Flow Cytometry-Based Bead-Binding Assay for Measuring Receptor Ligand Specificity

    Sprokholt, Joris K.; Hertoghs, Nina; Geijtenbeek, Teunis B. H.

    2016-01-01

    In this chapter we describe a fluorescent bead-binding assay, which is an efficient and feasible method to measure interaction between ligands and receptors on cells. In principle, any ligand can be coated on fluorescent beads either directly or via antibodies. Binding between ligand-coated beads

  15. Semiquantifying regional cerebral blood flow by dynamic CT scanning

    Takeuchi, Totaro; Kasahara, Eishi; Takahashi, Eriko; Kojima, Seiichi; Ogawa, Haruhiko; Suzuki, Keiko; Miyamae, Tatsuya; Yamazaki, Setsuo.

    1990-01-01

    The study was undertaken to evaluate the semi-quantitative significance of the absolute value obtained by calculating the regional cerebral blood flow index (rCBFI) from dynamic CT in comparison with SPECT. rCBFI was calculated from mean transit time (MTT) and blood capacity index (BCI) obtained by rapidly infusing 50 ml of Omnipurk into the elbow vein by the use of Hitachi's W-600. [rCBFI=BCI/MTT unit/sec (U/S)] measurment of the rCBF by SPECT was made according to the semi-quantitative method by Matsuda et al. by the use of SHIMADZU's improved type HEADTOME SET-050 with rapid infusion of 123 I-IMP in 3.5 m Ci from the elbow vein. Patients in whom no abnormality was observed in the cardiopulmonary function were enrolled as subjects. The rCBFI in each intracranial site was calculated from dynamic CT in 10 normal adults (aged 35-60, averaging 46.7) as subjects and compared with the rCBF obtained from SPECT in the same cases and same site. Comparative investigation was made similarly between rCBFI and rCBF regarding 10 patients with tracranial diseases (age 29-65, averaging 51.2). The mean rCBFIs in the normal adults obtained from dynamic CT were 1.15±0.18 U/S in the frontal lobar cortex, 1.28±0.19 U/S in the temporal lobar cortex, 1.43±0.1 U/S in the occipital lobar cortex, 1.27±0.2 U/S in the basal ganglia region and 0.43±0.1 U/S in the white matter. On the other hand, the mean rCBFs by SPECT were 47.36±3.93 ml/100 g/min, 55.19±2.22 ml/100 g/min, 61.92±5.42 ml/100 g/min, 54.38±3.51 ml/100 g/min and 38.68±6.18 ml/100 g/min, respectively. Positive correlation was observed between rCBFIs and rCBFs of 10 normal adults and 10 patients with intracranial disease, totalling 20 cases (r=0.79, P<0.005). The rCBFI by dynamic CT has a correlation with the rCBF by SPECT, suggesting the possibility of its evaluation as an absolute value, though semi-quantitatively. (author)

  16. The Src SH2 domain interacts dynamically with the focal adhesion kinase binding site as demonstrated by paramagnetic NMR spectroscopy.

    Lindfors, Hanna E; Drijfhout, Jan Wouter; Ubbink, Marcellus

    2012-06-01

    The interaction between the tyrosine kinases Src and focal adhesion kinase (FAK) is a key step in signaling processes from focal adhesions. The phosphorylated tyrosine residue 397 in FAK is able to bind the Src SH2 domain. To establish the extent of the FAK binding motif, the binding affinity of the SH2 domain for phosphorylated and unphosphorylated FAK-derived peptides of increasing length was determined and compared with that of the internal Src SH2 binding site. It is shown that the FAK peptides have higher affinity than the internal binding site and that seven negative residues adjacent to the core SH2 binding motif increase the binding constant 30-fold. A rigid spin-label incorporated in the FAK peptides was used to establish on the basis of paramagnetic relaxation enhancement whether the peptide-protein complex is well defined. A large spread of the paramagnetic effects on the surface of the SH2 domain suggests that the peptide-protein complex exhibits dynamics, despite the high affinity of the peptide. The strong electrostatic interaction between the positive side of the SH2 domain and the negative peptide results in a high affinity but may also favor a dynamic interaction. Copyright © 2012 Wiley Periodicals, Inc.

  17. Evaluation of steady flow torques and pressure losses in a rotary flow control valve by means of computational fluid dynamics

    Okhotnikov, Ivan; Noroozi, Siamak; Sewell, Philip; Godfrey, Philip

    2017-01-01

    Highlights: • A novel design of a rotary flow control valve driven by a stepper motor is proposed. • The intended use of the valve in the high flow rate independent metering hydraulic system is suggested. • Pressure drops, steady flow torques of the valve for various flow rates and orifice openings are studied by means of computational fluid dynamics. • The discharge coefficient and flow jet angles dependencies on the orifice opening are obtained. • A design method to decrease the flow forces without reducing the flow rate in single-staged valves is demonstrated. - Abstract: In this paper, a novel design of a rotary hydraulic flow control valve has been presented for high flow rate fluid power systems. High flow rates in these systems account for substantial flow forces acting on the throttling elements of the valves and cause the application of mechanically sophisticated multi-staged servo valves for flow regulation. The suggested design enables utilisation of single-stage valves in power hydraulics operating at high flow rates regimes. A spool driver and auxiliary mechanisms of the proposed valve design were discussed and selection criteria were suggested. Analytical expressions for metering characteristics as well as steady flow torques have been derived. Computational fluid dynamics (CFD) analysis of steady state flow regimes was conducted to evaluate the hydraulic behaviour of the proposed valve. This study represents a special case of an independent metering concept applied to the design of power hydraulic systems with direct proportional valve control operating at flow rates above 150 litres per minute. The result gained using parametric CFD simulations predicted the induced torque and the pressure drops due to a steady flow. Magnitudes of these values prove that by minimising the number of spool's mobile metering surfaces it is possible to reduce the flow-generated forces in the new generation of hydraulic valves proposed in this study

  18. Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

    Di Palma, Francesco; Tramontano, Anna

    2017-01-01

    The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.

  19. Tight-binding molecular dynamics simulation of charge state effects in semiconductors

    Khakimov, Z M; Sulaymonov, N T; Kiv, A E; Levin, A A

    2002-01-01

    New model of Si-H bond dissociation has been proposed and tested in the cluster Si sub 1 sub 0 H sub 1 sub 6 by the simulation approach that combines classical molecular dynamics method and the self-consistent tight-binding electronic and total energy calculation one. It is shown that the monohydride Si-H bond is unstable with respect to formation of silicon dangling bond and bend bridge Si-H-Si bond when this cluster traps the single positive charge. In this case hydrogen atom migrates rather rotating around Si-Si bond than crossing the center of this bond (the bond-centered position). The model can be useful for understanding hydrogen related phenomena at surfaces, interfaces, internal voids of various hydrogenated silicon systems: electronic devices, silicon solar cells, and nanocrystalline and porous silicon. (author)

  20. Dynamics behind affinity maturation of an anti-HCMV antibody family influencing antigen binding

    Di Palma, Francesco

    2017-08-03

    The investigation of antibody affinity maturation and its effects on antigen binding is important with respect to understanding the regulation of the immune response. To shed light on this crucial process, we analyzed two Igs neutralizing the human cytomegalovirus: the primary germline antibody M2J1 and its related mature antibody 8F9. Both antibodies target the AD-2S1 epitope of the gB envelope protein and are considered to establish similar interactions with the cognate antigen. We used molecular dynamics simulations to understand the effect of mutations on the antibody–antigen interactions. The results provide a qualitative explanation for the increased 8F9 peptide affinity compared with that of M2J1. The emerging atomistic-detailed description of these complexes reveals the molecular effects of the somatic hypermutations occurring during affinity maturation.

  1. Dynamic subgrid scale model of large eddy simulation of cross bundle flows

    Hassan, Y.A.; Barsamian, H.R.

    1996-01-01

    The dynamic subgrid scale closure model of Germano et. al (1991) is used in the large eddy simulation code GUST for incompressible isothermal flows. Tube bundle geometries of staggered and non-staggered arrays are considered in deep bundle simulations. The advantage of the dynamic subgrid scale model is the exclusion of an input model coefficient. The model coefficient is evaluated dynamically for each nodal location in the flow domain. Dynamic subgrid scale results are obtained in the form of power spectral densities and flow visualization of turbulent characteristics. Comparisons are performed among the dynamic subgrid scale model, the Smagorinsky eddy viscosity model (that is used as the base model for the dynamic subgrid scale model) and available experimental data. Spectral results of the dynamic subgrid scale model correlate better with experimental data. Satisfactory turbulence characteristics are observed through flow visualization

  2. Flux flow and flux dynamics in high-Tc superconductors

    Bennett, L.H.; Turchinskaya, M.; Swartzendruber, L.J.; Roitburd, A.; Lundy, D.; Ritter, J.; Kaiser, D.L.

    1991-01-01

    Because high temperature superconductors, including BYCO and BSSCO, are type 2 superconductors with relatively low H(sub c 1) values and high H(sub c 2) values, they will be in a critical state for many of their applications. In the critical state, with the applied field between H(sub c 1) and H(sub c 2), flux lines have penetrated the material and can form a flux lattice and can be pinned by structural defects, chemical inhomogeneities, and impurities. A detailed knowledge of how flux penetrates the material and its behavior under the influence of applied fields and current flow, and the effect of material processing on these properties, is required in order to apply, and to improve the properties of these superconductors. When the applied field is changed rapidly, the time dependence of flux change can be divided into three regions, an initial region which occurs very rapidly, a second region in which the magnetization has a 1n(t) behavior, and a saturation region at very long times. A critical field is defined for depinning, H(sub c,p) as that field at which the hysteresis loop changes from irreversible to reversible. As a function of temperature, it is found that H(sub c,p) is well described by a power law with an exponent between 1.5 and 2.5. The behavior of H(sub c,p) for various materials and its relationship to flux flow and flux dynamics are discussed

  3. Spatio-temporal organization of dynamics in a two-dimensional periodically driven vortex flow: A Lagrangian flow network perspective.

    Lindner, Michael; Donner, Reik V

    2017-03-01

    We study the Lagrangian dynamics of passive tracers in a simple model of a driven two-dimensional vortex resembling real-world geophysical flow patterns. Using a discrete approximation of the system's transfer operator, we construct a directed network that describes the exchange of mass between distinct regions of the flow domain. By studying different measures characterizing flow network connectivity at different time-scales, we are able to identify the location of dynamically invariant structures and regions of maximum dispersion. Specifically, our approach allows us to delimit co-existing flow regimes with different dynamics. To validate our findings, we compare several network characteristics to the well-established finite-time Lyapunov exponents and apply a receiver operating characteristic analysis to identify network measures that are particularly useful for unveiling the skeleton of Lagrangian chaos.

  4. Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.

    Zhang, Yuxin; Huang, Xiaoqin; Han, Keli; Zheng, Fang; Zhan, Chang-Guo

    2016-11-25

    The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (∼5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of ∼5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (∼0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental K M values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Nonlinear dynamics in flow through unsaturated fractured-porous media: Status and perspectives

    Faybishenko, Boris

    2002-11-27

    The need has long been recognized to improve predictions of flow and transport in partially saturated heterogeneous soils and fractured rock of the vadose zone for many practical applications, such as remediation of contaminated sites, nuclear waste disposal in geological formations, and climate predictions. Until recently, flow and transport processes in heterogeneous subsurface media with oscillating irregularities were assumed to be random and were not analyzed using methods of nonlinear dynamics. The goals of this paper are to review the theoretical concepts, present the results, and provide perspectives on investigations of flow and transport in unsaturated heterogeneous soils and fractured rock, using the methods of nonlinear dynamics and deterministic chaos. The results of laboratory and field investigations indicate that the nonlinear dynamics of flow and transport processes in unsaturated soils and fractured rocks arise from the dynamic feedback and competition between various nonlinear physical processes along with complex geometry of flow paths. Although direct measurements of variables characterizing the individual flow processes are not technically feasible, their cumulative effect can be characterized by analyzing time series data using the models and methods of nonlinear dynamics and chaos. Identifying flow through soil or rock as a nonlinear dynamical system is important for developing appropriate short- and long-time predictive models, evaluating prediction uncertainty, assessing the spatial distribution of flow characteristics from time series data, and improving chemical transport simulations. Inferring the nature of flow processes through the methods of nonlinear dynamics could become widely used in different areas of the earth sciences.

  6. Nonlinear dynamics in flow through unsaturated fractured porous media: Status and perspectives

    Faybishenko, Boris

    2002-01-01

    The need has long been recognized to improve predictions of flow and transport in partially saturated heterogeneous soils and fractured rock of the vadose zone for many practical applications, such as remediation of contaminated sites, nuclear waste disposal in geological formations, and climate predictions. Until recently, flow and transport processes in heterogeneous subsurface media with oscillating irregularities were assumed to be random and were not analyzed using methods of nonlinear dynamics. The goals of this paper are to review the theoretical concepts, present the results, and provide perspectives on investigations of flow and transport in unsaturated heterogeneous soils and fractured rock, using the methods of nonlinear dynamics and deterministic chaos. The results of laboratory and field investigations indicate that the nonlinear dynamics of flow and transport processes in unsaturated soils and fractured rocks arise from the dynamic feedback and competition between various nonlinear physical processes along with complex geometry of flow paths. Although direct measurements of variables characterizing the individual flow processes are not technically feasible, their cumulative effect can be characterized by analyzing time series data using the models and methods of nonlinear dynamics and chaos. Identifying flow through soil or rock as a nonlinear dynamical system is important for developing appropriate short- and long-time predictive models, evaluating prediction uncertainty, assessing the spatial distribution of flow characteristics from time series data, and improving chemical transport simulations. Inferring the nature of flow processes through the methods of nonlinear dynamics could become widely used in different areas of the earth sciences

  7. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

    Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian; Roitberg, Adrian E.

    2015-01-01

    The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data

  8. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

    Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian, E-mail: sfalberti@gmail.com [Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal (Argentina); Roitberg, Adrian E. [Departments of Physics and Chemistry, University of Florida, Gainesville, Florida 32611 (United States)

    2015-06-28

    The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

  9. Conformational Dynamics and Binding Free Energies of Inhibitors of BACE-1: From the Perspective of Protonation Equilibria.

    M Olivia Kim

    2015-10-01

    Full Text Available BACE-1 is the β-secretase responsible for the initial amyloidogenesis in Alzheimer's disease, catalyzing hydrolytic cleavage of substrate in a pH-sensitive manner. The catalytic mechanism of BACE-1 requires water-mediated proton transfer from aspartyl dyad to the substrate, as well as structural flexibility in the flap region. Thus, the coupling of protonation and conformational equilibria is essential to a full in silico characterization of BACE-1. In this work, we perform constant pH replica exchange molecular dynamics simulations on both apo BACE-1 and five BACE-1-inhibitor complexes to examine the effect of pH on dynamics and inhibitor binding properties of BACE-1. In our simulations, we find that solution pH controls the conformational flexibility of apo BACE-1, whereas bound inhibitors largely limit the motions of the holo enzyme at all levels of pH. The microscopic pKa values of titratable residues in BACE-1 including its aspartyl dyad are computed and compared between apo and inhibitor-bound states. Changes in protonation between the apo and holo forms suggest a thermodynamic linkage between binding of inhibitors and protons localized at the dyad. Utilizing our recently developed computational protocol applying the binding polynomial formalism to the constant pH molecular dynamics (CpHMD framework, we are able to obtain the pH-dependent binding free energy profiles for various BACE-1-inhibitor complexes. Our results highlight the importance of correctly addressing the binding-induced protonation changes in protein-ligand systems where binding accompanies a net proton transfer. This work comprises the first application of our CpHMD-based free energy computational method to protein-ligand complexes and illustrates the value of CpHMD as an all-purpose tool for obtaining pH-dependent dynamics and binding free energies of biological systems.

  10. Flow-pattern identification and nonlinear dynamics of gas-liquid two-phase flow in complex networks.

    Gao, Zhongke; Jin, Ningde

    2009-06-01

    The identification of flow pattern is a basic and important issue in multiphase systems. Because of the complexity of phase interaction in gas-liquid two-phase flow, it is difficult to discern its flow pattern objectively. In this paper, we make a systematic study on the vertical upward gas-liquid two-phase flow using complex network. Three unique network construction methods are proposed to build three types of networks, i.e., flow pattern complex network (FPCN), fluid dynamic complex network (FDCN), and fluid structure complex network (FSCN). Through detecting the community structure of FPCN by the community-detection algorithm based on K -mean clustering, useful and interesting results are found which can be used for identifying five vertical upward gas-liquid two-phase flow patterns. To investigate the dynamic characteristics of gas-liquid two-phase flow, we construct 50 FDCNs under different flow conditions, and find that the power-law exponent and the network information entropy, which are sensitive to the flow pattern transition, can both characterize the nonlinear dynamics of gas-liquid two-phase flow. Furthermore, we construct FSCN and demonstrate how network statistic can be used to reveal the fluid structure of gas-liquid two-phase flow. In this paper, from a different perspective, we not only introduce complex network theory to the study of gas-liquid two-phase flow but also indicate that complex network may be a powerful tool for exploring nonlinear time series in practice.

  11. Determining tumor blood flow parameters from dynamic image measurements

    Libertini, Jessica M.

    2008-11-01

    Many recent cancer treatments focus on preventing angiogenesis, the process by which a tumor promotes the growth of large and efficient capillary beds for the increased nourishment required to support the tumor's rapid growth[l]. To measure the efficacy of these treatments in a timely fashion, there is an interest in using data from dynamic sequences of contrast-enhanced medical imaging, such as MRI and CT, to measure blood flow parameters such as perfusion, permeability-surface-area product, and the relative volumes of the plasma and extracellular-extravascular space. Starting with a two compartment model presented by the radiology community[2], this work challenges the application of a simplification to this problem, which was originally developed to model capillary reuptake[3]. While the primary result of this work is the demonstration of the inaccuracy of this simplification, the remainder of the paper is dedicated to presenting alternative methods for calculating the perfusion and plasma volume coefficients. These methods are applied to model data sets based on real patient data, and preliminary results are presented.

  12. Zonal-flow dynamics from a phase-space perspective

    Ruiz, D. E.; Parker, J. B.; Shi, E. L.; Dodin, I. Y.

    2017-10-01

    The wave kinetic equation (WKE) describing drift-wave (DW) turbulence is widely used in the studies of zonal flows (ZFs) emerging from DW turbulence. However, this formulation neglects the exchange of enstrophy between DWs and ZFs and also ignores effects beyond the geometrical-optics (GO) limit. Here we present a new theory that captures both of these effects, while still treating DW quanta (``driftons'') as particles in phase space. In this theory, the drifton dynamics is described by an equation of the Wigner-Moyal type, which is analogous to the phase-space formulation of quantum mechanics. The ``Hamiltonian'' and the ``dissipative'' parts of the DW-ZF interactions are clearly identified. Moreover, this theory can be interpreted as a phase-space representation of the second-order cumulant expansion (CE2). In the GO limit, this formulation features additional terms missing in the traditional WKE that ensure conservation of the total enstrophy of the system, in addition to the total energy, which is the only conserved invariant in previous theories based on the traditional WKE. Numerical simulations are presented to illustrate the importance of these additional terms. Supported by the U.S. DOE through Contract Nos. DE-AC02-09CH11466 and DE-AC52-07NA27344, by the NNSA SSAA Program through DOE Research Grant No. DE-NA0002948, and by the U.S. DOD NDSEG Fellowship through Contract No. 32-CFR-168a.

  13. Conformational Entropy of FK506 Binding to FKBP12 Determined by Nuclear Magnetic Resonance Relaxation and Molecular Dynamics Simulations.

    Solomentsev, Gleb; Diehl, Carl; Akke, Mikael

    2018-03-06

    FKBP12 (FK506 binding protein 12 kDa) is an important drug target. Nuclear magnetic resonance (NMR) order parameters, describing amplitudes of motion on the pico- to nanosecond time scale, can provide estimates of changes in conformational entropy upon ligand binding. Here we report backbone and methyl-axis order parameters of the apo and FK506-bound forms of FKBP12, based on 15 N and 2 H NMR relaxation. Binding of FK506 to FKBP12 results in localized changes in order parameters, notably for the backbone of residues E54 and I56 and the side chains of I56, I90, and I91, all positioned in the binding site. The order parameters increase slightly upon FK506 binding, indicating an unfavorable entropic contribution to binding of TΔ S = -18 ± 2 kJ/mol at 293 K. Molecular dynamics simulations indicate a change in conformational entropy, associated with all dihedral angles, of TΔ S = -26 ± 9 kJ/mol. Both these values are significant compared to the total entropy of binding determined by isothermal titration calorimetry and referenced to a reactant concentration of 1 mM ( TΔ S = -29 ± 1 kJ/mol). Our results reveal subtle differences in the response to ligand binding compared to that of the previously studied rapamycin-FKBP12 complex, despite the high degree of structural homology between the two complexes and their nearly identical ligand-FKBP12 interactions. These results highlight the delicate dependence of protein dynamics on drug interactions, which goes beyond the view provided by static structures, and reinforce the notion that protein conformational entropy can make important contributions to the free energy of ligand binding.

  14. Flow Mode Dependent Partitioning Processes of Preferential Flow Dynamics in Unsaturated Fractures - Findings From Analogue Percolation Experiments

    Kordilla, J.; Noffz, T.; Dentz, M.; Sauter, M.

    2017-12-01

    To assess the vulnerability of an aquifer system it is of utmost importance to recognize the high potential for a rapid mass transport offered by ow through unsaturated fracture networks. Numerical models have to reproduce complex effects of gravity-driven flow dynamics to generate accurate predictions of flow and transport. However, the non-linear characteristics of free surface flow dynamics and partitioning behaviour at unsaturated fracture intersections often exceed the capacity of classical volume-effective modelling approaches. Laboratory experiments that manage to isolate single aspects of the mass partitioning process can enhance the understanding of underlying dynamics, which ultimately influence travel time distributions on multiple scales. Our analogue fracture network consists of synthetic cubes with dimensions of 20 x 20 x 20 cm creating simple geometries of a single or a cascade of consecutive horizontal fractures. Gravity-driven free surface flow (droplets; rivulets) is established via a high precision multichannel dispenser at flow rates ranging from 1.5 to 4.5 ml/min. Single-inlet experiments show the influence of variable flow rate, atmospheric pressure and temperature on the stability of flow modes and allow to delineate a droplet and rivulet regime. The transition between these regimes exhibits mixed flow characteristics. In addition, multi-inlet setups with constant total infow rates decrease the variance induced by erratic free-surface flow dynamics. We investigate the impacts of variable aperture widths, horizontal offsets of vertical fracture surfaces, and alternating injection methods for both flow regimes. Normalized fracture inflow rates allow to demonstrate and compare the effects of variable geometric features. Firstly, the fracture filling can be described by plug flow. At later stages it transitions into a Washburn-type flow, which we compare to an analytical solution for the case of rivulet flow. Observations show a considerably

  15. Spatial and temporal dynamics of corticosterone and corticosterone binding globulin are driven by environmental heterogeneity.

    Shultz, Michael Todd; Kitaysky, Alexander Stanislav

    2008-02-01

    The question of whether changes in glucocorticoid concentrations reflect consistent changes in physiology associated with transitions between different stages of reproduction, or whether they reflect responses to environmental conditions, is one the central issues in field endocrinology studies. We examined the temporal and spatial dynamics of corticosterone (CORT, baseline, and acute stress-induced) and corticosterone binding globulin (CBG) concentrations in blood of Black-legged Kittiwakes (Rissa tridactyla) breeding at four major colonies in the Bering Sea, Alaska, during 1999-2005. We found that total CORT, free CORT, and CBG capacity varied inconsistently among reproductive stages, colonies, and years. Total CORT levels were positively correlated with CBG capacity. Variation in free CORT was largely driven by variation in total CORT. Results suggest that the adrenocortical function and CBG in breeding kittiwakes do not vary as a consequence of stage-specific modulation associated with a particular reproductive stage as in some short-lived passerine birds. Rather, in accord with predictions for a long-lived species, the lack of consistent colony, year, and reproductive stage patterns in baseline and maximum CORT, and CBG indicates that environmental factors, probably local dynamics of food availability, drive variation in these factors.

  16. Dynamics of flow behind backward-facing step in a narrow channel

    Uruba V.

    2013-04-01

    Full Text Available The results and their analysis from experiments obtained by TR-PIV are presented on the model of backward-facing step in a narrow channel. The recirculation zone is studied in details. Mean structures are evaluated from fluctuating velocity fields. Then dynamics of the flow is characterized with help of POD (BOD technique. Substantial differences in high energy dynamical structures behaviour within the back-flow region and further downstream behind the flow reattachment have been found.

  17. Analysis of the flow dynamics characteristics of an axial piston pump based on the computational fluid dynamics method

    Bin Zhang

    2017-01-01

    Full Text Available To improve its working performance, the flow ripple characteristics of an axial piston pump were investigated with software which uses computational fluid dynamics (CFD technology. The simulation accuracy was significantly optimized through the use of the improved compressible fluid model. Flow conditions of the pump were tested using a pump flow ripple test rig, and the simulation results of the CFD model showed good agreement with the experimental data. Additionally, the composition of the flow ripple was analyzed using the improved CFD model, and the results showed that the compression ripple makes up 88% of the flow ripple. The flow dynamics of the piston pump is mainly caused by the pressure difference between the intake and discharge ports of the valve plates and the fluid oil compressibility.

  18. Lactose Binding Induces Opposing Dynamics Changes in Human Galectins Revealed by NMR-Based Hydrogen-Deuterium Exchange.

    Chien, Chih-Ta Henry; Ho, Meng-Ru; Lin, Chung-Hung; Hsu, Shang-Te Danny

    2017-08-16

    Galectins are β-galactoside-binding proteins implicated in a myriad of biological functions. Despite their highly conserved carbohydrate binding motifs with essentially identical structures, their affinities for lactose, a common galectin inhibitor, vary significantly. Here, we aimed to examine the molecular basis of differential lactose affinities amongst galectins using solution-based techniques. Consistent dissociation constants of lactose binding were derived from nuclear magnetic resonance (NMR) spectroscopy, intrinsic tryptophan fluorescence, isothermal titration calorimetry and bio-layer interferometry for human galectin-1 (hGal1), galectin-7 (hGal7), and the N-terminal and C-terminal domains of galectin-8 (hGal8 NTD and hGal8 CTD , respectively). Furthermore, the dissociation rates of lactose binding were extracted from NMR lineshape analyses. Structural mapping of chemical shift perturbations revealed long-range perturbations upon lactose binding for hGal1 and hGal8 NTD . We further demonstrated using the NMR-based hydrogen-deuterium exchange (HDX) that lactose binding increases the exchange rates of residues located on the opposite side of the ligand-binding pocket for hGal1 and hGal8 NTD , indicative of allostery. Additionally, lactose binding induces significant stabilisation of hGal8 CTD across the entire domain. Our results suggested that lactose binding reduced the internal dynamics of hGal8 CTD on a very slow timescale (minutes and slower) at the expense of reduced binding affinity due to the unfavourable loss of conformational entropy.

  19. Dynamics of lava flow - Thickness growth characteristics of steady two-dimensional flow

    Park, S.; Iversen, J. D.

    1984-01-01

    The thickness growth characteristics of flowing lava are investigated using a heat balance model and a two-dimensional model for flow of a Bingham plastic fluid down an inclined plane. It is found that yield strength plays a crucial role in the thickening of a lava flow of given flow rate. To illustrate this point, downstream thickness profiles and yield strength distributions were calculated for flows with mass flow rates of 10,000 and 100,000 kg/m-sec. Higher flow rates led to slow cooling rates which resulted in slow rate of increase of yield strength and thus greater flow lengths.

  20. Dynamics of shallow flows with and without background rotation

    Durán Matute, M.

    2010-01-01

    Large-scale oceanic and atmospheric flows tend to behave in a two-dimensional way. To further understand such flows, a large scientific effort has been devoted to the study of perfect two-dimensional flows. For the last 30 years, there has been a large interest in experimentally validating the

  1. Thermo-fluid dynamics of two-phase flow

    Ishii, Mamoru; Ishii, Mamoru; Ishii, M

    2006-01-01

    Provides a very systematic treatment of two phase flow problems from a theoretical perspectiveProvides an easy to follow treatment of modeling and code devlopemnt of two phase flow related phenomenaCovers new results of two phase flow research such as coverage of fuel cells technology.

  2. Tokamak turbulence in self-regulated differentially rotating flow and L-H transition dynamics

    Terry, P.W.; Carreras, B.A.; Sidikman, K.

    1992-01-01

    An analytical study of turbulence in the presence of turbulently generated differentially rotating flow is presented as a paradigm for fluctuation dynamics in L- and H-mode plasmas. Using a drift wave model, the role of both flow shear and flow curvature (second radial derivative of the poloidal ExB flow) is detailed in linear and saturated turbulence phases. In the strong turbulence saturated state, finite amplitude-induced modification of the fluctuation structure near low order rational surfaces strongly inhibits flow shear suppression. Suppression by curvature is not diminished, but it occurs through a frequency shift. A description of L-H mode transition dynamics based on the self-consistent linking of turbulence suppression by differentially rotating flow and generation of flow by turbulent momentum transport is presented. In this model, rising edge temperature triggers a transition characterized by spontaneous generation of differentially rotating flow and decreasing turbulence intensity

  3. Information Flow Through Stages of Complex Engineering Design Projects: A Dynamic Network Analysis Approach

    Parraguez, Pedro; Eppinger, Steven D.; Maier, Anja

    2015-01-01

    The pattern of information flow through the network of interdependent design activities is thought to be an important determinant of engineering design process results. A previously unexplored aspect of such patterns relates to the temporal dynamics of information transfer between activities...... design process and thus support theory-building toward the evolution of information flows through systems engineering stages. Implications include guidance on how to analyze and predict information flows as well as better planning of information flows in engineering design projects according...

  4. Constraints on the design of flow measuring structures over a large dynamic flow range

    Hickey, M.J.; Holmes, R.M.

    1979-01-01

    Topographical restraints for design storm flow are described as sharp-crested weirs for low flows in series with broad-crested weirs for the high flows. These design selections are considered to be most economical while providing the specified flow measuring capabilities for movement of radionuclides from the solid waste disposal areas into the surface streams around ORNL

  5. Estimation of flow stress of radiation induced F/M steels using molecular dynamics and discrete dislocation dynamics approach

    More, Ameya; Dutta, B.K.; Durgaprasad, P.V.; Arya, A.K.

    2012-01-01

    Fe-Cr based Ferritic/Martensitic (F/M) steels are the candidate structural materials for future fusion reactors. In this work, a multi-scale approach comprising atomistic Molecular Dynamics (MD) simulations and Discrete Dislocation Dynamics (DDD) simulations are used to model the effect of irradiation dose on the flow stress of F/M steels. At the atomic scale, molecular dynamics simulations are used to study the dislocation interaction with irradiation induced defects, i.e. voids and He bubbles. Whereas, the DDD simulations are used to estimate the change in flow stress of the material as a result of irradiation hardening. (author)

  6. Differences in dynamic autoregulation of renal blood flow between SHR and WKY rats

    Chen, Y M; Holstein-Rathlou, N H

    1993-01-01

    by chaotic fluctuations. We sought to determine whether this change was associated with a change in the dynamic autoregulation of renal blood flow. In halothane-anesthetized 250- to 320-g SHR and WKY rats, renal blood flow was measured during "white noise" forcing of arterial blood pressure. The frequency...... conclude that the change in the dynamics of TGF leads to a change in the dynamic autoregulation of renal blood flow between SHR and WKY rats. This change results in a more efficient dynamic autoregulation of renal blood flow in the SHR compared with the WKY rats. The functional consequences of this......In halothane-anesthetized Wistar-Kyoto (WKY) rats the single-nephron blood flow and the proximal tubule pressure oscillate at a frequency of 35-50 mHz because of the operation of the tubuloglomerular feedback (TGF) mechanism. In spontaneously hypertensive rats (SHR) the oscillations are replaced...

  7. DMPD: Silica binding and toxicity in alveolar macrophages. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18226603 Silica binding and toxicity in alveolar macrophages. Hamilton RF Jr, Thaku...l) Show Silica binding and toxicity in alveolar macrophages. PubmedID 18226603 Title Silica binding and toxicity in alveolar macropha...ges. Authors Hamilton RF Jr, Thakur SA, Holian A. Public

  8. DMPD: LPS-binding proteins and receptors. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 9665271 LPS-binding proteins and receptors. Fenton MJ, Golenbock DT. J Leukoc Biol.... 1998 Jul;64(1):25-32. (.png) (.svg) (.html) (.csml) Show LPS-binding proteins and receptors. PubmedID 9665271 Title LPS-binding prot...eins and receptors. Authors Fenton MJ, Golenbock DT. Publication J Leukoc Biol. 199

  9. DMPD: Lipopolysaccharide-binding molecules: transporters, blockers and sensors. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 15241548 Lipopolysaccharide-binding molecules: transporters, blockers and sensors. ...binding molecules: transporters, blockers and sensors. PubmedID 15241548 Title Lipopolysaccharide-binding molecules: transport...Chaby R. Cell Mol Life Sci. 2004 Jul;61(14):1697-713. (.png) (.svg) (.html) (.csml) Show Lipopolysaccharide-

  10. Visualization and PIV measurement of unsteady flow around a darrieus wind turbine in dynamic stall

    Shibuya, Satoshi; Fujisawa, Nobuyuki; Takano, Tsuyoshi [Dept. of Mechanical and Production Engineering, Niigata Univ., Niigata (Japan)

    1999-07-01

    Flow around a Darrieus wind turbine in dynamic stall is studied by flow visualization and PIV (particle image velocimeter) measurement in a rotating frame of reference, which allows the successive observation of the dynamic stall over the blade. The qualitative features of the flow field in dynamic stall observed by the flow visualization, such as the formation and shedding of the stall vortices, are quantitatively reproduced in the instantaneous velocity distributions near the blade by using PIV. These results indicate that two pairs of stall vortices are generated from the blade during one rotation of the blade and that the size and the generating blade angle of the stall vortices are enlarged as the tip-speed ratio decreases. These stall vortices are produced by the in-flow motion from the outer surface to the inner surface through the trailing edge of the blade and the flow separation over the inner surface of the blade. (author)

  11. Two-dimensional fluid dynamics in a sharply bent channel: Laminar flow, separation bubble, and vortex dynamics

    Matsumoto, Daichi; Fukudome, Koji; Wada, Hirofumi

    2016-10-01

    Understanding the hydrodynamic properties of fluid flow in a curving pipe and channel is important for controlling the flow behavior in technologies and biomechanics. The nature of the resulting flow in a bent pipe is extremely complicated because of the presence of a cross-stream secondary flow. In an attempt to disentangle this complexity, we investigate the fluid dynamics in a bent channel via the direct numerical simulation of the Navier-Stokes equation in two spatial dimensions. We exploit the absence of secondary flow from our model and systematically investigate the flow structure along the channel as a function of both the bend angle and Reynolds number of the laminar-to-turbulent regime. We numerically suggest a scaling relation between the shape of the separation bubble and the flow conductance, and construct an integrated phase diagram.

  12. Probing of possible olanzapine binding site on human serum albumin: Combination of spectroscopic methods and molecular dynamics simulation

    Shahlaei, Mohsen; Rahimi, Behnoosh; Ashrafi-Kooshk, Mohammad Reza; Sadrjavadi, Komail; Khodarahmi, Reza

    2015-01-01

    Human serum albumin (HSA)-drug binding affinity is one of the major factors that determine the pharmacokinetics, halftime and bioavailability of drugs in various tissues. In the present study, the interaction of olanzapine (OLZ), a thienobenzodiazepine drug, administered for the treatment of schizophrenia and bipolar disorder, with HSA has been studied using spectroscopic methods such as ultraviolet absorbance, fluorescence and FTIR combined with computational procedures. Analyzing of the Stern–Volmer quenching data showed only one primary binding site on HSA with a binding constant of 4.12×10 4 M −1 at 298 K. Thermodynamic analyses showed enthalpy change (ΔH°) and entropy change (ΔS°) were 28.03±3.42 kJ mol −1 and −25.52±11.52 J mol −1 K −1 , respectively. Molecular docking results suggested the hydrophobic residues such as Val 216 , Leu 327 , Ala 350 and polar residues such as Glu 354 play an important role in the drug binding. Decrement in α-helix content of the protein upon OLZ binding was also confirmed by evidences provided by molecular dynamics simulation as well as FTIR spectroscopy. - Highlights: • Leu 327 , Ala 350 as well as hydrophilic residues of HSA play an important role in the binding reaction. • The drug has only one primary binding site on HSA with a binding constant of 4.12×10 4 M −1 at 298 K. • The drug binds near to site I

  13. Probing of possible olanzapine binding site on human serum albumin: Combination of spectroscopic methods and molecular dynamics simulation

    Shahlaei, Mohsen, E-mail: mohsenshahlaei@yahoo.com [Nano drug delivery research Center, Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Rahimi, Behnoosh [Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Student research committee, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ashrafi-Kooshk, Mohammad Reza [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Sadrjavadi, Komail [Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Khodarahmi, Reza, E-mail: rkhodarahmi@mbrc.ac.ir [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of)

    2015-02-15

    Human serum albumin (HSA)-drug binding affinity is one of the major factors that determine the pharmacokinetics, halftime and bioavailability of drugs in various tissues. In the present study, the interaction of olanzapine (OLZ), a thienobenzodiazepine drug, administered for the treatment of schizophrenia and bipolar disorder, with HSA has been studied using spectroscopic methods such as ultraviolet absorbance, fluorescence and FTIR combined with computational procedures. Analyzing of the Stern–Volmer quenching data showed only one primary binding site on HSA with a binding constant of 4.12×10{sup 4} M{sup −1} at 298 K. Thermodynamic analyses showed enthalpy change (ΔH°) and entropy change (ΔS°) were 28.03±3.42 kJ mol{sup −1} and −25.52±11.52 J mol{sup −1} K{sup −1}, respectively. Molecular docking results suggested the hydrophobic residues such as Val{sub 216}, Leu{sub 327}, Ala{sub 350} and polar residues such as Glu{sub 354} play an important role in the drug binding. Decrement in α-helix content of the protein upon OLZ binding was also confirmed by evidences provided by molecular dynamics simulation as well as FTIR spectroscopy. - Highlights: • Leu{sub 327}, Ala{sub 350} as well as hydrophilic residues of HSA play an important role in the binding reaction. • The drug has only one primary binding site on HSA with a binding constant of 4.12×10{sup 4} M{sup −1} at 298 K. • The drug binds near to site I.

  14. Dynamics of Unusual Debris Flows on Martian Sand Dunes

    Miyamoto, Hideaki; Dohm, James M.; Baker, Victor R.; Beyer, Ross A.; Bourke, Mary

    2004-01-01

    Gullies that dissect sand dunes in Russell impact crater often display debris flow-like deposits in their distal reaches. The possible range of both the rheological properties and the flow rates are estimated using a numerical simulation code of a Bingham plastic flow to help explain the formation of these features. Our simulated results are best explained by a rapid debris flow. For example, a debris flow with the viscosity of 10(exp 2) Pa s and the yield strength of 10(exp 2) Pa can form the observed deposits with a flow rate of 0.5 cu m/s sustained over several minutes and total discharged water volume on the order of hundreds of cubic meters, which may be produced by melting a surface layer of interstitial ice within the dune deposits to several centimeters depth.

  15. RSAT matrix-clustering: dynamic exploration and redundancy reduction of transcription factor binding motif collections.

    Castro-Mondragon, Jaime Abraham; Jaeger, Sébastien; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

    2017-07-27

    Transcription factor (TF) databases contain multitudes of binding motifs (TFBMs) from various sources, from which non-redundant collections are derived by manual curation. The advent of high-throughput methods stimulated the production of novel collections with increasing numbers of motifs. Meta-databases, built by merging these collections, contain redundant versions, because available tools are not suited to automatically identify and explore biologically relevant clusters among thousands of motifs. Motif discovery from genome-scale data sets (e.g. ChIP-seq) also produces redundant motifs, hampering the interpretation of results. We present matrix-clustering, a versatile tool that clusters similar TFBMs into multiple trees, and automatically creates non-redundant TFBM collections. A feature unique to matrix-clustering is its dynamic visualisation of aligned TFBMs, and its capability to simultaneously treat multiple collections from various sources. We demonstrate that matrix-clustering considerably simplifies the interpretation of combined results from multiple motif discovery tools, and highlights biologically relevant variations of similar motifs. We also ran a large-scale application to cluster ∼11 000 motifs from 24 entire databases, showing that matrix-clustering correctly groups motifs belonging to the same TF families, and drastically reduced motif redundancy. matrix-clustering is integrated within the RSAT suite (http://rsat.eu/), accessible through a user-friendly web interface or command-line for its integration in pipelines. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

    Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

    2016-04-05

    Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

  17. Atomic and electronic structures of a-SiC:H from tight-binding molecular dynamics

    Ivashchenko, V I; Shevchenko, V I; Ivashchenko, L A; Rusakov, G V

    2003-01-01

    The atomic and electronic properties of amorphous unhydrogenated (a-SiC) and hydrogenated (a-SiC:H) silicon carbides are studied using an sp sup 3 s sup * tight-binding force model with molecular dynamics simulations. The parameters of a repulsive pairwise potential are determined from ab initio pseudopotential calculations. Both carbides are generated from dilute vapours condensed from high temperature, with post-annealing at low temperature for a-SiC:H. A plausible model for the inter-atomic correlations and electronic states in a-SiC:H is suggested. According to this model, the formation of the amorphous network is weakly sensitive to the presence of hydrogen. Hydrogen passivates effectively only the weak bonds of threefold-coordinated atoms. Chemical ordering is very much affected by the cooling rate and the structure of the high-temperature vapour. The as-computed characteristics are in rather good agreement with the results for a-SiC and a-Si:H from ab initio calculations.

  18. Dynamics of zonal flows and self-regulating drift-wave turbulence

    Diamond, P.H.; Fleischer, J.; Rosenbluth, M.N.; Hinton, F.L.; Malkov, M.; Smolyakov, A.

    1999-01-01

    We present a theory of zonal flow - drift wave dynamics. Zonal flows are generated by modulational instability of a drift wave spectrum, and are damped by collisions. Drift waves undergo random shearing-induced refraction, resulting in increased mean square radial wavenumber. Drift waves and zonal flows together form a simple dynamical system, which has a single stable fixed point. In this state, the fluctuation intensity and turbulent diffusivity are ultimately proportional to the collisional zonal flow damping. The implications of these results for transport models is discussed. (author)

  19. Dynamics of zonal flows and self-regulating drift-wave turbulence

    Diamond, P.H.; Fleischer, J.; Rosenbluth, M.; Hinton, F.L.; Malkov, M.; Smolyakov, A.

    2001-01-01

    We present a theory of zonal flow - drift wave dynamics. Zonal flows are generated by modulational instability of a drift wave spectrum, and are damped by collisions. Drift waves undergo random shearing-induced refraction, resulting in increased mean square radial wavenumber. Drift waves and zonal flows together form a simple dynamical system, which has a single stable fixed point. In this state, the fluctuation intensity and turbulent diffusivity are ultimately proportional to the collisional zonal flow damping. The implications of these results for transport models is discussed. (author)

  20. Dynamics of polymers in elongational flow studied by the neutron spin-echo technique

    Rheinstaedter, Maikel C.; Sattler, Rainer; Haeussler, Wolfgang; Wagner, Christian

    2010-01-01

    The nanoscale fluctuation dynamics of semidilute high molecular weight polymer solutions of polyethylenoxide (PEO) in D 2 O under non-equilibrium flow conditions were studied by the neutron spin-echo technique. The sample cell was in contraction flow geometry and provided a pressure driven flow with a high elongational component that stretched the polymers most efficiently. Neutron scattering experiments in dilute polymer solutions are challenging because of the low polymer concentration and corresponding small quasi-elastic signals. A relaxation process with relaxation times of about 10 ps was observed, which shows anisotropic dynamics with applied flow.

  1. Experimental study of poloidal flow effect on magnetic island dynamics in LHD and TJ-II

    Narushima, Y.; Sakakibara, S.; Castejon, F.

    2010-11-01

    The dynamics of a magnetic island are studied by focusing on the poloidal flows in the helical devices LHD and TJ-II. The temporal increment of the ExB poloidal flow prior to the magnetic island transition from growth to healing is observed. The direction of the poloidal flow is in the electron-diamagnetic direction in LHD and in the ion-diamagnetic direction in TJ-II. From the magnetic diagnostics, it is observed that a current structure flowing in the plasma moves ∼π rad poloidally in the electron-diamagnetic direction during the transition in LHD experiments. These experimental observations from LHD and TJ-II show that the temporal increment of the poloidal flow is followed by the transition (growth to healing) of the magnetic island regardless of the flow direction and clarify the fact that significant poloidal flow affects the magnetic island dynamics. (author)

  2. Complex network analysis of phase dynamics underlying oil-water two-phase flows

    Gao, Zhong-Ke; Zhang, Shan-Shan; Cai, Qing; Yang, Yu-Xuan; Jin, Ning-De

    2016-01-01

    Characterizing the complicated flow behaviors arising from high water cut and low velocity oil-water flows is an important problem of significant challenge. We design a high-speed cycle motivation conductance sensor and carry out experiments for measuring the local flow information from different oil-in-water flow patterns. We first use multivariate time-frequency analysis to probe the typical features of three flow patterns from the perspective of energy and frequency. Then we infer complex networks from multi-channel measurements in terms of phase lag index, aiming to uncovering the phase dynamics governing the transition and evolution of different oil-in-water flow patterns. In particular, we employ spectral radius and weighted clustering coefficient entropy to characterize the derived unweighted and weighted networks and the results indicate that our approach yields quantitative insights into the phase dynamics underlying the high water cut and low velocity oil-water flows. PMID:27306101

  3. Ligand receptor dynamics at streptavidin-coated particle surfaces: A flow cytometric and spectrofluorimetric study

    Buranda, T. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States)]|[Univ. of New Mexico, Albuquerque, NM (United States); Jones, G.M. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States); Nolan, J.P.; Keij, J. [Los Alamos National Labs., NM (United States); Lopez, G.P. [Univ. of New Mexico, Albuquerque, NM (United States); Sklar, L.A. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States)]|[Los Alamos National Lab., NM (United States)

    1999-04-29

    The authors have studied the binding of 5-((N-(5-(N-(6-(biotinoyl)amino)hexanoyl)amino)pentyl)thioureidyl)fluorescein (fluorescein biotin) to 6.2 {micro}m diameter, streptavidin-coated polystyrene beads using a combination of fluorimetric and flow cytometric methods. They have determined the average number of binding sites per bead, the extent of fluorescein quenching upon binding to the bead, and the association and dissociation kinetics. The authors estimate the site number to be {approx}1 million per bead. The binding of the fluorescein biotin ligand occurs in steps where the insertion of the biotin moiety into one receptor pocket is followed immediately by the capture of the fluorescein moiety by a neighboring binding pocket; fluorescence quenching is a consequence of this secondary binding. At high surface coverage, the dominant mechanism of quenching appears to be via the formation of nonfluorescent nearest-neighbor aggregates. At early times, the binding process is characterized by biphasic association and dissociation kinetics which are remarkably dependent on the initial concentration of the ligand. The rate constant for binding to the first receptor pocket of a streptavidin molecule is {approx}(1.3 {+-} 0.3) {times} 10{sup 7} 1{sup {minus}1} S{sup {minus}1}. The rate of binding of a second biotin may be reduced due to steric interference. The early time dissociative behavior is in sharp contrast to the typical stability associated with this system. The early time dissociative behavior is in sharp contrast to the typical stability associated with this system. The dissociation rate constant is as high as 0.05 s{sup {minus}1} shortly after binding, but decreases by 3 orders of magnitude after 3 h of binding. Potential sources for the time dependence of the dissociation rate constant are discussed.

  4. Measurement of Liquid-Metal Two-Phase Flow with a Dynamic Neutron Radiography

    Cha, J. E.; Lim, I. C.; Kim, H. R.; Kim, C. M.; Nam, H. Y.; Saito, Y.

    2005-01-01

    The dynamic neutron radiography(DNR) has complementary characteristics to X-ray radiography and is suitable to visualization and measurement of a multi-phase flow research in a metallic duct and liquid metal flow. The flow-field information of liquid metal system is very important for the safety analysis of fast breeder reactor and the design of the spallation target of accelerator driven system. A DNR technique was applied to visualize the flow field in the gas-liquid metal two-phase flow with the HANARO-beam facility. The lead bismuth eutectic and the nitrogen gas were used to construct the two-phase flow field in the natural circulation U-channel. The two-phase flow images in the riser were taken at various combinations of the liquid flow and gas flow with high frame-rate neutron radiography at 1000 fps

  5. Visualization and analysis of flow patterns of human carotid bifurcation by computational fluid dynamics

    Xue Yunjing; Gao Peiyi; Lin Yan

    2007-01-01

    Objective: To investigate flow patterns at carotid bifurcation in vivo by combining computational fluid dynamics (CFD)and MR angiography imaging. Methods: Seven subjects underwent contrast-enhanced MR angiography of carotid artery in Siemens 3.0 T MR. Flow patterns of the carotid artery bifurcation were calculated and visualized by combining MR vascular imaging post-processing and CFD. Results: The flow patterns of the carotid bifurcations in 7 subjects were varied with different phases of a cardiac cycle. The turbulent flow and back flow occurred at bifurcation and proximal of internal carotid artery (ICA) and external carotid artery (ECA), their occurrence and conformation were varied with different phase of a cardiac cycle. The turbulent flow and back flow faded out quickly when the blood flow to the distal of ICA and ECA. Conclusion: CFD combined with MR angiography can be utilized to visualize the cyclical change of flow patterns of carotid bifurcation with different phases of a cardiac cycle. (authors)

  6. Characterization of cardiac flow in heart disease patients by computational fluid dynamics and 4D flow MRI

    Lantz, Jonas; Gupta, Vikas; Henriksson, Lilian; Karlsson, Matts; Persson, Ander; Carhall, Carljohan; Ebbers, Tino

    2017-11-01

    In this study, cardiac blood flow was simulated using Computational Fluid Dynamics and compared to in vivo flow measurements by 4D Flow MRI. In total, nine patients with various heart diseases were studied. Geometry and heart wall motion for the simulations were obtained from clinical CT measurements, with 0.3x0.3x0.3 mm spatial resolution and 20 time frames covering one heartbeat. The CFD simulations included pulmonary veins, left atrium and ventricle, mitral and aortic valve, and ascending aorta. Mesh sizes were on the order of 6-16 million cells, depending on the size of the heart, in order to resolve both papillary muscles and trabeculae. The computed flow field agreed visually very well with 4D Flow MRI, with characteristic vortices and flow structures seen in both techniques. Regression analysis showed that peak flow rate as well as stroke volume had an excellent agreement for the two techniques. We demonstrated the feasibility, and more importantly, fidelity of cardiac flow simulations by comparing CFD results to in vivo measurements. Both qualitative and quantitative results agreed well with the 4D Flow MRI measurements. Also, the developed simulation methodology enables ``what if'' scenarios, such as optimization of valve replacement and other surgical procedures. Funded by the Wallenberg Foundation.

  7. Influence of steady shear flow on dynamic viscoelastic properties of ...

    Unknown

    temporary network formed by the fibres, their entangle- ment etc. The structural density is also a function of vol- ume fraction of reinforcing fibres (Amari et al 1992). The complex flow pattern encountered during moulding/ stamping are generally far from simple steady or oscilla- tory shear flow. Therefore, it is important to ...

  8. Dynamic Characteristics of Rotating Stall in Mixed Flow Pump

    Xiaojun Li

    2013-01-01

    Full Text Available Rotating stall, a phenomenon that causes flow instabilities and pressure hysteresis by propagating at some fraction of the impeller rotational speed, can occur in centrifugal impellers, mixed impellers, radial diffusers, or axial diffusers. Despite considerable efforts devoted to the study of rotating stall in pumps, the mechanics of this phenomenon are not sufficiently understood. The propagation mechanism and onset of rotating stall are not only affected by inlet flow but also by outlet flow as well as the pressure gradient in the flow passage. As such, the complexity of these concepts is not covered by the classical explanation. To bridge this research gap, the current study investigated prerotation generated at the upstream of the impeller, leakage flow at the tip clearance between the casing and the impeller, and strong reserve flow at the inlet of the diffuser. Understanding these areas will clarify the origin of the positive slope of the head-flow performance curve for a mixed flow pump. Nonuniform pressure distribution and adverse pressure gradient were also introduced to evaluate the onset and development of rotating stall within the diffuser.

  9. Understanding Ion Binding Affinity and Selectivity in β-Parvalbumin Using Molecular Dynamics and Mean Spherical Approximation Theory.

    Kucharski, Amir N; Scott, Caitlin E; Davis, Jonathan P; Kekenes-Huskey, Peter M

    2016-08-25

    Parvalbumin (PV) is a globular calcium (Ca(2+))-selective protein expressed in a variety of biological tissues. Our computational studies of the rat β-parvalbumin (β-PV) isoform seek to elucidate the molecular thermodynamics of Ca(2+) versus magnesium (Mg(2+)) binding at the protein's two EF-hand motifs. Specifically, we have utilized molecular dynamics (MD) simulations and a mean-field electrolyte model (mean spherical approximation (MSA) theory) to delineate how the EF-hand scaffold controls the "local" thermodynamics of Ca(2+) binding selectivity over Mg(2+). Our MD simulations provide the probability density of metal-chelating oxygens within the EF-hand scaffolds for both Ca(2+) and Mg(2+), as well the conformational strain induced by Mg(2+) relative to Ca(2+) binding. MSA theory utilizes the binding domain oxygen and charge distributions to predict the chemical potential of ion binding, as well as their corresponding concentrations within the binding domain. We find that the electrostatic and steric contributions toward ion binding were similar for Mg(2+) and Ca(2+), yet the latter was 5.5 kcal/mol lower in enthalpy when internal strain within the EF hand was considered. We therefore speculate that beyond differences in dehydration energies for the Ca(2+) versus Mg(2+), strain induced in the β-PV EF hand by cation binding significantly contributes to the nearly 10,000-fold difference in binding affinity reported in the literature. We further complemented our analyses of local factors governing cation binding selectivity with whole-protein (global) contributions, such as interhelical residue-residue contacts and solvent exposure of hydrophobic surface. These contributions were found to be comparable for both Ca(2+)- and Mg(2+)-bound β-PV, which may implicate local factors, EF-hand strain, and dehydration, in providing the primary means of selectivity. We anticipate these methods could be used to estimate metal binding thermodynamics across a broad range of

  10. Candida glabrata binds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists.

    Torres-Tirado, David; Knabb, Maureen; Castaño, Irene; Patrón-Soberano, Araceli; De Las Peñas, Alejandro; Rubio, Rafael

    2016-01-01

    Candida glabrata (CG) is an opportunistic fungal pathogen that initiates infection by binding to host cells via specific lectin-like adhesin proteins. We have previously shown the importance of lectin-oligosaccharide binding in cardiac responses to flow and agonists. Because of the lectinic-oligosaccharide nature of CG binding, we tested the ability of CG to alter the agonist- and flow-induced changes in cardiac function in isolated perfused guinea pig hearts. Both transmission and scanning electron microscopy showed strong attachment of CG to the coronary endothelium, even after extensive washing. CG shifted the coronary flow vs. auricular-ventricular (AV) delay relationship upward, indicating that greater flow was required to achieve the same AV delay. This effect was completely reversed with mannose, partially reversed with galactose and N-acetylgalactosamine, but hyaluronan had no effect. Western blot analysis was used to determine binding of CG to isolated coronary endothelial luminal membrane (CELM) receptors, and the results indicate that flow-sensitive CELM receptors, ANG II type I, α-adrenergic 1A receptor, endothelin-2, and VCAM-1 bind to CG. In addition, CG inhibited agonist-induced effects of bradykinin, angiotensin, and phenylephrine on AV delay, coronary perfusion pressure, and left ventricular pressure. Mannose reversed the inhibitory effects of CG on the agonist responses. These results suggest that CG directly binds to flow-sensitive CELM receptors via lectinic-oligosaccharide interactions with mannose and disrupts the lectin-oligosaccharide binding necessary for flow-induced cardiac responses. Copyright © 2016 the American Physiological Society.

  11. Fluid dynamics of cryogenic two-phase flows

    Verfondern, K.; Jahn, W.

    2004-01-01

    The objective of this study was to examine the flow behavior of a methane hydrate/methane-liquid hydrogen dispersed two-phase fluid through a given design of a moderator chamber for the ESS target system. The calculations under simplified conditions, e.g., taking no account of heat input from outside, have shown that the computer code used, CFX, was able to simulate the behavior of the two-phase flow through the moderator chamber, producing reasonable results up to a certain level of the solid phase fraction, that allowed a continuous flow process through the chamber. Inlet flows with larger solid phase fractions than 40 vol% were found to be a ''problem'' for the computer code. From the computer runs based on fractions between 20 and 40 vol%, it was observed that with increasing solid phase fraction at the inlet, the resulting flow pattern revealed a strong tendency for blockage within the chamber, supported by the ''heavy weight'' of the pellets compared to the carrying liquid. Locations which are prone to the development of such uneven flow behavior are the areas around the turning points in the semispheres and near the exit of the moderator. The considered moderator chamber with horizontal inlet and outlet flow for a solid-liquid two-phase fluid does not seem to be an appropriate design. (orig.)

  12. Flow dynamic study of a single-phase square NCL using recurrence ...

    Department of Mechanical Engineering, Jadavpur University, Kolkata 700 032, India ... With increase in heater power, a change in loop fluid flow dynamics has been observed. For ... reactor core cooling, solar water heaters, gas turbine.

  13. Technical report on prototype intelligent network flow optimization (INFLO) dynamic speed harmonization and queue warning.

    2015-06-01

    This Technical Report on Prototype Intelligent Network Flow Optimization (INFLO) Dynamic Speed Harmonization and : Queue Warning is the final report for the project. It describes the prototyping, acceptance testing and small-scale : demonstration of ...

  14. Homotopical Dynamics IV: Hopf invariants and hamiltonian flows

    Cornea, Octavian

    2001-01-01

    In a non-compact context the first natural step in the search for periodic orbits of a hamiltonian flow is to detect bounded ones. In this paper we show that, in a non-compact setting, certain algebraic topological constraints imposed to a gradient flow of the hamiltonian function $f$ imply the existence of bounded orbits for the hamiltonian flow of $f$. Once the existence of bounded orbits is established, under favorable circumstances, application of the $C^{1}$-closing lemma leads to period...

  15. Dynamic modelling for two-phase flow systems

    Guerra, M.A.

    1991-06-01

    Several models for two-phase flow have been studied, developing a thermal-hydraulic analysis code with one of these models. The program calculates, for one-dimensional cases with variable flow area, the transient behaviour of system process variables, when the boundary conditions (heat flux, flow rate, enthalpy and pressure) are functions of time. The modular structure of the code, eases the program growth. In fact, the present work is the basis for a general purpose accident and transient analysis code in nuclear reactors. Code verification has been made against RETRAN-02 results. Satisfactory results have been achieved with the present version of the code. (Author) [es

  16. Simulation of capillary flow with a dynamic contact angle

    van Mourik, S; Veldman, AEP; Dreyer, ME

    2005-01-01

    A number of theoretical and empirical dynamic contact angle (DCA) models have been tested in a numerical simulation of liquid reorientation in microgravity for which experimental validation data are available. It is observed that the DCA can have a large influence on liquid dynamics in microgravity.

  17. Magnetic resonance velocity mapping of 3D cerebrospinal fluid flow dynamics in hydrocephalus: preliminary results

    Stadlbauer, Andreas; Salomonowitz, Erich; Brenneis, Christian; Ungersboeck, Karl; Riet, Wilma van der; Buchfelder, Michael; Ganslandt, Oliver

    2012-01-01

    To investigate the detectability of CSF flow alterations in the ventricular system of patients with hydrocephalus using time-resolved 3D MR velocity mapping. MR velocity mapping was performed in 21 consecutive hydrocephalus patients and 21 age-matched volunteers using a 3D phase-contrast (PC) sequence. Velocity vectors and particle path lines were calculated for visualisation of flow dynamics. CSF flow was classified as ''hypomotile flow'' if it showed attenuated dynamics and as ''hypermotile flow'' if it showed increased dynamics compared with volunteers. Diagnostic efficacy was compared with routine 2D cine PC-MRI. Seven patients showed hypomotile CSF flow: six had non-communicating hydrocephalus due to aqueductal stenosis. One showed oscillating flow between the lateral ventricles after craniotomy for intracranial haemorrhage. Seven patients showed normal flow: six had hydrocephalus ex vacuo due to brain atrophy. One patient who underwent ventriculostomy 10 years ago showed a flow path through the opening. Seven patients showed hypermotile flow: three had normal pressure hydrocephalus, three had dementia, and in one the diagnosis remained unclear. The diagnostic efficacy of velocity mapping was significantly higher except for that of aqueductal stenosis. Our approach may be useful for diagnosis, therapy planning, and follow-up of different kinds of hydrocephalus. (orig.)

  18. Magnetic resonance velocity mapping of 3D cerebrospinal fluid flow dynamics in hydrocephalus: preliminary results

    Stadlbauer, Andreas [Landesklinikum St. Poelten, MR Physics Group, Department of Radiology, St. Poelten (Austria); University of Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany); Salomonowitz, Erich [Landesklinikum St. Poelten, MR Physics Group, Department of Radiology, St. Poelten (Austria); Brenneis, Christian [Landesklinikum St. Poelten, Department of Neurology, St. Poelten (Austria); Ungersboeck, Karl [Landesklinikum St. Poelten, Department of Neurosurgery, St. Poelten (Austria); Riet, Wilma van der [European MRI Consultancy (EMRIC), Strasbourg (France); Buchfelder, Michael; Ganslandt, Oliver [University of Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

    2012-01-15

    To investigate the detectability of CSF flow alterations in the ventricular system of patients with hydrocephalus using time-resolved 3D MR velocity mapping. MR velocity mapping was performed in 21 consecutive hydrocephalus patients and 21 age-matched volunteers using a 3D phase-contrast (PC) sequence. Velocity vectors and particle path lines were calculated for visualisation of flow dynamics. CSF flow was classified as ''hypomotile flow'' if it showed attenuated dynamics and as ''hypermotile flow'' if it showed increased dynamics compared with volunteers. Diagnostic efficacy was compared with routine 2D cine PC-MRI. Seven patients showed hypomotile CSF flow: six had non-communicating hydrocephalus due to aqueductal stenosis. One showed oscillating flow between the lateral ventricles after craniotomy for intracranial haemorrhage. Seven patients showed normal flow: six had hydrocephalus ex vacuo due to brain atrophy. One patient who underwent ventriculostomy 10 years ago showed a flow path through the opening. Seven patients showed hypermotile flow: three had normal pressure hydrocephalus, three had dementia, and in one the diagnosis remained unclear. The diagnostic efficacy of velocity mapping was significantly higher except for that of aqueductal stenosis. Our approach may be useful for diagnosis, therapy planning, and follow-up of different kinds of hydrocephalus. (orig.)

  19. A sequence-based dynamic ensemble learning system for protein ligand-binding site prediction

    Chen, Peng

    2015-12-03

    Background: Proteins have the fundamental ability to selectively bind to other molecules and perform specific functions through such interactions, such as protein-ligand binding. Accurate prediction of protein residues that physically bind to ligands is important for drug design and protein docking studies. Most of the successful protein-ligand binding predictions were based on known structures. However, structural information is not largely available in practice due to the huge gap between the number of known protein sequences and that of experimentally solved structures

  20. A sequence-based dynamic ensemble learning system for protein ligand-binding site prediction

    Chen, Peng; Hu, ShanShan; Zhang, Jun; Gao, Xin; Li, Jinyan; Xia, Junfeng; Wang, Bing

    2015-01-01

    Background: Proteins have the fundamental ability to selectively bind to other molecules and perform specific functions through such interactions, such as protein-ligand binding. Accurate prediction of protein residues that physically bind to ligands is important for drug design and protein docking studies. Most of the successful protein-ligand binding predictions were based on known structures. However, structural information is not largely available in practice due to the huge gap between the number of known protein sequences and that of experimentally solved structures

  1. Void fraction measurement in two-phase flow processes via symbolic dynamic filtering of ultrasonic signals

    Chakraborty, Subhadeep; Keller, Eric; Talley, Justin; Srivastav, Abhishek; Ray, Asok; Kim, Seungjin

    2009-01-01

    This communication introduces a non-intrusive method for void fraction measurement and identification of two-phase flow regimes, based on ultrasonic sensing. The underlying algorithm is built upon the recently reported theory of a statistical pattern recognition method called symbolic dynamic filtering (SDF). The results of experimental validation, generated on a laboratory test apparatus, show a one-to-one correspondence between the flow measure derived from SDF and the void fraction measured by a conductivity probe. A sharp change in the slope of flow measure is found to be in agreement with a transition from fully bubbly flow to cap-bubbly flow. (rapid communication)

  2. The promising gas-dynamic schemes of vacuum deposition from the supersonic gas mixture flows

    Maltsev, R V; Rebrov, A K

    2008-01-01

    Gas jet deposition (GJD) becomes promising method of thin film and nanoparticle deposition. This paper is focused on elaboration of new methods of GJD based on different gas dynamic schemes of flow formation and interaction with substrate. Using direct statistical simulation method, the analysis was performed for: a) interaction of the jet from the sonic nozzle with a substrate; b) fan flow in the result of interaction of two opposite jets; c) convergent flow from the ring nozzle, directional to the axis; d) interaction of the jet after convergent flow with the substrate; e) fan flow in the result of interaction of two opposite jets after convergent expansion

  3. Nonlinear dynamics near the stability margin in rotating pipe flow

    Yang, Z.; Leibovich, S.

    1991-01-01

    The nonlinear evolution of marginally unstable wave packets in rotating pipe flow is studied. These flows depend on two control parameters, which may be taken to be the axial Reynolds number R and a Rossby number, q. Marginal stability is realized on a curve in the (R, q)-plane, and the entire marginal stability boundary is explored. As the flow passes through any point on the marginal stability curve, it undergoes a supercritical Hopf bifurcation and the steady base flow is replaced by a traveling wave. The envelope of the wave system is governed by a complex Ginzburg-Landau equation. The Ginzburg-Landau equation admits Stokes waves, which correspond to standing modulations of the linear traveling wavetrain, as well as traveling wave modulations of the linear wavetrain. Bands of wavenumbers are identified in which the nonlinear modulated waves are subject to a sideband instability.

  4. Quantum dynamical time evolutions as stochastic flows on phase space

    Combe, P.; Rodriguez, R.; Guerra, F.; Sirigue, M.; Sirigue-Collin, M.

    1984-01-01

    We are mainly interested in describing the time development of the Wigner functions by means of stochastic processes. In the second section we recall the main properties of the Wigner functions as well as those of their Fourier transform. In the next one we derive the evolution equation of these functions for a class of Hamiltonians and we give a probabilistic expression for the solution of these equations by means of a stochastic flow in phase space which reminds of the classical flows. In the last section we remark that the previously defined flow can be extended to the bounded continuous functions on phase space and that this flow conserves the cone generated by the Wigner functions. (orig./HSI)

  5. Dynamic emission tomography of regional cerebral blood flow

    Lassen, N.A.

    1984-01-01

    The author reviews three tomographic methods for measuring the regional cerebral blood flow: single photon transmission tomography; dual photon emission tomography; and single photon emission tomography. The latter technique is discussed in detail. (Auth.)

  6. Computational fluid dynamics analysis of a mixed flow pump impeller

    ATHARVA

    International Journal of Engineering, Science and Technology ... From the CFD analysis software and advanced post processing tools the complex flow inside the ... The numerical simulation can provide quite accurate information on the fluid ...

  7. Benchmarking computational fluid dynamics models of lava flow simulation for hazard assessment, forecasting, and risk management

    Dietterich, Hannah; Lev, Einat; Chen, Jiangzhi; Richardson, Jacob A.; Cashman, Katharine V.

    2017-01-01

    Numerical simulations of lava flow emplacement are valuable for assessing lava flow hazards, forecasting active flows, designing flow mitigation measures, interpreting past eruptions, and understanding the controls on lava flow behavior. Existing lava flow models vary in simplifying assumptions, physics, dimensionality, and the degree to which they have been validated against analytical solutions, experiments, and natural observations. In order to assess existing models and guide the development of new codes, we conduct a benchmarking study of computational fluid dynamics (CFD) models for lava flow emplacement, including VolcFlow, OpenFOAM, FLOW-3D, COMSOL, and MOLASSES. We model viscous, cooling, and solidifying flows over horizontal planes, sloping surfaces, and into topographic obstacles. We compare model results to physical observations made during well-controlled analogue and molten basalt experiments, and to analytical theory when available. Overall, the models accurately simulate viscous flow with some variability in flow thickness where flows intersect obstacles. OpenFOAM, COMSOL, and FLOW-3D can each reproduce experimental measurements of cooling viscous flows, and OpenFOAM and FLOW-3D simulations with temperature-dependent rheology match results from molten basalt experiments. We assess the goodness-of-fit of the simulation results and the computational cost. Our results guide the selection of numerical simulation codes for different applications, including inferring emplacement conditions of past lava flows, modeling the temporal evolution of ongoing flows during eruption, and probabilistic assessment of lava flow hazard prior to eruption. Finally, we outline potential experiments and desired key observational data from future flows that would extend existing benchmarking data sets.

  8. Dynamic surface-pressure instrumentation for rods in parallel flow

    Mulcahy, T.M.; Lawrence, W.

    1979-01-01

    Methods employed and experience gained in measuring random fluid boundary layer pressures on the surface of a small diameter cylindrical rod subject to dense, nonhomogeneous, turbulent, parallel flow in a relatively noise-contaminated flow loop are described. Emphasis is placed on identification of instrumentation problems; description of transducer construction, mounting, and waterproofing; and the pretest calibration required to achieve instrumentation capable of reliable data acquisition

  9. Zonal Flow Dynamics and Size-scaling of Anomalous Transport

    Liu Chen; White, Roscoe B.; Zonca, F.

    2003-01-01

    Nonlinear equations for the slow space-time evolution of the radial drift wave envelope and zonal flow amplitude have been self-consistently derived for a model nonuniform tokamak equilibrium within the coherent 4-wave drift wave-zonal flow modulation interaction model of Chen, Lin, and White [Phys. Plasmas 7 (2000) 3129]. Solutions clearly demonstrate turbulence spreading due to nonlinearly enhanced dispersiveness and, consequently, the device-size dependence of the saturated wave intensities and transport coefficients

  10. Dynamic Characteristics of The DSI-Type Constant-Flow Valves

    Kang, Yuan; Hu, Sheng-Yan; Chou, Hsien-Chin; Lee, Hsing-Han

    Constant flow valves have been presented in industrial applications or academic studies, which compensate recess pressures of a hydrostatic bearing to resist load fluctuating. The flow rate of constant-flow valves can be constant in spite of the pressure changes in recesses, however the design parameters must be specified. This paper analyzes the dynamic responses of DSI-type constant-flow valves that is designed as double pistons on both ends of a spool with single feedback of working pressure and regulating restriction at inlet. In this study the static analysis presents the specific relationships among design parameters for constant flow rate and the dynamic analyses give the variations around the constant flow rate as the working pressure fluctuates.

  11. Reduction of gas flow nonuniformity in gas turbine engines by means of gas-dynamic methods

    Matveev, V.; Baturin, O.; Kolmakova, D.; Popov, G.

    2017-08-01

    Gas flow nonuniformity is one of the main sources of rotor blade vibrations in the gas turbine engines. Usually, the flow circumferential nonuniformity occurs near the annular frames, located in the flow channel of the engine. This leads to the increased dynamic stresses in blades and as a consequence to the blade damage. The goal of the research was to find an acceptable method of reducing the level of gas flow nonuniformity as the source of dynamic stresses in the rotor blades. Two different methods were investigated during this research. Thus, this study gives the ideas about methods of improving the flow structure in gas turbine engine. On the basis of existing conditions (under development or existing engine) it allows the selection of the most suitable method for reducing gas flow nonuniformity.

  12. Vesicle dynamics in a confined Poiseuille flow: from steady state to chaos.

    Aouane, Othmane; Thiébaud, Marine; Benyoussef, Abdelilah; Wagner, Christian; Misbah, Chaouqi

    2014-09-01

    Red blood cells (RBCs) are the major component of blood, and the flow of blood is dictated by that of RBCs. We employ vesicles, which consist of closed bilayer membranes enclosing a fluid, as a model system to study the behavior of RBCs under a confined Poiseuille flow. We extensively explore two main parameters: (i) the degree of confinement of vesicles within the channel and (ii) the flow strength. Rich and complex dynamics for vesicles are revealed, ranging from steady-state shapes (in the form of parachute and slipper shapes) to chaotic dynamics of shape. Chaos occurs through a cascade of multiple periodic oscillations of the vesicle shape. We summarize our results in a phase diagram in the parameter plane (degree of confinement and flow strength). This finding highlights the level of complexity of a flowing vesicle in the small Reynolds number where the flow is laminar in the absence of vesicles and can be rendered turbulent due to elasticity of vesicles.

  13. Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

    Eleanna Stamatakou

    Full Text Available Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1 and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling.

  14. Millisecond dynamics in glutaredoxin during catalytic turnover is dependent on substrate binding and absent in the resting states

    Jensen, Kristine Steen; Winther, Jakob R; Teilum, Kaare

    2011-01-01

    to the glutathione exchange rate was observed for 23 residues. Binding of reduced glutathione resulted in competitive inhibition of the reduced enzyme having kinetics similar to that of the reaction. This observation couples the motions observed during catalysis directly to substrate binding. Backbone motions......Conformational dynamics is important for enzyme function. Which motions of enzymes determine catalytic efficiency and whether the same motions are important for all enzymes, however, are not well understood. Here we address conformational dynamics in glutaredoxin during catalytic turnover...... with a combination of NMR magnetization transfer, R(2) relaxation dispersion, and ligand titration experiments. Glutaredoxins catalyze a glutathione exchange reaction, forming a stable glutathinoylated enzyme intermediate. The equilibrium between the reduced state and the glutathionylated state was biochemically...

  15. Combinatorial computational chemistry approach of tight-binding quantum chemical molecular dynamics method to the design of the automotive catalysts

    Ito, Yuki; Jung, Changho; Luo, Yi; Koyama, Michihisa; Endou, Akira; Kubo, Momoji; Imamura, Akira; Miyamoto, Akira

    2006-01-01

    Recently, we have developed a new tight-binding quantum chemical molecular dynamics program 'Colors' for combinatorial computational chemistry approach. This methodology is based on our original tight-binding approximation and realized over 5000 times acceleration compared to the conventional first-principles molecular dynamics method. In the present study, we applied our new program to the simulations on various realistic large-scale models of the automotive three-way catalysts, ultrafine Pt particle/CeO 2 (111) support. Significant electron transfer from the Pt particle to the CeO 2 (111) surface was observed and it was found to strongly depend on the size of the Pt particle. Furthermore, our simulation results suggest that the reduction of the Ce atom due to the electron transfer from the Pt particle to the CeO 2 surface is a main reason for the strong interaction of the Pt particle and CeO 2 (111) support

  16. Dynamic modeling of renal blood flow in Dahl hypertensive and normotensive rats

    Knudsen, Torben; Elmer, Henrik; Knudsen, Morten H

    2004-01-01

    A method is proposed in this paper which allows characterization of renal autoregulatory dynamics and efficiency using quantitative mathematical methods. Based on data from rat experiments, where arterial blood pressure and renal blood flow are measured, a quantitative model for renal blood flow...

  17. Forecasting Multivariate Road Traffic Flows Using Bayesian Dynamic Graphical Models, Splines and Other Traffic Variables

    Anacleto, Osvaldo; Queen, Catriona; Albers, Casper J.

    Traffic flow data are routinely collected for many networks worldwide. These invariably large data sets can be used as part of a traffic management system, for which good traffic flow forecasting models are crucial. The linear multiregression dynamic model (LMDM) has been shown to be promising for

  18. CrossFlow: Cross-Organizational Workflow Management in Dynamic Virtual Enterprises

    Grefen, P.W.P.J.; Aberer, Karl; Hoffner, Yigal; Ludwig, Heiko

    In this report, we present the approach to cross-organizational workflow management of the CrossFlow project. CrossFlow is a European research project aiming at the support of cross-organizational workflows in dynamic virtual enterprises. The cooperation in these virtual enterprises is based on

  19. CrossFlow : cross-organizational workflow management in dynamic virtual enterprises

    Grefen, P.W.P.J.; Aberer, K.; Hoffner, Y.

    2000-01-01

    This paper gives a detailed overview of the approach to cross-organizational workflow management developed in the CrossFlow project. CrossFlow is a European research project aiming at the support of cross-organizational workflows in dynamic virtual enterprises. The cooperation in these virtual

  20. Continuous positive airway pressure alters cranial blood flow and cerebrospinal fluid dynamics at the craniovertebral junction

    Theresia I. Yiallourou

    2015-09-01

    Conclusion: Application of CPAP via a full-fitted mask at 15 cm H2O was found to have a significant effect on intracranial venous outflow and spinal CSF flow at the C2 vertebral level in healthy adult-age awake volunteers. CPAP can be used to non-invasively provoke changes in intracranial and CSF flow dynamics.

  1. Exploring the Relationship of Exit Flow and Jam Density in Panic Scenarios Using Animal Dynamics

    Sobhani, A.; Sarvi, M.; Duives, D.C.; Ejtemai, O.; Aghabayk, K.; Hoogendoorn, S.P.

    2014-01-01

    There are few studies investigating crowd dynamics in panic situations. They used measures such as exit flow rate to explore the exit performance in evacuation scenarios. However, there is limited research exploring the relationship of exit flow rate and density behind the exit for panic scenarios.

  2. Enhanced peptide nucleic acid binding to supercoiled DNA: possible implications for DNA "breathing" dynamics

    Bentin, T; Nielsen, Peter E.

    1996-01-01

    The influence of DNA topology on peptide nucleic acid (PNA) binding was studied. Formation of sequence-specific PNA2/dsDNA (double-stranded DNA) complexes was monitored by a potassium permanganate probing/primer extension assay. At low ionic strengths, the binding of PNA was 2-3 times more...

  3. Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Sechi, Mario; Mukhtar, Hasan

    2015-01-01

    Microtubule targeting based therapies have revolutionized cancer treatment; however, resistance and side effects remain a major limitation. Therefore, novel strategies that can overcome these limitations are urgently needed. We made a novel discovery that fisetin, a hydroxyflavone, is a microtubule stabilizing agent. Fisetin binds to tubulin and stabilizes microtubules with binding characteristics far superior than paclitaxel. Surface plasmon resonance and computational docking studies sugges...

  4. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

    Mao, Grace; Brody, James P.

    2007-01-01

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16 bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16 bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014 s -1 . We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase

  5. Visualizing double-stranded RNA distribution and dynamics in living cells by dsRNA binding-dependent fluorescence complementation

    Cheng, Xiaofei; Deng, Ping; Cui, Hongguang; Wang, Aiming

    2015-01-01

    Double-stranded RNA (dsRNA) is an important type of RNA that plays essential roles in diverse cellular processes in eukaryotic organisms and a hallmark in infections by positive-sense RNA viruses. Currently, no in vivo technology has been developed for visualizing dsRNA in living cells. Here, we report a dsRNA binding-dependent fluorescence complementation (dRBFC) assay that can be used to efficiently monitor dsRNA distribution and dynamics in vivo. The system consists of two dsRNA-binding proteins, which are fused to the N- and C-terminal halves of the yellow fluorescent protein (YFP). Binding of the two fusion proteins to a common dsRNA brings the split YFP halves in close proximity, leading to the reconstitution of the fluorescence-competent structure and restoration of fluorescence. Using this technique, we were able to visualize the distribution and trafficking of the replicative RNA intermediates of positive-sense RNA viruses in living cells. - Highlights: • A live-cell imaging system was developed for visualizing dsRNA in vivo. • It uses dsRNA binding proteins fused with two halves of a fluorescent protein. • Binding to a common dsRNA enables the reporter to become fluorescent. • The system can efficiently monitor viral RNA replication in living cells.

  6. Visualizing double-stranded RNA distribution and dynamics in living cells by dsRNA binding-dependent fluorescence complementation

    Cheng, Xiaofei [Southern Crop Protection and Food Research Centre, Agriculture and Agri-Food Canada, London, Ontario N5V 4T3 (Canada); College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036 (China); Deng, Ping; Cui, Hongguang [Southern Crop Protection and Food Research Centre, Agriculture and Agri-Food Canada, London, Ontario N5V 4T3 (Canada); Wang, Aiming, E-mail: aiming.wang@agr.gc.ca [Southern Crop Protection and Food Research Centre, Agriculture and Agri-Food Canada, London, Ontario N5V 4T3 (Canada)

    2015-11-15

    Double-stranded RNA (dsRNA) is an important type of RNA that plays essential roles in diverse cellular processes in eukaryotic organisms and a hallmark in infections by positive-sense RNA viruses. Currently, no in vivo technology has been developed for visualizing dsRNA in living cells. Here, we report a dsRNA binding-dependent fluorescence complementation (dRBFC) assay that can be used to efficiently monitor dsRNA distribution and dynamics in vivo. The system consists of two dsRNA-binding proteins, which are fused to the N- and C-terminal halves of the yellow fluorescent protein (YFP). Binding of the two fusion proteins to a common dsRNA brings the split YFP halves in close proximity, leading to the reconstitution of the fluorescence-competent structure and restoration of fluorescence. Using this technique, we were able to visualize the distribution and trafficking of the replicative RNA intermediates of positive-sense RNA viruses in living cells. - Highlights: • A live-cell imaging system was developed for visualizing dsRNA in vivo. • It uses dsRNA binding proteins fused with two halves of a fluorescent protein. • Binding to a common dsRNA enables the reporter to become fluorescent. • The system can efficiently monitor viral RNA replication in living cells.

  7. Collective dynamics of particles from viscous to turbulent flows

    2017-01-01

    The book surveys the state-of-the-art methods that are currently available to model and simulate the presence of rigid particles in a fluid flow. For particles that are very small relative to the characteristic flow scales and move without interaction with other particles, effective equations of motion for particle tracking are formulated and applied (e.g. in gas-solid flows). For larger particles, for particles in liquid-solid flows and for particles that interact with each other or possibly modify the overall flow detailed model are presented. Special attention is given to the description of the approximate force coupling method (FCM) as a more general treatment for small particles, and derivations in the context of low Reynolds numbers for the particle motion as well as application at finite Reynolds numbers are provided. Other topics discussed in the book are the relation to higher resolution immersed boundary methods, possible extensions to non-spherical particles and examples of applications of such met...

  8. Investigation of Swirling Flow in Rod Bundle Subchannels Using Computational Fluid Dynamics

    Holloway, Mary V.; Beasley, Donald E.; Conner, Michael E.

    2006-01-01

    The fluid dynamics for turbulent flow through rod bundles representative of those used in pressurized water reactors is examined using computational fluid dynamics (CFD). The rod bundles of the pressurized water reactor examined in this study consist of a square array of parallel rods that are held on a constant pitch by support grids spaced axially along the rod bundle. Split-vane pair support grids are often used to create swirling flow in the rod bundle in an effort to improve the heat transfer characteristics for the rod bundle during both normal operating conditions and in accident condition scenarios. Computational fluid dynamics simulations for a two subchannel portion of the rod bundle were used to model the flow downstream of a split-vane pair support grid. A high quality computational mesh was used to investigate the choice of turbulence model appropriate for the complex swirling flow in the rod bundle subchannels. Results document a central swirling flow structure in each of the subchannels downstream of the split-vane pairs. Strong lateral flows along the surface of the rods, as well as impingement regions of lateral flow on the rods are documented. In addition, regions of lateral flow separation and low axial velocity are documented next to the rods. Results of the CFD are compared to experimental particle image velocimetry (PIV) measurements documenting the lateral flow structures downstream of the split-vane pairs. Good agreement is found between the computational simulation and experimental measurements for locations close to the support grid. (authors)

  9. Experimental Investigation of Hysteretic Dynamic Capillarity Effect in Unsaturated Flow

    Zhuang, Luwen; Hassanizadeh, S. Majid; Qin, Chao-Zhong; de Waal, Arjen

    2017-11-01

    The difference between average pressures of two immiscible fluids is commonly assumed to be the same as macroscopic capillary pressure, which is considered to be a function of saturation only. However, under transient conditions, a dependence of this pressure difference on the time rate of saturation change has been observed by many researchers. This is commonly referred to as dynamic capillarity effect. As a first-order approximation, the dynamic term is assumed to be linearly dependent on the time rate of change of saturation, through a material coefficient denoted by τ. In this study, a series of laboratory experiments were carried out to quantify the dynamic capillarity effect in an unsaturated sandy soil. Primary, main, and scanning drainage experiments, under both static and dynamic conditions, were performed on a sandy soil in a small cell. The value of the dynamic capillarity coefficient τ was calculated from the air-water pressure differences and average saturation values during static and dynamic drainage experiments. We found a dependence of τ on saturation, which showed a similar trend for all drainage conditions. However, at any given saturation, the value of τ for primary drainage was larger than the value for main drainage and that was in turn larger than the value for scanning drainage. Each data set was fit a simple log-linear equation, with different values of fitting parameters. This nonuniqueness of the relationship between τ and saturation and possible causes is discussed.

  10. Estimation of vessel diameter and blood flow dynamics from laser speckle images

    Postnov, Dmitry D.; Tuchin, Valery V.; Sosnovtseva, Olga

    2016-01-01

    Laser speckle imaging is a rapidly developing method to study changes of blood velocity in the vascular networks. However, to assess blood flow and vascular responses it is crucial to measure vessel diameter in addition to blood velocity dynamics. We suggest an algorithm that allows for dynamical...

  11. Alignment dynamics of diffusive scalar gradient in a two-dimensional model flow

    Gonzalez, M.

    2018-04-01

    The Lagrangian two-dimensional approach of scalar gradient kinematics is revisited accounting for molecular diffusion. Numerical simulations are performed in an analytic, parameterized model flow, which enables considering different regimes of scalar gradient dynamics. Attention is especially focused on the influence of molecular diffusion on Lagrangian statistical orientations and on the dynamics of scalar gradient alignment.

  12. On the Mutual Dynamics of Interregional Gross Migration Flows in Space and Time

    Mitze, Timo

    2016-01-01

    This paper applies spatial dynamic panel data models to analyse the labor market dimension of interregional population flows among German federal states in the period 1993–2009. Making use of recent improvements in the estimation of space-time dynamic panel data models and the computation of mean...

  13. Automated Analysis of Flow Cytometry Data to Reduce Inter-Lab Variation in the Detection of Major Histocompatibility Complex Multimer-Binding T Cells

    Pedersen, Natasja Wulff; Chandran, P. Anoop; Qian, Yu

    2017-01-01

    Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual labs. Therefore, strategies to provide...... automated analysis of major histocompatibility complex (MHC) multimer-binding T cells represent an attractive solution to decrease subjectivity and technical variation. The challenge of using an automated analysis approach is that MHC multimer-binding T cell populations are often rare and therefore...... laboratories. We used three different methods, FLOw Clustering without K (FLOCK), Scalable Weighted Iterative Flow-clustering Technique (SWIFT), and ReFlow to analyze flow cytometry data files from 28 laboratories. Each laboratory screened for antigen-responsive T cell populations with frequency ranging from 0...

  14. Large eddy simulation of spanwise rotating turbulent channel flow with dynamic variants of eddy viscosity model

    Jiang, Zhou; Xia, Zhenhua; Shi, Yipeng; Chen, Shiyi

    2018-04-01

    A fully developed spanwise rotating turbulent channel flow has been numerically investigated utilizing large-eddy simulation. Our focus is to assess the performances of the dynamic variants of eddy viscosity models, including dynamic Vreman's model (DVM), dynamic wall adapting local eddy viscosity (DWALE) model, dynamic σ (Dσ ) model, and the dynamic volumetric strain-stretching (DVSS) model, in this canonical flow. The results with dynamic Smagorinsky model (DSM) and direct numerical simulations (DNS) are used as references. Our results show that the DVM has a wrong asymptotic behavior in the near wall region, while the other three models can correctly predict it. In the high rotation case, the DWALE can get reliable mean velocity profile, but the turbulence intensities in the wall-normal and spanwise directions show clear deviations from DNS data. DVSS exhibits poor predictions on both the mean velocity profile and turbulence intensities. In all three cases, Dσ performs the best.

  15. Nuclear dynamics with the (finite range) Gogny force: flow effects

    Sebille, F.; Royer, G.; Schuck, P.; Gregoire, C.

    1988-01-01

    We introduce for the first time the effective finite range interaction of Gogny in the semi-classical description of heavy ion reactions based on the Landau-Vlasov equation. The characteristics of the flow for heavy ion collisions are studied as functions of the incident energy, the impact parameter and the mass number. The momentum dependence in the mean field together with the non linearities in the collision kernel decrease the flow in contradiction with other calculations; the origins of this discrepancy are studied in details

  16. Flow cytometric sex sorting affects CD4 membrane distribution and binding of exogenous DNA on bovine sperm cells.

    Domingues, William Borges; da Silveira, Tony Leandro Rezende; Komninou, Eliza Rossi; Monte, Leonardo Garcia; Remião, Mariana Härter; Dellagostin, Odir Antônio; Corcini, Carine Dahl; Varela Junior, Antônio Sergio; Seixas, Fabiana Kömmling; Collares, Tiago; Campos, Vinicius Farias

    2017-08-01

    Bovine sex-sorted sperm have been commercialized and successfully used for the production of transgenic embryos of the desired sex through the sperm-mediated gene transfer (SMGT) technique. However, sex-sorted sperm show a reduced ability to internalize exogenous DNA. The interaction between sperm cells and the exogenous DNA has been reported in other species to be a CD4-like molecule-dependent process. The flow cytometry-based sex-sorting process subjects the spermatozoa to different stresses causing changes in the cell membrane. The aim of this study was to elucidate the relationship between the redistribution of CD4-like molecules and binding of exogenous DNA to sex-sorted bovine sperm. In the first set of experiments, the membrane phospholipid disorder and the redistribution of the CD4 were evaluated. The second set of experiments was conducted to investigate the effect of CD4 redistribution on the mechanism of binding of exogenous DNA to sperm cells and the efficiency of lipofection in sex-sorted bovine sperm. Sex-sorting procedure increased the membrane phospholipid disorder and induced the redistribution of CD4-like molecules. Both X-sorted and Y-sorted sperm had decreased DNA bound to membrane in comparison with the unsorted sperm; however, the binding of the exogenous DNA was significantly increased with the addition of liposomes. Moreover, we demonstrated that the number of sperm-bound exogenous DNA was decreased when these cells were preincubated with anti-bovine CD4 monoclonal antibody, supporting our hypothesis that CD4-like molecules indeed play a crucial role in the process of exogenous DNA/bovine sperm cells interaction.

  17. Chaos in a dynamic model of urban transportation network flow based on user equilibrium states

    Xu Meng; Gao Ziyou

    2009-01-01

    In this study, we investigate the dynamical behavior of network traffic flow. We first build a two-stage mathematical model to analyze the complex behavior of network flow, a dynamical model, which is based on the dynamical gravity model proposed by Dendrinos and Sonis [Dendrinos DS, Sonis M. Chaos and social-spatial dynamic. Berlin: Springer-Verlag; 1990] is used to estimate the number of trips. Considering the fact that the Origin-Destination (O-D) trip cost in the traffic network is hard to express as a functional form, in the second stage, the user equilibrium network assignment model was used to estimate the trip cost, which is the minimum cost of used path when user equilibrium (UE) conditions are satisfied. It is important to use UE to estimate the O-D cost, since a connection is built among link flow, path flow, and O-D flow. The dynamical model describes the variations of O-D flows over discrete time periods, such as each day and each week. It is shown that even in a system with dimensions equal to two, chaos phenomenon still exists. A 'Chaos Propagation' phenomenon is found in the given model.

  18. The Verrucomicrobia LexA-binding Motif: Insights into the Evolutionary Dynamics of the SOS Response

    Ivan Erill

    2016-07-01

    Full Text Available The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls.

  19. The Verrucomicrobia LexA-Binding Motif: Insights into the Evolutionary Dynamics of the SOS Response.

    Erill, Ivan; Campoy, Susana; Kılıç, Sefa; Barbé, Jordi

    2016-01-01

    The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division, and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls.

  20. A dynamic globalization model for large eddy simulation of complex turbulent flow

    Choi, Hae Cheon; Park, No Ma; Kim, Jin Seok [Seoul National Univ., Seoul (Korea, Republic of)

    2005-07-01

    A dynamic subgrid-scale model is proposed for large eddy simulation of turbulent flows in complex geometry. The eddy viscosity model by Vreman [Phys. Fluids, 16, 3670 (2004)] is considered as a base model. A priori tests with the original Vreman model show that it predicts the correct profile of subgrid-scale dissipation in turbulent channel flow but the optimal model coefficient is far from universal. Dynamic procedures of determining the model coefficient are proposed based on the 'global equilibrium' between the subgrid-scale dissipation and viscous dissipation. An important feature of the proposed procedures is that the model coefficient determined is globally constant in space but varies only in time. Large eddy simulations with the present dynamic model are conducted for forced isotropic turbulence, turbulent channel flow and flow over a sphere, showing excellent agreements with previous results.

  1. Mode decomposition and Lagrangian structures of the flow dynamics in orbitally shaken bioreactors

    Weheliye, Weheliye Hashi; Cagney, Neil; Rodriguez, Gregorio; Micheletti, Martina; Ducci, Andrea

    2018-03-01

    In this study, two mode decomposition techniques were applied and compared to assess the flow dynamics in an orbital shaken bioreactor (OSB) of cylindrical geometry and flat bottom: proper orthogonal decomposition and dynamic mode decomposition. Particle Image Velocimetry (PIV) experiments were carried out for different operating conditions including fluid height, h, and shaker rotational speed, N. A detailed flow analysis is provided for conditions when the fluid and vessel motions are in-phase (Fr = 0.23) and out-of-phase (Fr = 0.47). PIV measurements in vertical and horizontal planes were combined to reconstruct low order models of the full 3D flow and to determine its Finite-Time Lyapunov Exponent (FTLE) within OSBs. The combined results from the mode decomposition and the FTLE fields provide a useful insight into the flow dynamics and Lagrangian coherent structures in OSBs and offer a valuable tool to optimise bioprocess design in terms of mixing and cell suspension.

  2. Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state.

    Becka M Warfield

    Full Text Available RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are

  3. Rescheduling of Railway Rolling Stock with Dynamic Passenger Flows

    L.G. Kroon (Leo); G. Maróti (Gábor); L.K. Nielsen (Lars Kjaer)

    2010-01-01

    textabstractTraditional rolling stock rescheduling applications either treat passengers as static objects whose influence on the system is unchanged in a disrupted situation, or they treat passenger behavior as a given input. In case of disruptions however, we may expect the flow of passengers to

  4. Pulsatility role in cylinder flow dynamics at low Reynolds number

    Qamar, Adnan; Samtaney, Ravi; Bull, Joseph L.

    2012-01-01

    range of TAL. Two distinct fluid regimes are identified. In both regimes, the size of the separated zone is much greater than the uniform flow case, the onset of separation is function of KC, and the separation vortex collapses rapidly during the last

  5. Modelling flow dynamics in water distribution networks using ...

    DR OKE

    was used for modelling the flow and simulate water demand using a Matlab .... This process requires that the neural network compute the error derivative of the .... Furthermore, Matlab was used as a simulation tool; and the first step was ...

  6. European Integration, Labour Market Dynamics and Migration Flows

    Martinoia, Michela

    2011-06-01

    Full Text Available The paper has two objectives. Firstly, we wish to evaluate whether a greater economic integration has effects, and of what type, on migration flows from Central and Eastern Europe (New Member States of the EU, NMS towards the fifteen countries of the European Union (EU-15. Secondly, we wish to understand what effect the migration flows from the NMS have on the labour market of the receiving countries in the EU-15. The most suitable theoretical context that seems to summarise European labour market characteristics is that of the insider/outsider model by Layard, Nickell and Jackman (Layard et al., 1991. We have modified the above mentioned model by introducing two innovations. Firstly, we constructed three measures that act as a proxy for economic integration: the Intra Regional Trade Index (IRTI, Global Trade Index (GTI and Financial Market Integration (FMI. Then we placed the three indicators into the insider/outsider model to arrive at a modified version of Layard, Nickell and Jackman (Layard et al., 1991. The second innovative contribution was the introduction of an equation modelling migration flows. The creation of this equation is inspired by the neo-classical approach to migration theory (Harris-Todaro, 1970. The theoretical model, based on rational expectations, has been solved to find the equilibrium solution and the impact multipliers. We then carried out an empirical analysis, which involved estimating a Structural Vector Autoregression Model (SVAR. The aim of this estimation was to evaluate, on the one hand, the effect that greater European integration (a positive shock to the integration indicators has on migration flows, and, on the other, to measure the type of effect that migration flows could have on the labour market of the EU-15 countries, considered as a single entity. The results of our empirical evidence show that economic integration does generate significant effects on migration flows from the enlargement countries

  7. Optimization of a new flow design for solid oxide cells using computational fluid dynamics modelling

    Duhn, Jakob Dragsbæk; Jensen, Anker Degn; Wedel, Stig

    2016-01-01

    Design of a gas distributor to distribute gas flow into parallel channels for Solid Oxide Cells (SOC) is optimized, with respect to flow distribution, using Computational Fluid Dynamics (CFD) modelling. The CFD model is based on a 3d geometric model and the optimized structural parameters include...... the width of the channels in the gas distributor and the area in front of the parallel channels. The flow of the optimized design is found to have a flow uniformity index value of 0.978. The effects of deviations from the assumptions used in the modelling (isothermal and non-reacting flow) are evaluated...... and it is found that a temperature gradient along the parallel channels does not affect the flow uniformity, whereas a temperature difference between the channels does. The impact of the flow distribution on the maximum obtainable conversion during operation is also investigated and the obtainable overall...

  8. Simultaneous injection effective mixing flow analysis of urinary albumin using dye-binding reaction.

    Ratanawimarnwong, Nuanlaor; Ponhong, Kraingkrai; Teshima, Norio; Nacapricha, Duangjai; Grudpan, Kate; Sakai, Tadao; Motomizu, Shoji

    2012-07-15

    A new four-channel simultaneous injection effective mixing flow analysis (SIEMA) system has been assembled for the determination of urinary albumin. The SIEMA system consisted of a syringe pump, two 5-way cross connectors, four holding coils, five 3-way solenoid valves, a 50-cm long mixing coil and a spectrophotometer. Tetrabromophenol blue anion (TBPB) in Triton X-100 micelle reacted with albumin at pH 3.2 to form a blue ion complex with a λ(max) 625nm. TBPB, Triton X-100, acetate buffer and albumin standard solutions were aspirated into four individual holding coils by a syringe pump and then the aspirated zones were simultaneously pushed in the reverse direction to the detector flow cell. Baseline drift, due to adsorption of TBPB-albumin complex on the wall of the hydrophobic PTFE tubing, was minimized by aspiration of Triton X-100 and acetate buffer solutions between samples. The calibration graph was linear in the range of 10-50μg/mL and the detection limit for albumin (3σ) was 0.53μg/mL. The RSD (n=11) at 30μg/mL was 1.35%. The sample throughput was 37/h. With a 10-fold dilution, interference from urine matrix was removed. The proposed method has advantages in terms of simple automation operation and short analysis time. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Dynamic Transitions and Baroclinic Instability for 3D Continuously Stratified Boussinesq Flows

    Şengül, Taylan; Wang, Shouhong

    2018-02-01

    The main objective of this article is to study the nonlinear stability and dynamic transitions of the basic (zonal) shear flows for the three-dimensional continuously stratified rotating Boussinesq model. The model equations are fundamental equations in geophysical fluid dynamics, and dynamics associated with their basic zonal shear flows play a crucial role in understanding many important geophysical fluid dynamical processes, such as the meridional overturning oceanic circulation and the geophysical baroclinic instability. In this paper, first we derive a threshold for the energy stability of the basic shear flow, and obtain a criterion for local nonlinear stability in terms of the critical horizontal wavenumbers and the system parameters such as the Froude number, the Rossby number, the Prandtl number and the strength of the shear flow. Next, we demonstrate that the system always undergoes a dynamic transition from the basic shear flow to either a spatiotemporal oscillatory pattern or circle of steady states, as the shear strength of the basic flow crosses a critical threshold. Also, we show that the dynamic transition can be either continuous or catastrophic, and is dictated by the sign of a transition number, fully characterizing the nonlinear interactions of different modes. Both the critical shear strength and the transition number are functions of the system parameters. A systematic numerical method is carried out to explore transition in different flow parameter regimes. In particular, our numerical investigations show the existence of a hypersurface which separates the parameter space into regions where the basic shear flow is stable and unstable. Numerical investigations also yield that the selection of horizontal wave indices is determined only by the aspect ratio of the box. We find that the system admits only critical eigenmodes with roll patterns aligned with the x-axis. Furthermore, numerically we encountered continuous transitions to multiple

  10. Hybrid Approximate Dynamic Programming Approach for Dynamic Optimal Energy Flow in the Integrated Gas and Power Systems

    Shuai, Hang; Ai, Xiaomeng; Wen, Jinyu

    2017-01-01

    This paper proposes a hybrid approximate dynamic programming (ADP) approach for the multiple time-period optimal power flow in integrated gas and power systems. ADP successively solves Bellman's equation to make decisions according to the current state of the system. So, the updated near future...

  11. Separation Dynamics of Controlled Internal Flow in an Adverse Pressure Gradient

    Peterson, C. J.; Vukasinovic, B.; Glezer, A.

    2017-11-01

    The effects of fluidic actuation on the dynamic evolution of aggressive internal flow separation is investigated at speeds up to M = 0.4 within a constant-width diffuser branching off of a primary flow duct. It is shown that a spanwise array of fluidic actuators upstream of the separation actively controls the flow constriction (and losses) within the diffuser and consequently the local pressure gradient at its entrance. The effectiveness of the actuation, as may be measured by the increased flow rate that is diverted through the diffuser, scales with its flow rate coefficient. In the presence of actuation (0.7% mass fraction), the mass flow rate in the primary duct increases by 10% while the fraction of the diverted mass flow rate in the diffuser increases by more than 45%. The flow dynamics near separation in the absence and presence of actuation are characterized using high speed particle image velocimetry and analyzed using proper orthogonal and spectral decompositions. In particular, the spectral contents of the incipient boundary layer separation are compared in the absence and presence of actuation with emphasis on the changes in local dynamics near separation as the characteristic cross stream scale of the boundary layer increases with separation delay.

  12. IBiSA_Tools: A Computational Toolkit for Ion-Binding State Analysis in Molecular Dynamics Trajectories of Ion Channels.

    Kota Kasahara

    Full Text Available Ion conduction mechanisms of ion channels are a long-standing conundrum. Although the molecular dynamics (MD method has been extensively used to simulate ion conduction dynamics at the atomic level, analysis and interpretation of MD results are not straightforward due to complexity of the dynamics. In our previous reports, we proposed an analytical method called ion-binding state analysis to scrutinize and summarize ion conduction mechanisms by taking advantage of a variety of analytical protocols, e.g., the complex network analysis, sequence alignment, and hierarchical clustering. This approach effectively revealed the ion conduction mechanisms and their dependence on the conditions, i.e., ion concentration and membrane voltage. Here, we present an easy-to-use computational toolkit for ion-binding state analysis, called IBiSA_tools. This toolkit consists of a C++ program and a series of Python and R scripts. From the trajectory file of MD simulations and a structure file, users can generate several images and statistics of ion conduction processes. A complex network named ion-binding state graph is generated in a standard graph format (graph modeling language; GML, which can be visualized by standard network analyzers such as Cytoscape. As a tutorial, a trajectory of a 50 ns MD simulation of the Kv1.2 channel is also distributed with the toolkit. Users can trace the entire process of ion-binding state analysis step by step. The novel method for analysis of ion conduction mechanisms of ion channels can be easily used by means of IBiSA_tools. This software is distributed under an open source license at the following URL: http://www.ritsumei.ac.jp/~ktkshr/ibisa_tools/.

  13. Dynamics of a two-phase flow through a minichannel: Transition from churn to slug flow

    Górski, Grzegorz; Litak, Grzegorz; Mosdorf, Romuald; Rysak, Andrzej

    2016-04-01

    The churn-to-slug flow bifurcations of two-phase (air-water) flow patterns in a 2mm diameter minichannel were investigated. With increasing a water flow rate, we observed the transition of slugs to bubbles of different sizes. The process was recorded by a digital camera. The sequences of light transmission time series were recorded by a laser-phototransistor sensor, and then analyzed using the recurrence plots and recurrence quantification analysis (RQA). Due to volume dependence of bubbles velocities, we observed the formation of periodic modulations in the laser signal.

  14. Multiphase flow dynamics 2 thermal and mechanical interactions

    Kolev, Nikolay I

    2007-01-01

    The industrial use of multi-phase systems requires analytical and numerical strategies for predicting their behavior. This book contains theory, methods and practical experience for describing complex transient multi-phase processes. It provides a systematic presentation of the theory and practice of numerical multi-phase fluid dynamics.

  15. Flow Dynamics and Nutrient Reduction in Rain Gardens

    The hydrological dynamics and changes in stormwater nutrient concentrations within rain gardens were studied by introducing captured stormwater runoff to rain gardens at EPA’s Urban Water Research Facility in Edison, New Jersey. The runoff used in these experiments was collected...

  16. Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans

    Boushel, Robert Christopher; Langberg, H; Green, Sara Marie Ehrenreich

    2000-01-01

    1. Circulation around tendons may act as a shunt for muscle during exercise. The perfusion and oxygenation of Achilles' peritendinous tissue was measured in parallel with that of calf muscle during exercise to determine (1) whether blood flow is restricted in peritendinous tissue during exercise......, and (2) whether blood flow is coupled to oxidative metabolism. 2. Seven individuals performed dynamic plantar flexion from 1 to 9 W. Radial artery and popliteal venous blood were sampled for O2, peritendinous blood flow was determined by 133Xe-washout, calf blood flow by plethysmography, cardiac output...

  17. Collective flow as a probe of heavy-ion reaction dynamics

    Awes, T.C.

    1997-01-01

    Collective flow of nuclear matter probes the dynamics of heavy-ion reactions and can provide information about the nuclear-matter equation of state. In particular, the incident energy dependences of collective flow may be a sensitive means to deduce the existence of a Quark Gluon Plasma phase in the equation of state. Collective flow measurements from 30 A MeV to 200 A GeV incident energies are briefly reviewed. Preliminary results on collective flow from the WA98 experiment at the CERN SPS are presented

  18. Two-phase flow dynamics in a model steam generator under vertical acceleration oscillation field

    Ishida, T.; Teshima, N.; Sakurai, S.

    1992-01-01

    The influence of periodically varying acceleration on hydrodynamic response has been studied experimentally using an experimental rig which models a marine reactor subject to vertical motion. The effect on the primary loop is small, but the effect on the secondary loop is large. The variables of the secondary loop, such as circulation flow rate and water level, oscillate with acceleration. The variation of gains in frequency response is analysed. The variations of flow in the secondary loop and in the downcome water level, increase in proportion to the acceleration. The effect of the flow resistance in the secondary loop on the two-phase flow dynamics is clarified. (7 figures) (Author)

  19. Low-angle dunes in the Changjiang (Yangtze) Estuary: Flow and sediment dynamics under tidal influence

    Hu, Hao; Wei, Taoyuan; Yang, Zhongyong; Hackney, Christopher R.; Parsons, Daniel R.

    2018-05-01

    It has long been highlighted that important feedbacks exist between river bed morphology, sediment transport and the turbulent flow field and that these feedbacks change in response to forcing mechanisms. However, our current understanding of bedform dynamics is largely based on studies of steady flow environments and cohesionless bed conditions. Few investigations have been made under rapidly changing flows. Here, we examine flow and sediment dynamics over low-angle dunes in unsteady flows in the Changjiang (Yangtze) Estuary, China. Topography, flow and sediment data were collected over a reach ca 1.8 km long through a semi-diurnal tidal cycle in a moderate tide of flood season. The results show that: (1) roughness length derived from the upper flow changes little with the flow reversing and displays the same value on both the ebb and flood tide. Moreover, the variability of individual bedform features plays an important role in roughness length variation. (2) Shear stress over the crest of low-angle dunes roughly represents the total spatially averaged stress over dunes in this study area, which has significant implications for advancing numerical models. (3) Changes in morphology, flow and sediment dynamics over dunes through time reveal how low-angle dunes evolve within a tidal cycle. (4) The clockwise hysteresis loops between flow dynamics and bedform features (height and aspect ratio) are also observed. The combination of suspended sediment transport and bedload transport on dune transformation and migration attributes to the clockwise hysteresis. The specific sediment composition of the riverbed, in some extent, affects the mechanism of sediment transport related to the exchange between suspended sediment and riverbed, but further investigation is needed to figure out the mechanism behind this for extended series of tides, such as spring/neap tide and tides in flooding and dry season.

  20. Affinity enhancement of nanobody binding to EGFR: in silico site-directed mutagenesis and molecular dynamics simulation approaches.

    Farasat, Alireza; Rahbarizadeh, Fatemeh; Hosseinzadeh, Ghader; Sajjadi, Sharareh; Kamali, Mehdi; Keihan, Amir Homayoun

    2017-06-01

    Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is overexpressed in many cancers such as head-neck, breast, prostate, and skin cancers for this reason it is a good target in cancer therapy and diagnosis. In nanobody-based cancer diagnosis and treatment, nanobodies with high affinity toward receptor (e.g. EGFR) results in effective treatment or diagnosis of cancer. In this regard, the main aim of this study is to develop a method based on molecular dynamic (MD) simulations for designing of 7D12 based nanobody with high affinity compared with wild-type nanobody. By surveying electrostatic and desolvation interactions between different residues of 7D12 and EGFR, the critical residues of 7D12 that play the main role in the binding of 7D12 to EGFR were elucidated and based on these residues, five logical variants were designed. Following the 50 ns MD simulations, pull and umbrella sampling simulation were performed for 7D12 and all its variants in complex with EGFR. Binding free energy of 7D12 (and all its variants) with EGFR was obtained by weighted histogram analysis method. According to binding free energy results, GLY101 to GLU mutation showed the highest binding affinity but this variant is unstable after 50 ns MD simulations. ALA100 to GLU mutation shows suitable binding enhancement with acceptable structural stability. Suitable position and orientation of GLU in residue 100 of 7D12 against related amino acids of EGFR formed some extra hydrogen and electrostatic interactions which resulted in binding enhancement.

  1. Computing the binding affinity of a ligand buried deep inside a protein with the hybrid steered molecular dynamics

    Villarreal, Oscar D.; Yu, Lili; Rodriguez, Roberto A.; Chen, Liao Y.

    2017-01-01

    Computing the ligand-protein binding affinity (or the Gibbs free energy) with chemical accuracy has long been a challenge for which many methods/approaches have been developed and refined with various successful applications. False positives and, even more harmful, false negatives have been and still are a common occurrence in practical applications. Inevitable in all approaches are the errors in the force field parameters we obtain from quantum mechanical computation and/or empirical fittings for the intra- and inter-molecular interactions. These errors propagate to the final results of the computed binding affinities even if we were able to perfectly implement the statistical mechanics of all the processes relevant to a given problem. And they are actually amplified to various degrees even in the mature, sophisticated computational approaches. In particular, the free energy perturbation (alchemical) approaches amplify the errors in the force field parameters because they rely on extracting the small differences between similarly large numbers. In this paper, we develop a hybrid steered molecular dynamics (hSMD) approach to the difficult binding problems of a ligand buried deep inside a protein. Sampling the transition along a physical (not alchemical) dissociation path of opening up the binding cavity- -pulling out the ligand- -closing back the cavity, we can avoid the problem of error amplifications by not relying on small differences between similar numbers. We tested this new form of hSMD on retinol inside cellular retinol-binding protein 1 and three cases of a ligand (a benzylacetate, a 2-nitrothiophene, and a benzene) inside a T4 lysozyme L99A/M102Q(H) double mutant. In all cases, we obtained binding free energies in close agreement with the experimentally measured values. This indicates that the force field parameters we employed are accurate and that hSMD (a brute force, unsophisticated approach) is free from the problem of error amplification suffered by

  2. A compact and versatile dynamic flow cryostat for photon science

    van der Linden, Peter J. E. M.; Moretti Sala, Marco; Henriquet, Christian; Rossi, Matteo; Ohgushi, Kenya; Fauth, François; Simonelli, Laura; Marini, Carlo; Fraga, Edmundo; Murray, Claire; Potter, Jonathan; Krisch, Michael

    2016-11-01

    We have developed a helium gas flow cryostat for use on synchrotron tender to hard X-ray beamlines. Very efficient sample cooling is achieved because the sample is placed directly in the cooling helium flow on a removable sample holder. The cryostat is compact and easy to operate; samples can be changed in less than 5 min at any temperature. The cryostat has a temperature range of 2.5-325 K with temperature stability better than 0.1 K. The very wide optical angle and the ability to operate in any orientation mean that the cryostat can easily be adapted for different X-ray techniques. It is already in use on different beamlines at the European Synchrotron Radiation Facility (ESRF), ALBA Synchrotron Light Facility (ALBA), and Diamond Light Source (DLS) for inelastic X-ray scattering, powder diffraction, and X-ray absorption spectroscopy. Results obtained at these beamlines are presented here.

  3. Tubuloglomerular feedback dynamics and renal blood flow autoregulation in rats

    Holstein-Rathlou, N H; Wagner, A J; Marsh, D J

    1991-01-01

    To decide whether tubuloglomerular feedback (TGF) can account for renal autoregulation, we tested predictions of a TGF simulation. Broad-band and single-frequency perturbations were applied to arterial pressure; arterial blood pressure, renal blood flow and proximal tubule pressure were measured....... Data were analyzed by linear systems analysis. Broad-band forcings of arterial pressure were also applied to the model to compare experimental results with simulations. With arterial pressure as the input and tubular pressure, renal blood flow, or renal vascular resistance as outputs, the model...... correctly predicted gain and phase only in the low-frequency range. Experimental results revealed a second component of vascular control active at 100-150 mHz that was not predicted by the simulation. Forcings at single frequencies showed that the system behaves linearly except in the band of 33-50 m...

  4. Zonal flow dynamics and control of turbulent transport in stellarators.

    Xanthopoulos, P; Mischchenko, A; Helander, P; Sugama, H; Watanabe, T-H

    2011-12-09

    The relation between magnetic geometry and the level of ion-temperature-gradient (ITG) driven turbulence in stellarators is explored through gyrokinetic theory and direct linear and nonlinear simulations. It is found that the ITG radial heat flux is sensitive to details of the magnetic configuration that can be understood in terms of the linear behavior of zonal flows. The results throw light on the question of how the optimization of neoclassical confinement is related to the reduction of turbulence.

  5. Dynamic Behavior of Reverse Flow Reactor for Lean Methane Combustion

    Yogi W. Budhi; M. Effendy; Yazid Bindar; Subagjo

    2014-01-01

    The stability of reactor operation for catalytic oxidation of lean CH4 has been investigated through modeling and simulation, particularly the influence of switching time and heat extraction on reverse flow reactor (RFR) performance. A mathematical model of the RFR was developed, based on one-dimensional pseudo-homogeneous model for mass and heat balances, incorporating heat loss through the reactor wall. The configuration of the RFR consisted of inert-catalyst-inert, with or without heat ext...

  6. Molecular dynamics study of Ar flow and He flow inside carbon nanotube junction as a molecular nozzle and diffuser

    Itsuo Hanasaki, Akihiro Nakatani and Hiroshi Kitagawa

    2004-01-01

    Full Text Available A carbon nanotube junction consists of two connected nanotubes with different diameters. It has been extensively investigated as a molecular electronic device since carbon nanotubes can be metallic and semiconductive, depending on their structure. However, a carbon nanotube junction can also be viewed as a nanoscale nozzle andv diffuser. Here, we focus on the nanotube junction from the perspective of an intersection between machine, material and device. We have conducted a molecular dynamics simulation of the molecular flow inside a modeled (12,12–(8,8 nanotube junction. A strong gravitational field and a periodic boundary condition are applied in the flow direction. We investigated dense-Ar flows and dense-He flows while controlling the temperature of the nanotube junction. The results show that Ar atoms tend to be near to the wall and the density of the Ar is higher in the wide (12,12 nanotube than in the narrow (8,8 nanotube, while it is lower in the wide tube when no flow occurs. The streaming velocities of both the Ar and the He are higher in the narrow nanotube than in the wide nanotube, but the velocity of the Ar is higher than the velocity of the He and the temperature of the flowing Ar is higher than the temperature of the He when the same magnitude of gravitational field is applied.

  7. Linear flow dynamics near a T/NT interface

    Teixeira, Miguel; Silva, Carlos

    2011-11-01

    The characteristics of a suddenly-inserted T/NT interface separating a homogeneous and isotropic shear-free turbulence region from a non-turbulent flow region are investigated using rapid distortion theory (RDT), taking full account of viscous effects. Profiles of the velocity variances, TKE, viscous dissipation rate, turbulence length scales, and pressure statistics are derived, showing very good agreement with DNS. The normalized inviscid flow statistics at the T/NT interface do not depend on the form of the assumed TKE spectrum. In the non-turbulent region, where the flow is irrotational (except within a thin viscous boundary layer), the dissipation rate decays as z-6, where z is distance from the T/NT interface. The mean pressure exhibits a decrease towards the turbulence due to the associated velocity fluctuations, consistent with the generation of a mean entrainment velocity. The vorticity variance and dissipation rate display large maxima at the T/NT interface due to the existing inviscid discontinuities of the tangential velocity, and these maxima are quantitatively related to the thickness of the viscous boundary layer (VBL). At equilibrium, RDT suggests that the thickness of the T/NT interface scales on the Kolmogorov microscale. We acknowledge the financial support of FCT under Project PTDC/EME-MFE/099636/2008.

  8. Monthly to seasonal low flow prediction: statistical versus dynamical models

    Ionita-Scholz, Monica; Klein, Bastian; Meissner, Dennis; Rademacher, Silke

    2016-04-01

    While the societal and economical impacts of floods are well documented and assessable, the impacts of lows flows are less studied and sometimes overlooked. For example, over the western part of Europe, due to intense inland waterway transportation, the economical loses due to low flows are often similar compared to the ones due to floods. In general, the low flow aspect has the tendency to be underestimated by the scientific community. One of the best examples in this respect is the facts that at European level most of the countries have an (early) flood alert system, but in many cases no real information regarding the development, evolution and impacts of droughts. Low flows, occurring during dry periods, may result in several types of problems to society and economy: e.g. lack of water for drinking, irrigation, industrial use and power production, deterioration of water quality, inland waterway transport, agriculture, tourism, issuing and renewing waste disposal permits, and for assessing the impact of prolonged drought on aquatic ecosystems. As such, the ever-increasing demand on water resources calls for better a management, understanding and prediction of the water deficit situation and for more reliable and extended studies regarding the evolution of the low flow situations. In order to find an optimized monthly to seasonal forecast procedure for the German waterways, the Federal Institute of Hydrology (BfG) is exploring multiple approaches at the moment. On the one hand, based on the operational short- to medium-range forecasting chain, existing hydrological models are forced with two different hydro-meteorological inputs: (i) resampled historical meteorology generated by the Ensemble Streamflow Prediction approach and (ii) ensemble (re-) forecasts of ECMWF's global coupled ocean-atmosphere general circulation model, which have to be downscaled and bias corrected before feeding the hydrological models. As a second approach BfG evaluates in cooperation with

  9. Spontaneous and Flow-Driven Interfacial Phase Change: Dynamics of Microemulsion Formation at the Pore Scale.

    Tagavifar, Mohsen; Xu, Ke; Jang, Sung Hyun; Balhoff, Matthew T; Pope, Gary A

    2017-11-14

    The dynamic behavior of microemulsion-forming water-oil-amphiphiles mixtures is investigated in a 2.5D micromodel. The equilibrium phase behavior of such mixtures is well-understood in terms of macroscopic phase transitions. However, what is less understood and where experimental data are lacking is the coupling between the phase change and the bulk flow. Herein, we study the flow of an aqueous surfactant solution-oil mixture in porous media and analyze the dependence of phase formation and spatial phase configurations on the bulk flow rate. We find that a microemulsion forms instantaneously as a boundary layer at the initial surface of contact between the surfactant solution and oil. The boundary layer is temporally continuous because of the imposed convection. In addition to the imposed flow, we observe spontaneous pulsed Marangoni flows that drag the microemulsion and surfactant solution into the oil stream, forming large (macro)emulsion droplets. The formation of the microemulsion phase at the interface distinguishes the situation from that of the more common Marangoni flow with only two phases present. Additionally, an emulsion forms via liquid-liquid nucleation or the Ouzo effect (i.e., spontaneous emulsification) at low flow rates and via mechanical mixing at high flow rates. With regard to multiphase flow, contrary to the common belief that the microemulsion is the wetting liquid, we observe that the minor oil phase wets the solid surface. We show that a layered flow pattern is formed because of the out-of-equilibrium phase behavior at high volumetric flow rates (order of 2 m/day) where advection is much faster than the diffusive interfacial mass transfer and transverse mixing, which promote equilibrium behavior. At lower flow rates (order of 30 cm/day), however, the dynamic and equilibrium phase behaviors are well-correlated. These results clearly show that the phase change influences the macroscale flow behavior.

  10. Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α

    Yanjuan Gao

    2016-06-01

    Full Text Available Phosphatidylinositol 3-kinase α (PI3Kα is an attractive target for anticancer drug design. Liphagal, isolated from the marine sponge Aka coralliphaga, possesses the special “liphagane” meroterpenoid carbon skeleton and has been demonstrated as a PI3Kα inhibitor. Molecular docking and molecular dynamics simulations were performed to explore the dynamic behaviors of PI3Kα binding with liphagal, and free energy calculations and energy decomposition analysis were carried out by use of molecular mechanics/Poisson-Boltzmann (generalized Born surface area (MM/PB(GBSA methods. The results reveal that the heteroatom rich aromatic D-ring of liphagal extends towards the polar region of the binding site, and the D-ring 15-hydroxyl and 16-hydroxyl form three hydrogen bonds with Asp810 and Tyr836. The cyclohexyl A-ring projects up into the upper pocket of the lipophilic region, and the hydrophobic/van der Waals interactions with the residues Met772, Trp780, Ile800, Ile848, Val850, Met922, Phe930, Ile932 could be the key interactions for the affinity of liphagal to PI3Kα. Thus, a new strategy for the rational design of more potent analogs of liphagal against PI3Kα is provided. Our proposed PI3Kα/liphagal binding mode would be beneficial for the discovery of new active analogs of liphagal against PI3Kα.

  11. Elucidating Dynamical Processes Relevant to Flow Encountering Abrupt Topography (FLEAT)

    2015-09-30

    Encountering Abrupt Topography (FLEAT) Bo Qiu Dept of Oceanography, University of Hawaii at Manoa 1000 Pope Rd. Honolulu, HI 96822 phone: (808) 956...c) to explore relevant dynamics by using both simplified models and OGCM output with realistic topography and surface boundary conditions...scale abyssal circulation, we propose to use the Hallberg Isopycnal Model (HIM). The HIM allows sloping isopycnals to interact with bottom topography

  12. Transitory powder flow dynamics during emptying of a continuous mixer

    Ammarcha , Chawki; Gatumel , Cendrine; Dirion , Jean-Louis; Cabassud , Michel; Mizonov , Vadim; Berthiaux , Henri

    2013-01-01

    International audience; This article investigates the emptying process of a continuous powder mixer, from both experimental and modelling points of view. The apparatus used in this work is a pilot scale commercial mixer Gericke GCM500, for which a specific experimental protocol has been developed to determine the hold up in the mixer and the real outflow. We demonstrate that the dynamics of the process is governed by the rotational speed of the stirrer, as it fixes characteristic values of th...

  13. Dynamical system analysis of unstable flow phenomena in centrifugal blower

    Garcia David

    2015-09-01

    Full Text Available Methods of dynamical system analysis were employed to analyze unsteady phenomena in a centrifugal blower. Pressure signals gathered at different control points were decomposed into their Principal Components (PCs by means of Singular Spectrum Analysis (SSA. Certain number of PCs was considered in the analysis based on their statistical correlation. Projection of the original signal onto its PCs allowed to draw the phase trajectory that clearly separated non-stable blower working conditions from its regular operation.

  14. Non-linear dynamics and alternating 'flip' solutions in ferrofluidic Taylor-Couette flow

    Altmeyer, Sebastian

    2018-04-01

    This study treats with the influence of a symmetry-breaking transversal magnetic field on the nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined between two concentric independently rotating cylinders. We detected alternating 'flip' solutions which are flow states featuring typical characteristics of slow-fast-dynamics in dynamical systems. The flip corresponds to a temporal change in the axial wavenumber and we find them to appear either as pure 2-fold axisymmetric (due to the symmetry-breaking nature of the applied transversal magnetic field) or involving non-axisymmetric, helical modes in its interim solution. The latter ones show features of typical ribbon solutions. In any case the flip solutions have a preferential first axial wavenumber which corresponds to the more stable state (slow dynamics) and second axial wavenumber, corresponding to the short appearing more unstable state (fast dynamics). However, in both cases the flip time grows exponential with increasing the magnetic field strength before the flip solutions, living on 2-tori invariant manifolds, cease to exist, with lifetime going to infinity. Further we show that ferrofluidic flow turbulence differ from the classical, ordinary (usually at high Reynolds number) turbulence. The applied magnetic field hinders the free motion of ferrofluid partials and therefore smoothen typical turbulent quantities and features so that speaking of mildly chaotic dynamics seems to be a more appropriate expression for the observed motion.

  15. Effect of flow rate on environmental variables and phytoplankton dynamics: results from field enclosures

    Zhang, Haiping; Chen, Ruihong; Li, Feipeng; Chen, Ling

    2015-03-01

    To investigate the effects of flow rate on phytoplankton dynamics and related environment variables, a set of enclosure experiments with different flow rates were conducted in an artificial lake. We monitored nutrients, temperature, dissolved oxygen, pH, conductivity, turbidity, chlorophyll- a and phytoplankton levels. The lower biomass in all flowing enclosures showed that flow rate significantly inhibited the growth of phytoplankton. A critical flow rate occurred near 0.06 m/s, which was the lowest relative inhibitory rate. Changes in flow conditions affected algal competition for light, resulting in a dramatic shift in phytoplankton composition, from blue-green algae in still waters to green algae in flowing conditions. These findings indicate that critical flow rate can be useful in developing methods to reduce algal bloom occurrence. However, flow rate significantly enhanced the inter-relationships among environmental variables, in particular by inducing higher water turbidity and vegetative reproduction of periphyton ( Spirogyra). These changes were accompanied by a decrease in underwater light intensity, which consequently inhibited the photosynthetic intensity of phytoplankton. These results warn that a universal critical flow rate might not exist, because the effect of flow rate on phytoplankton is interlinked with many other environmental variables.

  16. Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model

    Toyama, Hiroshi; Takeuchi, Akira; Koga, Sukehiko; Matsumura, Kaname; Nakashima, Hiromichi; Takeda, Kan; Yoshida, Toshimichi; Ichise, Masanori

    1998-01-01

    I-123-iomazenil is a SPECT probe for central benzodiazepine receptors (BZR) which may reflect intact cortical neuron density after ischemic insults. We evaluated whether neuronal damage in rats could be characterized by iomazenil as compared with cerebral blood flow (CBF). Serial changes in I-125-iomazenil for BZR and I-123-IMP for CBF were analyzed after the unilateral middle cerebral artery occlusion in rats by using an in vivo dualtracer technique. Uptake ratios of affected to contralateral regions were calculated. The iomazenil as well as IMP were decreased in all regions except for the cerebellum (remote area). Both iomazenil and IMP increased over time except in the temporal region (ischemic core). The iomazenil uptake was higher than IMP except in the ischemic core between 1 and 3-4 wk when iomazenil was lower than IMP. Iomazenil showed a moderate decrease in the proximal and middle parietal regions (peri-infarct areas) at 3-4 wk. The triphenyl-tetrazolium-chloride (TTC) stain at 1 wk demonstrated unstained tissue in the temporal region indicating tissue necrosis. With hematoxylin-eosin (HE) stain at 1 wk, widespread neuronal necrosis with occasional intact neurons were found in the proximal parietal region, and isolated necrotic neurons were represented in the distal parietal region. Iomazenil correlated well with the neuron distribution and the finding of a discrepancy between iomazenil and IMP might be useful in evaluating the neuronal damage. (author)

  17. Interface tracking computations of bubble dynamics in nucleate flow boiling

    Giustini, G.

    2015-01-01

    The boiling process is of utter importance for the design and operation of water-cooled nuclear reactors. Despite continuous effort over the past decades, a fully mechanistic model of boiling in the presence of a solid surface has not yet been achieved. Uncertainties exist at fundamental level, since the microscopic phenomena governing nucleate boiling are still not understood, and as regards 'component scale' modelling, which relies heavily on empirical representations of wall boiling. Accurate models of these phenomena at sub-milli-metric scale are capable of elucidating the various processes and to produce quantitative data needed for up-scaling. Within this context, Direct Numerical Simulation (DNS) represents a powerful tool for CFD analysis of boiling flows. In this contribution, DNS coupled with an Interface Tracking method (Y. Sato, B. Niceno, Journal of Computational Physics, Volume 249, 15 September 2013, Pages 127-161) are used to analyse the hydrodynamics and heat transfer associated with heat diffusion controlled bubble growth at a solid substrate during nucleate flow boiling. The growth of successive bubbles from a single nucleation site is simulated with a computational model that includes heat conduction in the solid substrate and evaporation from the liquid film (micro-layer) present beneath the bubble. Bubble evolution is investigated and the additional (with respect to single phase convection) heat transfer mechanisms due to the ebullition cycle are quantified. The simulations show that latent heat exchange due to evaporation in the micro-layer and sensible heat exchange during the waiting time after bubble departure are the main heat transfer mechanisms. It is found that the presence of an imposed flow normal to the bubble rising path determines a complex velocity and temperature distribution near the nucleation site. This conditions can result in bubble sliding, and influence bubble shape, departure diameter and departure frequency

  18. Interfacial dynamics of dissolving objects in fluid flow

    Rycroft, Chris; Bazant, Martin

    2013-11-01

    An advection-diffusion-limited dissolution model of an object being eroded by a two-dimensional potential flow will be presented. By taking advantage of conformal invariance of the model, a numerical method will be introduced that tracks the evolution of the object boundary in terms of a time-dependent Laurent series. Simulations of several dissolving objects will be shown, all of which show collapse to a single point in finite time. The simulations reveal a surprising connection between the position of the collapse point and the initial Laurent coefficients, which was subsequently derived analytically using residue calculus.

  19. Preferential flow in the vadose zone and interface dynamics: Impact of microbial exudates

    Li, Biting; Pales, Ashley R.; Clifford, Heather M.; Kupis, Shyla; Hennessy, Sarah; Liang, Wei-Zhen; Moysey, Stephen; Powell, Brian; Finneran, Kevin T.; Darnault, Christophe J. G.

    2018-03-01

    In the hydrological cycle, the infiltration process is a critical component in the distribution of water into the soil and in the groundwater system. The nonlinear dynamics of the soil infiltration process yield preferential flow which affects the water distribution in soil. Preferential flow is influenced by the interactions between water, soil, plants, and microorganisms. Although the relationship among the plant roots, their rhizodeposits and water transport in soil has been the subject of extensive study, the effect of microbial exudates has been studied in only a few cases. Here the authors investigated the influence of two artificial microbial exudates-catechol and riboflavin-on the infiltration process, particularly unstable fingered flow, one form of preferential flow. Flow experiments investigating the effects of types and concentrations of microbial exudates on unstable fingered flow were conducted in a two-dimensional tank that was filled with ASTM

  20. Assessment of Electromagnetic Stirrer Agitated Liquid Metal Flows by Dynamic Neutron Radiography

    Ščepanskis, Mihails; Sarma, Mārtiņš; Vontobel, Peter; Trtik, Pavel; Thomsen, Knud; Jakovičs, Andris; Beinerts, Toms

    2017-04-01

    This paper presents qualitative and quantitative characterization of two-phase liquid metal flows agitated by the stirrer on rotating permanent magnets. The stirrer was designed to fulfill various eddy flows, which may have different rates of solid particle entrapment from the liquid surface and their homogenization. The flow was characterized by visualization of the tailored tracer particles by means of dynamic neutron radiography, an experimental method well suited for liquid metal flows due to low opacity of some metals for neutrons. The rather high temporal resolution of the image acquisition (32 Hz image acquisition rate) allows for the quantitative investigation of the flows up to 30 cm/s using neutron particle image velocimetry. In situ visualization of the two-phase liquid metal flow is also demonstrated.

  1. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-02-22

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.

  2. Transient Flow Dynamics in Optical Micro Well Involving Gas Bubbles

    Johnson, B.; Chen, C. P.; Jenkins, A.; Spearing, S.; Monaco, L. A.; Steele, A.; Flores, G.

    2006-01-01

    The Lab-On-a-Chip Application Development (LOCAD) team at NASA s Marshall Space Flight Center is utilizing Lab-On-a-Chip to support technology development specifically for Space Exploration. In this paper, we investigate the transient two-phase flow patterns in an optic well configuration with an entrapped bubble through numerical simulation. Specifically, the filling processes of a liquid inside an expanded chamber that has bubbles entrapped. Due to the back flow created by channel expansion, the entrapped bubbles tend to stay stationary at the immediate downstream of the expansion. Due to the huge difference between the gas and liquid densities, mass conservation issues associated with numerical diffusion need to be specially addressed. The results are presented in terms of the movement of the bubble through the optic well. Bubble removal strategies are developed that involve only pressure gradients across the optic well. Results show that for the bubble to be moved through the well, pressure pulsations must be utilized in order to create pressure gradients across the bubble itself.

  3. Ill-posedness of Dynamic Equations of Compressible Granular Flow

    Shearer, Michael; Gray, Nico

    2017-11-01

    We introduce models for 2-dimensional time-dependent compressible flow of granular materials and suspensions, based on the rheology of Pouliquen and Forterre. The models include density dependence through a constitutive equation in which the density or volume fraction of solid particles with material density ρ* is taken as a function of an inertial number I: ρ = ρ * Φ(I), in which Φ(I) is a decreasing function of I. This modelling has different implications from models relying on critical state soil mechanics, in which ρ is treated as a variable in the equations, contributing to a flow rule. The analysis of the system of equations builds on recent work of Barker et al in the incompressible case. The main result is the identification of a criterion for well-posedness of the equations. We additionally analyze a modification that applies to suspensions, for which the rheology takes a different form and the inertial number reflects the role of the fluid viscosity.

  4. New approach for dynamic flow management within the PEMFC stack

    Varlam, Mihai; Culcer, Mihai; Carcadea, Elena; Stefanescu, Ioan; Iliescu, Mariana; Enache, Adrian

    2009-01-01

    An adequate gas and water flow management is a key issue to reach and maintain a higher output power for a PEM fuel cell stack. One of the main aspects which could limit the performance of a PEM fuel cell stack is the weak capability for a non-uniform water distribution management within the fuel cell. The produced water could become a handicap to attain the best working performance by blocking the catalytic surfaces and by preventing the mass transport process. Usually, the excess water is removed in one cell, comparatively to others from the stack and taking into account that all the cells are supplied in parallel from a common air admission pipe, a limitation of gas flow rate within that cell is created. Consequently, this constraint will reduce further the water removal speed. This feedback process will generate finally a drastic decrease of the fuel cell stack performance. A new practical solution to this water and gas non-uniformity of distributions problem is to use a sequential purge procedure of several fuel cell groups inside the stack which could guarantee a right management of water. An experimental setup has been built based on four fuel cell stack. Every fuel cell was connected to a single removal pipe via a solenoid valve. A computer-controlled hardware and software system has been designed and built, in order to generate a given opening-closing sequence for the automatic valve system. (authors)

  5. Functionalized Magnetic Resonance Contrast Agent Selectively Binds to Glycoprotein IIb/IIIa on Activated Human Platelets under Flow Conditions and Is Detectable at Clinically Relevant Field Strengths

    Constantin von zur Mühlen

    2008-03-01

    Full Text Available Recent progress in molecular magnetic resonance imaging (MRI provides the opportunity to image cells and cellular receptors using microparticles of iron oxide (MPIOs. However, imaging targets on vessel walls remains challenging owing to the quantity of contrast agents delivered to areas of interest under shear stress conditions. We evaluated ex vivo binding characteristics of a functional MRI contrast agent to ligand-induced binding sites (LIBSs on activated glycoprotein IIb/IIIa receptors of human platelets, which were lining rupture-prone atherosclerotic plaques and could therefore facilitate detection of platelet-mediated pathology in atherothrombotic disease. MPIOs were conjugated to anti-LIBS single-chain antibodies (LIBS-MPIO or control antibodies (control MPIO. Ex vivo binding to human platelet-rich clots in a dose-dependent manner was confirmed on a 3 T clinical MRI scanner and by histology (p < .05 for LIBS-MPIO vs control MPIO. By using a flow chamber setup, significant binding of LIBS-MPIO to a platelet matrix was observed under venous and arterial flow conditions, but not for control MPIO (p < .001. A newly generated MRI contrast agent detects activated human platelets at clinically relevant magnetic field strengths and binds to platelets under venous and arterial flow conditions, conveying high payloads of contrast to specific molecular targets. This may provide the opportunity to identify vulnerable, rupture-prone atherosclerotic plaques via noninvasive MRI.

  6. Applications of flow-networks to opinion-dynamics

    Tupikina, Liubov; Kurths, Jürgen

    2015-04-01

    Networks were successfully applied to describe complex systems, such as brain, climate, processes in society. Recently a socio-physical problem of opinion-dynamics was studied using network techniques. We present the toy-model of opinion-formation based on the physical model of advection-diffusion. We consider spreading of the opinion on the fixed subject, assuming that opinion on society is binary: if person has opinion then the state of the node in the society-network equals 1, if the person doesn't have opinion state of the node equals 0. Opinion can be spread from one person to another if they know each other, or in the network-terminology, if the nodes are connected. We include into the system governed by advection-diffusion equation the external field to model such effects as for instance influence from media. The assumptions for our model can be formulated as the following: 1.the node-states are influenced by the network structure in such a way, that opinion can be spread only between adjacent nodes (the advective term of the opinion-dynamics), 2.the network evolution can have two scenarios: -network topology is not changing with time; -additional links can appear or disappear each time-step with fixed probability which requires adaptive networks properties. Considering these assumptions for our system we obtain the system of equations describing our model-dynamics which corresponds well to other socio-physics models, for instance, the model of the social cohesion and the famous voter-model. We investigate the behavior of the suggested model studying "waiting time" of the system, time to get to the stable state, stability of the model regimes for different values of model parameters and network topology.

  7. Debris flow analysis with a one dimensional dynamic run-out model that incorporates entrained material

    Luna, Byron Quan; Remaître, Alexandre; van Asch, Theo; Malet, Jean-Philippe; van Westen, Cees

    2010-05-01

    Estimating the magnitude and the intensity of rapid landslides like debris flows is fundamental to evaluate quantitatively the hazard in a specific location. Intensity varies through the travelled course of the flow and can be described by physical features such as deposited volume, velocities, height of the flow, impact forces and pressures. Dynamic run-out models are able to characterize the distribution of the material, its intensity and define the zone where the elements will experience an impact. These models can provide valuable inputs for vulnerability and risk calculations. However, most dynamic run-out models assume a constant volume during the motion of the flow, ignoring the important role of material entrained along its path. Consequently, they neglect that the increase of volume enhances the mobility of the flow and can significantly influence the size of the potential impact area. An appropriate erosion mechanism needs to be established in the analyses of debris flows that will improve the results of dynamic modeling and consequently the quantitative evaluation of risk. The objective is to present and test a simple 1D debris flow model with a material entrainment concept based on limit equilibrium considerations and the generation of excess pore water pressure through undrained loading of the in situ bed material. The debris flow propagation model is based on a one dimensional finite difference solution of a depth-averaged form of the Navier-Stokes equations of fluid motions. The flow is treated as a laminar one phase material, which behavior is controlled by a visco-plastic Coulomb-Bingham rheology. The model parameters are evaluated and the model performance is tested on a debris flow event that occurred in 2003 in the Faucon torrent (Southern French Alps).

  8. Solution structure, copper binding and backbone dynamics of recombinant Ber e 1-the major allergen from Brazil nut.

    Louise Rundqvist

    Full Text Available BACKGROUND: The 2S albumin Ber e 1 is the major allergen in Brazil nuts. Previous findings indicated that the protein alone does not cause an allergenic response in mice, but the addition of components from a Brazil nut lipid fraction were required. Structural details of Ber e 1 may contribute to the understanding of the allergenic properties of the protein and its potential interaction partners. METHODOLOGY/PRINCIPAL FINDINGS: The solution structure of recombinant Ber e 1 was solved using NMR spectroscopy and measurements of the protein back bone dynamics at a residue-specific level were extracted using (15N-spin relaxation. A hydrophobic cavity was identified in the structure of Ber e 1. Using the paramagnetic relaxation enhancement property of Cu(2+ in conjunction with NMR, it was shown that Ber e 1 is able to specifically interact with the divalent copper ion and the binding site was modeled into the structure. The IgE binding region as well as the copper binding site show increased dynamics on both fast ps-ns timescale as well as slower µs-ms timescale. CONCLUSIONS/SIGNIFICANCE: The overall fold of Ber e 1 is similar to other 2S albumins, but the hydrophobic cavity resembles that of a homologous non-specific lipid transfer protein. Ber e 1 is the first 2S albumin shown to interact with Cu(2+ ions. This Cu(2+ binding has minimal effect on the electrostatic potential on the surface of the protein, but the charge distribution within the hydrophobic cavity is significantly altered. As the hydrophobic cavity is likely to be involved in a putative lipid interaction the Cu(2+ can in turn affect the interaction that is essential to provoke an allergenic response.

  9. Discrete Adjoint-Based Design Optimization of Unsteady Turbulent Flows on Dynamic Unstructured Grids

    Nielsen, Eric J.; Diskin, Boris; Yamaleev, Nail K.

    2009-01-01

    An adjoint-based methodology for design optimization of unsteady turbulent flows on dynamic unstructured grids is described. The implementation relies on an existing unsteady three-dimensional unstructured grid solver capable of dynamic mesh simulations and discrete adjoint capabilities previously developed for steady flows. The discrete equations for the primal and adjoint systems are presented for the backward-difference family of time-integration schemes on both static and dynamic grids. The consistency of sensitivity derivatives is established via comparisons with complex-variable computations. The current work is believed to be the first verified implementation of an adjoint-based optimization methodology for the true time-dependent formulation of the Navier-Stokes equations in a practical computational code. Large-scale shape optimizations are demonstrated for turbulent flows over a tiltrotor geometry and a simulated aeroelastic motion of a fighter jet.

  10. Universal dynamics in the onset of a Hagen-Poiseuille flow

    Mortensen, Asger; Bruus, Henrik

    2006-01-01

    The dynamics in the onset of a Hagen-Poiseuille flow of an incompressible liquid in a channel of circular cross section is well-studied theoretically. We use an eigenfunction expansion in a Hilbert space formalism to generalize the results to channels of an arbitrary cross section. We find that t...... that the steady state is reached after a characteristic time scale tau=(A/P)(2)(1/nu), where A and P are the cross-sectional area and perimeter, respectively, and nu is the kinematic viscosity of the liquid. For the initial dynamics of the flow rate Q for t......The dynamics in the onset of a Hagen-Poiseuille flow of an incompressible liquid in a channel of circular cross section is well-studied theoretically. We use an eigenfunction expansion in a Hilbert space formalism to generalize the results to channels of an arbitrary cross section. We find...

  11. Renal blood flow regulation and arterial pressure fluctuations: a case study in nonlinear dynamics

    Holstein-Rathlou, N H; Marsh, D J

    1994-01-01

    in which the kidney is obliged to operate. Were it not for renal blood flow autoregulation, it would be difficult to regulate renal excretory processes so as to maintain whole body variables within narrow bounds. Autoregulation is the noise filter on which other renal processes depend for maintaining...... a relatively noise-free environment in which to work. Because of the time-varying nature of the blood pressure, we have concentrated in this review on the now substantial body of work on the dynamics of renal blood flow regulation and the underlying mechanisms. Renal vascular control mechanisms are not simply....... The significance of deterministic chaos in the context of renal blood flow regulation is that the system regulating blood flow undergoes a physical change to a different dynamical state, and because the change is deterministic, there is every expectation that the critical change will yield itself to experimental...

  12. Dynamic gas flow during plasma operation in TMX-U

    Pickles, W.L.; Carter, M.R.; Clower, C.A.; Drake, R.P.; Hunt, A.L.; Simonen, T.C.; Turner, W.C.

    1982-01-01

    Control of the neutral density outside of the plasma radius is essential for proper operation of the various plasma configurations in TMX-U. TMX-U excess-beam, stream-gun, gas-box, and beam-reflux gases are pumped internally in regions defined by 73 0 Ti-gettered liners and warm Ti-gettered plasma liners. The array of fast and slow ion gauges - a large TMX-U diagnostic - has been used to measure the dynamic pressure in many of the liner-defined regions on three time scales. The natural divertor action, or plasma pump effect, of mirror plasmas has been measured using the ion gauge diagnostics on a fast time scale during operation of TMX-U with ECRH start-up. Routine operation of TMX-U is enhanced by the ability to verify the effectiveness of gettering and to locate leaks using pressure data collected on the two slow time scales. A computer code, DYNAVAC 6, which treats TMX-U as a set of conductance-coupled regions with pumping and sources in each region, has been used to successfully model the overall gas dynamics during all phases of TMX-U operation

  13. Quantifying Km-scale Hydrological Exchange Flows under Dynamic Flows and Their Influences on River Corridor Biogeochemistry

    Chen, X.; Song, X.; Shuai, P.; Hammond, G. E.; Ren, H.; Zachara, J. M.

    2017-12-01

    Hydrologic exchange flows (HEFs) in rivers play vital roles in watershed ecological and biogeochemical functions due to their strong capacity to attenuate contaminants and process significant quantities of carbon and nutrients. While most of existing HEF studies focus on headwater systems with the assumption of steady-state flow, there is lack of understanding of large-scale HEFs in high-order regulated rivers that experience high-frequency stage fluctuations. The large variability of HEFs is a result of interactions between spatial heterogeneity in hydrogeologic properties and temporal variation in river discharge induced by natural or anthropogenic perturbations. Our 9-year spatially distributed dataset (water elevation, specific conductance, and temperature) combined with mechanistic hydrobiogeochemical simulations have revealed complex spatial and temporal dynamics in km-scale HEFs and their significant impacts on contaminant plume mobility and hyporheic biogeochemical processes along the Hanford Reach. Extended multidirectional flow behaviors of unconfined, river corridor groundwater were observed hundreds of meters inland from the river shore resulting from discharge-dependent HEFs. An appropriately sized modeling domain to capture the impact of regional groundwater flow as well as knowledge of subsurface structures controlling intra-aquifer hydrologic connectivity were essential to realistically model transient storage in this large-scale river corridor. This work showed that both river water and mobile groundwater contaminants could serve as effective tracers of HEFs, thus providing valuable information for evaluating and validating the HEF models. Multimodal residence time distributions with long tails were resulted from the mixture of long and short exchange pathways, which consequently impact the carbon and nutrient cycling within the river corridor. Improved understanding of HEFs using integrated observational and modeling approaches sheds light on

  14. Molecular Binding Contributes to Concentration Dependent Acrolein Deposition in Rat Upper Airways: CFD and Molecular Dynamics Analyses

    Jinxiang Xi

    2018-03-01

    Full Text Available Existing in vivo experiments show significantly decreased acrolein uptake in rats with increasing inhaled acrolein concentrations. Considering that high-polarity chemicals are prone to bond with each other, it is hypothesized that molecular binding between acrolein and water will contribute to the experimentally observed deposition decrease by decreasing the effective diffusivity. The objective of this study is to quantify the probability of molecular binding for acrolein, as well as its effects on acrolein deposition, using multiscale simulations. An image-based rat airway geometry was used to predict the transport and deposition of acrolein using the chemical species model. The low Reynolds number turbulence model was used to simulate the airflows. Molecular dynamic (MD simulations were used to study the molecular binding of acrolein in different media and at different acrolein concentrations. MD results show that significant molecular binding can happen between acrolein and water molecules in human and rat airways. With 72 acrolein embedded in 800 water molecules, about 48% of acrolein compounds contain one hydrogen bond and 10% contain two hydrogen bonds, which agreed favorably with previous MD results. The percentage of hydrogen-bonded acrolein compounds is higher at higher acrolein concentrations or in a medium with higher polarity. Computational dosimetry results show that the size increase caused by the molecular binding reduces the effective diffusivity of acrolein and lowers the chemical deposition onto the airway surfaces. This result is consistent with the experimentally observed deposition decrease at higher concentrations. However, this size increase can only explain part of the concentration-dependent variation of the acrolein uptake and acts as a concurrent mechanism with the uptake-limiting tissue ration rate. Intermolecular interactions and associated variation in diffusivity should be considered in future dosimetry modeling of

  15. Molecular Binding Contributes to Concentration Dependent Acrolein Deposition in Rat Upper Airways: CFD and Molecular Dynamics Analyses.

    Xi, Jinxiang; Hu, Qin; Zhao, Linlin; Si, Xiuhua April

    2018-03-27

    Existing in vivo experiments show significantly decreased acrolein uptake in rats with increasing inhaled acrolein concentrations. Considering that high-polarity chemicals are prone to bond with each other, it is hypothesized that molecular binding between acrolein and water will contribute to the experimentally observed deposition decrease by decreasing the effective diffusivity. The objective of this study is to quantify the probability of molecular binding for acrolein, as well as its effects on acrolein deposition, using multiscale simulations. An image-based rat airway geometry was used to predict the transport and deposition of acrolein using the chemical species model. The low Reynolds number turbulence model was used to simulate the airflows. Molecular dynamic (MD) simulations were used to study the molecular binding of acrolein in different media and at different acrolein concentrations. MD results show that significant molecular binding can happen between acrolein and water molecules in human and rat airways. With 72 acrolein embedded in 800 water molecules, about 48% of acrolein compounds contain one hydrogen bond and 10% contain two hydrogen bonds, which agreed favorably with previous MD results. The percentage of hydrogen-bonded acrolein compounds is higher at higher acrolein concentrations or in a medium with higher polarity. Computational dosimetry results show that the size increase caused by the molecular binding reduces the effective diffusivity of acrolein and lowers the chemical deposition onto the airway surfaces. This result is consistent with the experimentally observed deposition decrease at higher concentrations. However, this size increase can only explain part of the concentration-dependent variation of the acrolein uptake and acts as a concurrent mechanism with the uptake-limiting tissue ration rate. Intermolecular interactions and associated variation in diffusivity should be considered in future dosimetry modeling of high

  16. Reversal of flow in the inferior vena cava and hepatic veins on dynamic CT

    Lelij, H. van der; Mallens, W.M.C.

    1988-01-01

    A tricuspid insufficiency may not be clinically evident and may remain unknown to the clinician. The phenomenon of a reversal of inferior vena caval blood flow and hepatic veins is known to occur in tricuspid regurgitation from right ventricular angiography and duplex scanning. Demonstration of such a reversal flow on a dynamic CT scan, as in our case, has, to our knowledge, not as yet been reported

  17. Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans.

    Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-11-15

    Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity. Copyright © 2015 the American Physiological Society.

  18. First-principles molecular dynamics simulation study on electrolytes for use in redox flow battery

    Choe, Yoong-Kee; Tsuchida, Eiji; Tokuda, Kazuya; Ootsuka, Jun; Saito, Yoshihiro; Masuno, Atsunobu; Inoue, Hiroyuki

    2017-11-01

    Results of first-principles molecular dynamics simulations carried out to investigate structural aspects of electrolytes for use in a redox flow battery are reported. The electrolytes studied here are aqueous sulfuric acid solutions where its property is of importance for dissolving redox couples in redox flow battery. The simulation results indicate that structural features of the acid solutions depend on the concentration of sulfuric acid. Such dependency arises from increase of proton dissociation from sulfuric acid.

  19. Flow dynamics in distillation columns packed with Dixon rings as used in isotope separation

    Gilath, C.; Cohen, H.; Wolf, D.

    1977-01-01

    Packed distillation columns are common in isotope separation. The pressure drop serves as an indication for the hydrodynamic state of the column. Models were formulated for flow and pressure drop dynamics in packed distillation columns. These models were confirmed on columns packed with Dixon rings and operated with water for separation of oxygen isotopes. Liquid holdup displacement is very important in isotope separation practice. Experiments proved that distillation columns packed with Dixon rings exhibit a behaviour close to plug flow. (author)

  20. THE EFFECTS OF ACCRETION FLOW DYNAMICS ON THE BLACK HOLE SHADOW OF SAGITTARIUS A*

    Pu, Hung-Yi; Asada, Keiichi [Institute of Astronomy and Astrophysics, Academia Sinica, 11F of Astronomy-Mathematics Building, AS/NTU No. 1, Taipei 10617, Taiwan (China); Akiyama, Kazunori [Massachusetts Institute of Technology, Haystack Observatory, Route 40, Westford, MA 01886 (United States)

    2016-11-01

    A radiatively inefficient accretion flow (RIAF), which is commonly characterized by its sub-Keplerian nature, is a favored accretion model for the supermassive black hole at the Galactic center, Sagittarius A*. To investigate the observable features of an RIAF, we compare the modeled shadow images, visibilities, and spectra of three flow models with dynamics characterized by (i) a Keplerian shell that is rigidly rotating outside the innermost stable circular orbit (ISCO) and infalling with a constant angular momentum inside ISCO, (ii) a sub-Keplerian motion, and (iii) a free-falling motion with zero angular momentum at infinity. At near-millimeter wavelengths, the emission is dominated by the flow within several Schwarzschild radii. The energy shift due to these flow dynamics becomes important and distinguishable, suggesting that the flow dynamics are an important model parameter for interpreting the millimeter/sub-millimeter very long baseline interferometric observations with the forthcoming, fully assembled Event Horizon Telescope (EHT). As an example, we demonstrate that structural variations of Sagittarius A* on event horizon-scales detected in previous EHT observations can be explained by the non-stationary dynamics of an RIAF.

  1. Prediction of flow- induced dynamic stress in an axial pump impeller using FEM

    Gao, J Y; Hou, Y S; Xi, S Z; Cai, Z H; Yao, P P; Shi, H L

    2013-01-01

    Axial pumps play an important role in water supply and flood control projects. Along with growing requirements for high reliability and large capacity, the dynamic stress of axial pumps has become a key problem. Unsteady flow is a significant reason which results structural dynamic stress of a pump. This paper reports on a flow-induced dynamic stress simulation in an axial pump impeller at three flow conditions by using FEM code. The pressure pulsation obtained from flow simulation using CFD code was set as the force boundary condition. The results show that the maximum stress of impeller appeared at joint between blade and root flange near trailing edge or joint between blade and root flange near leading edge. The dynamic stress of the two zones was investigated under three flow conditions (0.8Q d , 1.0Q d , 1.1Q d ) in time domain and frequency domain. The frequencies of stress at zones of maximum stress are 22.9Hz and 37.5Hz as the fundamental frequency and its harmonics. The fundamental frequencies are nearly equal to vane passing frequency (22.9 Hz) and 3 times blade passing frequency (37.5Hz). The first dominant frequency at zones of maximum stress is equal to the vane passing frequency due to rotor-stator interaction between the vane and the blade. This study would be helpful for axial pumps in reducing stress, improving structure design and fatigue life

  2. Stability of Intelligent Transportation Network Dynamics: A Daily Path Flow Adjustment considering Travel Time Differentiation

    Ming-Chorng Hwang

    2015-01-01

    Full Text Available A theoretic formulation on how traffic time information distributed by ITS operations influences the trajectory of network flows is presented in this paper. The interactions between users and ITS operator are decomposed into three parts: (i travel time induced path flow dynamics (PFDTT; (ii demand induced path flow dynamics (PFDD; and (iii predicted travel time dynamics for an origin-destination (OD pair (PTTDOD. PFDTT describes the collective results of user’s daily route selection by pairwise comparison of path travel time provided by ITS services. The other two components, PTTDOD and PFDD, are concentrated on the evolutions of system variables which are predicted and observed, respectively, by ITS operators to act as a benchmark in guiding the target system towards an expected status faster. In addition to the delivered modelings, the stability theorem of the equilibrium solution in the sense of Lyapunov stability is also provided. A Lyapunov function is developed and employed to the proof of stability theorem to show the asymptotic behavior of the aimed system. The information of network flow dynamics plays a key role in traffic control policy-making. The evaluation of ITS-based strategies will not be reasonable without a well-established modeling of network flow evolutions.

  3. Dynamics and rheology under continuous shear flow studied by x-ray photon correlation spectroscopy

    Fluerasu, Andrei [Brookhaven National Laboratory, NSLS-II, Upton, NY 11973 (United States); Kwasniewski, Pawel; Caronna, Chiara; Madsen, Anders [European Synchrotron Radiation Facility, ID10 (Troika), Grenoble 38043 (France); Destremaut, Fanny; Salmon, Jean-Baptiste [LOF, UMR 5258 CNRS-Rhodia Bordeaux 1, 33608 Pessac (France)], E-mail: fluerasu@bnl.gov

    2010-03-15

    X-ray photon correlation spectroscopy (XPCS) has emerged as a unique technique allowing the measurement of dynamics of materials on mesoscopic lengthscales. One of the most common problems associated with the use of bright x-ray beams is beam-induced radiation damage, and this is likely to become an even more limiting factor at future synchrotron and free-electron laser sources. Flowing the sample during data acquisition is one of the simplest methods allowing the radiation damage to be limited. In addition to distributing the dose over many different scatterers, the method also enables new functionalities such as time-resolved studies. Here, we further develop a recently proposed experimental technique that combines XPCS and continuously flowing samples. More specifically, we use a model colloidal suspension to show how the macroscopic advective response to flow and the microscopic dissipative dynamics (diffusion) can be quantified from the x-ray data. Our results show very good quantitative agreement with a Poisseuille-flow hydrodynamical model combined with Brownian mechanics. The method has many potential applications, e.g. in the study of dynamics of glasses and gels under continuous shear/flow, protein aggregation processes and the interplay between dynamics and rheology in complex fluids.

  4. Research on Dynamic Dissolving Model and Experiment for Rock Salt under Different Flow Conditions

    Xinrong Liu

    2015-01-01

    Full Text Available Utilizing deep rock salt cavern is not only a widely recognized energy reserve method but also a key development direction for implementing the energy strategic reserve plan. And rock salt cavern adopts solution mining techniques to realize building cavity. In view of this, the paper, based on the dissolving properties of rock salt, being simplified and hypothesized the dynamic dissolving process of rock salt, combined conditions between dissolution effect and seepage effect in establishing dynamic dissolving models of rock salt under different flow quantities. Devices were also designed to test the dynamic dissolving process for rock salt samples under different flow quantities and then utilized the finite-difference method to find the numerical solution of the dynamic dissolving model. The artificial intelligence algorithm, Particle Swarm Optimization algorithm (PSO, was finally introduced to conduct inverse analysis of parameters on the established model, whose calculation results coincide with the experimental data.

  5. Flow cytometry analysis of FITC-labeled concanavalin A binding to human blood cells as an indicator of radiation-induced membrane alterations

    Donnadieu-Claraz, M.; Paillole, N.; Voisin, P.

    1995-01-01

    The 3 H concanavalin-A binding to human blood cells have been described as a promising biological indicator of radiation overexposure. Flow cytometry adaptation of this technique using fluorescein-labelled concanavalin-A were performed to estimate time-dependent changes in binding on human blood cells membranes after in vitro γ irradiation ( 60 Co). Result revealed significant enhanced lectin-binding to platelets and erythrocytes in a dose range of 0,5-5 Gy, 1 and 3 hours after irradiation. However for both platelets and erythrocytes, it was impossible to discriminate between the different doses. Further studies are necessary to confirm the suitability of lectin-binding as a biological indicator for radiation dose assessment. (authors). 5 refs., 1 fig

  6. Locating Temporal Functional Dynamics of Visual Short-Term Memory Binding using Graph Modular Dirichlet Energy

    Smith, Keith; Ricaud, Benjamin; Shahid, Nauman; Rhodes, Stephen; Starr, John M.; Ibáñez, Augustin; Parra, Mario A.; Escudero, Javier; Vandergheynst, Pierre

    2017-02-01

    Visual short-term memory binding tasks are a promising early marker for Alzheimer’s disease (AD). To uncover functional deficits of AD in these tasks it is meaningful to first study unimpaired brain function. Electroencephalogram recordings were obtained from encoding and maintenance periods of tasks performed by healthy young volunteers. We probe the task’s transient physiological underpinnings by contrasting shape only (Shape) and shape-colour binding (Bind) conditions, displayed in the left and right sides of the screen, separately. Particularly, we introduce and implement a novel technique named Modular Dirichlet Energy (MDE) which allows robust and flexible analysis of the functional network with unprecedented temporal precision. We find that connectivity in the Bind condition is less integrated with the global network than in the Shape condition in occipital and frontal modules during the encoding period of the right screen condition. Using MDE we are able to discern driving effects in the occipital module between 100-140 ms, coinciding with the P100 visually evoked potential, followed by a driving effect in the frontal module between 140-180 ms, suggesting that the differences found constitute an information processing difference between these modules. This provides temporally precise information over a heterogeneous population in promising tasks for the detection of AD.

  7. Conformational Dynamics of the Receptor Protein Galactose/Glucose Binding Protein

    Messina, Troy; Talaga, David

    2006-03-01

    We have performed time-correlated single photon counting (TCSPC) anisotropy and Stokes Shift measurements on bulk solutions of galactose/glucose binding protein. Site-directed mutagenesis was used to provide a single cysteine amino acid near the sugar-binding center of the protein (glutamine 26 to cysteine -- Q26C). The cysteine was covalently labeled with the environmentally-sensitive fluorophore acrylodan, and a long-lived ruthenium complex was covalently attached to the N-terminus to provide a fluorescent reference. The TCSPC data were analyzed using global convolute-and-compare fitting routines over the entire glucose titration and temperature range to provide minimal reduced chi-squared values and the highest time resolution possible. Using a standard ligand-binding model, the resulting distributions show that the closed (ligand-bound) conformation exists even at zero glucose concentration. At 20^oC, the relative abundance of this conformation is as high as 40%. The temperature dependence of this conformational study will be discussed and related to the ligand-binding free energy surface.

  8. Framework for optimal power flow incorporating dynamic system security

    El-Kady, M.A.; Owayedh, M.S.

    2006-01-01

    This paper introduces a novel framework and methodologies which are capable of tackling the complex issue of power system economy versus security in a practical and effective manner. At heart of achieving such a challenging and far-reaching objective is the incorporation of the Dyanamic Security Assessment (DSA) into production optimization techniques using the Transient Energy Function (TEF) method. In addition, and in parallel with the already well established concept of the system security, two new concepts pertaining to power system performance will be introduced in this paper, namely the concept of system dynamic susceptibility, which measures the level of systems weakness to a particular contingency and the concept of system consequent restorability, which measures the extent of contingency severity in terms of the required subsequent system restoration work should a particular contingency occur. (author)

  9. The Dynamics of Controlled Flow Separation within a Diverter Duct Diffuser

    Peterson, C. J.; Vukasinovic, B.; Glezer, A.

    2016-11-01

    The evolution and receptivity to fluidic actuation of the flow separation within a rectangular, constant-width, diffuser that is branched off of a primary channel is investigated experimentally at speeds up to M = 0.4. The coupling between the diffuser's adverse pressure gradient and the internal separation that constricts nearly half of the flow passage through the duct is controlled using a spanwise array of fluidic actuators on the surface upstream of the diffuser's inlet plane. The dynamics of the separating surface vorticity layer in the absence and presence of actuation are investigated using high-speed particle image velocimetry combined with surface pressure measurements and total pressure distributions at the primary channel's exit plane. It is shown that the actuation significantly alters the incipient dynamics of the separating vorticity layer as the characteristic cross stream scales of the boundary layer upstream of separation and of the ensuing vorticity concentrations within the separated flow increase progressively with actuation level. It is argued that the dissipative (high frequency) actuation alters the balance between large- and small-scale motions near separation by intensifying the large-scale motions and limiting the small-scale dynamics. Controlling separation within the diffuser duct also has a profound effect on the global flow. In the presence of actuation, the mass flow rate in the primary duct increases 10% while the fraction of the diverted mass flow rate in the diffuser increases by more than 45% at 0.7% actuation mass fraction. Supported by the Boeing Company.

  10. On the evaluation of debris flows dynamics by means of mathematical models

    M. Arattano

    2003-01-01

    Full Text Available The prediction of debris flow dynamic characteristics in a debris flow prone torrent is generally made through the investigation of past events. This investigation can be carried out through a survey of the marks left by past debris flows along the channel and through a detailed analysis of the type and shape of the deposits found on the debris fan. The rheological behaviour of future debris flows can then be inferred from the results of these surveys and their dynamic characteristics can be estimated applying well known formulas proposed in literature. These latter will make use of the assumptions on the rheological behaviour previously made. This type of estimation has been performed for a debris flow occurred in an instrumented basin, on the North-Eastern Italian Alps, in 1996 and the results have been compared to those obtained by means of a mathematical simulation. For the calibration of the mathematical model the limnographs recorded by three different ultrasonic gauges installed along a torrent reach on the fan were used. The comparison evidenced the importance of time data recordings for a correct prediction of the debris flows dynamics. Without the availability of data recordings, the application of formulas based only on assumptions derived from field analysis could be misleading.

  11. Dynamic electro-thermal modeling of all-vanadium redox flow battery with forced cooling strategies

    Wei, Zhongbao; Zhao, Jiyun; Xiong, Binyu

    2014-01-01

    Highlights: • A dynamic electro-thermal model is proposed for VRB with forced cooling. • The Foster network is adopted to model the battery cooling process. • Both the electrolyte temperature and terminal voltage can be accurately predicted. • The flow rate of electrolyte and coolant significantly impact battery performance. - Abstract: The present study focuses on the dynamic electro-thermal modeling for the all-vanadium redox flow battery (VRB) with forced cooling strategies. The Foster network is adopted to dynamically model the heat dissipation of VRB with heat exchangers. The parameters of Foster network are extracted by fitting the step response of it to the results of linearized CFD model. Then a complete electro-thermal model is proposed by coupling the heat generation model, Foster network and electrical model. Results show that the established model has nearly the same accuracy with the nonlinear CFD model in electrolyte temperature prediction but drastically improves the computational efficiency. The modeled terminal voltage is also benchmarked with the experimental data under different current densities. The electrolyte temperature is found to be significantly influenced by the flow rate of coolant. As compared, although the electrolyte flow rate has unremarkable impact on electrolyte temperature, its effect on system pressure drop and battery efficiency is significant. Increasing the electrolyte flow rate improves the coulombic efficiency, voltage efficiency and energy efficiency simultaneously but at the expense of higher pump power demanded. An optimal flow rate exists for each operating condition to maximize the system efficiency

  12. Dynamic lift on an artificial static armor layer during highly unsteady open channel flow

    Spiller, Stephan Mark; Ruther, Nils; Friedrich, Heide

    2015-01-01

    The dynamic lift acting on a 100 mm × 100 mm section of a static armor layer during unsteady flow is directly measured in a series of physical experiments. The static armor layer is represented by an artificial streambed mold, made from an actual gravel bed. Data from a total of 190 experiments are presented, undertaken in identical conditions. Results show that during rapid discharge increases, the dynamic lift on the streambed repeatedly exhibits three clear peaks. The magnitude of the obse...

  13. Experimental Analysis of the Vorticity and Turbulent Flow Dynamics of a Pitching Airfoil at Realistic Flight Conditions

    Bowersox, Rodney D; Sahoo, Dipankar

    2007-01-01

    The primary objective of this research proposal was improved understanding of the fundamental vorticity and turbulent flow physics for a dynamically stalling airfoil at realistic helicopter flight conditions...

  14. Synchronized renal blood flow dynamics mapped with wavelet analysis of laser speckle flowmetry data

    Brazhe, Alexey R; Marsh, Donald J; von Holstein-Rathlou, Niels-Henrik

    2014-01-01

    of rat kidneys. The regulatory mechanism in the renal microcirculation generates oscillations in arterial blood flow at several characteristic frequencies. Our approach to laser speckle image processing allows detection of frequency and phase entrainments, visualization of their patterns, and estimation......Full-field laser speckle microscopy provides real-time imaging of superficial blood flow rate. Here we apply continuous wavelet transform to time series of speckle-estimated blood flow from each pixel of the images to map synchronous patterns in instantaneous frequency and phase on the surface...... of the extent of synchronization in renal cortex dynamics....

  15. Nonlinear transport processes and fluid dynamics: Cylindrical Couette flow of Lennard-Jones fluids

    Khayat, R.E.; Eu, B.C.

    1988-01-01

    In this paper we report on calculations of flow profiles for cylindrical Couette flow of a Lennard-Jones fluid. The flow is subjected to a temperature gradient and thermoviscous effects are taken into consideration. We apply the generalized fluid dynamic equations which are provided by the modified moment method for the Boltzmann equation reported previously. The results of calculations are in good agreement with the Monte Carlo direct simulation method by K. Nanbu [Phys. Fluids 27, 2632 (1984)] for most of Knudsen numbers for which the simulation data are available

  16. In-vivo imaging of blood flow dynamics using color Doppler optical coherence tomography

    Yazdanfar, Siavash; Rollins, Andrew M.; Izatt, Joseph A.

    2000-04-01

    Noninvasive quantitation of blood flow in the retinal micro circulation may elucidate the progression and treatment of ocular disorders including diabetic retinopathy, age-related degeneration, and glaucoma. Color Doppler optical coherence tomography was recently introduced as a technique allowing simultaneous micron-scale resolution cross-sectional imaging of tissue micro structure and blood flow in the human retina. Here, time-resolved imaging of dynamics of blood flow profiles was performed to measure cardiac pulsatility within retinal vessels. Retinal pulsatility has been shown to decrease throughout the progression of diabetic retinopathy.

  17. Turbulent flow structure at a discordant river confluence: Asymmetric jet dynamics with implications for channel morphology

    Sukhodolov, Alexander N.; Krick, Julian; Sukhodolova, Tatiana A.; Cheng, Zhengyang; Rhoads, Bruce L.; Constantinescu, George S.

    2017-06-01

    Only a handful of field studies have examined turbulent flow structure at discordant confluences; the dynamics of flow at such confluences have mainly been examined in the laboratory. This paper reports results of a field-based investigation of turbulent flow structure at a discordant river confluence. These results support the hypothesis that flow at a discordant alluvial confluence with a velocity ratio greater than 2 exhibits jet-like characteristics. Scaling analysis shows that the dynamics of the jet core are quite similar to those of free jets but that the complex structure of flow at the confluence imposes strong effects that can locally suppress or enhance the spreading rate of the jet. This jet-like behavior of the flow has important implications for morphodynamic processes at these types of confluences. The highly energetic core of the jet at this discordant confluence is displaced away from the riverbed, thereby inhibiting scour; however, helical motion develops adjacent to the jet, particularly at high flows, which may promote scour. Numerical experiments demonstrate that the presence or absence of a depositional wedge at the mouth of the tributary can strongly influence detachment of the jet from the bed and the angle of the jet within the confluence.

  18. Development of subchannel void measurement sensor and multidimensional two-phase flow dynamics in rod bundle

    Arai, T.; Furuya, M.; Kanai, T.; Shirakawa, K.

    2011-01-01

    An accurate subchannel database is crucial for modeling the multidimensional two-phase flow in a rod bundle and for validating subchannel analysis codes. Based on available reference, it can be said that a point-measurement sensor for acquiring void fractions and bubble velocity distributions do not infer interactions of the subchannel flow dynamics, such as a cross flow and flow distribution, etc. In order to acquire multidimensional two-phase flow in a 10×10 rod bundle with an o.d. of 10 mm and 3110 mm length, a new sensor consisting of 11-wire by 11-wire and 10-rod by 10-rod electrodes was developed. Electric potential in the proximity region between two wires creates a void fraction in the center subchannel region, like a so-called wire mesh sensor. A unique aspect of the devised sensor is that the void fraction near the rod surface can be estimated from the electric potential in the proximity region between one wire and one rod. The additional 400 points of void fraction and phasic velocity in 10×10 bundle can therefore be acquired. The devised sensor exhibits the quasi three-dimensional flow structures, i.e. void fraction, phasic velocity and bubble chord length distributions. These quasi three-dimensional structures exhibit the complexity of two-phase flow dynamics, such as coalescence and the breakup of bubbles in transient phasic velocity distributions. (author)

  19. Lattice Boltzmann simulations for wall-flow dynamics in porous ceramic diesel particulate filters

    Lee, Da Young; Lee, Gi Wook; Yoon, Kyu; Chun, Byoungjin; Jung, Hyun Wook

    2018-01-01

    Flows through porous filter walls of wall-flow diesel particulate filter are investigated using the lattice Boltzmann method (LBM). The microscopic model of the realistic filter wall is represented by randomly overlapped arrays of solid spheres. The LB simulation results are first validated by comparison to those from previous hydrodynamic theories and constitutive models for flows in porous media with simple regular and random solid-wall configurations. We demonstrate that the newly designed randomly overlapped array structures of porous walls allow reliable and accurate simulations for the porous wall-flow dynamics in a wide range of solid volume fractions from 0.01 to about 0.8, which is beyond the maximum random packing limit of 0.625. The permeable performance of porous media is scrutinized by changing the solid volume fraction and particle Reynolds number using Darcy's law and Forchheimer's extension in the laminar flow region.

  20. Multiphase Flow Dynamics 4 Turbulence, Gas Adsorption and Release, Diesel Fuel Properties

    Kolev, Nikolay Ivanov

    2012-01-01

    The present Volume 4 of the successful monograh package “Multiphase Flow Dynamics”is devoted to selected Chapters of the multiphase fluid dynamics that are important for practical applications but did not find place in the previous volumes. The state of the art of the turbulence modeling in multiphase flows is presented. As introduction, some basics of the single phase boundary layer theory including some important scales and flow oscillation characteristics in pipes and rod bundles are presented. Then the scales characterizing the dispersed flow systems are presented. The description of the turbulence is provided at different level of complexity: simple algebraic models for eddy viscosity, simple algebraic models based on the Boussinesq hypothesis, modification of the boundary layer share due to modification of the bulk turbulence, modification of the boundary layer share due to nucleate boiling. The role of the following forces on the mathematical description of turbulent flows is discussed: the lift fo...

  1. Dynamic fluid connectivity during steady-state multiphase flow in a sandstone.

    Reynolds, Catriona A; Menke, Hannah; Andrew, Matthew; Blunt, Martin J; Krevor, Samuel

    2017-08-01

    The current conceptual picture of steady-state multiphase Darcy flow in porous media is that the fluid phases organize into separate flow pathways with stable interfaces. Here we demonstrate a previously unobserved type of steady-state flow behavior, which we term "dynamic connectivity," using fast pore-scale X-ray imaging. We image the flow of N 2 and brine through a permeable sandstone at subsurface reservoir conditions, and low capillary numbers, and at constant fluid saturation. At any instant, the network of pores filled with the nonwetting phase is not necessarily connected. Flow occurs along pathways that periodically reconnect, like cars controlled by traffic lights. This behavior is consistent with an energy balance, where some of the energy of the injected fluids is sporadically converted to create new interfaces.

  2. Computational modeling of lava domes using particle dynamics to investigate the effect of conduit flow mechanics on flow patterns

    Husain, Taha Murtuza

    Large (1--4 x 106 m3) to major (> 4 x 106 m3) dome collapses for andesitic lava domes such as Soufriere Hills Volcano, Montserrat are observed for elevated magma discharge rates (6--13 m3/s). The gas rich magma pulses lead to pressure build up in the lava dome that result in structural failure of the over steepened canyon-like walls which may lead to rockfall or pyroclastic flow. This indicates that dome collapse intimately related to magma extrusion rate. Variation in magma extrusion rate for open-system magma chambers is observed to follow alternating periods of high and low activity. Periodic behavior of magma exhibits a rich diversity in the nature of its eruptive history due to variation in magma chamber size, total crystal content, linear crystal growth rate and magma replenishment rate. Distinguished patterns of growth were observed at different magma flow rates ranging from endogenous to exogenous dome growth for magma with varying strengths. Determining the key parameters that control the transition in flow pattern of the magma during its lava dome building eruption is the main focus. This dissertation examines the mechanical effects on the morphology of the evolving lava dome on the extrusion of magma from a central vent using a 2D particle dynamics model. The particle dynamics model is coupled with a conduit flow model that incorporates the kinetics of crystallization and rheological stiffening to investigate important mechanisms during lava dome building eruptions. Chapter I of this dissertation explores lava dome growth and failure mechanics using a two-dimensional particle-dynamics model. The model follows the evolution of fractured lava, with solidification driven by degassing induced crystallization of magma. The particle-dynamics model emulates the natural development of dome growth and rearrangement of the lava dome which is difficult in mesh-based analyses due to mesh entanglement effects. The deformable talus evolves naturally as a frictional

  3. Measurements of particle dynamics in slow, dense granular Couette flow

    Mueth, Daniel M.

    2003-01-01

    Experimental measurements of particle dynamics on the lower surface of a three-dimensional (3D) Couette cell containing monodisperse spheres are reported. The average radial density and velocity profiles are similar to those previously measured within the bulk and on the lower surface of the 3D cell filled with mustard seeds. Observations of the evolution of particle velocities over time reveal distinct motion events, intervals where previously stationary particles move for a short duration before jamming again. The cross correlation between the velocities of two particles at a given distance r from the moving wall reveals a characteristic length scale over which the particles are correlated. The autocorrelation of a single particle’s velocity reveals a characteristic time scale τ, which decreases with increasing distance from the inner moving wall. This may be attributed to the increasing rarity at which the discrete motion events occur and the reduced duration of those events at large r. The relationship between the rms azimuthal velocity fluctuations, δvθ(r), and average shear rate, γ˙(r), was found to be δvθ∝γ˙α with α=0.52±0.04. These observations are compared with other recent experiments and with the modified hydrodynamic model recently introduced by Bocquet et al.

  4. Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient

    Olson, L.; Nordberg, A.; Holst, H. von

    1992-01-01

    Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11 C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted. (authors)

  5. Mapping of barley alpha-amylases and outer subsite mutants reveals dynamic high-affinity subsites and barriers in the long substrate binding cleft

    Kandra, L.; Abou Hachem, Maher; Gyemant, G.

    2006-01-01

    Subsite affinity maps of long substrate binding clefts in barley alpha-amylases, obtained using a series of maltooligosaccharides of degree of polymerization of 3-12, revealed unfavorable binding energies at the internal subsites -3 and -5 and at subsites -8 and +3/+4 defining these subsites...... as binding barriers. Barley a-amylase I mutants Y105A and T212Y at subsite -6 and +4 resulted in release or anchoring of bound substrate, thus modifying the affinities of other high-affinity subsites (-2 and +2) and barriers. The double mutant Y105A-T212Y displayed a hybrid subsite affinity profile......, converting barriers to binding areas. These findings highlight the dynamic binding energy distribution and the versatility of long maltooligosaccharide derivatives in mapping extended binding clefts in a-amylases....

  6. Computational revelation of binding mechanisms of inhibitors to endocellular protein tyrosine phosphatase 1B using molecular dynamics simulations.

    Yan, Fangfang; Liu, Xinguo; Zhang, Shaolong; Su, Jing; Zhang, Qinggang; Chen, Jianzhong

    2017-11-06

    Endocellular protein tyrosine phosphatase 1B (PTP1B) is one of the most promising target for designing and developing drugs to cure type-II diabetes and obesity. Molecular dynamics (MD) simulations combined with molecular mechanics generalized Born surface area (MM-GBSA) and solvated interaction energy methods were applied to study binding differences of three inhibitors (ID: 901, 941, and 968) to PTP1B, the calculated results show that the inhibitor 901 has the strongest binding ability to PTP1B among the current inhibitors. Principal component (PC) analysis was also carried out to investigate the conformational change of PTP1B, and the results indicate that the associations of inhibitors with PTP1B generate a significant effect on the motion of the WPD-loop. Free energy decomposition method was applied to study the contributions of individual residues to inhibitor bindings, it is found that three inhibitors can generate hydrogen bonding interactions and hydrophobic interactions with different residues of PTP1B, which provide important forces for associations of inhibitors with PTP1B. This research is expected to give a meaningfully theoretical guidance to design and develop of effective drugs curing type-II diabetes and obesity.

  7. Dynamics of a vertical-flow windrow vermicomposting system.

    Hanc, Ales; Castkova, Tereza; Kuzel, Stanislav; Cajthaml, Tomas

    2017-11-01

    Large-scale vermicomposting under outdoor conditions may differ from small-scale procedures in the laboratory. The present study evaluated changes in selected properties of a large-scale vertical-flow windrow vermicomposting system with continuous feeding with household biowaste. The windrow profile was divided into five layers of differing thickness and age after more than 12 months of vermicomposting. The top layer (0-30 cm, age <3 months) was characterised by partially decomposed organic matter with a high pH value and an elevated carbon/nitrogen (C/N) ratio. The earthworm biomass was 15 g kg -1 with a population density of 125 earthworms per kilogram predominantly found in clusters. The greatest amount of fungi (3.5 µg g -1 dw) and bacteria (62 µg g -1 dw) (expressed as phospholipid fatty acid analysis) was found in this layer. Thus, the top layer could be used for an additional cycle of windrow vermicomposting and for the preparation of aqueous extracts to protect plants against diseases. The lower layers (graduated by 30 cm and by 3 months of age) were mature as reflected by the low content of ammonia nitrogen, ratio of ammonia to nitrate nitrogen and dissolved organic carbon, and high ion-exchange capacity and its ratio to carbon. These layers were characterised by elevated values for electrical conductivity, total content of nutrients, available magnesium content, and a relatively large bacterial/fungal ratio. On the basis of the observed properties, the bottom layers were predetermined as effective fertilisers.

  8. Dynamics of three-tori in a periodically forced navier-stokes flow

    Lopez; Marques

    2000-07-31

    Three-tori solutions of the Navier-Stokes equations and their dynamics are elucidated by use of a global Poincare map. The flow is contained in a finite annular gap between two concentric cylinders, driven by the steady rotation and axial harmonic oscillations of the inner cylinder. The three-tori solutions undergo global bifurcations, including a new gluing bifurcation, associated with homoclinic and heteroclinic connections to unstable solutions (two-tori). These unstable two-tori act as organizing centers for the three-tori dynamics. A discrete space-time symmetry influences the dynamics.

  9. A Computational Fluid Dynamics Study of Swirling Flow Reduction by Using Anti-Vortex Baffle

    Yang, H. Q.; Peugeot, John W.; West, Jeff S.

    2017-01-01

    An anti-vortex baffle is a liquid propellant management device placed adjacent to an outlet of the propellant tank. Its purpose is to substantially reduce or eliminate the formation of free surface dip and vortex, as well as prevent vapor ingestion into the outlet, as the liquid drains out through the flight. To design an effective anti-vortex baffle, Computational Fluid Dynamic (CFD) simulations were undertaken for the NASA Ares I vehicle LOX tank subjected to the simulated flight loads with and without the anti-vortex baffle. The Six Degree-Of-Freedom (6-DOF) dynamics experienced by the Crew Launch Vehicle (CLV) during ascent were modeled by modifying the momentum equations in a CFD code to accommodate the extra body forces from the maneuvering in a non-inertial frame. The present analysis found that due to large moments, the CLV maneuvering has a significant impact on the vortical flow generation inside the tank. Roll maneuvering and side loading due to pitch and yaw are shown to induce swirling flow. The vortical flow due to roll is symmetrical with respect to the tank centerline, while those induced by pitch and yaw maneuverings showed two vortices side by side. The study found that without the anti-vortex baffle, the swirling flow caused surface dip during the late stage of drainage and hence early vapor ingestion. The flow can also be non-uniform in the drainage pipe as the secondary swirling flow velocity component can be as high as 10% of the draining velocity. An analysis of the vortex dynamics shows that the swirling flow in the drainage pipe during the Upper Stage burn is mainly the result of residual vortices inside the tank due to the conservation of angular momentum. The study demonstrated that the swirling flow in the drainage pipe can be effectively suppressed by employing the anti-vortex baffle.

  10. Contribution to the study of two-phase flow analysis considering the exixtence of a dynamic flow between the phases

    Silva, M.C.

    1981-04-01

    The application of the dynamic slip technique to modify the conservation of the thermodynamic model use in Relap4/Mod5 is aimed at. The new model contain additional terms which allow take in account the influence of separated flows. The modified code has been submitted to a test. A simulation of a small LOCA has been performed with an equivalent area of 181.045 cm 2 in the piping between the reactor vessel and one of the main coolant pumps of Angra 1 plant. The same procedure was performed by using the original version of the code. The comparison between results of both versions show that the dynamic slip model gives more realistic (less conservative) results. (E.G.) [pt

  11. Dispersed plug flow model for upflow anaerobic sludge bed reactors with focus on granular sludge dynamics

    Kalyuzhnyi, S.V.; Fedorovich, V.V.; Lens, P.N.L.

    2006-01-01

    A new approach to model upflow anaerobic sludge bed (UASB)-reactors, referred to as a one-dimensional dispersed plug flow model, was developed. This model focusses on the granular sludge dynamics along the reactor height, based on the balance between dispersion, sedimentation and convection using

  12. Outlook of the world steel cycle based on the stock and flow dynamics.

    Hatayama, Hiroki; Daigo, Ichiro; Matsuno, Yasunari; Adachi, Yoshihiro

    2010-08-15

    We present a comprehensive analysis of steel use in the future compiled using dynamic material flow analysis (MFA). A dynamic MFA for 42 countries depicted the global in-use stock and flow up to the end of 2005. On the basis of the transition of steel stock for 2005, the growth of future steel stock was then estimated considering the economic growth for every country. Future steel demand was estimated using dynamic analysis under the new concept of "stocks drive flows". The significant results follow. World steel stock reached 12.7 billion t in 2005, and has doubled in the last 25 years. The world stock in 2005 mainly consisted of construction (60%) and vehicles (10%). Stock in these end uses will reach 55 billion t in 2050, driven by a 10-fold increase in Asia. Steel demand will reach 1.8 billion t in 2025, then slightly decrease, and rise again by replacement of buildings. The forecast of demand clearly represents the industrial shift; at first the increase is dominated by construction, and then, after 2025, demand for construction decreases and demand for vehicles increases instead. This study thus provides the dynamic mechanism of steel stock and flow toward the future, which contributes to the design of sustainable steel use.

  13. Simulant-material experimental investigation of flow dynamics in the CRBR Upper-Core Structure

    Wilhelm, D.; Starkovich, V.S.; Chapyak, E.J.

    1982-09-01

    The results of a simulant-material experimental investigation of flow dynamics in the Clinch River Breeder Reactor (CRBR) Upper Core Structure are described. The methodology used to design the experimental apparatus and select test conditions is detailed. Numerous comparisons between experimental data and SIMMER-II Code calculations are presented with both advantages and limitations of the SIMMER modeling features identified

  14. Hydrodynamically Coupled Brownian Dynamics simulations for flow on non-Newtonian fluids

    Ahuja, Vishal Raju

    2018-01-01

    This thesis deals with model development for particle-based flow simulations of non-Newtonian fluids such as polymer solutions. A novel computational technique called Hydrodynamically Coupled Brownian Dynamics (HCBD) is presented in this thesis. This technique essentially couples the Brownian motion

  15. An Effective Approach for Clustering InhA Molecular Dynamics Trajectory Using Substrate-Binding Cavity Features.

    Renata De Paris

    Full Text Available Protein receptor conformations, obtained from molecular dynamics (MD simulations, have become a promising treatment of its explicit flexibility in molecular docking experiments applied to drug discovery and development. However, incorporating the entire ensemble of MD conformations in docking experiments to screen large candidate compound libraries is currently an unfeasible task. Clustering algorithms have been widely used as a means to reduce such ensembles to a manageable size. Most studies investigate different algorithms using pairwise Root-Mean Square Deviation (RMSD values for all, or part of the MD conformations. Nevertheless, the RMSD only may not be the most appropriate gauge to cluster conformations when the target receptor has a plastic active site, since they are influenced by changes that occur on other parts of the structure. Hence, we have applied two partitioning methods (k-means and k-medoids and four agglomerative hierarchical methods (Complete linkage, Ward's, Unweighted Pair Group Method and Weighted Pair Group Method to analyze and compare the quality of partitions between a data set composed of properties from an enzyme receptor substrate-binding cavity and two data sets created using different RMSD approaches. Ensembles of representative MD conformations were generated by selecting a medoid of each group from all partitions analyzed. We investigated the performance of our new method for evaluating binding conformation of drug candidates to the InhA enzyme, which were performed by cross-docking experiments between a 20 ns MD trajectory and 20 different ligands. Statistical analyses showed that the novel ensemble, which is represented by only 0.48% of the MD conformations, was able to reproduce 75% of all dynamic behaviors within the binding cavity for the docking experiments performed. Moreover, this new approach not only outperforms the other two RMSD-clustering solutions, but it also shows to be a promising strategy to

  16. State diagram for adhesion dynamics of deformable capsules under shear flow.

    Luo, Zheng Yuan; Bai, Bo Feng

    2016-08-17

    Due to the significance of understanding the underlying mechanisms of cell adhesion in biological processes and cell capture in biomedical applications, we numerically investigate the adhesion dynamics of deformable capsules under shear flow by using a three-dimensional computational fluid dynamic model. This model is based on the coupling of the front tracking-finite element method for elastic mechanics of the capsule membrane and the adhesion kinetics simulation for adhesive interactions between capsules and functionalized surfaces. Using this model, three distinct adhesion dynamic states are predicted, such as detachment, rolling and firm-adhesion. Specifically, the effects of capsule deformability quantified by the capillary number on the transitions of these three dynamic states are investigated by developing an adhesion dynamic state diagram for the first time. At low capillary numbers (e.g. Ca state no longer appears, since capsules exhibit large deviation from the spherical shape.

  17. Development of an advanced fluid-dynamic analysis code: α-flow

    Akiyama, Mamoru

    1990-01-01

    A Project for development of large scale three-dimensional fluid-dynamic analysis code, α-FLOW, coping with the recent advancement of supercomputers and workstations, has been in progress. This project is called the α-Project, which has been promoted by the Association for Large Scale Fluid Dynamics Analysis Code comprising private companies and research institutions such as universities. The developmental period for the α-FLOW is four years, March 1989 to March 1992. To date, the major portions of basic design and program preparation have been completed and the project is in the stage of testing each module. In this paper, the present status of the α-Project, design policy and outline of α-FLOW are described. (author)

  18. An autonomous dynamical system captures all LCSs in three-dimensional unsteady flows.

    Oettinger, David; Haller, George

    2016-10-01

    Lagrangian coherent structures (LCSs) are material surfaces that shape the finite-time tracer patterns in flows with arbitrary time dependence. Depending on their deformation properties, elliptic and hyperbolic LCSs have been identified from different variational principles, solving different equations. Here we observe that, in three dimensions, initial positions of all variational LCSs are invariant manifolds of the same autonomous dynamical system, generated by the intermediate eigenvector field, ξ 2 (x 0 ), of the Cauchy-Green strain tensor. This ξ 2 -system allows for the detection of LCSs in any unsteady flow by classical methods, such as Poincaré maps, developed for autonomous dynamical systems. As examples, we consider both steady and time-aperiodic flows, and use their dual ξ 2 -system to uncover both hyperbolic and elliptic LCSs from a single computation.

  19. Supercritical droplet dynamics and emission in low speed cross-flows

    Chae, J. W.; Yang, H. S.; Yoon, W. S.

    2008-01-01

    Droplet dynamics and emission of a supercritical droplet in crossing gas stream are numerically investigated. Effects of ambient pressure and velocity of nitrogen gas on the dynamics of the supercritical oxygen droplet are parametrically examined. Unsteady conservative axisymmetric Navier-Stokes equations in curvilinear coordinates are preconditioned and solved by dual-time stepping method. A unified property evaluation scheme based on a fundamental equation of state and extended corresponding-state principle is established to deal with thermodynamic non-idealities and transport anomalies. At lower pressures and velocities of nitrogen cross flows, both the diffusion and the convection are important in determining the droplet dynamics. Relative flow motion causes a secondary breakup and cascading vortices, and the droplet lifetime is reduced with increasing in ambient pressure. At higher ambient pressures and velocities, however, the droplet dynamics become convection-controlled while the secondary breakup is hindered by reduced diffusivity of the oxygen. Gas-phase mixing depends on the convection and diffusion velocities in conjunction with corresponding droplet deformation and flow interaction. Supercritical droplet dynamics and emission is not similar with respect to the pressure and velocity of the ambient gas and thus provides no scale

  20. Finite element simulation of dynamic wetting flows as an interface formation process

    Sprittles, J.E.

    2013-01-01

    A mathematically challenging model of dynamic wetting as a process of interface formation has been, for the first time, fully incorporated into a numerical code based on the finite element method and applied, as a test case, to the problem of capillary rise. The motivation for this work comes from the fact that, as discovered experimentally more than a decade ago, the key variable in dynamic wetting flows - the dynamic contact angle - depends not just on the velocity of the three-phase contact line but on the entire flow field/geometry. Hence, to describe this effect, it becomes necessary to use the mathematical model that has this dependence as its integral part. A new physical effect, termed the \\'hydrodynamic resist to dynamic wetting\\', is discovered where the influence of the capillary\\'s radius on the dynamic contact angle, and hence on the global flow, is computed. The capabilities of the numerical framework are then demonstrated by comparing the results to experiments on the unsteady capillary rise, where excellent agreement is obtained. Practical recommendations on the spatial resolution required by the numerical scheme for a given set of non-dimensional similarity parameters are provided, and a comparison to asymptotic results available in limiting cases confirms that the code is converging to the correct solution. The appendix gives a user-friendly step-by-step guide specifying the entire implementation and allowing the reader to easily reproduce all presented results, including the benchmark calculations. © 2012 Elsevier Inc.

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

    Gao, Bo; Zhang, Ronghui; Lou, Xiaoming

    2016-01-01

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

  2. Modeling dynamic stall on wind turbine blades under rotationally augmented flow fields

    Guntur, Srinivas; Sørensen, Niels N.; Schreck, Scott

    2016-01-01

    a reduced order dynamic stall model that uses rotationally augmented steady-state polars obtained from steady Phase VI experimental sequences, instead of the traditional two-dimensional, non-rotating data. The aim of this work is twofold. First, the blade loads estimated by the DDES simulations are compared...... Experiment Phase VI experimental data, including constant as well as continuously pitching blade conditions during axial operation; (2) data from unsteady delayed detached eddy simulations (DDES) carried out using the Technical University of Denmark’s in-house flow solver Ellipsys3D; and (3) data from...... with those from the dynamic stall model. This allowed the differences between the stall phenomenon on the inboard parts of harmonically pitching blades on a rotating wind turbine and the classic dynamic stall representation in two-dimensional flow to be investigated. Results indicated a good qualitative...

  3. Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise

    Madsen, P L; Sperling, B K; Warming, T

    1993-01-01

    Results obtained by the 133Xe clearance method with external detectors and by transcranial Doppler sonography (TCD) suggest that dynamic exercise causes an increase of global average cerebral blood flow (CBF). These data are contradicted by earlier data obtained during less-well-defined conditions....... To investigate this controversy, we applied the Kety-Schmidt technique to measure the global average levels of CBF and cerebral metabolic rate of oxygen (CMRO2) during rest and dynamic exercise. Simultaneously with the determination of CBF and CMRO2, we used TCD to determine mean maximal flow velocity...... in the middle cerebral artery (MCA Vmean). For values of CBF and MCA Vmean a correction for an observed small drop in arterial PCO2 was carried out. Baseline values for global CBF and CMRO2 were 50.7 and 3.63 ml.100 g-1.min-1, respectively. The same values were found during dynamic exercise, whereas a 22% (P

  4. Effect of short-chain branching on interfacial polymer structure and dynamics under shear flow.

    Jeong, Sohdam; Kim, Jun Mo; Cho, Soowon; Baig, Chunggi

    2017-11-22

    We present a detailed analysis on the effect of short-chain branches on the structure and dynamics of interfacial chains using atomistic nonequilibrium molecular dynamics simulations of confined polyethylene melts in a wide range of shear rates. The intrinsically fast random motions of the short branches constantly disturb the overall chain conformation, leading to a more compact and less deformed chain structure of the short-chain branched (SCB) polymer against the imposed flow field in comparison with the corresponding linear polymer. Moreover, such highly mobile short branches along the backbone of the SCB polymer lead to relatively weaker out-of-plane wagging dynamics of interfacial chains, with highly curvy backbone structures in the intermediate flow regime. In conjunction with the contribution of short branches (as opposed to that of the backbone) to the total interfacial friction between the chains and the wall, the SCB polymer shows a nearly constant behavior in the degree of slip (d s ) with respect to shear rate in the weak-to-intermediate flow regimes. On the contrary, in the strong flow regime where irregular chain rotation and tumbling dynamics occur via intensive dynamical collisions between interfacial chains and the wall, an enhancement effect on the chain detachment from the wall, caused by short branches, leads to a steeper increase in d s for the SCB polymer than for the linear polymer. Remarkably, the SCB chains at the interface exhibit two distinct types of rolling mechanisms along the backbone, with a half-dumbbell mesoscopic structure at strong flow fields, in addition to the typical hairpin-like tumbling behavior displayed by the linear chains.

  5. Numerical analysis of air effect on the powder flow dynamics in the FT4 Powder Rheometer

    Nan Wenguang

    2017-01-01

    Full Text Available The FT4 powder rheometer of Freeman Technology is widely used nowadays in industry for characterisation of particle flow under dynamic conditions of shear strain rate. It measures the work (termed flow energy required to penetrate a rotating impeller into a powder bed. However, little is known about its underlying powder mechanics, i.e. the relationship between the flow energy and the prevailing local shear stress. This has recently been studied, but only for very simple and ideal systems amenable to analysis by DEM. We analyse the effect of gas flow through the powder bed on the flow behaviour of cohesionless particles in FT4 by DEM-CFD simulation. The results show that the relative particle velocities induced by the mean shear speed, is of the same order as that produced by the root of granular temperature. The shear stress in both cases with and without gas flow could be quantified by the inertial number. The flow energy correlates well with the shear stress in front of the blade, and both increase with the inertial number and could be significantly reduced by the upward gas flow.

  6. Flow of nucleons and fragments in 40Ar+27Al collisions studied with antisymmetrized molecular dynamics

    Ono, A.; Horiuchi, H.

    1995-01-01

    Collective transverse momentum flow of nucleons and fragments in intermediate energy 40 Ar+ 27 Al collisions is calculated with the antisymmetrized molecular dynamics (AMD). The observed flow and its balance energy are reproduced well by calculation with the Gogny force which corresponds to the soft equation of state (EOS) of nuclear matter. The calculated absolute value of the fragment flow is larger than that of the nucleon flow in the negative flow region, which can be explained by the existence of two components of flow. In addition to many similarities, the difference in the deuteron flow is found between 12 C+ 12 C and 40 Ar+ 27 Al collisions, and its origin is investigated by studying the production mechanism of light fragments. We also investigate the dependence of the flow of nucleons and fragments on the stochastic collision cross section and the effective interaction, and conclude that the stiff EOS without momentum dependence of the mean field is not consistent with the experimental data

  7. Computational fluid dynamics analysis and PIV validation of a bionic vortex flow pulsatile LVAD.

    Xu, Liang; Yang, Ming; Ye, Lin; Dong, Zhaopeng

    2015-01-01

    Hemocompatibility is highly affected by the flow field in Left Ventricular Assistant Devices (LVAD). An asymmetric inflow and outflow channel arrangement with a 45° intersection angle with respect to the blood chamber is proposed to approximate the vascular structure of the aorta and left atrium on the left ventricle. The structure is expected to develop uninterruptible vortex flow state which is similar to the flow state in human left ventricle. The Computational Fluid Dynamics (CFD) asymmetric model is simulated using ANSYS workbench. To validate the velocity field calculated by CFD, a Particle Image Velocimetry (PIV) experiment is conducted. The CFD results show that the proposed blood chamber could generate a shifting vortex flow that would be redirected to the aorta during ejection to form a persistent recirculating flow state, which is similar to the echocardiographic flow state in left ventricle. Both the PIV and the CFD results show the development of a persistent vortex during the pulsatile period. Comparison of the qualitative flow pattern and quantitative probed velocity histories in a pulsatile period shows a good agreement between the CFD and PIV data. The goal of developing persistent quasi intra-ventricle vortex flow state in LVAD is realized.

  8. Post-operative ventricular flow dynamics following atrioventricular valve surgical and device therapies: A review.

    Nguyen, Yen Ngoc; Ismail, Munirah; Kabinejadian, Foad; Tay, Edgar Lik Wui; Leo, Hwa Liang

    2018-04-01

    Intra-ventricular flow dynamics has recently emerged as an important evaluation and diagnosis tool in different cardiovascular conditions. The formation of vortex pattern during the cardiac cycle has been suggested to play important epigenetic and energy-modulation roles in cardiac remodelling, adaptations and mal-adaptations. In this new perspective, flow alterations due to different cardiovascular procedures can affect the long-term outcome of those procedures. Especially, repairs and replacements performed on atrioventricular valves are likely to exert direct impact on intra-ventricular flow pattern. In this review, current consensus around the roles of vortex dynamics in cardiac function is discussed. An overview of physiological vortex patterns found in healthy left and right ventricles as well as post-operative ventricular flow phenomenon owing to different atrioventricular valvular procedures are reviewed, followed by the summary of different vortex identification schemes used to characterise intraventricular flow. This paper also emphasises on future research directions towards a comprehensive understanding of intra-cardiac flow and its clinical relevance. The knowledge could encourage more effective pre-operative planning and better outcomes for current clinical practices. Copyright © 2018. Published by Elsevier Ltd.

  9. Nonlinear Dynamics of Non-uniform Current-Vortex Sheets in Magnetohydrodynamic Flows

    Matsuoka, C.; Nishihara, K.; Sano, T.

    2017-04-01

    A theoretical model is proposed to describe fully nonlinear dynamics of interfaces in two-dimensional MHD flows based on an idea of non-uniform current-vortex sheet. Application of vortex sheet model to MHD flows has a crucial difficulty because of non-conservative nature of magnetic tension. However, it is shown that when a magnetic field is initially parallel to an interface, the concept of vortex sheet can be extended to MHD flows (current-vortex sheet). Two-dimensional MHD flows are then described only by a one-dimensional Lagrange parameter on the sheet. It is also shown that bulk magnetic field and velocity can be calculated from their values on the sheet. The model is tested by MHD Richtmyer-Meshkov instability with sinusoidal vortex sheet strength. Two-dimensional ideal MHD simulations show that the nonlinear dynamics of a shocked interface with density stratification agrees fairly well with that for its corresponding potential flow. Numerical solutions of the model reproduce properly the results of the ideal MHD simulations, such as the roll-up of spike, exponential growth of magnetic field, and its saturation and oscillation. Nonlinear evolution of the interface is found to be determined by the Alfvén and Atwood numbers. Some of their dependence on the sheet dynamics and magnetic field amplification are discussed. It is shown by the model that the magnetic field amplification occurs locally associated with the nonlinear dynamics of the current-vortex sheet. We expect that our model can be applicable to a wide variety of MHD shear flows.

  10. Determination of Noncovalent Binding Using a Continuous Stirred Tank Reactor as a Flow Injection Device Coupled to Electrospray Ionization Mass Spectrometry

    Santos, Inês C.; Waybright, Veronica B.; Fan, Hui; Ramirez, Sabra; Mesquita, Raquel B. R.; Rangel, António O. S. S.; Fryčák, Petr; Schug, Kevin A.

    2015-07-01

    Described is a new method based on the concept of controlled band dispersion, achieved by hyphenating flow injection analysis with ESI-MS for noncovalent binding determinations. A continuous stirred tank reactor (CSTR) was used as a FIA device for exponential dilution of an equimolar host-guest solution over time. The data obtained was treated for the noncovalent binding determination using an equimolar binding model. Dissociation constants between vancomycin and Ac-Lys(Ac)-Ala-Ala-OH peptide stereoisomers were determined using both the positive and negative ionization modes. The results obtained for Ac- L-Lys(Ac)- D-Ala- D-Ala (a model for a Gram-positive bacterial cell wall) binding were in reasonable agreement with literature values made by other mass spectrometry binding determination techniques. Also, the developed method allowed the determination of dissociation constants for vancomycin with Ac- L-Lys(Ac)- D-Ala- L-Ala, Ac- L-Lys(Ac)- L-Ala- D-Ala, and Ac- L-Lys(Ac)- L-Ala- L-Ala. Although some differences in measured binding affinities were noted using different ionization modes, the results of each determination were generally consistent. Differences are likely attributable to the influence of a pseudo-physiological ammonium acetate buffer solution on the formation of positively- and negatively-charged ionic complexes.

  11. Petrological Geodynamics of Mantle Melting II. AlphaMELTS + Multiphase Flow: Dynamic Fractional Melting

    Tirone, Massimiliano

    2018-03-01

    In this second installment of a series that aims to investigate the dynamic interaction between the composition and abundance of the solid mantle and its melt products, the classic interpretation of fractional melting is extended to account for the dynamic nature of the process. A multiphase numerical flow model is coupled with the program AlphaMELTS, which provides at the moment possibly the most accurate petrological description of melting based on thermodynamic principles. The conceptual idea of this study is based on a description of the melting process taking place along a 1-D vertical ideal column where chemical equilibrium is assumed to apply in two local sub-systems separately on some spatial and temporal scale. The solid mantle belongs to a local sub-system (ss1) that does not interact chemically with the melt reservoir which forms a second sub-system (ss2). The local melt products are transferred in the melt sub-system ss2 where the melt phase eventually can also crystallize into a different solid assemblage and will evolve dynamically. The main difference with the usual interpretation of fractional melting is that melt is not arbitrarily and instantaneously extracted from the mantle, but instead remains a dynamic component of the model, hence the process is named dynamic fractional melting (DFM). Some of the conditions that may affect the DFM model are investigated in this study, in particular the effect of temperature, mantle velocity at the boundary of the mantle column. A comparison is made with the dynamic equilibrium melting (DEM) model discussed in the first installment. The implications of assuming passive flow or active flow are also considered to some extent. Complete data files of most of the DFM simulations, four animations and two new DEM simulations (passive/active flow) are available following the instructions in the supplementary material.

  12. Dynamic characteristics of a perforated cylindrical shell for flow distribution in SMART

    Lim, Seungho; Choi, Youngin; Ha, Kyungrok [Department of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Park, Kyoung-Su, E-mail: pks6348@yonsei.ac.kr [Department of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Park, No-Cheol; Park, Young-Pil [Department of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Jeong, Kyeong-Hoon; Park, Jin-Seok [Korea Atomic Energy Research Institute, 1045 Daedeokdaero, Yuseong, Daejeon 305-303 (Korea, Republic of)

    2011-10-15

    Highlights: > A 1/12 scaled-down flow skirt is manufactured and a modal test is performed. > A finite element model predicts the added mass effect of the perforated cylindrical shell. > Modal characteristics are extracted by considering the fluid-structure interaction. - Abstract: The System-integrated Modular Advanced ReacTor (SMART) is a small nuclear reactor under development in Korea. It is equipped with a perforated cylindrical shell, which is called a flow skirt, in the lower plenum of the reactor for uniform flow distribution and to prevent inflow of debris into the core. This perforated cylindrical shell can be excited by external forces such as seismic or pump pulsation loads. The dynamic characteristics of the perforated cylindrical shell must be identified for further dynamic analysis. This research explores the modal analysis of the scaled-down flow skirt model submerged in coolant water. For the numerical simulation, finite element analysis is carried out to extract modal characteristics of the structure considering the fluid-structure interaction and we introduce the NAVMI factor for similarity analysis. In the finite element model, the whole shape of the perforated cylindrical shell is simulated instead of using the effective material properties. In addition, a 1/12 scaled-down flow skirt is manufactured, and an experiment is designed using an exciter and waterproof accelerometers for the modal test. Due to excellent agreement between the modal test results and the finite element analysis results such as natural frequencies and mode shapes, the finite element model is validated and can be used to predict the dynamic characteristics of the real flow skirt. Moreover, the natural frequency of the real flow skirt can be calculated from the NAVMI factor and is in good agreement with the FEM result.

  13. Effect of counterion binding efficiency on structure and dynamics of wormlike micelles.

    Oelschlaeger, C; Suwita, P; Willenbacher, N

    2010-05-18

    We have studied the effect of counterion binding efficiency on the linear viscoelastic properties of wormlike micelles formed from hexadecyltrimethylammonium bromide (CTAB) in the presence of different nonpenetrating inorganic salts: potassium bromide (KBr), sodium nitrate (NaNO(3)), and sodium chlorate (NaClO(3)). We have varied the salt/surfactant ratio R at fixed surfactant concentration of 350 mM. Results are compared to data for the system cetylpyridinium chloride (CPyCl) and the penetrating counterion sodium salicylate (NaSal) (Oelschlaeger, C.; Schopferer, M.; Scheffold, F.; Willenbacher, N. Langmuir 2009, 25, 716-723). Mechanical high-frequency rheology and diffusing wave spectroscopy (DWS) based tracer microrheology are used to determine the shear moduli G' and G'' in the frequency range from 0.1 Hz up to 1 MHz (Willenbacher, N.; Oelschlaeger, C.; Schopferer, M.; Fischer, P.; Cardinaux, F.; Scheffold, F. Phys. Rev. Lett. 2007, 99, 068302, 1-4). This enables us to determine the plateau modulus G(0), which is related to the cross-link density or mesh size of the entanglement network, the bending stiffness kappa (also expressed as persistence length l(p) = kappa/k(B)T) corresponding to the semiflexible nature of the micelles, and the scission energy E(sciss), which is related to their contour length. The viscosity maximum shifts to higher R values, and the variation of viscosity with R is less pronounced as the binding strength decreases. The plateau modulus increases with R at low ionic strength and is constant around the viscosity maximum; the increase in G(0) at high R, which is presumably due to branching, is weak compared to the system with penetrating counterion. The scission energy E(sciss) approximately = 20 k(B)T is independent of counterion binding efficiency irrespective of R and is slightly higher compared to the system CPyCl/NaSal, indicating that branching may be significant already at the viscosity maximum in this latter case. The micellar

  14. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  15. Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

    Todor, Horia; Sharma, Kriti; Pittman, Adrianne M C; Schmid, Amy K

    2013-10-01

    Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

  16. PIV-measured versus CFD-predicted flow dynamics in anatomically realistic cerebral aneurysm models.

    Ford, Matthew D; Nikolov, Hristo N; Milner, Jaques S; Lownie, Stephen P; Demont, Edwin M; Kalata, Wojciech; Loth, Francis; Holdsworth, David W; Steinman, David A

    2008-04-01

    Computational fluid dynamics (CFD) modeling of nominally patient-specific cerebral aneurysms is increasingly being used as a research tool to further understand the development, prognosis, and treatment of brain aneurysms. We have previously developed virtual angiography to indirectly validate CFD-predicted gross flow dynamics against the routinely acquired digital subtraction angiograms. Toward a more direct validation, here we compare detailed, CFD-predicted velocity fields against those measured using particle imaging velocimetry (PIV). Two anatomically realistic flow-through phantoms, one a giant internal carotid artery (ICA) aneurysm and the other a basilar artery (BA) tip aneurysm, were constructed of a clear silicone elastomer. The phantoms were placed within a computer-controlled flow loop, programed with representative flow rate waveforms. PIV images were collected on several anterior-posterior (AP) and lateral (LAT) planes. CFD simulations were then carried out using a well-validated, in-house solver, based on micro-CT reconstructions of the geometries of the flow-through phantoms and inlet/outlet boundary conditions derived from flow rates measured during the PIV experiments. PIV and CFD results from the central AP plane of the ICA aneurysm showed a large stable vortex throughout the cardiac cycle. Complex vortex dynamics, captured by PIV and CFD, persisted throughout the cardiac cycle on the central LAT plane. Velocity vector fields showed good overall agreement. For the BA, aneurysm agreement was more compelling, with both PIV and CFD similarly resolving the dynamics of counter-rotating vortices on both AP and LAT planes. Despite the imposition of periodic flow boundary conditions for the CFD simulations, cycle-to-cycle fluctuations were evident in the BA aneurysm simulations, which agreed well, in terms of both amplitudes and spatial distributions, with cycle-to-cycle fluctuations measured by PIV in the same geometry. The overall good agreement

  17. Numerical simulation of unsteady free surface flow and dynamic performance for a Pelton turbine

    Xiao, Y X; Wang, Z W; Yan, Z G; Cui, T

    2012-01-01

    Different from the reaction turbines, the hydraulic performance of the Pelton turbine is dynamic due to the unsteady free surface flow in the rotating buckets in time and space. This paper aims to present the results of investigations conducted on the free surface flow in a Pelton turbine rotating buckets. The unsteady numerical simulations were performed with the CFX code by using the Realizable k-ε turbulence model coupling the two-phase flow volume of fluid method. The unsteady free surface flow patterns and torque varying with the bucket rotating were analysed. The predicted relative performance at five operating conditions was compared with the field test results. The study was also conducted the interactions between the bucket rear and the water jet.

  18. Numerical simulation of unsteady free surface flow and dynamic performance for a Pelton turbine

    Xiao, Y. X.; Cui, T.; Wang, Z. W.; Yan, Z. G.

    2012-11-01

    Different from the reaction turbines, the hydraulic performance of the Pelton turbine is dynamic due to the unsteady free surface flow in the rotating buckets in time and space. This paper aims to present the results of investigations conducted on the free surface flow in a Pelton turbine rotating buckets. The unsteady numerical simulations were performed with the CFX code by using the Realizable k-ε turbulence model coupling the two-phase flow volume of fluid method. The unsteady free surface flow patterns and torque varying with the bucket rotating were analysed. The predicted relative performance at five operating conditions was compared with the field test results. The study was also conducted the interactions between the bucket rear and the water jet.

  19. Analysis of phase dynamics in two-phase flow using latticegas automata

    Ohashi, H.; Hashimoto, Y.; Tsumaya, A.; Chen, Y.; Akiyama, M.

    1998-01-01

    In this paper, we describe lattice gas automaton models appropriate for two-phase flow simulation and their applications to study various phase dynamics of two-fluid mixtures. Several algorithms are added to the original immiscible Lattice Gas model to adjust surface tension and to introduce density difference between two fluids. Surface tension is controlled by the collision rules an difference in density is due to nonlocal forces between automaton particles. We simulate the relative motion of the dispersed phase in another continuous fluid. Deformation and disintegration of rising drops are reproduced. The interaction between multiple drops is also observed in calculations. Furutre, we obtain the transition of the two-phase flow pattern from bubbly, slug to annular flow. Density difference of two phase is one of the key ingredients to generate the annular flow pattern

  20. Predicting the onset of dynamic instability of a cylindrical plate under axial flow conditions

    Marcum, W.R., E-mail: marcumw@engr.orst.edu [Oregon State University, Department of Nuclear Engineering and Radiation Health Physics, 116 Radiation Center, Corvallis, OR 97330 (United States); Woods, B.G. [Oregon State University, Department of Nuclear Engineering and Radiation Health Physics, 116 Radiation Center, Corvallis, OR 97330 (United States)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer A semi-numerical flow induced vibration model is developed of a cylindrical plate. Black-Right-Pointing-Pointer Test case results are presented and agree well with previous studies data. Black-Right-Pointing-Pointer The model identifies a relationship between forces and the plate natural frequency. - Abstract: The dynamic mechanical stability of a single cylindrical plate under flow conditions is considered herein. Numerous plate-type research reactors such as the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL) comprise fuel elements which contain arrays of concentrically aligned cylindrical plates. Several of these reactors are licensed to operate at extreme heat fluxes; as a corollary their hydraulic designs require large flow rates sufficient to remove this heat. These flow rates may reach superficial velocities upwards of 15 m/s through individual flow channels. Given that fuel plates typically found in such research reactors are relatively long ({approx}1.2573 m), wide ({approx}0.1397 m), and extremely thin ({approx}0.00127 m) concern is drawn toward the susceptibility of flow induced vibration (FIV). In an attempt to gain a more comprehensive understanding toward the dynamic mechanical limit of stability of cylindrical plates, a FIV model was developed using semi-numerical methods. The FIV model was developed in two separate modules; a plate stability module, and a flow module. These modules were then coupled together to produce a FIV model. In this study, a set of test cases are presented on the plate stability module under free vibration conditions, comparing well against known available information from previous studies. Results are similarly presented on the flow module and compared against a RELAP5-3D model. Lastly, results of these coupled modules are presented and discussion is given toward the relationship between plate natural frequency, geometry, and plate membrane pressures.

  1. Dynamic alteration of regional cerebral blood flow during carotid compression and proof of reversibility

    Asahi, Kouichi; Hori, M; Hamasaki, N; Sato, S; Nakanishi, H; Kuwatsuru, R; Sasai, K; Aoki, S

    2012-01-01

    It is difficult to non-invasively visualize changes in regional cerebral blood flow caused by manual compression of the carotid artery. To visualize dynamic changes in regional cerebral blood flow during and after manual compression of the carotid artery. Two healthy volunteers were recruited. Anatomic features and flow directions in the circle of Willis were evaluated with time-of-flight magnetic resonance angiography (MRA) and two-dimensional phase-contrast (2DPC) MRA, respectively. Regional cerebral blood flow was visualized with territorial arterial spin-labeling magnetic resonance imaging (TASL-MRI). TASL-MRI and 2DPC-MRA were performed in three states: at rest, during manual compression of the right carotid artery, and after decompression. In one volunteer, time-space labeling inversion pulse (Time-SLIP) MRA was performed to confirm collateral flow. During manual carotid compression, in one volunteer, the right thalamus changed to be fed only by the vertebrobasilar system, and the right basal ganglia changed to be fed by the left internal carotid artery. In the other volunteer, the right basal ganglia changed to be fed by the vertebrobasilar system. 2DPC-MRA showed that the flow direction changed in the right A1 segment of the anterior cerebral artery and the right posterior communicating artery. Perfusion patterns and flow directions recovered after decompression. Time-SLIP MRA showed pial vessels and dural collateral circulation when the right carotid artery was manually compressed. Use of TASL-MRI and 2DPC-MRA was successful for non-invasive visualization of the dynamic changes in regional cerebral blood flow during and after manual carotid compression

  2. Inertia-dependent dynamics of three-dimensional vesicles and red blood cells in shear flow.

    Luo, Zheng Yuan; Wang, Shu Qi; He, Long; Xu, Feng; Bai, Bo Feng

    2013-10-28

    A three-dimensional (3D) simulation study of the effect of inertia on the dynamics of vesicles and red blood cells (RBCs) has not been reported. Here, we developed a 3D model based on the front tracking method to investigate how inertia affects the dynamics of spherical/non-spherical vesicles and biconcave-shaped RBCs with the Reynolds number ranging from 0.1 to 10. The results showed that inertia induced non-spherical vesicles transitioned from tumbling to swinging, which was not observed in previous 2D models. The critical viscosity ratio of inner/outer fluids for the tumbling–swinging transition remarkably increased with an increasing Reynolds number. The deformation of vesicles was greatly enhanced by inertia, and the frequency of tumbling and tank-treading was significantly decreased by inertia. We also found that RBCs can transit from tumbling to steady tank-treading through the swinging regime when the Reynolds number increased from 0.1 to 10. These results indicate that inertia needs to be considered at moderate Reynolds number (Re ~ 1) in the study of blood flow in the human body and the flow of deformable particle suspension in inertial microfluidic devices. The developed 3D model provided new insights into the dynamics of RBCs under shear flow, thus holding great potential to better understand blood flow behaviors under normal/disease conditions.

  3. Charging and Transport Dynamics of a Flow-Through Electrode Capacitive Deionization System.

    Qu, Yatian; Campbell, Patrick G; Hemmatifar, Ali; Knipe, Jennifer M; Loeb, Colin K; Reidy, John J; Hubert, Mckenzie A; Stadermann, Michael; Santiago, Juan G

    2018-01-11

    We present a study of the interplay among electric charging rate, capacitance, salt removal, and mass transport in "flow-through electrode" capacitive deionization (CDI) systems. We develop two models describing coupled transport and electro-adsorption/desorption which capture salt removal dynamics. The first model is a simplified, unsteady zero-dimensional volume-averaged model which identifies dimensionless parameters and figures of merits associated with cell performance. The second model is a higher fidelity area-averaged model which captures both spatial and temporal responses of charging. We further conducted an experimental study of these dynamics and considered two salt transport regimes: (1) advection-limited regime and (2) dispersion-limited regime. We use these data to validate models. The study shows that, in the advection-limited regime, differential charge efficiency determines the salt adsorption at the early stage of the deionization process. Subsequently, charging transitions to a quasi-steady state where salt removal rate is proportional to applied current scaled by the inlet flow rate. In the dispersion-dominated regime, differential charge efficiency, cell volume, and diffusion rates govern adsorption dynamics and flow rate has little effect. In both regimes, the interplay among mass transport rate, differential charge efficiency, cell capacitance, and (electric) charging current governs salt removal in flow-through electrode CDI.

  4. Numerical simulation of 3D unsteady flow in a rotating pump by dynamic mesh technique

    Huang, S; Guo, J; Yang, F X

    2013-01-01

    In this paper, the numerical simulation of unsteady flow for three kinds of typical rotating pumps, roots blower, roto-jet pump and centrifugal pump, were performed using the three-dimensional Dynamic Mesh technique. In the unsteady simulation, all the computational domains, as stationary, were set in one inertial reference frame. The motions of the solid boundaries were defined by the Profile file in FLUENT commercial code, in which the rotational orientation and speed of the rotors were specified. Three methods (Spring-based Smoothing, Dynamic Layering and Local Re-meshing) were used to achieve mesh deformation and re-meshing. The unsteady solutions of flow field and pressure distribution were solved. After a start-up stage, the flow parameters exhibit time-periodic behaviour corresponding to blade passing frequency of rotor. This work shows that Dynamic Mesh technique could achieve numerical simulation of three-dimensional unsteady flow field in various kinds of rotating pumps and have a strong versatility and broad application prospects

  5. Identification of a Common Binding Mode for Imaging Agents to Amyloid Fibrils from Molecular Dynamics Simulations

    Skeby, Katrine Kirkeby; Sørensen, Jesper; Schiøtt, Birgit

    2013-01-01

    experimentally due to the insoluble nature of amyloid fibrils. This study uses molecular dynamics simulations to investigate the interactions between 13 aromatic amyloid imaging agents, entailing 4 different organic scaffolds, and a model of an amyloid fibril. Clustering analysis combined with free energy...

  6. Molecular dynamics study of prolyl oligopeptidase with inhibitor in binding cavity

    Kaszuba, K.; Róg, T.; St-Pierre, J.-F.; Männistö, P.T.; Karttunen, M.E.J.; Bunker, A.

    2009-01-01

    We used the crystal structure of prolyl oligopeptidase (POP) with bound Z-pro-prolinal (ZPP) inhibitor (Protein Data Bank (PDB) structure 1QFS) to perform an intensive molecular dynamics study of the POP-ZPP complex. We performed 100 ns of simulation with the hemiacetal bond, through which the ZPP

  7. Putting the "ecology" into environmental flows: ecological dynamics and demographic modelling.

    Shenton, Will; Bond, Nicholas R; Yen, Jian D L; Mac Nally, Ralph

    2012-07-01

    There have been significant diversions of water from rivers and streams around the world; natural flow regimes have been perturbed by dams, barriers and excessive extractions. Many aspects of the ecological 'health' of riverine systems have declined due to changes in water flows, which has stimulated the development of thinking about the maintenance and restoration of these systems, which we refer to as environmental flow methodologies (EFMs). Most existing EFMs cannot deliver information on the population viability of species because they: (1) use habitat suitability as a proxy for population status; (2) use historical time series (usually of short duration) to forecast future conditions and flow sequences; (3) cannot, or do not, handle extreme flow events associated with climate variability; and (4) assume process stationarity for flow sequences, which means the past sequences are treated as good indicators of the future. These assumptions undermine the capacity of EFMs to properly represent risks associated with different flow management options; assumption (4) is untenable given most climate-change predictions. We discuss these concerns and advocate the use of demographic modelling as a more appropriate tool for linking population dynamics to flow regime change. A 'meta-species' approach to demographic modelling is discussed as a useful step from habitat based models towards modelling strategies grounded in ecological theory when limited data are available on flow-demographic relationships. Data requirements of demographic models will undoubtedly expose gaps in existing knowledge, but, in so doing, will strengthen future efforts to link changes in river flows with their ecological consequences.

  8. Putting the "Ecology" into Environmental Flows: Ecological Dynamics and Demographic Modelling

    Shenton, Will; Bond, Nicholas R.; Yen, Jian D. L.; Mac Nally, Ralph

    2012-07-01

    There have been significant diversions of water from rivers and streams around the world; natural flow regimes have been perturbed by dams, barriers and excessive extractions. Many aspects of the ecological `health' of riverine systems have declined due to changes in water flows, which has stimulated the development of thinking about the maintenance and restoration of these systems, which we refer to as environmental flow methodologies (EFMs). Most existing EFMs cannot deliver information on the population viability of species because they: (1) use habitat suitability as a proxy for population status; (2) use historical time series (usually of short duration) to forecast future conditions and flow sequences; (3) cannot, or do not, handle extreme flow events associated with climate variability; and (4) assume process stationarity for flow sequences, which means the past sequences are treated as good indicators of the future. These assumptions undermine the capacity of EFMs to properly represent risks associated with different flow management options; assumption (4) is untenable given most climate-change predictions. We discuss these concerns and advocate the use of demographic modelling as a more appropriate tool for linking population dynamics to flow regime change. A `meta-species' approach to demographic modelling is discussed as a useful step from habitat based models towards modelling strategies grounded in ecological theory when limited data are available on flow-demographic relationships. Data requirements of demographic models will undoubtedly expose gaps in existing knowledge, but, in so doing, will strengthen future efforts to link changes in river flows with their ecological consequences.

  9. Flight control of fruit flies: dynamic response to optic flow and headwind.

    Lawson, Kiaran K K; Srinivasan, Mandyam V

    2017-06-01

    Insects are magnificent fliers that are capable of performing many complex tasks such as speed regulation, smooth landings and collision avoidance, even though their computational abilities are limited by their small brain. To investigate how flying insects respond to changes in wind speed and surrounding optic flow, the open-loop sensorimotor response of female Queensland fruit flies ( Bactrocera tryoni ) was examined. A total of 136 flies were exposed to stimuli comprising sinusoidally varying optic flow and air flow (simulating forward movement) under tethered conditions in a virtual reality arena. Two responses were measured: the thrust and the abdomen pitch. The dynamics of the responses to optic flow and air flow were measured at various frequencies, and modelled as a multicompartment linear system, which accurately captured the behavioural responses of the fruit flies. The results indicate that these two behavioural responses are concurrently sensitive to changes of optic flow as well as wind. The abdomen pitch showed a streamlining response, where the abdomen was raised higher as the magnitude of either stimulus was increased. The thrust, in contrast, exhibited a counter-phase response where maximum thrust occurred when the optic flow or wind flow was at a minimum, indicating that the flies were attempting to maintain an ideal flight speed. When the changes in the wind and optic flow were in phase (i.e. did not contradict each other), the net responses (thrust and abdomen pitch) were well approximated by an equally weighted sum of the responses to the individual stimuli. However, when the optic flow and wind stimuli were presented in counterphase, the flies seemed to respond to only one stimulus or the other, demonstrating a form of 'selective attention'. © 2017. Published by The Company of Biologists Ltd.

  10. Ancestry dynamics in a South American population: The impact of gene flow and preferential mating.

    Hedrick, Philip W

    2017-07-01

    European ancestry in many populations in Latin America at autosomal loci is often higher than that from X-linked loci indicating more European male ancestry and more Amerindian female ancestry. Generally, this has been attributed to more European male gene flow but could also result from an advantage to European mating or reproductive success. Population genetic models were developed to investigate the dynamics of gene flow and mating or reproductive success. Using estimates of autosomal and X-chromosome European ancestry, the amount of male gene flow or mating or reproductive advantage for Europeans, or those with European ancestry, was estimated. In a population from Antioquia, Colombia with an estimated 79% European autosomal ancestry and an estimated 69% European X-chromosome ancestry, about 15% male gene flow from Europe or about 20% mating or reproductive advantage of Europeans over Amerindians resulted in these levels of European ancestry in the contemporary population. Combinations of gene flow and mating advantage were nearly additive in their impact. Gene flow, mating advantage, or a combination of both factors, are consistent with observed levels of European ancestry in a Latin American population. This approach provides a general methodology to determine the levels of gene flow and mating differences that can explain the observed contemporary differences in ancestry from autosomes and X-chromosomes. © 2017 Wiley Periodicals, Inc.

  11. Prediction of Separation Length of Turbulent Multiphase Flow Using Radiotracer and Computational Fluid Dynamics Simulation

    Sugiharto, S.; Kurniadi, R.; Abidin, Z.; Stegowski, Z.; Furman, L.

    2013-01-01

    Multiphase flow modeling presents great challenges due to its extreme importance in various industrial and environmental applications. In the present study, prediction of separation length of multiphase flow is examined experimentally by injection of two kinds of iodine-based radiotracer solutions into a hydrocarbon transport pipeline (HCT) having an inner diameter of 24 in (60,96 m). The main components of fluids in the pipeline are water 95%, crude oil 3% and gas 2%. A radiotracing experiment was carried out at the segment of pipe which is located far from branch points with assumptions that stratified flows in such segment were achieved. Two radiation detectors located at 80 and 100 m from injection point were used to generate residence time distribution (RTD) curve resulting from injection of radiotracer solutions. Multiphase computational fluid dynamics (CFD) simulations using Eulerian-Eulerian control volume and commercial CFD package Fluent 6.2 were employed to simulate separation length of multiphase flow. The results of study shows that the flow velocity of water is higher than the flow rate of crude oil in water-dominated system despite the higher density of water than the density of the crude oil. The separation length in multiphase flow predicted by Fluent mixture model is approximately 20 m, measured from injection point. This result confirms that the placement of the first radiation detector at the distance 80 m from the injection point was correct. (author)

  12. Prediction of Separation Length of Turbulent Multiphase Flow Using Radiotracer and Computational Fluid Dynamics Simulation

    S. Sugiharto1

    2013-04-01

    Full Text Available Multiphase flow modeling presents great challenges due to its extreme importance in various industrial and environmental applications. In the present study, prediction of separation length of multiphase flow is examined experimentally by injection of two kinds of iodine-based radiotracer solutions into a hydrocarbon transport pipeline (HCT having an inner diameter of 24 in (60,96 m. The main components of fluids in the pipeline are water 95%, crude oil 3% and gas 2%. A radiotracing experiment was carried out at the segment of pipe which is located far from branch points with assumptions that stratified flows in such segment were achieved. Two radiation detectors located at 80 and 100 m from injection point were used to generate residence time distribution (RTD curve resulting from injection of radiotracer solutions. Multiphase computational fluid dynamics (CFD simulations using Eulerian-Eulerian control volume and commercial CFD package Fluent 6.2 were employed to simulate separation length of multiphase flow. The results of study shows that the flow velocity of water is higher than the flow rate of crude oil in water-dominated system despite the higher density of water than the density of the crude oil. The separation length in multiphase flow predicted by Fluent mixture model is approximately 20 m, measured from injection point. This result confirms that the placement of the first radiation detector at the distance 80 m from the injection point was correct

  13. Spatially dynamic recurrent information flow across long-range dorsal motor network encodes selective motor goals.

    Yoo, Peter E; Hagan, Maureen A; John, Sam E; Opie, Nicholas L; Ordidge, Roger J; O'Brien, Terence J; Oxley, Thomas J; Moffat, Bradford A; Wong, Yan T

    2018-03-08

    Performing voluntary movements involves many regions of the brain, but it is unknown how they work together to plan and execute specific movements. We recorded high-resolution ultra-high-field blood-oxygen-level-dependent signal during a cued ankle-dorsiflexion task. The spatiotemporal dynamics and the patterns of task-relevant information flow across the dorsal motor network were investigated. We show that task-relevant information appears and decays earlier in the higher order areas of the dorsal motor network then in the primary motor cortex. Furthermore, the results show that task-relevant information is encoded in general initially, and then selective goals are subsequently encoded in specifics subregions across the network. Importantly, the patterns of recurrent information flow across the network vary across different subregions depending on the goal. Recurrent information flow was observed across all higher order areas of the dorsal motor network in the subregions encoding for the current goal. In contrast, only the top-down information flow from the supplementary motor cortex to the frontoparietal regions, with weakened recurrent information flow between the frontoparietal regions and bottom-up information flow from the frontoparietal regions to the supplementary cortex were observed in the subregions encoding for the opposing goal. We conclude that selective motor goal encoding and execution rely on goal-dependent differences in subregional recurrent information flow patterns across the long-range dorsal motor network areas that exhibit graded functional specialization. © 2018 Wiley Periodicals, Inc.

  14. Non-linear hydrotectonic phenomena: Part I - fluid flow in open fractures under dynamical stress loading

    Archambeau, C.B.

    1994-01-01

    A fractured solid under stress loading (or unloading) can be viewed as behaving macroscopically as a medium with internal, hidden, degrees of freedom, wherein changes in fracture geometry (i.e. opening, closing and extension) and flow of fluid and gas within fractures will produce major changes in stresses and strains within the solid. Likewise, the flow process within fractures will be strongly coupled to deformation within the solid through boundary conditions on the fracture surfaces. The effects in the solid can, in part, be phenomenologically represented as inelastic or plastic processes in the macroscopic view. However, there are clearly phenomena associated with fracture growth and open fracture fluid flows that produce effects that can not be described using ordinary inelastic phenomenology. This is evident from the fact that a variety of energy release phenomena can occur, including seismic emissions of previously stored strain energy due to fracture growth, release of disolved gas from fluids in the fractures resulting in enhanced buoyancy and subsequent energetic flows of gas and fluids through the fracture system which can produce raid extension of old fractures and the creation of new ones. Additionally, the flows will be modulated by the opening and closing of fractures due to deformation in the solid, so that the flow process is strongly coupled to dynamical processes in the surrounding solid matrix, some of which are induced by the flow itself

  15. Computational Fluid Dynamics Analysis of Pulsatile Blood Flow Behavior in Modelled Stenosed Vessels with Different Severities

    Mohsen Mehrabi

    2012-01-01

    Full Text Available This study focuses on the behavior of blood flow in the stenosed vessels. Blood is modelled as an incompressible non-Newtonian fluid which is based on the power law viscosity model. A numerical technique based on the finite difference method is developed to simulate the blood flow taking into account the transient periodic behaviour of the blood flow in cardiac cycles. Also, pulsatile blood flow in the stenosed vessel is based on the Womersley model, and fluid flow in the lumen region is governed by the continuity equation and the Navier-Stokes equations. In this study, the stenosis shape is cosine by using Tu and Devil model. Comparing the results obtained from three stenosed vessels with 30%, 50%, and 75% area severity, we find that higher percent-area severity of stenosis leads to higher extrapressure jumps and higher blood speeds around the stenosis site. Also, we observe that the size of the stenosis in stenosed vessels does influence the blood flow. A little change on the cross-sectional value makes vast change on the blood flow rate. This simulation helps the people working in the field of physiological fluid dynamics as well as the medical practitioners.

  16. Movable shark scales act as a passive dynamic micro-roughness to control flow separation

    Lang, Amy W; Bradshaw, Michael T; Smith, Jonathon A; Wheelus, Jennifer N; Motta, Philip J; Habegger, Maria L; Hueter, Robert E

    2014-01-01

    Shark scales on fast-swimming sharks have been shown to be movable to angles in excess of 50°, and we hypothesize that this characteristic gives this shark skin a preferred flow direction. During the onset of separation, flow reversal is initiated close to the surface. However, the movable scales would be actuated by the reversed flow thereby causing a greater resistance to any further flow reversal and this mechanism would disrupt the process leading to eventual flow separation. Here we report for the first time experimental evidence of the separation control capability of real shark skin through water tunnel testing. Using skin samples from a shortfin mako Isurus oxyrinchus, we tested a pectoral fin and flank skin attached to a NACA 4412 hydrofoil and separation control was observed in the presence of movable shark scales under certain conditions in both cases. We hypothesize that the scales provide a passive, flow-actuated mechanism acting as a dynamic micro-roughness to control flow separation. (paper)

  17. [The dynamic binding of resources for health in Brazil: 1995 to 2004].

    de França, José Rivaldo Melo; do Rosário Costa, Nilson

    2011-01-01

    The aim of this study is to discuss the Brazilian Federal participation in the financing health sector from 1995 to 2004, having the basis the resources of the institutional initiatives related to the indexation of expenses, considering the macroeconomic adjustment practiced in that period and the institutions role to protect the cash flow. Examining the performances of the institutional mechanism actually adopted with the purpose of guarantee the flow regularity and extension of the values, by the analisys of the Temporary Contribution on the Financial Movement (TCFM) and the Constitutional Amendment Number 29 (CA 29) whose initiatives has their efficiency questioned. It demonstrates the impact of the destination of such measures from the statistics analysis of the use of the resources of the TCFM regarding its levies and the indexation of Union resources effects measures from the CA 29 before and after the application of its determinations.

  18. Dynamical and statistical-dynamical modelling of wind farm flows with WRF

    Volker, Patrick; Badger, Jake; Hahmann, Andrea N.

    2016-01-01

    the power production of a target wind farm and (II) how large wind farms can get if they are to remain efficient and productive power generators. The modelling of wind farm wake flows is challenging, since it includes processes from the micro- to mesoscale meteorology. We use the Weather Research......A pledge to increase the share of renewable energies has led to a focus on offshore wind energy in many western European countries. With an increasing number of offshore wind farms to be installed it becomes important to understand (I) the degree to which wakes from neighbouring wind farms affect...... and Forecast (WRF) model that allows us to simulate mesoscale features of wind farm wakes. Its limited horizontal resolution – in microscale terms – however, requires flow characteristics, such as single turbine wakes, to be parametrised....

  19. Evaluations of CSF flow dynamics in elderly with dementia by metrizamide CT cisternography

    Nokura, Kazuya; Kabasawa, Hidehiro; Matsubara, Mitsutaka; Yamamoto, Masahiko; Nagai, Hajime

    1988-01-01

    We have investigated Metrizamide CT-cisternography in multi-infarct dementia (MID): 29 cases, senile dementia of the Alzheimer type (SDAT): 7 cases, normal pressure hydrocephalus (NPH): 8 cases and spinocerebellar degeneration (SCD): 3 cases. By quantitative manner the differences of cerebrospinal fluid (CSF) flowdynamics in each group have been evaluated. In comparison with SCD which show normal CSF flow, MID show tendency to ventricular reflux and convexity stasis. No difference was seen between MID and SDAT. Though NPH shows stronger ventricular reflux than that or MID, the stasis in MID is more severe than that of NPH. In MID group subject of older than 70 years show more severe SCF flow disturbances. When divided into two groups by ADL (Activities of daily living) scale (full of 15 points) the group of less than 6 points show slight disturbances in comparison with that of more than 6 points. And the same is true in Hasegawas dementia rating scales, namely the group of less than 21 points (full of 32.5) shows slight disturbances in comparison with that of more than 21 points. The flow dynamics pattern of slight ventricular reflux in 24 hours and stasis in convexity from 24 to 48 hours seems to be typical in either MID or SDAT. But such a pattern has never been reported in SCF flow dynamics studies. These findings may suggest that CSF flow disturbances have a close relation with aging and dementia. (author)

  20. The dynamic behavior of chemically "stiffened" red blood cells in microchannel flows.

    Forsyth, Alison M; Wan, Jiandi; Ristenpart, William D; Stone, Howard A

    2010-07-01

    The rigidity of red blood cells (RBCs) plays an important role in whole blood viscosity and is correlated with several cardiovascular diseases. Two chemical agents that are commonly used to study cell deformation are diamide and glutaraldehyde. Despite diamide's common usage, there are discrepancies in the literature surrounding diamide's effect on the deformation of RBCs in shear and pressure-driven flows; in particular, shear flow experiments have shown that diamide stiffens cells, while pressure-driven flow in capillaries did not give this result. We performed pressure-driven flow experiments with RBCs in a microfluidic constriction and quantified the cell dynamics using high-speed imaging. Diamide, which affects RBCs by cross-linking spectrin skeletal membrane proteins, did not reduce deformation and showed an unchanged effective strain rate when compared to healthy cells. In contrast, glutaraldehyde, which is a non-specific fixative that acts on all components of the cell, did reduce deformation and showed increased instances of tumbling, both of which are characteristic features of stiffened, or rigidified, cells. Because glutaraldehyde increases the effective viscosity of the cytoplasm and lipid membrane while diamide does not, one possible explanation for our results is that viscous effects in the cytoplasm and/or lipid membrane are a dominant factor in dictating dynamic responses of RBCs in pressure-driven flows. Finally, literature on the use of diamide as a stiffening agent is summarized, and provides supporting evidence for our conclusions. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Evaluations of CSF flow dynamics in elderly with dementia by metrizamide CT cisternography

    Nokura, Kazuya; Kabasawa, Hidehiro; Matsubara, Mitsutaka; Yamamoto, Masahiko; Nagai, Hajime

    1988-06-01

    We have investigated Metrizamide CT-cisternography in multi-infarct dementia (MID): 29 cases, senile dementia of the Alzheimer type (SDAT): 7 cases, normal pressure hydrocephalus (NPH): 8 cases and spinocerebellar degeneration (SCD): 3 cases. By quantitative manner the differences of cerebrospinal fluid (CSF) flowdynamics in each group have been evaluated. In comparison with SCD which show normal CSF flow, MID show tendency to ventricular reflux and convexity stasis. No difference was seen between MID and SDAT. Though NPH shows stronger ventricular reflux than that or MID, the stasis in MID is more severe than that of NPH. In MID group subject of older than 70 years show more severe SCF flow disturbances. When divided into two groups by ADL (Activities of daily living) scale (full of 15 points) the group of less than 6 points show slight disturbances in comparison with that of more than 6 points. And the same is true in Hasegawas dementia rating scales, namely the group of less than 21 points (full of 32.5) shows slight disturbances in comparison with that of more than 21 points. The flow dynamics pattern of slight ventricular reflux in 24 hours and stasis in convexity from 24 to 48 hours seems to be typical in either MID or SDAT. But such a pattern has never been reported in SCF flow dynamics studies. These findings may suggest that CSF flow disturbances have a close relation with aging and dementia.

  2. Computational Fluid Dynamics and Visualisation of Coastal Flows in Tidal Channels Supporting Ocean Energy Development

    Enayatollah Zangiabadi

    2015-06-01

    Full Text Available Flow characteristics in coastal regions are strongly influenced by the topography of the seabed and understanding the fluid dynamics is necessary before installation of tidal stream turbines (TST. In this paper, the bathymetry of a potential TST deployment site is used in the development of the a CFD (Computational Fluid Dynamics model. The steady state k-ϵ and transient Large Eddy Simulation (LES turbulence methods are employed and compared. The simulations are conducted with a fixed representation of the ocean surface, i.e., a rigid lid representation. In the vicinity of Horse Rock a study of the pressure difference shows that the small change in height of the water column is negligible, providing confidence in the simulation results. The stream surface method employed to visualise the results has important inherent characteristics that can enhance the visual perception of complex flow structures. The results of all cases are compared with the flow data transect gathered by an Acoustic Doppler Current Profiler (ADCP. It has been understood that the k-ϵ method can predict the flow pattern relatively well near the main features of the domain and the LES model has the ability to simulate some important flow patterns caused by the bathymetry.

  3. Cortical dynamics of feature binding and reset: control of visual persistence.

    Francis, G; Grossberg, S; Mingolla, E

    1994-04-01

    An analysis of the reset of visual cortical circuits responsible for the binding or segmentation of visual features into coherent visual forms yields a model that explains properties of visual persistence. The reset mechanisms prevent massive smearing of visual percepts in response to rapidly moving images. The model simulates relationships among psychophysical data showing inverse relations of persistence to flash luminance and duration, greater persistence of illusory contours than real contours, a U-shaped temporal function for persistence of illusory contours, a reduction of persistence due to adaptation with a stimulus of like orientation, an increase of persistence with spatial separation of a masking stimulus. The model suggests that a combination of habituative, opponent, and endstopping mechanisms prevent smearing and limit persistence. Earlier work with the model has analyzed data about boundary formation, texture segregation, shape-from-shading, and figure-ground separation. Thus, several types of data support each model mechanism and new predictions are made.

  4. Speciation dynamics of metals in dispersion of nanoparticles with discrete distribution of charged binding sites.

    Polyakov, Pavel D; Duval, Jérôme F L

    2014-02-07

    We report a comprehensive theory to evaluate the kinetics of complex formation between metal ions and charged spherical nanoparticles. The latter consist of an ion-impermeable core surrounded by a soft shell layer characterized by a discrete axisymmetric 2D distribution of charged sites that bind metal ions. The theory explicitly integrates the conductive diffusion of metal ions from bulk solution toward the respective locations of the reactive sites within the particle shell volume. The kinetic constant k for outer-sphere nanoparticle-metal association is obtained from the sum of the contributions stemming from all reactive sites, each evaluated from the corresponding incoming flux of metal ions derived from steady-state Poisson-Nernst-Planck equations. Illustrations are provided to capture the basic intertwined impacts of particle size, overall particle charge, spatial heterogeneity in site distribution, type of particle (hard, core-shell or porous) and concentration of the background electrolyte on k. As a limit, k converges with predictions from previously reported analytical expressions derived for porous particles with low and high charge density, cases that correspond to coulombic and mean-field (smeared-out) electrostatic treatments, respectively. The conditions underlying the applicability of these latter approaches are rigorously identified in terms of (i) the extent of overlap between electric double layers around charged neighbouring sites, and (ii) the magnitude of the intraparticulate metal concentration gradient. For the first time, the proposed theory integrates the differentiated impact of the local potential around the charged binding sites amidst the overall particle field, together with that of the so-far discarded intraparticulate flux of metal ions.

  5. Multiscale Modeling of Blood Flow: Coupling Finite Elements with Smoothed Dissipative Particle Dynamics

    Moreno Chaparro, Nicolas; Vignal, Philippe; Li, Jun; Calo, Victor M.

    2013-01-01

    A variational multi scale approach to model blood flow through arteries is proposed. A finite element discretization to represent the coarse scales (macro size), is coupled to smoothed dissipative particle dynamics that captures the fine scale features (micro scale). Blood is assumed to be incompressible, and flow is described through the Navier Stokes equation. The proposed cou- pling is tested with two benchmark problems, in fully coupled systems. Further refinements of the model can be incorporated in order to explicitly include blood constituents and non-Newtonian behavior. The suggested algorithm can be used with any particle-based method able to solve the Navier-Stokes equation.

  6. Turbulent swirling flow in a dynamic model of a uniflow-scavenged two-stroke engine

    Ingvorsen, Kristian Mark; Meyer, Knud Erik; Walther, Jens Honore

    2014-01-01

    turbulence models. In the present work, the flow in a dynamic scale model of a uniflowscavenged cylinder is investigated experimentally. The model has a transparent cylinder and a moving piston driven by a linear motor. The flow is investigated using phase-locked stereoscopic particle image velocimetry (PIV...... cannot be assumed to be quasi-steady. The temporal development of the swirl strength is investigated by computing the angular momentum. The swirl strength shows an exponential decay from scavenge port closing to scavenge port opening corresponding to a reduction of 34 %, which is in good agreement...

  7. Multiscale Modeling of Blood Flow: Coupling Finite Elements with Smoothed Dissipative Particle Dynamics

    Moreno Chaparro, Nicolas

    2013-06-01

    A variational multi scale approach to model blood flow through arteries is proposed. A finite element discretization to represent the coarse scales (macro size), is coupled to smoothed dissipative particle dynamics that captures the fine scale features (micro scale). Blood is assumed to be incompressible, and flow is described through the Navier Stokes equation. The proposed cou- pling is tested with two benchmark problems, in fully coupled systems. Further refinements of the model can be incorporated in order to explicitly include blood constituents and non-Newtonian behavior. The suggested algorithm can be used with any particle-based method able to solve the Navier-Stokes equation.

  8. A dynamic model of gas flow in a non-uniform pipe

    Mensah, S.; Lepp, R.M.

    1979-08-01

    A gas-line model, based on the analysis of compressible flow with friction, has been developed to describe the dynamics of gas flow in a non-uniform line, i.e. one comprising segments of different lengths and diameters. Acoustic wave analysis was used in a novel way, by considering the line as a cascaded connection of uniform pipes separated by discontinuities. The transmission matrix representing this non-uniform line is the product of the matrices for each element in the system. To facilitate implementation of the theoretical model on a hybrid computer, modal approximatons to its transfer functions were derived. Both models were validated against experimental data. (author)

  9. Modeling dynamic stall on wind turbine blades under rotationally augmented flow fields

    Guntur, S. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Schreck, S. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Sorensen, N. N. [Technical Univ. of Denmark, Lyngby (Denmark); Bergami, L. [Technical Univ. of Denmark, Lyngby (Denmark)

    2015-04-22

    It is well known that airfoils under unsteady flow conditions with a periodically varying angle of attack exhibit aerodynamic characteristics different from those under steady flow conditions, a phenomenon commonly known as dynamic stall. It is also well known that the steady aerodynamic characteristics of airfoils in the inboard region of a rotating blade differ from those under steady two-dimensional (2D) flow conditions, a phenomenon commonly known as rotational augmentation. This paper presents an investigation of these two phenomena together in the inboard parts of wind turbine blades. This analysis is carried out using data from three sources: (1) the National Renewable Energy Laboratory’s Unsteady Aerodynamics Experiment Phase VI experimental data, including constant as well as continuously pitching blade conditions during axial operation, (2) data from unsteady Delayed Detached Eddy Simulations (DDES) carried out using the Technical University of Denmark’s in-house flow solver Ellipsys3D, and (3) data from a simplified model based on the blade element momentum method with a dynamic stall subroutine that uses rotationally augmented steady-state polars obtained from steady Phase VI experimental sequences, instead of the traditional 2D nonrotating data. The aim of this work is twofold. First, the blade loads estimated by the DDES simulations are compared to three select cases of the N sequence experimental data, which serves as a validation of the DDES method. Results show reasonable agreement between the two data in two out of three cases studied. Second, the dynamic time series of the lift and the moment polars obtained from the experiments are compared to those from the dynamic stall subroutine that uses the rotationally augmented steady polars. This allowed the differences between the stall phenomenon on the inboard parts of harmonically pitching blades on a rotating wind turbine and the classic dynamic stall representation in 2D flow to be

  10. Characterizing dynamic hysteresis and fractal statistics of chaotic two-phase flow and application to fuel cells

    Burkholder, Michael B.; Litster, Shawn

    2016-01-01

    In this study, we analyze the stability of two-phase flow regimes and their transitions using chaotic and fractal statistics, and we report new measurements of dynamic two-phase pressure drop hysteresis that is related to flow regime stability and channel water content. Two-phase flow dynamics are relevant to a variety of real-world systems, and quantifying transient two-phase flow phenomena is important for efficient design. We recorded two-phase (air and water) pressure drops and flow images in a microchannel under both steady and transient conditions. Using Lyapunov exponents and Hurst exponents to characterize the steady-state pressure fluctuations, we develop a new, measurable regime identification criteria based on the dynamic stability of the two-phase pressure signal. We also applied a new experimental technique by continuously cycling the air flow rate to study dynamic hysteresis in two-phase pressure drops, which is separate from steady-state hysteresis and can be used to understand two-phase flow development time scales. Using recorded images of the two-phase flow, we show that the capacitive dynamic hysteresis is related to channel water content and flow regime stability. The mixed-wettability microchannel and in-channel water introduction used in this study simulate a polymer electrolyte fuel cell cathode air flow channel.

  11. Characterizing dynamic hysteresis and fractal statistics of chaotic two-phase flow and application to fuel cells

    Burkholder, Michael B.; Litster, Shawn, E-mail: litster@andrew.cmu.edu [Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States)

    2016-05-15

    In this study, we analyze the stability of two-phase flow regimes and their transitions using chaotic and fractal statistics, and we report new measurements of dynamic two-phase pressure drop hysteresis that is related to flow regime stability and channel water content. Two-phase flow dynamics are relevant to a variety of real-world systems, and quantifying transient two-phase flow phenomena is important for efficient design. We recorded two-phase (air and water) pressure drops and flow images in a microchannel under both steady and transient conditions. Using Lyapunov exponents and Hurst exponents to characterize the steady-state pressure fluctuations, we develop a new, measurable regime identification criteria based on the dynamic stability of the two-phase pressure signal. We also applied a new experimental technique by continuously cycling the air flow rate to study dynamic hysteresis in two-phase pressure drops, which is separate from steady-state hysteresis and can be used to understand two-phase flow development time scales. Using recorded images of the two-phase flow, we show that the capacitive dynamic hysteresis is related to channel water content and flow regime stability. The mixed-wettability microchannel and in-channel water introduction used in this study simulate a polymer electrolyte fuel cell cathode air flow channel.

  12. Suitability of magnetic single- and multi-core nanoparticles to detect protein binding with dynamic magnetic measurement techniques

    Remmer, Hilke; Dieckhoff, Jan; Schilling, Meinhard; Ludwig, Frank

    2015-01-01

    We investigated the binding of biotinylated proteins to various streptavidin functionalized magnetic nanoparticles with different dynamic magnetic measurement techniques to examine their potential for homogeneous bioassays. As particle systems, single-core nanoparticles with a nominal core diameter of 30 nm as well as multi-core nanoparticles with hydrodynamic sizes varying between nominally 60 nm and 100 nm were chosen. As experimental techniques, fluxgate magnetorelaxometry (MRX), complex ac susceptibility (ACS) and measurements of the phase lag between rotating field and sample magnetization are applied. MRX measurements are only suited for the detection of small analytes if the multivalency of functionalized nanoparticles and analytes causes cross-linking, thus forming larger aggregates. ACS measurements showed for all nanoparticle systems a shift of the imaginary part's maximum towards small frequencies. In rotating field measurements only the single-core nanoparticle systems with dominating Brownian mechanism exhibit an increase of the phase lag upon binding in the investigated frequency range. The coexistence of Brownian and Néel relaxation processes can cause a more complex phase lag change behavior, as demonstrated for multi-core nanoparticle systems. - Highlights: • Cealization of homogeneous magnetic bioassays using different magnetic techniques. • Comparison of single- and multi-core nanoparticle systems. • ac Susceptibility favorable for detection of small analytes. • Magnetorelaxometry favorable for detection of large analytes or cross-linking assays

  13. Probing ligand binding modes of Mycobacterium tuberculosis MurC ligase by molecular modeling, dynamics simulation and docking.

    Anuradha, C M; Mulakayala, Chaitanya; Babajan, Banaganapalli; Naveen, M; Rajasekhar, Chikati; Kumar, Chitta Suresh

    2010-01-01

    Multi drug resistance capacity for Mycobacterium tuberculosis (MDR-Mtb) demands the profound need for developing new anti-tuberculosis drugs. The present work is on Mtb-MurC ligase, which is an enzyme involved in biosynthesis of peptidoglycan, a component of Mtb cell wall. In this paper the 3-D structure of Mtb-MurC has been constructed using the templates 1GQQ and 1P31. Structural refinement and energy minimization of the predicted Mtb-MurC ligase model has been carried out by molecular dynamics. The streochemical check failures in the energy minimized model have been evaluated through Procheck, Whatif ProSA, and Verify 3D. Further torsion angles for the side chains of amino acid residues of the developed model were determined using Predictor. Docking analysis of Mtb-MurC model with ligands and natural substrates enabled us to identify specific residues viz. Gly125, Lys126, Arg331, and Arg332, within the Mtb-MurC binding pocket to play an important role in ligand and substrate binding affinity and selectivity. The availability of Mtb-MurC ligase built model, together with insights gained from docking analysis will promote the rational design of potent and selective Mtb-MurC ligase inhibitors as antituberculosis therapeutics.

  14. Theoretical study of the structure, energetics, and dynamics of silicon and carbon systems using tight-binding approaches

    Xu, Chunhui.

    1991-01-01

    Semiempirical interatomic potentials are developed for silicon and carbon by modeling the total energy of the system using tight-binding approaches. The parameters of the models were obtained by fitting to results from accurate first-principles Local Density Functional calculations. Applications to the computation of phonons as a function of volume for diamond-structured silicon and carbon and the thermal expansions for silicon and diamond yields results which agree well with experiment. The physical origin of the negative thermal expansion observed in silicon is explained. A tight-binding total energy model is generated capable of describing carbon systems with a variety of atomic coordinations and topologies. The model reproduces the total energy versus volume curves of various carbon polytypes as well as phonons and elastic constants of diamond and graphite. The model has also been used in the molecular-dynamics simulation of the properties of carbon clusters. The calculated ground-state geometries of small clusters (C 2 --C 10 ) correlates well with results from accurate quantum chemical calculations, and the structural trend of clusters from C 2 to C 60 are investigated. 67 refs., 19 figs

  15. Comparisons of Prostate Cancer Inhibitors Abiraterone and TOK-001 Binding with CYP17A1 through Molecular Dynamics

    Fei Xiao

    2015-01-01

    However, biology-driven inhibitor development of prostate cancer is poorly elucidated. The aims of this study are to address structural differences at atomic-level between CYP17A1 and inhibitors i.e., abiraterone and TOK-001, and further investigate the effect of point mutation of CYP17A1 on the active site stability and the local interactions that are hydrophobic interaction and hydrogen bonding throughout molecular dynamics (MD simulation. After performing multiple comparisons among four different complexes across CYP17A1 and inhibitors, interestingly TOK-001 oriented toward the active pocket and formed larger volume with I-helix of CYP17A1 than abiraterone, whereas abiraterone showed tighter binding and more active site stability. Considering on the effect of hydrophobic interaction and hydrogen bonding between abiraterone and CYP17A1, the key residues of Phe114, Ile371, Val482, and Asn202 were identified. This contributes into tight binding interactions; however abiraterone is effectively weakened along with the global conformation mobility increased in A105L mutation. Surprisingly, overall conformation of the CYP17A1 remained stable when bound to TOK-001. This basic knowledge can guide future experiments on design of efficient inhibitors for CYP17A1, which provides theoretical basis of androgen-dependent disease therapy.

  16. The Ties That Bind: Mapping the Dynamic Enhancer-Promoter Interactome.

    Spurrell, Cailyn H; Dickel, Diane E; Visel, Axel

    2016-11-17

    Coupling chromosome conformation capture to molecular enrichment for promoter-containing DNA fragments enables the systematic mapping of interactions between individual distal regulatory sequences and their target genes. In this Minireview, we describe recent progress in the application of this technique and related complementary approaches to gain insight into the lineage- and cell-type-specific dynamics of interactions between regulators and gene promoters. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Advances and applications in the FIREBALL ab initio tight-binding molecular-dynamics formalism

    Lewis, J.P.; Jelínek, Pavel; Ortega, J.; Demkov, A.A.; Trabada, D.G.; Haycock, B.; Wang, H.; Adams, G.; Tomfohr, J.K.; Abad, E.; Wang, Ho.; Drabold, D.A.

    2011-01-01

    Roč. 248, č. 9 (2011), 1989-2007 ISSN 0370-1972 R&D Projects: GA ČR GA202/09/0545; GA ČR GAP204/10/0952 Grant - others:AVČR(CZ) M100100904 Institutional research plan: CEZ:AV0Z10100521 Keywords : DFT * ab initio molecular-dynamics Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.316, year: 2011

  18. Computational Fluid Dynamic Pressure Drop Estimation of Flow between Parallel Plates

    Son, Hyung Min; Yang, Soo Hyung; Park, Jong Hark [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    Many pool type reactors have forced downward flows inside the core during normal operation; there is a chance of flow inversion when transients occur. During this phase, the flow undergo transition between turbulent and laminar regions where drastic changes take place in terms of momentum and heat transfer, and the decrease in safety margin is usually observed. Additionally, for high Prandtl number fluids such as water, an effect of the velocity profile inside the channel on the temperature distribution is more pronounced over the low Prandtl number ones. This makes the checking of its pressure drop estimation accuracy less important, assuming the code verification is complete. With an advent of powerful computer hardware, engineering applications of computational fluid dynamics (CFD) methods have become quite common these days. Especially for a fully-turbulent and single phase convective heat transfer, the predictability of the commercial codes has matured enough so that many well-known companies adopt those to accelerate a product development cycle and to realize an increased profitability. In contrast to the above, the transition models for the CFD code are still under development, and the most of the models show limited generality and prediction accuracy. Unlike the system codes, the CFD codes estimate the pressure drop from the velocity profile which is obtained by solving momentum conservation equations, and the resulting friction factor can be a representative parameter for a constant cross section channel flow. In addition, the flow inside a rectangular channel with a high span to gap ratio can be approximated by flow inside parallel plates. The computational fluid dynamics simulation on the flow between parallel plates showed reasonable prediction capability for the laminar and the turbulent regime.

  19. Study of Dynamic Flow and Mixing Performances of Tri-Screw Extruders with Finite Element Method

    X. Z. Zhu; G. Wang; Y. D. He; Z. F. Cheng

    2013-01-01

    There is a special circumfluence in the center region of cross-section for a tri-screw extruder. To study the effect of the dynamic center region on the flow and mixing mechanism of the tri-screw extruder, 2D finite element modeling was used to reduce the axial effects. Based on the particle tracking technology, the nonlinear dynamics of a typical particle motions in the center region was carried out and the mixing process in the tri-screw extruder was analyzed with Poincaré maps. Moreover, m...

  20. Dynamics of nuclear fuel assemblies in vertical flow channels: computer modelling and associated studies

    Mason, V.A.; Pettigrew, M.J.; Lelli, G.; Kates, L.; Reimer, E.

    1978-10-01

    A computer model, designed to predict the dynamic behaviour of nuclear fuel assemblies in axial flow, is described in this report. The numerical methods used to construct and solve the matrix equations of motion in the model are discussed together with an outline of the method used to interpret the fuel assembly stability data. The mathematics developed for forced response calculations are described in detail. Certain structural and hydrodynamic modelling parameters must be determined by experiment. These parameters are identified and the methods used for their evaluation are briefly described. Examples of typical applications of the dynamic model are presented towards the end of the report. (author)

  1. Analysis of compressible light dynamic stall flow at transitional Reynolds numbers

    Dyken, R.D. Van; Ekaterinaris, John A.; Chandrasekhara, M.S.

    1996-01-01

    Numerical and experimental results of steady and light dynamic stall flow over an oscillating NACA 0012 airfoil at a freestream Mach number of 0.3 and Reynolds number of 0.54 x 10(6) are compared, The experimental observation that dynamic stall is induced from the bursting of a laminar separation...... point is specified suitably and a simple transition length model is incorporated to determine the extent of the laminar separation bubble. The thin-layer approximations of compressible, Reynolds-averaged, Navier-Stokes equations are used for the numerical solution, with an implicit, upwind-biased, third...

  2. Open-end tube dynamic flow model with an oscillatory extortion

    Tulwin Tytus

    2017-01-01

    Full Text Available This paper presents a derivation of dynamic 2d mathematical model for open end tube with oscillatory extortion in the region of the closed end. The aim the research is to investigate possible uses of the increased pressure in the enclosed tube chamber, especially for energy efficient lift generation. The mathematical model allows to test and predict how flow modifications impact the resultant lifting force. A derivation of the proposed mathematical model is shown. The mathematical model is then compared to the computational fluid dynamics discrete model. The results prove the accuracy of the mathematical physical model.

  3. The role of ice dynamics in shaping vegetation in flowing waters.

    Lind, Lovisa; Nilsson, Christer; Polvi, Lina E; Weber, Christine

    2014-11-01

    Ice dynamics is an important factor affecting vegetation in high-altitude and high-latitude streams and rivers. During the last few decades, knowledge about ice in streams and rivers has increased significantly and a respectable body of literature is now available. Here we review the literature on how ice dynamics influence riparian and aquatic vegetation. Traditionally, plant ecologists have focused their studies on the summer period, largely ignoring the fact that processes during winter also impact vegetation dynamics. For example, the freeze-up period in early winter may result in extensive formation of underwater ice that can restructure the channel, obstruct flow, and cause flooding and thus formation of more ice. In midwinter, slow-flowing reaches develop a surface-ice cover that accumulates snow, protecting habitats under the ice from formation of underwater ice but also reducing underwater light, thus suppressing photosynthesis. Towards the end of winter, ice breaks up and moves downstream. During this transport, ice floes can jam up and cause floods and major erosion. The magnitudes of the floods and their erosive power mainly depend on the size of the watercourse, also resulting in different degrees of disturbance to the vegetation. Vegetation responds both physically and physiologically to ice dynamics. Physical action involves the erosive force of moving ice and damage caused by ground frost, whereas physiological effects - mostly cell damage - happen as a result of plants freezing into the ice. On a community level, large magnitudes of ice dynamics seem to favour species richness, but can be detrimental for individual plants. Human impacts, such as flow regulation, channelisation, agriculturalisation and water pollution have modified ice dynamics; further changes are expected as a result of current and predicted future climate change. Human impacts and climate change can both favour and disfavour riverine vegetation dynamics. Restoration of streams

  4. Plasma sheet fast flows and auroral dynamics during substorm: a case study

    N. L. Borodkova

    2002-03-01

    Full Text Available Interball-1 observations of a substorm development in the mid-tail on 16 December 1998 are compared with the auroral dynamics obtained from the Polar UV imager. Using these data, the relationship between plasma flow directions in the tail and the location of the auroral activation is examined. Main attention is given to tailward and earth-ward plasma flows, interpreted as signatures of a Near Earth Neutral Line (NENL. It is unambiguously shown that in the mid-plasma sheet the flows were directed tailward when the auroral bulge developed equatorward of the spacecraft ionospheric footprint. On the contrary, when active auroras moved poleward of the Interball-1 projection, earthward fast flow bursts were observed. This confirms the concept that the NENL (or flow reversal region is the source of auroras forming the poleward edge of the auroral bulge. The observed earthward flow bursts have all typical signatures of Bursty Bulk Flows (BBFs, described by Angelopolous et al. (1992. These BBFs are related to substorm activations starting at the poleward edge of the expanded auroral bulge. We interpret the BBFs as a result of reconnection pulses occurring tail-ward of Interball-1. In addition, some non-typically observed phenomena were detected in the plasma sheet during this substorm: (i tailward/earthward flows were superimposed on a very strong duskward flow, and (ii wavy structures of both magnetic field and plasma density were registered. The latter observation is probably linked to the filamentary structure of the current sheet.Key words. Magnetospheric physics (auroral phenomena; plasma sheet; storms and substorms

  5. Eruption and emplacement dynamics of a thick trachytic lava flow of the Sancy volcano (France)

    Latutrie, Benjamin; Harris, Andrew; Médard, Etienne; Gurioli, Lucia

    2017-01-01

    A 70-m-thick, 2200-m-long (51 × 106 m3) trachytic lava flow unit underlies the Puy de Cliergue (Mt. Dore, France). Excellent exposure along a 400-m-long and 60- to 85-m-high section allows the flow interior to be accessed on two sides of a glacial valley that cuts through the unit. We completed an integrated morphological, structural, textural, and chemical analysis of the unit to gain insights into eruption and flow processes during emplacement of this thick silicic lava flow, so as to elucidate the chamber and flow dynamic processed that operate during the emplacement of such systems. The unit is characterized by an inverse chemical stratification, where there is primitive lava beneath the evolved lava. The interior is plug dominated with a thin basal shear zone overlying a thick basal breccia, with ramping affecting the entire flow thickness. To understand these characteristics, we propose an eruption model that first involves processes operating in the magma chamber whereby a primitive melt is injected into an evolved magma to create a mixed zone at the chamber base. The eruption triggered by this event first emplaced a trachytic dome, into which banded lava from the chamber base was injected. Subsequent endogenous dome growth led to flow down the shallow slope to the east on which the highly viscous (1012 Pa s) coulée was emplaced. The flow likely moved extremely slowly, being emplaced over a period of 4-10 years in a glacial manner, where a thick (>60-m) plug slid over a thin (5-m-thick) basal shear zone. Excellent exposure means that the Puy de Cliergue complex can be viewed as a case type location for understanding and defining the eruption and emplacement of thick, high-viscosity, silicic lava flow systems.

  6. Fluctuations of cytoskeleton-bound microbeads-the effect of bead-receptor binding dynamics

    Metzner, C; Raupach, C; Mierke, C T; Fabry, B

    2010-01-01

    The cytoskeleton (CSK) of living cells is a crosslinked fiber network, subject to ongoing biochemical remodeling processes that can be visualized by tracking the spontaneous motion of CSK-bound microbeads. The bead motion is characterized by anomalous diffusion with a power-law time evolution of the mean square displacement (MSD), and can be described as a stochastic transport process with apparent diffusivity D and power-law exponent β: MSD ∼ D (t/t 0 ) β . Here we studied whether D and β change with the time that has passed after the initial bead-cell contact, and whether they are sensitive to bead coating (fibronectin, integrin antibodies, poly-L-lysine, albumin) and bead size (0.5-4.5 μm). The measurements are interpreted in the framework of a simple model that describes the bead as an overdamped particle coupled to the fluctuating CSK network by an elastic spring. The viscous damping coefficient characterizes the degree of bead internalization into the cell, and the spring constant characterizes the strength of the binding of the bead to the CSK. The model predicts distinctive signatures of the MSD that change with time as the bead couples more tightly to the CSK and becomes internalized. Experimental data show that the transition from the unbound to the tightly bound state occurs in an all-or-nothing manner. The time point of this transition shows considerable variability between individual cells (2-30 min) and depends on the bead size and bead coating. On average, this transition occurs later for smaller beads and beads coated with ligands that trigger the formation of adhesion complexes (fibronectin, integrin antibodies). Once the bead is linked to the CSK, however, the ligand type and bead size have little effect on the MSD. On longer timescales of several hours after bead addition, smaller beads are internalized into the cell more readily, leading to characteristic changes in the MSD that are consistent with increased viscous damping by the

  7. Computational Fluid Dynamics simulation of hydrothermal liquefaction of microalgae in a continuous plug-flow reactor.

    Ranganathan, Panneerselvam; Savithri, Sivaraman

    2018-06-01

    Computational Fluid Dynamics (CFD) technique is used in this work to simulate the hydrothermal liquefaction of Nannochloropsis sp. microalgae in a lab-scale continuous plug-flow reactor to understand the fluid dynamics, heat transfer, and reaction kinetics in a HTL reactor under hydrothermal condition. The temperature profile in the reactor and the yield of HTL products from the present simulation are obtained and they are validated with the experimental data available in the literature. Furthermore, the parametric study is carried out to study the effect of slurry flow rate, reactor temperature, and external heat transfer coefficient on the yield of products. Though the model predictions are satisfactory in comparison with the experimental results, it still needs to be improved for better prediction of the product yields. This improved model will be considered as a baseline for design and scale-up of large-scale HTL reactor. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Dynamics of a confined dusty fluid in a sheared ion flow

    Laishram, Modhuchandra; Sharma, Devendra; Kaw, Predhiman K. [Institute for Plasma Research, Bhat, Gandhinagar 382428 (India)

    2014-07-15

    Dynamics of an isothermally driven dust fluid is analyzed which is confined in an azimuthally symmetric cylindrical setup by an effective potential and is in equilibrium with an unconfined sheared flow of a streaming plasma. Cases are analyzed where the confining potential constitutes a barrier for the driven fluid, limiting its spatial extension and boundary velocity. The boundary effects entering the formulation are characterized by applying the appropriate boundary conditions and a range of solutions exhibiting single and multiple vortex are obtained. The equilibrium solutions considered in the cylindrical setup feature a transition from single to multiple vortex state of the driven flow. Effects of (i) the variation in dust viscosity, (ii) coupling between the driving and the driven fluid, and (iii) a friction determining the equilibrium dynamics of the driven system are characterized.

  9. Inertial-particle dynamics in turbulent flows: caustics, concentration fluctuations and random uncorrelated motion

    Gustavsson, K; Mehlig, B; Meneguz, E; Reeks, M

    2012-01-01

    We have performed numerical simulations of inertial particles in random model flows in the white-noise limit (at zero Kubo number, Ku = 0) and at finite Kubo numbers. Our results for the moments of relative inertial-particle velocities are in good agreement with recent theoretical results (Gustavsson and Mehlig 2011a) based on the formation of phase-space singularities in the inertial-particle dynamics (caustics). We discuss the relation between three recent approaches describing the dynamics and spatial distribution of inertial particles suspended in turbulent flows: caustic formation, real-space singularities of the deformation tensor and random uncorrelated motion. We discuss how the phase- and real-space singularities are related. Their formation is well understood in terms of a local theory. We summarise the implications for random uncorrelated motion. (paper)

  10. Fast Virtual Fractional Flow Reserve Based Upon Steady-State Computational Fluid Dynamics Analysis

    Paul D. Morris, PhD

    2017-08-01

    Full Text Available Fractional flow reserve (FFR-guided percutaneous intervention is superior to standard assessment but remains underused. The authors have developed a novel “pseudotransient” analysis protocol for computing virtual fractional flow reserve (vFFR based upon angiographic images and steady-state computational fluid dynamics. This protocol generates vFFR results in 189 s (cf >24 h for transient analysis using a desktop PC, with <1% error relative to that of full-transient computational fluid dynamics analysis. Sensitivity analysis demonstrated that physiological lesion significance was influenced less by coronary or lesion anatomy (33% and more by microvascular physiology (59%. If coronary microvascular resistance can be estimated, vFFR can be accurately computed in less time than it takes to make invasive measurements.

  11. Unified solver for fluid dynamics and aeroacoustics in isentropic gas flows

    Pont, Arnau; Codina, Ramon; Baiges, Joan; Guasch, Oriol

    2018-06-01

    The high computational cost of solving numerically the fully compressible Navier-Stokes equations, together with the poor performance of most numerical formulations for compressible flow in the low Mach number regime, has led to the necessity for more affordable numerical models for Computational Aeroacoustics. For low Mach number subsonic flows with neither shocks nor thermal coupling, both flow dynamics and wave propagation can be considered isentropic. Therefore, a joint isentropic formulation for flow and aeroacoustics can be devised which avoids the need for segregating flow and acoustic scales. Under these assumptions density and pressure fluctuations are directly proportional, and a two field velocity-pressure compressible formulation can be derived as an extension of an incompressible solver. Moreover, the linear system of equations which arises from the proposed isentropic formulation is better conditioned than the homologous incompressible one due to the presence of a pressure time derivative. Similarly to other compressible formulations the prescription of boundary conditions will have to deal with the backscattering of acoustic waves. In this sense, a separated imposition of boundary conditions for flow and acoustic scales which allows the evacuation of waves through Dirichlet boundaries without using any tailored damping model will be presented.

  12. Reconstruction of the dynamics of the 1800-1801 Hualalai eruption: Implications for planetary lava flows

    Baloga, Stephen; Spudis, Paul

    1993-01-01

    The 1800-1801 eruption of alkalic basalt from the Hualalai volcano, Hawaii provides a unique opportunity for investigating the dynamics of lava flow emplacement with eruption rates and compositions comparable to those that have been suggested for planetary eruptions. Field observations suggest new considerations must be used to reconstruct the emplacement of these lava flows. These observations are: (1) the flow traversed the 15 km from the vent to the sea so rapidly that no significant crust formed and an observation of the eruption reported that the flow reach the sea from the vent in approximately 1 hour; (2) the drainage of beds of xenolith nodules indicates a highly fluid, low viscosity lava; (3) overspills and other morphologic evidence for a very low viscosity host fluid; (4) no significant longitudinal increase in flow thickness that might be associated with an increase in the rheological properties of the lava; and (5) the relatively large size of channels associated with the flow, up to 80 meters across and several km long. Models for many geologic mass movements and fast moving fluids with various loadings and suspensions are discussed.

  13. Unsteady Flow Dynamics and Acoustics of Two-Outlet Centrifugal Fan Design

    Wong, I. Y. W.; Leung, R. C. K.; Law, A. K. Y.

    2011-09-01

    In this study, a centrifugal fan design with two flow outlets is investigated. This design aims to provide high mass flow rate but low noise performance. Two dimensional unsteady flow simulation with CFD code (FLUENT 6.3) is carried out to analyze the fan flow dynamics and its acoustics. The calculations were done using the unsteady Reynolds averaged Navier Stokes (URANS) approach in which effects of turbulence were accounted for using κ-ɛ model. This work aims to provide an insight how the dominant noise source mechanisms vary with a key fan geometrical paramters, namely, the ratio between cutoff distance and the radius of curvature of the fan housing. Four new fan designs were calculated. Simulation results show that the unsteady flow-induced forces on the fan blades are found to be the main noise sources. The blade force coefficients are then used to build the dipole source terms in Ffowcs Williams and Hawkings (FW-H) Equation for estimating their noise effects. It is found that one design is able to deliver a mass flow 34% more, but with sound pressure level (SPL) 10 dB lower, than the existing design .

  14. MINIMUM QUANTITY LUBRICANT FLOW ANALYSIS IN END MILLING PROCESSES: A COMPUTATIONAL FLUID DYNAMICS APPROACH

    M. S. Najiha

    2012-12-01

    Full Text Available This paper presents a two-dimensional steady-state incompressible analysis for the minimum quantity of lubricant flow in milling operations using a computational fluid dynamics (CFD approach. The analysis of flow and heat transfer in a four-teeth milling cutter operation was undertaken. The domain of the rotating cutter along with the spray nozzle is defined. Operating cutting and boundary conditions are taken from the literature. A steady-state, pressure-based, planar analysis was performed with a viscous, realizable k-ε model. A mixture of oils and air were sprayed on the tool, which is considered to be rotating and is at a temperature near the melting temperature of the workpiece. Flow fields are obtained from the study. The vector plot of the flow field shows that the flow is not evenly distributed over the cutter surface, as well as the uneven distribution of the lubricant in the direction of the cutter rotation. It can be seen that the cutting fluid has not completely penetrated the tool edges. The turbulence created by the cutter rotation in the proximity of the tool throws oil drops out of the cutting zone. The nozzle position in relation to the feed direction is very important in order to obtain the optimum effect of the MQL flow.

  15. Debris flow run-out simulation and analysis using a dynamic model

    Melo, Raquel; van Asch, Theo; Zêzere, José L.

    2018-02-01

    Only two months after a huge forest fire occurred in the upper part of a valley located in central Portugal, several debris flows were triggered by intense rainfall. The event caused infrastructural and economic damage, although no lives were lost. The present research aims to simulate the run-out of two debris flows that occurred during the event as well as to calculate via back-analysis the rheological parameters and the excess rain involved. Thus, a dynamic model was used, which integrates surface runoff, concentrated erosion along the channels, propagation and deposition of flow material. Afterwards, the model was validated using 32 debris flows triggered during the same event that were not considered for calibration. The rheological and entrainment parameters obtained for the most accurate simulation were then used to perform three scenarios of debris flow run-out on the basin scale. The results were confronted with the existing buildings exposed in the study area and the worst-case scenario showed a potential inundation that may affect 345 buildings. In addition, six streams where debris flow occurred in the past and caused material damage and loss of lives were identified.

  16. Comparison of Chlorpyrifos-Oxon and Paraoxon Acetylcholinesterase Inhibition Dynamics: Potential role of a peripheral binding site

    Kousba, Ahmed A.; Sultatos, L G.; Poet, Torka S.; Timchalk, Chuck

    2004-08-02

    The primary mechanism of action for organophosphorus (OP) insecticides involves the inhibition of acetylcholinesterase (AChE) by oxygenated metabolites (oxons). This inhibition has been attributed to the phosphorylation of the serine hydroxyl group located in the active site of the AChE molecule. The rate of phosphorylation is described by the bimolecular inhibitory rate constant (ki), which has been utilized for quantification of OP inhibitory capacity. It has been previously proposed that a peripheral binding site exists on the AChE molecule, which when occupied, reduces the capacity of additional oxon molecules to phosphorylate the active site. The objective of the current study was to evaluate the interaction of chlorpyrifos oxon (CPO) and paraoxon (PO) with rat brain AChE using a modified Ellman assay in conjunction with a pharmacodynamic model to further assess the dynamics of AChE inhibition and the potential role of a peripheral binding site. The ki for AChE inhibition determined at oxon concentrations of 5 x 10{sup -4} 100 nM were 0.212 and 0.0216 nM-1h-1 for CPO and PO, respectively. The spontaneous reactivation rates of the inhibited AChE for CPO and PO were 0.087 and 0.078 h-1, respectively. In contrast, the ki estimated at a low oxon concentration (1 pM) were {approx} 1,000 and 10,000 -fold higher than those determined at high CPO and PO concentrations, respectively. At these low concentrations, the ki estimates were approximately similar for both CPO and PO (180 and 250 nM-1h-1, respectively). This implies that at low exposure concentrations, both oxons exhibited similar inhibitory potency in contrast to the marked difference exhibited at higher concentrations, which is consistent with the presence of a peripheral binding site on the AChE enzyme. These results support the potential importance of a secondary binding site associated with AChE kinetics, particularly at low environmentally relevant concentrations.

  17. Parallel decomposition of the tight-binding fictitious Lagrangian algorithm for molecular dynamics simulations of semiconductors

    Yeh, M.; Kim, J.; Khan, F.S.

    1995-01-01

    We present a parallel decomposition of the tight-binding fictitious Lagrangian algorithm for the Intel iPSC/860 and the Intel Paragon parallel computers. We show that it is possible to perform long simulations, of the order of 10 000 time steps, on semiconducting clusters consisting of as many as 512 atoms, on a time scale of the order of 20 h or less. We have made a very careful timing analysis of all parts of our code, and have identified the bottlenecks. We have also derived formulas which can predict the timing of our code, based on the number of processors, message passing bandwidth, floating point performance of each node, and the set up time for message passing, appropriate to the machine being used. The time of the simulation scales as the square of the number of particles, if the number of processors is made to scale linearly with the number of particles. We show that for a system as large as 512 atoms, the main bottleneck of the computation is the orthogonalization of the wave functions, which consumes about 90% of the total time of the simulation

  18. Binding neutral information to emotional contexts: Brain dynamics of long-term recognition memory.

    Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Moltó, Javier; Poy, Rosario; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

    2016-04-01

    There is abundant evidence in memory research that emotional stimuli are better remembered than neutral stimuli. However, effects of an emotionally charged context on memory for associated neutral elements is also important, particularly in trauma and stress-related disorders, where strong memories are often activated by neutral cues due to their emotional associations. In the present study, we used event-related potentials (ERPs) to investigate long-term recognition memory (1-week delay) for neutral objects that had been paired with emotionally arousing or neutral scenes during encoding. Context effects were clearly evident in the ERPs: An early frontal ERP old/new difference (300-500 ms) was enhanced for objects encoded in unpleasant compared to pleasant and neutral contexts; and a late central-parietal old/new difference (400-700 ms) was observed for objects paired with both pleasant and unpleasant contexts but not for items paired with neutral backgrounds. Interestingly, objects encoded in emotional contexts (and novel objects) also prompted an enhanced frontal early (180-220 ms) positivity compared to objects paired with neutral scenes indicating early perceptual significance. The present data suggest that emotional--particularly unpleasant--backgrounds strengthen memory for items encountered within these contexts and engage automatic and explicit recognition processes. These results could help in understanding binding mechanisms involved in the activation of trauma-related memories by neutral cues.

  19. Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation.

    David J Huggins

    2010-08-01

    Full Text Available The Polo-Like Kinase 1 (PLK1 acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD. The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors.

  20. Surging Versus Continuous Turbidity Currents: Flow Dynamics and Deposits in an Experimental Intraslope Minibasin

    Lamb, Michael P.; Hickson, Thomas; Marr, Jeffrey G.; Sheets, Ben; Paola, Chris; Parker, Gary

    2004-01-01

    Small intraslope basins (~100 km^2), or "minibasins," such as those found on the continental slope of the Gulf of Mexico, have been filled predominantly by turbidity currents. Each minibasin is the result of local subsidence and is partially or completely isolated from neighboring basins by ridges formed from compensational uplift. We undertook a series of experiments to investigate the relationship between the flow dynamics of turbidity currents entering a minibasin and the stratal architect...