Dissipative particle dynamics parameterization and simulations to predict negative volume excess and structure of PEG and water mixtures

NASA Astrophysics Data System (ADS)

Kacar, Gokhan

2017-12-01

We report the results of dissipative particle dynamics (DPD) parameterization and simulations of a mixture of hydrophilic polymer, PEG 400, and water which are known to exhibit negative volume excess property upon mixing. The addition of a Morse potential to the conventional DPD potential mimics the hydrogen bond attraction, where the parameterization takes the internal chemistry of the beads into account. The results indicate that the mixing of PEG and water are maintained by the influence of hydrogen bonds, and the mesoscopic structure is characterized by the trade-off of enthalpic and entropic effects.

LAMMPS Implementation of Constant Energy Dissipative Particle Dynamics (DPD-E)

DTIC Science & Technology

2014-03-01

LAMMPS Implementation of Constant Energy Dissipative Particle Dynamics (DPD-E) by James P. Larentzos, John K. Brennan, Joshua D. Moore, and...MD 21005-5069 ARL-TR-6863 March 2014 LAMMPS Implementation of Constant Energy Dissipative Particle Dynamics (DPD-E) James P...13 September 2013 4. TITLE AND SUBTITLE LAMMPS Implementation of Constant Energy Dissipative Particle Dynamics (DPD-E) 5a. CONTRACT NUMBER 5b

Accelerating Calculations of Reaction Dissipative Particle Dynamics in LAMMPS

DTIC Science & Technology

2017-05-17

order reaction mechanism, the best acceleration was 6.1 times. For a larger, more chemically detailed mechanism, the best acceleration exceeded 60 times...simulations at previously inaccessible scales. A principle feature of DPD-RX is its ability to model chemical reactions within each CG particle. The...change in composition due to chemical reactions is described by a system of ordinary differential equations (ODEs) that are evaluated at each DPD time

Non-equilibrium dynamics due to moving deflagration front at RDX/HTPB interface

NASA Astrophysics Data System (ADS)

Chaudhuri, Santanu; Joshi, Kaushik; Lacevic, Naida

Reactive dissipative particle dynamics (DPD-RX), a promising tool in characterizing the sensitivity and performance of heterogeneous solid propellants like polymer bonded explosives (PSXs), requires further testing for non-equilibrium dynamics. It is important to understand detailed atomistic chemistry for developing coarse grain reactive models needed for the DPD-RX. In order to obtain insights into combustion chemistry of RDX/HTPB binder, we used reactive molecular dynamics (RMD) to obtain energy up-pumping and reaction mechanisms at RDX/HTPB interface when exposed to a self-sustaining deflagration front. Hot spots are ignited near and away from the heterogeneous interface using the thermal pulse. The results show that the hot spot near interface significantly delays the transition from ignition to deflagration. We will present the mechanical response and the combustion chemistry of HTPB when the propagating deflagration front hits the polymer binder. We will discuss our efforts to incorporate this RMD based chemistry into the DPD-RX which will enable us to perform such non-equilibrium dynamics simulations on large-length scale with microstructural heterogeneities. Funding from DTRA Grant Number HDTRA1-15-1-0034 is acknowledged.

Imposition of physical parameters in dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Mai-Duy, N.; Phan-Thien, N.; Tran-Cong, T.

2017-12-01

In the mesoscale simulations by the dissipative particle dynamics (DPD), the motion of a fluid is modelled by a set of particles interacting in a pairwise manner, and it has been shown to be governed by the Navier-Stokes equation, with its physical properties, such as viscosity, Schmidt number, isothermal compressibility, relaxation and inertia time scales, in fact its whole rheology resulted from the choice of the DPD model parameters. In this work, we will explore the response of a DPD fluid with respect to its parameter space, where the model input parameters can be chosen in advance so that (i) the ratio between the relaxation and inertia time scales is fixed; (ii) the isothermal compressibility of water at room temperature is enforced; and (iii) the viscosity and Schmidt number can be specified as inputs. These impositions are possible with some extra degrees of freedom in the weighting functions for the conservative and dissipative forces. Numerical experiments show an improvement in the solution quality over conventional DPD parameters/weighting functions, particularly for the number density distribution and computed stresses.

Analysis of hydrodynamic fluctuations in heterogeneous adjacent multidomains in shear flow

NASA Astrophysics Data System (ADS)

Bian, Xin; Deng, Mingge; Tang, Yu-Hang; Karniadakis, George Em

2016-03-01

We analyze hydrodynamic fluctuations of a hybrid simulation under shear flow. The hybrid simulation is based on the Navier-Stokes (NS) equations on one domain and dissipative particle dynamics (DPD) on the other. The two domains overlap, and there is an artificial boundary for each one within the overlapping region. To impose the artificial boundary of the NS solver, a simple spatial-temporal averaging is performed on the DPD simulation. In the artificial boundary of the particle simulation, four popular strategies of constraint dynamics are implemented, namely the Maxwell buffer [Hadjiconstantinou and Patera, Int. J. Mod. Phys. C 08, 967 (1997), 10.1142/S0129183197000837], the relaxation dynamics [O'Connell and Thompson, Phys. Rev. E 52, R5792 (1995), 10.1103/PhysRevE.52.R5792], the least constraint dynamics [Nie et al., J. Fluid Mech. 500, 55 (2004), 10.1017/S0022112003007225; Werder et al., J. Comput. Phys. 205, 373 (2005), 10.1016/j.jcp.2004.11.019], and the flux imposition [Flekkøy et al., Europhys. Lett. 52, 271 (2000), 10.1209/epl/i2000-00434-8], to achieve a target mean value given by the NS solver. Going beyond the mean flow field of the hybrid simulations, we investigate the hydrodynamic fluctuations in the DPD domain. Toward that end, we calculate the transversal autocorrelation functions of the fluctuating variables in k space to evaluate the generation, transport, and dissipation of fluctuations in the presence of a hybrid interface. We quantify the unavoidable errors in the fluctuations, due to both the truncation of the domain and the constraint dynamics performed in the artificial boundary. Furthermore, we compare the four methods of constraint dynamics and demonstrate how to reduce the errors in fluctuations. The analysis and findings of this work are directly applicable to other hybrid simulations of fluid flow with thermal fluctuations.

Development of DPD coarse-grained models: From bulk to interfacial properties

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

Solano Canchaya, José G.; Dequidt, Alain, E-mail: alain.dequidt@univ-bpclermont.fr; Goujon, Florent

2016-08-07

A new Bayesian method was recently introduced for developing coarse-grain (CG) force fields for molecular dynamics. The CG models designed for dissipative particle dynamics (DPD) are optimized based on trajectory matching. Here we extend this method to improve transferability across thermodynamic conditions. We demonstrate the capability of the method by developing a CG model of n-pentane from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG-DPD model to the calculation of the surface tension of the liquid-vapor interface over a large range of temperatures. The coexisting densities, vapor pressures, and surface tensions calculated with different CG andmore » atomistic models are compared to experiments. Depending on the database used for the development of the potentials, it is possible to build a CG model which performs very well in the reproduction of the surface tension on the orthobaric curve.« less

Modeling and Bio molecular Self-assembly via Molecular Dynamics and Dissipative Particle Dynamics

NASA Astrophysics Data System (ADS)

Rakesh, L.

2009-09-01

Surfactants like materials can be used to increase the solubility of poorly soluble drugs in water and to increase drug bioavailability. A typical case study will be demonstrated using DPD simulation to model the distribution of anti-inflammatory drug molecules. Computer simulation is a convenient approach to understand drug distribution and solubility concepts without much wastage and costly experiments in the laboratory. Often in molecular dynamics (MD) the atoms are represented explicitly and the equation of motion as described by Newtonian dynamics is integrated explicitly. MD has been used to study spontaneous formation of micelles by hydrophobic molecules with amphiphilic head groups in bulk water, as well as stability of pre-configured micelles and membranes. DPD is a state-of the- art mesoscale simulation, it is a more recent molecular dynamics technique, originally developed for simulating complex fluids but lately also applied to membrane dynamics, hemodynamic in biomedical applications. Such fluids pervade industrial research from paints to pharmaceuticals and from cosmetics to the controlled release of drugs. Dissipative particle dynamics (DPD) can provide structural and dynamic properties of fluids in equilibrium, under shear or confined to narrow cavities, at length- and time-scales beyond the scope of traditional atomistic molecular dynamics simulation methods. Mesoscopic particles are used to represent clusters of molecules. The interaction conserves mass and momentum and as a consequence the dynamics is consistent with Navier-Stokes equations. In addition to the conservative forces, stochastic drive and dissipation is introduced to represent internal degrees of freedom in the mesoscopic particles. In this research, an initial study is being conducted using the aqueous solubilization of the nonsteroidal, anti-inflammatory drug is studied theoretically in micellar solution of nonionic (dodecyl hexa(ethylene oxide), C12E6) surfactants possessing the hydrocarbon "tail" and their hydrophilic head groups. We find that, for the surfactants, the aqueous solubility of anti-inflammatory molecules increases linearly with increasing surfactant concentration. In particular, we observed a 10-fold increase in the solubility of anti-inflammatory drugs relative to that in the aqueous buffer upon the addition of 100 mM dodecyltrimethyl ammonium bromide -DTAB.

Application of mesoscale simulation to explore the aggregate morphology of pH-sensitive nanoparticles used as the oral drug delivery carriers under different conditions.

PubMed

Wang, Yan; Chen, Bo Zhi; Liu, Yue Jin; Wu, Zhi Min; Guo, Xin Dong

2017-03-01

The pH-sensitive nanoparticles are selected as the potentially promising oral protein and peptide drug carriers due to their excellent performance. With the poly (lactic-co-glycolic acid)/hydroxypropyl methylcellulose phthalate (PLGA/HP55) nanoparticle as a model nanoparticle, the structure-property relationship of nanoparticles with different conditions is investigated by dissipative particle dynamics (DPD) simulations in our work. In the oral drug delivery system, the poly (lactic-co-glycolic acid) (PLGA) is hydrophobic polymer, hydroxypropyl methylcellulose phthalate (HP55) is pH-sensitive enteric polymer which used to protect the nanoparticles through the stomach and polyvinyl alcohol (PVA) is hydrophilic polymer as the stabilizer. It can be seen from DPD simulations that all polymer molecules form spherical core-shell nanoparticles with stabilizer PVA molecules adsorbed on the outer surface of the PLGA/HP55 matrix at certain compositions. The DPD simulation study can provide microscopic insight into the formation and morphological changes of pH-sensitive nanoparticles which is useful for the design of new materials for high-efficacy oral drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

GPU-accelerated Red Blood Cells Simulations with Transport Dissipative Particle Dynamics.

PubMed

Blumers, Ansel L; Tang, Yu-Hang; Li, Zhen; Li, Xuejin; Karniadakis, George E

2017-08-01

Mesoscopic numerical simulations provide a unique approach for the quantification of the chemical influences on red blood cell functionalities. The transport Dissipative Particles Dynamics (tDPD) method can lead to such effective multiscale simulations due to its ability to simultaneously capture mesoscopic advection, diffusion, and reaction. In this paper, we present a GPU-accelerated red blood cell simulation package based on a tDPD adaptation of our red blood cell model, which can correctly recover the cell membrane viscosity, elasticity, bending stiffness, and cross-membrane chemical transport. The package essentially processes all computational workloads in parallel by GPU, and it incorporates multi-stream scheduling and non-blocking MPI communications to improve inter-node scalability. Our code is validated for accuracy and compared against the CPU counterpart for speed. Strong scaling and weak scaling are also presented to characterizes scalability. We observe a speedup of 10.1 on one GPU over all 16 cores within a single node, and a weak scaling efficiency of 91% across 256 nodes. The program enables quick-turnaround and high-throughput numerical simulations for investigating chemical-driven red blood cell phenomena and disorders.

Multiscale Universal Interface: A concurrent framework for coupling heterogeneous solvers

NASA Astrophysics Data System (ADS)

Tang, Yu-Hang; Kudo, Shuhei; Bian, Xin; Li, Zhen; Karniadakis, George Em

2015-09-01

Concurrently coupled numerical simulations using heterogeneous solvers are powerful tools for modeling multiscale phenomena. However, major modifications to existing codes are often required to enable such simulations, posing significant difficulties in practice. In this paper we present a C++ library, i.e. the Multiscale Universal Interface (MUI), which is capable of facilitating the coupling effort for a wide range of multiscale simulations. The library adopts a header-only form with minimal external dependency and hence can be easily dropped into existing codes. A data sampler concept is introduced, combined with a hybrid dynamic/static typing mechanism, to create an easily customizable framework for solver-independent data interpretation. The library integrates MPI MPMD support and an asynchronous communication protocol to handle inter-solver information exchange irrespective of the solvers' own MPI awareness. Template metaprogramming is heavily employed to simultaneously improve runtime performance and code flexibility. We validated the library by solving three different multiscale problems, which also serve to demonstrate the flexibility of the framework in handling heterogeneous models and solvers. In the first example, a Couette flow was simulated using two concurrently coupled Smoothed Particle Hydrodynamics (SPH) simulations of different spatial resolutions. In the second example, we coupled the deterministic SPH method with the stochastic Dissipative Particle Dynamics (DPD) method to study the effect of surface grafting on the hydrodynamics properties on the surface. In the third example, we consider conjugate heat transfer between a solid domain and a fluid domain by coupling the particle-based energy-conserving DPD (eDPD) method with the Finite Element Method (FEM).

Multiscale Universal Interface: A concurrent framework for coupling heterogeneous solvers

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

Tang, Yu-Hang, E-mail: yuhang_tang@brown.edu; Kudo, Shuhei, E-mail: shuhei-kudo@outlook.jp; Bian, Xin, E-mail: xin_bian@brown.edu

2015-09-15

Graphical abstract: - Abstract: Concurrently coupled numerical simulations using heterogeneous solvers are powerful tools for modeling multiscale phenomena. However, major modifications to existing codes are often required to enable such simulations, posing significant difficulties in practice. In this paper we present a C++ library, i.e. the Multiscale Universal Interface (MUI), which is capable of facilitating the coupling effort for a wide range of multiscale simulations. The library adopts a header-only form with minimal external dependency and hence can be easily dropped into existing codes. A data sampler concept is introduced, combined with a hybrid dynamic/static typing mechanism, to create anmore » easily customizable framework for solver-independent data interpretation. The library integrates MPI MPMD support and an asynchronous communication protocol to handle inter-solver information exchange irrespective of the solvers' own MPI awareness. Template metaprogramming is heavily employed to simultaneously improve runtime performance and code flexibility. We validated the library by solving three different multiscale problems, which also serve to demonstrate the flexibility of the framework in handling heterogeneous models and solvers. In the first example, a Couette flow was simulated using two concurrently coupled Smoothed Particle Hydrodynamics (SPH) simulations of different spatial resolutions. In the second example, we coupled the deterministic SPH method with the stochastic Dissipative Particle Dynamics (DPD) method to study the effect of surface grafting on the hydrodynamics properties on the surface. In the third example, we consider conjugate heat transfer between a solid domain and a fluid domain by coupling the particle-based energy-conserving DPD (eDPD) method with the Finite Element Method (FEM)« less

Dissipative particle dynamics: Systematic parametrization using water-octanol partition coefficients

NASA Astrophysics Data System (ADS)

Anderson, Richard L.; Bray, David J.; Ferrante, Andrea S.; Noro, Massimo G.; Stott, Ian P.; Warren, Patrick B.

2017-09-01

We present a systematic, top-down, thermodynamic parametrization scheme for dissipative particle dynamics (DPD) using water-octanol partition coefficients, supplemented by water-octanol phase equilibria and pure liquid phase density data. We demonstrate the feasibility of computing the required partition coefficients in DPD using brute-force simulation, within an adaptive semi-automatic staged optimization scheme. We test the methodology by fitting to experimental partition coefficient data for twenty one small molecules in five classes comprising alcohols and poly-alcohols, amines, ethers and simple aromatics, and alkanes (i.e., hexane). Finally, we illustrate the transferability of a subset of the determined parameters by calculating the critical micelle concentrations and mean aggregation numbers of selected alkyl ethoxylate surfactants, in good agreement with reported experimental values.

Direct construction of mesoscopic models from microscopic simulations

NASA Astrophysics Data System (ADS)

Lei, Huan; Caswell, Bruce; Karniadakis, George Em

2010-02-01

Starting from microscopic molecular-dynamics (MD) simulations of constrained Lennard-Jones (LJ) clusters (with constant radius of gyration Rg ), we construct two mesoscopic models [Langevin dynamics and dissipative particle dynamics (DPD)] by coarse graining the LJ clusters into single particles. Both static and dynamic properties of the coarse-grained models are investigated and compared with the MD results. The effective mean force field is computed as a function of the intercluster distance, and the corresponding potential scales linearly with the number of particles per cluster and the temperature. We verify that the mean force field can reproduce the equation of state of the atomistic systems within a wide density range but the radial distribution function only within the dilute and the semidilute regime. The friction force coefficients for both models are computed directly from the time-correlation function of the random force field of the microscopic system. For high density or a large cluster size the friction force is overestimated and the diffusivity underestimated due to the omission of many-body effects as a result of the assumed pairwise form of the coarse-grained force field. When the many-body effect is not as pronounced (e.g., smaller Rg or semidilute system), the DPD model can reproduce the dynamic properties of the MD system.

Effectively parameterizing dissipative particle dynamics using COSMO-SAC: A partition coefficient study

NASA Astrophysics Data System (ADS)

Saathoff, Jonathan

2018-04-01

Dissipative Particle Dynamics (DPD) provides a tool for studying phase behavior and interfacial phenomena for complex mixtures and macromolecules. Methods to quickly and automatically parameterize DPD greatly increase its effectiveness. One such method is to map predicted activity coefficients derived from COSMO-SAC onto DPD parameter sets. However, there are serious limitations to the accuracy of this mapping, including the inability of single DPD beads to reproduce asymmetric infinite dilution activity coefficients, the loss of precision when reusing parameters for different molecular fragments, and the error due to bonding beads together. This report describes these effects in quantitative detail and provides methods to mitigate much of their deleterious effects. This includes a novel approach to remove errors caused by bonding DPD beads together. Using these methods, logarithm hexane/water partition coefficients were calculated for 61 molecules. The root mean-squared error for these calculations was determined to be 0.14—a very low value—with respect to the final mapping procedure. Cognizance of the above limitations can greatly enhance the predictive power of DPD.

Smoothed dissipative particle dynamics with angular momentum conservation

NASA Astrophysics Data System (ADS)

Müller, Kathrin; Fedosov, Dmitry A.; Gompper, Gerhard

2015-01-01

Smoothed dissipative particle dynamics (SDPD) combines two popular mesoscopic techniques, the smoothed particle hydrodynamics and dissipative particle dynamics (DPD) methods, and can be considered as an improved dissipative particle dynamics approach. Despite several advantages of the SDPD method over the conventional DPD model, the original formulation of SDPD by Español and Revenga (2003) [9], lacks angular momentum conservation, leading to unphysical results for problems where the conservation of angular momentum is essential. To overcome this limitation, we extend the SDPD method by introducing a particle spin variable such that local and global angular momentum conservation is restored. The new SDPD formulation (SDPD+a) is directly derived from the Navier-Stokes equation for fluids with spin, while thermal fluctuations are incorporated similarly to the DPD method. We test the new SDPD method and demonstrate that it properly reproduces fluid transport coefficients. Also, SDPD with angular momentum conservation is validated using two problems: (i) the Taylor-Couette flow with two immiscible fluids and (ii) a tank-treading vesicle in shear flow with a viscosity contrast between inner and outer fluids. For both problems, the new SDPD method leads to simulation predictions in agreement with the corresponding analytical theories, while the original SDPD method fails to capture properly physical characteristics of the systems due to violation of angular momentum conservation. In conclusion, the extended SDPD method with angular momentum conservation provides a new approach to tackle fluid problems such as multiphase flows and vesicle/cell suspensions, where the conservation of angular momentum is essential.

Simulation and experimental study of rheological properties of CeO2-water nanofluid

NASA Astrophysics Data System (ADS)

Loya, Adil; Stair, Jacqueline L.; Ren, Guogang

2015-10-01

Metal oxide nanoparticles offer great merits over controlling rheological, thermal, chemical and physical properties of solutions. The effectiveness of a nanoparticle to modify the properties of a fluid depends on its diffusive properties with respect to the fluid. In this study, rheological properties of aqueous fluids (i.e. water) were enhanced with the addition of CeO2 nanoparticles. This study was characterized by the outcomes of simulation and experimental results of nanofluids. The movement of nanoparticles in the fluidic media was simulated by a large-scale molecular thermal dynamic program (i.e. LAMMPS). The COMPASS force field was employed with smoothed particle hydrodynamic potential (SPH) and discrete particle dynamics potential (DPD). However, this study develops the understanding of how the rheological properties are affected due to the addition of nanoparticles in a fluid and the way DPD and SPH can be used for accurately estimating the rheological properties with Brownian effect. The rheological results of the simulation were confirmed by the convergence of the stress autocorrelation function, whereas experimental properties were measured using a rheometer. These rheological values of simulation were obtained and agreed within 5 % of the experimental values; they were identified and treated with a number of iterations and experimental tests. The results of the experiment and simulation show that 10 % CeO2 nanoparticles dispersion in water has a viscosity of 2.0-3.3 mPas.

A dissipative particle dynamics method for arbitrarily complex geometries

NASA Astrophysics Data System (ADS)

Li, Zhen; Bian, Xin; Tang, Yu-Hang; Karniadakis, George Em

2018-02-01

Dissipative particle dynamics (DPD) is an effective Lagrangian method for modeling complex fluids in the mesoscale regime but so far it has been limited to relatively simple geometries. Here, we formulate a local detection method for DPD involving arbitrarily shaped geometric three-dimensional domains. By introducing an indicator variable of boundary volume fraction (BVF) for each fluid particle, the boundary of arbitrary-shape objects is detected on-the-fly for the moving fluid particles using only the local particle configuration. Therefore, this approach eliminates the need of an analytical description of the boundary and geometry of objects in DPD simulations and makes it possible to load the geometry of a system directly from experimental images or computer-aided designs/drawings. More specifically, the BVF of a fluid particle is defined by the weighted summation over its neighboring particles within a cutoff distance. Wall penetration is inferred from the value of the BVF and prevented by a predictor-corrector algorithm. The no-slip boundary condition is achieved by employing effective dissipative coefficients for liquid-solid interactions. Quantitative evaluations of the new method are performed for the plane Poiseuille flow, the plane Couette flow and the Wannier flow in a cylindrical domain and compared with their corresponding analytical solutions and (high-order) spectral element solution of the Navier-Stokes equations. We verify that the proposed method yields correct no-slip boundary conditions for velocity and generates negligible fluctuations of density and temperature in the vicinity of the wall surface. Moreover, we construct a very complex 3D geometry - the "Brown Pacman" microfluidic device - to explicitly demonstrate how to construct a DPD system with complex geometry directly from loading a graphical image. Subsequently, we simulate the flow of a surfactant solution through this complex microfluidic device using the new method. Its effectiveness is demonstrated by examining the rich dynamics of surfactant micelles, which are flowing around multiple small cylinders and stenotic regions in the microfluidic device without wall penetration. In addition to stationary arbitrary-shape objects, the new method is particularly useful for problems involving moving and deformable boundaries, because it only uses local information of neighboring particles and satisfies the desired boundary conditions on-the-fly.

Dissipative-particle-dynamics model of biofilm growth

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

Xu, Zhijie; Meakin, Paul; Tartakovsky, Alexandre M.

2011-06-13

A dissipative particle dynamics (DPD) model for the quantitative simulation of biofilm growth controlled by substrate (nutrient) consumption, advective and diffusive substrate transport, and hydrodynamic interactions with fluid flow (including fragmentation and reattachment) is described. The model was used to simulate biomass growth, decay, and spreading. It predicts how the biofilm morphology depends on flow conditions, biofilm growth kinetics, the rheomechanical properties of the biofilm and adhesion to solid surfaces. The morphology of the model biofilm depends strongly on its rigidity and the magnitude of the body force that drives the fluid over the biofilm.

Morphology and Performance of Polymer Solar Cell Characterized by DPD Simulation and Graph Theory.

PubMed

Du, Chunmiao; Ji, Yujin; Xue, Junwei; Hou, Tingjun; Tang, Jianxin; Lee, Shuit-Tong; Li, Youyong

2015-11-19

The morphology of active layers in the bulk heterojunction (BHJ) solar cells is critical to the performance of organic photovoltaics (OPV). Currently, there is limited information for the morphology from transmission electron microscopy (TEM) techniques. Meanwhile, there are limited approaches to predict the morphology /efficiency of OPV. Here we use Dissipative Particle Dynamics (DPD) to determine 3D morphology of BHJ solar cells and show DPD to be an efficient approach to predict the 3D morphology. Based on the 3D morphology, we estimate the performance indicator of BHJ solar cells by using graph theory. Specifically, we study poly (3-hexylthiophene)/[6, 6]-phenyl-C61butyric acid methyl ester (P3HT/PCBM) BHJ solar cells. We find that, when the volume fraction of PCBM is in the region 0.4 ∼ 0.5, P3HT/PCBM will show bi-continuous morphology and optimum performance, consistent with experimental results. Further, the optimum temperature (413 K) for the morphology and performance of P3HT/PCBM is in accord with annealing results. We find that solvent additive plays a critical role in the desolvation process of P3HT/PCBM BHJ solar cell. Our approach provides a direct method to predict dynamic 3D morphology and performance indicator for BHJ solar cells.

Dissipative particle dynamics study of velocity autocorrelation function and self-diffusion coefficient in terms of interaction potential strength

NASA Astrophysics Data System (ADS)

Zohravi, Elnaz; Shirani, Ebrahim; Pishevar, Ahmadreza; Karimpour, Hossein

2018-07-01

This research focuses on numerically investigating the self-diffusion coefficient and velocity autocorrelation function (VACF) of a dissipative particle dynamics (DPD) fluid as a function of the conservative interaction strength. Analytic solutions to VACF and self-diffusion coefficients in DPD were obtained by many researchers in some restricted cases including ideal gases, without the account of conservative force. As departure from the ideal gas conditions are accentuated with increasing the relative proportion of conservative force, it is anticipated that the VACF should gradually deviate from its normally expected exponentially decay. This trend is confirmed through numerical simulations and an expression in terms of the conservative force parameter, density and temperature is proposed for the self-diffusion coefficient. As it concerned the VACF, the equivalent Langevin equation describing Brownian motion of particles with a harmonic potential is adapted to the problem and reveals an exponentially decaying oscillatory pattern influenced by the conservative force parameter, dissipative parameter and temperature. Although the proposed model for obtaining the self-diffusion coefficient with consideration of the conservative force could not be verified due to computational complexities, nonetheless the Arrhenius dependency of the self-diffusion coefficient to temperature and pressure permits to certify our model over a definite range of DPD parameters.

In silico modelling of drug–polymer interactions for pharmaceutical formulations

PubMed Central

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

2010-01-01

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

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

Müller, Kathrin, E-mail: k.mueller@fz-juelich.de; Fedosov, Dmitry A., E-mail: d.fedosov@fz-juelich.de; Gompper, Gerhard, E-mail: g.gompper@fz-juelich.de

Smoothed dissipative particle dynamics (SDPD) combines two popular mesoscopic techniques, the smoothed particle hydrodynamics and dissipative particle dynamics (DPD) methods, and can be considered as an improved dissipative particle dynamics approach. Despite several advantages of the SDPD method over the conventional DPD model, the original formulation of SDPD by Español and Revenga (2003) [9], lacks angular momentum conservation, leading to unphysical results for problems where the conservation of angular momentum is essential. To overcome this limitation, we extend the SDPD method by introducing a particle spin variable such that local and global angular momentum conservation is restored. The new SDPDmore » formulation (SDPD+a) is directly derived from the Navier–Stokes equation for fluids with spin, while thermal fluctuations are incorporated similarly to the DPD method. We test the new SDPD method and demonstrate that it properly reproduces fluid transport coefficients. Also, SDPD with angular momentum conservation is validated using two problems: (i) the Taylor–Couette flow with two immiscible fluids and (ii) a tank-treading vesicle in shear flow with a viscosity contrast between inner and outer fluids. For both problems, the new SDPD method leads to simulation predictions in agreement with the corresponding analytical theories, while the original SDPD method fails to capture properly physical characteristics of the systems due to violation of angular momentum conservation. In conclusion, the extended SDPD method with angular momentum conservation provides a new approach to tackle fluid problems such as multiphase flows and vesicle/cell suspensions, where the conservation of angular momentum is essential.« less

Transport of diseased red blood cells in the spleen

NASA Astrophysics Data System (ADS)

Peng, Zhangli; Pivkin, Igor; Dao, Ming

2012-11-01

A major function of the spleen is to remove old and diseased red blood cells (RBCs) with abnormal mechanical properties. We investigated this mechanical filtering mechanism by combining experiments and computational modeling, especially for red blood cells in malaria and sickle cell disease (SCD). First, utilizing a transgenic line for 3D confocal live imaging, in vitro capillary assays and 3D finite element modeling, we extracted the mechanical properties of both the RBC membrane and malaria parasites for different asexual malaria stages. Secondly, using a non-invasive laser interferometric technique, we optically measured the dynamic membrane fluctuations of SCD RBCs. By simulating the membrane fluctuation experiment using the dissipative particle dynamics (DPD) model, we retrieved mechanical properties of SCD RBCs with different shapes. Finally, based on the mechanical properties obtained from these experiments, we simulated the full fluid-structure interaction problem of diseased RBCs passing through endothelial slits in the spleen under different fluid pressure gradients using the DPD model. The effects of the mechanical properties of the lipid bilayer, the cytoskeleton and the parasite on the critical pressure of splenic passage of RBCs were investigated separately. This work is supported by NIH and Singapore-MIT Alliance for Science and Technology (SMART).

Structural and dynamic characterization of ultrafine fibers based on the poly-3-hydroxybutyrate-dipyridamole system

NASA Astrophysics Data System (ADS)

Olkhov, A. A.; Karpova, S. G.; Staroverova, O. V.; Krutikova, A. A.; Orlov, N. A.; Kucherenko, E. L.; Iordanskii, A. L.

2016-11-01

The fibrous materials (the mats) based on poly-3-hydroxybutyrate (PHB) containing the drug, dipiridomole (DPD) were produced by electrospinning (ES). Thermophysical and dynamical properties of the single filaments and the mats were studied by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and probe electron paramagnetic resonance spectroscopy (EPR). The effect of annealing temperature on the structure and crystallinity of the fibers was examined. It was shown that the loading of DPD influences on both the melting enthalpy and the morphology of the fibers. Besides the analysis of EPR spectra revealed that there are two populations of spin-probes distributed in the rigid and nonrigid amorphous regions of the PHB fibers respectively. For all fibrous materials with different content of DPD (0-5%) the correlation between thermophysical (DSC) and dynamic data (EPR) was observed.

Conservative and dissipative force field for simulation of coarse-grained alkane molecules: A bottom-up approach

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

Trément, Sébastien; Rousseau, Bernard, E-mail: bernard.rousseau@u-psud.fr; Schnell, Benoît

2014-04-07

We apply operational procedures available in the literature to the construction of coarse-grained conservative and friction forces for use in dissipative particle dynamics (DPD) simulations. The full procedure rely on a bottom-up approach: large molecular dynamics trajectories of n-pentane and n-decane modeled with an anisotropic united atom model serve as input for the force field generation. As a consequence, the coarse-grained model is expected to reproduce at least semi-quantitatively structural and dynamical properties of the underlying atomistic model. Two different coarse-graining levels are studied, corresponding to five and ten carbon atoms per DPD bead. The influence of the coarse-graining levelmore » on the generated force fields contributions, namely, the conservative and the friction part, is discussed. It is shown that the coarse-grained model of n-pentane correctly reproduces self-diffusion and viscosity coefficients of real n-pentane, while the fully coarse-grained model for n-decane at ambient temperature over-predicts diffusion by a factor of 2. However, when the n-pentane coarse-grained model is used as a building block for larger molecule (e.g., n-decane as a two blobs model), a much better agreement with experimental data is obtained, suggesting that the force field constructed is transferable to large macro-molecular systems.« less

Dissipative particle dynamics simulations of deformation and aggregation of healthy and diseased red blood cells in a tube flow

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

Ye, Ting; Phan-Thien, Nhan, E-mail: Nhan@nus.edu.sg; Khoo, Boo Cheong

In this paper, we report simulation results assessing the deformation and aggregation of mixed healthy and malaria-infected red blood cells (RBCs) in a tube flow. A three dimensional particle model based on Dissipative Particle Dynamics (DPD) is developed to predict the tube flow containing interacting cells. The cells are also modelled by DPD, with a Morse potential to characterize the cell-cell interaction. As validation tests, a single RBC in a tube flow and two RBCs in a static flow are simulated to examine the cell deformation and intercellular interaction, respectively. The study of two cells, one healthy and the othermore » malaria-infected RBCs in a tube flow demonstrates that the malaria-infected RBC (in the leading position along flow direction) has different effects on the healthy RBC (in the trailing position) at the different stage of parasite development or at the different capillary number. With parasitic development, the malaria-infected RBC gradually loses its deformability, and in turn the corresponding trailing healthy RBC also deforms less due to the intercellular interaction. With increasing capillary number, both the healthy and malaria-infected RBCs are likely to undergo an axisymmetric motion. The minimum intercellular distance becomes small enough so that rouleaux is easily formed, i.e., the healthy and malaria-infected RBCs are difficultly disaggregated.« less

Nonsimultaneous chains and dominos in kidney- paired donation-revisited.

PubMed

Ashlagi, I; Gilchrist, D S; Roth, A E; Rees, M A

2011-05-01

Since 2008, kidney exchange in America has grown in part from the incorporation of nondirected donors in transplant chains rather than simple exchanges. It is controversial whether these chains should be performed simultaneously 'domino-paired donation', (DPD) or nonsimultaneously 'nonsimultaneous extended altruistic donor, chains (NEAD). NEAD chains create 'bridge donors' whose incompatible recipients receive kidneys before the bridge donor donates, and so risk reneging by bridge donors, but offer the opportunity to create more transplants by overcoming logistical barriers inherent in simultaneous chains. Gentry et al. simulated whether DPD or NEAD chains would produce more transplants when chain segment length was limited to three transplants, and reported that DPD performed at least as well as NEAD chains. As this finding contrasts with the experience of several groups involved in kidney-paired donation, we performed simulations that allowed for longer chain segments and used actual patient data from the Alliance for Paired Donation. When chain segments of 4-6 transplants are allowed in the simulations, NEAD chains produce more transplants than DPD. Our simulations showed not only more transplants as chain length increased, but also that NEAD chains produced more transplants for highly sensitized and blood type O recipients. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

User Manual and Source Code for a LAMMPS Implementation of Constant Energy Dissipative Particle Dynamics (DPD-E)

DTIC Science & Technology

2014-06-01

User Manual and Source Code for a LAMMPS Implementation of Constant Energy Dissipative Particle Dynamics (DPD-E) by James P. Larentzos...Laboratory Aberdeen Proving Ground, MD 21005-5069 ARL-SR-290 June 2014 User Manual and Source Code for a LAMMPS Implementation of Constant...3. DATES COVERED (From - To) September 2013–February 2014 4. TITLE AND SUBTITLE User Manual and Source Code for a LAMMPS Implementation of

Mori-Zwanzig theory for dissipative forces in coarse-grained dynamics in the Markov limit

NASA Astrophysics Data System (ADS)

Izvekov, Sergei

2017-01-01

We derive alternative Markov approximations for the projected (stochastic) force and memory function in the coarse-grained (CG) generalized Langevin equation, which describes the time evolution of the center-of-mass coordinates of clusters of particles in the microscopic ensemble. This is done with the aid of the Mori-Zwanzig projection operator method based on the recently introduced projection operator [S. Izvekov, J. Chem. Phys. 138, 134106 (2013), 10.1063/1.4795091]. The derivation exploits the "generalized additive fluctuating force" representation to which the projected force reduces in the adopted projection operator formalism. For the projected force, we present a first-order time expansion which correctly extends the static fluctuating force ansatz with the terms necessary to maintain the required orthogonality of the projected dynamics in the Markov limit to the space of CG phase variables. The approximant of the memory function correctly accounts for the momentum dependence in the lowest (second) order and indicates that such a dependence may be important in the CG dynamics approaching the Markov limit. In the case of CG dynamics with a weak dependence of the memory effects on the particle momenta, the expression for the memory function presented in this work is applicable to non-Markov systems. The approximations are formulated in a propagator-free form allowing their efficient evaluation from the microscopic data sampled by standard molecular dynamics simulations. A numerical application is presented for a molecular liquid (nitromethane). With our formalism we do not observe the "plateau-value problem" if the friction tensors for dissipative particle dynamics (DPD) are computed using the Green-Kubo relation. Our formalism provides a consistent bottom-up route for hierarchical parametrization of DPD models from atomistic simulations.

Dissipative particle dynamics simulation on the self-assembly and disassembly of pH-sensitive polymeric micelle with coating repair agent

NASA Astrophysics Data System (ADS)

Wang, Xiumin; Gao, Jianbang; Wang, Zhikun; Xu, Jianchang; Li, Chunling; Sun, Shuangqing; Hu, Songqing

2017-10-01

Dissipative particle dynamics (DPD) simulations were applied to investigate the coating repair agent dicyclopentadience (DCPD) in pH-sensitive micelles. The results show micelles self-assembled from triblock copolymers with strong hydrophobic interaction are not conducive to loading DCPD, and only micelles with weak interaction parameter can encapsulate DCPD well. After protonation, the structure of micelle was disassembled and DCPD beads have a stronger ability to shrink polymer chains and exposed to water. This work provides mesoscopic insight into self-assembly and disassembly of desired agent-loaded micelle, and might be useful for the design of new materials for agent delivery.

Systematic parameter inference in stochastic mesoscopic modeling

NASA Astrophysics Data System (ADS)

Lei, Huan; Yang, Xiu; Li, Zhen; Karniadakis, George Em

2017-02-01

We propose a method to efficiently determine the optimal coarse-grained force field in mesoscopic stochastic simulations of Newtonian fluid and polymer melt systems modeled by dissipative particle dynamics (DPD) and energy conserving dissipative particle dynamics (eDPD). The response surfaces of various target properties (viscosity, diffusivity, pressure, etc.) with respect to model parameters are constructed based on the generalized polynomial chaos (gPC) expansion using simulation results on sampling points (e.g., individual parameter sets). To alleviate the computational cost to evaluate the target properties, we employ the compressive sensing method to compute the coefficients of the dominant gPC terms given the prior knowledge that the coefficients are "sparse". The proposed method shows comparable accuracy with the standard probabilistic collocation method (PCM) while it imposes a much weaker restriction on the number of the simulation samples especially for systems with high dimensional parametric space. Fully access to the response surfaces within the confidence range enables us to infer the optimal force parameters given the desirable values of target properties at the macroscopic scale. Moreover, it enables us to investigate the intrinsic relationship between the model parameters, identify possible degeneracies in the parameter space, and optimize the model by eliminating model redundancies. The proposed method provides an efficient alternative approach for constructing mesoscopic models by inferring model parameters to recover target properties of the physics systems (e.g., from experimental measurements), where those force field parameters and formulation cannot be derived from the microscopic level in a straight forward way.

Parameterization of a mesoscopic model for the self-assembly of linear sodium alkyl sulfates

NASA Astrophysics Data System (ADS)

Mai, Zhaohuan; Couallier, Estelle; Rakib, Mohammed; Rousseau, Bernard

2014-05-01

A systematic approach to develop mesoscopic models for a series of linear anionic surfactants (CH3(CH2)n - 1OSO3Na, n = 6, 9, 12, 15) by dissipative particle dynamics (DPD) simulations is presented in this work. The four surfactants are represented by coarse-grained models composed of the same head group and different numbers of identical tail beads. The transferability of the DPD model over different surfactant systems is carefully checked by adjusting the repulsive interaction parameters and the rigidity of surfactant molecules, in order to reproduce key equilibrium properties of the aqueous micellar solutions observed experimentally, including critical micelle concentration (CMC) and average micelle aggregation number (Nag). We find that the chain length is a good index to optimize the parameters and evaluate the transferability of the DPD model. Our models qualitatively reproduce the essential properties of these surfactant analogues with a set of best-fit parameters. It is observed that the logarithm of the CMC value decreases linearly with the surfactant chain length, in agreement with Klevens' rule. With the best-fit and transferable set of parameters, we have been able to calculate the free energy contribution to micelle formation per methylene unit of -1.7 kJ/mol, very close to the experimentally reported value.

Counterintuitive cooperative endocytosis of like-charged nanoparticles in cellular internalization: computer simulation and experiment

NASA Astrophysics Data System (ADS)

Li, Ye; Yuan, Bing; Yang, Kai; Zhang, Xianren; Yan, Bing; Cao, Dapeng

2017-02-01

The nanoparticles (NPs) functionalized with charged ligands are of particular significance due to their potential drug/gene delivery and biomedical applications. However, the molecular mechanism of endocytosis of the charged NPs by cells, especially the effect of the NP-NP and NP-biomembrane interactions on the internalization pathways is still poorly understood. In this work, we systematically investigate the internalization behaviors of the positively charged NPs by combining experiment technology and dissipative particle dynamics (DPD) simulation. We experimentally find an interesting but highly counterintuitive phenomenon, i.e. the multiple positively charged NPs prefer to enter cells cooperatively although the like-charged NPs have obvious electrostatic repulsion. Furthermore, we adopt the DPD simulation to confirm the experimental findings, and reveal that the mechanism of the cooperative endocytosis between like-charged NPs is definitely caused by the interplay of particle size, the charged ligand density on particle surface and local concentration of NPs. Importantly, we not only observe the normal cooperative endocytosis of like-charged NPs in cell biomembrane like neutral NP case, but also predict the ‘bud’ cooperative endocytosis of like-charged NPs which is absence in the neutral NP case. The results indicate that electrostatic repulsion between the positively charged nanoparticles plays an important role in the ‘bud’ cooperative endocytosis of like-charged NPs.

A Direct Position-Determination Approach for Multiple Sources Based on Neural Network Computation.

PubMed

Chen, Xin; Wang, Ding; Yin, Jiexin; Wu, Ying

2018-06-13

The most widely used localization technology is the two-step method that localizes transmitters by measuring one or more specified positioning parameters. Direct position determination (DPD) is a promising technique that directly localizes transmitters from sensor outputs and can offer superior localization performance. However, existing DPD algorithms such as maximum likelihood (ML)-based and multiple signal classification (MUSIC)-based estimations are computationally expensive, making it difficult to satisfy real-time demands. To solve this problem, we propose the use of a modular neural network for multiple-source DPD. In this method, the area of interest is divided into multiple sub-areas. Multilayer perceptron (MLP) neural networks are employed to detect the presence of a source in a sub-area and filter sources in other sub-areas, and radial basis function (RBF) neural networks are utilized for position estimation. Simulation results show that a number of appropriately trained neural networks can be successfully used for DPD. The performance of the proposed MLP-MLP-RBF method is comparable to the performance of the conventional MUSIC-based DPD algorithm for various signal-to-noise ratios and signal power ratios. Furthermore, the MLP-MLP-RBF network is less computationally intensive than the classical DPD algorithm and is therefore an attractive choice for real-time applications.

Coarse-grained model of nanoscale segregation, water diffusion, and proton transport in Nafion membranes

NASA Astrophysics Data System (ADS)

Vishnyakov, Aleksey; Mao, Runfang; Lee, Ming-Tsung; Neimark, Alexander V.

2018-01-01

We present a coarse-grained model of the acid form of Nafion membrane that explicitly includes proton transport. This model is based on a soft-core bead representation of the polymer implemented into the dissipative particle dynamics (DPD) simulation framework. The proton is introduced as a separate charged bead that forms dissociable Morse bonds with water beads. Morse bond formation and breakup artificially mimics the Grotthuss hopping mechanism of proton transport. The proposed DPD model is parameterized to account for the specifics of the conformations and flexibility of the Nafion backbone and sidechains; it treats electrostatic interactions in the smeared charge approximation. The simulation results qualitatively, and in many respects quantitatively, predict the specifics of nanoscale segregation in the hydrated Nafion membrane into hydrophobic and hydrophilic subphases, water diffusion, and proton mobility. As the hydration level increases, the hydrophilic subphase exhibits a percolation transition from a collection of isolated water clusters to a 3D network of pores filled with water embedded in the hydrophobic matrix. The segregated morphology is characterized in terms of the pore size distribution with the average size growing with hydration from ˜1 to ˜4 nm. Comparison of the predicted water diffusivity with the experimental data taken from different sources shows good agreement at high and moderate hydration and substantial deviation at low hydration, around and below the percolation threshold. This discrepancy is attributed to the dynamic percolation effects of formation and rupture of merging bridges between the water clusters, which become progressively important at low hydration, when the coarse-grained model is unable to mimic the fine structure of water network that includes singe molecule bridges. Selected simulations of water diffusion are performed for the alkali metal substituted membrane which demonstrate the effects of the counter-ions on membrane self-assembly and transport. The hydration dependence of the proton diffusivity reproduces semi-qualitatively the trend of the diverse experimental data, showing a sharp decrease around the percolation threshold. Overall, the proposed model opens up an opportunity to study self-assembly and water and proton transport in polyelectrolytes using computationally efficient DPD simulations, and, with further refinement, it may become a practical tool for theory informed design and optimization of perm-selective and ion-conducting membranes with improved properties.

Systematic parameter inference in stochastic mesoscopic modeling

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

Lei, Huan; Yang, Xiu; Li, Zhen

2017-02-01

We propose a method to efficiently determine the optimal coarse-grained force field in mesoscopic stochastic simulations of Newtonian fluid and polymer melt systems modeled by dissipative particle dynamics (DPD) and energy conserving dissipative particle dynamics (eDPD). The response surfaces of various target properties (viscosity, diffusivity, pressure, etc.) with respect to model parameters are constructed based on the generalized polynomial chaos (gPC) expansion using simulation results on sampling points (e.g., individual parameter sets). To alleviate the computational cost to evaluate the target properties, we employ the compressive sensing method to compute the coefficients of the dominant gPC terms given the priormore » knowledge that the coefficients are “sparse”. The proposed method shows comparable accuracy with the standard probabilistic collocation method (PCM) while it imposes a much weaker restriction on the number of the simulation samples especially for systems with high dimensional parametric space. Fully access to the response surfaces within the confidence range enables us to infer the optimal force parameters given the desirable values of target properties at the macroscopic scale. Moreover, it enables us to investigate the intrinsic relationship between the model parameters, identify possible degeneracies in the parameter space, and optimize the model by eliminating model redundancies. The proposed method provides an efficient alternative approach for constructing mesoscopic models by inferring model parameters to recover target properties of the physics systems (e.g., from experimental measurements), where those force field parameters and formulation cannot be derived from the microscopic level in a straight forward way.« less

Structure and rheology of star polymers in confined geometries: a mesoscopic simulation study.

PubMed

Zheng, Feiwo; Goujon, Florent; Mendonça, Ana C F; Malfreyt, Patrice; Tildesley, Dominic J

2015-11-28

Mesoscopic simulations of star polymer melts adsorbed onto solid surfaces are performed using the dissipative particle dynamics (DPD) method. A set of parameters is developed to study the low functionality star polymers under shear. The use of a new bond-angle potential between the arms of the star creates more rigid chains and discriminates between different functionalities at equilibrium, but still allows the polymers to deform appropriately under shear. The rheology of the polymer melts is studied by calculating the kinetic friction and viscosity and there is good agreement with experimental properties of these systems. The study is completed with predictive simulations of star polymer solutions in an athermal solvent.

Degenerate pressure driven self-gravito-acoustic solitary waves in a self-gravitating degenerate quantum plasma system

NASA Astrophysics Data System (ADS)

Mamun, A. A.

2018-02-01

A general (but realistic) self-gravitating degenerate quantum plasma system (SG-DQPS) containing inertialess degenerate electron species, inertial degenerate light, and heavy ion/nucleus species is considered to examine the possibility for the existence of degenerate pressure driven self-gravito-acoustic (DPD-SGA) solitary waves (SWs) formed in such a SG-DQPS. The pseudo-potential approach, which is valid for the arbitrary amplitude DPD-SGA SWs, is employed. It is found that depending on the value of the number density of heavy ion/nucleus species, the SG-DQPS under consideration supports the existence of positive or the coexistence of positive and negative DPD-SGA SWs. The basic features (polarity, amplitude, and width) of both positive and negative DPD-SGA SWs are found to be significantly modified by the dynamics of heavy ion/nucleus species. The theoretical investigation presented here is so general that it can be applied not only in astrophysical SG-DQPSs (such as white dwarf and neutron star SG-DQPSs), but also in laboratory SG-DQPSs (viz., solid density and laser-produced SG-DQPSs) to identify the salient features of the DPD-SGA SWs formed in them.

Strong scaling of general-purpose molecular dynamics simulations on GPUs

NASA Astrophysics Data System (ADS)

Glaser, Jens; Nguyen, Trung Dac; Anderson, Joshua A.; Lui, Pak; Spiga, Filippo; Millan, Jaime A.; Morse, David C.; Glotzer, Sharon C.

2015-07-01

We describe a highly optimized implementation of MPI domain decomposition in a GPU-enabled, general-purpose molecular dynamics code, HOOMD-blue (Anderson and Glotzer, 2013). Our approach is inspired by a traditional CPU-based code, LAMMPS (Plimpton, 1995), but is implemented within a code that was designed for execution on GPUs from the start (Anderson et al., 2008). The software supports short-ranged pair force and bond force fields and achieves optimal GPU performance using an autotuning algorithm. We are able to demonstrate equivalent or superior scaling on up to 3375 GPUs in Lennard-Jones and dissipative particle dynamics (DPD) simulations of up to 108 million particles. GPUDirect RDMA capabilities in recent GPU generations provide better performance in full double precision calculations. For a representative polymer physics application, HOOMD-blue 1.0 provides an effective GPU vs. CPU node speed-up of 12.5 ×.

DPD simulation on the dynamics of a healthy and infected red blood cell in flow through a constricted channel

NASA Astrophysics Data System (ADS)

Hoque, Sazid Zamal; Anand, D. Vijay; Patnaik, B. S. V.

2017-11-01

The state of the red blood cell (either healthy or infected RBC) will influence its deformation dynamics. Since the pathological condition related to RBC, primarily originates from a single cell infection, therefore, it is important to relate the deformation dynamics to the mechanical properties (such as, bending rigidity and membrane elasticity). In the present study, numerical simulation of a healthy and malaria infected RBC in a constricted channel is analyzed. The flow simulations are carried out using finite sized dissipative particle dynamics (FDPD) method in conjunction with a discrete model that represents the membrane of the RBC. The numerical equivalent of optical tweezers test is validated against the experimental studies. Two different types of constrictions, viz., a converging-diverging type tapered channel and a stenosed microchannel are considered for the simulation. The effect of degree of constriction and the flow rate effect on the RBC is investigated. It was observed that, as the flow rate decreases, the infected RBC completely blocks the micro vessel. The transit time for infected cell drastically increases compared to healthy RBC. Our simulations indicate that, there is a critical flow rate below which infected RBC cannot pass through the micro capillary.

Computational studies on self-assembled paclitaxel structures: templates for hierarchical block copolymer assemblies and sustained drug release.

PubMed

Guo, Xin D; Tan, Jeremy P K; Kim, Sung H; Zhang, Li J; Zhang, Ying; Hedrick, James L; Yang, Yi Y; Qian, Yu

2009-11-01

Paclitaxel-loaded poly(ethylene oxide)-b-poly(lactide) (PEO-b-PLA) systems have been observed to assemble into fiber structures with remarkably different properties using different chirality and molecular weight of PLA segments. In this study, dissipative particle dynamics (DPD) simulations were carried out to elaborate the microstructures and properties of pure paclitaxel and paclitaxel-loaded PEO-b-PLA systems. Paclitaxel molecules formed ribbon or fiber like structures in water. With the addition of PEO-b-PDLA, PEO-b-PLLA and their stereocomplex, paclitaxel acted as a template and polymer molecules assembled around the paclitaxel structure to form core/shell structured fibers having a PEO shell. For PEO19-b-PDLA27 and PEO19-b-PLLA27 systems, PLA segments and paclitaxel molecules were distributed homogeneously in the core of fibers based on the hydrophobic interactions. In the stereocomplex formulation, paclitaxel molecules were more concentrated in the inner PLA stereocomplex core, which led to slower release of paclitaxel. By increasing the length of PLA segments (e.g. 8,16,22 and 27), the crystalline structure of paclitaxel was gradually weakened and destroyed, which was further proved by X-ray diffraction studies. All the simulation results agreed well with experimental data, suggesting that the DPD simulations may provide a powerful tool for designing drug delivery systems.

Multiscale Particle-Based Modeling of Flowing Platelets in Blood Plasma Using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics

PubMed Central

Zhang, Peng; Gao, Chao; Zhang, Na; Slepian, Marvin J.; Deng, Yuefan; Bluestein, Danny

2014-01-01

We developed a multiscale particle-based model of platelets, to study the transport dynamics of shear stresses between the surrounding fluid and the platelet membrane. This model facilitates a more accurate prediction of the activation potential of platelets by viscous shear stresses - one of the major mechanisms leading to thrombus formation in cardiovascular diseases and in prosthetic cardiovascular devices. The interface of the model couples coarse-grained molecular dynamics (CGMD) with dissipative particle dynamics (DPD). The CGMD handles individual platelets while the DPD models the macroscopic transport of blood plasma in vessels. A hybrid force field is formulated for establishing a functional interface between the platelet membrane and the surrounding fluid, in which the microstructural changes of platelets may respond to the extracellular viscous shear stresses transferred to them. The interaction between the two systems preserves dynamic properties of the flowing platelets, such as the flipping motion. Using this multiscale particle-based approach, we have further studied the effects of the platelet elastic modulus by comparing the action of the flow-induced shear stresses on rigid and deformable platelet models. The results indicate that neglecting the platelet deformability may overestimate the stress on the platelet membrane, which in turn may lead to erroneous predictions of the platelet activation under viscous shear flow conditions. This particle-based fluid-structure interaction multiscale model offers for the first time a computationally feasible approach for simulating deformable platelets interacting with viscous blood flow, aimed at predicting flow induced platelet activation by using a highly resolved mapping of the stress distribution on the platelet membrane under dynamic flow conditions. PMID:25530818

Direct Position Determination of Multiple Non-Circular Sources with a Moving Coprime Array.

PubMed

Zhang, Yankui; Ba, Bin; Wang, Daming; Geng, Wei; Xu, Haiyun

2018-05-08

Direct position determination (DPD) is currently a hot topic in wireless localization research as it is more accurate than traditional two-step positioning. However, current DPD algorithms are all based on uniform arrays, which have an insufficient degree of freedom and limited estimation accuracy. To improve the DPD accuracy, this paper introduces a coprime array to the position model of multiple non-circular sources with a moving array. To maximize the advantages of this coprime array, we reconstruct the covariance matrix by vectorization, apply a spatial smoothing technique, and converge the subspace data from each measuring position to establish the cost function. Finally, we obtain the position coordinates of the multiple non-circular sources. The complexity of the proposed method is computed and compared with that of other methods, and the Cramer⁻Rao lower bound of DPD for multiple sources with a moving coprime array, is derived. Theoretical analysis and simulation results show that the proposed algorithm is not only applicable to circular sources, but can also improve the positioning accuracy of non-circular sources. Compared with existing two-step positioning algorithms and DPD algorithms based on uniform linear arrays, the proposed technique offers a significant improvement in positioning accuracy with a slight increase in complexity.

Direct position determination for digital modulation signals based on improved particle swarm optimization algorithm

NASA Astrophysics Data System (ADS)

Yu, Wan-Ting; Yu, Hong-yi; Du, Jian-Ping; Wang, Ding

2018-04-01

The Direct Position Determination (DPD) algorithm has been demonstrated to achieve a better accuracy with known signal waveforms. However, the signal waveform is difficult to be completely known in the actual positioning process. To solve the problem, we proposed a DPD method for digital modulation signals based on improved particle swarm optimization algorithm. First, a DPD model is established for known modulation signals and a cost function is obtained on symbol estimation. Second, as the optimization of the cost function is a nonlinear integer optimization problem, an improved Particle Swarm Optimization (PSO) algorithm is considered for the optimal symbol search. Simulations are carried out to show the higher position accuracy of the proposed DPD method and the convergence of the fitness function under different inertia weight and population size. On the one hand, the proposed algorithm can take full advantage of the signal feature to improve the positioning accuracy. On the other hand, the improved PSO algorithm can improve the efficiency of symbol search by nearly one hundred times to achieve a global optimal solution.

A computational study of liposome logic: towards cellular computing from the bottom up

PubMed Central

Smaldon, James; Romero-Campero, Francisco J.; Fernández Trillo, Francisco; Gheorghe, Marian; Alexander, Cameron

2010-01-01

In this paper we propose a new bottom-up approach to cellular computing, in which computational chemical processes are encapsulated within liposomes. This “liposome logic” approach (also called vesicle computing) makes use of supra-molecular chemistry constructs, e.g. protocells, chells, etc. as minimal cellular platforms to which logical functionality can be added. Modeling and simulations feature prominently in “top-down” synthetic biology, particularly in the specification, design and implementation of logic circuits through bacterial genome reengineering. The second contribution in this paper is the demonstration of a novel set of tools for the specification, modelling and analysis of “bottom-up” liposome logic. In particular, simulation and modelling techniques are used to analyse some example liposome logic designs, ranging from relatively simple NOT gates and NAND gates to SR-Latches, D Flip-Flops all the way to 3 bit ripple counters. The approach we propose consists of specifying, by means of P systems, gene regulatory network-like systems operating inside proto-membranes. This P systems specification can be automatically translated and executed through a multiscaled pipeline composed of dissipative particle dynamics (DPD) simulator and Gillespie’s stochastic simulation algorithm (SSA). Finally, model selection and analysis can be performed through a model checking phase. This is the first paper we are aware of that brings to bear formal specifications, DPD, SSA and model checking to the problem of modeling target computational functionality in protocells. Potential chemical routes for the laboratory implementation of these simulations are also discussed thus for the first time suggesting a potentially realistic physiochemical implementation for membrane computing from the bottom-up. PMID:21886681

Multi-scale coarse-graining of non-conservative interactions in molecular liquids

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

Izvekov, Sergei, E-mail: sergiy.izvyekov.civ@mail.mil; Rice, Betsy M.

2014-03-14

A new bottom-up procedure for constructing non-conservative (dissipative and stochastic) interactions for dissipative particle dynamics (DPD) models is described and applied to perform hierarchical coarse-graining of a polar molecular liquid (nitromethane). The distant-dependent radial and shear frictions in functional-free form are derived consistently with a chosen form for conservative interactions by matching two-body force-velocity and three-body velocity-velocity correlations along the microscopic trajectories of the centroids of Voronoi cells (clusters), which represent the dissipative particles within the DPD description. The Voronoi tessellation is achieved by application of the K-means clustering algorithm at regular time intervals. Consistently with a notion of many-bodymore » DPD, the conservative interactions are determined through the multi-scale coarse-graining (MS-CG) method, which naturally implements a pairwise decomposition of the microscopic free energy. A hierarchy of MS-CG/DPD models starting with one molecule per Voronoi cell and up to 64 molecules per cell is derived. The radial contribution to the friction appears to be dominant for all models. As the Voronoi cell sizes increase, the dissipative forces rapidly become confined to the first coordination shell. For Voronoi cells of two and more molecules the time dependence of the velocity autocorrelation function becomes monotonic and well reproduced by the respective MS-CG/DPD models. A comparative analysis of force and velocity correlations in the atomistic and CG ensembles indicates Markovian behavior with as low as two molecules per dissipative particle. The models with one and two molecules per Voronoi cell yield transport properties (diffusion and shear viscosity) that are in good agreement with the atomistic data. The coarser models produce slower dynamics that can be appreciably attributed to unaccounted dissipation introduced by regular Voronoi re-partitioning as well as by larger numerical errors in mapping out the dissipative forces. The framework presented herein can be used to develop computational models of real liquids which are capable of bridging the atomistic and mesoscopic scales.« less

Shear-induced aggregation or disaggregation in edible oils: Models, computer simulation, and USAXS measurements

NASA Astrophysics Data System (ADS)

Townsend, B.; Peyronel, F.; Callaghan-Patrachar, N.; Quinn, B.; Marangoni, A. G.; Pink, D. A.

2017-12-01

The effects of shear upon the aggregation of solid objects formed from solid triacylglycerols (TAGs) immersed in liquid TAG oils were modeled using Dissipative Particle Dynamics (DPD) and the predictions compared to experimental data using Ultra-Small Angle X-ray Scattering (USAXS). The solid components were represented by spheres interacting via attractive van der Waals forces and short range repulsive forces. A velocity was applied to the liquid particles nearest to the boundary, and Lees-Edwards boundary conditions were used to transmit this motion to non-boundary layers via dissipative interactions. The shear was created through the dissipative forces acting between liquid particles. Translational diffusion was simulated, and the Stokes-Einstein equation was used to relate DPD length and time scales to SI units for comparison with USAXS results. The SI values depended on how large the spherical particles were (250 nm vs. 25 nm). Aggregation was studied by (a) computing the Structure Function and (b) quantifying the number of pairs of solid spheres formed. Solid aggregation was found to be enhanced by low shear rates. As the shear rate was increased, a transition shear region was manifested in which aggregation was inhibited and shear banding was observed. Aggregation was inhibited, and eventually eliminated, by further increases in the shear rate. The magnitude of the transition region shear, γ˙ t, depended on the size of the solid particles, which was confirmed experimentally.

Modeling of Red Blood Cells and Related Spleen Function

NASA Astrophysics Data System (ADS)

Peng, Zhangli; Pivkin, Igor; Dao, Ming

2011-11-01

A key function of the spleen is to clear red blood cells (RBCs) with abnormal mechanical properties from the circulation. These abnormal mechanical properties may be due to RBC aging or RBC diseases, e.g., malaria and sickle cell anemia. Specifically, 10% of RBCs passing through the spleen are forced to squeeze into the narrow slits between the endothelial cells, and stiffer cells which get stuck are killed and digested by macrophages. To investigate this important physiological process, we employ three different approaches to study RBCs passage through these small slits, including analytical theory, Dissipative Particle Dynamics (DPD) simulation and Multiscale Finite Element Method (MS-FEM). By applying the analytical theory, we estimate the critical limiting geometries RBCs can pass. By using the DPD method, we study the full fluid-structure interaction problem, and compute RBC deformation under different pressure gradients. By employing the MS-FEM approach, we model the lipid bilayer and the cytoskeleton as two distinct layers, and focus on the cytoskeleton deformation and the bilayer-skeleton interaction force at the molecular level. Finally the results of these three approaches are compared to each other and correlated to the experimental observations.

Equilibrium Field Theoretic and Dynamic Mean Field Simulations of Inhomogeneous Polymeric Materials

NASA Astrophysics Data System (ADS)

Chao, Huikuan

Inhomogeneous polymeric materials is a large family of promising materials including but limited to block copolymers (BCPs), polymer nanocomposites (PNCs) and microscopically confined polymer films. The promising application of the materials originates from the materials' unique microstructures, which offer enhanced mechanical, thermal, optical and electrical properties to the materials. Due to the complex interactions and the large parameter space, behaviors of the microstructures formed by grafted nanoparticles and nanorods in PNCs are difficult to understand. Separately, because of relatively weak interactions, the microstructures are typically achieved through rapid processing that are kinetically controlled and beyond equilibrium. However, efficient simulation framework to study nonequilbrium dynamics of the materials is currently not available. To attack the first difficulty, I extended an efficient simulation framework, polymer nanocomposite field theory (PNC-FT), to incorporate grafted nanoparticles and nanorods. This extended framework is demonstrated against existing experimental studies and implemented to study how the nanoparticle design affects the nanoparticle distribution in binary homopolymer blends. The grafted nanoparticle model is also used as a platform to adopt an advanced optimization method to inversely design nanoparticles which are able to self-assemble into targeted two dimensional lattices. The nanorod model under PNC-FT framework is used to investigate the design of nanorod and block copolymer thin films to control the nanorod distribution. To attack the second difficulty, I established an efficient framework (SCMF-LD) based on a recently proposed dynamic mean field theory and used SCMF-LD to study how to kinetically control the nanoparticle distribution at the end of solvent annealing block copolymer thin films. The framework is then extended to incorporate hydrodynamics (SCMF-DPD) and the extended framework is implemented to study morphology development in phase inversion processing polymer thin films, where hydrodynamic effects play an important role. By exploring both equilibrium and nonequilibrium properties in a spectrum of inhomogeneous polymeric material systems, I successfully extended PNC-FT and established SCMF-LD and SCMF-DPD frameworks, which are expected to be efficient and powerful tools in studies of inhomogeneous polymeric material design and processing.

Structural evolution of Colloidal Gels under Flow

NASA Astrophysics Data System (ADS)

Boromand, Arman; Maia, Joao; Jamali, Safa

Colloidal suspensions are ubiquitous in different industrial applications ranging from cosmetic and food industries to soft robotics and aerospace. Owing to the fact that mechanical properties of colloidal gels are controlled by its microstructure and network topology, we trace the particles in the networks formed under different attraction potentials and try to find a universal behavior in yielding of colloidal gels. Many authors have implemented different simulation techniques such as molecular dynamics (MD) and Brownian dynamics (BD) to capture better picture during phase separation and yielding mechanism in colloidal system with short-ranged attractive force. However, BD neglects multi-body hydrodynamic interactions (HI) which are believed to be responsible for the second yielding of colloidal gels. We envision using dissipative particle dynamics (DPD) with modified depletion potential and hydrodynamic interactions, as a coarse-grain model, can provide a robust simulation package to address the gel formation process and yielding in short ranged-attractive colloidal systems. The behavior of colloidal gels with different attraction potentials under flow is examined and structural fingerprints of yielding in these systems will be discussed.

PLLA-PHB fiber membranes obtained by solvent-free electrospinning for short-time drug delivery.

PubMed

Cao, K; Liu, Y; Olkhov, A A; Siracusa, V; Iordanskii, A L

2018-02-01

Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite. The interactions between PLLA and PHB mainly occurred at a proportion of 7:3, and drug encapsulation in the fibers was verified. The kinetic profiles of drug release demonstrated the predominant multiple patterns involving a diffusional stage in the short-term mode of release and kinetic process related to the hydrolysis of the biopolymers. Furthermore, the dynamic behavior of the polymer molecules was evaluated based on the segmental mobility using probe electron spin resonance spectroscopy. The segmental mobility in the amorphous fraction of PLLA decreased with increasing PLLA content. The 9:1 PLLA/PHB system was more resistant to polymer hydrolysis than to the 7:3 system and the rate of diffusion transport was approximately two times higher for the 7:3 PLLA/PHB fibers than for the 9:1 PLLA/PHB fibers.

Multiscale Modeling of Primary Cilium Deformations Under Local Forces and Shear Flows

NASA Astrophysics Data System (ADS)

Peng, Zhangli; Feng, Zhe; Resnick, Andrew; Young, Yuan-Nan

2017-11-01

We study the detailed deformations of a primary cilium under local forces and shear flows by developing a multiscale model based on the state-of-the-art understanding of its molecular structure. Most eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, thermosensation, and mechanosensation, but the detailed mechanism for mechanosensation is not well understood. We apply the dissipative particle dynamics (DPD) to model an entire well with a primary cilium and consider its different components, including the basal body, microtubule doublets, actin cortex, and lipid bilayer. We calibrate the mechanical properties of individual components and their interactions from experimental measurements and molecular dynamics simulations. We validate the simulations by comparing the deformation profile of the cilium and the rotation of the basal body with optical trapping experiments. After validations, we investigate the deformation of the primary cilium under shear flows. Furthermore, we calculate the membrane tensions and cytoskeleton stresses, and use them to predict the activation of mechanosensitive channels.

Molecular and mesoscopic study of ionic liquids and their use as solvents of active agents released by polymeric vehicles

NASA Astrophysics Data System (ADS)

Ramos-Rodríguez, Daniel-Apolinar; Rodríguez-Hidalgo, María-del-Rosario; Soto-Figueroa, César; Vicente, Luis

2010-03-01

This work explores the diffusivity of the drug albendazole contained in a polymeric vehicle, Styrene-Divinylbenzene (ST-DVD), when it is subject to different environments. The environments consist of water and three different ionic liquids. First, the solubility parameters of these ionic liquids, [BMIM][PF6], [HMIM][Br] and [BMIM][BF4], and albendazole were evaluated by means of molecular dynamics employing COMPASS force-field and a NPT ensemble at 298 K. Then a mesoscopic simulation using Dissipative Particle Dynamics (DPD) was used. In the presence of ionic liquids the albendazole exhibits a diffusivity in [BMIM][PF6] around ten times that shown in [BMIM][BF4] or [HMIM][Br]. This is connected with the corresponding solvent power. The results obtained from these molecular and mesoscopic simulations are consistent with reported experimental results and are useful to predict and evaluate the solvent power of ionic liquids applied to drugs of pharmaceutical use.

Coarse-Grained Models for Automated Fragmentation and Parametrization of Molecular Databases.

PubMed

Fraaije, Johannes G E M; van Male, Jan; Becherer, Paul; Serral Gracià, Rubèn

2016-12-27

We calibrate coarse-grained interaction potentials suitable for screening large data sets in top-down fashion. Three new algorithms are introduced: (i) automated decomposition of molecules into coarse-grained units (fragmentation); (ii) Coarse-Grained Reference Interaction Site Model-Hypernetted Chain (CG RISM-HNC) as an intermediate proxy for dissipative particle dynamics (DPD); and (iii) a simple top-down coarse-grained interaction potential/model based on activity coefficient theories from engineering (using COSMO-RS). We find that the fragment distribution follows Zipf and Heaps scaling laws. The accuracy in Gibbs energy of mixing calculations is a few tenths of a kilocalorie per mole. As a final proof of principle, we use full coarse-grained sampling through DPD thermodynamics integration to calculate log P OW for 4627 compounds with an average error of 0.84 log unit. The computational speeds per calculation are a few seconds for CG RISM-HNC and a few minutes for DPD thermodynamic integration.

Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.

PubMed

Shen, Xiao-Ming; Zhou, Chong; Lian, Lian; Li, Li-Qun; Li, Wei; Tao, Min

2015-04-01

The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC) patients to see whether these enzymes affected the patients' response to S-1-based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA expressions were determined in 40 AGC patients using RT-PCR. The patients were then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were recorded. The relationship between the DPD/TS mRNA expressions and the chemotherapy response, drug resistance, and prognosis was analyzed. The data show that DPD mRNA expression correlated significantly with Lauren type while TS mRNA expression correlated with distant metastasis. Patients with higher DPD and/or TS mRNA expression(s) showed poor response, while those with low DPD mRNA expression showed better response to the chemotherapy. Pooled analysis showed that the patients with low DPD/TS mRNA expressions had better therapeutic response. The incidence of bone marrow suppression, diarrhea, and oral mucositis was high in patients with low DPD mRNA expression. Median overall survival (OS) in 40 patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.

Blood-plasma separation in Y-shaped bifurcating microfluidic channels: A dissipative particle dynamics simulation study

PubMed Central

Li, Xuejin; Popel, Aleksander S.; Karniadakis, George Em

2012-01-01

The motion of a suspension of red blood cells (RBCs) flowing in a Y-shaped bifurcating microfluidic channel is investigated using a validated low-dimensional RBC (LD-RBC) model based on dissipative particle dynamics (DPD). Specifically, the RBC is represented as a closed torus-like ring of ten colloidal particles, which leads to efficient simulations of blood flow in microcirculation over a wide range of hematocrits. Adaptive no-slip wall boundary conditions were implemented to model hydrodynamic flow within a specific wall structure of diverging 3D microfluidic channels, paying attention to controlling density fluctuations. Plasma skimming and the all-or-nothing phenomenon of RBCs in a bifurcating microfluidic channel have been investigated in our simulations for healthy and diseased blood, including the size of cell-free layer on the daughter branches. The feed hematocrit level in the parent channel has considerable influence on blood-plasma separation. Compared to the blood-plasma separation efficiencies of healthy RBCs, malaria-infected stiff RBCs (iRBCs) have a tendency to travel into the low flowrate daughter branch because of their different initial distribution in the parent channel. Our simulation results are consistent with previously published experimental results and theoretical predictions. PMID:22476709

A mesoscopic bridging scale method for fluids and coupling dissipative particle dynamics with continuum finite element method

PubMed Central

Kojic, Milos; Filipovic, Nenad; Tsuda, Akira

2012-01-01

A multiscale procedure to couple a mesoscale discrete particle model and a macroscale continuum model of incompressible fluid flow is proposed in this study. We call this procedure the mesoscopic bridging scale (MBS) method since it is developed on the basis of the bridging scale method for coupling molecular dynamics and finite element models [G.J. Wagner, W.K. Liu, Coupling of atomistic and continuum simulations using a bridging scale decomposition, J. Comput. Phys. 190 (2003) 249–274]. We derive the governing equations of the MBS method and show that the differential equations of motion of the mesoscale discrete particle model and finite element (FE) model are only coupled through the force terms. Based on this coupling, we express the finite element equations which rely on the Navier–Stokes and continuity equations, in a way that the internal nodal FE forces are evaluated using viscous stresses from the mesoscale model. The dissipative particle dynamics (DPD) method for the discrete particle mesoscale model is employed. The entire fluid domain is divided into a local domain and a global domain. Fluid flow in the local domain is modeled with both DPD and FE method, while fluid flow in the global domain is modeled by the FE method only. The MBS method is suitable for modeling complex (colloidal) fluid flows, where continuum methods are sufficiently accurate only in the large fluid domain, while small, local regions of particular interest require detailed modeling by mesoscopic discrete particles. Solved examples – simple Poiseuille and driven cavity flows illustrate the applicability of the proposed MBS method. PMID:23814322

Analysis of structure and dynamics of superfine polyhydroxybutyrate fibers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Olkhov, A.; Kucherenko, E.; Pantyukhov, P.; Zykova, A.; Karpova, S.; Iordanskii, A.

2017-02-01

Creation of polymer matrix systems for targeted drug delivery into a living organism is a challenging problem of modern treatment of various diseases and injuries. Poly-3-hydroxybutyrate (PHB) is commonly used for development of therapeutic systems. The aim of this article is to examine the changes in structure and morphology of fibers in presence of dipyridamole (DPD) as model drug for controlled release. It was found that addition of dipyridamole led to disappearance of spindle-shaped nodules on fibers of PHB in comparison with pure PHB. The research of thermophysical parameters showed that specific melting enthalpy (and the degree of crystallinity) of PHB fibers increased with the addition of DPD. With the increasing of DPD content in PHB fibers, more perfect and equilibrium crystal structure was formed. According to analysis of intercrystalline regions of PHB fibers, it was found that as the crystallinity of PHB in intergranular regions rose, the corresponding decrease of radical rotation speed was observed. It was concluded that fibers of PHB can be used for creating therapeutic systems for targeted and prolonged drug delivery.

Morphological Evolution of Block Copolymer Particles: Effect of Solvent Evaporation Rate on Particle Shape and Morphology.

PubMed

Shin, Jae Man; Kim, YongJoo; Yun, Hongseok; Yi, Gi-Ra; Kim, Bumjoon J

2017-02-28

Shape and morphology of polymeric particles are of great importance in controlling their optical properties or self-assembly into unusual superstructures. Confinement of block copolymers (BCPs) in evaporative emulsions affords particles with diverse structures, including prolate ellipsoids, onion-like spheres, oblate ellipsoids, and others. Herein, we report that the evaporation rate of solvent from emulsions encapsulating symmetric polystyrene-b-polybutadiene (PS-b-PB) determines the shape and internal nanostructure of micron-sized BCP particles. A distinct morphological transition from the ellipsoids with striped lamellae to the onion-like spheres was observed with decreasing evaporation rate. Experiments and dissipative particle dynamics (DPD) simulations showed that the evaporation rate affected the organization of BCPs at the particle surface, which determined the final shape and internal nanostructure of the particles. Differences in the solvent diffusion rates in PS and PB at rapid evaporation rates induced alignment of both domains perpendicular to the particle surface, resulting in ellipsoids with axial lamellar stripes. Slower evaporation rates provided sufficient time for BCP organization into onion-like structures with PB as the outermost layer, owing to the preferential interaction of PB with the surroundings. BCP molecular weight was found to influence the critical evaporation rate corresponding to the morphological transition from ellipsoid to onion-like particles, as well as the ellipsoid aspect ratio. DPD simulations produced morphologies similar to those obtained from experiments and thus elucidated the mechanism and driving forces responsible for the evaporation-induced assembly of BCPs into particles with well-defined shapes and morphologies.

Predicting dynamics and rheology of blood flow: A comparative study of multiscale and low-dimensional models of red blood cells

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

Pan, Wenxiao; Fedosov, Dmitry A.; Caswell, Bruce

In this work we compare the predictive capability of two mathematical models for red blood cells (RBCs) focusing on blood flow in capillaries and arterioles. Both RBC models as well as their corresponding blood flows are based on the dissipative particle dynamics (DPD) method, a coarse-grained molecular dynamics approach. The first model employs a multiscale description of the RBC (MS-RBC), with its membrane represented by hundreds or even thousands of DPD-particles connected by springs into a triangular network in combination with out-of-plane elastic bending resistance. Extra dissipation within the network accounts for membrane viscosity, while the characteristic biconcave RBC shapemore » is achieved by imposition of constraints for constant membrane area and constant cell volume. The second model is based on a low-dimensional description (LD-RBC) constructed as a closed torus-like ring of only 10 large DPD colloidal particles. They are connected into a ring by worm-like chain (WLC) springs combined with bending resistance. The LD-RBC model can be fitted to represent the entire range of nonlinear elastic deformations as measured by optical-tweezers for healthy and for infected RBCs in malaria. MS-RBCs suspensions model the dynamics and rheology of blood flow accurately for any size vessel but this approach is computationally expensive above 100 microns. Surprisingly, the much more economical suspensions of LD-RBCs also capture the blood flow dynamics and rheology accurately except for vessels with sizes comparable to RBC diameter. In particular, the LD-RBC suspensions are shown to properly capture the experimental data for the apparent viscosity of blood and its cell-free layer (CFL) in tube flow. Taken together, these findings suggest a hierarchical approach in modeling blood flow in the arterial tree, whereby the MS-RBC model should be employed for capillaries and arterioles below 100 microns, the LD-RBC model for arterioles, and the continuum description for arteries.« less

Effect of Sodium Dodecyl Sulfate Adsorption on the Behavior of Water inside Single Walled Carbon Nanotubes with Dissipative Particle Dynamics Simulation.

PubMed

Vo, Minh D; Papavassiliou, Dimitrios V

2016-04-15

Dissipative particle dynamics (DPD) simulations were utilized to investigate the ability of sodium dodecyl sulfate (SDS) to adsorb inside a single-walled, arm-chair carbon nanotube (SWCNT), as well as the effect of surfactant on the properties of water inside the SWCNT. The diameter of the SWCNT varied from 1 to 5 nm. The radial and axial density profiles of water inside the SWCNTs were computed and compared with published molecular dynamics results. The average residence time and diffusivity were also calculated to show the size effect on mobility of water inside the SWCNT. It was found that nanotubes with diameter smaller than 3 nm do not allow SDS molecules to enter the SWCNT space. For larger SWCNT diameter, SDS adsorbed inside and outside the nanotube. When SDS was adsorbed in the hollow part of the SWCNT, the behavior of water inside the nanotube was found to be significantly changed. Both radial and axial density profiles of water inside the SWCNT fluctuated strongly and were different from those in bulk phase. In addition, SDS molecules increased the retention of water beads inside SWCNT (d ≥ 3nm) while water diffusivity was decreased.

Mesoscopic Modeling of Blood Clotting: Coagulation Cascade and Platelets Adhesion

NASA Astrophysics Data System (ADS)

Yazdani, Alireza; Li, Zhen; Karniadakis, George

2015-11-01

The process of clot formation and growth at a site on a blood vessel wall involve a number of multi-scale simultaneous processes including: multiple chemical reactions in the coagulation cascade, species transport and flow. To model these processes we have incorporated advection-diffusion-reaction (ADR) of multiple species into an extended version of Dissipative Particle Dynamics (DPD) method which is considered as a coarse-grained Molecular Dynamics method. At the continuum level this is equivalent to the Navier-Stokes equation plus one advection-diffusion equation for each specie. The chemistry of clot formation is now understood to be determined by mechanisms involving reactions among many species in dilute solution, where reaction rate constants and species diffusion coefficients in plasma are known. The role of blood particulates, i.e. red cells and platelets, in the clotting process is studied by including them separately and together in the simulations. An agonist-induced platelet activation mechanism is presented, while platelets adhesive dynamics based on a stochastic bond formation/dissociation process is included in the model.

Comparison of prototypic cases of depressive personality disorder and dysthymic disorder.

PubMed

Sprock, June; Fredendall, Laura

2008-12-01

Although depressive personality disorder (DPD) was included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994) appendix as a proposed category needing further research, there are concerns that it overlaps excessively with dysthymic disorder (DD). The purpose of this investigation was to identify the characteristic features of representative patients with DPD and patients with DD, and to determine whether they could be distinguished by their symptoms. Two matched samples of psychologists (n=57, n=48) identified a prototypic patient with DPD or DD, provided demographic and treatment information about the patient, and rated the patient's symptoms on a series of mood and personality disorder symptoms taken from the DSM-IV and the literature. When composite descriptions were constructed using the highest rated symptoms, there was considerable overlap in symptoms of identified DPD and DD patients. The DSM-IV research criteria for DPD provided the best description of the DPD patients; however, there was a high degree of correlation between DPD and DD criteria sets. There was also considerable comorbidity, with the majority of the patients in both groups meeting criteria for DPD and DD. However, there was a significant difference in comorbid diagnoses (and other differences in family history, outcome, and treatment history that failed to reach the more stringent level of statistical significance, i.e., p<.001) suggesting that there may be some important differences between DPD and DD. Nevertheless, the symptom ratings imply blurred boundaries between DPD and DD, suggesting the need for clearer differentiation between the two disorders or the need to adopt an alternative model of classification. (c) 2008 Wiley Periodicals, Inc.

Human spleen and red blood cells

NASA Astrophysics Data System (ADS)

Pivkin, Igor; Peng, Zhangli; Karniadakis, George; Buffet, Pierre; Dao, Ming

2016-11-01

Spleen plays multiple roles in the human body. Among them is removal of old and altered red blood cells (RBCs), which is done by filtering cells through the endothelial slits, small micron-sized openings. There is currently no experimental technique available that allows us to observe RBC passage through the slits. It was previously noticed that people without a spleen have less deformable red blood cells, indicating that the spleen may play a role in defining the size and shape of red blood cells. We used detailed RBC model implemented within the Dissipative Particle Dynamics (DPD) simulation framework to study the filter function of the spleen. Our results demonstrate that spleen indeed plays major role in defining the size and shape of the healthy human red blood cells.

Spatial averaging of a dissipative particle dynamics model for active suspensions

NASA Astrophysics Data System (ADS)

Panchenko, Alexander; Hinz, Denis F.; Fried, Eliot

2018-03-01

Starting from a fine-scale dissipative particle dynamics (DPD) model of self-motile point particles, we derive meso-scale continuum equations by applying a spatial averaging version of the Irving-Kirkwood-Noll procedure. Since the method does not rely on kinetic theory, the derivation is valid for highly concentrated particle systems. Spatial averaging yields stochastic continuum equations similar to those of Toner and Tu. However, our theory also involves a constitutive equation for the average fluctuation force. According to this equation, both the strength and the probability distribution vary with time and position through the effective mass density. The statistics of the fluctuation force also depend on the fine scale dissipative force equation, the physical temperature, and two additional parameters which characterize fluctuation strengths. Although the self-propulsion force entering our DPD model contains no explicit mechanism for aligning the velocities of neighboring particles, our averaged coarse-scale equations include the commonly encountered cubically nonlinear (internal) body force density.

Depersonalization Disorder: Disconnection of Cognitive Evaluation from Autonomic Responses to Emotional Stimuli

PubMed Central

Michal, Matthias; Koechel, Ansgar; Canterino, Marco; Adler, Julia; Reiner, Iris; Vossel, Gerhard; Beutel, Manfred E.; Gamer, Matthias

2013-01-01

Background Patients with depersonalization disorder (DPD) typically complain about emotional detachment. Previous studies found reduced autonomic responsiveness to emotional stimuli for DPD patients as compared to patients with anxiety disorders. We aimed to investigate autonomic responsiveness to emotional auditory stimuli of DPD patients as compared to patient controls. Furthermore, we examined the modulatory effect of mindful breathing on these responses as well as on depersonalization intensity. Methods 22 DPD patients and 15 patient controls balanced for severity of depression and anxiety, age, sex and education, were compared regarding 1) electrodermal and heart rate data during a resting period, and 2) autonomic responses and cognitive appraisal of standardized acoustic affective stimuli in two conditions (normal listening and mindful breathing). Results DPD patients rated the emotional sounds as significantly more neutral as compared to patient controls and standardized norm ratings. At the same time, however, they responded more strongly to acoustic emotional stimuli and their electrodermal response pattern was more modulated by valence and arousal as compared to patient controls. Mindful breathing reduced severity of depersonalization in DPD patients and increased the arousal modulation of electrodermal responses in the whole sample. Finally, DPD patients showed an increased electrodermal lability in the rest period as compared to patient controls. Conclusions These findings demonstrated that the cognitive evaluation of emotional sounds in DPD patients is disconnected from their autonomic responses to those emotional stimuli. The increased electrodermal lability in DPD may reflect increased introversion and cognitive control of emotional impulses. The findings have important psychotherapeutic implications. PMID:24058547

Effect of graphite particle size and content on the formation mechanism of detonation polycrystalline diamond

NASA Astrophysics Data System (ADS)

Tong, Y.; Cao, Y.; Liu, R.; Shang, S. Y.; Huang, F. L.

2018-03-01

The formation mechanism of detonation polycrystalline diamond (DPD) generated from the detonation of a mixed RDX/graphite explosive is investigated. It is found experimentally that the DPD conversion rate decreases with both the content and the particle size of the graphite. Moreover, the particle sizes of the generated DPD powder are analyzed, which shows that, with the decrease in the graphite particle size, the mean number diameter of DPD decreases, but the mean volume diameter increases. In addition, with the help of scanning electron microscopy, it is observed that the in situ phase change occurs in the graphite particles, by which the small particles combine to form numerous large DPD particles. Based on both the experimental data and the classical ZND detonation model, we divide such a DPD synthesis process into two stages: In the first stage, the in situ phase change from graphite to diamond is dominant, supplemented by some coalescence growth at high pressure and temperature, which is affected mainly by the detonation performance of the mixed explosive under consideration. In the second stage, the graphitization of DPD caused by the residual heat is dominant, which is affected mainly by the unloading rate of the particle temperature.

Depressive personality disorder, dysthymia, and their relationship to perfectionism.

PubMed

Huprich, Steven K; Porcerelli, John; Keaschuk, Rachel; Binienda, Juliann; Engle, Benjamin

2008-01-01

This paper reports the results of two studies in a nonclinical (n=105) and primary care outpatient sample (n=110), in which Depressive Personality Disorder (DPD), Dysthymia, and depression were assessed for their distinctive relationship with perfectionism. Results from both studies found that self-reported DPD, Dysthymia, and depressive symptoms were all intercorrelated, and that DPD, Dysthymia, and depressive symptoms were correlated with three dimensions of perfectionism-Concern over Mistakes, Doubts about Actions, and Parental Criticism. In the nonclinical sample, variance in measures of DPD was predicted by measures of perfectionism after controlling for depression and Dysthymia symptoms. A similar pattern of findings was observed in the primary care sample. This relationship with perfectionism did not occur when Dysthymia or depressive symptoms were predicted. Nevertheless, much of the variance in measures of DPD, Dysthymia, and depressive symptoms is associated with each other and not perfectionism. It is concluded that a common factor or set of factors underlies these disorders, but that DPD may be more strongly related to perfectionism than Dysthymia and depression. As a common factor(s) is identified, measures of DPD and Dysthymia may be refined, thereby increasing the discriminant validity of their measures.

Computational Biorheology of Human Blood Flow in Health and Disease

PubMed Central

Fedosov, Dmitry A.; Dao, Ming; Karniadakis, George Em; Suresh, Subra

2014-01-01

Hematologic disorders arising from infectious diseases, hereditary factors and environmental influences can lead to, and can be influenced by, significant changes in the shape, mechanical and physical properties of red blood cells (RBCs), and the biorheology of blood flow. Hence, modeling of hematologic disorders should take into account the multiphase nature of blood flow, especially in arterioles and capillaries. We present here an overview of a general computational framework based on dissipative particle dynamics (DPD) which has broad applicability in cell biophysics with implications for diagnostics, therapeutics and drug efficacy assessments for a wide variety of human diseases. This computational approach, validated by independent experimental results, is capable of modeling the biorheology of whole blood and its individual components during blood flow so as to investigate cell mechanistic processes in health and disease. DPD is a Lagrangian method that can be derived from systematic coarse-graining of molecular dynamics but can scale efficiently up to arterioles and can also be used to model RBCs down to the spectrin level. We start from experimental measurements of a single RBC to extract the relevant biophysical parameters, using single-cell measurements involving such methods as optical tweezers, atomic force microscopy and micropipette aspiration, and cell-population experiments involving microfluidic devices. We then use these validated RBC models to predict the biorheological behavior of whole blood in healthy or pathological states, and compare the simulations with experimental results involving apparent viscosity and other relevant parameters. While the approach discussed here is sufficiently general to address a broad spectrum of hematologic disorders including certain types of cancer, this paper specifically deals with results obtained using this computational framework for blood flow in malaria and sickle cell anemia. PMID:24419829

GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO THE CO-OCCURRENCE OF DEPRESSIVE PERSONALITY DISORDER AND DSM-IV PERSONALITY DISORDERS

PubMed Central

Ørstavik, Ragnhild E.; Kendler, Kenneth S.; Røysamb, Espen; Czajkowski, Nikolai; Tambs, Kristian; Reichborn-Kjennerud, Ted

2012-01-01

One of the main controversies with regard to depressive personality disorder (DPD) concerns the co-occurrence with the established DSM-IV personality disorders (PDs). The main aim of this study was to examine to what extent DPD and the DSM-IV PDs share genetic and environmental risk factors, using multivariate twin modeling. The DSM-IV Structured Interview for Personality was applied to 2,794 young adult twins. Paranoid PD from Cluster A, borderline PD from Cluster B, and all three PDs from Cluster C were independently and significantly associated with DPD in multiple regression analysis. The genetic correlations between DPD and the other PDs were strong (.53–.83), while the environmental correlations were moderate (.36–.40). Close to 50% of the total variance in DPD was disorder specific. However, only 5% was due to disorder-specific genetic factors, indicating that a substantial part of the genetic vulnerability to DPD also increases the vulnerability to other PDs. PMID:22686231

Genetic and environmental contributions to the co-occurrence of depressive personality disorder and DSM-IV personality disorders.

PubMed

Ørstavik, Ragnhild E; Kendler, Kenneth S; Røysamb, Espen; Czajkowski, Nikolai; Tambs, Kristian; Reichborn-Kjennerud, Ted

2012-06-01

One of the main controversies with regard to depressive personality disorder (DPD) concerns the co-occurrence with the established DSM-IV personality disorders (PDs). The main aim of this study was to examine to what extent DPD and the DSM-IV PDs share genetic and environmental risk factors, using multivariate twin modeling. The DSM-IV Structured Interview for Personality was applied to 2,794 young adult twins. Paranoid PD from Cluster A, borderline PD from Cluster B, and all three PDs from Cluster C were independently and significantly associated with DPD in multiple regression analysis. The genetic correlations between DPD and the other PDs were strong (.53-.83), while the environmental correlations were moderate (.36-.40). Close to 50% of the total variance in DPD was disorder specific. However, only 5% was due to disorder-specific genetic factors, indicating that a substantial part of the genetic vulnerability to DPD also increases the vulnerability to other PDs.

Implicit Self-Esteem in Borderline Personality and Depersonalization Disorder

PubMed Central

Hedrick, Alexis N.; Berlin, Heather A.

2012-01-01

Self-perception is disrupted in people with borderline personality disorder (BPD) and depersonalization disorder (DPD), fluctuating with sudden shifts in affect in BPD and experienced as detached in DPD. Measures of implicit self-esteem (ISE), free from conscious control and presentation biases, may highlight how such disruptions of self-concept differentially affect these two populations on an unconscious level. We examined ISE using the Implicit Association Test, along with measures of emotion, behavior, and temperament, in BPD (n = 18), DPD (n = 18), and healthy control (n = 35) participants. DPD participants had significantly higher ISE and were more harm avoidant than BPD and control participants, while BPD participants had more “frontal” behaviors and impulsivity and less self-directedness and cooperativeness than DPD and control participants. Thus, while BPD and DPD commonly overlap in terms of dissociative symptoms and emotional irregularities, differences in self-esteem, behavior, and temperament can help identify where they diverge in terms of their cognition, behavior, and ultimately underlying neurobiology. PMID:22493585

A DPYD variant (Y186C) in individuals of African ancestry associated with reduced DPD enzyme activity

PubMed Central

Offer, Steven M.; Lee, Adam M.; Mattison, Lori K.; Fossum, Croix; Wegner, Natalie J.; Diasio, Robert B.

2013-01-01

5-fluorouracil (5-FU) is used to treat many aggressive cancers, such as those of the colon, breast, and head & neck. The responses to 5-FU, both toxicity and efficacy, vary between racial groups, potentially due to variability in enzyme activity of dihydropyrimidine dehydrogenase (DPD, encoded by DPYD). In the present study, the genetic associations between DPYD variations and circulating mononuclear cell DPD enzyme activity were evaluated in 94 African American and 81 European American volunteers. The DPYD-Y186C variant was unique to individuals of African ancestry, and DPD activity was 46% reduced in carriers compared to non-carriers (279±35 compared to 514±168 pmol 5-FU min−1 mg−1; P=0.00029). 26% of the African Americans with reduced DPD activity in this study carried Y186C. In the African American cohort, following exclusion of Y186C carriers, homozygous carriers of C29R showed 27% higher DPD activity compared to non-carriers (609±152 and 480±152 pmol 5-FU min−1 mg−1, respectively; P=0.013). PMID:23588312

Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

PubMed Central

Marques, João C.; Lamosa, Pedro; Russell, Caitlin; Ventura, Rita; Maycock, Christopher; Semmelhack, Martin F.; Miller, Stephen T.; Xavier, Karina B.

2011-01-01

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior. PMID:21454635

Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

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

J Marques; P Lamosa; C Russell

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsiblemore » for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.« less

Verbal learning on depressive pseudodementia: accentuate impairment of free recall, moderate on learning processes, and spared short-term and recognition memory.

PubMed

Paula, Jonas Jardim de; Miranda, Débora Marques; Nicolato, Rodrigo; Moraes, Edgar Nunes de; Bicalho, Maria Aparecida Camargos; Malloy-Diniz, Leandro Fernandes

2013-09-01

Depressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and functional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study aims to assess the verbal learning profile of elderly patients with DPD. Ninety-six older adults (34 DPD and 62 controls) were assessed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess group differences and controlled for demographic factors. Moderate or large effects were found on all RAVLT components, except for short-term and recognition memory. DPD impairs verbal memory, with large effect size on free recall and moderate effect size on the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required.

Distinguishing Depressive Pseudodementia from Alzheimer Disease: A Comparative Study of Hippocampal Volumetry and Cognitive Tests

PubMed Central

Sahin, Sevki; Okluoglu Önal, Tugba; Cinar, Nilgun; Bozdemir, Meral; Çubuk, Rahmi; Karsidag, Sibel

2017-01-01

Background and Aim Depressive pseudodementia (DPD) is a condition which may develop secondary to depression. The aim of this study was to contribute to the differential diagnosis between Alzheimer disease (AD) and DPD by comparing the neurocognitive tests and hippocampal volume. Materials and Methods Patients who met criteria of AD/DPD were enrolled in the study. All patients were assessed using the Wechsler Memory Scale (WMS), clock-drawing test, Stroop test, Benton Facial Recognition Test (BFRT), Boston Naming Test, Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Hippocampal volume was measured by importing the coronal T1-weighted magnetic resonance images to the Vitrea 2 workstation. Results A significant difference was found between the AD and DPD groups on the WMS test, clock-drawing test, Stroop test, Boston Naming Test, MMSE, GDS, and left hippocampal volume. A significant correlation between BFRT and bilateral hippocampal volumes was found in the AD group. No correlation was found among parameters in DPD patients. Conclusions Our results suggest that evaluation of facial recognition and left hippocampal volume may provide more reliable evidence for distinguishing DPD from AD. Further investigations combined with functional imaging techniques including more patients are needed. PMID:28868066

A resilient and efficient CFD framework: Statistical learning tools for multi-fidelity and heterogeneous information fusion

NASA Astrophysics Data System (ADS)

Lee, Seungjoon; Kevrekidis, Ioannis G.; Karniadakis, George Em

2017-09-01

Exascale-level simulations require fault-resilient algorithms that are robust against repeated and expected software and/or hardware failures during computations, which may render the simulation results unsatisfactory. If each processor can share some global information about the simulation from a coarse, limited accuracy but relatively costless auxiliary simulator we can effectively fill-in the missing spatial data at the required times by a statistical learning technique - multi-level Gaussian process regression, on the fly; this has been demonstrated in previous work [1]. Based on the previous work, we also employ another (nonlinear) statistical learning technique, Diffusion Maps, that detects computational redundancy in time and hence accelerate the simulation by projective time integration, giving the overall computation a "patch dynamics" flavor. Furthermore, we are now able to perform information fusion with multi-fidelity and heterogeneous data (including stochastic data). Finally, we set the foundations of a new framework in CFD, called patch simulation, that combines information fusion techniques from, in principle, multiple fidelity and resolution simulations (and even experiments) with a new adaptive timestep refinement technique. We present two benchmark problems (the heat equation and the Navier-Stokes equations) to demonstrate the new capability that statistical learning tools can bring to traditional scientific computing algorithms. For each problem, we rely on heterogeneous and multi-fidelity data, either from a coarse simulation of the same equation or from a stochastic, particle-based, more "microscopic" simulation. We consider, as such "auxiliary" models, a Monte Carlo random walk for the heat equation and a dissipative particle dynamics (DPD) model for the Navier-Stokes equations. More broadly, in this paper we demonstrate the symbiotic and synergistic combination of statistical learning, domain decomposition, and scientific computing in exascale simulations.

Simulation and modelling of slip flow over surfaces grafted with polymer brushes and glycocalyx fibres

PubMed Central

Deng, Mingge; Li, Xuejin; Liang, Haojun; Caswell, Bruce; Karniadakis, George Em

2013-01-01

Fabrication of functionalized surfaces using polymer brushes is a relatively simple process and parallels the presence of glycocalyx filaments coating the luminal surface of our vasculature. In this paper, we perform atomistic-like simulations based on dissipative particle dynamics (DPD) to study both polymer brushes and glycocalyx filaments subject to shear flow, and we apply mean-field theory to extract useful scaling arguments on their response. For polymer brushes, a weak shear flow has no effect on the brush density profile or its height, while the slip length is independent of the shear rate and is of the order of the brush mesh size as a result of screening by hydrodynamic interactions. However, for strong shear flow, the polymer brush is penetrated deeper and is deformed, with a corresponding decrease of the brush height and an increase of the slip length. The transition from the weak to the strong shear regime can be described by a simple ‘blob’ argument, leading to the scaling γ̇0 ∝ σ3/2, where γ̇0 is the critical transition shear rate and σ is the grafting density. Furthermore, in the strong shear regime, we observe a cyclic dynamic motion of individual polymers, causing a reversal in the direction of surface flow. To study the glycocalyx layer, we first assume a homogeneous flow that ignores the discrete effects of blood cells, and we simulate microchannel flows at different flow rates. Surprisingly, we find that, at low Reynolds number, the slip length decreases with the mean flow velocity, unlike the behaviour of polymer brushes, for which the slip length remains constant under similar conditions. (The slip length and brush height are measured with respect to polymer mesh size and polymer contour length, respectively.) We also performed additional DPD simulations of blood flow in a tube with walls having a glycocalyx layer and with the deformable red blood cells modelled accurately at the spectrin level. In this case, a plasma cell-free layer is formed, with thickness more than three times the glycocalyx layer. We then find our scaling arguments based on the homogeneous flow assumption to be valid for this physiologically correct case as well. Taken together, our findings point to the opposing roles of conformational entropy and bending rigidity – dominant effects for the brush and glycocalyx, respectively – which, in turn, lead to different flow characteristics, despite the apparent similarity of the two systems. PMID:24353347

Coarse-graining to the meso and continuum scales with molecular-dynamics-like models

NASA Astrophysics Data System (ADS)

Plimpton, Steve

Many engineering-scale problems that industry or the national labs try to address with particle-based simulations occur at length and time scales well beyond the most optimistic hopes of traditional coarse-graining methods for molecular dynamics (MD), which typically start at the atomic scale and build upward. However classical MD can be viewed as an engine for simulating particles at literally any length or time scale, depending on the models used for individual particles and their interactions. To illustrate I'll highlight several coarse-grained (CG) materials models, some of which are likely familiar to molecular-scale modelers, but others probably not. These include models for water droplet freezing on surfaces, dissipative particle dynamics (DPD) models of explosives where particles have internal state, CG models of nano or colloidal particles in solution, models for aspherical particles, Peridynamics models for fracture, and models of granular materials at the scale of industrial processing. All of these can be implemented as MD-style models for either soft or hard materials; in fact they are all part of our LAMMPS MD package, added either by our group or contributed by collaborators. Unlike most all-atom MD simulations, CG simulations at these scales often involve highly non-uniform particle densities. So I'll also discuss a load-balancing method we've implemented for these kinds of models, which can improve parallel efficiencies. From the physics point-of-view, these models may be viewed as non-traditional or ad hoc. But because they are MD-style simulations, there's an opportunity for physicists to add statistical mechanics rigor to individual models. Or, in keeping with a theme of this session, to devise methods that more accurately bridge models from one scale to the next.

Probing eukaryotic cell mechanics via mesoscopic simulations

PubMed Central

Shang, Menglin; Lim, Chwee Teck

2017-01-01

Cell mechanics has proven to be important in many biological processes. Although there is a number of experimental techniques which allow us to study mechanical properties of cell, there is still a lack of understanding of the role each sub-cellular component plays during cell deformations. We present a new mesoscopic particle-based eukaryotic cell model which explicitly describes cell membrane, nucleus and cytoskeleton. We employ Dissipative Particle Dynamics (DPD) method that provides us with the unified framework for modeling of a cell and its interactions in the flow. Data from micropipette aspiration experiments were used to define model parameters. The model was validated using data from microfluidic experiments. The validated model was then applied to study the impact of the sub-cellular components on the cell viscoelastic response in micropipette aspiration and microfluidic experiments. PMID:28922399

Formation of incoherent deformation twin boundaries in a coarse-grained Al-7Mg alloy

NASA Astrophysics Data System (ADS)

Jin, S. B.; Zhang, K.; Bjørge, R.; Tao, N. R.; Marthinsen, K.; Lu, K.; Li, Y. J.

2015-08-01

Deformation twinning has rarely been observed in coarse grained Al and its alloys except under some extreme conditions such as ultrahigh deformation strain or strain rates. Here, we report that a significant amount of Σ3 deformation twins could be generated in a coarse-grained Al-7 Mg alloy by dynamic plastic deformation (DPD). A systematic investigation of the Σ3 boundaries shows that they are Σ3{112} type incoherent twin boundaries (ITBs). These ITBs have formed by gradual evolution from copious low-angle deformation bands through <111>-twist Σ boundaries by lattice rotation. These findings provide an approach to generate deformation twin boundaries in high stacking fault energy metallic alloys. It is suggested that high solution content of Mg in the alloy and the special deformation mode of DPD played an important role in formation of the Σ and ITBs.

Assessing depression and factors possibly associated with depression during the course of Parkinson’s disease

PubMed Central

Farabaugh, Amy H.; Locascio, Joseph J.; Yap, Liang; Fava, Maurizio; Bitran, Stella; Sousa, Jessica L.; Growdon, John H.

2011-01-01

BACKGROUND Although research suggests depression is common among individuals with Parkinson’s disease (PD), it is unclear how to best assess depression in PD (dPD). We wanted to examine the prevalence of dPD using different definitions of depression, as well as examine factors associated with dPD. METHODS One hundred fifty-eight individuals (68% male; age 66.8 ± 9.6 SD) with a primary diagnosis of PD were assessed for depression using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) in an outpatient setting at the Movement Disorders Clinic at Massachusetts General Hospital. We defined depression using 4 thresholds based on the HANDS and whether or not an individual was ever on an antidepressant regimen. We also examined potential predictors of the presence of dPD. RESULTS The prevalence of depression among study participants ranged from 11% to 57%, depending on which of the 4 definitions of depression was applied. Younger age and longer duration of PD predicted a relatively higher prevalence of depression. Having a history of depression prior to onset of PD also was predictive of dPD. CONCLUSIONS Depression appears to be relatively common among individuals with PD, and history of depression, younger age, and longer PD duration may be factors associated with dPD. PMID:21808748

Receptor-mediated membrane adhesion of lipid-polymer hybrid (LPH) nanoparticles studied by dissipative particle dynamics simulations

NASA Astrophysics Data System (ADS)

Li, Zhenlong; Gorfe, Alemayehu A.

2014-12-01

Lipid-polymer hybrid (LPH) nanoparticles represent a novel class of targeted drug delivery platforms that combine the advantages of liposomes and biodegradable polymeric nanoparticles. However, the molecular details of the interaction between LPHs and their target cell membranes remain poorly understood. We have investigated the receptor-mediated membrane adhesion process of a ligand-tethered LPH nanoparticle using extensive dissipative particle dynamics (DPD) simulations. We found that the spontaneous adhesion process follows a first-order kinetics characterized by two distinct stages: a rapid nanoparticle-membrane engagement, followed by a slow growth in the number of ligand-receptor pairs coupled with structural re-organization of both the nanoparticle and the membrane. The number of ligand-receptor pairs increases with the dynamic segregation of ligands and receptors toward the adhesion zone causing an out-of-plane deformation of the membrane. Moreover, the fluidity of the lipid shell allows for strong nanoparticle-membrane interactions to occur even when the ligand density is low. The LPH-membrane avidity is enhanced by the increased stability of each receptor-ligand pair due to the geometric confinement and the cooperative effect arising from multiple binding events. Thus, our results reveal the unique advantages of LPH nanoparticles as active cell-targeting nanocarriers and provide some general principles governing nanoparticle-cell interactions that may aid future design of LPHs with improved affinity and specificity for a given target of interest.

Effect of short range hydrodynamic on bimodal colloidal gel systems

NASA Astrophysics Data System (ADS)

Boromand, Arman; Jamali, Safa; Maia, Joao

2015-03-01

Colloidal Gels and disordered arrested systems has been studied extensively during the past decades. Although, they have found their place in multiple industries such as cosmetic, food and so on, their physical principals are still far beyond being understood. The interplay between different types of interactions from quantum scale, Van der Waals interaction, to short range interactions, depletion interaction, and long range interactions such as electrostatic double layer makes this systems challenging from simulation point of view. Many authors have implemented different simulation techniques such as molecular dynamics (MD) and Brownian dynamics (BD) to capture better picture during phase separation of colloidal system with short range attractive force. However, BD is not capable to include multi-body hydrodynamic interaction and MD is limited by the computational resources and is limited to short time and length scales. In this presentation we used Core-modified dissipative particle dynamics (CM-DPD) with modified depletion potential, as a coarse-grain model, to address the gel formation process in short ranged-attractive colloidal suspensions. Due to the possibility to include and separate short and long ranged-hydrodynamic forces in this method we studied the effect of each of those forces on the final morphology and report one of the controversial question in this field on the effect of hydrodynamics on the cluster formation process on bimodal, soft-hard colloidal mixtures.

Using drug sales data to evaluate the epidemiology of cardiometabolic risk factors and their inequality: an ecological study on atorvastatin and total cholesterol in Iran.

PubMed

Ahmadvand, Alireza; Farzadfar, Farshad; Jamshidi, Hamid Reza; Mohammadi, Naser; Holakouie-Naieni, Kourosh

2015-01-01

Statins have been effective medications in lowering serum total cholesterol (TC) concentrations across populations over time. The aim of this study was to estimate national and provincial trends in atorvastatin sales in Iran, to systematically quantify its relationship with socioeconomic indicators, and changes in TC level. In this retrospective ecological study, conducted in Iran, we examined trends in atorvastatin sales, the wealth index (WI) as a validly-available socio-economic indicator, and TC level between 2004 and 2011. The main outcome variable was mean atorvastatin sold in defined daily dose per 100,000 people per day (DPD). We analyzed the relationship between WI and DPD and between DPD and mean TC across time and space. At national level, both mean WI and mean DPD showed increasing trend over time, while we observed decreasing trend for TC. Mean WI and DPD in 2011 was nearly 5 and 50 time that of their respective figures in 2004, while the mean TC decreased for nearly 10%. Increases in both WI and DPD had happened in every province, but with different patterns. The maximum and minimum changes in DPD versus WI were seen in Gilan and North Khorasan respectively. A striking increase occurred in the sales for atorvastatin in Iran from 2004-2012 in most provinces examined. The wealthier a province became, the more sales were seen for atorvastatin. TC optimistically decreased from 2005 to 2011 and its decrease was positively correlated with increasing sales for atorvastatin.

Hidden Sylvatic Foci of the Main Vector of Chagas Disease Triatoma infestans: Threats to the Vector Elimination Campaign?

PubMed Central

Schachter-Broide, Judith; Dujardin, Jean-Pierre; Dotson, Ellen M.; Kitron, Uriel; Gürtler, Ricardo E.

2011-01-01

Background Establishing the sources of reinfestation after residual insecticide spraying is crucial for vector elimination programs. Triatoma infestans, traditionally considered to be limited to domestic or peridomestic (abbreviated as D/PD) habitats throughout most of its range, is the target of an elimination program that has achieved limited success in the Gran Chaco region in South America. Methodology/Principal Findings During a two-year period we conducted semi-annual searches for triatomine bugs in every D/PD site and surrounding sylvatic habitats after full-coverage spraying of pyrethroid insecticides of all houses in a well-defined rural area in northwestern Argentina. We found six low-density sylvatic foci with 24 T. infestans in fallen or standing trees located 110–2,300 m from the nearest house or infested D/PD site detected after insecticide spraying, when house infestations were rare. Analysis of two mitochondrial gene fragments of 20 sylvatic specimens confirmed their species identity as T. infestans and showed that their composite haplotypes were the same as or closely related to D/PD haplotypes. Population studies with 10 polymorphic microsatellite loci and wing geometric morphometry consistently indicated the occurrence of unrestricted gene flow between local D/PD and sylvatic populations. Mitochondrial DNA and microsatellite sibship analyses in the most abundant sylvatic colony revealed descendents from five different females. Spatial analysis showed a significant association between two sylvatic foci and the nearest D/PD bug population found before insecticide spraying. Conclusions Our study shows that, despite of its high degree of domesticity, T. infestans has sylvatic colonies with normal chromatic characters (not melanic morphs) highly connected to D/PD conspecifics in the Argentinean Chaco. Sylvatic habitats may provide a transient or permanent refuge after control interventions, and function as sources for D/PD reinfestation. The occurrence of sylvatic foci of T. infestans in the Gran Chaco may pose additional threats to ongoing vector elimination efforts. PMID:22039559

Deoxypyridinoline in the Urine of Rats with Unloaded Hindlimbs

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Navidi, M.; Wren, J.; Holton, Emily M. (Technical Monitor)

1997-01-01

The urinary excretion of deoxypyridinoline (U-Dpd), a nonreducible collagen crosslink in bone released by osteoclastic activity, is thought to be an accurate marker of bone resorption. The role of increased resorption in the osteopenia of a space flight model which unloads the hindlimbs by suspending the tail is controversial. To assess skeletal resorption in the model we measured U-Dpd (Pyrilinks-D, Metro Biosystems, Inc.) in serial 24 hour urine specimens collected from 250 a (Y) and 450 a (M) male rats with unloaded hindlimbs for four weeks. Both groups of rats were fed AIN76 diets with calcium restricted to 0.2% in Y and to 0.1 % in M. Blood was obtained after 28 days for parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25-D) and alkaline phosphatase (Alkptase). Basal U-Dpd was higher and more variable in Y than M (475+/-200 vs 67+/-9, nM/mM creatinine, p<.001). Repeated measures ANOVA in Y revealed decreases in U-Dpd, 36% in control (C) and 24% in unloaded (S) rats (p<.005). There was a nadir in YS on the 14th day not observed in YC (p<.05). U-Dpd in MC showed no change, but increased in MS by the 14th day and remained elevated. At the end of the experiment, body weights in both Y and M were less in S than C (337+/-16 vs 306+/-12g and 485+/-10 vs 461+/-6g, p=.002). Bill was inversely related to U-Dpd only in M (r=0.699, p=.024). PTH, similar in C and S in Y (52+/-15 vs 42+/-7pg/ml, NS) and M (68+/-13 vs 61+/-12, NS), was unrelated to U-Dpd. 1,25-D tended toward higher values in YC than YS (197+/-103 vs 119+/-30, NS) and correlated with U-Dpd (0.773, p=.015). Alkptase, 1.3 times higher in Y than M, was similar in C and S at the end of unloading. These findings indicate that bone resorption, as reflected by U-Dpd, is suppressed in young and stimulated in mature rats exposed to a space flight model. U-Dpd reflects reduced growth from the diet change in young control and experimental rats and loss of Bill in mature animals exposed to the space flight model, 2 situations with opposite effects on bone resorption.

Numerical methods for multi-scale modeling of non-Newtonian flows

NASA Astrophysics Data System (ADS)

Symeonidis, Vasileios

This work presents numerical methods for the simulation of Non-Newtonian fluids in the continuum as well as the mesoscopic level. The former is achieved with Direct Numerical Simulation (DNS) spectral h/p methods, while the latter employs the Dissipative Particle Dynamics (DPD) technique. Physical results are also presented as a motivation for a clear understanding of the underlying numerical approaches. The macroscopic simulations employ two non-Newtonian models, namely the Reiner-Ravlin (RR) and the viscoelastic FENE-P model. (1) A spectral viscosity method defined by two parameters ε, M is used to stabilize the FENE-P conformation tensor c. Convergence studies are presented for different combinations of these parameters. Two boundary conditions for the tensor c are also investigated. (2) Agreement is achieved with other works for Stokes flow of a two-dimensional cylinder in a channel. Comparison of the axial normal stress and drag coefficient on the cylinder is presented. Further, similar results from unsteady two- and three-dimensional turbulent flows past a flat plate in a channel are shown. (3) The RR problem is formulated for nearly incompressible flows, with the introduction of a mathematically equivalent tensor formulation. A spectral viscosity method and polynomial over-integration are studied. Convergence studies, including a three-dimensional channel flow with a parallel slot, investigate numerical problems arising from elemental boundaries and sharp corners. (4) The round hole pressure problem is presented for Newtonian and RR fluids in geometries with different hole sizes. Comparison with experimental data is made for the Newtonian case. The flaw in the experimental assumptions of undisturbed pressure opposite the hole is revealed, while good agreement with the data is shown. The Higashitani-Pritchard kinematical theory for RR, fluids is recovered for round holes and an approximate formula for the RR Stokes hole pressure is presented. The mesoscopic simulations assume bead-spring representations of polymer chains and investigate different integrating schemes of the DPD equations and different intra-polymer force combinations. (1) A novel family of time-staggered integrators is presented, taking advantage of the time-scale disparity between polymer-solvent and solvent-solvent interactions. Convergence tests for relaxation parameters for the velocity-Verlet and Lowe's schemes are presented. (2) Wormlike chains simulating lambda- DNA molecules subject to constant shear are studied, and direct comparison with Brownian Dynamics and experimental results is made. The effect of the number of beads per chain is examined through the extension autocorrelation function. (3) The Schmidt number (Sc) for each numerical scheme is investigated and the dependence on the scheme's parameters is shown. Re-visiting the wormlike chain problem under shear, we recover a better agreement with the experimental data through proper adjustment of Sc.

Experimental research on microhardness and wear resistances of pure Cu subjected to surface dynamic plastic deformation by ultrasonic impact

NASA Astrophysics Data System (ADS)

Chen, Zhaoxia; He, Yangming

2018-04-01

Dynamic plastic deformation (DPD) has been induced in the surface of pure Cu by ultrasonic impact treating (UIT) with the varied impact current and coverage percentage. The microstructures of the treated surface were analyzed by a scanning electron microscope (SEM). And the wear resistance of pure Cu was experimentally researched both with the treated and untreated specimens. The effect of DPD on the hardness was also investigated using microhardness tester. The results show that the grains on the top surfaces of pure Cu are highly refined. The maximum depth of the plastic deformation layer is approximately 1400 µm. The larger the current and coverage percentage, the greater of the microhardness and wear resistance the treated surface layer of pure Cu will be. When the impact current is 2 A and coverage percentage is 300%, the microhardness and wear resistance of the treated sample is about 276.1% and 68.8% higher than that of the untreated specimen, respectively. But the properties of the treated sample deteriorate when the UIT current is 3 A and the coverage percentage is 300% because of the formation of a new phase forms in the treated surface.

Multiscale Modeling of Hematologic Disorders

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

Fedosov, Dmitry A.; Pivkin, Igor; Pan, Wenxiao

Parasitic infectious diseases and other hereditary hematologic disorders are often associated with major changes in the shape and viscoelastic properties of red blood cells (RBCs). Such changes can disrupt blood flow and even brain perfusion, as in the case of cerebral malaria. Modeling of these hematologic disorders requires a seamless multiscale approach, where blood cells and blood flow in the entire arterial tree are represented accurately using physiologically consistent parameters. In this chapter, we present a computational methodology based on dissipative particle dynamics (DPD) which models RBCs as well as whole blood in health and disease. DPD is a Lagrangianmore » method that can be derived from systematic coarse-graining of molecular dynamics but can scale efficiently up to small arteries and can also be used to model RBCs down to spectrin level. To this end, we present two complementary mathematical models for RBCs and describe a systematic procedure on extracting the relevant input parameters from optical tweezers and microfluidic experiments for single RBCs. We then use these validated RBC models to predict the behavior of whole healthy blood and compare with experimental results. The same procedure is applied to modeling malaria, and results for infected single RBCs and whole blood are presented.« less

Time-dependent and outflow boundary conditions for Dissipative Particle Dynamics

PubMed Central

Lei, Huan; Fedosov, Dmitry A.; Karniadakis, George Em

2011-01-01

We propose a simple method to impose both no-slip boundary conditions at fluid-wall interfaces and at outflow boundaries in fully developed regions for Dissipative Particle Dynamics (DPD) fluid systems. The procedure to enforce the no-slip condition is based on a velocity-dependent shear force, which is a generalized force to represent the presence of the solid-wall particles and to maintain locally thermodynamic consistency. We show that this method can be implemented in both steady and time-dependent fluid systems and compare the DPD results with the continuum limit (Navier-Stokes) results. We also develop a force-adaptive method to impose the outflow boundary conditions for fully developed flow with unspecified outflow velocity profile or pressure value. We study flows over the backward-facing step and in idealized arterial bifurcations using a combination of the two new boundary methods with different flow rates. Finally, we explore the applicability of the outflow method in time-dependent flow systems. The outflow boundary method works well for systems with Womersley number of O(1), i.e., when the pressure and flowrate at the outflow are approximately in-phase. PMID:21499548

White matter network alterations in patients with depersonalization/derealization disorder.

PubMed

Sierk, Anika; Daniels, Judith K; Manthey, Antje; Kok, Jelmer G; Leemans, Alexander; Gaebler, Michael; Lamke, Jan-Peter; Kruschwitz, Johann; Walter, Henrik

2018-06-06

Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date. We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure. Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology. To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation. In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

5-ethynyl-2(1H)-pyrimidinone: aldehyde oxidase-activation to 5-ethynyluracil, a mechanism-based inactivator of dihydropyrimidine dehydrogenase.

PubMed

Porter, D J; Harrington, J A; Almond, M R; Lowen, G T; Zimmerman, T P; Spector, T

1994-03-29

5-Ethynyluracil is a potent mechanism-based inactivator of dihydropyrimidine dehydrogenase (DPD, EC 1.3.1.2) in vitro (Porter et al., J Biol Chem 267: 5236-5242, 1992) and in vivo (Spector et al., Biochem Pharmacol, 46: 2243-2248, 1993. 5-Ethynyl-2(1H)-pyrimidinone was rapidly oxidized to 5-ethynyluracil by aldehyde oxidase. The substrate efficiency (kcat/Km) was 60-fold greater than that for N-methylnicotinamide. In contrast, xanthine oxidase oxidized 5-ethynyl-2(1H)-pyrimidinone to 5-ethynyluracil with a substrate efficiency that was only 0.02% that of xanthine. Because 5-ethynyl-2(1H)-pyrimidinone did not itself inactivate purified DPD in vitro and aldehyde oxidase is predominately found in liver, we hypothesized that 5-ethynyl-2(1H)-pyrimidinone could be a liver-specific inactivator of DPD. We found that 5-ethynyl-2(1H)-pyrimidinone administered orally to rats at 2 micrograms/kg inactivated DPD in all tissues studied. Although 5-ethynyl-2(1H)-pyrimidinone produced slightly less inactivation than 5-ethynyluracil, the two compounds showed fairly similar patterns of inactivation of DPD in these tissues. At doses of 20 micrograms/kg, however, 5-ethynyl-2-pyrimidinone and 5-ethynyluracil produced equivalent inactivation of DPD. Thus, 5-ethynyl-2(1H)-pyrimidinone appeared to be an efficient, but not highly liver-selective prodrug of 5-ethynyluracil.

Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage.

PubMed

Chen, Xiaoyan; Saravelos, Sotirios H; Liu, Yingyu; Huang, Jin; Wang, Chi Chiu; Li, Tin Chiu

2017-06-01

Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.

Dependent personality disorder: a critical review.

PubMed

Disney, Krystle L

2013-12-01

Dependent personality disorder (DPD) has evolved from an abstract idea rooted in a historic and psychoanalytic context to a codified diagnosis in the DSM-IV-TR. This comprehensive review paper chronicles the evolution of DPD through each version of the DSM. Major topics relevant to the disorder are also investigated, including gender and cultural considerations, stability and manifestations of DPD across different developmental stages, comorbidity issues, and others. The purpose of this review is to provide a broad yet comprehensive examination of the complex angles of maladaptive dependency and to identify essential next steps in furthering our knowledge of this disorder. The paper concludes with a discussion of shortcomings in the body of research relevant to DPD, along with specific suggestions for improvement in this field of study. © 2013.

Hydrodynamic effects on phase transition in active matter

NASA Astrophysics Data System (ADS)

Gidituri, Harinadha; Akella, V. S.; Panchagnula, Mahesh; Vedantam, Srikanth; Multiphase flow physics lab Team

2017-11-01

Organized motion of active (self-propelled) objects are ubiquitous in nature. The objective of this study to investigate the effect of hydrodynamics on the coherent structures in active and passive particle mixtures. We use a mesoscopic method Dissipative Particle Dynamics (DPD). The system shows three different states viz. meso-turbulent (disordered state), polar flock and vortical (ordered state) for different values of activity and volume fraction of active particles. From our numerical simulations we construct a phase diagram between activity co-efficient, volume fraction and viscosity of the passive fluid. Transition from vortical to polar is triggered by increasing the viscosity of passive fluid which causes strong short-range hydrodynamic interactions. However, as the viscosity of the fluid decreases, both vortical and meso-turbulent states transition to polar flock phase. We also calculated the diffusion co-efficients via mean square displacement (MSD) for passive and active particles. We observe ballistic and diffusive regimes in the present system.

From aggregative adsorption to surface depletion: Aqueous systems of C nE m amphiphiles at hydrophilic surfaces

DOE PAGES

Rother, Gernot; Müter, Dirk; Bock, Henry; ...

2017-03-27

Adsorption of a short-chain nonionic amphiphile (C 6E 3) at the surface of mesoporous silica glass (CPG-10) was studied by a combination of adsorption measurements and mesoscale simulations. Adsorption measurements covering a wide composition range of the C 6E 3 + water system show that no adsorption occurs up to the critical micelle concentration (cmc), at which a sharp increase of adsorption is observed that is attributed to ad-micelle formation at the pore walls. Intriguingly, as the concentration is increased further, the surface excess of the amphiphile begins to decrease and eventually becomes negative, which corresponds to preferential adsorption ofmore » water rather than amphiphile at high amphiphile concentrations. The existence of such a surface-azeotropic point has not previously been reported in the surfactant adsorption field. Dissipative particle dynamics (DPD) simulations were performed to reveal the structural origin of this transition from aggregative adsorption to surface depletion. Finally, the simulations indicate that this transition can be attributed to the repulsive interaction between head groups, causing amphiphilic depletion in the region around the corona of the surface micelles.« less

Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation

PubMed Central

Liao, Zhenhua; Fogel, Guy R.; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

2015-01-01

Background The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Material/Methods Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Results Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). Conclusions ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion. PMID:26529430

Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation.

PubMed

Liao, Zhenhua; Fogel, Guy R; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

2015-11-03

The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion.

Behavior of a nano-particle and a polymer molecule in a nano-scale four-roll mill

NASA Astrophysics Data System (ADS)

Vo, Minh; Papavassiliou, Dimitrios

2016-11-01

The four-roll mill device could be used to create a mixed flow from purely extensional stresses to completely rotational through the proper selection of speed and direction of each of the four cylindrical rollers. Considerable research has been done with this device for macroscale rheological studies.. In our study, the dissipative particle dynamics (DPD) method was employed to investigate the behavior of a nano-sphere and a polymer molecule in different conditions within a four-roll mill device. Hydrophilic properties of each roll were generated by adjusting interaction parameters and using bounce back boundary condition at the solid surface. All simulations were run up to 4x106 time steps at room temperature using the open source LAMMPS package. After the flow in the system reached equilibrium, a nano-sphere and then a polymer chain were released at the center of the simulation box. Their trajectories were recorded at different shear rate conditions. The propagation of nanosphere in different rotational flow will be discussed. Additionally, the deformation of polymer chains will be compared to that in a simple shear flow.

Combined Analyses of hENT1, TS, and DPD Predict Outcomes of Borderline-resectable Pancreatic Cancer.

PubMed

Yabushita, Yasuhiro; Mori, Ryutaro; Taniguchi, Koichi; Matsuyama, Ryusei; Kumamoto, Takafumi; Sakamaki, Kentaro; Kubota, Kensuke; Endo, Itaru

2017-05-01

Predicting chemosensitivity to neoadjuvant chemoradiotherapy (NACRT) in pancreatic cancer is desired. The present study aimed to examine the relationship between intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) and the outcomes of NACRT with gemcitabine (GEM) combined with S-1 in patients with borderline-resectable pancreatic cancer (BRPC). Forty-seven patients who underwent NACRT with GEM plus S-1, following curative surgery, were recruited in our Institution between 2009 and 2012. Immunohistochemical expressions of hENT1, TS, and DPD in fine-needle aspiration (FNA) biopsies and resected specimens were examined. The correlation between these enzyme expressions and long-term outcome was analyzed. In 21 FNA specimens, no relationship between clinical responses to NACRT and long-term survival was found. However, in 47 resected specimens, patients were classified according to the number of favorable hENT1, TS, and DPD expression factors (hENT1 positive/TS negative/DPD negative). The presence of three favorable factors was strongly associated with improved partial response rates to NACRT (p=0.002). Patients with 2 or more favorable factors showed a significantly longer overall survival than the other patients (p=0.002). Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

White matter microstructure changes in the thalamus in Parkinson disease with depression: A diffusion tensor MR imaging study.

PubMed

Li, W; Liu, J; Skidmore, F; Liu, Y; Tian, J; Li, K

2010-11-01

Depression occurs frequently in PD; however the neural basis of depression in PD remains unclear. The aim of this study was to characterize possible depression-related white matter microstructural changes in the thalamus of patients with DPD compared with those with NDPD. FA and MD maps from DTI were obtained in 14 patients with DPD and 18 patients with NDPD. Region-of-interest-guided VBA was conducted on the FA maps to detect possible microstructural differences in the thalamus between these 2 patient groups. Moreover, mean FA and MD in regions with a detected difference were compared between DPD and NDPD groups, and correlations between diffusion quantities and the severity of depression were analyzed. White matter microstructure differences were found between the patients with DPD and NDPD in the bilateral mediodorsal thalamic regions. In these regions, patients with DPD showed significantly decreased FA values (P < .005) compared with patients with NDPD, and the mean values of FA were negatively correlated with the scores of depression severity (P < .05) for patients with PD. No significant differences of MD were found in the mediodorsal thalamus between these 2 groups. Our results provide preliminary evidence that the mediodorsal thalamus may play an important role in depression in PD and suggest a relationship between FA in the mediodorsal thalamus and the presence of depressive symptoms in patients with DPD. These findings may be helpful for further understanding the potential mechanisms of depression in PD.

Conditional reasoning in Asperger's syndrome and depersonalization disorder.

PubMed

Lawrence, Emma Jane; Dumigan, Rachael; Schoenberg, Poppy; Mauricio, Sierra; Murphy, Declan G; David, Anthony S

2012-09-01

Conditional reasoning premises can be systematically manipulated to elicit specific response patterns. This is useful for investigating the reasoning style of people who report clinical symptoms. We administered a standardized conditional reasoning task to 16 participants with a diagnosis of Asperger's syndrome (AS), 16 participants with a diagnosis of depersonalization disorder (DPD), and 32 intelligence-quotient-matched controls. Premises were manipulated for a) context, with some being embedded within extra statements, and b) content, neutral or emotional. Both the AS and DPD participants were less likely to incorporate exceptions to the given premises than the controls, indicating difficulties with mental flexibility, although this effect was less marked in the DPD group. It seems the AS participants were also less influenced than the controls by statements that highlight possible alternative consequences. However, this effect was less robust than that observed with statements detailing exceptions, suggesting it may be because of general problems with executive function rather than difficulties in processing contextual information. We did not observe the expected difference between the DPD participants and the controls when reasoning with emotional premises. Overall, these data suggest that the DPD and AS participants have distinct reasoning styles, which may be of use for interventions based on cognitive change.

Polymer-mediated nanorod self-assembly predicted by dissipative particle dynamics simulations.

PubMed

Khani, Shaghayegh; Jamali, Safa; Boromand, Arman; Hore, Michael J A; Maia, Joao

2015-09-14

Self-assembly of nanoparticles in polymer matrices is an interesting and growing subject in the field of nanoscience and technology. We report herein on modelling studies of the self-assembly and phase behavior of nanorods in a homopolymer matrix, with the specific goal of evaluating the role of deterministic entropic and enthalpic factors that control the aggregation/dispersion in such systems. Grafting polymer brushes from the nanorods is one approach to control/impact their self-assembly capabilities within a polymer matrix. From an energetic point of view, miscible interactions between the brush and the matrix are required for achieving a better dispersibility; however, grafting density and brush length are the two important parameters in dictating the morphology. Unlike in previous computational studies, the present Dissipative Particle Dynamics (DPD) simulation framework is able to both predict dispersion or aggregation of nanorods and determine the self-assembled structure, allowing for the determination of a phase diagram, which takes all of these factors into account. Three types of morphologies are predicted: dispersion, aggregation and partial aggregation. Moreover, favorable enthalpic interactions between the brush and the matrix are found to be essential for expanding the window for achieving a well-dispersed morphology. A three-dimensional phase diagram is mapped on which all the afore-mentioned parameters are taken into account. Additionally, in the case of immiscibility between brushes and the matrix, simulations predict the formation of some new and tunable structures.

Psychophysiological investigations in depersonalization disorder and effects of electrodermal biofeedback.

PubMed

Schoenberg, Poppy L A; Sierra, Mauricio; David, Anthony S

2012-01-01

Previous studies investigating depersonalization disorder (DPD) report a lower baseline skin conductance level (SCL) and attenuated skin conductance response (SCR) to emotive stimuli. We hypothesized that increasing physiological arousal levels via electrodermal biofeedback may ameliorate disembodiment and emotional numbing symptomatology. Real-time versus sham biofeedback yielded a significant SCL increase after just 3 real-time biofeedback sessions in healthy volunteers. Subsequently, a randomized controlled biofeedback trial was administered with DPD patients. Findings were not replicated as SCL tended to fall, curiously more substantially in the real-time condition, concomitant with increased low- and high-frequency heart rate variability. To further investigate abnormal autonomic regulation in DPD, we compared basal autonomic activity between patients and healthy volunteers and found the former to be significantly more labile, indexed by greater nonspecific SCRs and higher resting SCLs. Rather than low sympathetic arousal, DPD might be better characterized by abnormal autonomic regulation affecting emotional and physiological responsivity.

Danish Palliative Care Database.

PubMed

Groenvold, Mogens; Adsersen, Mathilde; Hansen, Maiken Bang

2016-01-01

The aim of the Danish Palliative Care Database (DPD) is to monitor, evaluate, and improve the clinical quality of specialized palliative care (SPC) (ie, the activity of hospital-based palliative care teams/departments and hospices) in Denmark. The study population is all patients in Denmark referred to and/or in contact with SPC after January 1, 2010. The main variables in DPD are data about referral for patients admitted and not admitted to SPC, type of the first SPC contact, clinical and sociodemographic factors, multidisciplinary conference, and the patient-reported European Organisation for Research and Treatment of Cancer Quality of Life Questionaire-Core-15-Palliative Care questionnaire, assessing health-related quality of life. The data support the estimation of currently five quality of care indicators, ie, the proportions of 1) referred and eligible patients who were actually admitted to SPC, 2) patients who waited <10 days before admission to SPC, 3) patients who died from cancer and who obtained contact with SPC, 4) patients who were screened with European Organisation for Research and Treatment of Cancer Quality of Life Questionaire-Core-15-Palliative Care at admission to SPC, and 5) patients who were discussed at a multidisciplinary conference. In 2014, all 43 SPC units in Denmark reported their data to DPD, and all 9,434 cancer patients (100%) referred to SPC were registered in DPD. In total, 41,104 unique cancer patients were registered in DPD during the 5 years 2010-2014. Of those registered, 96% had cancer. DPD is a national clinical quality database for SPC having clinically relevant variables and high data and patient completeness.

The roles of dominos and nonsimultaneous chains in kidney paired donation.

PubMed

Gentry, S E; Montgomery, R A; Swihart, B J; Segev, D L

2009-06-01

Efforts to expand kidney paired donation have included matching nondirected donors (NDDs) to incompatible pairs. In domino paired donation (DPD), an NDD gives to the recipient of an incompatible pair, beginning a string of simultaneous transplants that ends with a living donor giving to a recipient on the deceased donor waitlist. Recently, nonsimultaneous extended altruistic donor (NEAD) chains were introduced. In a NEAD chain, the last donor of the string of transplants initiated by an NDD is reserved to donate at a later time. Our aim was to project the impact of each of these strategies over 2 years of operation for paired donation programs that also allocate a given number of NDDs. Each NDD facilitated an average of 1.99 transplants using DPD versus 1.90 transplants using NEAD chains (p = 0.3), or 1.0 transplants donating directly to the waitlist (p < 0.001). NEAD chains did not yield more transplants compared with simultaneous DPD. Both DPD and NEAD chains relax reciprocality requirements and rebalance the blood-type distribution of donors. Because traditional paired donation will leave many incompatible pairs unmatched, novel approaches like DPD and NEAD chains must be explored if paired donation programs are to help a greater number of people.

Effect of amiloride and bumetanide on transepithelial ion transport in isolated rabbit cecal and colonic wall.

PubMed

Kosik-Bogacka, Danuta; Młodzik-Danielewicz, Natalia; Banach, Bolesław; Tyrakowski, Tomasz

2005-06-03

The aim of the study was to compare the effects of amiloride and bumetanide on the baseline transepithelial electrical potential difference (PD) and changes in PD during mechanical stimulation (dPD) in isolated cecal and colonic wall of rabbits. The experiments were performed with a modified Ussing chamber system. Isolated tissue specimens were incubated in Ringer's solution, in amiloride and/or bumetanide, or in dimethyl sulfoxide (DMSO). Under control conditions, i.e. when all the experimental fluids were Ringer's solution, the PD and R values of the rabbit cecum and colon were similar, while during mechanical stimulation, dPD of the colon was twice as high as that of the cecum. Addition of amiloride and/or bumetanide to all experimental fluids diminished the electrophysiological parameters of both tissues. DMSO added to all experimental fluids significantly diminished the values of the electrophysiological parameters of the cecum. Addition of amiloride to the stimulation fluid only diminished the PD and dPD values in the colon, whereas addition of bumetanide to the stimulation fluid only diminished the PD and dPD values in the cecum. It was found that the PD and dPD values of the rabbit cecum depend primarily on chloride ion transport, while those of the colon depend on sodium ion transport.

A Conserved, Mg2+-Dependent Exonuclease Degrades Organelle DNA during Arabidopsis Pollen Development[C][W

PubMed Central

Matsushima, Ryo; Tang, Lay Yin; Zhang, Lingang; Yamada, Hiroshi; Twell, David; Sakamoto, Wataru

2011-01-01

In plant cells, mitochondria and plastids contain their own genomes derived from the ancestral bacteria endosymbiont. Despite their limited genetic capacity, these multicopy organelle genomes account for a substantial fraction of total cellular DNA, raising the question of whether organelle DNA quantity is controlled spatially or temporally. In this study, we genetically dissected the organelle DNA decrease in pollen, a phenomenon that appears to be common in most angiosperm species. By staining mature pollen grains with fluorescent DNA dye, we screened Arabidopsis thaliana for mutants in which extrachromosomal DNAs had accumulated. Such a recessive mutant, termed defective in pollen organelle DNA degradation1 (dpd1), showing elevated levels of DNAs in both plastids and mitochondria, was isolated and characterized. DPD1 encodes a protein belonging to the exonuclease family, whose homologs appear to be found in angiosperms. Indeed, DPD1 has Mg2+-dependent exonuclease activity when expressed as a fusion protein and when assayed in vitro and is highly active in developing pollen. Consistent with the dpd phenotype, DPD1 is dual-targeted to plastids and mitochondria. Therefore, we provide evidence of active organelle DNA degradation in the angiosperm male gametophyte, primarily independent of maternal inheritance; the biological function of organellar DNA degradation in pollen is currently unclear. PMID:21521697

Nano-colloid electrophoretic transport: Fully explicit modelling via dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Hassanzadeh Afrouzi, Hamid; Farhadi, Mousa; Sedighi, Kurosh; Moshfegh, Abouzar

2018-02-01

In present study, a novel fully explicit approach using dissipative particle dynamics (DPD) method is introduced for modelling electrophoretic transport of nano-colloids in an electrolyte solution. Slater type charge smearing function included in 3D Ewald summation method is employed to treat electrostatic interaction. Moreover, capability of different thermostats are challenged to control the system temperature and study the dynamic response of colloidal electrophoretic mobility under practical ranges of external electric field in nano scale application (0.072 < E < 0.361 v / nm) covering non-linear response regime, and ionic salt concentration (0.049 < SC < 0.69 [M]) covering weak to strong Debye screening of the colloid. The effect of different colloidal repulsions are then studied on temperature, reduced mobility and zeta potential which is computed based on charge distribution within the spherical colloidal EDL. System temperature and electrophoretic mobility both show a direct and inverse relationship respectively with electric field and colloidal repulsion. Mobility declining with colloidal repulsion reaches a plateau which is a relatively constant value at each electrolyte salinity for Aii > 600 in DPD units regardless of electric field intensity. Nosé-Hoover-Lowe-Andersen and Lowe-Andersen thermostats are found to function more effectively under high electric fields (E > 0.145 [ v / nm ]) while thermal equilibrium is maintained. Reasonable agreements are achieved by benchmarking the radial distribution function with available electrolyte structure modellings, as well as comparing reduced mobility against conventional Smoluchowski and Hückel theories, and numerical solution of Poisson-Boltzmann equation.

Automated HPLC assay for urinary collagen cross-links: effect of age, menopause, and metabolic bone diseases.

PubMed

Kraenzlin, Marius E; Kraenzlin, Claude A; Meier, Christian; Giunta, Cecilia; Steinmann, Beat

2008-09-01

The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20-49 years. In men, cross-link values peaked at 20-29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%-60% at age 11-14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.

Frequency specific brain networks in Parkinson's disease and comorbid depression.

PubMed

Qian, Long; Zhang, Yi; Zheng, Li; Fu, Xuemei; Liu, Weiguo; Shang, Yuqing; Zhang, Yaoyu; Xu, Yuanyuan; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

2017-02-01

The topological organization underlying the human brain was extensively investigated using resting-state functional magnetic resonance imaging, focusing on a low frequency of signal oscillation from 0.01 to 0.1 Hz. However, the frequency specificities with regard to the topological properties of the brain networks have not been fully revealed. In this study, a novel complementary ensemble empirical mode decomposition (CEEMD) method was used to separate the fMRI time series into five characteristic oscillations with distinct frequencies. Then, the small world properties of brain networks were analyzed for each of these five oscillations in patients (n = 67) with depressed Parkinson's disease (DPD, n = 20) , non-depressed Parkinson's disease (NDPD, n = 47) and healthy controls (HC, n = 46). Compared with HC, the results showed decreased network efficiency in characteristic oscillations from 0.05 to 0.12 Hz and from 0.02 to 0.05 Hz for the DPD and NDPD patients, respectively. Furthermore, compared with HC, the most significant inter-group difference across five brain oscillations was found in the basal ganglia (0.01 to 0.05 Hz) and paralimbic-limbic network (0.02 to 0.22 Hz) for the DPD patients, and in the visual cortex (0.02 to 0.05 Hz) for the NDPD patients. Compared with NDPD, the DPD patients showed reduced efficiency of nodes in the basal ganglia network (0.01 to 0.05 Hz). Our results demonstrated that DPD is characterized by a disrupted topological organization in large-scale brain functional networks. Moreover, the CEEMD analysis suggested a prominent dissociation in the topological organization of brain networks between DPD and NDPD in both space and frequency domains. Our findings indicated that these characteristic oscillatory activities in different functional circuits may contribute to distinct motor and non-motor components of clinical impairments in Parkinson's disease.

Pharmacogenetics and Metabolism from Science to Implementation in Clinical Practice: The Example of Dihydropyrimidine Dehydrogenase.

PubMed

Del Re, Marzia; Restante, Giuliana; Di Paolo, Antonello; Crucitta, Stefania; Rofi, Eleonora; Danesi, Romano

2017-01-01

Fluoropyrimidines are widely used in the treatment of solid tumors and remain the backbone of many combination chemotherapy regimens. Despite their clinical benefit, they are associated with frequent gastrointestinal and hematological toxicities, which often lead to treatment discontinuation. Fluoropyrimidines undergo complex anabolic and catabolic biotransformation. Enzymes involved in this pathway include dihydropyrimidine dehydrogenase (DPD), which breaks down 5-FU and its prodrugs. Candidate gene approaches have demonstrated associations between 5-FU treatment outcomes and germline polymorphisms in DPD. The aim of this review is to report and discuss the latest results on fluoropyrimidine pharmacogenetics. Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such DPD, DPYD, fluoropyrimdines, polymorphisms, toxicity, pharmacogenetics. To date, many sequence variations have been identified within DPYD gene, although the majority of these have no functional consequences on enzymatic activity. Nowadays, there is a general agreement on the clinical significance of the importance of DPD deficiency in patients who suffer from severe, life-threatening drug toxicity although preemptive testing is not applied to all patients. Considering the published literature, clinicians are strongly encouraged to consider testing for DPD poor metabolizer variants as a rational pre-treatment screening for patients candidate to a fluoropyrimidine-based regimens, in order to prevent toxicities and personalise treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mesoscopic Simulations of Adsorption and Association of PEO-PPO-PEO Triblock Copolymers on a Hydrophobic Surface: From Mushroom Hemisphere to Rectangle Brush.

PubMed

Song, Xianyu; Zhao, Shuangliang; Fang, Shenwen; Ma, Yongzhang; Duan, Ming

2016-11-08

The dissipative particle dynamics (DPD) method is used to investigate the adsorption behavior of PEO-PPO-PEO triblock copolymers at the liquid/solid interface. The effect of molecular architecture on the self-assembled monolayer adsorption of PEO-PPO-PEO triblock copolymers on hydrophobic surfaces is elucidated by the adsorption process, film properties, and adsorption morphologies. The adsorption thicknesses on hydrophobic surfaces and the diffusion coefficient as well as the aggregation number of Pluronic copolymers in aqueous solution observed in our simulations agree well with previous experimental and numerical observations. The radial distribution function revealed that the ability of self-assembly on hydrophobic surfaces is P123 > P84 > L64 > P105 > F127, which increased with the EO ratio of the Pluronic copolymers. Moreover, the shape parameter and the degree of anisotropy increase with increasing molecular weight and mole ratio of PO of the Pluronic copolymers. Depending on the conformation of different Pluronic copolymers, the morphology transition of three regimes on hydrophobic surfaces is present: mushroom or hemisphere, progressively semiellipsoid, and rectangle brush regimes induced by decreasing molecular weight and mole ratio of EO of Pluronic copolymers.

Shell-corona microgels from double interpenetrating networks.

PubMed

Rudyak, Vladimir Yu; Gavrilov, Alexey A; Kozhunova, Elena Yu; Chertovich, Alexander V

2018-04-18

Polymer microgels with a dense outer shell offer outstanding features as universal carriers for different guest molecules. In this paper, microgels formed by an interpenetrating network comprised of collapsed and swollen subnetworks are investigated using dissipative particle dynamics (DPD) computer simulations, and it is found that such systems can form classical core-corona structures, shell-corona structures, and core-shell-corona structures, depending on the subchain length and molecular mass of the system. The core-corona structures consisting of a dense core and soft corona are formed at small microgel sizes when the subnetworks are able to effectively separate in space. The most interesting shell-corona structures consist of a soft cavity in a dense shell surrounded with a loose corona, and are found at intermediate gel sizes; the area of their existence depends on the subchain length and the corresponding mesh size. At larger molecular masses the collapsing network forms additional cores inside the soft cavity, leading to the core-shell-corona structure.

Underlying Manifestations of Developmental Phonological Disorders in French-Speaking Pre-Schoolers

ERIC Educational Resources Information Center

Brosseau-Lapré, Françoise; Rvachew, Susan

2017-01-01

This study examined the psycholinguistic profiles of Quebec French-speaking children with developmental phonological disorders (DPD). The purpose was to determine whether the endophenotypes that have been identified in English-speaking children with DPD are similarly associated with speech impairment in French-speaking children. Seventy-two…

DPD epitope-specific glutamic acid decarboxylase GAD)65 autoantibodies in children with Type 1 diabetes

USDA-ARS?s Scientific Manuscript database

To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical dat...

Short-term dynamic behavior of Escherichia coli in response to successive glucose pulses on glucose-limited chemostat cultures.

PubMed

Sunya, Sirichai; Bideaux, Carine; Molina-Jouve, Carole; Gorret, Nathalie

2013-04-15

The effect of repeated glucose perturbations on dynamic behavior of Escherichia coli DPD2085, yciG::LuxCDABE reporter strain, was studied and characterized on a short-time scale using glucose-limited chemostat cultures at dilution rates close to 0.18h(-1). The substrate disturbances were applied on independent steady-state cultures, firstly using a single glucose pulse under different aeration conditions and secondly using repeated glucose pulses under fully aerobic condition. The dynamic responses of E. coli to a single glucose pulse of different intensities (0.25 and 0.6gL(-1)) were significantly similar at macroscopic level, revealing the independency of the macroscopic microbial behavior to the perturbation intensity in the range of tested glucose concentrations. The dynamic responses of E. coli to repeated glucose pulses to simulate fluctuating environments between glucose-limited and glucose-excess conditions were quantified; similar behavior regarding respiration and by-product formations was observed, except for the first perturbation denoted by an overshoot of the specific oxygen uptake rate in the first minutes after the pulse. In addition, transcriptional induction of yciG promoter gene involved in general stress response, σ(S), was monitored through the bioluminescent E. coli strain. This study aims to provide and compare short-term quantitative kinetics data describing the dynamic behavior of E. coli facing repeated transient substrate conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Measurement of Chlorine Dioxide in Water by DPD Colorimetric Method

NASA Astrophysics Data System (ADS)

Song, Min; Yan, Panping; Yao, Jun

2018-01-01

In order to solve the problems of chlorine dioxide in water by DPD colorimetric method, this paper discusses the effects of the formulation, temperature, color development time and amount of color reagent on the measurement process, improving the on-line instrument for domestic and drinking water in chlorine dioxide measurement precision and accuracy.

Illuminating a neglected clinical issue: societal costs of interpersonal dependency and dependent personality disorder.

PubMed

Bornstein, Robert F

2012-07-01

To determine the degree to which patients with high levels of trait dependency or dependent personality disorder (DPD) engage in behaviors that harm themselves and others (e.g., domestic violence, child abuse). Six domains of literature were reviewed: (a) dependency as a risk factor for physical illness; (b) health care utilization and expenditures; (c) global and domain-specific functional impairment; (d) violence toward others; (e) victimization by others; and (f) self-harm. High levels of trait dependency and DPD are associated with elevated risk for physical illness, partner and child abuse, and suicidality, as well as with high levels of functional impairment and increased health care expenditure. Contrary to clinical lore, trait dependency and DPD are associated with behaviors that lead to myriad negative consequences for the dependent person, those close to them, and society as a whole. These patterns have noteworthy implications for assessment and treatment of dependent patients and suggest that DPD should be included as a diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition. © 2012 Wiley Periodicals, Inc.

Altered orientation of spatial attention in depersonalization disorder.

PubMed

Adler, Julia; Beutel, Manfred E; Knebel, Achim; Berti, Stefan; Unterrainer, Josef; Michal, Matthias

2014-05-15

Difficulties with concentration are frequent complaints of patients with depersonalization disorder (DPD). Standard neuropsychological tests suggested alterations of the attentional and perceptual systems. To investigate this, the well-validated Spatial Cueing paradigm was used with two different tasks, consisting either in the detection or in the discrimination of visual stimuli. At the start of each trial a cue indicated either the correct (valid) or the incorrect (invalid) position of the upcoming stimulus or was uninformative (neutral). Only under the condition of increased task difficulty (discrimination task) differences between DPD patients and controls were observed. DPD patients showed a smaller total attention directing effect (RT in valid vs. invalid trials) compared to healthy controls only in the discrimination condition. RT costs (i.e., prolonged RT in neutral vs. invalid trials) mainly accounted for this difference. These results indicate that DPD is associated with altered attentional mechanisms, especially with a stronger responsiveness to unexpected events. From an evolutionary perspective this may be advantageous in a dangerous environment, in daily life it may be experienced as high distractibility. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Longitudinal comparison of depressive personality disorder and dysthymic disorder.

PubMed

Markowitz, John C; Skodol, Andrew E; Petkova, Eva; Xie, Hui; Cheng, Jianfeng; Hellerstein, David J; Gunderson, John G; Sanislow, Charles A; Grilo, Carlos M; McGlashan, Thomas H

2005-01-01

Few studies have compared the related diagnostic constructs of depressive personality disorder (DPD) and dysthymic disorder (DD). The authors attempted to replicate findings of Klein and Shih in longitudinally followed patients with personality disorder or major depressive disorder (MDD) in the Collaborative Longitudinal Personality Disorders Study. Subjects (N = 665) were evaluated at baseline and over 2 years (n = 546) by reliably trained clinical interviewers using semistructured interviews and self-report personality questionnaires. Only 44 subjects (24.6% of 179 DPD and 49.4% of 89 early-onset dysthymic subjects) met criteria for both disorders at baseline. Depressive personality disorder was associated with increased comorbidity of some axis I anxiety disorders and other axis II diagnoses, particularly avoidant (71.5%) and borderline (55.9%) personality disorders. Depressive personality disorder was associated with low positive and high negative affectivity on dimensional measures of temperament. Depressive personality disorder subjects had lower likelihood of remission of baseline MDD at 2-year follow-up, whereas DD subjects did not. The DPD diagnosis appeared unstable over 2 years of follow-up, as only 31% (n = 47) of 154 subjects who had DPD at baseline and also had follow-up assessment met criteria on blind retesting. Results from this sample may not generalize to other populations. Depressive personality disorder and dysthymic disorder appear to be related but differ in diagnostic constructs. Its moderating effect on MDD and predicted relationship to measures of temperament support the validity of DPD, but its diagnostic instability raises questions about its course, utility, and measurement.

Effects of soy isoflavone supplements on bone turnover markers in menopausal women: systematic review and meta-analysis of randomized controlled trials.

PubMed

Taku, Kyoko; Melby, Melissa K; Kurzer, Mindy S; Mizuno, Shoichi; Watanabe, Shaw; Ishimi, Yoshiko

2010-08-01

Effects of soy isoflavone supplements on bone turnover markers remain unclear. This up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) was performed primarily to more completely and precisely clarify the effects on urinary deoxypyridinoline (DPD) and serum bone alkaline phosphatase (BAP) and secondarily to evaluate the effects on other bone turnover markers, compared with placebo in menopausal women. PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant studies of RCTs. Data on study design, participants, interventions, and outcomes were extracted and methodological quality of each included trial was assessed. From 3740 identified relevant articles, 10 (887 participants), 10 (1210 participants), and 8 (380 participants) RCTs were selected for meta-analysis of effects on DPD, BAP, and serum osteocalcin (OC), respectively, using Review Manager 5.0.22. Daily ingestion of an average 56 mg soy isoflavones (aglycone equivalents) for 10 weeks to 12 months significantly decreased DPD by 14.1% (95% CI: -26.8% to -1.5%; P=0.03) compared to baseline (heterogeneity: P<0.00001; I(2)=93%; random effects model). The overall effect of soy isoflavones on DPD compared with placebo was a significant decrease of -18.0% (95% CI: -28.4% to -7.7%, P=0.0007; heterogeneity: P=0.0001; I(2)=73%; random effects model). Subgroup analyses and meta-regressions revealed that isoflavone dose and intervention duration did not significantly relate to the variable effects on DPD. Daily supplementation of about 84 mg and 73 mg of soy isoflavones for up to 12 months insignificantly increased BAP by 8.0% (95% CI: -4.2% to 20.2%, P=0.20; heterogeneity: P<0.00001; I(2)=98%) and OC by 10.3% (95% CI: -3.1% to 23.7%, P=0.13; heterogeneity: P=0.002; I(2)=69%) compared with placebo (random effects model), respectively. Soy isoflavone supplements moderately decreased the bone resorption marker DPD, but did not affect bone formation markers BAP and OC in menopausal women. The effects varied between studies, and further studies are needed to address factors relating to the observed effects of soy isoflavones on DPD and to verify effects on other bone turnover markers. Copyright 2010 Elsevier Inc. All rights reserved.

Amino acid supplementation alters bone metabolism during simulated weightlessness

NASA Technical Reports Server (NTRS)

Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

2005-01-01

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Adsorption and Depletion Regimes of a Nonionic Surfactant in Hydrophilic Mesopores: An Experimental and Simulation Study

DOE PAGES

Müter, Dirk; Rother, Gernot; Bock, Henry; ...

2017-08-15

Adsorption and aggregation of nonionic surfactants at oxide surfaces has been studied extensively in the past, but only for concentrations below and near the critical micelle concentration. In this paper, we report an adsorption study of a short-chain surfactant (C 6E 3) in porous silica glass of different pore sizes (7.5 to 50 nm), covering a wide composition range up to 50 wt % in a temperature range from 20 °C to the LCST. Aggregative adsorption is observed at low concentrations, but the excess concentration of C 6E 3 in the pores decreases and approaches zero at higher bulk concentrations.more » Strong depletion of surfactant (corresponding to enrichment of water in the pores) is observed in materials with wide pores at high bulk concentrations. We propose an explanation for the observed pore-size dependence of the azeotropic point. Mesoscale simulations based on dissipative particle dynamics (DPD) were performed to reveal the structural origin of this transition from the adsorption to the depletion regime. The simulated adsorption isotherms reproduce the behavior found in the 7.5 nm pores. Finally, the calculated bead density profiles indicate that the repulsive interaction of surfactant head groups causes a depletion of surfactant in the region around the corona of the surface micelles.« less

Depression in Parkinson's disease: symptom improvement and residual symptoms after acute pharmacologic management.

PubMed

Dobkin, Roseanne DeFronzo; Menza, Matthew; Bienfait, Karina L; Gara, Michael; Marin, Humberto; Mark, Margery H; Dicke, Allison; Friedman, Jill

2011-03-01

Parkinson's disease (PD) is frequently complicated by depression and there is a paucity of controlled research that can inform the management of this disabling nonmotor complaint. A randomized controlled trial of nortriptyline, paroxetine, and placebo for the treatment of depression in PD (dPD) was recently completed. The purpose of this article is to describe the baseline pattern of depressive symptom presentation in PD, the specific symptoms of dPD that improve with pharmacotherapy, and the residual symptoms that remain in patients who meet a priori criteria for response or remission after acute treatment (8 weeks). The Departments of Psychiatry and Neurology at Robert Wood Johnson Medical School, New Jersey. : Fifty-two depressed patients (major depression or dysthymia based on Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) with Parkinson's disease (by research criteria). A randomized controlled trial of nortriptyline, paroxetine, and placebo. The four subscales (core mood, anxiety, insomnia, and somatic) and individual items from the Hamilton Rating Scale for Depression-17 were the focus of this study. These measures were assessed at baseline and Week 8. Baseline depressive symptoms were unrelated to motor functioning. Treatment response was associated with significant improvements in the core mood, anxiety, insomnia, and somatic symptoms seen in dPD. Residual symptoms, such as sadness and loss of interest, persisted in treatment responders in a milder form than was initially present. Antidepressants may influence all symptoms of dPD, including those that share great overlap with the physical disease process. Additional research regarding adjunctive interventions is needed to help optimize the management of dPD.

Investigation of broadband digital predistortion for broadband radio over fiber transmission systems

NASA Astrophysics Data System (ADS)

Zhang, Xiupu; Liu, Taijun; Shen, Dongya

2016-12-01

In future broadband cloud radio access networks (C-RAN), front-haul transmission systems play a significant role in performance and cost of C-RAN. Broadband and high linearity radio over fiber (RoF) transmission systems are considered a promising solution for the front-haul. Digital linearization is one possible solution for RoF front-haul. In this paper, we investigate RF domain digital predistortion (DPD) linearization for broadband RoF front-haul. The implemented DPD is first investigated in 2.4 GHz WiFi over fiber transmission systems at 36 Mb/s, and more than 8-dB and 5.6-dB improvements of error vector magnitude (EVM) are achieved in back to back (BTB) and after 10 km single mode fiber (SMF) transmission. Further, both WiFi and ultra wide band (UWB) wireless signals are transmitted together, in which the DPD has linearization bandwidth of 2.4 GHz. It is shown that the implemented DPD leads to EVM improvements of 4.5-dB (BTB) and 3.1-dB (10 km SMF) for the WiFi signal, and 4.6-dB (BTB) and 4-dB (10 km SMF) for the broadband UWB signal.

Effect of surfactants on the deformation of single droplet in shear flow studied by dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Zhang, Yuzhou; Xu, Junbo; He, Xianfeng

2018-07-01

The behaviour of a single droplet in shear flow is a fundamental problem in immiscible liquid-liquid multiphase fluid systems. In this article, the deformation and inclination angle of single droplet covered with surfactants in shear flow at moderate Reynolds number, when both the inertial effects and interfacial tension are the key governing factors, were simulated by dissipative particle dynamics (DPD). Weber number We was adopted to indicate the force state of the droplet and a linear relationship between the deformation parameter D and We was found when Reynolds number Re is about 1-10, which is similar to the relation of D and Capillary number Ca when Re ≪ 1. When the surfactant concentration is lower than the critical micelle concentration (CMC), the distribution of surfactants, the droplet inclination angle θ and the droplet deformation parameter D were investigated at different surfactant density at interface ds and shear rate ?. When the droplet size is close to the characteristic size of surfactant molecules, phase interfaces of water in oil (W/O) and oil in water (O/W) systems have different microstructures, which result in differences in the surfactant distribution, the droplet inclination angle and deformation of the two systems.

A Theoretically Informed Model for the Rheology of Entangled Block Copolymer Nanocomposites

NASA Astrophysics Data System (ADS)

Su, Yongrui; Ramirez-Hernandez, Abelardo; Peters, Brandon; de Pablo, Juan J.

2014-03-01

The addition of nanoparticles to block copolymer systems has been shown to have important effects on their equilibrium structure and properties. Less is known about the non-equilibrium behavior of block polymer nanocomposites. A new particle-based, theoretically informed coarse-grained model for multicomponent nanocomposites is proposed to examine the effects of nanoparticles on the rheology of entangled block copolymer melts. Entanglements are treated at the two-molecule level, through slip-springs that couple the dynamics of neighboring pairs of chains. The inclusion of slip-springs changes the polymer dynamics from unentangled to entangled. The nanoparticles are functionalized with short polymer chains that can entangle with the copolymers. We study the nonlinear rheology of the resulting nanocomposites under shear flow with a dissipative particle dynamics (DPD) thermostat.

A simple analytical procedure to replace HPLC for monitoring treatment concentrations of chloramine-T on fish culture facilities

USGS Publications Warehouse

Dawson, Verdel K.; Meinertz, Jeffery R.; Schmidt, Larry J.; Gingerich, William H.

2003-01-01

Concentrations of chloramine-T must be monitored during experimental treatments of fish when studying the effectiveness of the drug for controlling bacterial gill disease. A surrogate analytical method for analysis of chloramine-T to replace the existing high-performance liquid chromatography (HPLC) method is described. A surrogate method was needed because the existing HPLC method is expensive, requires a specialist to use, and is not generally available at fish hatcheries. Criteria for selection of a replacement method included ease of use, analysis time, cost, safety, sensitivity, accuracy, and precision. The most promising approach was to use the determination of chlorine concentrations as an indicator of chloramine-T. Of the currently available methods for analysis of chlorine, the DPD (N,N-diethyl-p-phenylenediamine) colorimetric method best fit the established criteria. The surrogate method was evaluated under a variety of water quality conditions. Regression analysis of all DPD colorimetric analyses with the HPLC values produced a linear model (Y=0.9602 X+0.1259) with an r2 value of 0.9960. The average accuracy (percent recovery) of the DPD method relative to the HPLC method for the combined set of water quality data was 101.5%. The surrogate method was also evaluated with chloramine-T solutions that contained various concentrations of fish feed or selected densities of rainbow trout. When samples were analyzed within 2 h, the results of the surrogate method were consistent with those of the HPLC method. When samples with high concentrations of organic material were allowed to age more than 2 h before being analyzed, the DPD method seemed to be susceptible to interference, possibly from the development of other chloramine compounds. However, even after aging samples 6 h, the accuracy of the surrogate DPD method relative to the HPLC method was within the range of 80–120%. Based on the data comparing the two methods, the U.S. Food and Drug Administration has concluded that the DPD colorimetric method is appropriate to use to measure chloramine-T in water during pivotal efficacy trials designed to support the approval of chloramine-T for use in fish culture.

Blood Flow: Multi-scale Modeling and Visualization (July 2011)

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

None

2011-01-01

Multi-scale modeling of arterial blood flow can shed light on the interaction between events happening at micro- and meso-scales (i.e., adhesion of red blood cells to the arterial wall, clot formation) and at macro-scales (i.e., change in flow patterns due to the clot). Coupled numerical simulations of such multi-scale flow require state-of-the-art computers and algorithms, along with techniques for multi-scale visualizations. This animation presents early results of two studies used in the development of a multi-scale visualization methodology. The fisrt illustrates a flow of healthy (red) and diseased (blue) blood cells with a Dissipative Particle Dynamics (DPD) method. Each bloodmore » cell is represented by a mesh, small spheres show a sub-set of particles representing the blood plasma, while instantaneous streamlines and slices represent the ensemble average velocity. In the second we investigate the process of thrombus (blood clot) formation, which may be responsible for the rupture of aneurysms, by concentrating on the platelet blood cells, observing as they aggregate on the wall of an aneruysm. Simulation was performed on Kraken at the National Institute for Computational Sciences. Visualization was produced using resources of the Argonne Leadership Computing Facility at Argonne National Laboratory.« less

The Preemptive Stocker Dispatching Rule of Automatic Material Handling System in 300 mm Semiconductor Manufacturing Factories

NASA Astrophysics Data System (ADS)

Wang, C. N.; Lin, H. S.; Hsu, H. P.; Wang, Yen-Hui; Chang, Y. P.

2016-04-01

The integrated circuit (IC) manufacturing industry is one of the biggest output industries in this century. The 300mm wafer fabs is the major fab size of this industry. The automatic material handling system (AMHS) has become one of the most concerned issues among semiconductor manufacturers. The major lot delivery of 300mm fabs is used overhead hoist transport (OHT). The traffic jams are happened frequently due to the wide variety of products and big amount of OHTs moving in the fabs. The purpose of this study is to enhance the delivery performance of automatic material handling and reduce the delay and waiting time of product transportation for both hot lots and normal lots. Therefore, this study proposes an effective OHT dispatching rule: preemptive stocker dispatching (PSD). Simulation experiments are conducted and one of the best differentiated preemptive rule, differentiated preemptive dispatching (DPD), is used for comparison. Compared with DPD, The results indicated that PSD rule can reduce average variable delivery time of normal lots by 13.15%, decreasing average variable delivery time of hot lots by 17.67%. Thus, the PSD rule can effectively reduce the delivery time and enhance productivity in 300 mm wafer fabs.

Innovative Procedure for the, in Situ, Measurement of the Resistive Thermal Coefficient of H(D)/Pd during Electrolysis:. Cross-Comparison of New Elements Detected in the Th-Hg-Pd-D(H) Electrolytic Cells

NASA Astrophysics Data System (ADS)

Celani, Francesco; Spallone, A.; Righi, E.; Trenta, G.; Catena, C.; D'Agostaro, G.; Quercia, P.; Andreassi, V.; Marini, P.; di Stefano, V.; Nakamura, M.; Mancini, A.; Sona, P. G.; Fontana, F.; Gamberale, L.; Garbelli, D.; Celia, E.; Falcioni, F.; Marchesini, M.; Novaro, E.; Mastromatteo, U.

2006-02-01

In the framework of cold fusion studies one of the most important parameters is the deuterium (D) to palladium (Pd) ratio, D/Pd. It is well known that the value of this parameter is related to the normalised resistivity (R/R0) of the D-Pd system. When at high D/Pd ratios (i.e. at low R/R0 values) some excess heat occurs, the Pd wire temperature increase and, as a consequence, the apparent R/R0 value also increases. This effect might give raise to ambiguous data interpretation: similar results are in fact expected in case of a Pd wire degassing (i.e. decreasing of D/Pd ratio). To solve this problem, we developed an innovative procedure and a suitable experimental set-up for the in situ measurement of the Resistive Temperature Coefficient (which is affected only by the real D/Pd ratio) during electrolysis. We will report the results on the hydrogen and deuterium loading of thin (50 μm), and long (60cm) Pd wires, immersed in a solution of C2H5OD (or C2H5OH) and D2O (or H2O), with addition of thorium (Th) and mercury (Hg) salts at micromolar concentrations. Evidence of "transmutations" of some elements occasionally present on the Pd surface, and sometimes also in the electrolytic solution, have often been claimed in cold fusion experiments. In the present work, unexpected elements have been detected by high-resolution ICP-MS analysis. Some of these elements have also an isotopic composition different from the natural one.

BONE TURNOVER IN OSTEOPOROTIC WOMEN DURING LONG-TERM ORAL BISPHOSPHONATES TREATMENT: IMPLICATIONS FOR TREATMENT FAILURE AND "DRUG HOLIDAY" IN THE REAL WORLD.

PubMed

Liel, Yair; Plakht, Ygal; Tailakh, Muhammad Abu

2017-07-01

Little data exist to support concerns over bone turnover suppression during prolonged oral bisphosphonate treatment and on consequences of the recommended "drug holiday." This study was performed to assess bone resorption rates in postmenopausal osteoporotic women on prolonged oral bisphosphonate treatment and in response to switching to "drug holiday" intravenous bisphosphonate, or continuation of oral bisphosphonates. The frequency distribution of the bone resorption marker urinary deoxypyridinoline crosslinks (uDPD), was obtained retrospectively from 211 osteoporotic women attended at an academic hospital endocrine clinic, treated for >2 years with oral bisphosphonates. In some patients, uDPD was re-assessed following modification or continuation of treatment. The mean duration of oral bisphosphonates treatment was 7.2 ± 3.1 years. uDPD was within reference range for premenopausal women in 61.6% of the patients, below in 7.6% of the patients, and above upper limit in 30.8%. uDPD decreased significantly following intravenous zoledronic acid, increased significantly during "drug holiday," and slightly decreased in those continued on oral bisphosphonate treatment. In this real-world study, the majority of women on prolonged oral bisphosphonates maintained bone resorption rates within the normal reference range for premenopausal women. The likelihood for inadequate suppression was considerably greater than that of over-suppression. Implementing a "drug holiday" resulted in a marked increase in bone resorption rates. Additional studies should explore the potential role of bone turnover markers in the evaluation of patients on prolonged oral bisphosphonates and during "drug holiday" in different settings and using additional markers. BMD = bone mineral density; IQR = interquartile range; uDPD = urinary deoxypyridinoline crosslinks.

Use of Daily Phone Diary to study religiosity and mood: Convergent validity

PubMed Central

Szczesniak, Rhonda D.; Zou, Yuanshu; Dimitriou, Sophia M.; Quittner, Alexandra L.; Grossoehme, Daniel H.

2017-01-01

Studies of religious/spiritual behavior frequently rely on self-reported questionnaire data, which is susceptible to bias. The Daily Phone Diary (DPD) was developed to minimize bias in reporting activities and behavior across a 24-hour period. A cross-sectional study of 126 parents of children with cystic fibrosis was used to establish the validity of the DPD to study religious/spiritual behaviors. Longitudinal models were used to determine the odds of improved mood during religious/spiritual activities. Convergent validity was found. Participants had increased odds of improved mood during religious/spiritual activities compared to non-religious/spiritual activities. Associations with gender and religious affiliations were found. The DPD is a valid tool for studying religious/spiritual activities and opens novel avenues for chaplaincy research and the development of chaplaincy interventions incorporating these findings. PMID:27869567

Mesoscale simulations of confined Nafion thin films.

PubMed

Vanya, P; Sharman, J; Elliott, J A

2017-12-07

The morphology and transport properties of thin films of the ionomer Nafion, with thicknesses on the order of the bulk cluster size, have been investigated as a model system to explain the anomalous behaviour of catalyst/electrode-polymer interfaces in membrane electrode assemblies. We have employed dissipative particle dynamics (DPD) to investigate the interaction of water and fluorocarbon chains, with carbon and quartz as confining materials, for a wide range of operational water contents and film thicknesses. We found confinement-induced clustering of water perpendicular to the thin film. Hydrophobic carbon forms a water depletion zone near the film interface, whereas hydrophilic quartz results in a zone with excess water. There are, on average, oscillating water-rich and fluorocarbon-rich regions, in agreement with experimental results from neutron reflectometry. Water diffusivity shows increasing directional anisotropy of up to 30% with decreasing film thickness, depending on the hydrophilicity of the confining material. A percolation analysis revealed significant differences in water clustering and connectivity with the confining material. These findings indicate the fundamentally different nature of ionomer thin films, compared to membranes, and suggest explanations for increased ionic resistances observed in the catalyst layer.

Mesoscale simulations of confined Nafion thin films

NASA Astrophysics Data System (ADS)

Vanya, P.; Sharman, J.; Elliott, J. A.

2017-12-01

The morphology and transport properties of thin films of the ionomer Nafion, with thicknesses on the order of the bulk cluster size, have been investigated as a model system to explain the anomalous behaviour of catalyst/electrode-polymer interfaces in membrane electrode assemblies. We have employed dissipative particle dynamics (DPD) to investigate the interaction of water and fluorocarbon chains, with carbon and quartz as confining materials, for a wide range of operational water contents and film thicknesses. We found confinement-induced clustering of water perpendicular to the thin film. Hydrophobic carbon forms a water depletion zone near the film interface, whereas hydrophilic quartz results in a zone with excess water. There are, on average, oscillating water-rich and fluorocarbon-rich regions, in agreement with experimental results from neutron reflectometry. Water diffusivity shows increasing directional anisotropy of up to 30% with decreasing film thickness, depending on the hydrophilicity of the confining material. A percolation analysis revealed significant differences in water clustering and connectivity with the confining material. These findings indicate the fundamentally different nature of ionomer thin films, compared to membranes, and suggest explanations for increased ionic resistances observed in the catalyst layer.

Spectrophotometric methods as a novel screening approach for analysis of dihydropyrimidine dehydrogenase activity before treatment with 5-fluorouracil chemotherapy.

PubMed

Dolegowska, B; Ostapowicz, A; Stanczyk-Dunaj, M; Blogowski, W

2012-08-01

5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutics in the treatment of malignancies originating from breast, prostate, ovarian, skin and gastrointestinal tissues. Around 80% of administered dose of 5-FU is catabolized by dihydropirymidine dehydrogenase (DPD). Patients, in whom a deficiency or insufficient activity of this enzyme is observed, are at great risk of development of severe, even lethal, 5-FU toxicity. According to recent studies, so far over 30 mutations of DPYD gene, which are associated with DPD deficiency/insufficiency, have already been discovered. Currently, there are several analytical methods used for measurements of DPD activity. However, in this paper we report a novel, simple, economical and more accessible spectrophotometric method for measurements of DPD activity in the peripheral blood mononuclear cells (PBMCs) that was developed and validated on analysis of 200 generally healthy volunteers aged 22-63. We present two spectrophotometric protocols in this study, and as a reference method we used already described reverse phase high-performance liquid chromatography (RP HPLC) analysis. Basing on our findings, we conclude that spectrophotometric methods may be used as a screening protocol preceding 5-FU-based chemotherapy. Nevertheless, before introduction into clinical reality, our results should be confirmed in further larger studies.

Revisiting AI-2 quorum sensing inhibitors: direct comparison of alkyl-DPD analogues and a natural product fimbrolide.

PubMed

Lowery, Colin A; Abe, Takumi; Park, Junguk; Eubanks, Lisa M; Sawada, Daisuke; Kaufmann, Gunnar F; Janda, Kim D

2009-11-04

Quorum sensing (QS) systems have been discovered in a wide variety of bacteria, and mediate both intra- and interspecies communication. The AI-2-based QS system represents the most studied of these proposed interspecies systems and has been shown to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the study of unknown AI-2-based QS systems and the potential treatment of bacterial infections. The fimbrolide class of natural products has exhibited excellent inhibitory activity against AI-2-based QS and as such may be considered the "gold standard" of AI-2 inhibitors. Thus, we sought to include a fimbrolide as a control compound for our recently developed alkyl-DPD panel of AI-2 modulators. Herein, we present a revised synthesis of a commonly studied fimbrolide as well as a direct comparison between the fimbrolide and alkyl-DPD analogues. We demonstrate that our alkyl-DPD analogues are more potent inhibitors of QS in both Vibrio harveyi and Salmonella typhimurium, the two organisms with defined AI-2 QS systems, and in doing so call into question the widely accepted use of fimbrolide-derived compounds as the "gold standard" of AI-2 inhibition.

Maladaptive variants of conscientiousness and agreeableness.

PubMed

Samuel, Douglas B; Gore, Whitney L

2012-12-01

Although reasonably strong support has been obtained for the Five-Factor Model's (FFM) ability to account for the existing personality disorder (PD) constructs, the support for obsessive-compulsive PD (OCPD) and dependent PD (DPD) has been relatively less consistent. Specifically, the expected correlation between OCPD and the FFM trait of Conscientiousness has varied in magnitude across studies while DPD has, at times, also evinced rather weak relationships with FFM Agreeableness. We determined that these inconsistencies were due primarily to the reliance on FFM measures that lack adequate fidelity to assess the maladaptive aspects of high Conscientiousness and Agreeableness. When alternative measures were utilized, the correlations were generally large and in line with expectations. We conclude that OCPD and DPD can be fruitfully conceptualized within the FFM but encourage the use of measures that provide a comprehensive assessment of both the adaptive and maladaptive aspects of the FFM traits. © 2012 The Authors. Journal of Personality © 2012, Wiley Periodicals, Inc.

Bone Remodeling Monitor

NASA Technical Reports Server (NTRS)

Foucar, Charlie; Goldberg, Leslie; Hon, Bodin; Moore, Shannon; Williams, Evan

2009-01-01

The impact of bone loss due to different mechanical loadings in microgravity is a major concern for astronauts upon reintroduction to gravitational forces in exploration missions to the Moon and Mars. it has been shown that astronauts not only lose bone at differing rates, with levels up to 2% per month, but each astronaut will respond to bone loss treatments differently. Pre- and post-flight imaging techniques and frozen urine samples for post-flight laboratory immunoassays To develop a novel, non-invasive, highly . sensitive, portable, intuitive, and low-powered device to measure bone resorption levels in 'real time' to provide rapid and Individualized feedback to maximize the efficacy of bone loss countermeasures 1. Collect urine specimen and analyze the level of bone resorption marker, DPD (deoxypridinoline) excreted. 2. Antibodies specific to DPD conjugated with nanoshells and mixed with specimen, the change in absorbance from agglutination is measured by an optical device. 3. The concentration of DPD is displayed and recorded on a PDA

pH-responsive unimolecular micelle-gold nanoparticles-drug nanohybrid system for cancer theranostics.

PubMed

Lin, Wenjing; Yao, Na; Qian, Long; Zhang, Xiaofang; Chen, Quan; Wang, Jufang; Zhang, Lijuan

2017-08-01

The development of an in situ formed pH-responsive theranostic nanocomposite for anticancer drug delivery and computed tomography (CT) imaging was reported. β-cyclodextrin-{poly(lactide)-poly(2-(dimethylamino) ethyl methacrylate)-poly[oligo(2-ethyl-2-oxazoline)methacrylate]} 21 [β-CD-(PLA-PDMAEMA-PEtOxMA) 21 ] unimolecular micelles served as a template for the in situ formation of gold nanoparticles (GNPs) and the subsequent encapsulation of doxorubicin (DOX). The formation of unimolecular micelles, microstructures and the distributions of GNPs and DOX were investigated through the combination of experiments and dissipative particle dynamics (DPD) simulations. β-CD-(PLA-PDMAEMA-PEtOxMA) 21 formed spherical unimolecular micelles in aqueous solution within a certain range of polymer concentrations. GNPs preferentially distributed in the PDMAEMA area. The maximum wavelength (λ max ) and the size of GNPs increased with increasing concentration of HAuCl 4 . DOX preferentially distributed in the PDMAEMA mesosphere, but penetrated the inner PLA core with increasing DOX concentration. DOX-loaded micelles with 41-61% entrapment efficiency showed fast release (88% after 102h) under acidic tumor conditions. Both in vitro and in vivo experiments revealed superior anticancer efficacy and effective CT imaging properties for β-CD-(PLA-PDMAEMA-PEtOxMA) 21 /Au/DOX. We conclude that the reported unimolecular micelles represent a class of versatile smart nanocarriers for theranostic application. Developing polymeric nanoplatforms as integrated theranostic vehicles for improving cancer diagnostics and therapy is an emerging field of much importance. This article aims to develop an in situ formed pH-responsive theranostic nanocomposite for anticancer drug delivery and computed tomography (CT) imaging. Specific emphases is on structure-properties relationship. There is a sea of literature on polymeric drug nanocarriers, and a couple of polymer-stabilized gold nanoparticles (GNPs) systems for cancer diagnosis are also known. However, to our knowledge, there has been no report on polymeric unimolecular micelles capable of dual loading of GNPs without external reducing agents and anticancer drugs for cancer diagnosis and treatment. To this end, the target of the current work was to develop an in situ formed nanocarrier, which actively dual wrapped CT contrast agent GNPs and hydrophobic anticancer drug doxorubicin (DOX), achieving high CT imaging and antitumor efficacy under in vitro and in vivo acid tumor condition. Meanwhile, by taking advantage of dissipative particle dynamics (DPD) simulation, we further obtained the formation process and mechanism of unimolecular micelles, and detailed distributions and microstructures of GNPs and DOX on unimolecular micelles. Taken together, our results here provide insight and guidance for the design of more effective nanocarriers for cancer theranostic application. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Multiscale modeling of sickle anemia blood blow by Dissipative Partice Dynamics

NASA Astrophysics Data System (ADS)

Lei, Huan; Caswell, Bruce; Karniadakis, George

2011-11-01

A multi-scale model for sickle red blood cell is developed based on Dissipative Particle Dynamics (DPD). Different cell morphologies (sickle, granular, elongated shapes) typically observed in in vitro and in vivo are constructed and the deviations from the biconcave shape is quantified by the Asphericity and Elliptical shape factors. The rheology of sickle blood is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. However, the vaso-occulusion phenomenon, reported in a recent microfluid experiment, is not observed in the pipe flow system unless the adhesive interactions between sickle blood cells and endothelium properly introduced into the model.

A simple analytical procedure to replace HPLC for monitoring treatment concentrations of chloramine-T on fish culture facilities

USGS Publications Warehouse

Dawson, V.K.; Meinertz, J.R.; Schmidt, L.J.; Gingerich, W.H.

2003-01-01

Concentrations of chloramine-T must be monitored during experimental treatments of fish when studying the effectiveness of the drug for controlling bacterial gill disease. A surrogate analytical method for analysis of chloramine-T to replace the existing high-performance liquid chromatography (HPLC) method is described. A surrogate method was needed because the existing HPLC method is expensive, requires a specialist to use, and is not generally available at fish hatcheries. Criteria for selection of a replacement method included ease of use, analysis time, cost, safety, sensitivity, accuracy, and precision. The most promising approach was to use the determination of chlorine concentrations as an indicator of chloramine-T. Of the currently available methods for analysis of chlorine, the DPD (N,N-diethyl-p-phenylenediamine) colorimetric method best fit the established criteria. The surrogate method was evaluated under a variety of water quality conditions. Regression analysis of all DPD colorimetric analyses with the HPLC values produced a linear model (Y=0.9602 X+0.1259) with an r2 value of 0.9960. The average accuracy (percent recovery) of the DPD method relative to the HPLC method for the combined set of water quality data was 101.5%. The surrogate method was also evaluated with chloramine-T solutions that contained various concentrations of fish feed or selected densities of rainbow trout. When samples were analyzed within 2 h, the results of the surrogate method were consistent with those of the HPLC method. When samples with high concentrations of organic material were allowed to age more than 2 h before being analyzed, the DPD method seemed to be susceptible to interference, possibly from the development of other chloramine compounds. However, even after aging samples 6 h, the accuracy of the surrogate DPD method relative to the HPLC method was within the range of 80-120%. Based on the data comparing the two methods, the U.S. Food and Drug Administration has concluded that the DPD colorimetric method is appropriate to use to measure chloramine-T in water during pivotal efficacy trials designed to support the approval of chloramine-T for use in fish culture. ?? 2003 Elsevier Science B.V. All rights reserved.

Stimulation of in vivo hepatic uptake and in vitro hepatic binding of (/sup 125/I)2-lodo-3,7,8-trichlorodibenzo-p-dioxin by the administration of agonist for the Ah receptor

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

Poland, A.; Teitelbaum, P.; Glover, E.

1989-07-01

(125I)2-lodo-3,7,8-trichlorodibenzo-p-dioxin ((125I)Cl3DpD), a radiolabeled, isosteric, analogue of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was synthesized and used to study in vivo tissue localization and in vivo tissue binding. Twenty-four hours after the administration of a tracer dose (1 X 10(-10) mol/kg) of (125I) Cl3DpD to C57BL/6J mice, the hepatic concentration of radioactivity was 1-2% of the administered dose, whereas in mice pretreated with TCDD (1 X 10(-7) mol/kg), the hepatic accumulation of radiolabel was 25-30% of that administered. Liver homogenate from TCDD-treated mice bound 4 to 10 times more (125I)Cl3DpD than homogenate from control mice. The enhancement of in vivo uptake and in vitromore » tissue binding of (125I)Cl3DpD by TCDD administration was confined to liver and was not observed in other tissues examined, kidney, lung, spleen, small intestines, and muscle. The administration of TCDD to C57BL/6J mice produces dose-related stimulation of in vivo hepatic uptake of (125I)Cl3DpD, binding of radioligand to liver homogenate, and hepatic aryl hydrocarbon hydroxylase activity, with the dose for half-maximal stimulation, ED50, varying from 1.5 to 4.0 x 10(-9) mol/kg. In congenic C57BL/6J (Ahd/Ahd) mice, which express the lower affinity Ah receptor, the ED50 values for all three responses were shifted to approximately 10-fold higher doses. 3,3',4,4',5,5'-Hexabromobiphenyl, a weak agonist for the Ah receptor produced a dose-related stimulation of these three responses in C57BL/6J mice (ED50 values of approximately 5 X 10(-7) mol/kg), but was without effect in C57BL/6J (Ahd/Ahd) mice. Stimulation of vivo hepatic uptake and in vitro liver homogenate binding of (125I)Cl3DpD was produced by administration of Ah agonists, such as 2,3,7,8-tetrachlorodibenzofuran and beta-naphthoflavone, but inactive congeners and other compounds that do not act via the Ah receptor.« less

An evaluation of the effect of age and the peri-parturient period on bone metabolism in dairy cows as measured by serum bone-specific alkaline phosphatase activity and urinary deoxypyridinoline concentration.

PubMed

Sato, Reiichiro; Onda, Ken; Kato, Hajime; Ochiai, Hideharu; Kawai, Kazuhiro; Iriki, Tsunenori; Kaneko, Kazuyuki; Yamazaki, Yukio; Wada, Yasunori

2013-08-01

Various biochemical markers help to evaluate the state of bone turnover in humans and could be used during the peri-parturient period in dairy cows when calcium (Ca) metabolism changes dramatically. To investigate this, the peri-partum characteristics of serum bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were investigated. Both serum BAP activity and urinary DPD concentrations were increased and demonstrated wide variability in younger animals, and these findings were consistent with other bone turnover markers. Around the time of parturition, serum Ca concentration and serum BAP activity in multiparous cows were significantly lower than in primiparous cows, but urinary DPD concentration was unchanged. The use of BAP as a bone formation marker appears to be valuable for evaluating bone remodelling status in cows, but the specificity of the test needs to be confirmed. The DPD/BAP ratio around parturition demonstrated a clear difference in bone turnover status between the two parity groups with multiparous cows demonstrating increased signs of bone resorption compared with primiparous cows, corresponding to the Ca requirement for milk production. In future studies, the applicability of the ratio of bone resorption marker to bone formation marker should be evaluated for bone turnover assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Traveling magnetopause distortion related to a large-scale magnetosheath plasma jet: THEMIS and ground-based observations

NASA Astrophysics Data System (ADS)

Dmitriev, A. V.; Suvorova, A. V.

2012-08-01

Here, we present a case study of THEMIS and ground-based observations of the perturbed dayside magnetopause and the geomagnetic field in relation to the interaction of an interplanetary directional discontinuity (DD) with the magnetosphere on 16 June 2007. The interaction resulted in a large-scale local magnetopause distortion of an "expansion - compression - expansion" (ECE) sequence that lasted for ˜15 min. The compression was caused by a very dense, cold, and fast high-βmagnetosheath plasma flow, a so-called plasma jet, whose kinetic energy was approximately three times higher than the energy of the incident solar wind. The plasma jet resulted in the effective penetration of magnetosheath plasma inside the magnetosphere. A strong distortion of the Chapman-Ferraro current in the ECE sequence generated a tripolar magnetic pulse "decrease - peak- decrease" (DPD) that was observed at low and middle latitudes by some ground-based magnetometers of the INTERMAGNET network. The characteristics of the ECE sequence and the spatial-temporal dynamics of the DPD pulse were found to be very different from any reported patterns of DD interactions with the magnetosphere. The observed features only partially resembled structures such as FTE, hot flow anomalies, and transient density events. Thus, it is difficult to explain them in the context of existing models.

MaMiCo: Transient multi-instance molecular-continuum flow simulation on supercomputers

NASA Astrophysics Data System (ADS)

Neumann, Philipp; Bian, Xin

2017-11-01

We present extensions of the macro-micro-coupling tool MaMiCo, which was designed to couple continuum fluid dynamics solvers with discrete particle dynamics. To enable local extraction of smooth flow field quantities especially on rather short time scales, sampling over an ensemble of molecular dynamics simulations is introduced. We provide details on these extensions including the transient coupling algorithm, open boundary forcing, and multi-instance sampling. Furthermore, we validate the coupling in Couette flow using different particle simulation software packages and particle models, i.e. molecular dynamics and dissipative particle dynamics. Finally, we demonstrate the parallel scalability of the molecular-continuum simulations by using up to 65 536 compute cores of the supercomputer Shaheen II located at KAUST. Program Files doi:http://dx.doi.org/10.17632/w7rgdrhb85.1 Licensing provisions: BSD 3-clause Programming language: C, C++ External routines/libraries: For compiling: SCons, MPI (optional) Subprograms used: ESPResSo, LAMMPS, ls1 mardyn, waLBerla For installation procedures of the MaMiCo interfaces, see the README files in the respective code directories located in coupling/interface/impl. Journal reference of previous version: P. Neumann, H. Flohr, R. Arora, P. Jarmatz, N. Tchipev, H.-J. Bungartz. MaMiCo: Software design for parallel molecular-continuum flow simulations, Computer Physics Communications 200: 324-335, 2016 Does the new version supersede the previous version?: Yes. The functionality of the previous version is completely retained in the new version. Nature of problem: Coupled molecular-continuum simulation for multi-resolution fluid dynamics: parts of the domain are resolved by molecular dynamics or another particle-based solver whereas large parts are covered by a mesh-based CFD solver, e.g. a lattice Boltzmann automaton. Solution method: We couple existing MD and CFD solvers via MaMiCo (macro-micro coupling tool). Data exchange and coupling algorithmics are abstracted and incorporated in MaMiCo. Once an algorithm is set up in MaMiCo, it can be used and extended, even if other solvers are used (as soon as the respective interfaces are implemented/available). Reasons for the new version: We have incorporated a new algorithm to simulate transient molecular-continuum systems and to automatically sample data over multiple MD runs that can be executed simultaneously (on, e.g., a compute cluster). MaMiCo has further been extended by an interface to incorporate boundary forcing to account for open molecular dynamics boundaries. Besides support for coupling with various MD and CFD frameworks, the new version contains a test case that allows to run molecular-continuum Couette flow simulations out-of-the-box. No external tools or simulation codes are required anymore. However, the user is free to switch from the included MD simulation package to LAMMPS. For details on how to run the transient Couette problem, see the file README in the folder coupling/tests, Remark on MaMiCo V1.1. Summary of revisions: Open boundary forcing; Multi-instance MD sampling; support for transient molecular-continuum systems Restrictions: Currently, only single-centered systems are supported. For access to the LAMMPS-based implementation of DPD boundary forcing, please contact Xin Bian, xin.bian@tum.de. Additional comments: Please see file license_mamico.txt for further details regarding distribution and advertising of this software.

Effects of thermal noise on the transitional dynamics of an inextensible elastic filament in stagnation flow.

PubMed

Deng, Mingge; Grinberg, Leopold; Caswell, Bruce; Karniadakis, George Em

2015-06-28

We investigate the dynamics of a single inextensible elastic filament subject to anisotropic friction in a viscous stagnation-point flow, by employing both a continuum model represented by Langevin type stochastic partial differential equations (SPDEs) and a dissipative particle dynamics (DPD) method. Unlike previous works, the filament is free to rotate and the tension along the filament is determined by the local inextensible constraint. The kinematics of the filament is recorded and studied with normal modes analysis. The results show that the filament displays an instability induced by negative tension, which is analogous to Euler buckling of a beam. Symmetry breaking of normal modes dynamics and stretch-coil transitions are observed above the threshold of the buckling instability point. Furthermore, both temporal and spatial noise are amplified resulting from the interaction of thermal fluctuations and nonlinear filament dynamics. Specifically, the spatial noise is amplified with even normal modes being excited due to symmetry breaking, while the temporal noise is amplified with increasing time correlation length and variance.

Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers.

PubMed

Mekata, Eiji; Murata, Satoshi; Sonoda, Hiromichi; Shimizu, Tomoharu; Umeda, Tomoko; Shiomi, Hisanori; Naka, Shigeyuki; Yamamoto, Hiroshi; Abe, Hajime; Edamatsu, Takeo; Fujieda, Ayako; Fujioka, Masaki; Wada, Tsutomu; Tani, Tohru

2013-12-01

Protein-bound polysaccharide-K (PSK) enhances the antitumor effect of anticancer drug when used clinically in combination with such drugs. PSK is known to act by immune-mediated mechanisms; however, the relationship between PSK and metabolic enzymes of anticancer drugs is unknown. We used the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) clinically to evaluate the sensitivity of anticancer drugs. In the present study, we modified the CD-DST by adding peripheral blood mononuclear cells (PBMCs) (immuno-CD-DST) and examined the antitumor effect of PSK in combination with anticancer drugs. First, HCT116 human colon cancer cells were cultured with PSK and 5-fluorouracil (5-FU) or 5'-deoxy-5-fluorouridine (5'-DFUR) in the presence or absence of PBMCs, and the antiproliferative effects were compared. In the presence of PBMCs, PSK augmented the inhibitory effects of 5-FU and 5'-DFUR on HCT116 cell proliferation. Next, using human gastric cancer and colon cancer cell lines, the effects of PSK on mRNA expression of various metabolic enzymes of fluoropyrimidines: dihydropyrimidine dehydrogenase (DPD), thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl transferase, were examined by real-time PCR. PSK significantly enhanced DPD mRNA expression in all of the cancer cell lines tested, but not those of the other enzymes. Addition of IFN-α and TRAIL, cytokines known to inhibit DPD expression, to the cultures reduced DPD mRNA expression in the cancer cells. When PBMC samples collected from healthy volunteers were cultured with PSK, IFN-α mRNA expression increased in 3 of the 5 PBMC samples, while TRAIL mRNA expression was unchanged. The present results propose the possibility that PSK induces PBMCs to express IFN-α which inhibits DPD expression, and consequently augments the antitumor effect of 5-FU or 5'-DFUR. Immuno-CD-DST is useful for evaluating drugs with immunological mechanisms of action.

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

PubMed Central

Fisher, A; Srikusalanukul, W; Davis, M; Smith, P

2013-01-01

Background Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures. Aims and methods To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured. Results CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death. Conclusion SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets. PMID:23460043

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

NASA Technical Reports Server (NTRS)

Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

1996-01-01

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

Single droplet drying step characterization in microsphere preparation.

PubMed

Al Zaitone, Belal; Lamprecht, Alf

2013-05-01

Spray drying processes are difficult to characterize since process parameters are not directly accessible. Acoustic levitation was used to investigate microencapsulation by spray drying on one single droplet facilitating the analyses of droplet behavior upon drying. Process parameters were simulated on a poly(lactide-co-glycolide)/ethyl acetate combination for microencapsulation. The results allowed quantifying the influence of process parameters such as temperature (0-40°C), polymer concentration (5-400 mg/ml), and droplet size (0.5-1.37 μl) on the drying time and drying kinetics as well as the particle morphology. The drying of polymer solutions at temperature of 21°C and concentration of 5 mg/ml, shows that the dimensionless particle diameter (Dp/D0) approaches 0.25 and the particle needs 350 s to dry. At 400 mg/ml, Dp/D0=0.8 and the drying time increases to one order of magnitude and a hollow particle is formed. The study demonstrates the benefit of using the acoustic levitator as a lab scale method to characterize and study the microparticle formation. This method can be considered as a helpful tool to mimic the full scale spray drying process by providing identical operational parameters such as air velocity, temperature, and variable droplet sizes. Copyright © 2013 Elsevier B.V. All rights reserved.

Can Spatiotemporal Fluoride (18F-) Uptake be Used to Assess Bone Formation in the Tibia? A Longitudinal Study Using PET/CT.

PubMed

Lundblad, Henrik; Karlsson-Thur, Charlotte; Maguire, Gerald Q; Jonsson, Cathrine; Noz, Marilyn E; Zeleznik, Michael P; Weidenhielm, Lars

2017-05-01

When a bone is broken for any reason, it is important for the orthopaedic surgeon to know how bone healing is progressing. There has been resurgence in the use of the fluoride ( 18 F - ) ion to evaluate various bone conditions. This has been made possible by availability of positron emission tomography (PET)/CT hybrid scanners together with cyclotrons. Absorbed on the bone surface from blood flow, 18 F - attaches to the osteoblasts in cancellous bone and acts as a pharmacokinetic agent, which reflects the local physiologic activity of bone. This is important because it shows bone formation indicating that the bone is healing or no bone formation indicating no healing. As 18 F - is extracted from blood in proportion to blood flow and bone formation, it thus enables determination of bone healing progress. The primary objective of this study was to determine whether videos showing the spatiotemporal uptake of 18 F - via PET bone scans could show problematic bone healing in patients with complex tibia conditions. A secondary objective was to determine if semiquantification of radionuclide uptake was consistent with bone healing. This study investigated measurements of tibia bone formation in patients with complex fractures, osteomyelitis, and osteotomies treated with a Taylor Spatial Frame TM (TSF) by comparing clinical healing progress with spatiotemporal fluoride ( 18 F - ) uptake and the semiquantitative standardized uptake value (SUV). This procedure included static and dynamic image acquisition. For intrapatient volumes acquired at different times, the CT and PET data were spatially registered to bring the ends of the bones that were supposed to heal into alignment. To qualitatively observe how and where bone formation was occurring, time-sequenced volumes were reconstructed and viewed as a video. To semiquantify the uptake, the mean and maximum SUVs (SUVmean, SUVmax) were calculated for the ends of the bones that were supposed to heal and for normal bone, using a spherical volume of interest drawn on the registered volumes. To make the semiquantitative data comparable for all patients with multiple examinations, the SUVmean and SUVmax difference per day (SUVmeanDPD and SUVmaxDPD) between the first PET/CT scan and each subsequent one was calculated. Indicators of poor healing progress were (1) uneven distribution of the radionuclide uptake between ends of the bones that were supposed to heal as seen in the video or, (2) low absolute magnitude of the SUV difference data. Twenty-four patients treated between October 2013 and April 2015 with a TSF gave informed consent to be examined with 18 F - PET/CT bone scans. Twenty-two patients successfully completed treatment, one of whom had only one PET/CT scan. Observation of 18 F - uptake was able to identify three patients whose healing progress was poor, indicated by uneven distribution of radionuclide uptake across the ends of the bones that were supposed to heal. An absolute magnitude of the SUVmaxDPD of 0.18 or greater indicated good bone formation progress. This was verified in 10 patients by the days between the operation to attach and to remove the TSF being less than 250 days, whereas other SUVmaxDPD values were ambiguous, with 11 patients achieving successful completion. Observation of the spatiotemporal uptake of 18 F - appears to be a promising method to enable the clinician to assess the progress of bone formation in different parts of the bone. Bone uptake which is uneven across the ends of bone that were supposed to heal or very low bone uptake might indicate impaired bone healing where early intervention may then be needed. However, semiquantification of 18 F - uptake (SUVmaxDPD), SUVmeanDPD) was ambiguous in showing consistency with the bone-healing progress. Level III, diagnostic study.

Sensorimotor gating characteristics of violent men with comorbid psychosis and dissocial personality disorder: Relationship with antisocial traits and psychosocial deprivation.

PubMed

Sedgwick, Ottilie; Young, Susan; Greer, Ben; Arnold, Jack; Parsons, Aisling; Puzzo, Ignazio; Terracciano, Mariafatima; Das, Mrigendra; Kumari, Veena

2017-07-06

Evidence suggests violence amongst those with psychosis is not aetiologically homogeneous, and that a large proportion of those who engage in violent behaviour have a comorbid antisocial personality disorder. Initial investigations indicate that this subgroup has distinct historical and neuropsychological characteristics, which may indicate diverse treatment needs. This study investigated sensorimotor gating characteristics of violent men with diagnoses of both psychosis and dissocial personality disorder (DPD) (n=21) relative to violent men with psychosis alone (n=12), DPD alone (n=14) and healthy, non-violent male controls (n=27), using the prepulse inhibition (PPI) paradigm. The results indicated that, relative to the psychosis alone and healthy control groups, the comorbid group had lower PPI, especially at 60-ms prepulse-to-pulse interval. The DPD group took an intermediary position and did not differ from any group. Antisocial personality traits (factor two scores of the Psychopathy Checklist - Revised), and greater severity of childhood psychosocial deprivation (including physical and sexual abuse), were significantly correlated with poor PPI across the clinical sample. The findings suggest diverse sensorimotor gating profiles amongst subgroups of violent offenders, with comorbid psychosis and DPD showing most impairment. This is consistent with a 'double dose' of deficit explanation amongst those with both diagnoses, explained at least in part by presence of antisocial personality traits and childhood psychosocial deprivation. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparison of bone-related biomarkers and CA27.29 to assess response to treatment of osseous metastatic breast cancer.

PubMed

Lüfter, D; Richter, A; Günther, S; Flath, B; Akrivakis, C; Geppert, R; Wernecke, K D; Possinger, K

2000-01-01

The assessment of bone metastases by clinical examination or imaging techniques is still considered unreliable. We compared a specific marker of bone resorption, urinary deoxypyridinoline (DPD)-crosslinks, with serum calcium (Ca), alkaline phosphatase (AP) and CA27.29, to evaluate the status of bone metastases in patients with breast cancer. Second morning voided urine was collected from 2 groups of patient (pts), those without evidence of disease (n = 118), and those with bone metastases (n = 85) under specific therapy plus pamidronate. DPD and CA27.29 were measured on the automated ACS180 system (Bayer Diagnostics, Tarrytown, NY, USA). Receiver operating characteristics (ROC) curves were established for each of the 4 biomarkers to determine whether they could distinguish the 2 subsets of pts with clinically sufficient validity, and to establish the corresponding cut-off values. Neither Ca nor AP was useful in discriminating the 2 subgroups. At a DPD cut-off of 13 nmol/mmol, we found a specificity of 69% and a sensitivity of 53% for diagnosing bone metastases. Best results, however, were seen for CA27.29. A cut-off value of 30 U/ml resulted in a specificity of 62% and a sensitivity of 81%. CA27.29 was the best parameter for the discrimination of stage IV breast cancer with bone metastases. The primary advantage of DPD lies in the monitoring of bone metastases under specific therapy.

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

PubMed

Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

2007-03-01

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxic effects: potential for an individualized medicine approach.

PubMed

Saif, M Wasif; Lee, Adam M; Offer, Steven M; McConnell, Kathleen; Relias, Valerie; Diasio, Robert B

2014-01-01

5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effect-associated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxic effects in individuals of African ancestry. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation

PubMed Central

Yu, Hongyi

2018-01-01

A novel geolocation architecture, termed “Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE)” is proposed in this paper. Existing Direct Position Determination (DPD) methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations) and a simplified MUltiple SIgnal Classification (MUSIC) algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD) in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC) method and the Active Set Algorithm (ASA) are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML) method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér–Rao Lower Bound (CRLB) is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML. PMID:29562601

Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation.

PubMed

Du, Jianping; Wang, Ding; Yu, Wanting; Yu, Hongyi

2018-03-17

A novel geolocation architecture, termed "Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE)" is proposed in this paper. Existing Direct Position Determination (DPD) methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations) and a simplified MUltiple SIgnal Classification (MUSIC) algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD) in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC) method and the Active Set Algorithm (ASA) are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML) method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér-Rao Lower Bound (CRLB) is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML.

Anisotropic Energy Transport Properties of 1,3,5-Triamino-2,4,6-Trinitrobenzene (TATB)

NASA Astrophysics Data System (ADS)

Kroonblawd, Matthew P.

Anisotropic energy transport properties were determined theoretically for crystals of the insensitive explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) using molecular dynamics simulations. Determination of these properties is necessary for the analysis and interpretation of molecular dynamics predictions of transient processes such as shock response and hot spot formation/relaxation and is similarly important for the accurate parameterization of meso- and continuum-scale engineering models aimed at understanding complex processes such as ignition and growth leading to detonation. TATB crystal exhibits a graphitic-like layered packing structure with a two-dimensional hydrogen-bonding network that forms within, but not between, the molecule-thick layers that comprise the crystal. This structure is thought to be the primary factor behind the significant anisotropy in many physical properties of TATB crystals. Anisotropic thermal conductivity coefficients were determined for initially defect-free and defective TATB crystals and isotropic values were determined for the liquid at temperatures and pressures up to (1800 K, 2.0 GPa). The room temperature, atmospheric pressure thermal conductivity for TATB is predicted to be generally greater and more anisotropic than the thermal conductivities of other molecular explosives; conduction within the layers is approximately 70% greater than conduction between the layers. The conductivity is predicted to decrease with temperature approximately as λ ∝ 1/T over the interval 200 K ≤ T ≤ 700 K and to linearly increase with pressure up to 2.5 GPa. Direction-dependent relaxation of idealized one-dimensional hot spots was studied. Results from hot spot relaxation simulations were compared with and fit to solutions for the one-dimensional diffusive heat equation by treating the thermal di.usivity as a parameter to assess the validity of using continuum models to describe heat transport in TATB on length scales below 10 nm. A dissipative particle dynamics (DPD) at constant energy (DPDE) coarsegrained model is developed for TATB and applied to micron-scale shock simulations wherein the predicted shock response is shown to be highly sensitive to a model parameter controlling kinetics of energy transport between inter- and intramolecular degrees of freedom. A generalized crystal-cutting method is developed that enables facile construction of three-dimensionally periodic simulation cells containing arbitrarily oriented single crystals and crystal-crystal interfaces for materials of arbitrary symmetry class. Strategies for non-uniform sampling of molecular dynamics simulations of transient phenomena are proposed that have the potential to drastically reduce data storage costs.

Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

PubMed

Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

2016-11-24

Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

Prediction of in vivo drug-drug interactions based on mechanism-based inhibition from in vitro data: inhibition of 5-fluorouracil metabolism by (E)-5-(2-Bromovinyl)uracil.

PubMed

Kanamitsu, S I; Ito, K; Okuda, H; Ogura, K; Watabe, T; Muro, K; Sugiyama, Y

2000-04-01

The fatal drug-drug interaction between sorivudine, an antiviral drug, and 5-fluorouracil (5-FU) has been shown to be caused by a mechanism-based inhibition. In this interaction, sorivudine is converted by gut flora to (E)-5-(2-bromovinyl)uracil (BVU), which is metabolically activated by dihydropyrimidine dehydrogenase (DPD), and the activated BVU irreversibly binds to DPD itself, thereby inactivating it. In an attempt to predict this interaction in vivo from in vitro data, inhibition of 5-FU metabolism by BVU was investigated by using rat and human hepatic cytosol and human recombinant DPD. Whichever enzyme was used, increased inhibition was observed that depended on the preincubation time of BVU and enzyme in the presence of NADPH and BVU concentration. The kinetic parameters obtained for inactivation represented by k(inact) and K'(app) were 2.05 +/- 1.52 min(-1), 69.2 +/- 60.8 microM (rat hepatic cytosol), 2.39 +/- 0.13 min(-1), 48.6 +/- 11.8 microM (human hepatic cytosol), and 0.574 +/- 0.121 min(-1), 2.20 +/- 0.57 microM (human recombinant DPD). The drug-drug interaction in vivo was predicted quantitatively based on a physiologically based pharmacokinetic model, using pharmacokinetic parameters obtained from the literature and kinetic parameters for the enzyme inactivation obtained in the in vitro studies. In rats, DPD was predicted to be completely inactivated by administration of BVU and the area under the curve of 5-FU was predicted to increase 11-fold, which agreed well with the reported data. In humans, a 5-fold increase in the area under the curve of 5-FU was predicted after administration of sorivudine, 150 mg/day for 5 days. Mechanism-based inhibition of drug metabolism is supposed to be very dangerous. We propose that such in vitro studies should be carried out during the drug-developing phase so that in vivo drug-drug interactions can be predicted.

Novel 5-fluorouracil-resistant human esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase overexpression

PubMed Central

Kikuchi, Osamu; Ohashi, Shinya; Nakai, Yukie; Nakagawa, Shunsaku; Matsuoka, Kazuaki; Kobunai, Takashi; Takechi, Teiji; Amanuma, Yusuke; Yoshioka, Masahiro; Ida, Tomomi; Yamamoto, Yoshihiro; Okuno, Yasushi; Miyamoto, Shin’ichi; Nakagawa, Hiroshi; Matsubara, Kazuo; Chiba, Tsutomu; Muto, Manabu

2015-01-01

5-Fluorouracil (5-FU) is a key drug for the treatment of esophageal squamous cell carcinoma (ESCC); however, resistance to it remains a critical limitation to its clinical use. To clarify the mechanisms of 5-FU resistance of ESCC, we originally established 5-FU-resistant ESCC cells, TE-5R, by step-wise treatment with continuously increasing concentrations of 5-FU. The half maximal inhibitory concentration of 5-FU showed that TE-5R cells were 15.6-fold more resistant to 5-FU in comparison with parental TE-5 cells. TE-5R cells showed regional copy number amplification of chromosome 1p including the DPYD gene, as well as high mRNA and protein expressions of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU degradation. 5-FU treatment resulted in a significant decrease of the intracellular 5-FU concentration and increase of the concentration of α-fluoro-ureidopropionic acid (FUPA), a metabolite of 5-FU, in TE-5R compared with TE-5 cells in vitro. Conversely, gimeracil, a DPD inhibitor, markedly increased the intracellular 5-FU concentration, decreased the intracellular FUPA concentration, and attenuated 5-FU resistance of TE-5R cells. These results indicate that 5-FU resistance of TE-5R cells is due to the rapid degradation of 5-FU by DPD overexpression. The investigation of 5-FU-resistant ESCC with DPYD gene copy number amplification and consequent DPD overexpression may generate novel biological evidence to explore strategies against ESCC with 5-FU resistance. PMID:26396918

Effects of Thermal Noise on the Transitional Dynamics of an Inextensible Elastic Filament in Stagnation Flow

PubMed Central

Deng, Mingge; Grinberg, Leopold; Caswell, Bruce

2015-01-01

We investigate the dynamics of a single inextensible elastic filament subject to anisotropic friction in a viscous stagnation-point flow, by employing both a continuum model represented by Langevin type stochastic partial differential equations (SPDEs) and a Dissipative Particle Dynamics (DPD) method. Unlike previous works1, the filament is free to rotate and the tension along the filament is determined by the local inextensible constraint. The kinematics of the filament is recorded and studied with normal modes analysis. The results show that the filament displays an instability induced by negative tension, which is analogous to Euler buckling of a beam. Symmetry breaking of normal modes dynamics and stretch-coil transitions are observed above the threshold of the buckling instability point. Furthermore, both temporal and spatial noise are amplified resulting from the interaction of thermal fluctuations and nonlinear filament dynamics. Specifically, the spatial noise is amplified with even normal modes being excited due to symmetry breaking, while the temporal noise is amplified with increasing time correlation length and variance. PMID:26023834

Discordance Between Physician Assessment and Patient-Reported Depressive Symptoms in Parkinson Disease.

PubMed

Lachner, Christian; Armstrong, Melissa J; Gruber-Baldini, Ann L; Rezvani, Zahra; Reich, Stephen G; Fishman, Paul S; Salazar, Richard; Shulman, Lisa M

2017-07-01

To assess concordance between physician assessment and patient-reported symptoms when screening for depression in Parkinson disease (dPD). Depression in Parkinson disease is highly prevalent (∼40%) and has a significant impact on quality of life and disability, yet physician recognition and treatment remain inadequate. One thousand seventy-six patients with PD completed the Brief Symptom Inventory-18 (BSI-18), a screening questionnaire for psychiatric symptoms, which was compared to item #3 (depression) on the Unified Parkinson's Disease Rating Scale (UPDRS). The mean BSI-18 depression score was 51.4 (9.7). Of the 170 (16%) patients screening positive for dPD on the BSI-18, 104 (61%) were not recognized as depressed by neurologists on the UPDRS. Factors associated with lower neurologist recognition included male gender, better mental health quality of life, and lack of antidepressant use. More than 60% of patients screening positive for depression on self-report were not recognized by neurologists on the UPDRS. A patient-reported screening tool for depression may improve recognition and management of dPD.

Development of new two-dimensional spectral/spatial code based on dynamic cyclic shift code for OCDMA system

NASA Astrophysics Data System (ADS)

Jellali, Nabiha; Najjar, Monia; Ferchichi, Moez; Rezig, Houria

2017-07-01

In this paper, a new two-dimensional spectral/spatial codes family, named two dimensional dynamic cyclic shift codes (2D-DCS) is introduced. The 2D-DCS codes are derived from the dynamic cyclic shift code for the spectral and spatial coding. The proposed system can fully eliminate the multiple access interference (MAI) by using the MAI cancellation property. The effect of shot noise, phase-induced intensity noise and thermal noise are used to analyze the code performance. In comparison with existing two dimensional (2D) codes, such as 2D perfect difference (2D-PD), 2D Extended Enhanced Double Weight (2D-Extended-EDW) and 2D hybrid (2D-FCC/MDW) codes, the numerical results show that our proposed codes have the best performance. By keeping the same code length and increasing the spatial code, the performance of our 2D-DCS system is enhanced: it provides higher data rates while using lower transmitted power and a smaller spectral width.

Study of structural morphologies of thermoresponsive diblock AB and triblock BAB copolymers (A = poly(N-isopropylacrylamide), B = polystyrene)

NASA Astrophysics Data System (ADS)

Rodríguez-Hidalgo, María del Rosario; Soto-Figueroa, César; Vicente, Luis

2018-03-01

Structural morphologies of diblock AB and triblock BAB copolymers (A = poly(N-isopropylacrylamide), B = polystyrene) in aqueous environment have been investigated by dissipative particle dynamics (DPD). In triblock copolymers insoluble PS blocks contract while soluble pNIPAM blocks stay at the periphery forming looped chains as corona. As the temperature is increased there is a continuous morphological transition and micelles form ellipsoidal structures with segregated polymer zones. The phase transition of looped pNIPAM chains occurs at lower temperature than for linear chains and within broader temperature range. It is discussed how the chain topology of pNIPAM affects the phase transition.

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

McAfee, J.G.; Krauss, D.J.; Subramanian, G.

The 3-hour biodistribution of /sup 99m/Tc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. /sup 95m/Tc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidneymore » levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of /sup 99m/Tc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.« less

Clinical response to dorsal duct drainage via the minor papilla in refractory obstructing chronic calcific pancreatitis

PubMed Central

Kwon, Chang-Il; Gromski, Mark A.; Sherman, Stuart; El Hajj, Ihab I.; Easler, Jeffrey J.; Watkins, James; McHenry, Lee; Lehman, Glen A.; Fogel, Evan L.

2017-01-01

Background and study aims Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). Patients and methods 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period. Results Among 16 patients meeting entry criteria, 10 (62.5%) had a history of unsuccessful endoscopic therapy, and 8 had failed extracorporeal shockwave lithotripsy (ESWL). Clinical success was achieved in 12 patients (75 %). Among these responders, 10 patients (83.3 %) had markedly improved or complete pain relief after the first stent placement, which persisted throughout the follow-up period; 11 patients (91.7 %) were able to discontinue their daily analgesics. Conclusions In selected patients with obstructive chronic calcific pancreatitis, the DPD bypass may be considered as a rescue endoscopic therapy, potentially obviating the need for surgery when standard endoscopic methods and ESWL fail. PMID:28201840

Mesoscopic simulation of a micellar poly(N-isopropyl acrylamide)-b-(polyethylene oxide) copolymer system

NASA Astrophysics Data System (ADS)

Bautista-Reyes, Rubén; Soto-Figueroa, César; Vicente, Luis

2016-05-01

In this article we studied the micellar formation of poly(N-isopropyl acrylamide)-b-polyethylene oxide (PNIPAM-b-PEO) copolymers in an aqueous system. From molecular simulations the dependence on temperature of the Flory-Huggins interaction parameter χ for PNIPAM and PEO in water is obtained and compared with available experimental results and values from other theoretical calculations. By means of dissipative particle dynamics (DPD) we then simulated the coil-globule transition for PNIPAM chains in water with a transition temperature of around 305 K. The simulations for PNIPAM-b-PEO copolymers showed that at room temperature the chains are miscible in an aqueous phase but with a temperature increase the system turns into micelles at T  =  305 K. The change in micelle anisotropy due to a different ratio PNIPAM/PEO of chains is also analyzed. What is observed is that for large PEO the large number of dissolved PEO chains gives a large corona size and the micelle is not spherical but obloide and as the number of PNIPAM is increased the micelle acquires a spherical shape. As an important application we considered the system micelle-water/anionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate [BMIM]+[PF6]-). By increasing the temperature of the system from 306 K it is shown that at T  =  345 K there is a transfer of the micelle from water to the ionic liquid phase and this was due to the change in the relative affinity of PEO to water and ionic liquid expressed by the change in χ. All the simulation outcomes are qualitatively consistent with experimental results and thus to our knowledge we give the first set of χ values for the interaction between PNIPAM and water in a wide range of temperature values.

Coarse-grained simulation of polymer-filler blends

NASA Astrophysics Data System (ADS)

Legters, Gregg; Kuppa, Vikram; Beaucage, Gregory; Univ of Dayton Collaboration; Univ of Cincinnati Collaboration

The practical use of polymers often relies on additives that improve the property of the mixture. Examples of such complex blends include tires, pigments, blowing agents and other reactive additives in thermoplastics, and recycled polymers. Such systems usually exhibit a complex partitioning of the components. Most prior work has either focused on fine-grained details such as molecular modeling of chains at interfaces, or on coarse, heuristic, trial-and-error approaches to compounding (eg: tire industry). Thus, there is a significant gap in our understanding of how complex hierarchical structure (across several decades in length) develops in these multicomponent systems. This research employs dissipative particle thermodynamics in conjunction with a pseudo-thermodynamic parameter derived from scattering experiments to represent polymer-filler interactions. DPD simulations will probe how filler dispersion and hierarchical morphology develops in these complex blends, and are validated against experimental (scattering) data. The outcome of our approach is a practical solution to compounding issues, based on a mutually validating experimental and simulation methodology. Support from the NSF (CMMI-1636036/1635865) is gratefully acknowledged.

Partner-facilitating transmembrane penetration of nanoparticles: a biological test in silico.

PubMed

Wang, W; Yang, R; Zhang, F; Yuan, B; Yang, K; Ma, Y

2018-06-21

Transmembrane penetration of nanoparticles (NPs) promises an effective pathway for cargo delivery into cells, and offers the possibility of organelle-specific targeting for biomedical applications. However, a full understanding of the underlying NP-membrane interaction mechanism is still lacking. In this work, the membrane penetration behavior of NPs is statistically analyzed based on the simulations of over 2.2 ms, which are performed with dissipative particle dynamics (DPD). Influences from multiple factors including the NP concentration, shape and surface chemistry are taken into account. It is interesting to find that, the introduction of a partner NP would greatly facilitate the transmembrane penetration of a host spherical NP. This is probably due to the membrane-mediated cooperation between the NPs. Moreover, the proper selection of a partner NP with specific surface chemistry is of great significance. For example, the best partner for a hydrophilic NP to achieve transmembrane penetration is a Janus-like one, in comparison with the hydrophilic, hydrophobic or randomly surface-decorated NPs. Furthermore, such a partner-facilitating effect in NP translocation also works for a shaped NP although less pronounced. Our results are helpful for a better understanding of the complicated nano-bio interactions, and offer a practical guide to the NP-based drug delivery strategy with high efficiency.

Influence of surface modification of halloysite nanotubes on their dispersion in epoxy matrix: Mesoscopic DPD simulation

NASA Astrophysics Data System (ADS)

Komarov, P.; Markina, A.; Ivanov, V.

2016-06-01

The problems of constructing of a meso-scale model of composites based on polymers and aluminosilicate nanotubes for prediction of the filler's spatial distribution at early stages of material formation have been considered. As a test system for the polymer matrix, the mixture of 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexanecarboxylate as epoxy resin monomers and 4-methylhexahydrophthalic anhydride as curing agent has been used. It is shown that the structure of a mixture of uncured epoxy resin and nanotubes is (mainly) determined by the surface functionalization of nanotubes. The results indicate that only nanotubes with maximum functionalization can preserve a uniform distribution in space.

Heritability of markers of bone metabolism

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Zwart, S. R.; Hargens, A. R.

2005-01-01

Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

Establishing a clinically relevant cutoff to the Dependency Scale from the dimensional clinical personality inventory.

PubMed

Carvalho, Lucas de F; Pianowski, Giselle; Filho, Nelson H

2017-05-01

The Clinical Dimensional Personality Inventory (IDCP) is a 163-item self-report tool developed for the assessment of 12 dimensions of personality pathology. One of the scales comprising the instrument-the Dependency scale-is intended to provide psychometric information on traits closely related to the Dependent Personality Disorder (DPD). In the present study, we used both Item Response Theory modeling and Receiver Operating Characteristic curve analysis to establishing a clinically meaningful cutoff for the IDCP Dependency Scale. Participants were 2.481 adults, comprised by outpatients diagnosed with DPD, outpatients diagnosed with other PDs, and adults from the general population. The Wright's item map graphing technique revealed that outpatients were located at the very high levels in the latent scale continuum of the Dependency Scale, with a very large effect size for the mean difference between patients and non-patients. The ROC curve analysis supported a cutoff at 2.3 points in the Dependency Scale, which yielded 0.86 of sensitivity and 0.79 of specificity. Findings from the present investigation suggest the IDCP Dependency Scale is useful as a screening tool of the core features of the DPD. We address potential clinical applications for the instrument, and discuss limitations from the present study. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Elevated urinary excretion of free pyridinoline in Friesian horses suggests a breed-specific increase in collagen degradation.

PubMed

Saey, Veronique; Tang, Jonathan; Ducatelle, Richard; Croubels, Siska; De Baere, Siegrid; Schauvliege, Stijn; van Loon, Gunther; Chiers, Koen

2018-04-25

Friesian horses are known for their high inbreeding rate resulting in several genetic diseases such as hydrocephaly and dwarfism. This last decade, several studies focused on two other presumed hereditary traits in Friesian horses: megaoesophagus and aortic rupture. The pathogenesis of these diseases remains obscure but an important role of collagen has been hypothesized. The purpose of this study was to examine possible breed-related differences in collagen catabolism. Urinary specimens from Friesian (n = 17, median age 10 years old) and Warmblood horses (n = 17, median age 10 years old) were assessed for mature collagen cross-links, i.e. pyridinoline (PYD) (=hydroxylysylpyridinoline/HP) and deoxypyridinoline (DPD) (lysylpyridinoline /LP). Solid-phase extraction was performed, followed by reversed-phase ion-paired liquid chromatography prior to tandem mass spectrometry (MS/MS) detection. Mean urinary concentrations of free PYD, expressed as fPYD/creatinine ratio, were significantly higher in Friesian horses compared to Warmblood horses (28.5 ± 5.2 versus 22.2 ± 9.6 nmol/mmol, p = 0.02) while mean fDPD/creatinine ratios were similar in both horse breeds (3.0 ± 0.7 versus 4.6 ± 3.7 nmol/mmol, p = 0.09). Since DPD is considered a specific bone degradation marker and PYD is more widely distributed in connective tissues, the significant elevation in the mean PYD/DPD ratio in Friesian versus Warmblood horses (9.6 ± 1.6 versus 5.7 ± 1.8, p < 0.0001) suggests a soft tissue origin for the increased fPYD levels. Considering that a previous study found no differences in total collagen content between Friesian and Warmblood horses for tendon and aortic tissue, this indicates a higher rate of collagen degradation. The latter might, at least in part, explain the predisposition of Friesians to connective tissue disorders.

Using Resistivity to Measure H/Pd and D/Pd Loading:. Method and Significance

NASA Astrophysics Data System (ADS)

McKubre, M. C. H.; Tanzella, F. L.

The resistance ratio method is the most frequent technique used to determine the extent of interstitial loading of hydrogen or deuterium atoms into palladium electrodes, or extended structures used in electrolytic or gas phase cold fusion experiments. Specifically, advantage is taken of an empirical relationship between the measured resistance, R, normalized to that of the same body at the same temperature in the absence of hydrogen isotope, R0, hence R/R0, and the atomic fraction occupancy of octahedral interstitials, x = H/Pd or D/Pd. This method was first suggested and employed in cold fusion studies by the present authors, and received immediate and widespread acceptance because of the ease with which this experimental technique could be used to make in situ, real-time measurements of a parameter, D/Pd, anticipated or hypothesized at that time to relate to cold fusion heat excess or nuclear production. We take up this topic again 15 years later in an attempt to clear up some errors and misunderstandings regarding the resistance ratio method and its application in cold fusion studies. The relationship between R/R0 and x is empirical. That is, calibrations are only as good as the experiments that support the shape of the curve and cannot be used outside the range (P, T, x) in which data are taken. The original calibration (unaccountably and erroneously immortalized as the "famous Baranowski curve") involved an extrapolation of known data into the region of cold fusion interest in the D-Pd system, at x > 0.6. Present theory and results focus new attention on the very high loading region as x approaches or even exceeds unity, where double occupation of octahedral sites, tetrahedral site occupancy, new phase formation or new electrical states, may be relevant to the underlying physical process of excess heat and nuclear production. Rather than simply using the resistance ratio as a qualitative tool to determine whether an electrode is better or lesser loaded, it is now important to obtain accurate quantitative information for x close to unity. With further experimentation and analysis of published data it is apparent that the curve originally published in 1990 is in error in the high loading condition. This paper describes how this empirical fit has been improved over the years for both H/Pd and D/Pd by employing new data, new analysis of old data, new experimental methods and results.

Biochemical markers of bone turnover in children with clinical bone fragility.

PubMed

Bowden, Sasigarn A; Akusoba, Chiazor I; Hayes, John R; Mahan, John D

2016-06-01

The role of biochemical bone turnover markers (BTMs) in assessing low bone mass and monitoring bisphosphonate treatment in pediatric patients with clinical bone fragility is not well established. The aim of the study was to examine the correlations of BTMs and the bone mineral density (BMD), and evaluate the effects of bisphosphonates therapy on BTMs in children with clinical bone fragility. Clinical data of 115 patients with clinical bone fragility (mean age 9.7±5.8 years), 102 of whom received bisphosphonates, were studied. Serum alkaline phosphatase (ALP), osteocalcin (OC), urine pyridinoline (PD) and deoxypyridinoline (DPD), BMD at baseline and subsequent years were analyzed. There was a significant negative correlation between urine PD and lumbar BMD (slope=-0.29, p<0.001). There were no correlations between BTMs and lumbar BMD Z-score. There was a significant positive correlation between serum OC and serum ALP, urine PD and DPD (p<0.001). Serum OC, urine PD and DPD index, as expressed as measured value/upper limit of normal value for age, decreased during the first 3 years of bisphosphonate therapy. In children with clinical bone fragility, BTMs correlated with each other, but not with lumbar BMD Z-score. While they were not reliable predictors of degree of low BMD, the bone markers showed suppression during bisphosphonate therapy and may be helpful in monitoring the response to therapy.

Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models.

PubMed

Li, Jian-Ang; Xu, Xue-Feng; Han, Xu; Fang, Yuan; Shi, Chen-Ye; Jin, Da-Yong; Lou, Wen-Hui

2016-03-01

To investigate the antitumor activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1 in patient-derived pancreatic cancer xenograft mouse models and to explore biomarkers that could predict drug efficacy. Ten patient-derived xenograft models were established. The third-generation tumor-bearing mice were randomized into 4 treatment groups: (1) control; (2) S-1; (3) nab-paclitaxel; (4) S-1 plus nab-paclitaxel. Resected tumors were tested by immunohistochemistry for the expression of thymidylate synthase, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), secreted protein that is acidic and rich in cysteine, human epidermal growth factor receptor 2 (HER2), collagen-1, and CD31. Tumor growth inhibition of the S-1 group, nab-paclitaxel group, and combination group was 69.52%, 86.63%, 103.56%, respectively (P < 0.05). The efficacy of S-1 is better in thymidylate synthase-negative, OPRT-positive, and DPD-negative tumors. The efficacy of nab-paclitaxel is better in HER2-positive tumors. Collagen-1 was decreased and CD31 was increased in tumors treated with nab-paclitaxel and S-1 plus nab-paclitaxel compared with control or S-1. This preclinical study showed that S-1 plus nab-paclitaxel exerted significantly better antitumor activity than S-1 or nab-paclitaxel alone. Thymidylate synthase, OPRT, and DPD were possibly biomarkers of S-1 and HER2 of nab-paclitaxel.

A new data format for the commissioning phase of the ATLAS detector

NASA Astrophysics Data System (ADS)

Köneke, Karsten; ATLAS Collaboration

2010-04-01

In the commissioning phase of the ATLAS experiment, low-level Event Summary Data (ESD) are analyzed to evaluate the performance of the individual subdetectors, the performance of the reconstruction and particle identification algorithms, and to obtain calibration coefficients. In the grid model of distributed analysis, these data must be transferred to Tier-1 and Tier-2 sites before they can be analyzed. However, the large size of ESD (approxeq1 MByte/event) constrains the amount of data that can be distributed on the grid and is available on disks. In order to overcome this constraint and make the data fully available, new data sets — collectively known as Derived Physics Data (DPD) — have been designed. Each DPD set contains a subset of the ESD data, tailored to specific needs of the subdetector and object reconstruction and identification performance groups. Filtering algorithms perform a selection based on physics contents and trigger response, further reducing the data volume. Thanks to these techniques, the total volume of DPD to be distributed on the grid amounts to 20% of the initial ESD data. An evolution of the tools developed in this context serves to produce another set of DPDs that are specifically tailored for physics analysis. All selection criteria and other relevant information is stored inside these DPDs as meta-data and a connection to external databases is also established.

A look-up-table digital predistortion technique for high-voltage power amplifiers in ultrasonic applications.

PubMed

Gao, Zheng; Gui, Ping

2012-07-01

In this paper, we present a digital predistortion technique to improve the linearity and power efficiency of a high-voltage class-AB power amplifier (PA) for ultrasound transmitters. The system is composed of a digital-to-analog converter (DAC), an analog-to-digital converter (ADC), and a field-programmable gate array (FPGA) in which the digital predistortion (DPD) algorithm is implemented. The DPD algorithm updates the error, which is the difference between the ideal signal and the attenuated distorted output signal, in the look-up table (LUT) memory during each cycle of a sinusoidal signal using the least-mean-square (LMS) algorithm. On the next signal cycle, the error data are used to equalize the signal with negative harmonic components to cancel the amplifier's nonlinear response. The algorithm also includes a linear interpolation method applied to the windowed sinusoidal signals for the B-mode and Doppler modes. The measurement test bench uses an arbitrary function generator as the DAC to generate the input signal, an oscilloscope as the ADC to capture the output waveform, and software to implement the DPD algorithm. The measurement results show that the proposed system is able to reduce the second-order harmonic distortion (HD2) by 20 dB and the third-order harmonic distortion (HD3) by 14.5 dB, while at the same time improving the power efficiency by 18%.

Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study.

PubMed

Amado Leon, Luciane Almeida; de Almeida, Adilson José; de Paula, Vanessa Salete; Tourinho, Renata Santos; Villela, Daniel Antunes Maciel; Gaspar, Ana Maria Coimbra; Lewis-Ximenez, Lia Laura; Pinto, Marcelo Alves

2015-01-01

Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV) markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd). Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05). Most of the patients (80%) were found to contain HAV-RNA in saliva, mainly at early acute phase (30th day). However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 104 copies/mL). These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30-90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the assessment of salivary antibodies a useful tool for diagnosis and epidemiological studies. The high frequency of HAV-RNA in saliva and the probability of detection of about 50%, during the first 30 dpd, demonstrate that saliva is also useful for molecular investigation of hepatitis A cases, mainly during the early course of infection. Therefore, the collection of saliva may provide a simple, cheap and non-invasive means of diagnosis, epidemiological surveys and monitoring of hepatitis A infection purposes.

Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study

PubMed Central

Amado Leon, Luciane Almeida; de Almeida, Adilson José; de Paula, Vanessa Salete; Tourinho, Renata Santos; Villela, Daniel Antunes Maciel; Gaspar, Ana Maria Coimbra; Lewis-Ximenez, Lia Laura; Pinto, Marcelo Alves

2015-01-01

Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV) markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd). Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05). Most of the patients (80%) were found to contain HAV-RNA in saliva, mainly at early acute phase (30th day). However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 104 copies/mL). These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30–90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the assessment of salivary antibodies a useful tool for diagnosis and epidemiological studies. The high frequency of HAV-RNA in saliva and the probability of detection of about 50%, during the first 30 dpd, demonstrate that saliva is also useful for molecular investigation of hepatitis A cases, mainly during the early course of infection. Therefore, the collection of saliva may provide a simple, cheap and non-invasive means of diagnosis, epidemiological surveys and monitoring of hepatitis A infection purposes. PMID:26690904

Remote sensing at the University of Kansas in radar systems

NASA Technical Reports Server (NTRS)

Moore, R. K.

1970-01-01

Demonstration that a spectral response across an octave bandwidth in the microwave region is as variable as the comparable response in the visible and infrared region is a major mile-stone and indicates the potential of polypanchromatic radar systems is analogous with that of color photography. Averaging of the returns from a target element appears necessary to obtain a grey scale adequate for many earth-science applications of radar systems. This result can be obtained either by azimuth averaging or by the use of panchromatic techniques (range averaging). Improvement with panchromatic techniques has been demonstrated both with a landbased electromagnetic system and with an ultrasonic simulator. The advantage of the averaging achieved in azimuth with the real-aperture version of the DPD-2 when compared with the synthetic aperture version confirms the concept.

Movement patterns of peak-dose levodopa-induced dyskinesias in patients with Parkinson's disease.

PubMed

Gour, Jackie; Edwards, Roderick; Lemieux, Sarah; Ghassemi, Mehrdad; Jog, Mandar; Duval, Christian

2007-09-14

The present study characterized involuntary movements associated with levodopa-induced dyskinesias (LID) in patients with Parkinson's disease. We used amplitude, proportional energy, frequency dispersion and sample entropy to determine whether LID movement patterns are truly random, as clinical description seems to suggest, or possess some underlying pattern that is not visible to the naked eye. LID was captured using a magnetic tracker system, which provided 3D rendering of whole-body LID. Patients were instructed to maintain a standing position, with arms extended in front of them. We compared the measurements of the dyskinetic PD group (DPD) with 10 patients without dyskinesias (NDPD) and 10 control subjects. In comparison to the other two groups, movement patterns from the DPD group had significantly higher amplitude, confirming the presence of dyskinesias. In addition, higher frequency components in the power spectrum of velocity were detected, suggestive of higher velocity in LID movement. Furthermore, there was a concentration in narrow frequency bands, which suggested stable oscillatory activity. Finally, sample entropy revealed more regularity in the DPD group. Although not statistically significant, we found that the amplitude from the NDPD group had a tendency to be smaller than those of controls. As well, the spectra were often more dispersed for the NDPD group. In conclusion, the present results suggest that LID cannot be considered as purely random movement since they possess some deterministic pattern of motion. This may provide a way for patients to adapt to these involuntary movements while performing voluntary motor acts.

RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP

PubMed Central

Armbruster, Chelsie E.; Pang, Bing; Murrah, Kyle; Juneau, Richard A.; Perez, Antonia C.; Weimer, Kristin E.D.; Swords, W. Edward

2011-01-01

Summary Nontypeable Haemophilus influenzae (NTHI) is a respiratory commensal and opportunistic pathogen, which persists within biofilms on airway mucosal surfaces. For many species, biofilm formation is impacted by quorum signaling. Our prior work shows that production of autoinducer-2 (AI-2) promotes biofilm development and persistence for NTHI 86-028NP. NTHI 86-028NP encodes an ABC transporter annotated as a ribose transport system that includes a protein (RbsB) with similarity to the Escherichia coli LsrB and Aggregatibacter actinomycetemcomitans RbsB proteins that bind AI-2. In this study, inactivation of rbsB significantly reduced uptake of AI-2 and the AI-2 precursor dihydroxypentanedione (DPD) by NTHI 86-028NP. Moreover, DPD uptake was not competitively inhibited by ribose or other pentose sugars. Transcript levels of rbsB increased in response to DPD and as bacteria approached stationary-phase growth. The NTHI 86-028NP rbsB mutant also formed biofilms with significantly reduced thickness and total biomass and reduced surface phosphorylcholine, similar to a luxS mutant. Infection studies revealed that loss of rbsB impaired bacterial persistence in the chinchilla middle-ear, similar to our previous results with luxS mutants. Based on these data, we conclude that in NTHI 86-028NP, RbsB is a LuxS/AI-2 regulated protein that is required for uptake of and response to AI-2. PMID:21923771

RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP.

PubMed

Armbruster, Chelsie E; Pang, Bing; Murrah, Kyle; Juneau, Richard A; Perez, Antonia C; Weimer, Kristin E D; Swords, W Edward

2011-11-01

Nontypeable Haemophilus influenzae (NTHI) is a respiratory commensal and opportunistic pathogen, which persists within biofilms on airway mucosal surfaces. For many species, biofilm formation is impacted by quorum signalling. Our prior work shows that production of autoinducer-2 (AI-2) promotes biofilm development and persistence for NTHI 86-028NP. NTHI 86-028NP encodes an ABC transporter annotated as a ribose transport system that includes a protein (RbsB) with similarity to the Escherichia coli LsrB and Aggregatibacter actinomycetemcomitans RbsB proteins that bind AI-2. In this study, inactivation of rbsB significantly reduced uptake of AI-2 and the AI-2 precursor dihydroxypentanedione (DPD) by NTHI 86-028NP. Moreover, DPD uptake was not competitively inhibited by ribose or other pentose sugars. Transcript levels of rbsB increased in response to DPD and as bacteria approached stationary-phase growth. The NTHI 86-028NP rbsB mutant also formed biofilms with significantly reduced thickness and total biomass and reduced surface phosphorylcholine, similar to a luxS mutant. Infection studies revealed that loss of rbsB impaired bacterial persistence in the chinchilla middle ear, similar to our previous results with luxS mutants. Based on these data, we conclude that in NTHI 86-028NP, RbsB is a LuxS/AI-2 regulated protein that is required for uptake of and response to AI-2. © 2011 Blackwell Publishing Ltd.

Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

PubMed

Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

2012-10-01

Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (p<0.0001). This was associated with a trend of higher Tb.N, Tb.Th, DA, an inferior Conn.D and a lower bone turnover as shown by the decreases of osteoid parameters, MS/BS, Ac.f in LV1 when compared to IC. In addition, the ratio PYD/DPD was 4 times higher in LV1 than IC. After 3 months, significant decreases of sALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly only in LV1 (p<0.05) with a trend of increases in MS/BS and BFR/BS, compared to LV1-CTRL. In conclusion, in adult ewes, the bone mass, microarchitecture, remodeling and collagen crosslink content differ according to the bone site (iliac crest and vertebra). Furthermore, after 3 months, the responses to ZOL and TPTD were of different magnitude and delay between the two bone sites. The distinction of bone sites to study the early effects of anti-osteoporotic therapies appears meaningful in order to approach their site-specific anti-fracture efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

CBT for the treatment of depression in Parkinson's disease: a promising nonpharmacological approach.

PubMed

Dobkin, Roseanne DeFronzo; Menza, Matthew; Bienfait, Karina L

2008-01-01

Depression is very common in Parkinson's disease (PD) and linked with a faster progression of physical symptoms, greater cognitive decline and poorer quality of life. Nonpharmacological approaches, such as cognitive-behavioral therapy (CBT), for the treatment of depression in PD (dPD) have received little experimental attention despite strong demonstrated efficacy in other geriatric and medical populations. Depressed PD patients often differ from the depressed non-PD elderly in that they present with increased rates of both executive dysfunction and comorbid psychiatric diagnoses, may differ in their depressive symptom presentation and typically have caregivers who are highly involved in their treatment. Therefore, it is not possible to conclude that empirically validated treatments in the depressed aged will generalize to those with PD. In order to be most effective for PD patients, CBT should be tailored to their unique needs. Additional controlled research is needed to further explore the efficacy of CBT for dPD.

Short-term variability in biomarkers of bone metabolism in sheep.

PubMed

Sousa, Cristina P; de Azevedo, Jorge T; Reis, Rui L; Gomes, Manuela E; Dias, Isabel R

2014-01-01

Changes in bone remodeling during pathological states and during their treatment can be assessed noninvasively by measuring biomarkers of bone metabolism. Their application is limited, however, by the potential biological variability in the levels of these biomarkers over time. To determine the short-term variability in biomarkers of bone metabolism in adult sheep, the authors measured serum levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N-terminal propeptide of type-III procollagen (PIIINP), deoxypyridinoline (DPD), tartrate-resistant acid phosphatase (TRAP), calcium and phosphorus intermittently over a 12-week period. There were significant differences in mean ALP activity and in phosphorus concentrations over time, but all other biomarkers showed no significant short-term variability. The results suggest that biomarkers of bone metabolism in sheep, especially the bone resorption marker DPD and the bone formation marker BALP, can be used reliably to detect changes in bone cellular activity.

Dislocation-pipe diffusion in nitride superlattices observed in direct atomic resolution.

PubMed

Garbrecht, Magnus; Saha, Bivas; Schroeder, Jeremy L; Hultman, Lars; Sands, Timothy D

2017-04-06

Device failure from diffusion short circuits in microelectronic components occurs via thermally induced migration of atoms along high-diffusivity paths: dislocations, grain boundaries, and free surfaces. Even well-annealed single-grain metallic films contain dislocation densities of about 10 14  m -2 ; hence dislocation-pipe diffusion (DPD) becomes a major contribution at working temperatures. While its theoretical concept was established already in the 1950s and its contribution is commonly measured using indirect tracer, spectroscopy, or electrical methods, no direct observation of DPD at the atomic level has been reported. We present atomically-resolved electron microscopy images of the onset and progression of diffusion along threading dislocations in sequentially annealed nitride metal/semiconductor superlattices, and show that this type of diffusion can be independent of concentration gradients in the system but governed by the reduction of strain fields in the lattice.

Equalizing Si photodetectors fabricated in standard CMOS processes

NASA Astrophysics Data System (ADS)

Guerrero, E.; Aguirre, J.; Sánchez-Azqueta, C.; Royo, G.; Gimeno, C.; Celma, S.

2017-05-01

This work presents a new continuous-time equalization approach to overcome the limited bandwidth of integrated CMOS photodetectors. It is based on a split-path topology that features completely decoupled controls for boosting and gain; this capability allows a better tuning of the equalizer in comparison with other architectures based on the degenerated differential pair, which is particularly helpful to achieve a proper calibration of the system. The equalizer is intended to enhance the bandwidth of CMOS standard n-well/p-bulk differential photodiodes (DPDs), which falls below 10MHz representing a bottleneck in fully integrated optoelectronic interfaces to fulfill the low-cost requirements of modern smart sensors. The proposed equalizer has been simulated in a 65nm CMOS process and biased with a single supply voltage of 1V, where the bandwidth of the DPD has been increased up to 3 GHz.

Large-angle production of charged pions with 3-12.9 GeV/c incident protons on nuclear targets

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

Catanesi, M. G.; Radicioni, E.; Edgecock, R.

2008-05-15

Measurements of the double-differential {pi}{sup {+-}} production cross section in the momentum range 100{<=}p{<=}800 MeV/c and angle range 0.35{<=}{theta}{<=}2.15 rad in proton-beryllium, proton-carbon, proton-aluminium, proton-copper, proton-tin, proton-tantalum, and proton-lead collisions are presented. The data were taken with the large-acceptance HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 to 12.9 GeV/c hitting a target with a thickness of 5% of a nuclear interaction length. Tracking and identification of the produced particles was performed by using a small-radius cylindrical Time Projection Chamber (TPC) placed inside amore » solenoidal magnet. Incident particles were identified by an elaborate system of beam detectors. Results are obtained for the double-differential cross sections d{sup 2}{sigma}/(dpd{theta}) at six incident proton beam momenta [3, 5, 8, and 8.9 GeV/c (Be only) and 12 and 12.9 GeV/c (Al only)]. They are based on a complete correction of static and dynamic distortions of tracks in the HARP TPC, which allows the complete statistics of the collected data set to be used. The results include and supersede our previously published results and are compatible with these. Results are compared with the GEANT4 and MARS Monte Carlo simulation.« less

Decision peptide-driven: a free software tool for accurate protein quantification using gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry.

PubMed

Santos, Hugo M; Reboiro-Jato, Miguel; Glez-Peña, Daniel; Nunes-Miranda, J D; Fdez-Riverola, Florentino; Carvallo, R; Capelo, J L

2010-09-15

The decision peptide-driven tool implements a software application for assisting the user in a protocol for accurate protein quantification based on the following steps: (1) protein separation through gel electrophoresis; (2) in-gel protein digestion; (3) direct and inverse (18)O-labeling and (4) matrix assisted laser desorption ionization time of flight mass spectrometry, MALDI analysis. The DPD software compares the MALDI results of the direct and inverse (18)O-labeling experiments and quickly identifies those peptides with paralleled loses in different sets of a typical proteomic workflow. Those peptides are used for subsequent accurate protein quantification. The interpretation of the MALDI data from direct and inverse labeling experiments is time-consuming requiring a significant amount of time to do all comparisons manually. The DPD software shortens and simplifies the searching of the peptides that must be used for quantification from a week to just some minutes. To do so, it takes as input several MALDI spectra and aids the researcher in an automatic mode (i) to compare data from direct and inverse (18)O-labeling experiments, calculating the corresponding ratios to determine those peptides with paralleled losses throughout different sets of experiments; and (ii) allow to use those peptides as internal standards for subsequent accurate protein quantification using (18)O-labeling. In this work the DPD software is presented and explained with the quantification of protein carbonic anhydrase. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Recurrence and 5-FU sensitivity of stage I/II node-negative breast, lung, or gastric cancer with occult neoplastic cells in lymph node sinuses.

PubMed

Mukai, Masaya; Sato, Shinkichi; Tajima, Takayuki; Ninomiya, Hiromi; Wakui, Kanako; Komatsu, Nobukazu; Tsuchiya, Kazutoshi; Nakasaki, Hisao; Makuuchi, Hiroyasu

2006-04-01

This study was designed to examine the relationship between the presence of occult neoplastic cells (ONCs) in lymph nodes (LNs) and survival in 238 patients with stage I/II LN-negative cancer of the breast, lung, or stomach. In addition, immunohistochemistry for TS and DPD was used to compare the 5-FU sensitivity of the primary tumor in ONC (+) patients. The 5-year relapse-free survival (RFS) rate of 215 ONC (-) patients and 23 ONC (+) patients was 95.2 and 82.6%, respectively (p=0.0107). The 5-year overall survival (OS) rate of the ONC (-) and (+) patients was 97.4 and 77.4%, respectively (p=0.0000). The 6 ONC (+) patients with recurrence showed high and low TS expression in 33.3% (2/6) and 66.7% (4/6), respectively, while high and low DPD expression was observed in 16.7% (1/6) and 83.3% (5/6), respectively. In the 17 ONC (+) patients without recurrence, the corresponding values were 64.7% (11/17), 35.3% (6/17), 29.4% (5/17), and 70.6% (12/17). Patients with a combination of high TS and low DPD expression accounted for 33.3% (2/6) of the ONC (+) patients with recurrence and 52.9% (9/17) of those without recurrence, showing no significant difference between the two groups. These results suggest that ONCs are associated with a lower survival rate and that ONC (+) patients are unlikely to respond to 5-FU+LV therapy.

Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro

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

Deng, Jun; Lei, Wan; Fu, Jian-Chun

2014-01-17

Highlight: •MiR-21 plays a significant role in 5-FU resistance. •This role might be attributed to targeting of hMSH2 as well as TP and DPD via miR-21 targeted hMSH2. •Indirectly targeted TP and DPD to influence 5-FU chemotherapy sensitivity. -- Abstract: 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibilitymore » and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells.« less

Bupropion improves attention but does not affect impulsive behavior in healthy young adults.

PubMed

Acheson, Ashley; de Wit, Harriet

2008-04-01

Bupropion is an effective abstinence aid for cessation of smoking and possibly other drug use as well. There is evidence that bupropion improves attention and impulse control in certain patient populations, and improvements in these processes could mediate its efficacy as an abstinence aid. In the present study, we tested the effects of acute bupropion on measures of attention and impulsivity in healthy adults with d-amphetamine included as a positive control. Twenty-two nonsmokers (11 women) and 11 smokers (4 women) completed four 4-hr sessions where they received placebo, bupropion (150 or 300 mg), or d-amphetamine (20 mg) in capsules. Ninety minutes after capsule administration, participants were tested on attention with a simple reaction time task (SRT) and on impulsivity with the stop task, a delay and probability discounting task (DPD), and the balloon analogue risk task (BART). Participants also completed mood questionnaires during sessions. Bupropion (150 mg) decreased lapses in attention on the SRT, but did not affect performance on the stop task, DPD, or BART. Amphetamine decreased lapses in attention and speeded sensory motor processing time on the SRT but did not significantly affect responding on the stop task or DPD. On the BART, d-amphetamine tended to decrease risk taking in men but increased risk taking in women. Bupropion (300 mg) and d-amphetamine increased ratings of arousal. These results suggest that bupropion improves attention without affecting impulsive behavior in healthy adults. Improvements in attention may contribute to the effectiveness of bupropion as a pharmacotherapy for smoking.

Bupropion improves attention but does not affect impulsive behavior in healthy young adults

PubMed Central

Acheson, Ashley; de Wit, Harriet

2014-01-01

Bupropion is an effective abstinence aid for cessation of smoking and possibly other drug use as well. There is evidence that bupropion improves attention and impulse control in certain patient populations, and improvements in these processes could mediate its efficacy as an abstinence aid. In the present study, we tested the effects of acute bupropion on measures of attention and impulsivity in healthy adults with d-amphetamine included as a positive control. Twenty-two nonsmokers (11 women) and 11 smokers (4 women) completed four 4-h sessions where they received placebo, bupropion (150 or 300 mg) or d-amphetamine (20 mg) in capsules. Ninety minutes after capsule administration, participants were tested on attention with a Simple Reaction Time Task (SRT) and on impulsivity with the Stop Task, a Delay and Probability Discounting Task (DPD), and the Balloon Analogue Risk Task (BART). Participants also completed mood questionnaires during sessions. Bupropion (150 mg) decreased lapses in attention on the SRT, but did not affect performance on the Stop Task, DPD or BART. d-Amphetamine decreased lapses in attention and speeded sensory motor processing time on the SRT but did not significantly affect responding on the Stop Task or DPD. On the BART, d-amphetamine tended to decrease risk taking in men but increased risk taking in women. Bupropion (300 mg) and d-amphetamine increased ratings of arousal. These results suggest that bupropion improves attention without affecting impulsive behavior in healthy adults. Improvements in attention may contribute to the effectiveness of bupropion as a pharmacotherapy for smoking. PMID:18489015

Collagen degradation products and proinflammatory cytokines in systemic and localized scleroderma.

PubMed

Becvár, R; Hulejová, H; Braun, M; Stork, J

2007-01-01

The aim of this study was to assess the degradation of collagen type I and proinflammatory cytokines in systemic and localized scleroderma compared with psoriasis and healthy controls. Total 99 individuals were examined - 24 with SSc, 22 with LSc, 39 patients with PsV and 14 healthy controls. U-PD and U-DPD were measured using a sensitive isocratic HPLC method. Serum levels of IL-6 and soluble IL-2R were assayed using commercial ELISA kits. In the SSc group U-PD and U-DPD levels (nmol/mmol creatinine) were increased compared with controls (P = 0.001) and with PsV (P = 0.006). IL-6 levels were increased compared with controls (P = 0.004) and with PsV (P = 0.002). IL-2R concentrations were insignificantly increased in comparison with controls and were lower than in PsV, but the difference was not significant. In the LSc group excretion of U-PD and U-DPD did not differ from controls, but was insignificantly decreased compared with PsV. IL-6 levels were increased compared with controls (P = 0.001) and also with PsV (P = 0.03). IL-2R concentrations were significantly increased in comparison with controls only (P = 0.03). In patients with SSc our data have shown the most intensive collagen degradation and simultaneously an active inflammation, as documented by IL-6, which reflects the pathological processes in the skin and visceral organs compared with PsV patients and healthy individuals. In the LSc group collagen degradation was similar to that in control groups, but a certain inflammatory activity was observed.

Activity restriction increases deoxypyridinoline excretion in hospitalized high-risk pregnant women.

PubMed

Vanderspank, Dana; Bernier, Suzanne M; Sopper, Maggie M; Watson, Patricia; Mottola, Michelle F

2014-01-01

Activity restriction (AR), one of the most common interventions used in high-risk pregnancies, may exacerbate loss of bone mass. The purpose of this study was to determine changes over time in bone resorption in hospitalized AR women during late pregnancy. This was a short-term prospective study conducted in two tertiary-care obstetric hospitals. We measured urinary deoxypyridinoline (Dpd) excretion, a marker of bone resorption, once per week in a convenience sample of 14 hospitalized AR women in the third trimester and compared values at 28-31 and 34-36 weeks' gestation to those of 11 ambulatory control women. Both groups completed a bone-loading questionnaire, 3-day food intake record, and pedometer step counts at the same gestational age. Urinary Dpd excretion increased from Days 1-7 (2.60 ± 0.32 nmol/mmol creatinine) to Days 22-28 (5.36 ± 0.83 nmol/mmol creatinine; p ≤ .05). Dpd excretion was higher in AR women (4.51 ± 0.31 nmol/mmol creatinine) than ambulatory women (2.72 ± 0.39 nmol/mmol creatinine) at 34-36 weeks' gestation (p ≤ .05). Energy intake between ambulatory and AR women was not different (p ≥ .05). All women met the daily requirements for calcium and vitamin D intake during pregnancy. Average daily pedometer steps for the AR women were significantly less compared to controls (1,329 ± 936 and 8,024 ± 1,890 steps/day, respectively; p ≤ .05). AR leads to increased bone resorption in hospitalized pregnant women, which may impact future risk of developing osteopenia and osteoporosis.

Developing Mesoscale Model of Fibrin-Platelet Network Representing Blood Clotting =

NASA Astrophysics Data System (ADS)

Sun, Yueyi; Nikolov, Svetoslav; Bowie, Sam; Alexeev, Alexander; Lam, Wilbur; Myers, David

Blood clotting disorders which prevent the body's natural ability to achieve hemostasis can lead to a variety of life threatening conditions such as, excessive bleeding, stroke, or heart attack. Treatment of these disorders is highly dependent on understanding the underlying physics behind the clotting process. Since clotting is a highly complex multi scale mechanism developing a fully atomistic model is currently not possible. We develop a mesoscale model based on dissipative particle dynamics (DPD) to gain fundamental understanding of the underlying principles controlling the clotting process. In our study, we examine experimental data on clot contraction using stacks of confocal microscopy images to estimate the crosslink density in the fibrin networks and platelet location. Using this data we reconstruct the platelet rich fibrin network and study how platelet-fibrin interactions affect clotting. Furthermore, we probe how different system parameters affect clot contraction. ANSF CAREER Award DMR-1255288.

Variations of Solar Non-axisymmetric Activity

NASA Astrophysics Data System (ADS)

Gyenge, N.; Baranyi, T.; Ludmány, A.

The temporal behaviour of solar active longitudes has been examined by using two sunspot catalogues, the Greenwich Photoheliographic Results (GPR) and the Debrecen Photoheliographic Data (DPD). The time-longitude diagrams of the activity distribution reveal the preferred longitudinal zones and their migration with respect to the Carrington frame. The migration paths outline a set of patterns in which the activity zone has alternating prograde/retrograde angular velocities with respect to the Carrington rotation rate. The time profiles of these variations can be described by a set of successive parabolae. Two similar migration paths have been selected from these datasets, one northern path during cycles 21 - 22 and one southern path during cycles 13 - 14, for closer examination and comparison of their dynamical behaviours. The rates of sunspot emergence exhibited in both migration paths similar periodicities, close to 1.3 years. This behaviour may imply that the active longitude is connected to the bottom of convection zone.

Dissipative particle dynamics: Effects of thermostating schemes on nano-colloid electrophoresis

NASA Astrophysics Data System (ADS)

Hassanzadeh Afrouzi, Hamid; Moshfegh, Abouzar; Farhadi, Mousa; Sedighi, Kurosh

2018-05-01

A novel fully explicit approach using dissipative particle dynamics (DPD) method is introduced in the present study to model the electrophoretic transport of nano-colloids in an electrolyte solution. Slater type charge smearing function included in 3D Ewald summation method is employed to treat electrostatic interaction. Performance of various thermostats are challenged to control the system temperature and study the dynamic response of colloidal electrophoretic mobility under practical ranges of external electric field (0 . 072 < E < 0 . 361 v/nm) covering linear to non-linear response regime, and ionic salt concentration (0.049 < SC < 0 . 69 [M]) covering weak to strong Debye screening of the colloid. System temperature and electrophoretic mobility both show a direct and inverse relationships respectively with electric field and colloidal repulsion; although they each respectively behave direct and inverse trends with salt concentration under various thermostats. Nosé-Hoover-Lowe-Andersen and Lowe-Andersen thermostats are found to function more effectively under high electric fields (E > 0 . 145[v/nm ]) while thermal equilibrium is maintained. Reasonable agreements are achieved by benchmarking the system radial distribution function with available EW3D modellings, as well as comparing reduced mobility against conventional Smoluchowski and Hückel theories, and numerical solution of Poisson-Boltzmann equation.

Polymorphism of TS 3'-UTR predicts survival of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.

PubMed

Gao, J; He, Q; Hua, D; Mao, Y; Li, Y; Shen, L

2013-08-01

Capecitabine-containing chemotherapy was widely used in clinic medication. We investigated the association of the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD) polymorphisms with the clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Blood samples were collected prior to treatment from 125 patients with advanced gastric cancer and the TS (two or three repeats of a 28 bp sequence in 5'-untranslated region and 6 bp insertion or deletion in 3'-untranslated region), MTHFR (C677T) and DPD (IVS14+1G > A) polymorphisms were determined using PCR amplification and Sanger sequencing. The median age of 125 patients was 58 years (range, 23-76) with female 42 and male 83, and the response rate, median progression-free survival and overall survival (OS) were 43.2 %, 5.2 and 11.0 months. The median OS in patients with TS ins6/ins6 genotype (6.8 months) was significantly shorter than those in patients with ins6/del6 (11.0 months, P = 0.016) and del6/del6 (11.5 months, P = 0.039) genotypes. Cox multivariate analysis also showed that TS ins6/ins6 genotype was the independent poor OS predictor (P = 0.001, HR = 3.182). No significant associations were found between the polymorphisms of TS 5'-UTR/MTHFR and clinical outcome, and no IVS14+1G > A polymorphism of DPD was found in this study. We first reported that TS 3'-UTR ins6/ins6 genotype could predict the poor survival of advanced gastric cancer patients treated with capecitabine plus paclitaxel, which would be further verified in a large multicenter study.

Variability of collagen crosslinks: impact of sample collection period

NASA Technical Reports Server (NTRS)

Smith, S. M.; Dillon, E. L.; DeKerlegand, D. E.; Davis-Street, J. E.

2004-01-01

Because of the variability of collagen crosslinks, their use as markers for bone resorption is often criticized. We hypothesized that the variability could be reduced by collecting urine for 24 hours (or longer) instead of using single voids, and by not normalizing to creatinine. Urine samples were collected from 22 healthy subjects during two or more 24-hour periods. Each 24-hour pool and each 2nd void of the day were analyzed for N-telopeptide (NTX), pyridinium (PYD), and deoxypyridinoline (DPD) crosslinks. Data were analyzed by using linear regression. For NTX, R2 for the two, 2nd-void samples (n = 38) was 0.55, whereas R2 for the two 24-hour pools was 0.51 or 0.52, expressed per day or per creatinine. For PYD and DPD, R2 for the 2nd-void samples was 0.26 and 0.18, R2 for the 24-hour pools expressed per day was 0.58 and 0.74, and R2 for the 24-hour pools expressed per creatinine was 0.65 and 0.76, respectively. Regression of the 2nd void and the corresponding 24-hour pool, expressed per day, yielded R2 = 0.19, 0.19, and 0.08, for NTX, PYD, and DPD, respectively (n = 76 each). For the 2nd-void sample and its corresponding 24-hour pool, expressed per creatinine, R2 = 0.24, 0.33, and 0.08, respectively. In a separate study, the coefficient of variation for NTX was reduced (P < 0.05) when data from more than one 24-hour collection were combined. Thus, the variability inherent in crosslink determinations can be reduced by collecting urine for longer periods. In research studies, the high variability of single-void collections, compounded by creatinine normalization, may alter or obscure findings.

Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU- and capecitabine-related toxicity using full sequencing of DPYD.

PubMed

Saif, Muhammad Wasif

2013-01-01

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of the degradation of pyrimidine base, and plays a pivotal role in the pharmacogenetic syndrome of 5-fluorouracil (5-FU). Deficiency of DPD activity leads to severe toxicities, even death, following administration of 5-FU. Several studies have demonstrated that molecular defects of the dihydropyrimidine dehydrogenase gene (DPYD) lead to the deficiency of DPD activity and cause this pharmacogenetic syndrome. We present the analysis of DPYD genotyping in untreated Caucasian patients (control group) and Caucasian patients with 5-FU/CAP-related grade 3/4 toxicities (toxicity group) who underwent a capecitabine TheraGuide 5-FU testing. Full sequencing of DPYD was performed in the Myriad Genetic Laboratories, Inc. as part of TheraGuide 5-FU test. Among 227 patients from the toxicity group, 27 (12%) had deleterious mutations in DPYD: twelve (5%) had IVS14 +1 G>A, eleven (5%) had D949V and four (2%) had other mutations. Only 7/192 (4%) patients from the control group had DPYD genotype abnormalities: two (1%) had IVS14 +1 G>A, four (2%) had D949V and one (1%) had other mutation. Genotype abnormalities were observed more frequently in the toxicity group (p=0.001). Among 65 patients with toxicities due to capecitabine, nine (14%) had mutated DPYD, which was more frequent than in the control group (p=0.006). Mutated DPYD is frequently observed in Caucasian patients who experience toxicities while receiving 5-FU/capecitabine. Screening of patients for DPYD mutations prior to administration of 5-FU/capecitabine using new pharmacogenetic testing methods, may help for identify those patients who are at greatest risk for adverse effects, allowing a more individualized approach to their chemotherapy management.

CASPR2 autoantibodies are raised during pregnancy in mothers of children with mental retardation and disorders of psychological development but not autism

PubMed Central

Coutinho, Ester; Jacobson, Leslie; Pedersen, Marianne Giørtz; Benros, Michael Eriksen; Nørgaard-Pedersen, Bent; Mortensen, Preben Bo; Harrison, Paul J; Vincent, Angela

2017-01-01

Background, Methods and Objectives Maternal autoantibodies to neuronal proteins may be one cause of neurodevelopmental disorders. This exploratory study used the Danish archived midgestational sera and their nationwide registers to search for antibodies to the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein-like 2 (CASPR2) in maternal sera, and to relate them to subsequent psychiatric diagnoses in the woman or her child. Results In a sample of 192 women, there was no association between antibody status and subsequent psychosis in the mothers. However, NMDAR antibodies (n=4) or CASPR2 antibodies (n=1) were identified in 5/11 (45.5%) women whose children were given a diagnosis of mild or unspecified mental retardation or disorders of psychological and motor development (collectively abbreviated as mental retardation and/or disorders of psychological development (MR/DPD)) compared with 9/176 (5.1%) of the remaining mother (p<0.001). These findings were followed up in a specifically selected cohort, in which CASPR2 antibodies were detected in 7/171 (4.1%) mothers of MR/DPD progeny, compared with only 1/171 (0.6%) control mother (p=0.067). The combined sample showed a significantly higher frequency of CASPR2 antibodies in mothers of MD/DPD children (p=0.01). These autoantibodies were not increased in mothers of children with autistic spectrum disorder. Conclusions These findings complement the known roles of CASPR2 in brain development, and warrant further epidemiological and experimental studies to clarify the role of CASPR2 and possibly other antibodies in neurodevelopmental disorders. PMID:28572274

Feasibility of ecological momentary assessment to characterize adolescent postoperative diet and activity patterns after weight loss surgery.

PubMed

Ratcliff, Megan B; Zeller, Meg H; Inge, Thomas H; Hrovat, Kathleen B; Modi, Avani C

2014-01-01

Adherence to postoperative lifestyle recommendations may be associated with weight outcomes among weight loss surgery (WLS) patients, but it is difficult to objectively assess and has not been reported among adolescents. Methods of assessment that are ecologically valid and provide important contextual information related to adherence are needed. The objective of this pilot study was to demonstrate the feasibility of using a form of ecological momentary assessment (i.e., daily phone diaries; DPD) to assess postoperative diet and activity patterns among a sample of adolescent WLS patients to determine adherence to best-practice lifestyle recommendations. University Hospital. Eight adolescent WLS patients completed 3 consecutive DPDs at 12 and 18 months postsurgery. Ninety-four percent of DPD's were completed with an average 20.9 ± 5.0 activities/day. Although adolescents engaged in recommended lifestyle behaviors (e.g.,≥ 30 min moderate physical activity/d; duration of meals/snacks ≥ 20 min) some of the time, few were adherent to postoperative physical activity and dietary recommendations the majority of the time. The DPD provides a feasible and informative methodology for assessing adherence behaviors among adolescent WLS patients. It is a relatively low burden method that may be useful in identifying behavioral targets for postoperative intervention. Adherence to postoperative lifestyle recommendations may be a serious concern among this cohort. These preliminary data shed light on potential targets for postoperative intervention. Targeting nonadherence is essential in not only improving health outcomes but in deciphering the true potential effectiveness of WLS in this at-risk population. Copyright © 2014 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Changes in markers of bone formation and resorption in a bed rest model of weightlessness

NASA Technical Reports Server (NTRS)

Lueken, S. A.; Arnaud, S. B.; Taylor, A. K.; Baylink, D. J.

1993-01-01

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

Depressive Personality Disorder: A Comparison of Three Self-Report Measures

ERIC Educational Resources Information Center

Miller, Joshua D.; Tant, Adam; Bagby, R. Michael

2010-01-01

Depressive personality disorder (DPD) was included in the appendix of the "Diagnostic and Statistical Manual of Mental Disorders", Fourth Edition ("DSM-IV") for further study. Questions abound regarding this disorder in terms of its distinctiveness from extant diagnostic constructs and clinical significance.This study examines…

A hybrid parallel architecture for electrostatic interactions in the simulation of dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Yang, Sheng-Chun; Lu, Zhong-Yuan; Qian, Hu-Jun; Wang, Yong-Lei; Han, Jie-Ping

2017-11-01

In this work, we upgraded the electrostatic interaction method of CU-ENUF (Yang, et al., 2016) which first applied CUNFFT (nonequispaced Fourier transforms based on CUDA) to the reciprocal-space electrostatic computation and made the computation of electrostatic interaction done thoroughly in GPU. The upgraded edition of CU-ENUF runs concurrently in a hybrid parallel way that enables the computation parallelizing on multiple computer nodes firstly, then further on the installed GPU in each computer. By this parallel strategy, the size of simulation system will be never restricted to the throughput of a single CPU or GPU. The most critical technical problem is how to parallelize a CUNFFT in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Furthermore, the upgraded method is capable of computing electrostatic interactions for both the atomistic molecular dynamics (MD) and the dissipative particle dynamics (DPD). Finally, the benchmarks conducted for validation and performance indicate that the upgraded method is able to not only present a good precision when setting suitable parameters, but also give an efficient way to compute electrostatic interactions for huge simulation systems. Program Files doi:http://dx.doi.org/10.17632/zncf24fhpv.1 Licensing provisions: GNU General Public License 3 (GPL) Programming language: C, C++, and CUDA C Supplementary material: The program is designed for effective electrostatic interactions of large-scale simulation systems, which runs on particular computers equipped with NVIDIA GPUs. It has been tested on (a) single computer node with Intel(R) Core(TM) i7-3770@ 3.40 GHz (CPU) and GTX 980 Ti (GPU), and (b) MPI parallel computer nodes with the same configurations. Nature of problem: For molecular dynamics simulation, the electrostatic interaction is the most time-consuming computation because of its long-range feature and slow convergence in simulation space, which approximately take up most of the total simulation time. Although the parallel method CU-ENUF (Yang et al., 2016) based on GPU has achieved a qualitative leap compared with previous methods in electrostatic interactions computation, the computation capability is limited to the throughput capacity of a single GPU for super-scale simulation system. Therefore, we should look for an effective method to handle the calculation of electrostatic interactions efficiently for a simulation system with super-scale size. Solution method: We constructed a hybrid parallel architecture, in which CPU and GPU are combined to accelerate the electrostatic computation effectively. Firstly, the simulation system is divided into many subtasks via domain-decomposition method. Then MPI (Message Passing Interface) is used to implement the CPU-parallel computation with each computer node corresponding to a particular subtask, and furthermore each subtask in one computer node will be executed in GPU in parallel efficiently. In this hybrid parallel method, the most critical technical problem is how to parallelize a CUNFFT (nonequispaced fast Fourier transform based on CUDA) in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Restrictions: The HP-ENUF is mainly oriented to super-scale system simulations, in which the performance superiority is shown adequately. However, for a small simulation system containing less than 106 particles, the mode of multiple computer nodes has no apparent efficiency advantage or even lower efficiency due to the serious network delay among computer nodes, than the mode of single computer node. References: (1) S.-C. Yang, H.-J. Qian, Z.-Y. Lu, Appl. Comput. Harmon. Anal. 2016, http://dx.doi.org/10.1016/j.acha.2016.04.009. (2) S.-C. Yang, Y.-L. Wang, G.-S. Jiao, H.-J. Qian, Z.-Y. Lu, J. Comput. Chem. 37 (2016) 378. (3) S.-C. Yang, Y.-L. Zhu, H.-J. Qian, Z.-Y. Lu, Appl. Chem. Res. Chin. Univ., 2017, http://dx.doi.org/10.1007/s40242-016-6354-5. (4) Y.-L. Zhu, H. Liu, Z.-W. Li, H.-J. Qian, G. Milano, Z.-Y. Lu, J. Comput. Chem. 34 (2013) 2197.

Chlorine Analysis - Wastewater. Training Module 5.125.2.77.

ERIC Educational Resources Information Center

Kirkwood Community Coll., Cedar Rapids, IA.

This document is an instructional module package prepared in objective form for use by an instructor familiar with the laboratory procedures for determining the combined chlorine residual of a wastewater sample. Included are objectives, instructor guides, student handouts, and transparency masters. This module considers the amperometric, DPD,…

Teaching for Change: The Difference, Power, and Discrimination Model

ERIC Educational Resources Information Center

Xing, Jun, Ed.; Li, Judith, Ed.; Roper, Larry D., Ed.; Shaw, Susan M., Ed.

2006-01-01

Over the past three decades, American higher education has witnessed a shift in demographics which has created a more diverse student body. However, many university campuses remain unsupportive or even hostile to minority faculty and students. This anthology introduces to readers the Difference, Power, and Discrimination (DPD) Program, a…

Douglas-fir displays a range of growth responses to temperature, water, and Swiss needle cast in western Oregon, USA

EPA Science Inventory

Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) growth in the Pacific Northwest is affected by climatic, edaphic factors and Swiss needle cast (SNC) disease. We examine Douglas-fir growth responses to temperature, dewpoint deficit (DPD), soil moisture, and SNC ...

Space station MSFC-DPD-235/DR no. CM-03 specification, modular space station project, Part 1 CEI

NASA Technical Reports Server (NTRS)

1971-01-01

Contract engineering item specifications for the modular space station are presented. These specifications resulted from the development and allocations of requirements which are concise statements of performance or constraints on performance. Specifications contain requirements for functional performance and for the verification of design solutions.

SUNREL Applications | Buildings | NREL

Science.gov Websites

used by the building design team for energy analysis. Zion National Park Visitor's Center Grand Canyon National Park Bookstore NREL Thermal Test Facility NREL Wind Site Entrance Building DPD Office Building Performance Analysis of a High-Mass Residential Building Van Geet residence The Van Geet Off-Grid Home: An

Quantifying the abnormal hemodynamics of sickle cell anemia

NASA Astrophysics Data System (ADS)

Lei, Huan; Karniadakis, George

2012-02-01

Sickle red blood cells (SS-RBC) exhibit heterogeneous morphologies and abnormal hemodynamics in deoxygenated states. A multi-scale model for SS-RBC is developed based on the Dissipative Particle Dynamics (DPD) method. Different cell morphologies (sickle, granular, elongated shapes) typically observed in deoxygenated states are constructed and quantified by the Asphericity and Elliptical shape factors. The hemodynamics of SS-RBC suspensions is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. Moreover, SS-RBCs exhibit abnormal adhesive interactions with both the vessel endothelium cells and the leukocytes. The effect of the abnormal adhesive interactions on the hemodynamics of sickle blood is investigated using the current model. It is found that both the SS-RBC - endothelium and the SS-RBC - leukocytes interactions, can potentially trigger the vicious ``sickling and entrapment'' cycles, resulting in vaso-occlusion phenomena widely observed in micro-circulation experiments.

Multiscale modeling of particle in suspension with smoothed dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Bian, Xin; Litvinov, Sergey; Qian, Rui; Ellero, Marco; Adams, Nikolaus A.

2012-01-01

We apply smoothed dissipative particle dynamics (SDPD) [Español and Revenga, Phys. Rev. E 67, 026705 (2003)] to model solid particles in suspension. SDPD is a thermodynamically consistent version of smoothed particle hydrodynamics (SPH) and can be interpreted as a multiscale particle framework linking the macroscopic SPH to the mesoscopic dissipative particle dynamics (DPD) method. Rigid structures of arbitrary shape embedded in the fluid are modeled by frozen particles on which artificial velocities are assigned in order to satisfy exactly the no-slip boundary condition on the solid-liquid interface. The dynamics of the rigid structures is decoupled from the solvent by solving extra equations for the rigid body translational/angular velocities derived from the total drag/torque exerted by the surrounding liquid. The correct scaling of the SDPD thermal fluctuations with the fluid-particle size allows us to describe the behavior of the particle suspension on spatial scales ranging continuously from the diffusion-dominated regime typical of sub-micron-sized objects towards the non-Brownian regime characterizing macro-continuum flow conditions. Extensive tests of the method are performed for the case of two/three dimensional bulk particle-system both in Brownian/ non-Brownian environment showing numerical convergence and excellent agreement with analytical theories. Finally, to illustrate the ability of the model to couple with external boundary geometries, the effect of confinement on the diffusional properties of a single sphere within a micro-channel is considered, and the dependence of the diffusion coefficient on the wall-separation distance is evaluated and compared with available analytical results.

Tumor 5-FU-related mRNA Expression and Efficacy of Oral Fluoropyrimidines in Adjuvant Chemotherapy of Colorectal Cancer.

PubMed

Koda, Keiji; Miyauchi, Hideaki; Kosugi, Chihiro; Kaiho, Takashi; Takiguchi, Nobuhiro; Kobayashi, Susumu; Maruyama, Takashi; Matsubara, Hisahiro

2016-10-01

It has not been elucidated whether the clinical efficacy of oral fluoropyrimidines for adjuvant chemotherapy of colorectal cancer varies with tumor biological characteristics. A multicenter randomized trial was performed comparing oral tegafur/gimeracil/oteracil (S-1) and uracil-tegafur/ leucovorin (UFT/LV) as adjuvant therapy for stage III colorectal cancer. Postoperative survival was compared based on the 5-FU-related mRNA levels in cancer tissues. Among patients with tumor expressing dihydropyrimidine dehydrogenase (DPD) mRNA within the 66.7th percentile (lower 2/3) of all cases, overall survival (OS) was significantly better in the S-1 than in the UFT/LV group. In the S-1 group, patients with low DPD-expressing tumors had significantly better OS than those with highly expressing tumors. Patients with low thymidine synthase (TS)-expressing tumors had significantly better OS than those with highly expressing tumors. The efficacy of oral fluoropyrimidines as adjuvant chemotherapy for colorectal cancer may be influenced by the level of 5-FU-related mRNA in cancer tissues. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Graphene quantum dot as a green and facile sensor for free chlorine in drinking water.

PubMed

Dong, Yongqiang; Li, Geli; Zhou, Nana; Wang, Ruixue; Chi, Yuwu; Chen, Guonan

2012-10-02

Free chlorine was found to be able to destroy the passivated surface of the graphene quantum dots (GQDs) obtained by pyrolyzing citric acid, resulting in significant quenching of their fluorescence (FL) signal. After optimizing some experimental conditions (including response time, concentration of GQDs, and pH value of solution), a green and facile sensing system has been developed for the detection of free residual chlorine in water based on FL quenching of GQDs. The sensing system exhibits many advantages, such as short response time, excellent selectivity, wide linear response range, and high sensitivity. The linear response range of free chlorine (R(2) = 0.992) was from 0.05 to 10 μM. The detection limit (S/N = 3) was as low as 0.05 μM, which is much lower than that of the most widely used N-N-diethyl-p-phenylenediamine (DPD) colorimetric method. This sensing system was finally used to detect free residual chlorine in local tap water samples. The result agreed well with that by the DPD colorimetric method, suggesting the potential application of this new, green, sensitive, and facile sensing system in drinking water quality monitoring.

Therapeutic drug monitoring of antimetabolic cytotoxic drugs

PubMed Central

Lennard, L

1999-01-01

Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are several reasons, but one major drawback is the lack of established therapeutic concentration ranges. Combination chemotherapy makes the establishment of therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as that when the drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centres, and some of these protocols are now part of large multicentre trials. Nonetheless, methotrexate is the only agent which is routinely monitored in most treatment centres. An additional factor, especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes which play a major role in drug metabolism. Monitoring of therapy could include assay of phenotypic enzyme activities or genotype in addition to, or instead of, the more traditional measurement of parent drug or drug metabolites. The cytotoxic activities of mercaptopurine and fluorouracil are regulated by thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD), respectively. Lack of TPMT functional activity produces life-threatening mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can influence the bioavailability, pharmacokinetics, toxicity and efficacy of their substrate drugs. PMID:10190647

A case of squamous cell carcinoma of the head and neck producing granulocyte-colony stimulating factor with marked leukocytosis.

PubMed

Toyoda, Minoru; Chikamatsu, Kazuaki; Sakakura, Koichi; Fukuda, Yoichiro; Takahashi, Katsumasa; Miyashita, Motoaki; Shimamura, Kazuo; Furuya, Nobuhiko

2007-06-01

In squamous cell carcinoma of the head and neck (SCCHN), tumor cells have been shown to secrete detectable amounts of various cytokines, such as interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta. These tumor-derived factors might be responsible for promoting malignancy. Here, we describe a SCCHN patient with tumor produced G-CSF and characterized by marked leukocytosis. In this 45-year-old man, severe leukocytosis developed in parallel with aggressive tumor growth. G-CSF production by the tumor was confirmed by immunohistochemistry (IHC). Serum G-CSF levels were elevated. The leukocyte counts and the blood G-CSF level decreased following a course of radiotherapy. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, the tumor cells were also investigated by IHC with anti-p53, anti-P-glycoprotein (P-gp), anti-thymidylate synthase (TS), and anti-dihydropyrimidine dehydrogenase (DPD), which molecules are thought to contribute the acquisition of therapeutic resistance. The tumor cells were positively stained for TS and DPD, but neither p53 nor P-gp. These results suggest that a variety of molecules may be responsible for acquisition of high malignancy.

An optimized, universal hardware-based adaptive correlation receiver architecture

NASA Astrophysics Data System (ADS)

Zhu, Zaidi; Suarez, Hernan; Zhang, Yan; Wang, Shang

2014-05-01

The traditional radar RF transceivers, similar to communication transceivers, have the basic elements such as baseband waveform processing, IF/RF up-down conversion, transmitter power circuits, receiver front-ends, and antennas, which are shown in the upper half of Figure 1. For modern radars with diversified and sophisticated waveforms, we can frequently observe that the transceiver behaviors, especially nonlinear behaviors, are depending on the waveform amplitudes, frequency contents and instantaneous phases. Usually, it is a troublesome process to tune an RF transceiver to optimum when different waveforms are used. Another issue arises from the interference caused by the waveforms - for example, the range side-lobe (RSL) caused by the waveforms, once the signals pass through the entire transceiver chain, may be further increased due to distortions. This study is inspired by the two existing solutions from commercial communication industry, digital pre-distortion (DPD) and adaptive channel estimation and Interference Mitigation (AIM), while combining these technologies into a single chip or board that can be inserted into the existing transceiver system. This device is then named RF Transceiver Optimizer (RTO). The lower half of Figure 1 shows the basic element of RTO. With RTO, the digital baseband processing does not need to take into account the transceiver performance with diversified waveforms, such as the transmitter efficiency and chain distortion (and the intermodulation products caused by distortions). Neither does it need to concern the pulse compression (or correlation receiver) process and the related mitigation. The focus is simply the information about the ground truth carried by the main peak of correlation receiver outputs. RTO can be considered as an extension of the existing calibration process, while it has the benefits of automatic, adaptive and universal. Currently, the main techniques to implement the RTO are the digital pre- or -post distortions (DPD), and the main technique to implement the AIM is the Adaptive Pulse Compression (APC). The basic algorithms and experiments with DPD will be introduced which is also the focus of this paper. The discussion of AIM algorithms will be presented in other papers, while the initial implementation of AIM and correlation receiver in FPGA devices will also be introduced in this paper.

A Systematic Evaluation of Collagen Crosslinks in the Human Cervix

PubMed Central

Zork, Noelia M; Myers, Kristin Marie; Yoshida, Ms. Kyoko; Cremers, Serge; Jiang, Hongfeng; Ananth, Cande V; Wapner, Ronald; Kitajewski, Jan; Vink, Joy

2014-01-01

Objective The mechanical strength of the cervix relies on crosslinking of the tissue’s collagen network. Clinically, the internal os is functionally distinct from the external os. We sought to detect specific collagen crosslinks in human cervical tissue and determine if crosslink profiles were similar at the internal and external os. Study Design Transverse slices of cervical tissue were obtained at the internal and external os from 13 non-pregnant, premenopausal women undergoing a benign hysterectomy. To understand how crosslinks were distributed throughout the entire cervix and at the internal and external os, biopsies were obtained from three circumferential zones in four quadrants from each slice. Biopsies were pulverized, lyophilized, reduced with sodium borohydride, hydrolyzed with hydrochloric acid and reconstituted in heptafluorobutyric acid buffer. Hydroxyproline was measured by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), converted to total collagen, and normalized by dry weight. Collagen crosslinks pyridinoline (PYD), deoxypyridinoline (DPD), dihydroxylysinonorleucine (DHLNL), and the nonenzymatic advanced glycation end product pentosidine [PEN] were measured by UPLC-ESI-MS/MS and reported as crosslink density ratio (crosslink:total collagen). Generalized estimated equation analysis was used to compare results between the internal and external os and to compare quadrants and zones within slices from the internal and external os to determine if crosslink profiles were similar. Results 592 samples from 13 patients were analyzed. Collagen crosslinks are detectable in the human cervix by UPLC-ESI-MS/MS. When comparing all samples from the internal and external os, similar levels of collagen content, PYD, DHLNL and DPD were found but PEN density was higher at the external os (0.005 vs 0.004, P=0.001). When comparing all internal os samples, significant heterogeneity was found in collagen content and crosslink densities across zones and quadrants. The external os exhibited heterogeneity only across zones. Conclusion Collagen crosslinks (PYD, DPD, DHLNL, and PEN) are detectable by UPLC-ESI-MS/MS in the human cervix. The internal os exhibits significant collagen crosslink heterogeneity compared to the external os. Further studies are needed to evaluate how collagen crosslink heterogeneity correlates to the mechanical strength and function of the human cervix. PMID:25281365

Comparison of the transient responses of Escherichia coli to a glucose pulse of various intensities.

PubMed

Sunya, Sirichai; Delvigne, Frank; Uribelarrea, Jean-Louis; Molina-Jouve, Carole; Gorret, Nathalie

2012-08-01

Dynamic stimulus-responses of Escherichia coli DPD2085, yciG::LuxCDABE reporter strain, to glucose pulses of different intensities (0.08, 0.4 and 1 g L(-1)) were compared using glucose-limited chemostat cultures at dilution rate close to 0.15 h(-1). After at least five residence times, the steady-state cultures were disturbed by a pulse of glucose, engendering conditions of glucose excess with concomitant oxygen limitation. In all conditions, glucose consumption, acetate and formate accumulations followed a linear relationship with time. The resulting specific uptake and production rates as well as respiratory rates were rapidly increased within the first seconds, which revealed a high ability of E. coli strain to modulate its metabolism to a new environment. For transition from glucose-excess to glucose-limited conditions, the cells rapidly re-established its pseudo-steady state. The dynamics of transient responses at the macroscopic viewpoint were shown to be independent on the glucose pulse intensity in the tested range. On the contrary, the E. coli biosensor yciG::luxCDABE revealed a transcriptional induction of yciG gene promoter depending on the quantities of the glucose added, through in situ and online monitoring of the bioluminescence emitted by the cells. Despite many studies describing the dynamics of the transient response of E. coli to glucose perturbations, it is the first time that a direct comparison is reported, using the same experimental design (strain, medium and experimental set up), to study the impact of the glucose pulse intensity on the dynamics of microbial behaviour regarding growth, respiration and metabolite productions.

[On the relationship between emotional dependency and abuse].

PubMed

Leemans, C; Loas, S

2016-01-01

Abuse is a complex psychosocial issue with multiple implications. This paper takes a look at the physical and psychological manifestations of domestic violence, i.e. between adult (romantic) partners as well as abuse of the elderly. Past studies have looked at the relationship between emotional dependency, the occurence and sustainability of abuse and the likehood that a victimized person will terminate a relationship. Indeed, individuals with Dependent Personality Disorder (DPD) or with dependent characteristics present a higher risk of becoming abusive (both physically and mentally) as well as becoming a victim of abuse. Regarding the elderly, the concept of "reverse violence"--where the current abuser was the victim of the senior who is being abused-, also entails dependent relationships. We identified three concepts that are necessary in the understanding of how dependent relationships underpin abuse: Rusbult's model of commitment in intimate relationships, the notion of dependency-possessiveness and Murphy et al's notion of escalating affective dependency. Thus, it is imperative that future studies in the field of domestic violence look at the dynamics of dyads rather than the individuals alone.

Utilization of an Accelerated Queso Fresco Recipe to Teach Concepts of Food Science in a Didactic Program in Dietetics

ERIC Educational Resources Information Center

Therrien, Mona; Calder, Beth L.; Castonguay, Zakkary J.

2018-01-01

Students in the Didactic Program in Dietetics (DPD) at the University of Maine were exposed to the cheese-making process, within a lab setting of two hours, utilizing an accelerated recipe for a Queso Fresco-style cheese. The purpose of this project was to provide students with a novel, hands-on learning experience, which covered concepts of…

Amount of Genetics Education is Low Among Didactic Programs in Dietetics.

PubMed

Beretich, Kaitlan; Pope, Janet; Erickson, Dawn; Kennedy, Angela

2017-01-01

Nutritional genomics is a growing area of research. Research has shown registered dietitian nutritionists (RDNs) have limited knowledge of genetics. Limited research is available regarding how didactic programs in dietetics (DPDs) meet the genetics knowledge requirement of the Accreditation Council for Education in Nutrition and Dietetics (ACEND®). The purpose of this study was to determine the extent to which the study of nutritional genomics is incorporated into undergraduate DPDs in response to the Academy of Nutrition and Dietetics position statement on nutritional genomics. The sample included 62 DPD directors in the U.S. Most programs (63.9%) reported the ACEND genetics knowledge requirement was being met by integrating genetic information into the current curriculum. However, 88.7% of programs reported devoting only 1-10 clock hours to genetics education. While 60.3% of directors surveyed reported they were confident in their program's ability to teach information related to genetics, only 6 directors reported having specialized training in genetics. The overall amount of clock hours devoted to genetics education is low. DPD directors, faculty, and instructors are not adequately trained to provide this education to students enrolled in DPDs. Therefore, the primary recommendation of this study is the development of a standardized curriculum for genetics education in DPDs.

Limitations of three-dimensional power Doppler angiography in preoperative evaluation of ovarian tumors.

PubMed

Silvestre, Liliane; Martins, Wellington P; Candido-Dos-Reis, Francisco J

2015-07-29

This study describes the accuracy of three-dimensional power Doppler (3D-PD) angiography as secondary method for differential diagnosis of ovarian tumors. Seventy-five women scheduled for surgical removal of adnexal masses were assessed by transvaginal ultrasound. Ovarian tumors were classified by IOTA simple rules and two three-dimensional blocks were recorded. In a second step analyses, a 4 cm(3) spherical sample was obtained from the highest vascularized solid area of each stored block. Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were calculated. The repeatability was assessed by concordance correlation coefficient (CCC) and limits of agreement (LoA), and diagnostic accuracy by area under ROC curve. IOTA simple rules classified 26 cases as benign, nine as inconclusive and 40 as malignant. There were eight false positive and no false negative. Among the masses classified as inconclusive or malignant by IOTA simple rules, the CCCs were 0.91 for VI, 0.70 for FI, and 0.86 for VFI. The areas under ROC curve were 0.82 for VI, 0.67 for FI and 0.81 for VFI. 3D-PD angiography presented considerable intraobserver variability and low accuracy for identifying false positive results of IOTA simple rules.

Institutional analysis of milkfish supply chain using interpretive structural modelling (ISM) (case study of UD. Bunda Foods, Sidoarjo District)

NASA Astrophysics Data System (ADS)

Silalahi, R. L. R.; Mustaniroh, S. A.; Ikasari, D. M.; Sriulina, R. P.

2018-03-01

UD. Bunda Foods is an SME located in the district of Sidoarjo. UD. Bunda Foods has problems of maintaining its milkfish’s quality assurance and developing marketing strategies. Improving those problems enables UD. Bunda Foods to compete with other similar SMEs and to market its product for further expansion of their business. The objectives of this study were to determine the model of the institutional structure of the milkfish supply chain, to determine the elements, the sub-elements, and the relationship among each element. The method used in this research was Interpretive Structural Modeling (ISM), involving 5 experts as respondents consisting of 1 practitioner, 1 academician, and 3 government organisation employees. The results showed that there were two key elements include requirement and goals elements. Based on the Drive Power-Dependence (DP-D) matrix, the key sub-elements of requirement element, consisted of raw material continuity, appropriate marketing strategy, and production capital, were positioned in the Linkage sector quadrant. The DP-D matrix for the key sub-elements of the goal element also showed a similar position. The findings suggested several managerial implications to be carried out by UD. Bunda Foods include establishing good relationships with all involved institutions, obtaining capital assistance, and attending the marketing training provided by the government.

Evaluation of approaches to quantify total residual oxidants in ballast water management systems employing chlorine for disinfection.

PubMed

Zimmer-Faust, Amity G; Ambrose, Richard F; Tamburri, Mario N

2014-01-01

With the maturation and certification of several ballast water management systems that employ chlorine as biocide to prevent the spread of invasive species, there is a clear need for accurate and reliable total residual oxidants (TRO) technology to monitor treatment dose and assure the environmental safety of treated water discharged from ships. In this study, instruments used to measure TRO in wastewater and drinking water applications were evaluated for their performance in scenarios mimicking a ballast water treatment application (e.g., diverse hold times, temperatures, and salinities). Parameters chosen for testing these technologies in the past do not reflect conditions expected during ballast water treatment. Salinity, temperature, and oxidant concentration all influenced the response of amperometric sensors. Oxidation reduction potential (ORP) sensors performed more consistently than amperometric sensors under different conditions but it may be difficult to correlate ORP and TRO measurements for the multitude of biogeochemical conditions found naturally in ballast water. N,N-diethyl-p-phenylenediamine (DPD) analyzers and amperometric sensors were also tested under intermittent sampling conditions mimicking a ballasting scenario, with cyclical dosage and discharge operations. When sampling was intermittent, amperometric sensors required excessive response and conditioning times, whereas DPD analyzers provided reasonable estimates of TRO under the ballasting scenario.

Pharmacogenetics in cancer therapy - 8 years of experience at the Institute for Oncology and Radiology of Serbia.

PubMed

Cavic, Milena; Krivokuca, Ana; Boljevic, Ivana; Brotto, Ksenija; Jovanovic, Katarina; Tanic, Miljana; Filipovic, Lana; Zec, Manja; Malisic, Emina; Jankovic, Radmila; Radulovic, Sinisa

2016-01-01

Pharmacogenetics is a study of possible mechanism by which an individual's response to drugs is genetically determined by variations in their DNA sequence. The aim of pharmacogenetics is to identify the optimal drug and dose for each individual based on their genetic constitution, i.e. to individualize drug treatment. This leads to achieving the maximal therapeutic response for each patient, while reducing adverse side effects of therapy and the cost of treatment. A centralized pharmacogenetics service was formed at the Institute for Oncology and Radiology of Serbia (IORS) with the aim to provide a personalized approach to cancer treatment of Serbian patients. Analyses of KRAS mutations in metastatic colorectal cancer, EGFR mutations in advanced non-small cell lung cancer, CYP2D6 polymorphism in breast cancer, DPD polymorphism in colorectal cancer and MTHFR polymorphism in osteosarcoma have been performed by real time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Mutation testing analyses were successful for 1694 KRAS samples and 1821 EGFR samples, while polymorphism testing was successful for 9 CYP2D6 samples, 65 DPD samples and 35 MTHFR samples. Pharmacogenetic methods presented in this paper provide cancer patients in Serbia the best possible choice of treatment at the moment.

Douglas-fir displays a range of growth responses to ...

EPA Pesticide Factsheets

Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) growth in the Pacific Northwest is affected by climatic, edaphic factors and Swiss needle cast (SNC) disease. We examine Douglas-fir growth responses to temperature, dewpoint deficit (DPD), soil moisture, and SNC using time series intervention analysis of intra-annual tree-ring width data collected at nine forest stands in western Oregon, USA. The effects of temperature and SNC were similar in importance on tree growth at all sites. Previous-year DPD during the annual drought period was a key factor limiting growth regionally. Winter temperature was more important at high elevation cool sites, whereas summer temperature was more important at warm and dry sites. Growth rate increased with summer temperature to an optimum (Topt) then decreased at higher temperatures. At drier sites, temperature and water affected growth interactively such that Topt decreased with decreasing summer soil moisture. With climate change, growth rates increased at high elevation sites and declined at mid-elevation inland sites since ~1990. Growth response to climate is masked by SNC regionally. We conclude that as temperature rises and precipitation patterns shift towards wetter winters and drier summers, Douglas-fir will experience greater temperature and water stress and an increase in severity of SNC. By the end of the 21st century, climate models predict hotter, drier summers and warmer, wetter winters in the Pac

In long-term bedridden elderly patients with dietary copper deficiency, biochemical markers of bone resorption are increased with copper supplementation during 12 weeks.

PubMed

Kawada, Etsuo; Moridaira, Kazuaki; Itoh, Katsuhiko; Hoshino, Ayami; Tamura, Jun'ichi; Morita, Toyoho

2006-01-01

Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. This study included 10 patients (83.7 +/- 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation. Copyright (c) 2006 S. Karger AG, Basel.

Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols

PubMed Central

Holy, Xavier; Bégot, Laurent; Renault, Sylvie; Butigieg, Xavier; André, Catherine; Bonneau, Dominique; Savourey, Gustave; Collombet, Jean-Marc

2015-01-01

Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid–base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na+) or potassium (K+), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners’ renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na+ and K+) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID:26265754

Job optimization in ATLAS TAG-based distributed analysis

NASA Astrophysics Data System (ADS)

Mambelli, M.; Cranshaw, J.; Gardner, R.; Maeno, T.; Malon, D.; Novak, M.

2010-04-01

The ATLAS experiment is projected to collect over one billion events/year during the first few years of operation. The efficient selection of events for various physics analyses across all appropriate samples presents a significant technical challenge. ATLAS computing infrastructure leverages the Grid to tackle the analysis across large samples by organizing data into a hierarchical structure and exploiting distributed computing to churn through the computations. This includes events at different stages of processing: RAW, ESD (Event Summary Data), AOD (Analysis Object Data), DPD (Derived Physics Data). Event Level Metadata Tags (TAGs) contain information about each event stored using multiple technologies accessible by POOL and various web services. This allows users to apply selection cuts on quantities of interest across the entire sample to compile a subset of events that are appropriate for their analysis. This paper describes new methods for organizing jobs using the TAGs criteria to analyze ATLAS data. It further compares different access patterns to the event data and explores ways to partition the workload for event selection and analysis. Here analysis is defined as a broader set of event processing tasks including event selection and reduction operations ("skimming", "slimming" and "thinning") as well as DPD making. Specifically it compares analysis with direct access to the events (AOD and ESD data) to access mediated by different TAG-based event selections. We then compare different ways of splitting the processing to maximize performance.

Hip fractures in the elderly in Israel-possible impact of preventable conditions.

PubMed

Segal, Elena; Raichlin, Valentina; Rimbrot, Sophia; Zinman, Chaim; Raz, Batia; Ish-Shalom, Sophia

2009-01-01

In the present study we evaluated the possible contribution of different factors to the occurrence of hip fractures in Israel. We assessed medical history, physical activity, body mass index, smoking status, bone turnover markers and calcium regulating hormones levels of 142 consecutive elderly hip fracture patients (HFP), and compared them to 96 community dwelling elderly people without a history of hip fracture. Age and female gender were the strongest predictors of hip fracture, p<0.001 and 0.013. Stepwise logistic regression demonstrated that HFP had higher PTH and lower 25(OH)D(3) levels, p=0.002, p<0.001; they were less physically active, p<0.001, and had higher rate of vitamin D insufficiency during winter-spring, compared to summer-autumn, p=0.033. Diabetics had higher risk for hip fracture, p=0.06, OR=3.9 (95% CI 1.50-10.4). Deoxypyridinoline (DPD) cross links levels were 19.35+/-10.58mg/mg creatinine in HFP and 9.12+/-3.52 in controls, p<0.0001. Bone alkaline phosphatase (BAP)/DPD ratio was 1.5 in controls compared to 0.53 in HFP. We conclude that age and female gender were the strongest predictors for hip fracture. Diabetic patients had threefold risk for hip fracture. Bone formation/bone resorption ratio was lower in HFP. Vitamin D deficiency and physical inactivity are important preventable risk factors for hip fracture.

Comparison of large-angle production of charged pions with incident protons on cylindrical long and short targets

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

Apollonio, M.; Chimenti, P.; Giannini, G.

2009-12-15

The HARP Collaboration has presented measurements of the double-differential {pi}{sup {+-}} production cross section in the range of momentum 100 MeV/c{<=}p{<=}800 MeV/c and angle 0.35 rad{<=}{theta}{<=}2.15 rad with proton beams hitting thin nuclear targets. In many applications the extrapolation to long targets is necessary. In this article the analysis of data taken with long (one interaction length) solid cylindrical targets made of carbon, tantalum, and lead is presented. The data were taken with the large-acceptance HARP detector in the T9 beam line of the CERN proton synchrotron. The secondary pions were produced by beams of protons with momenta of 5,more » 8, and 12GeV/c. The tracking and identification of the produced particles were performed using a small-radius cylindrical time projection chamber placed inside a solenoidal magnet. Incident protons were identified by an elaborate system of beam detectors. Results are obtained for the double-differential yields per target nucleon d{sup 2}{sigma}/dpd{theta}. The measurements are compared with predictions of the MARS and GEANT4 Monte Carlo simulations.« less

Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil

DTIC Science & Technology

2015-04-01

those of the author( s ) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other...Improved Cognition on Donepezil. 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Davangere Devanand, M.D. Betty Diamond 5d. PROJECT NUMBER...5e. TASK NUMBER E-Mail: dpd3@cumc.columbia.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) AND ADDRESS(ES) 8

Localization of effective actions in open superstring field theory

NASA Astrophysics Data System (ADS)

Maccaferri, Carlo; Merlano, Alberto

2018-03-01

We consider the construction of the algebraic part of D-branes tree-level effective action from Berkovits open superstring field theory. Applying this construction to the quartic potential of massless fields carrying a specific worldsheet charge, we show that the full contribution to the potential localizes at the boundary of moduli space, reducing to elementary two-point functions. As examples of this general mechanism, we show how the Yang-Mills quartic potential and the instanton effective action of a Dp/D( p - 4) system are reproduced.

LDEF - 69 Months in Space: First Post-Retrieval Symposium, Part 1,

DTIC Science & Technology

1991-01-01

Whitaker and Leighton E. Young EXPERIMENT M0003-4 ADVANCED SOLAR CELL AND COVERGLASS ANALYSIS AN OVERVIEW ’ 19,<- TerryM.Trumble PRELIMINARY ANALYSES...this effort. Much of the surveying work was performed by Jack Warren, Miria Finckenor, Frank Cardenas, Eric Christiansen , Samantha Lapin, Lt. Mike...Cour-Palais (ref. 14) and as amended by E. Christiansen (personal communications, 1991) for all aluminum surfaces: P=5.24Dp 19/18H-°-25(dp/d,)0-5

5-Fluorouracil sensitivity varies among oral micro-organisms.

PubMed

Vanlancker, Eline; Vanhoecke, Barbara; Smet, Rozel; Props, Ruben; Van de Wiele, Tom

2016-08-01

5-Fluorouracil (5-FU), a commonly used chemotherapeutic agent, often causes oral mucositis, an inflammation and ulceration of the oral mucosa. Micro-organisms in the oral cavity are thought to play an important role in the aggravation and severity of mucositis, but the mechanisms behind this remain unclear. Although 5-FU has been shown to elicit antibacterial effects at high concentrations (>100 µM), its antibacterial effect at physiologically relevant concentrations in the oral cavity is unknown. This study reports the effect of different concentrations of 5-FU (range 0.1-50 µM) on the growth and viability of bacterial monocultures that are present in the oral cavity and the possible role in the activity of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU resistance. Our data showed a differential sensitivity among the tested oral species towards physiological concentrations of 5-FU. Klebsiellaoxytoca, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis, Pseudomonas aeruginosa and Lactobacillus salivarius appeared to be highly resistant to all tested concentrations. In contrast, Lactobacillusoris, Lactobacillus plantarum, Streptococcus pyogenes, Fusobacterium nucleatum and Neisseria mucosa showed a significant reduction in growth and viability starting from very low concentrations (0.2-3.1 µM). We can also provide evidence that DPD is not involved in the 5-FU resistance of the selected species. The observed variability in response to physiological 5-FU concentrations may explain why certain microbiota lead to a community dysbiosis and/or an overgrowth of certain resistant micro-organisms in the oral cavity following cancer treatment.

High-dose cisplatin with dipyridamole in advanced non-small cell lung cancer. A Grupo Oncológico Cooperativo del Sur study.

PubMed

Vallejo, C T; Rabinovich, M G; Perez, J E; Rodriguez, R; Machiavelli, M R; Leone, B A; Romero, A D; Lacava, J A; Cuevas, M A; Langhi, M J

1995-06-01

From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.

Skin conductance and memory fragmentation after exposure to an emotional film clip in depersonalization disorder.

PubMed

Giesbrecht, Timo; Merckelbach, Harald; van Oorsouw, Kim; Simeon, Daphne

2010-05-30

It is often assumed that when confronted with an emotional event, patients with DPD inhibit information processing. It is also thought that this fosters memory fragmentation. This hypothesis has not been tested in chronic depersonalization. The aim of this study was to investigate the temporal pattern of autonomic responding to emotional material in depersonalization disorder, along with concomitant deficits in subjective and objective memory formation (i.e., difficulties to form a coherent narrative consisting of an ordered sequence of events). Participants with depersonalization disorder (n=14) and healthy control participants (n=14) viewed an emotional video clip while their skin conductance (SC) levels were measured. Peritraumatic dissociation was measured before and after the clip, and memory performance was measured 35 min after viewing. Compared to controls, depersonalized participants exhibited a distinctly different temporal pattern of autonomic responding, characterized by an earlier peak and subsequent flattening of SCLs. Maximum SCLs did not differ between the two groups. Moreover, unlike the control group, depersonalized participants showed no SC recovery after clip offset. In terms of memory performance, patients exhibited objective memory fragmentation, which they also reported subjectively. However, they did not differ from controls in free recall performance. Apparently, emotional responding in DPD is characterized by a shortened latency to peak with subsequent flattening and is accompanied by memory fragmentation in the light of otherwise unremarkable memory functioning. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

[Examination of placental three-dimensional power Doppler indices and perinatal outcome in pregnancies complicated by intrauterine growth restriction].

PubMed

Molnár, András; Surányi, Andrea; Jakó, Mária; Nyári, Tibor; Németh, Gábor

2017-07-01

Development of intrauterine growth restriction (IUGR) can be traced back to maternal or fetal factors, but in many cases we find placental factors (reduced placental circulation) in the background. Our aim was to examine whether the reduced placental bloodperfusion and vascularity show any correlation with cesarean section frequency and the clinical outcome in IUGR pregnancies. The aim of the present study was also to use a properly calibrated and reproducible method for evaluating placental blood flow, that can later be incorporated into the routine examination. 254 women were recruited in our prospective case-control study. The 3 dimensional power Doppler (3DPD) ultrasound indices; vascularisation index (VI), flow index (FI) and vascularization flow index (VFI) were measured on each participant. Median VI was 3.7% (interquartile range [IQR] 3.2%-4.2%) in the IUGR group and 10.1% (IQR 8.6%-10.9%) in the control group (p = 0.001). Median FI value was 40.0 (IQR 39.7-42.5) in the IUGR group and 45.1 (IQR 44.1-53.1) in the control group (p = 0.012). Median VFI was 2.2 (IQR 2.1-2.4) in the IUGR group and 4.8 (IQR 4.4-5.3) in the control. The 3DPD indices may be useful for examining changes in circulation in IUGR pregnancies to characterize the underlying pathology. Orv Hetil. 2017; 158(26): 1008-1013.

Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical parameters of bone turnover in German RA patients.

PubMed

Goertz, B; Fassbender, W J; Williams, J C; Marzeion, A M; Bretzel, R G; Stracke, H; Berliner, M N

2003-01-01

Vitamin D is known to exert immunomodulatory effects. An overrepresentation of the b allele of the vitamin D receptor (VDR) has been detected in autoimmune diseases as type-1-diabetes and multiple sclerosis. VDR polymorphisms have been shown to influence bone metabolism and bone density. The aim of the present study was to examine the distribution of VDR alleles in German rheumatoid arthritis (RA) patients and their relation to bone turnover parameters. 62 German RA patients were included and compared to 40 controls. Three VDR alleles were examined (Bsm I, Taq I and Fok I). In addition, serum intact osteocalcin (OC), parathyroid hormone, bone specific alkaline phosphatase (B-ALP), the carboxyterminal extension peptide of type I procollagen, 25-OH-vitamin D and urinary deoxypyridinoline (DPD) excretion were measured. Furthermore, C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were measured. We found a slightly higher frequency of the bB and tT-genotype in RA patients compared to controls, which was not statistically significant. OC and B-ALP were found to be significantly higher in RA patients with positive correlations between bone formation and resorption parameters indicating higher bone turnover in RA patients with maintained coupling. CRP in RA patients correlated with DPD and inversely with PTH. VDR genotype showed no association with bone turnover, family history or the presence of rheumatoid factor. Our results suggest that VDR polymorphisms do not play a major role in RA predisposition in Germans.

Computational Design of Biomimetic Gels With Properties of Human Tissues

DTIC Science & Technology

2008-12-01

poly(styrene-block- isoprene -block-styrene) copolymer or SIS in the I-selective solvent has been chosen as a model triblock copolymer for this study...our model. A A B B B RC Fig. 2. Schematic representation of A1B3A1 triblock copolymer mapped on DPD model. Poly(styrene-block- isoprene -block...Pa making G 2.25 times higher for c changes from 0.16 to 0.33 (density of styrene and isoprene blocks are taken to be 1.04 and 0.913 g/cm3

Modeling pH-Responsive Adsorption of Polyelectrolytes at Oil-Water Interfaces

NASA Astrophysics Data System (ADS)

Qin, Shiyi; Yong, Xin

We use dissipative particle dynamics (DPD) to discover the interfacial adsorption of pH-responsive polyelectrolytes in oil-water binary systems under different pH values. The electrostatic interactions between charged beads and the dielectric discontinuity across the interface are modeled by exploiting a modified Particle-Particle-Particle-Mesh (PPPM) method, which uses an iterative method to solve the Poisson equation on a uniform grid. We first model the adsorption behavior of a single linear polyelectrolyte from the aqueous phase. The Henderson-Hasselbalch equation describes the relation between pH and the degree of ionization of the modeled polyelectrolytes. Through changing the degree of ionization, we explore the influence of pH on the adsorption behavior and show that the electrostatic interactions significantly modulate the adsorption. Time evolutions of the position and conformation of the polyelectrolytes and the variation in the oil-water surface tension will be measured to characterize the adsorption behavior. Furthermore, we model the pH-dependent adsorption behavior of polyelectrolytes with more complicated structures, namely, branched polyelectrolytes with hydrophobic backbones and hydrophilic side chains. We also find that the addition of salts in the medium and the lengths of the backbone and ionized side chain affect the adsorption. This research supported by the American Chemical Society Petroleum Research Fund (Award 56884-DNI9).

COLLABORATIVE RESEARCH AND DEVELOPMENT (CR&D) Delivery Order 0059: Molecular Dynamics Modeling Support

DTIC Science & Technology

2008-03-01

Molecular Dynamics Simulations 5 Theory: Equilibrium Molecular Dynamics Simulations 6 Theory: Non...Equilibrium Molecular Dynamics Simulations 8 Carbon Nanotube Simulations : Approach and results from equilibrium and non-equilibrium molecular dynamics ...touched from the perspective of molecular dynamics simulations . However, ordered systems such as “Carbon Nanotubes” have been investigated in terms

Associations between dietary flavonoid intakes and bone health in a Scottish population.

PubMed

Hardcastle, Antonia C; Aucott, Lorna; Reid, David M; Macdonald, Helen M

2011-05-01

Flavonoids are bioactive polyphenols found particularly in fruit and vegetables, but little is known about their role in bone health in humans. The aim of this observational study was to investigate whether dietary flavonoid intake was associated with bone mineral density (BMD) and bone resorption in a large group of perimenopausal Scottish women. Over 3000 women completed a food frequency questionnaire as part of an osteoporosis screening study. The diets were analyzed for flavonoid intake using a food composition database. BMD was measured at the femoral neck (FN) and lumbar spine (LS) by dual-energy X-ray absorptiometry (DXA). Free pyridinoline (PYD) and deoxypyridinoline (DPD) were measured by high-performance liquid chromatography (HPLC) in second early morning fasted urine samples. The mean flavonoid intake of the diet was 307 ±199 mg/d. The catechin family contributed the most to flavonoid intakes (55%), and the flavones the least (<1%). Associations were found between energy-adjusted total flavonoid intakes and BMD at the FN and LS (FN r = 0.054, LS r = 0.036, p ≤ .05). Annual percent change in BMD was associated with intakes of procyanidins and catechins (p ≤ .05), and flavanones were negatively associated with bone-resorption markers (PYD r = -0.049, DPD r = -0.057, p ≤ .001). These associations were still seen after adjusting for confounders. It is concluded that dietary flavonoid intakes are associated with BMD, supporting the evidence from animal and cellular studies. Copyright © 2011 American Society for Bone and Mineral Research.

Ivermectin dissipation and movement from feces to soil under field conditions.

PubMed

Iglesias, Lucía Emilia; Saumell, Carlos; Sagüés, Federica; Sallovitz, Juan Manuel; Lifschitz, Adrián Luis

2018-01-02

The aim of this work was to evaluate the fate of ivermectin (IVM) at two concentrations in cattle feces and its movement to the nearby soil and plants. Feces were spiked with IVM at two levels: 3000 ng g -1 (high group, HG) and 300 ng g -1 (low group, LG). Artificial dung pats were prepared and deposited in an experimental field area. Feces and underlying soil were sampled up to 60 days post-deposition (dpd). As an additional analysis, grasses growing around the pats were sampled at 30 and 60 dpd. Ivermectin concentrations in all matrices were determined by HPLC. Mean IVM fecal concentrations were in the range between 3901.9 ng g -1 and 2419.2 ng g -1 (high group) and 375.3 ng g -1 and 177.49 ng g -1 (low group). Mean times for 50% and 90% dissipation were 88.23 and 293.03 days (HG) and 39.1 and 129.9 days (LG). Soil concentrations ranged from 26.1 ng g -1 to 71.1 ng g -1 (HG) and 3.4 to 5.9 ng g -1 (LG); in plants, concentrations were between 71.4 and 380.8 ng g -1 and 5.40 and 51.8 ng g -1 in HG and LG, respectively. These results confirm that IVM moves from feces to the underlying soil as well as to nearby plants. The potential risk of detrimental effects on soil organisms and the impact on herbivorous animals should be further evaluated.

Bioluminescence enhancement through an added washing protocol enabling a greater sensitivity to carbofuran toxicity.

PubMed

Jia, Kun; Eltzov, Evgeni; Marks, Robert S; Ionescu, Rodica E

2013-10-01

The effects of carbofuran toxicity on a genetically modified bacterial strain E. coli DPD2794 were enhanced using a new bioluminescent protocol which consisted of three consecutive steps: incubation, washing and luminescence reading. Specifically, in the first step, several concentrations of carbofuran aqueous solutions were incubated with different bacterial suspensions at recorded optical densities for different lengths of time. Thereafter, the resulting bacterial/toxicant mixtures were centrifuged and the aged cellular supernatant replaced with fresh medium. In the final step, the carbofuran- induced bioluminescence to the exposed E. coli DPD2794 bacteria was shown to provide a faster and higher intensity when recorded at a higher temperature at30°C which is not usually used in the literature. It was found that the incubation time and the replacement of aged cellular medium were essential factors to distinguish different concentrations of carbofuran in the bioluminescent assays. From our results, the optimum incubation time for a "light ON" bioluminescence detection of the effect of carbofuran was 6h. Thanks to the replacement of the aged cellular medium, a group of additional peaks starting around 30min were observed and we used the corresponding areas under the curve (AUC) at different contents of carbofuran to produce the calibration curve. Based on the new protocol, a carbofuran concentration of 0.5pg/mL can be easily determined in a microtiter plate bioluminescent assay, while a non-wash protocol provides an unexplainable order of curve evolutionswhich does not allow the user to determine the concentration. Copyright © 2013 Elsevier Inc. All rights reserved.

Site specific solubility improvement using solid dispersions of HPMC-AS/HPC SSL--mixtures.

PubMed

Zecevic, Damir Elmar; Meier, Robin; Daniels, Rolf; Wagner, Karl-Gerhard

2014-07-01

Many upcoming drug candidates are pH-dependent poorly soluble weak bases in the pH range of the gastrointestinal tract. This often leads to a high in vivo variability and bioavailability issues. Aiming to overcome these limitations, the design of solid dispersions for site specific dissolution improvement or maintenance of a potent supersaturation over the entire gastro-intestinal pH-range, is proposed to assure a reliable drug therapy. Solid dispersions containing different ratios of Dipyridamole (DPD) or Griseofulvin (GRI) and the enteric polymer hydroxypropylmethylcellulose-acetate succinate (HPMC-AS) and the water soluble low-viscosity hydroxypropylcellulose (HPC-SSL) were prepared by hot melt extrusion (HME). The solid dispersions were evaluated for their solid state, dissolution characteristics applying a three pH-step dissolution method following an acidic to neutral pH transition and stability. The use of HPMC-AS in binary mixtures with DPD and GRI facilitated increased solubility and supersaturation at pH-controlled release of the preserved amorphous state of the dispersed drug, which even inverted the pH-dependent solubility profile of the weakly basic model drug (Dipyridamole). I.e. a potent site specific delivery system was created. With ternary solid dispersions of API, HPMC-AS and HPC-SSL, tailored release profiles with superior supersaturation over the applied pH-range could be obtained. At the same time, binary and ternary mixtures showed favorable stability properties at a temperature difference between glass transition temperature and the applied storage temperature of down to 16°C. Copyright © 2014 Elsevier B.V. All rights reserved.

Abnormal ventral tegmental area-anterior cingulate cortex connectivity in Parkinson's disease with depression.

PubMed

Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong

2018-07-16

Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.

High frequency dynamic engine simulation. [TF-30 engine

NASA Technical Reports Server (NTRS)

Schuerman, J. A.; Fischer, K. E.; Mclaughlin, P. W.

1977-01-01

A digital computer simulation of a mixed flow, twin spool turbofan engine was assembled to evaluate and improve the dynamic characteristics of the engine simulation to disturbance frequencies of at least 100 Hz. One dimensional forms of the dynamic mass, momentum and energy equations were used to model the engine. A TF30 engine was simulated so that dynamic characteristics could be evaluated against results obtained from testing of the TF30 engine at the NASA Lewis Research Center. Dynamic characteristics of the engine simulation were improved by modifying the compression system model. Modifications to the compression system model were established by investigating the influence of size and number of finite dynamic elements. Based on the results of this program, high frequency engine simulations using finite dynamic elements can be assembled so that the engine dynamic configuration is optimum with respect to dynamic characteristics and computer execution time. Resizing of the compression systems finite elements improved the dynamic characteristics of the engine simulation but showed that additional refinements are required to obtain close agreement simulation and actual engine dynamic characteristics.

Comparison of Facts and DPD-Steadifac Procedures for Free and Combined Chlorine in Aqueous Solution.

DTIC Science & Technology

1980-01-01

REPIT . //, ONina Matheny!Roscherl Edwi n/Hal 11- Beth/Rosenthal1 William 3./Cooper2 D T Ie ’* Eugene P./Meier2- ELECT*..<: OCT 2 4 1980 d Supported by...DATE U.S. Army Medical Research & Development Command January 1980 Fort Detrick 13. NUMBER OF PAGES rederick MD 21701 55 T G AGENCY NAME & ADDRESS(If...STEADIFAC Modified procedure were shown to have comparable accuracy and D W t ir lo m 14 13 E m, no .o , o r V 6 I 0 O ILIF TANU 147UNCLASSIFIED

Seasonal dynamics of water and air chemistry in an indoor chlorinated swimming pool.

PubMed

Zare Afifi, Mehrnaz; Blatchley, Ernest R

2015-01-01

Although swimming is known to be beneficial in terms of cardiovascular health, as well as for some forms of rehabilitation, swimming is also known to present risks to human health, largely in the form of exposure to microbial pathogens and disinfection byproducts (DBPs). Relatively little information is available in the literature to characterize the seasonal dynamics of air and water chemistry in indoor chlorinated swimming pools. To address this issue, water samples were collected five days per week from an indoor chlorinated swimming pool facility at a high school during the academic year and once per week during summer over a fourteen-month period. The samples were analyzed for free and combined chlorine, urea, volatile DBPs, pH, temperature and total alkalinity. Membrane Introduction Mass Spectrometry (MIMS) was used to identify and measure the concentrations of eleven aqueous-phase volatile DBPs. Variability in the concentrations of these DBPs was observed. Factors that influenced variability included bather loading and mixing by swimmers. These compounds have the ability to adversely affect water and air quality and human health. A large fraction of the existing literature regarding swimming pool air quality has focused on trichloramine (NCl₃). For this work, gas-phase NCl₃ was analyzed by an air sparging-DPD/KI method. The results showed that gas-phase NCl₃ concentration is influenced by bather loading and liquid-phase NCl₃ concentration. Urea is the dominant organic-N compound in human urine and sweat, and is known to be an important precursor for producing NCl₃ in swimming pools. Results of daily measurements of urea indicated a link between bather load and urea concentration in the pool.

A data-driven dynamics simulation framework for railway vehicles

NASA Astrophysics Data System (ADS)

Nie, Yinyu; Tang, Zhao; Liu, Fengjia; Chang, Jian; Zhang, Jianjun

2018-03-01

The finite element (FE) method is essential for simulating vehicle dynamics with fine details, especially for train crash simulations. However, factors such as the complexity of meshes and the distortion involved in a large deformation would undermine its calculation efficiency. An alternative method, the multi-body (MB) dynamics simulation provides satisfying time efficiency but limited accuracy when highly nonlinear dynamic process is involved. To maintain the advantages of both methods, this paper proposes a data-driven simulation framework for dynamics simulation of railway vehicles. This framework uses machine learning techniques to extract nonlinear features from training data generated by FE simulations so that specific mesh structures can be formulated by a surrogate element (or surrogate elements) to replace the original mechanical elements, and the dynamics simulation can be implemented by co-simulation with the surrogate element(s) embedded into a MB model. This framework consists of a series of techniques including data collection, feature extraction, training data sampling, surrogate element building, and model evaluation and selection. To verify the feasibility of this framework, we present two case studies, a vertical dynamics simulation and a longitudinal dynamics simulation, based on co-simulation with MATLAB/Simulink and Simpack, and a further comparison with a popular data-driven model (the Kriging model) is provided. The simulation result shows that using the legendre polynomial regression model in building surrogate elements can largely cut down the simulation time without sacrifice in accuracy.

Protein Folding Simulations Combining Self-Guided Langevin Dynamics and Temperature-Based Replica Exchange

DTIC Science & Technology

2010-01-01

formulations of molecular dynamics (MD) and Langevin dynamics (LD) simulations for the prediction of thermodynamic folding observables of the Trp-cage...ad hoc force term in the SGLD model. Introduction Molecular dynamics (MD) simulations of small proteins provide insight into the mechanisms and... molecular dynamics (MD) and Langevin dynamics (LD) simulations for the prediction of thermodynamic folding observables of the Trp-cage mini-protein. All

Quantitative Evaluation of Collagen Crosslinks and Corresponding Tensile Mechanical Properties in Mouse Cervical Tissue during Normal Pregnancy

PubMed Central

Yoshida, Kyoko; Jiang, Hongfeng; Kim, MiJung; Vink, Joy; Cremers, Serge; Paik, David; Wapner, Ronald; Mahendroo, Mala; Myers, Kristin

2014-01-01

The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31–0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15. PMID:25397407

Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma.

PubMed

Jacobs, Bart A W; Rosing, Hilde; de Vries, Niels; Meulendijks, Didier; Henricks, Linda M; Schellens, Jan H M; Beijnen, Jos H

2016-07-15

Quantification of the endogenous dihydropyrimidine dehydrogenase (DPD) substrate uracil (U) and the reaction product dihydrouracil (UH2) in plasma might be suitable for identification of patients at risk of fluoropyrimidine-induced toxicity as a result of DPD deficiency. In this paper, we describe the development and validation of a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantification of U and UH2 in human plasma. Analytes were extracted by protein precipitation, chromatographically separated on an Acquity UPLC(®) HSS T3 column with gradient elution and analyzed with a tandem mass spectrometer equipped with an electrospray ionization source. U was quantified in the negative ion mode and UH2 in the positive ion mode. Stable isotopes for U and UH2 were used as internal standards. Total chromatographic run time was 5min. Validated concentration ranges for U and UH2 were from 1 to 100ng/mL and 10 to 1000ng/mL, respectively. Inter-assay bias and inter-assay precision for U were within ±2.8% and ≤12.4%. For UH2, inter-assay bias and inter-assay precision were within ±2.9% and ≤7.2%. Adequate stability of U and UH2 in dry extract, final extract, stock solution and plasma was demonstrated. Stability of U and UH2 in whole blood was only satisfactory when stored up to 4hours at 2-8°C, but not at ambient temperatures. An accurate, precise and sensitive UPLC-MS/MS assay for quantification of U and UH2 in plasma was developed. This assay is now applied to support clinical studies with fluoropyrimidine drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Combination therapy with ONO-KK1-300-01, a cathepsin K inhibitor, and parathyroid hormone results in additive beneficial effect on bone mineral density in ovariectomized rats.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Kawada, Naoki; Tanaka, Makoto; Imagawa, Akira; Ohmoto, Kazuyuki; Kawabata, Kazuhito

2016-01-01

This study examined the effects of a novel cathepsin K inhibitor, ONO-KK1-300-01 (KK1-300), used concurrently with parathyroid hormone (PTH) in ovariectomized (OVX) rats. KK1-300 (3 mg/kg, twice daily), alendronate (1 mg/kg, once daily) or vehicle were orally administered to OVX rats for 56 days, starting the day after ovariectomy, followed by combination treatment with or without PTH (3 μg/kg, subcutaneously three times a week) for another 28 days. OVX control animals exhibited a significant increase in both bone resorption (urinary deoxypyridinoline; DPD) and formation markers (serum osteocalcin) as well as microstructural changes associated with decreased bone mineral density (BMD). Combination treatment with KK1-300 and PTH significantly decreased urinary DPD and increased serum osteocalcin, indicating a sustained beneficial effect compared to the effect of each mono-therapy. On the other hand, combination therapy with alendronate and PTH weakened the PTH-induced increase in osteocalcin. In proximal tibia, combination treatment with KK1-300 and PTH increased BMD to a level significantly higher than that achieved following single treatment with KK1-300 or PTH alone. On the other hand, combination treatment with alendronate and PTH failed to produce any significant additive effect on BMD following single treatment with alendronate or PTH alone. Microstructural analysis revealed that the PTH-induced increase in bone formation (MS/BS and BFR/BS) was fully maintained following combination treatment with KK1-300 and PTH, but not following combination treatment with alendronate and PTH. These findings indicate that KK1-300, unlike alendronate, has an additive effect on the preventive action of PTH on bone loss in OVX rats.

Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration.

PubMed

Kinai, Ei; Gatanaga, Hiroyuki; Mizushima, Daisuke; Nishijima, Takeshi; Aoki, Takahiro; Genka, Ikumi; Teruya, Katsuji; Tsukada, Kunihisa; Kikuchi, Yoshimi; Oka, Shinichi

2017-05-01

Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure. This single-center, cross-sectional study included 184 HIV-infected patients treated with PI who underwent dual-energy X-ray absorptiometry scan. Serum phosphorus, percentage of tubular reabsorption of phosphate (%TRP), thyroid and parathyroid function (iPTH), vitamin D, osteocalcin (OC), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type I collagen (u-NTx) were measured. The rate of hypothyroidism in PI-users [32/117 (27%)] was double that in non-PI users [8/67 (12%), p = 0.016] and was significantly associated with PI use in multivariate analysis [odds ratio (OR) 11.37, 95% confidence interval (CI) 1.358-95.17, p = 0.025]. Spine BMD was significantly lower in hypothyroid patients than euthyroid, for both total population (-1.37 vs. -1.00, p = 0.041) and PI users (-1.56 vs. -1.13, p = 0.029). Multivariate regression analysis identified inverse correlation between hypothyroidism and spine BMD [estimate -0.437, 95% CI -0.858 to -0.024, p = 0.042]. OC, DPD and u-NTx were significantly higher in PI users than in non-PI users (p = 0.01, 0.05, and 0.01, respectively). PI use is associated with hypothyroidism as well as bone turnover acceleration, which worsens PI-associated BMD loss. In PI-treated patients, thyroid function tests are warranted to prevent further progression of PI-associated BMD loss. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients

PubMed Central

Ruzzo, A; Graziano, F; Galli, Fabio; Galli, Francesca; Rulli, E; Lonardi, S; Ronzoni, M; Massidda, B; Zagonel, V; Pella, N; Mucciarini, C; Labianca, R; Ionta, M T; Bagaloni, I; Veltri, E; Sozzi, P; Barni, S; Ricci, V; Foltran, L; Nicolini, M; Biondi, E; Bramati, A; Turci, D; Lazzarelli, S; Verusio, C; Bergamo, F; Sobrero, A; Frontini, L; Menghi, M; Magnani, M

2017-01-01

Background: Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients’ risk of fluoropyrimidine-related severe toxicity. Methods: The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg’s False Discovery Rate (FDR) procedure was used. Results: FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia. Conclusions: This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy. PMID:29065426

Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients.

PubMed

Ruzzo, A; Graziano, F; Galli, Fabio; Galli, Francesca; Rulli, E; Lonardi, S; Ronzoni, M; Massidda, B; Zagonel, V; Pella, N; Mucciarini, C; Labianca, R; Ionta, M T; Bagaloni, I; Veltri, E; Sozzi, P; Barni, S; Ricci, V; Foltran, L; Nicolini, M; Biondi, E; Bramati, A; Turci, D; Lazzarelli, S; Verusio, C; Bergamo, F; Sobrero, A; Frontini, L; Menghi, M; Magnani, M

2017-10-24

Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False Discovery Rate (FDR) procedure was used. FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia. This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.

Training-related improvements in musculoskeletal health and balance: a 13-week pilot study of female cancer survivors.

PubMed

Almstedt, H C; Grote, S; Perez, S E; Shoepe, T C; Strand, S L; Tarleton, H P

2017-03-01

Cancer survivors often experience poor post-treatment musculoskeletal health. This study examined the feasibility of combined aerobic and resistant training (CART) for improving strength, skeletal health and balance. Cancer survivors (n = 24) were identified by convenience sampling in Los Angeles County with 11 survivors consenting to 13 weeks of CART. Pre- and post-intervention assessments of bone mineral density (BMD), strength, flexibility and biomarker analysis were performed. Paired t-test analysis suggested increases in lower and upper body strength. The average T-score for BMD at the femoral neck improved from -1.46 to -1.36 and whole body BMD improved from -1.65 to -1.55. From baseline to follow-up, participants also displayed decreases in sway velocity on the eyes open (7%) and eyes closed (27%) conditions. Improvement in lower body strength was associated with increases in lean body mass (LBM) (r = 0.721) and an inverse association was observed between sway velocity and LBM (r = 0.838). Age and time since last treatment were related with biomarkers of anabolic growth (IGF-1, IGFbp-3) and bone (DPD, BAP). In summary, observed physiological changes were consistent with functional improvements, suggesting that isometric and dynamic exercise prescription may reduce the risk for falls and fall-related fractures among survivors. © 2016 John Wiley & Sons Ltd.

Multiscale molecular dynamics simulations of rotary motor proteins.

PubMed

Ekimoto, Toru; Ikeguchi, Mitsunori

2018-04-01

Protein functions require specific structures frequently coupled with conformational changes. The scale of the structural dynamics of proteins spans from the atomic to the molecular level. Theoretically, all-atom molecular dynamics (MD) simulation is a powerful tool to investigate protein dynamics because the MD simulation is capable of capturing conformational changes obeying the intrinsically structural features. However, to study long-timescale dynamics, efficient sampling techniques and coarse-grained (CG) approaches coupled with all-atom MD simulations, termed multiscale MD simulations, are required to overcome the timescale limitation in all-atom MD simulations. Here, we review two examples of rotary motor proteins examined using free energy landscape (FEL) analysis and CG-MD simulations. In the FEL analysis, FEL is calculated as a function of reaction coordinates, and the long-timescale dynamics corresponding to conformational changes is described as transitions on the FEL surface. Another approach is the utilization of the CG model, in which the CG parameters are tuned using the fluctuation matching methodology with all-atom MD simulations. The long-timespan dynamics is then elucidated straightforwardly by using CG-MD simulations.

Look-ahead Dynamic Simulation

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

2015-10-20

Look-ahead dynamic simulation software system incorporates the high performance parallel computing technologies, significantly reduces the solution time for each transient simulation case, and brings the dynamic simulation analysis into on-line applications to enable more transparency for better reliability and asset utilization. It takes the snapshot of the current power grid status, functions in parallel computing the system dynamic simulation, and outputs the transient response of the power system in real time.

A pseudo-thermodynamic description of dispersion for nanocomposites

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

Jin, Yan; Beaucage, Gregory; Vogtt, Karsten

Dispersion in polymer nanocomposites is determined by the kinetics of mixing and chemical affinity. Compounds like reinforcing filler/elastomer blends display some similarity to colloidal solutions in that the filler particles are close to randomly dispersed through processing. It is attractive to apply a pseudo-thermodynamic approach taking advantage of this analogy between the kinetics of mixing for polymer compounds and thermally driven dispersion for colloids. In order to demonstrate this pseudo-thermodynamic approach, two polybutadienes and one polyisoprene were milled with three carbon blacks and two silicas. These samples were examined using small-angle x-ray scattering as a function of filler concentration tomore » determine a pseudo-second order virial coefficient, A2, which is used as an indicator for compatibility of the filler and polymer. It is found that A2 follows the expected behavior with lower values for smaller primary particles indicating that smaller particles are less compatible and more difficult to mix. The measured values of A2 can be used to specify repulsive interaction potentials for coarse grain DPD simulations of filler/elastomer systems. In addition, new methods to quantify the filler percolation threshold and filler mesh size as a function of filler concentration are obtained. Moreover, the results represent a new approach to understanding and predicting compatibility in polymer nanocomposites based on a pseudo-thermodynamic approach.« less

A pseudo-thermodynamic description of dispersion for nanocomposites

DOE PAGES

Jin, Yan; Beaucage, Gregory; Vogtt, Karsten; ...

2017-09-18

Dispersion in polymer nanocomposites is determined by the kinetics of mixing and chemical affinity. Compounds like reinforcing filler/elastomer blends display some similarity to colloidal solutions in that the filler particles are close to randomly dispersed through processing. It is attractive to apply a pseudo-thermodynamic approach taking advantage of this analogy between the kinetics of mixing for polymer compounds and thermally driven dispersion for colloids. In order to demonstrate this pseudo-thermodynamic approach, two polybutadienes and one polyisoprene were milled with three carbon blacks and two silicas. These samples were examined using small-angle x-ray scattering as a function of filler concentration tomore » determine a pseudo-second order virial coefficient, A2, which is used as an indicator for compatibility of the filler and polymer. It is found that A2 follows the expected behavior with lower values for smaller primary particles indicating that smaller particles are less compatible and more difficult to mix. The measured values of A2 can be used to specify repulsive interaction potentials for coarse grain DPD simulations of filler/elastomer systems. In addition, new methods to quantify the filler percolation threshold and filler mesh size as a function of filler concentration are obtained. Moreover, the results represent a new approach to understanding and predicting compatibility in polymer nanocomposites based on a pseudo-thermodynamic approach.« less

Space station MSFC-DPD-235/DR no. MA-05 phase C/D program development plan. Volume 2: Phase C/D, programmatic requirements

NASA Technical Reports Server (NTRS)

1971-01-01

The design plan requirements define the design implementation and control requirements for Phase C/D of the Modular Space Station Project and specifically address the Initial Space Station phase of the Space Station Program (modular). It is based primarily on the specific objective of translating the requirements of the Space Station Program, Project, Interface, and Support Requirements and preliminary contract end x item specifications into detail design of the operational systems which comprise the initial space station. This document is designed to guide aerospace contractors in the planning and bidding for Phase C/D.

VETA-I x ray test analysis

NASA Technical Reports Server (NTRS)

Brissenden, R. J. V.; Chartas, G.; Freeman, M. D.; Hughes, J. P.; Kellogg, E. M.; Podgorski, W. A.; Schwartz, D. A.; Zhao, P.

1992-01-01

This interim report presents some definitive results from our analysis of the VETA-I x-ray testing data. It also provides a description of the hardware and software used in the conduct of the VETA-I x-ray test program performed at the MSFC x-ray Calibration Facility (XRCF). These test results also serve to supply data and information to include in the TRW final report required by DPD 692, DR XC04. To provide an authoritative compendium of results, we have taken nine papers as published in the SPIE Symposium, 'Grazing Incidence X-ray/EUV Optics for Astronomy and Projection Lithography' and have reproduced them as the content of this report.

Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide into a Membrane Bilayer

DTIC Science & Technology

2008-07-01

Molecular Dynamics Simulations of Folding and Insertion of the Ebola Virus Fusion Peptide into a Membrane Bilayer Mark A. Olson1, In...presents replica-exchange molecular dynamics simulations of the folding and insertion of a 16- residue Ebola virus fusion peptide into a membrane...separate calculated structures into conformational basins. 2.1 Simulation models Molecular dynamics simulations were performed using the all-atom

Quasi-Dynamic Versus Fully-Dynamic Simulations of Slip Accumulation on Faults with Enhanced Dynamic Weakening

NASA Astrophysics Data System (ADS)

Lapusta, N.; Thomas, M.; Noda, H.; Avouac, J.

2012-12-01

Long-term simulations that incorporate both seismic events and aseismic slip are quite important for studies of earthquake physics but challenging computationally. To study long deformation histories, most simulation methods do not incorporate full inertial effects (wave propagation) during simulated earthquakes, using quasi-dynamic approximations instead. Here we compare the results of quasi-dynamic simulations to the fully dynamic ones for a range of problems to determine the applicability of the quasi-dynamic approach. Intuitively, the quasi-dynamic approach should do relatively well in problems where wave-mediated effects are relatively simple but should have substantially different (and hence wrong) response when the wave-mediated stress transfers dominate the character of the seismic events. This is exactly what we observe in our simulations. We consider a 2D model of a rate-and-state fault with a seismogenic (steady-state velocity-weakening) zone surrounded by creeping (steady-state velocity-strengthening) areas. If the seismogenic zone is described by the standard Dieterich-Ruina rate-and-state friction, the resulting earthquake sequences consist of relatively simple crack-like ruptures, and the inclusion of true wave-propagation effects mostly serves to concentrate stress more efficiently at the rupture front. Hence, in such models, rupture speeds and slip rates are significantly (several times) lower in the quasi-dynamic simulations compared to the fully dynamic ones, but the total slip, the crack-like nature of seismic events, and the overall pattern of earthquake sequences is comparable, consistently with prior studies. Such behavior can be classified as qualitatively similar but quantitatively different, and it motivates the popularity of the quasi-dynamic methods in simulations. However, the comparison changes dramatically once we consider a model with enhanced dynamic weakening in the seismogenic zone in the form of flash heating. In this case, the fully dynamic simulations produce seismic ruptures in the form of short-duration slip pulses, where the pulses form due to a combination of enhanced weakening and wave effects. The quasi-dynamic simulations in the same model produce completely different results, with large crack-like ruptures, different total slips, different rupture patterns, and different prestress state before large, model-spanning events. Such qualitative differences between the quasi-dynamic and fully-dynamic simulation should result in any model where inertial effects lead to qualitative differences, such as cases with supershear transition or fault with different materials on the two sides. We will present results on our current work on how the quasi-dynamic and fully dynamic simulations compare for the cases with heterogeneous fault properties.

Mapping Conformational Dynamics of Proteins Using Torsional Dynamics Simulations

PubMed Central

Gangupomu, Vamshi K.; Wagner, Jeffrey R.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-01-01

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein’s experimentally established conformational substates. Conformational transition of calmodulin from the Ca2+-bound to the Ca2+-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in proteins. PMID:23663843

Mapping conformational dynamics of proteins using torsional dynamics simulations.

PubMed

Gangupomu, Vamshi K; Wagner, Jeffrey R; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-05-07

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in proteins. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Metrics for comparing dynamic earthquake rupture simulations

USGS Publications Warehouse

Barall, Michael; Harris, Ruth A.

2014-01-01

Earthquakes are complex events that involve a myriad of interactions among multiple geologic features and processes. One of the tools that is available to assist with their study is computer simulation, particularly dynamic rupture simulation. A dynamic rupture simulation is a numerical model of the physical processes that occur during an earthquake. Starting with the fault geometry, friction constitutive law, initial stress conditions, and assumptions about the condition and response of the near‐fault rocks, a dynamic earthquake rupture simulation calculates the evolution of fault slip and stress over time as part of the elastodynamic numerical solution (Ⓔ see the simulation description in the electronic supplement to this article). The complexity of the computations in a dynamic rupture simulation make it challenging to verify that the computer code is operating as intended, because there are no exact analytic solutions against which these codes’ results can be directly compared. One approach for checking if dynamic rupture computer codes are working satisfactorily is to compare each code’s results with the results of other dynamic rupture codes running the same earthquake simulation benchmark. To perform such a comparison consistently, it is necessary to have quantitative metrics. In this paper, we present a new method for quantitatively comparing the results of dynamic earthquake rupture computer simulation codes.

Rotational Brownian Dynamics simulations of clathrin cage formation

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

Ilie, Ioana M.; Briels, Wim J.; MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE Enschede

2014-08-14

The self-assembly of nearly rigid proteins into ordered aggregates is well suited for modeling by the patchy particle approach. Patchy particles are traditionally simulated using Monte Carlo methods, to study the phase diagram, while Brownian Dynamics simulations would reveal insights into the assembly dynamics. However, Brownian Dynamics of rotating anisotropic particles gives rise to a number of complications not encountered in translational Brownian Dynamics. We thoroughly test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter [Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithmmore » to simulate a patchy particle model of clathrin, a three-legged protein involved in vesicle production from lipid membranes during endocytosis. Using this algorithm we recover time scales for cage assembly comparable to those from experiments. We also briefly discuss the undulatory dynamics of the polyhedral cage.« less

Molecular dynamics simulations of large macromolecular complexes.

PubMed

Perilla, Juan R; Goh, Boon Chong; Cassidy, C Keith; Liu, Bo; Bernardi, Rafael C; Rudack, Till; Yu, Hang; Wu, Zhe; Schulten, Klaus

2015-04-01

Connecting dynamics to structural data from diverse experimental sources, molecular dynamics simulations permit the exploration of biological phenomena in unparalleled detail. Advances in simulations are moving the atomic resolution descriptions of biological systems into the million-to-billion atom regime, in which numerous cell functions reside. In this opinion, we review the progress, driven by large-scale molecular dynamics simulations, in the study of viruses, ribosomes, bioenergetic systems, and other diverse applications. These examples highlight the utility of molecular dynamics simulations in the critical task of relating atomic detail to the function of supramolecular complexes, a task that cannot be achieved by smaller-scale simulations or existing experimental approaches alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Development and Comparison of Molecular Dynamics Simulation and Monte Carlo Simulation

NASA Astrophysics Data System (ADS)

Chen, Jundong

2018-03-01

Molecular dynamics is an integrated technology that combines physics, mathematics and chemistry. Molecular dynamics method is a computer simulation experimental method, which is a powerful tool for studying condensed matter system. This technique not only can get the trajectory of the atom, but can also observe the microscopic details of the atomic motion. By studying the numerical integration algorithm in molecular dynamics simulation, we can not only analyze the microstructure, the motion of particles and the image of macroscopic relationship between them and the material, but can also study the relationship between the interaction and the macroscopic properties more conveniently. The Monte Carlo Simulation, similar to the molecular dynamics, is a tool for studying the micro-molecular and particle nature. In this paper, the theoretical background of computer numerical simulation is introduced, and the specific methods of numerical integration are summarized, including Verlet method, Leap-frog method and Velocity Verlet method. At the same time, the method and principle of Monte Carlo Simulation are introduced. Finally, similarities and differences of Monte Carlo Simulation and the molecular dynamics simulation are discussed.

Convergence and reproducibility in molecular dynamics simulations of the DNA duplex d(GCACGAACGAACGAACGC).

PubMed

Galindo-Murillo, Rodrigo; Roe, Daniel R; Cheatham, Thomas E

2015-05-01

The structure and dynamics of DNA are critically related to its function. Molecular dynamics simulations augment experiment by providing detailed information about the atomic motions. However, to date the simulations have not been long enough for convergence of the dynamics and structural properties of DNA. Molecular dynamics simulations performed with AMBER using the ff99SB force field with the parmbsc0 modifications, including ensembles of independent simulations, were compared to long timescale molecular dynamics performed with the specialized Anton MD engine on the B-DNA structure d(GCACGAACGAACGAACGC). To assess convergence, the decay of the average RMSD values over longer and longer time intervals was evaluated in addition to assessing convergence of the dynamics via the Kullback-Leibler divergence of principal component projection histograms. These molecular dynamics simulations-including one of the longest simulations of DNA published to date at ~44μs-surprisingly suggest that the structure and dynamics of the DNA helix, neglecting the terminal base pairs, are essentially fully converged on the ~1-5μs timescale. We can now reproducibly converge the structure and dynamics of B-DNA helices, omitting the terminal base pairs, on the μs time scale with both the AMBER and CHARMM C36 nucleic acid force fields. Results from independent ensembles of simulations starting from different initial conditions, when aggregated, match the results from long timescale simulations on the specialized Anton MD engine. With access to large-scale GPU resources or the specialized MD engine "Anton" it is possible for a variety of molecular systems to reproducibly and reliably converge the conformational ensemble of sampled structures. This article is part of a Special Issue entitled: Recent developments of molecular dynamics. Copyright © 2014. Published by Elsevier B.V.

Faster than Real-Time Dynamic Simulation for Large-Size Power System with Detailed Dynamic Models using High-Performance Computing Platform

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

Huang, Renke; Jin, Shuangshuang; Chen, Yousu

This paper presents a faster-than-real-time dynamic simulation software package that is designed for large-size power system dynamic simulation. It was developed on the GridPACKTM high-performance computing (HPC) framework. The key features of the developed software package include (1) faster-than-real-time dynamic simulation for a WECC system (17,000 buses) with different types of detailed generator, controller, and relay dynamic models, (2) a decoupled parallel dynamic simulation algorithm with optimized computation architecture to better leverage HPC resources and technologies, (3) options for HPC-based linear and iterative solvers, (4) hidden HPC details, such as data communication and distribution, to enable development centered on mathematicalmore » models and algorithms rather than on computational details for power system researchers, and (5) easy integration of new dynamic models and related algorithms into the software package.« less

Swarm Counter-Asymmetric-Threat (CAT) 6-DOF Dynamics Simulation

DTIC Science & Technology

2005-07-01

NAWCWD TP 8593 Swarm Counter-Asymmetric-Threat ( CAT ) 6-DOF Dynamics Simulation by James Bobinchak Weapons and Energetics...mathematical models used in the swarm counter- asymmetric-threat ( CAT ) simulation and the results of extensive Monte Carlo simulations. The swarm CAT ...Asymmetric-Threat ( CAT ) 6-DOF Dynamics Simulation (U) 6. AUTHOR(S) James Bobinchak and Gary Hewer 7. PERFORMING ORGANIZATION NAME(S) AND

Membrane Insertion Profiles of Peptides Probed by Molecular Dynamics Simulations

DTIC Science & Technology

2008-07-17

Membrane insertion profiles of peptides probed by molecular dynamics simulations In-Chul Yeh,* Mark A. Olson,# Michael S. Lee,*#§ and Anders...a methodology based on molecular dynamics simulation techniques to probe the insertion profiles of small peptides across the membrane interface. The...profiles of peptides probed by molecular dynamics simulations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method

DTIC Science & Technology

2011-12-01

REMD while reproducing the energy landscape of explicit solvent simulations . ’ INTRODUCTION Molecular dynamics (MD) simulations of proteins can pro...Mongan, J.; McCammon, J. A. Accelerated molecular dynamics : a promising and efficient simulation method for biomolecules. J. Chem. Phys. 2004, 120 (24...Chemical Theory and Computation ARTICLE (8) Abraham,M. J.; Gready, J. E. Ensuringmixing efficiency of replica- exchange molecular dynamics simulations . J

Validation of the train energy and dynamics simulator (TEDS).

DOT National Transportation Integrated Search

2015-01-01

FRA has developed Train Energy and Dynamics Simulator (TEDS) based upon a longitudinal train dynamics and operations : simulation model which allows users to conduct safety and risk evaluations, incident investigations, studies of train operations, :...

Molecular dynamics simulations of thermally activated edge dislocation unpinning from voids in α -Fe

NASA Astrophysics Data System (ADS)

Byggmästar, J.; Granberg, F.; Nordlund, K.

2017-10-01

In this study, thermal unpinning of edge dislocations from voids in α -Fe is investigated by means of molecular dynamics simulations. The activation energy as a function of shear stress and temperature is systematically determined. Simulations with a constant applied stress are compared with dynamic simulations with a constant strain rate. We found that a constant applied stress results in a temperature-dependent activation energy. The temperature dependence is attributed to the elastic softening of iron. If the stress is normalized with the softening of the specific shear modulus, the activation energy is shown to be temperature-independent. From the dynamic simulations, the activation energy as a function of critical shear stress was determined using previously developed methods. The results from the dynamic simulations are in good agreement with the constant stress simulations, after the normalization. This indicates that the computationally more efficient dynamic method can be used to obtain the activation energy as a function of stress and temperature. The obtained relation between stress, temperature, and activation energy can be used to introduce a stochastic unpinning event in larger-scale simulation methods, such as discrete dislocation dynamics.

MCC level C formulation requirements. Shuttle TAEM guidance and flight control, STS-1 baseline

NASA Technical Reports Server (NTRS)

Carman, G. L.; Montez, M. N.

1980-01-01

The TAEM guidance and body rotational dynamics models required for the MCC simulation of the TAEM mission phase are defined. This simulation begins at the end of the entry phase and terminates at TAEM autoland interface. The logic presented is the required configuration for the first shuttle orbital flight (STS-1). The TAEM guidance is simulated in detail. The rotational dynamics simulation is a simplified model that assumes that the commanded rotational rates can be achieved in the integration interval. Thus, the rotational dynamics simulation is essentially a simulation of the autopilot commanded rates and integration of these rates to determine orbiter attitude. The rotational dynamics simulation also includes a simulation of the speedbrake deflection. The body flap and elevon deflections are computed in the orbiter aerodynamic simulation.

Experimental verification of dynamic simulation

NASA Technical Reports Server (NTRS)

Yae, K. Harold; Hwang, Howyoung; Chern, Su-Tai

1989-01-01

The dynamics model here is a backhoe, which is a four degree of freedom manipulator from the dynamics standpoint. Two types of experiment are chosen that can also be simulated by a multibody dynamics simulation program. In the experiment, recorded were the configuration and force histories; that is, velocity and position, and force output and differential pressure change from the hydraulic cylinder, in the time domain. When the experimental force history is used as driving force in the simulation model, the forward dynamics simulation produces a corresponding configuration history. Then, the experimental configuration history is used in the inverse dynamics analysis to generate a corresponding force history. Therefore, two sets of configuration and force histories--one set from experiment, and the other from the simulation that is driven forward and backward with the experimental data--are compared in the time domain. More comparisons are made in regard to the effects of initial conditions, friction, and viscous damping.

[Brownian dynamics simulations of protein-protein interactions in photosynthetic electron transport chain].

PubMed

Khruschev, S S; Abaturova, A M; Diakonova, A N; Fedorov, V A; Ustinin, D M; Kovalenko, I B; Riznichenko, G Yu; Rubin, A B

2015-01-01

The application of Brownian dynamics for simulation of transient protein-protein interactions is reviewed. The review focuses on theoretical basics of Brownian dynamics method, its particular implementations, advantages and drawbacks of the method. The outlook for future development of Brownian dynamics-based simulation techniques is discussed. Special attention is given to analysis of Brownian dynamics trajectories. The second part of the review is dedicated to the role of Brownian dynamics simulations in studying photosynthetic electron transport. Interactions of mobile electron carriers (plastocyanin, cytochrome c6, and ferredoxin) with their reaction partners (cytochrome b6f complex, photosystem I, ferredoxin:NADP-reductase, and hydrogenase) are considered.

Implementation of Parallel Dynamic Simulation on Shared-Memory vs. Distributed-Memory Environments

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

Jin, Shuangshuang; Chen, Yousu; Wu, Di

2015-12-09

Power system dynamic simulation computes the system response to a sequence of large disturbance, such as sudden changes in generation or load, or a network short circuit followed by protective branch switching operation. It consists of a large set of differential and algebraic equations, which is computational intensive and challenging to solve using single-processor based dynamic simulation solution. High-performance computing (HPC) based parallel computing is a very promising technology to speed up the computation and facilitate the simulation process. This paper presents two different parallel implementations of power grid dynamic simulation using Open Multi-processing (OpenMP) on shared-memory platform, and Messagemore » Passing Interface (MPI) on distributed-memory clusters, respectively. The difference of the parallel simulation algorithms and architectures of the two HPC technologies are illustrated, and their performances for running parallel dynamic simulation are compared and demonstrated.« less

Toll-Like Receptor-9-Mediated Invasion in Breast Cancer

DTIC Science & Technology

2011-07-01

Molecular Dynamics Simulations. Theoretical structural models were obtained from molecular dynamics simulations using explicit solvation by...with AMBER by MARDIGRAS. The solution structure was then derived by coupling the resulting NMR distance restraints with a molecular dynamic ...Overlay of NMR restrained structure (red) with theoretical molecular dynamic simulated annealing structure (blue). Energetic stability of the 9-mer

Simulating Open Quantum Systems with Hamiltonian Ensembles and the Nonclassicality of the Dynamics

NASA Astrophysics Data System (ADS)

Chen, Hong-Bin; Gneiting, Clemens; Lo, Ping-Yuan; Chen, Yueh-Nan; Nori, Franco

2018-01-01

The incoherent dynamical properties of open quantum systems are generically attributed to an ongoing correlation between the system and its environment. Here, we propose a novel way to assess the nature of these system-environment correlations by examining the system dynamics alone. Our approach is based on the possibility or impossibility to simulate open-system dynamics with Hamiltonian ensembles. As we show, such (im)possibility to simulate is closely linked to the system-environment correlations. We thus define the nonclassicality of open-system dynamics in terms of the nonexistence of a Hamiltonian-ensemble simulation. This classifies any nonunital open-system dynamics as nonclassical. We give examples for open-system dynamics that are unital and classical, as well as unital and nonclassical.

Coupled binding-bending-folding: The complex conformational dynamics of protein-DNA binding studied by atomistic molecular dynamics simulations.

PubMed

van der Vaart, Arjan

2015-05-01

Protein-DNA binding often involves dramatic conformational changes such as protein folding and DNA bending. While thermodynamic aspects of this behavior are understood, and its biological function is often known, the mechanism by which the conformational changes occur is generally unclear. By providing detailed structural and energetic data, molecular dynamics simulations have been helpful in elucidating and rationalizing protein-DNA binding. This review will summarize recent atomistic molecular dynamics simulations of the conformational dynamics of DNA and protein-DNA binding. A brief overview of recent developments in DNA force fields is given as well. Simulations have been crucial in rationalizing the intrinsic flexibility of DNA, and have been instrumental in identifying the sequence of binding events, the triggers for the conformational motion, and the mechanism of binding for a number of important DNA-binding proteins. Molecular dynamics simulations are an important tool for understanding the complex binding behavior of DNA-binding proteins. With recent advances in force fields and rapid increases in simulation time scales, simulations will become even more important for future studies. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014. Published by Elsevier B.V.

Selecting a dynamic simulation modeling method for health care delivery research-part 2: report of the ISPOR Dynamic Simulation Modeling Emerging Good Practices Task Force.

PubMed

Marshall, Deborah A; Burgos-Liz, Lina; IJzerman, Maarten J; Crown, William; Padula, William V; Wong, Peter K; Pasupathy, Kalyan S; Higashi, Mitchell K; Osgood, Nathaniel D

2015-03-01

In a previous report, the ISPOR Task Force on Dynamic Simulation Modeling Applications in Health Care Delivery Research Emerging Good Practices introduced the fundamentals of dynamic simulation modeling and identified the types of health care delivery problems for which dynamic simulation modeling can be used more effectively than other modeling methods. The hierarchical relationship between the health care delivery system, providers, patients, and other stakeholders exhibits a level of complexity that ought to be captured using dynamic simulation modeling methods. As a tool to help researchers decide whether dynamic simulation modeling is an appropriate method for modeling the effects of an intervention on a health care system, we presented the System, Interactions, Multilevel, Understanding, Loops, Agents, Time, Emergence (SIMULATE) checklist consisting of eight elements. This report builds on the previous work, systematically comparing each of the three most commonly used dynamic simulation modeling methods-system dynamics, discrete-event simulation, and agent-based modeling. We review criteria for selecting the most suitable method depending on 1) the purpose-type of problem and research questions being investigated, 2) the object-scope of the model, and 3) the method to model the object to achieve the purpose. Finally, we provide guidance for emerging good practices for dynamic simulation modeling in the health sector, covering all aspects, from the engagement of decision makers in the model design through model maintenance and upkeep. We conclude by providing some recommendations about the application of these methods to add value to informed decision making, with an emphasis on stakeholder engagement, starting with the problem definition. Finally, we identify areas in which further methodological development will likely occur given the growing "volume, velocity and variety" and availability of "big data" to provide empirical evidence and techniques such as machine learning for parameter estimation in dynamic simulation models. Upon reviewing this report in addition to using the SIMULATE checklist, the readers should be able to identify whether dynamic simulation modeling methods are appropriate to address the problem at hand and to recognize the differences of these methods from those of other, more traditional modeling approaches such as Markov models and decision trees. This report provides an overview of these modeling methods and examples of health care system problems in which such methods have been useful. The primary aim of the report was to aid decisions as to whether these simulation methods are appropriate to address specific health systems problems. The report directs readers to other resources for further education on these individual modeling methods for system interventions in the emerging field of health care delivery science and implementation. Copyright © 2015. Published by Elsevier Inc.

A simple dynamic engine model for use in a real-time aircraft simulation with thrust vectoring

NASA Technical Reports Server (NTRS)

Johnson, Steven A.

1990-01-01

A simple dynamic engine model was developed at the NASA Ames Research Center, Dryden Flight Research Facility, for use in thrust vectoring control law development and real-time aircraft simulation. The simple dynamic engine model of the F404-GE-400 engine (General Electric, Lynn, Massachusetts) operates within the aircraft simulator. It was developed using tabular data generated from a complete nonlinear dynamic engine model supplied by the manufacturer. Engine dynamics were simulated using a throttle rate limiter and low-pass filter. Included is a description of a method to account for axial thrust loss resulting from thrust vectoring. In addition, the development of the simple dynamic engine model and its incorporation into the F-18 high alpha research vehicle (HARV) thrust vectoring simulation. The simple dynamic engine model was evaluated at Mach 0.2, 35,000 ft altitude and at Mach 0.7, 35,000 ft altitude. The simple dynamic engine model is within 3 percent of the steady state response, and within 25 percent of the transient response of the complete nonlinear dynamic engine model.

Dynamic Simulation over Long Time Periods with 100% Solar Generation.

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

Concepcion, Ricky James; Elliott, Ryan Thomas

2015-12-01

This project aimed to identify the path forward for dynamic simulation tools to accommodate these needs by characterizing the properties of power systems (with high PV penetration), analyzing how these properties affect dynamic simulation software, and offering solutions for potential problems.

Generalized Green's function molecular dynamics for canonical ensemble simulations

NASA Astrophysics Data System (ADS)

Coluci, V. R.; Dantas, S. O.; Tewary, V. K.

2018-05-01

The need of small integration time steps (˜1 fs) in conventional molecular dynamics simulations is an important issue that inhibits the study of physical, chemical, and biological systems in real timescales. Additionally, to simulate those systems in contact with a thermal bath, thermostating techniques are usually applied. In this work, we generalize the Green's function molecular dynamics technique to allow simulations within the canonical ensemble. By applying this technique to one-dimensional systems, we were able to correctly describe important thermodynamic properties such as the temperature fluctuations, the temperature distribution, and the velocity autocorrelation function. We show that the proposed technique also allows the use of time steps one order of magnitude larger than those typically used in conventional molecular dynamics simulations. We expect that this technique can be used in long-timescale molecular dynamics simulations.

Coupling all-atom molecular dynamics simulations of ions in water with Brownian dynamics.

PubMed

Erban, Radek

2016-02-01

Molecular dynamics (MD) simulations of ions (K + , Na + , Ca 2+ and Cl - ) in aqueous solutions are investigated. Water is described using the SPC/E model. A stochastic coarse-grained description for ion behaviour is presented and parametrized using MD simulations. It is given as a system of coupled stochastic and ordinary differential equations, describing the ion position, velocity and acceleration. The stochastic coarse-grained model provides an intermediate description between all-atom MD simulations and Brownian dynamics (BD) models. It is used to develop a multiscale method which uses all-atom MD simulations in parts of the computational domain and (less detailed) BD simulations in the remainder of the domain.

Molecular Dynamics Analysis of Lysozyme Protein in Ethanol- Water Mixed Solvent

DTIC Science & Technology

2012-01-01

molecular dynamics simulations of solvent effect on lysozyme protein, using water, ethanol, and different concentrations of water-ethanol mixtures as...understood. This work focuses on detailed molecular dynamics simulations of solvent effect on lysozyme protein, using water, ethanol, and different...using GROMACS molecular dynamics simulation (MD) code. Compared to water environment, the lysozyme structure showed remarkable changes in water

The Distributed Diagonal Force Decomposition Method for Parallelizing Molecular Dynamics Simulations

PubMed Central

Boršnik, Urban; Miller, Benjamin T.; Brooks, Bernard R.; Janežič, Dušanka

2011-01-01

Parallelization is an effective way to reduce the computational time needed for molecular dynamics simulations. We describe a new parallelization method, the distributed-diagonal force decomposition method, with which we extend and improve the existing force decomposition methods. Our new method requires less data communication during molecular dynamics simulations than replicated data and current force decomposition methods, increasing the parallel efficiency. It also dynamically load-balances the processors' computational load throughout the simulation. The method is readily implemented in existing molecular dynamics codes and it has been incorporated into the CHARMM program, allowing its immediate use in conjunction with the many molecular dynamics simulation techniques that are already present in the program. We also present the design of the Force Decomposition Machine, a cluster of personal computers and networks that is tailored to running molecular dynamics simulations using the distributed diagonal force decomposition method. The design is expandable and provides various degrees of fault resilience. This approach is easily adaptable to computers with Graphics Processing Units because it is independent of the processor type being used. PMID:21793007

A Force Balanced Fragmentation Method for ab Initio Molecular Dynamic Simulation of Protein.

PubMed

Xu, Mingyuan; Zhu, Tong; Zhang, John Z H

2018-01-01

A force balanced generalized molecular fractionation with conjugate caps (FB-GMFCC) method is proposed for ab initio molecular dynamic simulation of proteins. In this approach, the energy of the protein is computed by a linear combination of the QM energies of individual residues and molecular fragments that account for the two-body interaction of hydrogen bond between backbone peptides. The atomic forces on the caped H atoms were corrected to conserve the total force of the protein. Using this approach, ab initio molecular dynamic simulation of an Ace-(ALA) 9 -NME linear peptide showed the conservation of the total energy of the system throughout the simulation. Further a more robust 110 ps ab initio molecular dynamic simulation was performed for a protein with 56 residues and 862 atoms in explicit water. Compared with the classical force field, the ab initio molecular dynamic simulations gave better description of the geometry of peptide bonds. Although further development is still needed, the current approach is highly efficient, trivially parallel, and can be applied to ab initio molecular dynamic simulation study of large proteins.

Real-time electron dynamics for massively parallel excited-state simulations

NASA Astrophysics Data System (ADS)

Andrade, Xavier

The simulation of the real-time dynamics of electrons, based on time dependent density functional theory (TDDFT), is a powerful approach to study electronic excited states in molecular and crystalline systems. What makes the method attractive is its flexibility to simulate different kinds of phenomena beyond the linear-response regime, including strongly-perturbed electronic systems and non-adiabatic electron-ion dynamics. Electron-dynamics simulations are also attractive from a computational point of view. They can run efficiently on massively parallel architectures due to the low communication requirements. Our implementations of electron dynamics, based on the codes Octopus (real-space) and Qball (plane-waves), allow us to simulate systems composed of thousands of atoms and to obtain good parallel scaling up to 1.6 million processor cores. Due to the versatility of real-time electron dynamics and its parallel performance, we expect it to become the method of choice to apply the capabilities of exascale supercomputers for the simulation of electronic excited states.

Evaluation of a grid based molecular dynamics approach for polypeptide simulations.

PubMed

Merelli, Ivan; Morra, Giulia; Milanesi, Luciano

2007-09-01

Molecular dynamics is very important for biomedical research because it makes possible simulation of the behavior of a biological macromolecule in silico. However, molecular dynamics is computationally rather expensive: the simulation of some nanoseconds of dynamics for a large macromolecule such as a protein takes very long time, due to the high number of operations that are needed for solving the Newton's equations in the case of a system of thousands of atoms. In order to obtain biologically significant data, it is desirable to use high-performance computation resources to perform these simulations. Recently, a distributed computing approach based on replacing a single long simulation with many independent short trajectories has been introduced, which in many cases provides valuable results. This study concerns the development of an infrastructure to run molecular dynamics simulations on a grid platform in a distributed way. The implemented software allows the parallel submission of different simulations that are singularly short but together bring important biological information. Moreover, each simulation is divided into a chain of jobs to avoid data loss in case of system failure and to contain the dimension of each data transfer from the grid. The results confirm that the distributed approach on grid computing is particularly suitable for molecular dynamics simulations thanks to the elevated scalability.

Integration of Molecular Dynamics Based Predictions into the Optimization of De Novo Protein Designs: Limitations and Benefits.

PubMed

Carvalho, Henrique F; Barbosa, Arménio J M; Roque, Ana C A; Iranzo, Olga; Branco, Ricardo J F

2017-01-01

Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

Structure and Dynamics of End-to-End Loop Formation of the Penta-Peptide Cys-Ala-Gly-Gln-Trp in Implicit Solvents

DTIC Science & Technology

2009-01-01

implicit solvents on peptide structure and dynamics , we performed extensive molecular dynamics simulations on the penta-peptide Cys-Ala-Gly-Gln-Trp. Two...end-to-end distances and dihedral angles obtained from molecular dynamics simulations with implicit solvent models were in a good agreement with those...to maintain the temperature of the systems. Introduction Molecular dynamics (MD) simulation techniques are widely used to study structure and

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

DTIC Science & Technology

2009-11-01

dynamics of the complex predicted by multiple molecular dynamics simulations , and discuss further structural optimization to achieve better in vivo efficacy...complex with BoNTAe and the dynamics of the complex predicted by multiple molecular dynamics simulations (MMDSs). On the basis of the 3D model, we discuss...is unlimited whereas AHP exhibited 54% inhibition under the same conditions (Table 1). Computer Simulation Twenty different molecular dynamics

Determination of concentration and molar absorptivity of hypochlorous acid and hypobromous acid species by hydrogen peroxide titration

NASA Astrophysics Data System (ADS)

Uehara, H.; Arakaki, T.

2017-12-01

Hypochlorous acid and hypobromous acid (abbreviated as "HypoX acids") are the main ingredients of bleaching and bactericides. The HypoX acids change their chemical forms depending on environmental factors such as pH and various chemical reactions. For example, it has been reported that hypobromite ion in water changes to carcinogenic bromate by photochemical reaction with ultraviolet light. In this study, concentrations of HypoX acids were determined by UV-VIS absorbance measurement utilizing the fact that HypoX acids react with hydrogen peroxide and do not co-exist in the solution. The method for determining the concentration by titration with hydrogen peroxide can be carried out simpler and more efficiently than the DPD method or the current titration method generally used for chlorine concentration measurement. Molar absorptivity between 250 - 500 nm of HypoX acids, including their conjugate base species, was determined by solving theoretical acid-base formula including molar fraction of each chemical species at various pHs. Molar absorptivity of OCl- and OBr- between 250 - 500 nm was determined based on the concentrations obtained from titration with hydrogen peroxide and absorbance at pH > 10, where OCl- and OBr- dominate. Furthermore, the HypoX acids solutions were irradiated with a solar simulator, and the photolysis rate constants were obtained. Based on those values, the half-lives were calculated and the behavior of HypoX acids in the environment was elucidated.

Investigation of the Dynamic Contact Angle Using a Direct Numerical Simulation Method.

PubMed

Zhu, Guangpu; Yao, Jun; Zhang, Lei; Sun, Hai; Li, Aifen; Shams, Bilal

2016-11-15

A large amount of residual oil, which exists as isolated oil slugs, remains trapped in reservoirs after water flooding. Numerous numerical studies are performed to investigate the fundamental flow mechanism of oil slugs to improve flooding efficiency. Dynamic contact angle models are usually introduced to simulate an accurate contact angle and meniscus displacement of oil slugs under a high capillary number. Nevertheless, in the oil slug flow simulation process, it is unnecessary to introduce the dynamic contact angle model because of a negligible change in the meniscus displacement after using the dynamic contact angle model when the capillary number is small. Therefore, a critical capillary number should be introduced to judge whether the dynamic contact model should be incorporated into simulations. In this study, a direct numerical simulation method is employed to simulate the oil slug flow in a capillary tube at the pore scale. The position of the interface between water and the oil slug is determined using the phase-field method. The capacity and accuracy of the model are validated using a classical benchmark: a dynamic capillary filling process. Then, different dynamic contact angle models and the factors that affect the dynamic contact angle are analyzed. The meniscus displacements of oil slugs with a dynamic contact angle and a static contact angle (SCA) are obtained during simulations, and the relative error between them is calculated automatically. The relative error limit has been defined to be 5%, beyond which the dynamic contact angle model needs to be incorporated into the simulation to approach the realistic displacement. Thus, the desired critical capillary number can be determined. A three-dimensional universal chart of critical capillary number, which functions as static contact angle and viscosity ratio, is given to provide a guideline for oil slug simulation. Also, a fitting formula is presented for ease of use.

Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training.

PubMed

Lester, Mark E; Urso, Maria L; Evans, Rachel K; Pierce, Joseph R; Spiering, Barry A; Maresh, Carl M; Hatfield, Disa L; Kraemer, William J; Nindl, Bradley C

2009-10-01

Prescribing exercise based on intensity, frequency, and duration of loading may maximize osteogenic responses in bone, but a model of the osteogenic potential of exercise has not been established in humans. In rodents, an osteogenic index (OI) has been used to predict the osteogenic potential of exercise. The current study sought to determine whether aerobic, resistance, or combined aerobic and resistance exercise programs conducted over eight weeks and compared to a control group could produce changes in biochemical markers of bone turnover indicative of bone formation. We further sought to determine whether an OI could be calculated for each of these programs that would reflect observed biochemical changes. We collected serum biomarkers [bone-specific alkaline phosphatase (BAP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide fragment of type I collagen (CTx), deoxypyridinoline (DPD), 25-hydroxy vitamin D (25(OH)D), and parathyroid hormone (PTH)] in 56 women (20.3+/-1.8 years) before, during and after eight weeks of training. We also measured bone mineral density (BMD) at regional areas of interest using DXA and pQCT. Biomarkers of bone formation (BAP and osteocalcin) increased in the Resistance and Combined groups (p<0.05), while biomarkers of bone resorption (TRAP and DPD) decreased and increased, respectively, after training (p<0.05) in all groups. Small changes in volumetric and areal BMD (p<0.05) were observed in the distal tibia in the Aerobic and Combined groups, respectively. Mean weekly OIs were 16.0+/-1.9, 20.6+/-2.2, and 36.9+/-5.2 for the Resistance, Aerobic, and Combined groups, respectively. The calculated osteogenic potential of our programs did not correlate with the observed changes in biomarkers of bone turnover. The results of the present study demonstrate that participation in an eight week physical training program that incorporates a resistance component by previously inactive young women results in alterations in biomarkers of bone remodeling indicative of increased formation without substantial alterations in markers of resorption.

Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil

PubMed Central

Hahnvajanawong, Chariya; Chaiyagool, Jariya; Seubwai, Wunchana; Bhudhisawasdi, Vajarabhongsa; Namwat, Nisana; Khuntikeo, Narong; Sripa, Banchob; Pugkhem, Ake; Tassaneeyakul, Wichittra

2012-01-01

AIM: To determine whether expression of certain enzymes related to 5-fluorouracil (5-FU) metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma (CCA). METHODS: The histoculture drug response assay (HDRA) was performed using surgically resected CCA tissues. Tumor cell viability was determined morphologically with hematoxylin and eosin- and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues. The mRNA expression of thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) was determined with real-time reverse transcriptase-polymerase chain reaction. The levels of gene expression and the sensitivity to 5-FU were evaluated. RESULTS: Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital, Khon Kaen University from 2007 to 2009. HDRA was used to determine the response of these CCA tissues to 5-FU. Based on the dose-response curve, 200 μg/mL 5-FU was selected as the test concentration. The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU. When the relationship between TP, OPRT, TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined, only OPRT mRNA expression was significantly correlated with the response to 5-FU. The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group (0.41 ± 0.25 vs 0.22 ± 0.12, P < 0.05). CONCLUSION: OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA. Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients. PMID:22912546

Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated esophageal cancer patients.

PubMed

Grimminger, Peter P; Maus, Martin K H; Bergenthal, Juliane; Wandhöfer, Christoph; Fetzner, Ullrich K; Herbold, Till; Bollschweiler, Elfriede; Hölscher, Arnulf H; Brabender, Jan

2015-03-01

The prognostic value of TS (thymidylate synthase) and DPD (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with esophageal cancer is not known. The aim of the present study was to evaluate the significance of these molecular alterations in the blood as a prognostic marker for patients with neoadjuvant-treated esophageal cancer. A total of 29 patients with locally advanced esophageal cancer (cT3-T4, Nx, M0) were enrolled in this prospective study. All patients received neoadjuvant chemoradiation followed by a transthoracic resection (curative transthoracic en bloc esophagectomy, RO). Peripheral blood samples were drawn before initiation of therapy. The analysis was performed using quantitative real-time-polymerase chain reaction (RT-PCR). The histomorphological regressions grading after neoadjuvant therapy was defined as follows: major response (MaR)=less than 10% vital tumor tissue, minor response (MiR)=more than 10% vital tumor tissue. Nineteen out of 29 patients (65.5%) had a MiR and 10 (34.5%) had a MaR. The median survival of patients was 2.08 years (range=0.15-4.53). Among the tested genes, the RNA expression of TS was significantly associated with prognosis of patients. Patients with TS expression above 0.78 had a median survival of 1.1 years (range=0.21-3.96) compared to 2.6 years (range=0.15 to 4.53) in patients with TS expression lower than 0.78 (p=0.031, log rank test). There was no association between clinical variables (e.g., tumor stage, gender, age, etc.) and the RNA expression of TS in the serum. The RNA expression of TS in the blood is a potential prognostic marker in patients with neoadjuvant-treated esophageal cancer. The significance of these molecular alterations as non-invasive prognostic marker for esophageal cancer should be evaluated in prospective studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

PubMed

Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

2003-01-01

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

Effects of two types of medical contrast media on routine chemistry results by three automated chemistry analyzers.

PubMed

Park, Yu Jin; Rim, John Hoon; Yim, Jisook; Lee, Sang-Guk; Kim, Jeong-Ho

2017-08-01

The use of iodinated contrast media has grown in popularity in the past two decades, but relatively little attention has been paid to the possible interferential effects of contrast media on laboratory test results. Herein, we investigate medical contrast media interference with routine chemistry results obtained by three automated chemistry analyzers. Ten levels of pooled serum were used in the study. Two types of medical contrast media [Iopamiro (iopamidol) and Omnipaque (iohexol)] were evaluated. To evaluate the dose-dependent effects of the contrast media, iopamidol and iohexol were spiked separately into aliquots of serum for final concentrations of 1.8%, 3.6%, 5.5%, 7.3%, and 9.1%. The 28 analytes included in the routine chemistry panel were measured by using Hitachi 7600, AU5800, and Cobas c702 analyzers. We calculated the delta percentage difference (DPD) between the samples and the control, and examined dose-dependent trends. When the mean DPD values were compared with the reference cut-off criteria, the only uniformly interferential effect observed for all analyzers was in total protein with iopamidol. Two additional analytes that showed trends toward interferential effects only in few analyzers and exceeded the limits of the allowable error were the serum iron and the total CO 2 . The other combinations of analyzer and contrast showed no consistent dose-dependent propensity for change in any analyte level. Our study suggests that many of the analytes included in routine chemistry results, except total protein and serum iron, are not significantly affected by iopamidol and iohexol. These results suggest that it would be beneficial to apply a flexible medical evaluation process for patients requiring both laboratory tests and imaging studies, minimizing the need for strict regulations for sequential tests. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Quorum Sensing Signal Production and Microbial Interactions in a Polymicrobial Disease of Corals and the Coral Surface Mucopolysaccharide Layer

PubMed Central

Zimmer, Beth L.; May, Amanda L.; Bhedi, Chinmayee D.; Dearth, Stephen P.; Prevatte, Carson W.; Pratte, Zoe; Campagna, Shawn R.; Richardson, Laurie L.

2014-01-01

Black band disease (BBD) of corals is a complex polymicrobial disease considered to be a threat to coral reef health, as it can lead to mortality of massive reef-building corals. The BBD community is dominated by gliding, filamentous cyanobacteria with a highly diverse population of heterotrophic bacteria. Microbial interactions such as quorum sensing (QS) and antimicrobial production may be involved in BBD disease pathogenesis. In this study, BBD (whole community) samples, as well as 199 bacterial isolates from BBD, the surface mucopolysaccharide layer (SML) of apparently healthy corals, and SML of apparently healthy areas of BBD-infected corals were screened for the production of acyl homoserine lactones (AHLs) and for autoinducer-2 (AI-2) activity using three bacterial reporter strains. AHLs were detected in all BBD (intact community) samples tested and in cultures of 5.5% of BBD bacterial isolates. Over half of a subset (153) of the isolates were positive for AI-2 activity. AHL-producing isolates were further analyzed using LC-MS/MS to determine AHL chemical structure and the concentration of (S)-4,5-dihydroxy-2,3-pentanedione (DPD), the biosynthetic precursor of AI-2. C6-HSL was the most common AHL variant detected, followed by 3OC4-HSL. In addition to QS assays, 342 growth challenges were conducted among a subset of the isolates, with 27% of isolates eliciting growth inhibition and 2% growth stimulation. 24% of BBD isolates elicited growth inhibition as compared to 26% and 32% of the bacteria from the two SML sources. With one exception, only isolates that exhibited AI-2 activity or produced DPD inhibited growth of test strains. These findings demonstrate for the first time that AHLs are present in an active coral disease. It is possible that AI-2 production among BBD and coral SML bacteria may structure the microbial communities of both a polymicrobial infection and the healthy coral microbiome. PMID:25268348

Physiologically based pharmacokinetic modelling of the three-step metabolism of pyrimidine using C-uracil as an in vivo probe.

PubMed

Ito, Suminobu; Kawamura, Takeshi; Inada, Makoto; Inoue, Yoshiharu; Hirao, Yukihiro; Koga, Toshihisa; Kunizaki, Jun-ichi; Shimizu, Takefumi; Sato, Hitoshi

2005-12-01

Approximately 80% of uracil is excreted as beta-alanine, ammonia and CO2 via three sequential reactions. The activity of the first enzyme in this scheme, dihydropyrimidine dehydrogenase (DPD), is reported to be the key determinant of the cytotoxicity and side-effects of 5-fluorouracil. The aim of the present study was to re-evaluate the pharmacokinetics of uracil and its metabolites using a sensitive assay and based on a newly developed, physiologically based pharmacokinetic (PBPK) model. [2-(13)C]Uracil was orally administrated to 12 healthy males at escalating doses of 50, 100 and 200 mg, and the concentrations of [2-(13)C]uracil, [2-(13)C]5,6-dihydrouracil and beta-ureidopropionic acid (ureido-(13)C) in plasma and urine and (13)CO2 in breath were measured by liquid chromatography-tandem mass spectrometry and gas chromatograph-isotope ratio mass spectrometry, respectively. The pharmacokinetics of [2-(13)C]uracil were nonlinear. The elimination half-life of [2-(13)C]5,6-dihydrouracil was 0.9-1.4 h, whereas that of [2-(13)C]uracil was 0.2-0.3 h. The AUC of [2-(13)C]5,6-dihydrouracil was 1.9-3.1 times greater than that of [2-(13)C]uracil, whereas that of ureido-(13)C was 0.13-0.23 times smaller. The pharmacokinetics of (13)CO2 in expired air were linear and the recovery of (13)CO2 was approximately 80% of the dose. The renal clearance of [2-(13)C]uracil was negligible. A PBPK model to describe (13)CO2 exhalation after orally administered [2-(13)C]uracil was successfully developed. Using [2-(13)C]uracil as a probe, this model could be useful in identifying DPD-deficient patients at risk of 5-fluorouracil toxicity.

A parameters optimization method for planar joint clearance model and its application for dynamics simulation of reciprocating compressor

NASA Astrophysics Data System (ADS)

Hai-yang, Zhao; Min-qiang, Xu; Jin-dong, Wang; Yong-bo, Li

2015-05-01

In order to improve the accuracy of dynamics response simulation for mechanism with joint clearance, a parameter optimization method for planar joint clearance contact force model was presented in this paper, and the optimized parameters were applied to the dynamics response simulation for mechanism with oversized joint clearance fault. By studying the effect of increased clearance on the parameters of joint clearance contact force model, the relation of model parameters between different clearances was concluded. Then the dynamic equation of a two-stage reciprocating compressor with four joint clearances was developed using Lagrange method, and a multi-body dynamic model built in ADAMS software was used to solve this equation. To obtain a simulated dynamic response much closer to that of experimental tests, the parameters of joint clearance model, instead of using the designed values, were optimized by genetic algorithms approach. Finally, the optimized parameters were applied to simulate the dynamics response of model with oversized joint clearance fault according to the concluded parameter relation. The dynamics response of experimental test verified the effectiveness of this application.

Conformational dynamics and internal friction in homopolymer globules: equilibrium vs. non-equilibrium simulations.

PubMed

Einert, T R; Sing, C E; Alexander-Katz, A; Netz, R R

2011-12-01

We study the conformational dynamics within homopolymer globules by solvent-implicit Brownian dynamics simulations. A strong dependence of the internal chain dynamics on the Lennard-Jones cohesion strength ε and the globule size N (G) is observed. We find two distinct dynamical regimes: a liquid-like regime (for ε < ε(s) with fast internal dynamics and a solid-like regime (for ε > ε(s) with slow internal dynamics. The cohesion strength ε(s) of this freezing transition depends on N (G) . Equilibrium simulations, where we investigate the diffusional chain dynamics within the globule, are compared with non-equilibrium simulations, where we unfold the globule by pulling the chain ends with prescribed velocity (encompassing low enough velocities so that the linear-response, viscous regime is reached). From both simulation protocols we derive the internal viscosity within the globule. In the liquid-like regime the internal friction increases continuously with ε and scales extensive in N (G) . This suggests an internal friction scenario where the entire chain (or an extensive fraction thereof) takes part in conformational reorganization of the globular structure.

Dynamic CFD Simulations of the Supersonic Inflatable Aerodynamic Decelerator (SIAD) Ballistic Range Tests

NASA Technical Reports Server (NTRS)

Brock, Joseph M; Stern, Eric

2016-01-01

Dynamic CFD simulations of the SIAD ballistic test model were performed using US3D flow solver. Motivation for performing these simulations is for the purpose of validation and verification of the US3D flow solver as a viable computational tool for predicting dynamic coefficients.

High performance computing in biology: multimillion atom simulations of nanoscale systems

PubMed Central

Sanbonmatsu, K. Y.; Tung, C.-S.

2007-01-01

Computational methods have been used in biology for sequence analysis (bioinformatics), all-atom simulation (molecular dynamics and quantum calculations), and more recently for modeling biological networks (systems biology). Of these three techniques, all-atom simulation is currently the most computationally demanding, in terms of compute load, communication speed, and memory load. Breakthroughs in electrostatic force calculation and dynamic load balancing have enabled molecular dynamics simulations of large biomolecular complexes. Here, we report simulation results for the ribosome, using approximately 2.64 million atoms, the largest all-atom biomolecular simulation published to date. Several other nanoscale systems with different numbers of atoms were studied to measure the performance of the NAMD molecular dynamics simulation program on the Los Alamos National Laboratory Q Machine. We demonstrate that multimillion atom systems represent a 'sweet spot' for the NAMD code on large supercomputers. NAMD displays an unprecedented 85% parallel scaling efficiency for the ribosome system on 1024 CPUs. We also review recent targeted molecular dynamics simulations of the ribosome that prove useful for studying conformational changes of this large biomolecular complex in atomic detail. PMID:17187988

ReaDDy - A Software for Particle-Based Reaction-Diffusion Dynamics in Crowded Cellular Environments

PubMed Central

Schöneberg, Johannes; Noé, Frank

2013-01-01

We introduce the software package ReaDDy for simulation of detailed spatiotemporal mechanisms of dynamical processes in the cell, based on reaction-diffusion dynamics with particle resolution. In contrast to other particle-based reaction kinetics programs, ReaDDy supports particle interaction potentials. This permits effects such as space exclusion, molecular crowding and aggregation to be modeled. The biomolecules simulated can be represented as a sphere, or as a more complex geometry such as a domain structure or polymer chain. ReaDDy bridges the gap between small-scale but highly detailed molecular dynamics or Brownian dynamics simulations and large-scale but little-detailed reaction kinetics simulations. ReaDDy has a modular design that enables the exchange of the computing core by efficient platform-specific implementations or dynamical models that are different from Brownian dynamics. PMID:24040218

Dynamic Mesh CFD Simulations of Orion Parachute Pendulum Motion During Atmospheric Entry

NASA Technical Reports Server (NTRS)

Halstrom, Logan D.; Schwing, Alan M.; Robinson, Stephen K.

2016-01-01

This paper demonstrates the usage of computational fluid dynamics to study the effects of pendulum motion dynamics of the NASAs Orion Multi-Purpose Crew Vehicle parachute system on the stability of the vehicles atmospheric entry and decent. Significant computational fluid dynamics testing has already been performed at NASAs Johnson Space Center, but this study sought to investigate the effect of bulk motion of the parachute, such as pitching, on the induced aerodynamic forces. Simulations were performed with a moving grid geometry oscillating according to the parameters observed in flight tests. As with the previous simulations, OVERFLOW computational fluid dynamics tool is used with the assumption of rigid, non-permeable geometry. Comparison to parachute wind tunnel tests is included for a preliminary validation of the dynamic mesh model. Results show qualitative differences in the flow fields of the static and dynamic simulations and quantitative differences in the induced aerodynamic forces, suggesting that dynamic mesh modeling of the parachute pendulum motion may uncover additional dynamic effects.

High Speed Civil Transport Aircraft Simulation: Reference-H Cycle 1, MATLAB Implementation

NASA Technical Reports Server (NTRS)

Sotack, Robert A.; Chowdhry, Rajiv S.; Buttrill, Carey S.

1999-01-01

The mathematical model and associated code to simulate a high speed civil transport aircraft - the Boeing Reference H configuration - are described. The simulation was constructed in support of advanced control law research. In addition to providing time histories of the dynamic response, the code includes the capabilities for calculating trim solutions and for generating linear models. The simulation relies on the nonlinear, six-degree-of-freedom equations which govern the motion of a rigid aircraft in atmospheric flight. The 1962 Standard Atmosphere Tables are used along with a turbulence model to simulate the Earth atmosphere. The aircraft model has three parts - an aerodynamic model, an engine model, and a mass model. These models use the data from the Boeing Reference H cycle 1 simulation data base. Models for the actuator dynamics, landing gear, and flight control system are not included in this aircraft model. Dynamic responses generated by the nonlinear simulation are presented and compared with results generated from alternate simulations at Boeing Commercial Aircraft Company and NASA Langley Research Center. Also, dynamic responses generated using linear models are presented and compared with dynamic responses generated using the nonlinear simulation.

Coarse-Grained Lattice Model Simulations of Sequence-Structure Fitness of a Ribosome-Inactivating Protein

DTIC Science & Technology

2007-11-05

limits of what is considered practical when applying all-atom molecular - dynamics simulation methods. Lattice models provide computationally robust...of expectation values from the density of states. All-atom molecular - dynamics simulations provide the most rigorous sampling method to generate con... molecular - dynamics simulations of protein folding,6–9 reported studies of computing a heat capacity or other calorimetric observables have been limited to

Quantum Fragment Based ab Initio Molecular Dynamics for Proteins.

PubMed

Liu, Jinfeng; Zhu, Tong; Wang, Xianwei; He, Xiao; Zhang, John Z H

2015-12-08

Developing ab initio molecular dynamics (AIMD) methods for practical application in protein dynamics is of significant interest. Due to the large size of biomolecules, applying standard quantum chemical methods to compute energies for dynamic simulation is computationally prohibitive. In this work, a fragment based ab initio molecular dynamics approach is presented for practical application in protein dynamics study. In this approach, the energy and forces of the protein are calculated by a recently developed electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. For simulation in explicit solvent, mechanical embedding is introduced to treat protein interaction with explicit water molecules. This AIMD approach has been applied to MD simulations of a small benchmark protein Trpcage (with 20 residues and 304 atoms) in both the gas phase and in solution. Comparison to the simulation result using the AMBER force field shows that the AIMD gives a more stable protein structure in the simulation, indicating that quantum chemical energy is more reliable. Importantly, the present fragment-based AIMD simulation captures quantum effects including electrostatic polarization and charge transfer that are missing in standard classical MD simulations. The current approach is linear-scaling, trivially parallel, and applicable to performing the AIMD simulation of proteins with a large size.

Dynamic system simulation of small satellite projects

NASA Astrophysics Data System (ADS)

Raif, Matthias; Walter, Ulrich; Bouwmeester, Jasper

2010-11-01

A prerequisite to accomplish a system simulation is to have a system model holding all necessary project information in a centralized repository that can be accessed and edited by all parties involved. At the Institute of Astronautics of the Technische Universitaet Muenchen a modular approach for modeling and dynamic simulation of satellite systems has been developed called dynamic system simulation (DySyS). DySyS is based on the platform independent description language SysML to model a small satellite project with respect to the system composition and dynamic behavior. A library of specific building blocks and possible relations between these blocks have been developed. From this library a system model of the satellite of interest can be created. A mapping into a C++ simulation allows the creation of an executable system model with which simulations are performed to observe the dynamic behavior of the satellite. In this paper DySyS is used to model and simulate the dynamic behavior of small satellites, because small satellite projects can act as a precursor to demonstrate the feasibility of a system model since they are less complex compared to a large scale satellite project.

Comparisons of Kinematics and Dynamics Simulation Software Tools

NASA Technical Reports Server (NTRS)

Shiue, Yeu-Sheng Paul

2002-01-01

Kinematic and dynamic analyses for moving bodies are essential to system engineers and designers in the process of design and validations. 3D visualization and motion simulation plus finite element analysis (FEA) give engineers a better way to present ideas and results. Marshall Space Flight Center (MSFC) system engineering researchers are currently using IGRIP from DELMIA Inc. as a kinematic simulation tool for discrete bodies motion simulations. Although IGRIP is an excellent tool for kinematic simulation with some dynamic analysis capabilities in robotic control, explorations of other alternatives with more powerful dynamic analysis and FEA capabilities are necessary. Kinematics analysis will only examine the displacement, velocity, and acceleration of the mechanism without considering effects from masses of components. With dynamic analysis and FEA, effects such as the forces or torques at the joint due to mass and inertia of components can be identified. With keen market competition, ALGOR Mechanical Event Simulation (MES), MSC visualNastran 4D, Unigraphics Motion+, and Pro/MECHANICA were chosen for explorations. In this study, comparisons between software tools were presented in terms of following categories: graphical user interface (GUI), import capability, tutorial availability, ease of use, kinematic simulation capability, dynamic simulation capability, FEA capability, graphical output, technical support, and cost. Propulsion Test Article (PTA) with Fastrac engine model exported from IGRIP and an office chair mechanism were used as examples for simulations.

Mosquito population dynamics from cellular automata-based simulation

NASA Astrophysics Data System (ADS)

Syafarina, Inna; Sadikin, Rifki; Nuraini, Nuning

2016-02-01

In this paper we present an innovative model for simulating mosquito-vector population dynamics. The simulation consist of two stages: demography and dispersal dynamics. For demography simulation, we follow the existing model for modeling a mosquito life cycles. Moreover, we use cellular automata-based model for simulating dispersal of the vector. In simulation, each individual vector is able to move to other grid based on a random walk. Our model is also capable to represent immunity factor for each grid. We simulate the model to evaluate its correctness. Based on the simulations, we can conclude that our model is correct. However, our model need to be improved to find a realistic parameters to match real data.

Tethered satellite system dynamics and control

NASA Technical Reports Server (NTRS)

Musetti, B.; Cibrario, B.; Bussolino, L.; Bodley, C. S.; Flanders, H. A.; Mowery, D. K.; Tomlin, D. D.

1990-01-01

The first tethered satellite system, scheduled for launch in May 1991, is reviewed. The system dynamics, dynamics control, and dynamics simulations are discussed. Particular attention is given to in-plane and out-of-plane librations; tether oscillation modes; orbiter and sub-satellite dynamics; deployer control system; the sub-satellite attitude measurement and control system; the Aeritalia Dynamics Model; the Martin-Marietta and NASA-MSFC Dynamics Model; and simulation results.

Numerical Simulation of Rolling-Airframes Using a Multi-Level Cartesian Method

NASA Technical Reports Server (NTRS)

Murman, Scott M.; Aftosmis, Michael J.; Berger, Marsha J.; Kwak, Dochan (Technical Monitor)

2002-01-01

A supersonic rolling missile with two synchronous canard control surfaces is analyzed using an automated, inviscid, Cartesian method. Sequential-static and time-dependent dynamic simulations of the complete motion are computed for canard dither schedules for level flight, pitch, and yaw maneuver. The dynamic simulations are compared directly against both high-resolution viscous simulations and relevant experimental data, and are also utilized to compute dynamic stability derivatives. The results show that both the body roll rate and canard dither motion influence the roll-averaged forces and moments on the body. At the relatively, low roll rates analyzed in the current work these dynamic effects are modest, however the dynamic computations are effective in predicting the dynamic stability derivatives which can be significant for highly-maneuverable missiles.

Analysis, simulation and visualization of 1D tapping via reduced dynamical models

NASA Astrophysics Data System (ADS)

Blackmore, Denis; Rosato, Anthony; Tricoche, Xavier; Urban, Kevin; Zou, Luo

2014-04-01

A low-dimensional center-of-mass dynamical model is devised as a simplified means of approximately predicting some important aspects of the motion of a vertical column comprised of a large number of particles subjected to gravity and periodic vertical tapping. This model is investigated first as a continuous dynamical system using analytical, simulation and visualization techniques. Then, by employing an approach analogous to that used to approximate the dynamics of a bouncing ball on an oscillating flat plate, it is modeled as a discrete dynamical system and analyzed to determine bifurcations and transitions to chaotic motion along with other properties. The predictions of the analysis are then compared-primarily qualitatively-with visualization and simulation results of the reduced continuous model, and ultimately with simulations of the complete system dynamics.

A CONTINUUM HARD-SPHERE MODEL OF PROTEIN ADSORPTION

PubMed Central

Finch, Craig; Clarke, Thomas; Hickman, James J.

2012-01-01

Protein adsorption plays a significant role in biological phenomena such as cell-surface interactions and the coagulation of blood. Two-dimensional random sequential adsorption (RSA) models are widely used to model the adsorption of proteins on solid surfaces. Continuum equations have been developed so that the results of RSA simulations can be used to predict the kinetics of adsorption. Recently, Brownian dynamics simulations have become popular for modeling protein adsorption. In this work a continuum model was developed to allow the results from a Brownian dynamics simulation to be used as the boundary condition in a computational fluid dynamics (CFD) simulation. Brownian dynamics simulations were used to model the diffusive transport of hard-sphere particles in a liquid and the adsorption of the particles onto a solid surface. The configuration of the adsorbed particles was analyzed to quantify the chemical potential near the surface, which was found to be a function of the distance from the surface and the fractional surface coverage. The near-surface chemical potential was used to derive a continuum model of adsorption that incorporates the results from the Brownian dynamics simulations. The equations of the continuum model were discretized and coupled to a CFD simulation of diffusive transport to the surface. The kinetics of adsorption predicted by the continuum model closely matched the results from the Brownian dynamics simulation. This new model allows the results from mesoscale simulations to be incorporated into micro- or macro-scale CFD transport simulations of protein adsorption in practical devices. PMID:23729843

Advanced Polymer Network Structures

DTIC Science & Technology

2016-02-01

double networks in a single step was identified from coarse-grained molecular dynamics simulations of polymer solvents bearing rigid side chains dissolved...in a polymer network. Coarse-grained molecular dynamics simulations also explored the mechanical behavior of traditional double networks and...DRI), polymer networks, polymer gels, molecular dynamics simulations , double networks 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

A cable-driven parallel robots application: modelling and simulation of a dynamic cable model in Dymola

NASA Astrophysics Data System (ADS)

Othman, M. F.; Kurniawan, R.; Schramm, D.; Ariffin, A. K.

2018-05-01

Modeling a cable model in multibody dynamics simulation tool which dynamically varies in length, mass and stiffness is a challenging task. Simulation of cable-driven parallel robots (CDPR) for instance requires a cable model that can dynamically change in length for every desired pose of the platform. Thus, in this paper, a detailed procedure for modeling and simulation of a dynamic cable model in Dymola is proposed. The approach is also applicable for other types of Modelica simulation environments. The cable is modeled using standard mechanical elements like mass, spring, damper and joint. The parameters of the cable model are based on the factsheet of the manufacturer and experimental results. Its dynamic ability is tested by applying it on a complete planar CDPR model in which the parameters are based on a prototype named CABLAR, which is developed in Chair of Mechatronics, University of Duisburg-Essen. The prototype has been developed to demonstrate an application of CDPR as a goods storage and retrieval machine. The performance of the cable model during the simulation is analyzed and discussed.

Multiscale simulations of patchy particle systems combining Molecular Dynamics, Path Sampling and Green's Function Reaction Dynamics

NASA Astrophysics Data System (ADS)

Bolhuis, Peter

Important reaction-diffusion processes, such as biochemical networks in living cells, or self-assembling soft matter, span many orders in length and time scales. In these systems, the reactants' spatial dynamics at mesoscopic length and time scales of microns and seconds is coupled to the reactions between the molecules at microscopic length and time scales of nanometers and milliseconds. This wide range of length and time scales makes these systems notoriously difficult to simulate. While mean-field rate equations cannot describe such processes, the mesoscopic Green's Function Reaction Dynamics (GFRD) method enables efficient simulation at the particle level provided the microscopic dynamics can be integrated out. Yet, many processes exhibit non-trivial microscopic dynamics that can qualitatively change the macroscopic behavior, calling for an atomistic, microscopic description. The recently developed multiscale Molecular Dynamics Green's Function Reaction Dynamics (MD-GFRD) approach combines GFRD for simulating the system at the mesocopic scale where particles are far apart, with microscopic Molecular (or Brownian) Dynamics, for simulating the system at the microscopic scale where reactants are in close proximity. The association and dissociation of particles are treated with rare event path sampling techniques. I will illustrate the efficiency of this method for patchy particle systems. Replacing the microscopic regime with a Markov State Model avoids the microscopic regime completely. The MSM is then pre-computed using advanced path-sampling techniques such as multistate transition interface sampling. I illustrate this approach on patchy particle systems that show multiple modes of binding. MD-GFRD is generic, and can be used to efficiently simulate reaction-diffusion systems at the particle level, including the orientational dynamics, opening up the possibility for large-scale simulations of e.g. protein signaling networks.

Real-time dynamics simulation of the Cassini spacecraft using DARTS. Part 1: Functional capabilities and the spatial algebra algorithm

NASA Technical Reports Server (NTRS)

Jain, A.; Man, G. K.

1993-01-01

This paper describes the Dynamics Algorithms for Real-Time Simulation (DARTS) real-time hardware-in-the-loop dynamics simulator for the National Aeronautics and Space Administration's Cassini spacecraft. The spacecraft model consists of a central flexible body with a number of articulated rigid-body appendages. The demanding performance requirements from the spacecraft control system require the use of a high fidelity simulator for control system design and testing. The DARTS algorithm provides a new algorithmic and hardware approach to the solution of this hardware-in-the-loop simulation problem. It is based upon the efficient spatial algebra dynamics for flexible multibody systems. A parallel and vectorized version of this algorithm is implemented on a low-cost, multiprocessor computer to meet the simulation timing requirements.

An AD100 implementation of a real-time STOVL aircraft propulsion system

NASA Technical Reports Server (NTRS)

Ouzts, Peter J.; Drummond, Colin K.

1990-01-01

A real-time dynamic model of the propulsion system for a Short Take-Off and Vertical Landing (STOVL) aircraft was developed for the AD100 simulation environment. The dynamic model was adapted from a FORTRAN based simulation using the dynamic programming capabilities of the AD100 ADSIM simulation language. The dynamic model includes an aerothermal representation of a turbofan jet engine, actuator and sensor models, and a multivariable control system. The AD100 model was tested for agreement with the FORTRAN model and real-time execution performance. The propulsion system model was also linked to an airframe dynamic model to provide an overall STOVL aircraft simulation for the purposes of integrated flight and propulsion control studies. An evaluation of the AD100 system for use as an aircraft simulation environment is included.

CADLIVE toolbox for MATLAB: automatic dynamic modeling of biochemical networks with comprehensive system analysis.

PubMed

Inoue, Kentaro; Maeda, Kazuhiro; Miyabe, Takaaki; Matsuoka, Yu; Kurata, Hiroyuki

2014-09-01

Mathematical modeling has become a standard technique to understand the dynamics of complex biochemical systems. To promote the modeling, we had developed the CADLIVE dynamic simulator that automatically converted a biochemical map into its associated mathematical model, simulated its dynamic behaviors and analyzed its robustness. To enhance the feasibility by CADLIVE and extend its functions, we propose the CADLIVE toolbox available for MATLAB, which implements not only the existing functions of the CADLIVE dynamic simulator, but also the latest tools including global parameter search methods with robustness analysis. The seamless, bottom-up processes consisting of biochemical network construction, automatic construction of its dynamic model, simulation, optimization, and S-system analysis greatly facilitate dynamic modeling, contributing to the research of systems biology and synthetic biology. This application can be freely downloaded from http://www.cadlive.jp/CADLIVE_MATLAB/ together with an instruction.

Software-Engineering Process Simulation (SEPS) model

NASA Technical Reports Server (NTRS)

Lin, C. Y.; Abdel-Hamid, T.; Sherif, J. S.

1992-01-01

The Software Engineering Process Simulation (SEPS) model is described which was developed at JPL. SEPS is a dynamic simulation model of the software project development process. It uses the feedback principles of system dynamics to simulate the dynamic interactions among various software life cycle development activities and management decision making processes. The model is designed to be a planning tool to examine tradeoffs of cost, schedule, and functionality, and to test the implications of different managerial policies on a project's outcome. Furthermore, SEPS will enable software managers to gain a better understanding of the dynamics of software project development and perform postmodern assessments.

Molecular dynamics simulations of collision-induced absorption: Implementation in LAMMPS

NASA Astrophysics Data System (ADS)

Fakhardji, W.; Gustafsson, M.

2017-02-01

We pursue simulations of collision-induced absorption in a mixture of argon and xenon gas at room temperature by means of classical molecular dynamics. The established theoretical approach (Hartmann et al. 2011 J. Chem. Phys. 134 094316) is implemented with the molecular dynamics package LAMMPS. The bound state features in the absorption spectrum are well reproduced with the molecular dynamics simulation in comparison with a laboratory measurement. The magnitude of the computed absorption, however, is underestimated in a large part of the spectrum. We suggest some aspects of the simulation that could be improved.

Simulating Food Web Dynamics along a Gradient: Quantifying Human Influence

PubMed Central

Jordán, Ferenc; Gjata, Nerta; Mei, Shu; Yule, Catherine M.

2012-01-01

Realistically parameterized and dynamically simulated food-webs are useful tool to explore the importance of the functional diversity of ecosystems, and in particular relations between the dynamics of species and the whole community. We present a stochastic dynamical food web simulation for the Kelian River (Borneo). The food web was constructed for six different locations, arrayed along a gradient of increasing human perturbation (mostly resulting from gold mining activities) along the river. Along the river, the relative importance of grazers, filterers and shredders decreases with increasing disturbance downstream, while predators become more dominant in governing eco-dynamics. Human activity led to increased turbidity and sedimentation which adversely impacts primary productivity. Since the main difference between the study sites was not the composition of the food webs (structure is quite similar) but the strengths of interactions and the abundance of the trophic groups, a dynamical simulation approach seemed to be useful to better explain human influence. In the pristine river (study site 1), when comparing a structural version of our model with the dynamical model we found that structurally central groups such as omnivores and carnivores were not the most important ones dynamically. Instead, primary consumers such as invertebrate grazers and shredders generated a greater dynamical response. Based on the dynamically most important groups, bottom-up control is replaced by the predominant top-down control regime as distance downstream and human disturbance increased. An important finding, potentially explaining the poor structure to dynamics relationship, is that indirect effects are at least as important as direct ones during the simulations. We suggest that our approach and this simulation framework could serve systems-based conservation efforts. Quantitative indicators on the relative importance of trophic groups and the mechanistic modeling of eco-dynamics could greatly contribute to understanding various aspects of functional diversity. PMID:22768346

System Simulation by Recursive Feedback: Coupling a Set of Stand-Alone Subsystem Simulations

NASA Technical Reports Server (NTRS)

Nixon, D. D.

2001-01-01

Conventional construction of digital dynamic system simulations often involves collecting differential equations that model each subsystem, arran g them to a standard form, and obtaining their numerical gin solution as a single coupled, total-system simultaneous set. Simulation by numerical coupling of independent stand-alone subsimulations is a fundamentally different approach that is attractive because, among other things, the architecture naturally facilitates high fidelity, broad scope, and discipline independence. Recursive feedback is defined and discussed as a candidate approach to multidiscipline dynamic system simulation by numerical coupling of self-contained, single-discipline subsystem simulations. A satellite motion example containing three subsystems (orbit dynamics, attitude dynamics, and aerodynamics) has been defined and constructed using this approach. Conventional solution methods are used in the subsystem simulations. Distributed and centralized implementations of coupling have been considered. Numerical results are evaluated by direct comparison with a standard total-system, simultaneous-solution approach.

Simulating the flow of entangled polymers.

PubMed

Masubuchi, Yuichi

2014-01-01

To optimize automation for polymer processing, attempts have been made to simulate the flow of entangled polymers. In industry, fluid dynamics simulations with phenomenological constitutive equations have been practically established. However, to account for molecular characteristics, a method to obtain the constitutive relationship from the molecular structure is required. Molecular dynamics simulations with atomic description are not practical for this purpose; accordingly, coarse-grained models with reduced degrees of freedom have been developed. Although the modeling of entanglement is still a challenge, mesoscopic models with a priori settings to reproduce entangled polymer dynamics, such as tube models, have achieved remarkable success. To use the mesoscopic models as staging posts between atomistic and fluid dynamics simulations, studies have been undertaken to establish links from the coarse-grained model to the atomistic and macroscopic simulations. Consequently, integrated simulations from materials chemistry to predict the macroscopic flow in polymer processing are forthcoming.

Motions and entropies in proteins as seen in NMR relaxation experiments and molecular dynamics simulations.

PubMed

Allnér, Olof; Foloppe, Nicolas; Nilsson, Lennart

2015-01-22

Molecular dynamics simulations of E. coli glutaredoxin1 in water have been performed to relate the dynamical parameters and entropy obtained in NMR relaxation experiments, with results extracted from simulated trajectory data. NMR relaxation is the most widely used experimental method to obtain data on dynamics of proteins, but it is limited to relatively short timescales and to motions of backbone amides or in some cases (13)C-H vectors. By relating the experimental data to the all-atom picture obtained in molecular dynamics simulations, valuable insights on the interpretation of the experiment can be gained. We have estimated the internal dynamics and their timescales by calculating the generalized order parameters (O) for different time windows. We then calculate the quasiharmonic entropy (S) and compare it to the entropy calculated from the NMR-derived generalized order parameter of the amide vectors. Special emphasis is put on characterizing dynamics that are not expressed through the motions of the amide group. The NMR and MD methods suffer from complementary limitations, with NMR being restricted to local vectors and dynamics on a timescale determined by the rotational diffusion of the solute, while in simulations, it may be difficult to obtain sufficient sampling to ensure convergence of the results. We also evaluate the amount of sampling obtained with molecular dynamics simulations and how it is affected by the length of individual simulations, by clustering of the sampled conformations. We find that two structural turns act as hinges, allowing the α helix between them to undergo large, long timescale motions that cannot be detected in the time window of the NMR dipolar relaxation experiments. We also show that the entropy obtained from the amide vector does not account for correlated motions of adjacent residues. Finally, we show that the sampling in a total of 100 ns molecular dynamics simulation can be increased by around 50%, by dividing the trajectory into 10 replicas with different starting velocities.

Dielectric Properties of Poly(ethylene oxide) from Molecular Dynamics Simulations

NASA Technical Reports Server (NTRS)

Smith, Grant D.

1994-01-01

The order, conformations and dynamics of poly(oxyethylene) (POE) melts have been investigated through molecular dynamics simulations. The potential energy functions were determined from detailed ab initio electronic structure calculations of the conformational energies of the model molecules 1,2-dimethoxyethane (DME) and diethylether. The x-ray structure factor for POE from simulation will be compared to experiment. In terms of conformation, simulations reveal that chains are extended in the melt relative to isolated chains due to the presence of strong intermolecular O...H interactions, which occur at the expense of intramolecular O...H interactions. Conformational dynamics about the C-C bond were found to be significantly faster than in polymethylene, while conformational dynamics about the C-O bond even faster than the C-C dynamics. The faster local dynamics in POE relative to polymethylene is consistent with C-13 NMR spin-lattice relaxation experiments. Conformational transitions showed significant second-neighbor correlation, as was found for polymethylene. This correlation of transitions with C-C neighbors was found to be reduced relative to C-O neighbors. Dielectric relaxation from simulation will also be compared with experiment.

Similarities between principal components of protein dynamics and random diffusion

NASA Astrophysics Data System (ADS)

Hess, Berk

2000-12-01

Principal component analysis, also called essential dynamics, is a powerful tool for finding global, correlated motions in atomic simulations of macromolecules. It has become an established technique for analyzing molecular dynamics simulations of proteins. The first few principal components of simulations of large proteins often resemble cosines. We derive the principal components for high-dimensional random diffusion, which are almost perfect cosines. This resemblance between protein simulations and noise implies that for many proteins the time scales of current simulations are too short to obtain convergence of collective motions.

Development of a Dynamically Configurable, Object-Oriented Framework for Distributed, Multi-modal Computational Aerospace Systems Simulation

NASA Technical Reports Server (NTRS)

Afjeh, Abdollah A.; Reed, John A.

2003-01-01

The following reports are presented on this project:A first year progress report on: Development of a Dynamically Configurable,Object-Oriented Framework for Distributed, Multi-modal Computational Aerospace Systems Simulation; A second year progress report on: Development of a Dynamically Configurable, Object-Oriented Framework for Distributed, Multi-modal Computational Aerospace Systems Simulation; An Extensible, Interchangeable and Sharable Database Model for Improving Multidisciplinary Aircraft Design; Interactive, Secure Web-enabled Aircraft Engine Simulation Using XML Databinding Integration; and Improving the Aircraft Design Process Using Web-based Modeling and Simulation.

Dynamics of Protonated Peptide Ion Collisions with Organic Surfaces: Consonance of Simulation and Experiment

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

Pratihar, Subha; Barnes, George L.; Laskin, Julia

In this Perspective mass spectrometry experiments and chemical dynamics simulations are described which have explored the atomistic dynamics of protonated peptide ions, peptide-H+, colliding with organic surfaces. These studies have investigated surface-induced dissociation (SID) for which peptide-H+ fragments upon collision with the surface, peptide-H+ physisorption on the surface, soft landing (SL), and peptide-H+ reaction with the surface, reactive landing (RL). The simulations include QM+MM and QM/MM direct dynamics. For collisions with self-assembled monolayer (SAM) surfaces there is quite good agreement between experiment and simulation in the efficiency of energy transfer to the peptide-H+ ion’s internal degrees of freedom. Both themore » experiments and simulations show two mechanisms for peptide-H+ fragmentation, i.e. shattering and statistical, RRKM dynamics. Mechanisms for SL are probed in simulations of collisions of protonated dialanine with a perfluorinated SAM surface. RL has been studied experimentally for a number of peptide-H+ + surface systems, and qualitative agreement between simulation and experiment is found for two similar systems.« less

Dynamic computer simulations of electrophoresis: three decades of active research.

PubMed

Thormann, Wolfgang; Caslavska, Jitka; Breadmore, Michael C; Mosher, Richard A

2009-06-01

Dynamic models for electrophoresis are based upon model equations derived from the transport concepts in solution together with user-inputted conditions. They are able to predict theoretically the movement of ions and are as such the most versatile tool to explore the fundamentals of electrokinetic separations. Since its inception three decades ago, the state of dynamic computer simulation software and its use has progressed significantly and Electrophoresis played a pivotal role in that endeavor as a large proportion of the fundamental and application papers were published in this periodical. Software is available that simulates all basic electrophoretic systems, including moving boundary electrophoresis, zone electrophoresis, ITP, IEF and EKC, and their combinations under almost exactly the same conditions used in the laboratory. This has been employed to show the detailed mechanisms of many of the fundamental phenomena that occur in electrophoretic separations. Dynamic electrophoretic simulations are relevant for separations on any scale and instrumental format, including free-fluid preparative, gel, capillary and chip electrophoresis. This review includes a historical overview, a survey of current simulators, simulation examples and a discussion of the applications and achievements of dynamic simulation.

Next Generation Extended Lagrangian Quantum-based Molecular Dynamics

NASA Astrophysics Data System (ADS)

Negre, Christian

2017-06-01

A new framework for extended Lagrangian first-principles molecular dynamics simulations is presented, which overcomes shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while maintaining important advantages of the unified extended Lagrangian formulation of density functional theory pioneered by Car and Parrinello three decades ago. The new framework allows, for the first time, energy conserving, linear-scaling Born-Oppenheimer molecular dynamics simulations, which is necessary to study larger and more realistic systems over longer simulation times than previously possible. Expensive, self-consinstent-field optimizations are avoided and normal integration time steps of regular, direct Born-Oppenheimer molecular dynamics can be used. Linear scaling electronic structure theory is presented using a graph-based approach that is ideal for parallel calculations on hybrid computer platforms. For the first time, quantum based Born-Oppenheimer molecular dynamics simulation is becoming a practically feasible approach in simulations of +100,000 atoms-representing a competitive alternative to classical polarizable force field methods. In collaboration with: Anders Niklasson, Los Alamos National Laboratory.

Equivalence of Brownian dynamics and dynamic Monte Carlo simulations in multicomponent colloidal suspensions.

PubMed

Cuetos, Alejandro; Patti, Alessandro

2015-08-01

We propose a simple but powerful theoretical framework to quantitatively compare Brownian dynamics (BD) and dynamic Monte Carlo (DMC) simulations of multicomponent colloidal suspensions. By extending our previous study focusing on monodisperse systems of rodlike colloids, here we generalize the formalism described there to multicomponent colloidal mixtures and validate it by investigating the dynamics in isotropic and liquid crystalline phases containing spherical and rodlike particles. In order to investigate the dynamics of multicomponent colloidal systems by DMC simulations, it is key to determine the elementary time step of each species and establish a unique timescale. This is crucial to consistently study the dynamics of colloidal particles with different geometry. By analyzing the mean-square displacement, the orientation autocorrelation functions, and the self part of the van Hove correlation functions, we show that DMC simulation is a very convenient and reliable technique to describe the stochastic dynamics of any multicomponent colloidal system. Our theoretical formalism can be easily extended to any colloidal system containing size and/or shape polydisperse particles.

Flight Dynamic Simulation of Fighter In the Asymmetric External Store Release Process

NASA Astrophysics Data System (ADS)

Safi’i, Imam; Arifianto, Ony; Nurohman, Chandra

2018-04-01

In the fighter design, it is important to evaluate and analyze the flight dynamic of the aircraft earlier in the development process. One of the case is the dynamics of external store release process. A simulation tool can be used to analyze the fighter/external store system’s dynamics in the preliminary design stage. This paper reports the flight dynamics of Jet Fighter Experiment (JF-1 E) in asymmetric Advance Medium Range Air to Air Missile (AMRAAM) release process through simulations. The JF-1 E and AIM 120 AMRAAAM models are built by using Advanced Aircraft Analysis (AAA) and Missile Datcom software. By using these softwares, the aerodynamic stability and control derivatives can be obtained and used to model the dynamic characteristic of the fighter and the external store. The dynamic system is modeled by using MATLAB/Simulink software. By using this software, both the fighter/external store integration and the external store release process is simulated, and the dynamic of the system can be analyzed.

Molecular dynamics simulations of a K+ channel blocker: Tc1 toxin from Tityus cambridgei.

PubMed

Grottesi, Alessandro; Sansom, Mark S P

2003-01-30

Toxins that block voltage-gated potassium (Kv) channels provide a possible template for improved homology models of the Kv pore. In assessing the interactions of Kv channels and their toxins it is important to determine the dynamic flexibility of the toxins. Multiple 10 ns duration molecular dynamics simulations combined with essential dynamics analysis have been used to explore the flexibility of four different Kv channel-blocking toxins. Three toxins (Tc1, AgTx and ChTx) share a common fold. They also share a common pattern of conformational dynamics, as revealed by essential dynamics analysis of the simulation results. This suggests that some aspects of dynamic behaviour are conserved across a single protein fold class. In each of these three toxins, the residue exhibiting minimum flexibility corresponds to a conserved lysine residue that is suggested to interact with the filter domain of the channel. Thus, comparative simulations reveal functionally important conservation of molecular dynamics as well as protein fold across a family of related toxins.

Application of control theory to dynamic systems simulation

NASA Technical Reports Server (NTRS)

Auslander, D. M.; Spear, R. C.; Young, G. E.

1982-01-01

The application of control theory is applied to dynamic systems simulation. Theory and methodology applicable to controlled ecological life support systems are considered. Spatial effects on system stability, design of control systems with uncertain parameters, and an interactive computing language (PARASOL-II) designed for dynamic system simulation, report quality graphics, data acquisition, and simple real time control are discussed.

Rob Guglielmetti | NREL

Science.gov Websites

2009. Rob's areas of expertise are daylighting, physically based lighting simulation, the integration of lighting simulation with whole-building energy simulations, and high-dynamic range imaging. He has simulation, and high-dynamic range imaging. Rob is an advisory member of the Illuminating Engineering Society

Characterizing rare-event property distributions via replicate molecular dynamics simulations of proteins.

PubMed

Krishnan, Ranjani; Walton, Emily B; Van Vliet, Krystyn J

2009-11-01

As computational resources increase, molecular dynamics simulations of biomolecules are becoming an increasingly informative complement to experimental studies. In particular, it has now become feasible to use multiple initial molecular configurations to generate an ensemble of replicate production-run simulations that allows for more complete characterization of rare events such as ligand-receptor unbinding. However, there are currently no explicit guidelines for selecting an ensemble of initial configurations for replicate simulations. Here, we use clustering analysis and steered molecular dynamics simulations to demonstrate that the configurational changes accessible in molecular dynamics simulations of biomolecules do not necessarily correlate with observed rare-event properties. This informs selection of a representative set of initial configurations. We also employ statistical analysis to identify the minimum number of replicate simulations required to sufficiently sample a given biomolecular property distribution. Together, these results suggest a general procedure for generating an ensemble of replicate simulations that will maximize accurate characterization of rare-event property distributions in biomolecules.

Structure and dynamics of complex liquid water: Molecular dynamics simulation

NASA Astrophysics Data System (ADS)

S, Indrajith V.; Natesan, Baskaran

2015-06-01

We have carried out detailed structure and dynamical studies of complex liquid water using molecular dynamics simulations. Three different model potentials, namely, TIP3P, TIP4P and SPC-E have been used in the simulations, in order to arrive at the best possible potential function that could reproduce the structure of experimental bulk water. All the simulations were performed in the NVE micro canonical ensemble using LAMMPS. The radial distribution functions, gOO, gOH and gHH and the self diffusion coefficient, Ds, were calculated for all three models. We conclude from our results that the structure and dynamical parameters obtained for SPC-E model matched well with the experimental values, suggesting that among the models studied here, the SPC-E model gives the best structure and dynamics of bulk water.

The influence of fatty acids on the GpA dimer interface by coarse-grained molecular dynamics simulation.

PubMed

Flinner, Nadine; Mirus, Oliver; Schleiff, Enrico

2014-08-15

The hydrophobic thickness of membranes, which is manly defined by fatty acids, influences the packing of transmembrane domains of proteins and thus can modulate the activity of these proteins. We analyzed the dynamics of the dimerization of Glycophorin A (GpA) by molecular dynamics simulations to describe the fatty acid dependence of the transmembrane region assembly. GpA represents a well-established model for dimerization of single transmembrane helices containing a GxxxG motif in vitro and in silico. We performed simulations of the dynamics of the NMR-derived dimer as well as self-assembly simulations of monomers in membranes composed of different fatty acid chains and monitored the formed interfaces and their transitions. The observed dimeric interfaces, which also include the one known from NMR, are highly dynamic and converted into each other. The frequency of interface formation and the preferred transitions between interfaces similar to the interface observed by NMR analysis strongly depend on the fatty acid used to build the membrane. Molecular dynamic simulations after adaptation of the helix topology parameters to better represent NMR derived structures of single transmembrane helices yielded an enhanced occurrence of the interface determined by NMR in molecular dynamics simulations. Taken together we give insights into the influence of fatty acids and helix conformation on the dynamics of the transmembrane domain of GpA.

The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation

PubMed Central

Flinner, Nadine; Mirus, Oliver; Schleiff, Enrico

2014-01-01

The hydrophobic thickness of membranes, which is manly defined by fatty acids, influences the packing of transmembrane domains of proteins and thus can modulate the activity of these proteins. We analyzed the dynamics of the dimerization of Glycophorin A (GpA) by molecular dynamics simulations to describe the fatty acid dependence of the transmembrane region assembly. GpA represents a well-established model for dimerization of single transmembrane helices containing a GxxxG motif in vitro and in silico. We performed simulations of the dynamics of the NMR-derived dimer as well as self-assembly simulations of monomers in membranes composed of different fatty acid chains and monitored the formed interfaces and their transitions. The observed dimeric interfaces, which also include the one known from NMR, are highly dynamic and converted into each other. The frequency of interface formation and the preferred transitions between interfaces similar to the interface observed by NMR analysis strongly depend on the fatty acid used to build the membrane. Molecular dynamic simulations after adaptation of the helix topology parameters to better represent NMR derived structures of single transmembrane helices yielded an enhanced occurrence of the interface determined by NMR in molecular dynamics simulations. Taken together we give insights into the influence of fatty acids and helix conformation on the dynamics of the transmembrane domain of GpA. PMID:25196522

Dynamic performance of accommodating intraocular lenses in a negative feedback control system: a simulation-based study.

PubMed

Schor, Clifton M; Bharadwaj, Shrikant R; Burns, Christopher D

2007-07-01

A dynamic model of ocular accommodation is used to simulate the stability and dynamic performance of accommodating intraocular lenses (A-IOLs) that replace the hardened natural ocular lens that is unable to change focus. Accommodation simulations of an older eye with A-IOL materials having biomechanical properties of a younger eye illustrate overshoots and oscillations resulting from decreased visco-elasticity of the A-IOL. Stable dynamics of an A-IOL are restored by adaptation of phasic and tonic neural-control properties of accommodation. Simulations indicate that neural control must be recalibrated to avoid unstable dynamic accommodation with A-IOLs. An interactive web-model of A-IOL illustrating these properties is available at http://schorlab.berkeley.edu.

Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale.

PubMed

Chavent, Matthieu; Duncan, Anna L; Sansom, Mark Sp

2016-10-01

Molecular dynamics simulations provide a computational tool to probe membrane proteins and systems at length scales ranging from nanometers to close to a micrometer, and on microsecond timescales. All atom and coarse-grained simulations may be used to explore in detail the interactions of membrane proteins and specific lipids, yielding predictions of lipid binding sites in good agreement with available structural data. Building on the success of protein-lipid interaction simulations, larger scale simulations reveal crowding and clustering of proteins, resulting in slow and anomalous diffusional dynamics, within realistic models of cell membranes. Current methods allow near atomic resolution simulations of small membrane organelles, and of enveloped viruses to be performed, revealing key aspects of their structure and functionally important dynamics. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Molecular Dynamics Simulations of Shear Induced Transformations in Nitromethane

NASA Astrophysics Data System (ADS)

Larentzos, James; Steele, Brad

2017-06-01

Recent experiments demonstrate that NM undergoes explosive chemical initiation under compressive shear stress. The atomistic dynamics of the shear response of single-crystalline and bi-crystalline nitromethane (NM) are simulated using molecular dynamics simulations under high pressure conditions to aid in interpreting these experiments. The atomic interactions are described using a recently re-optimized ReaxFF-lg potential trained specifically for NM under pressure. The simulations demonstrate that the NM crystal transforms into a disordered state upon sufficient application of shear stress; its maximum value, shear angle, and atomic-scale dynamics being highly dependent on crystallographic orientation of the applied shear. Shear simulations in bi-crystalline NM show more complex behavior resulting in the appearance of the disordered state at the grain boundary.

Molecular Dynamics Simulations of Shear Induced Transformations in Nitromethane

NASA Astrophysics Data System (ADS)

Larentzos, James; Steele, Brad

Recent experiments demonstrate that NM undergoes explosive chemical initiation under compressive shear stress. The atomistic dynamics of the shear response of single-crystalline and bi-crystalline nitromethane (NM) are simulated using molecular dynamics simulations under high pressure conditions to aid in interpreting these experiments. The atomic interactions are described using a recently re-optimized ReaxFF-lg potential trained specifically for NM under pressure. The simulations demonstrate that the NM crystal transforms into a disordered state upon sufficient application of shear stress; its maximum value, shear angle, and atomic-scale dynamics being highly dependent on crystallographic orientation of the applied shear. Shear simulations in bi-crystalline NM show more complex behavior resulting in the appearance of the disordered state at the grain boundary.

Near real-time traffic routing

NASA Technical Reports Server (NTRS)

Yang, Chaowei (Inventor); Xie, Jibo (Inventor); Zhou, Bin (Inventor); Cao, Ying (Inventor)

2012-01-01

A near real-time physical transportation network routing system comprising: a traffic simulation computing grid and a dynamic traffic routing service computing grid. The traffic simulator produces traffic network travel time predictions for a physical transportation network using a traffic simulation model and common input data. The physical transportation network is divided into a multiple sections. Each section has a primary zone and a buffer zone. The traffic simulation computing grid includes multiple of traffic simulation computing nodes. The common input data includes static network characteristics, an origin-destination data table, dynamic traffic information data and historical traffic data. The dynamic traffic routing service computing grid includes multiple dynamic traffic routing computing nodes and generates traffic route(s) using the traffic network travel time predictions.

Compression Behavior and Energy Absorption of Aluminum Alloy AA6061 Tubes with Multiple Holes

NASA Astrophysics Data System (ADS)

Simhachalam, Bade; Lakshmana Rao, C.; Srinivas, Krishna

2014-05-01

In this article, compression behavior and energy absorption of aluminum alloy AA6061 tubes are investigated both experimentally and numerically. Static and dynamic simulations are done using LS-Dyna Software for AA6061 tubes. True stress-plastic strain curves from the tensile test are used in the static and dynamic simulations of AA6061 tubes. The energy absorption values between experimental compression results and numeral simulation are found to be in good agreement. Dynamic simulations are done with drop velocity of up to 10 m/s to understand the inertia effects on energy absorption. The deformed modes from the numerical simulation are compared between tubes with and without holes in static and dynamic conditions.

Code Samples Used for Complexity and Control

NASA Astrophysics Data System (ADS)

Ivancevic, Vladimir G.; Reid, Darryn J.

2015-11-01

The following sections are included: * MathematicaⓇ Code * Generic Chaotic Simulator * Vector Differential Operators * NLS Explorer * 2C++ Code * C++ Lambda Functions for Real Calculus * Accelerometer Data Processor * Simple Predictor-Corrector Integrator * Solving the BVP with the Shooting Method * Linear Hyperbolic PDE Solver * Linear Elliptic PDE Solver * Method of Lines for a Set of the NLS Equations * C# Code * Iterative Equation Solver * Simulated Annealing: A Function Minimum * Simple Nonlinear Dynamics * Nonlinear Pendulum Simulator * Lagrangian Dynamics Simulator * Complex-Valued Crowd Attractor Dynamics * Freeform Fortran Code * Lorenz Attractor Simulator * Complex Lorenz Attractor * Simple SGE Soliton * Complex Signal Presentation * Gaussian Wave Packet * Hermitian Matrices * Euclidean L2-Norm * Vector/Matrix Operations * Plain C-Code: Levenberg-Marquardt Optimizer * Free Basic Code: 2D Crowd Dynamics with 3000 Agents

Liquid li structure and dynamics: A comparison between OFDFT and second nearest-neighbor embedded-atom method

DOE PAGES

Chen, Mohan; Vella, Joseph R.; Panagiotopoulos, Athanassios Z.; ...

2015-04-08

The structure and dynamics of liquid lithium are studied using two simulation methods: orbital-free (OF) first-principles molecular dynamics (MD), which employs OF density functional theory (DFT), and classical MD utilizing a second nearest-neighbor embedded-atom method potential. The properties we studied include the dynamic structure factor, the self-diffusion coefficient, the dispersion relation, the viscosity, and the bond angle distribution function. Our simulation results were compared to available experimental data when possible. Each method has distinct advantages and disadvantages. For example, OFDFT gives better agreement with experimental dynamic structure factors, yet is more computationally demanding than classical simulations. Classical simulations can accessmore » a broader temperature range and longer time scales. The combination of first-principles and classical simulations is a powerful tool for studying properties of liquid lithium.« less

Advanced Simulation of Coupled Earthquake and Tsunami Events

NASA Astrophysics Data System (ADS)

Behrens, Joern

2013-04-01

Tsunami-Earthquakes represent natural catastrophes threatening lives and well-being of societies in a solitary and unexpected extreme event as tragically demonstrated in Sumatra (2004), Samoa (2009), Chile (2010), or Japan (2011). Both phenomena are consequences of the complex system of interactions of tectonic stress, fracture mechanics, rock friction, rupture dynamics, fault geometry, ocean bathymetry, and coastline geometry. The ASCETE project forms an interdisciplinary research consortium that couples the most advanced simulation technologies for earthquake rupture dynamics and tsunami propagation to understand the fundamental conditions of tsunami generation. We report on the latest research results in physics-based dynamic rupture and tsunami wave propagation simulation, using unstructured and adaptive meshes with continuous and discontinuous Galerkin discretization approaches. Coupling both simulation tools - the physics-based dynamic rupture simulation and the hydrodynamic tsunami wave propagation - will give us the possibility to conduct highly realistic studies of the interaction of rupture dynamics and tsunami impact characteristics.

Accelerated molecular dynamics: A promising and efficient simulation method for biomolecules

NASA Astrophysics Data System (ADS)

Hamelberg, Donald; Mongan, John; McCammon, J. Andrew

2004-06-01

Many interesting dynamic properties of biological molecules cannot be simulated directly using molecular dynamics because of nanosecond time scale limitations. These systems are trapped in potential energy minima with high free energy barriers for large numbers of computational steps. The dynamic evolution of many molecular systems occurs through a series of rare events as the system moves from one potential energy basin to another. Therefore, we have proposed a robust bias potential function that can be used in an efficient accelerated molecular dynamics approach to simulate the transition of high energy barriers without any advance knowledge of the location of either the potential energy wells or saddle points. In this method, the potential energy landscape is altered by adding a bias potential to the true potential such that the escape rates from potential wells are enhanced, which accelerates and extends the time scale in molecular dynamics simulations. Our definition of the bias potential echoes the underlying shape of the potential energy landscape on the modified surface, thus allowing for the potential energy minima to be well defined, and hence properly sampled during the simulation. We have shown that our approach, which can be extended to biomolecules, samples the conformational space more efficiently than normal molecular dynamics simulations, and converges to the correct canonical distribution.

Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics: strength in unity.

PubMed

Papaleo, Elena

2015-01-01

In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations.

Peptide crystal simulations reveal hidden dynamics

PubMed Central

Janowski, Pawel A.; Cerutti, David S.; Holton, James; Case, David A.

2013-01-01

Molecular dynamics simulations of biomolecular crystals at atomic resolution have the potential to recover information on dynamics and heterogeneity hidden in the X-ray diffraction data. We present here 9.6 microseconds of dynamics in a small helical peptide crystal with 36 independent copies of the unit cell. The average simulation structure agrees with experiment to within 0.28 Å backbone and 0.42 Å all-atom rmsd; a model refined against the average simulation density agrees with the experimental structure to within 0.20 Å backbone and 0.33 Å all-atom rmsd. The R-factor between the experimental structure factors and those derived from this unrestrained simulation is 23% to 1.0 Å resolution. The B-factors for most heavy atoms agree well with experiment (Pearson correlation of 0.90), but B-factors obtained by refinement against the average simulation density underestimate the coordinate fluctuations in the underlying simulation where the simulation samples alternate conformations. A dynamic flow of water molecules through channels within the crystal lattice is observed, yet the average water density is in remarkable agreement with experiment. A minor population of unit cells is characterized by reduced water content, 310 helical propensity and a gauche(−) side-chain rotamer for one of the valine residues. Careful examination of the experimental data suggests that transitions of the helices are a simulation artifact, although there is indeed evidence for alternate valine conformers and variable water content. This study highlights the potential for crystal simulations to detect dynamics and heterogeneity in experimental diffraction data, as well as to validate computational chemistry methods. PMID:23631449

Convergence and reproducibility in molecular dynamics simulations of the DNA duplex d(GCACGAACGAACGAACGC)

PubMed Central

Galindo-Murillo, Rodrigo; Roe, Daniel R.; Cheatham, Thomas E.

2014-01-01

Background The structure and dynamics of DNA are critically related to its function. Molecular dynamics (MD) simulations augment experiment by providing detailed information about the atomic motions. However, to date the simulations have not been long enough for convergence of the dynamics and structural properties of DNA. Methods MD simulations performed with AMBER using the ff99SB force field with the parmbsc0 modifications, including ensembles of independent simulations, were compared to long timescale MD performed with the specialized Anton MD engine on the B-DNA structure d(GCACGAACGAACGAACGC). To assess convergence, the decay of the average RMSD values over longer and longer time intervals was evaluated in addition to assessing convergence of the dynamics via the Kullback-Leibler divergence of principal component projection histograms. Results These MD simulations —including one of the longest simulations of DNA published to date at ~44 μs—surprisingly suggest that the structure and dynamics of the DNA helix, neglecting the terminal base pairs, are essentially fully converged on the ~1–5 μs timescale. Conclusions We can now reproducibly converge the structure and dynamics of B-DNA helices, omitting the terminal base pairs, on the μs time scale with both the AMBER and CHARMM C36 nucleic acid force fields. Results from independent ensembles of simulations starting from different initial conditions, when aggregated, match the results from long timescale simulations on the specialized Anton MD engine. General Significance With access to large-scale GPU resources or the specialized MD engine “Anton” it is possibly for a variety of molecular systems to reproducibly and reliably converge the conformational ensemble of sampled structures. PMID:25219455

A Quantitative Dynamic Simulation of Bremia lactucae Airborne Conidia Concentration above a Lettuce Canopy.

PubMed

Fall, Mamadou Lamine; Van der Heyden, Hervé; Carisse, Odile

2016-01-01

Lettuce downy mildew, caused by the oomycete Bremia lactucae Regel, is a major threat to lettuce production worldwide. Lettuce downy mildew is a polycyclic disease driven by airborne spores. A weather-based dynamic simulation model for B. lactucae airborne spores was developed to simulate the aerobiological characteristics of the pathogen. The model was built using the STELLA platform by following the system dynamics methodology. The model was developed using published equations describing disease subprocesses (e.g., sporulation) and assembled knowledge of the interactions among pathogen, host, and weather. The model was evaluated with four years of independent data by comparing model simulations with observations of hourly and daily airborne spore concentrations. The results show an accurate simulation of the trend and shape of B. lactucae temporal dynamics of airborne spore concentration. The model simulated hourly and daily peaks in airborne spore concentrations. More than 95% of the simulation runs, the daily-simulated airborne conidia concentration was 0 when airborne conidia were not observed. Also, the relationship between the simulated and the observed airborne spores was linear. In more than 94% of the simulation runs, the proportion of the linear variation in the hourly-observed values explained by the variation in the hourly-simulated values was greater than 0.7 in all years except one. Most of the errors came from the deviation from the 1:1 line, and the proportion of errors due to the model bias was low. This model is the only dynamic model developed to mimic the dynamics of airborne inoculum and represents an initial step towards improved lettuce downy mildew understanding, forecasting and management.

A Quantitative Dynamic Simulation of Bremia lactucae Airborne Conidia Concentration above a Lettuce Canopy

PubMed Central

Fall, Mamadou Lamine; Van der Heyden, Hervé; Carisse, Odile

2016-01-01

Lettuce downy mildew, caused by the oomycete Bremia lactucae Regel, is a major threat to lettuce production worldwide. Lettuce downy mildew is a polycyclic disease driven by airborne spores. A weather-based dynamic simulation model for B. lactucae airborne spores was developed to simulate the aerobiological characteristics of the pathogen. The model was built using the STELLA platform by following the system dynamics methodology. The model was developed using published equations describing disease subprocesses (e.g., sporulation) and assembled knowledge of the interactions among pathogen, host, and weather. The model was evaluated with four years of independent data by comparing model simulations with observations of hourly and daily airborne spore concentrations. The results show an accurate simulation of the trend and shape of B. lactucae temporal dynamics of airborne spore concentration. The model simulated hourly and daily peaks in airborne spore concentrations. More than 95% of the simulation runs, the daily-simulated airborne conidia concentration was 0 when airborne conidia were not observed. Also, the relationship between the simulated and the observed airborne spores was linear. In more than 94% of the simulation runs, the proportion of the linear variation in the hourly-observed values explained by the variation in the hourly-simulated values was greater than 0.7 in all years except one. Most of the errors came from the deviation from the 1:1 line, and the proportion of errors due to the model bias was low. This model is the only dynamic model developed to mimic the dynamics of airborne inoculum and represents an initial step towards improved lettuce downy mildew understanding, forecasting and management. PMID:26953691

SS-mPMG and SS-GA: tools for finding pathways and dynamic simulation of metabolic networks.

PubMed

Katsuragi, Tetsuo; Ono, Naoaki; Yasumoto, Keiichi; Altaf-Ul-Amin, Md; Hirai, Masami Y; Sriyudthsak, Kansuporn; Sawada, Yuji; Yamashita, Yui; Chiba, Yukako; Onouchi, Hitoshi; Fujiwara, Toru; Naito, Satoshi; Shiraishi, Fumihide; Kanaya, Shigehiko

2013-05-01

Metabolomics analysis tools can provide quantitative information on the concentration of metabolites in an organism. In this paper, we propose the minimum pathway model generator tool for simulating the dynamics of metabolite concentrations (SS-mPMG) and a tool for parameter estimation by genetic algorithm (SS-GA). SS-mPMG can extract a subsystem of the metabolic network from the genome-scale pathway maps to reduce the complexity of the simulation model and automatically construct a dynamic simulator to evaluate the experimentally observed behavior of metabolites. Using this tool, we show that stochastic simulation can reproduce experimentally observed dynamics of amino acid biosynthesis in Arabidopsis thaliana. In this simulation, SS-mPMG extracts the metabolic network subsystem from published databases. The parameters needed for the simulation are determined using a genetic algorithm to fit the simulation results to the experimental data. We expect that SS-mPMG and SS-GA will help researchers to create relevant metabolic networks and carry out simulations of metabolic reactions derived from metabolomics data.

Complex double-mass dynamic model of rotor on thrust foil gas dynamic bearings

NASA Astrophysics Data System (ADS)

Sytin, A.; Babin, A.; Vasin, S.

2017-08-01

The present paper considers simulation of a rotor’s dynamics behaviour on thrust foil gas dynamic bearings based on simultaneous solution of gas dynamics differential equations, equations of theory of elasticity, motion equations and some additional equations. A double-mass dynamic system was considered during the rotor’s motion simulation which allows not only evaluation of rotor’s dynamic behaviour, but also to evaluate the influence of operational and load parameters on the dynamics of the rotor-bearing system.

Experimental simulation of decoherence in photonics qudits

PubMed Central

Marques, B.; Matoso, A. A.; Pimenta, W. M.; Gutiérrez-Esparza, A. J.; Santos, M. F.; Pádua, S.

2015-01-01

We experimentally perform the simulation of open quantum dynamics in single-qudit systems. Using a spatial light modulator as a dissipative optical device, we implement dissipative-dynamical maps onto qudits encoded in the transverse momentum of spontaneous parametric down-converted photon pairs. We show a well-controlled technique to prepare entangled qudits states as well as to implement dissipative local measurements; the latter realize two specific dynamics: dephasing and amplitude damping. Our work represents a new analogy-dynamical experiment for simulating an open quantum system. PMID:26527330

Gamma ray observatory dynamics simulator in Ada (GRODY)

NASA Technical Reports Server (NTRS)

1990-01-01

This experiment involved the parallel development of dynamics simulators for the Gamma Ray Observatory in both FORTRAN and Ada for the purpose of evaluating the applicability of Ada to the NASA/Goddard Space Flight Center's flight dynamics environment. The experiment successfully demonstrated that Ada is a viable, valuable technology for use in this environment. In addition to building a simulator, the Ada team evaluated training approaches, developed an Ada methodology appropriate to the flight dynamics environment, and established a baseline for evaluating future Ada projects.

Brownian dynamics simulation of protein diffusion in crowded environments

NASA Astrophysics Data System (ADS)

Mereghetti, Paolo; Wade, Rebecca C.

2013-02-01

High macromolecular concentrations are a distinguishing feature of living organisms. Understanding how the high concentration of solutes affects the dynamic properties of biological macromolecules is fundamental for the comprehension of biological processes in living systems. We first describe the development of a Brownian dynamics simulation methodology to investigate the dynamic and structural properties of protein solutions using atomic-detail protein structures. We then discuss insights obtained from applying this approach to simulation of solutions of a range of types of proteins.

Digital Quantum Simulation of Z2 Lattice Gauge Theories with Dynamical Fermionic Matter

NASA Astrophysics Data System (ADS)

Zohar, Erez; Farace, Alessandro; Reznik, Benni; Cirac, J. Ignacio

2017-02-01

We propose a scheme for digital quantum simulation of lattice gauge theories with dynamical fermions. Using a layered optical lattice with ancilla atoms that can move and interact with the other atoms (simulating the physical degrees of freedom), we obtain a stroboscopic dynamics which yields the four-body plaquette interactions, arising in models with (2 +1 ) and higher dimensions, without the use of perturbation theory. As an example we show how to simulate a Z2 model in (2 +1 ) dimensions.

Robust state preparation in quantum simulations of Dirac dynamics

NASA Astrophysics Data System (ADS)

Song, Xue-Ke; Deng, Fu-Guo; Lamata, Lucas; Muga, J. G.

2017-02-01

A nonrelativistic system such as an ultracold trapped ion may perform a quantum simulation of a Dirac equation dynamics under specific conditions. The resulting Hamiltonian and dynamics are highly controllable, but the coupling between momentum and internal levels poses some difficulties to manipulate the internal states accurately in wave packets. We use invariants of motion to inverse engineer robust population inversion processes with a homogeneous, time-dependent simulated electric field. This exemplifies the usefulness of inverse-engineering techniques to improve the performance of quantum simulation protocols.

Dynamic Simulation of AN Helium Refrigerator

NASA Astrophysics Data System (ADS)

Deschildre, C.; Barraud, A.; Bonnay, P.; Briend, P.; Girard, A.; Poncet, J. M.; Roussel, P.; Sequeira, S. E.

2008-03-01

A dynamic simulation of a large scale existing refrigerator has been performed using the software Aspen Hysys®. The model comprises the typical equipments of a cryogenic system: heat exchangers, expanders, helium phase separators and cold compressors. It represents the 400 W @ 1.8 K Test Facility located at CEA—Grenoble. This paper describes the model development and shows the possibilities and limitations of the dynamic module of Aspen Hysys®. Then, comparison between simulation results and experimental data are presented; the simulation of cooldown process was also performed.

Digital Quantum Simulation of Z_{2} Lattice Gauge Theories with Dynamical Fermionic Matter.

PubMed

Zohar, Erez; Farace, Alessandro; Reznik, Benni; Cirac, J Ignacio

2017-02-17

We propose a scheme for digital quantum simulation of lattice gauge theories with dynamical fermions. Using a layered optical lattice with ancilla atoms that can move and interact with the other atoms (simulating the physical degrees of freedom), we obtain a stroboscopic dynamics which yields the four-body plaquette interactions, arising in models with (2+1) and higher dimensions, without the use of perturbation theory. As an example we show how to simulate a Z_{2} model in (2+1) dimensions.

A Low Cost Microcomputer System for Process Dynamics and Control Simulations.

ERIC Educational Resources Information Center

Crowl, D. A.; Durisin, M. J.

1983-01-01

Discusses a video simulator microcomputer system used to provide real-time demonstrations to strengthen students' understanding of process dynamics and control. Also discusses hardware/software and simulations developed using the system. The four simulations model various configurations of a process liquid level tank system. (JN)

System Simulation by Recursive Feedback: Coupling A Set of Stand-Alone Subsystem Simulations

NASA Technical Reports Server (NTRS)

Nixon, Douglas D.; Hanson, John M. (Technical Monitor)

2002-01-01

Recursive feedback is defined and discussed as a framework for development of specific algorithms and procedures that propagate the time-domain solution for a dynamical system simulation consisting of multiple numerically coupled self-contained stand-alone subsystem simulations. A satellite motion example containing three subsystems (other dynamics, attitude dynamics, and aerodynamics) has been defined and constructed using this approach. Conventional solution methods are used in the subsystem simulations. Centralized and distributed versions of coupling structure have been addressed. Numerical results are evaluated by direct comparison with a standard total-system simultaneous-solution approach.

Validation of Potential Models for Li2O in Classical Molecular Dynamics Simulation

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

Oda, Takuji; Oya, Yasuhisa; Tanaka, Satoru

2007-08-01

Four Buckingham-type pairwise potential models for Li2O were assessed by molecular static and dynamics simulations. In the static simulation, all models afforded acceptable agreement with experimental values and ab initio calculation results for the crystalline properties. Moreover, the superionic phase transition was realized in the dynamics simulation. However, the Li diffusivity and the lattice expansion were not adequately reproduced at the same time by any model. When using these models in future radiation simulation, these features should be taken into account, in order to reduce the model dependency of the results.

FAST Simulation Tool Containing Methods for Predicting the Dynamic Response of Wind Turbines

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

Jonkman, Jason

2015-08-12

FAST is a simulation tool (computer software) for modeling tlie dynamic response of horizontal-axis wind turbines. FAST employs a combined modal and multibody structural-dynamics formulation in the time domain.

Molecular dynamics simulation of low-energy recoil events in titanate pyrochlores

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

Dong, Liyuan; Setyawan, Wahyu; Li, Yuhong

2017-01-01

Molecular dynamics simulations of low-energy displacements in titanate pyrochlores have been carried out along three main directions, to determineE dfor A, Ti and O, corresponding defect configurations, and defect formation dynamics.

Explicit symplectic algorithms based on generating functions for relativistic charged particle dynamics in time-dependent electromagnetic field

NASA Astrophysics Data System (ADS)

Zhang, Ruili; Wang, Yulei; He, Yang; Xiao, Jianyuan; Liu, Jian; Qin, Hong; Tang, Yifa

2018-02-01

Relativistic dynamics of a charged particle in time-dependent electromagnetic fields has theoretical significance and a wide range of applications. The numerical simulation of relativistic dynamics is often multi-scale and requires accurate long-term numerical simulations. Therefore, explicit symplectic algorithms are much more preferable than non-symplectic methods and implicit symplectic algorithms. In this paper, we employ the proper time and express the Hamiltonian as the sum of exactly solvable terms and product-separable terms in space-time coordinates. Then, we give the explicit symplectic algorithms based on the generating functions of orders 2 and 3 for relativistic dynamics of a charged particle. The methodology is not new, which has been applied to non-relativistic dynamics of charged particles, but the algorithm for relativistic dynamics has much significance in practical simulations, such as the secular simulation of runaway electrons in tokamaks.

Space station dynamics, attitude control and momentum management

NASA Technical Reports Server (NTRS)

Sunkel, John W.; Singh, Ramen P.; Vengopal, Ravi

1989-01-01

The Space Station Attitude Control System software test-bed provides a rigorous environment for the design, development and functional verification of GN and C algorithms and software. The approach taken for the simulation of the vehicle dynamics and environmental models using a computationally efficient algorithm is discussed. The simulation includes capabilities for docking/berthing dynamics, prescribed motion dynamics associated with the Mobile Remote Manipulator System (MRMS) and microgravity disturbances. The vehicle dynamics module interfaces with the test-bed through the central Communicator facility which is in turn driven by the Station Control Simulator (SCS) Executive. The Communicator addresses issues such as the interface between the discrete flight software and the continuous vehicle dynamics, and multi-programming aspects such as the complex flow of control in real-time programs. Combined with the flight software and redundancy management modules, the facility provides a flexible, user-oriented simulation platform.

Supersonic Flight Dynamics Test 1 - Post-Flight Assessment of Simulation Performance

NASA Technical Reports Server (NTRS)

Dutta, Soumyo; Bowes, Angela L.; Striepe, Scott A.; Davis, Jody L.; Queen, Eric M.; Blood, Eric M.; Ivanov, Mark C.

2015-01-01

NASA's Low Density Supersonic Decelerator (LDSD) project conducted its first Supersonic Flight Dynamics Test (SFDT-1) on June 28, 2014. Program to Optimize Simulated Trajectories II (POST2) was one of the flight dynamics codes used to simulate and predict the flight performance and Monte Carlo analysis was used to characterize the potential flight conditions experienced by the test vehicle. This paper compares the simulation predictions with the reconstructed trajectory of SFDT-1. Additionally, off-nominal conditions seen during flight are modeled in post-flight simulations to find the primary contributors that reconcile the simulation with flight data. The results of these analyses are beneficial for the pre-flight simulation and targeting of the follow-on SFDT flights currently scheduled for summer 2015.

Influence of feedbacks from simulated crop growth on integrated regional hydrologic simulations under climate scenarios

NASA Astrophysics Data System (ADS)

van Walsum, P. E. V.

2011-11-01

Climate change impact modelling of hydrologic responses is hampered by climate-dependent model parameterizations. Reducing this dependency was one of the goals of extending the regional hydrologic modelling system SIMGRO with a two-way coupling to the crop growth simulation model WOFOST. The coupling includes feedbacks to the hydrologic model in terms of the root zone depth, soil cover, leaf area index, interception storage capacity, crop height and crop factor. For investigating whether such feedbacks lead to significantly different simulation results, two versions of the model coupling were set up for a test region: one with exogenous vegetation parameters, the "static" model, and one with endogenous simulation of the crop growth, the "dynamic" model WOFOST. The used parameterization methods of the static/dynamic vegetation models ensure that for the current climate the simulated long-term average of the actual evapotranspiration is the same for both models. Simulations were made for two climate scenarios. Owing to the higher temperatures in combination with a higher CO2-concentration of the atmosphere, a forward time shift of the crop development is simulated in the dynamic model; the used arable land crop, potatoes, also shows a shortening of the growing season. For this crop, a significant reduction of the potential transpiration is simulated compared to the static model, in the example by 15% in a warm, dry year. In consequence, the simulated crop water stress (the unit minus the relative transpiration) is lower when the dynamic model is used; also the simulated increase of crop water stress due to climate change is lower; in the example, the simulated increase is 15 percentage points less (of 55) than when a static model is used. The static/dynamic models also simulate different absolute values of the transpiration. The difference is most pronounced for potatoes at locations with ample moisture supply; this supply can either come from storage release of a good soil or from capillary rise. With good supply of moisture, the dynamic model simulates up to 10% less actual evapotranspiration than the static one in the example. This can lead to cases where the dynamic model predicts a slight increase of the recharge in a climate scenario, where the static model predicts a decrease. The use of a dynamic model also affects the simulated demand for surface water from external sources; especially the timing is affected. The proposed modelling approach uses postulated relationships that require validation with controlled field trials. In the Netherlands there is a lack of experimental facilities for performing such validations.

Man-in-the-control-loop simulation of manipulators

NASA Technical Reports Server (NTRS)

Chang, J. L.; Lin, Tsung-Chieh; Yae, K. Harold

1989-01-01

A method to achieve man-in-the-control-loop simulation is presented. Emerging real-time dynamics simulation suggests a potential for creating an interactive design workstation with a human operator in the control loop. The recursive formulation for multibody dynamics simulation is studied to determine requirements for man-in-the-control-loop simulation. High speed computer graphics techniques provides realistic visual cues for the simulator. Backhoe and robot arm simulations are implemented to demonstrate the capability of man-in-the-control-loop simulation.

Wavelet-based surrogate time series for multiscale simulation of heterogeneous catalysis

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

Savara, Aditya Ashi; Daw, C. Stuart; Xiong, Qingang

We propose a wavelet-based scheme that encodes the essential dynamics of discrete microscale surface reactions in a form that can be coupled with continuum macroscale flow simulations with high computational efficiency. This makes it possible to simulate the dynamic behavior of reactor-scale heterogeneous catalysis without requiring detailed concurrent simulations at both the surface and continuum scales using different models. Our scheme is based on the application of wavelet-based surrogate time series that encodes the essential temporal and/or spatial fine-scale dynamics at the catalyst surface. The encoded dynamics are then used to generate statistically equivalent, randomized surrogate time series, which canmore » be linked to the continuum scale simulation. As a result, we illustrate an application of this approach using two different kinetic Monte Carlo simulations with different characteristic behaviors typical for heterogeneous chemical reactions.« less

Molecular dynamics and dynamic Monte-Carlo simulation of irradiation damage with focused ion beams

NASA Astrophysics Data System (ADS)

Ohya, Kaoru

2017-03-01

The focused ion beam (FIB) has become an important tool for micro- and nanostructuring of samples such as milling, deposition and imaging. However, this leads to damage of the surface on the nanometer scale from implanted projectile ions and recoiled material atoms. It is therefore important to investigate each kind of damage quantitatively. We present a dynamic Monte-Carlo (MC) simulation code to simulate the morphological and compositional changes of a multilayered sample under ion irradiation and a molecular dynamics (MD) simulation code to simulate dose-dependent changes in the backscattering-ion (BSI)/secondary-electron (SE) yields of a crystalline sample. Recent progress in the codes for research to simulate the surface morphology and Mo/Si layers intermixing in an EUV lithography mask irradiated with FIBs, and the crystalline orientation effect on BSI and SE yields relating to the channeling contrast in scanning ion microscopes, is also presented.

Wavelet-based surrogate time series for multiscale simulation of heterogeneous catalysis

DOE PAGES

Savara, Aditya Ashi; Daw, C. Stuart; Xiong, Qingang; ...

2016-01-28

We propose a wavelet-based scheme that encodes the essential dynamics of discrete microscale surface reactions in a form that can be coupled with continuum macroscale flow simulations with high computational efficiency. This makes it possible to simulate the dynamic behavior of reactor-scale heterogeneous catalysis without requiring detailed concurrent simulations at both the surface and continuum scales using different models. Our scheme is based on the application of wavelet-based surrogate time series that encodes the essential temporal and/or spatial fine-scale dynamics at the catalyst surface. The encoded dynamics are then used to generate statistically equivalent, randomized surrogate time series, which canmore » be linked to the continuum scale simulation. As a result, we illustrate an application of this approach using two different kinetic Monte Carlo simulations with different characteristic behaviors typical for heterogeneous chemical reactions.« less

Ultrafast spectroscopy reveals subnanosecond peptide conformational dynamics and validates molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Spörlein, Sebastian; Carstens, Heiko; Satzger, Helmut; Renner, Christian; Behrendt, Raymond; Moroder, Luis; Tavan, Paul; Zinth, Wolfgang; Wachtveitl, Josef

2002-06-01

Femtosecond time-resolved spectroscopy on model peptides with built-in light switches combined with computer simulation of light-triggered motions offers an attractive integrated approach toward the understanding of peptide conformational dynamics. It was applied to monitor the light-induced relaxation dynamics occurring on subnanosecond time scales in a peptide that was backbone-cyclized with an azobenzene derivative as optical switch and spectroscopic probe. The femtosecond spectra permit the clear distinguishing and characterization of the subpicosecond photoisomerization of the chromophore, the subsequent dissipation of vibrational energy, and the subnanosecond conformational relaxation of the peptide. The photochemical cis/trans-isomerization of the chromophore and the resulting peptide relaxations have been simulated with molecular dynamics calculations. The calculated reaction kinetics, as monitored by the energy content of the peptide, were found to match the spectroscopic data. Thus we verify that all-atom molecular dynamics simulations can quantitatively describe the subnanosecond conformational dynamics of peptides, strengthening confidence in corresponding predictions for longer time scales.

Dynamical simulation of E-ELT segmented primary mirror

NASA Astrophysics Data System (ADS)

Sedghi, B.; Muller, M.; Bauvir, B.

2011-09-01

The dynamical behavior of the primary mirror (M1) has an important impact on the control of the segments and the performance of the telescope. Control of large segmented mirrors with a large number of actuators and sensors and multiple control loops in real life is a challenging problem. In virtual life, modeling, simulation and analysis of the M1 bears similar difficulties and challenges. In order to capture the dynamics of the segment subunits (high frequency modes) and the telescope back structure (low frequency modes), high order dynamical models with a very large number of inputs and outputs need to be simulated. In this paper, different approaches for dynamical modeling and simulation of the M1 segmented mirror subject to various perturbations, e.g. sensor noise, wind load, vibrations, earthquake are presented.

Review of Dynamic Modeling and Simulation of Large Scale Belt Conveyor System

NASA Astrophysics Data System (ADS)

He, Qing; Li, Hong

Belt conveyor is one of the most important devices to transport bulk-solid material for long distance. Dynamic analysis is the key to decide whether the design is rational in technique, safe and reliable in running, feasible in economy. It is very important to study dynamic properties, improve efficiency and productivity, guarantee conveyor safe, reliable and stable running. The dynamic researches and applications of large scale belt conveyor are discussed. The main research topics, the state-of-the-art of dynamic researches on belt conveyor are analyzed. The main future works focus on dynamic analysis, modeling and simulation of main components and whole system, nonlinear modeling, simulation and vibration analysis of large scale conveyor system.

Generalized dynamic engine simulation techniques for the digital computer

NASA Technical Reports Server (NTRS)

Sellers, J.; Teren, F.

1974-01-01

Recently advanced simulation techniques have been developed for the digital computer and used as the basis for development of a generalized dynamic engine simulation computer program, called DYNGEN. This computer program can analyze the steady state and dynamic performance of many kinds of aircraft gas turbine engines. Without changes to the basic program, DYNGEN can analyze one- or two-spool turbofan engines. The user must supply appropriate component performance maps and design-point information. Examples are presented to illustrate the capabilities of DYNGEN in the steady state and dynamic modes of operation. The analytical techniques used in DYNGEN are briefly discussed, and its accuracy is compared with a comparable simulation using the hybrid computer. The impact of DYNGEN and similar all-digital programs on future engine simulation philosophy is also discussed.

Generalized dynamic engine simulation techniques for the digital computer

NASA Technical Reports Server (NTRS)

Sellers, J.; Teren, F.

1974-01-01

Recently advanced simulation techniques have been developed for the digital computer and used as the basis for development of a generalized dynamic engine simulation computer program, called DYNGEN. This computer program can analyze the steady state and dynamic performance of many kinds of aircraft gas turbine engines. Without changes to the basic program DYNGEN can analyze one- or two-spool turbofan engines. The user must supply appropriate component performance maps and design-point information. Examples are presented to illustrate the capabilities of DYNGEN in the steady state and dynamic modes of operation. The analytical techniques used in DYNGEN are briefly discussed, and its accuracy is compared with a comparable simulation using the hybrid computer. The impact of DYNGEN and similar all-digital programs on future engine simulation philosophy is also discussed.

Generalized dynamic engine simulation techniques for the digital computers

NASA Technical Reports Server (NTRS)

Sellers, J.; Teren, F.

1975-01-01

Recently advanced simulation techniques have been developed for the digital computer and used as the basis for development of a generalized dynamic engine simulation computer program, called DYNGEN. This computer program can analyze the steady state and dynamic performance of many kinds of aircraft gas turbine engines. Without changes to the basic program, DYNGEN can analyze one- or two-spool turbofan engines. The user must supply appropriate component performance maps and design point information. Examples are presented to illustrate the capabilities of DYNGEN in the steady state and dynamic modes of operation. The analytical techniques used in DYNGEN are briefly discussed, and its accuracy is compared with a comparable simulation using the hybrid computer. The impact of DYNGEN and similar digital programs on future engine simulation philosophy is also discussed.

A high performance system for molecular dynamics simulation of biomolecules using a special-purpose computer.

PubMed

Komeiji, Y; Yokoyama, H; Uebayasi, M; Taiji, M; Fukushige, T; Sugimoto, D; Takata, R; Shimizu, A; Itsukashi, K

1996-01-01

GRAPE (GRavity PipE) processors are special purpose computers for simulation of classical particles. The performance of MD-GRAPE, one of the GRAPEs developed for molecular dynamics, was investigated. The effective speed of MD-GRAPE was equivalent to approximately 6 Gflops. The precision of MD-GRAPE was good judging from the acceptable fluctuation of the total energy. Then a software named PEACH (Program for Energetic Analysis of bioCHemical molecules) was developed for molecular dynamics of biomolecules in combination with MD-GRAPE. Molecular dynamics simulation was performed for several protein-solvent systems with different sizes. Simulation of the largest system investigated (27,000 atoms) took only 5 sec/step. Thus, the PEACH-GRAPE system is expected to be useful in accurate and reliable simulation of large biomolecules.

A GPU-accelerated immersive audio-visual framework for interaction with molecular dynamics using consumer depth sensors.

PubMed

Glowacki, David R; O'Connor, Michael; Calabró, Gaetano; Price, James; Tew, Philip; Mitchell, Thomas; Hyde, Joseph; Tew, David P; Coughtrie, David J; McIntosh-Smith, Simon

2014-01-01

With advances in computational power, the rapidly growing role of computational/simulation methodologies in the physical sciences, and the development of new human-computer interaction technologies, the field of interactive molecular dynamics seems destined to expand. In this paper, we describe and benchmark the software algorithms and hardware setup for carrying out interactive molecular dynamics utilizing an array of consumer depth sensors. The system works by interpreting the human form as an energy landscape, and superimposing this landscape on a molecular dynamics simulation to chaperone the motion of the simulated atoms, affecting both graphics and sonified simulation data. GPU acceleration has been key to achieving our target of 60 frames per second (FPS), giving an extremely fluid interactive experience. GPU acceleration has also allowed us to scale the system for use in immersive 360° spaces with an array of up to ten depth sensors, allowing several users to simultaneously chaperone the dynamics. The flexibility of our platform for carrying out molecular dynamics simulations has been considerably enhanced by wrappers that facilitate fast communication with a portable selection of GPU-accelerated molecular force evaluation routines. In this paper, we describe a 360° atmospheric molecular dynamics simulation we have run in a chemistry/physics education context. We also describe initial tests in which users have been able to chaperone the dynamics of 10-alanine peptide embedded in an explicit water solvent. Using this system, both expert and novice users have been able to accelerate peptide rare event dynamics by 3-4 orders of magnitude.

Multibody dynamic simulation of knee contact mechanics

PubMed Central

Bei, Yanhong; Fregly, Benjamin J.

2006-01-01

Multibody dynamic musculoskeletal models capable of predicting muscle forces and joint contact pressures simultaneously would be valuable for studying clinical issues related to knee joint degeneration and restoration. Current three-dimensional multi-body knee models are either quasi-static with deformable contact or dynamic with rigid contact. This study proposes a computationally efficient methodology for combining multibody dynamic simulation methods with a deformable contact knee model. The methodology requires preparation of the articular surface geometry, development of efficient methods to calculate distances between contact surfaces, implementation of an efficient contact solver that accounts for the unique characteristics of human joints, and specification of an application programming interface for integration with any multibody dynamic simulation environment. The current implementation accommodates natural or artificial tibiofemoral joint models, small or large strain contact models, and linear or nonlinear material models. Applications are presented for static analysis (via dynamic simulation) of a natural knee model created from MRI and CT data and dynamic simulation of an artificial knee model produced from manufacturer’s CAD data. Small and large strain natural knee static analyses required 1 min of CPU time and predicted similar contact conditions except for peak pressure, which was higher for the large strain model. Linear and nonlinear artificial knee dynamic simulations required 10 min of CPU time and predicted similar contact force and torque but different contact pressures, which were lower for the nonlinear model due to increased contact area. This methodology provides an important step toward the realization of dynamic musculoskeletal models that can predict in vivo knee joint motion and loading simultaneously. PMID:15564115

Time scale bridging in atomistic simulation of slow dynamics: viscous relaxation and defect activation

NASA Astrophysics Data System (ADS)

Kushima, A.; Eapen, J.; Li, Ju; Yip, S.; Zhu, T.

2011-08-01

Atomistic simulation methods are known for timescale limitations in resolving slow dynamical processes. Two well-known scenarios of slow dynamics are viscous relaxation in supercooled liquids and creep deformation in stressed solids. In both phenomena the challenge to theory and simulation is to sample the transition state pathways efficiently and follow the dynamical processes on long timescales. We present a perspective based on the biased molecular simulation methods such as metadynamics, autonomous basin climbing (ABC), strain-boost and adaptive boost simulations. Such algorithms can enable an atomic-level explanation of the temperature variation of the shear viscosity of glassy liquids, and the relaxation behavior in solids undergoing creep deformation. By discussing the dynamics of slow relaxation in two quite different areas of condensed matter science, we hope to draw attention to other complex problems where anthropological or geological-scale time behavior can be simulated at atomic resolution and understood in terms of micro-scale processes of molecular rearrangements and collective interactions. As examples of a class of phenomena that can be broadly classified as materials ageing, we point to stress corrosion cracking and cement setting as opportunities for atomistic modeling and simulations.

Si amorphization by focused ion beam milling: Point defect model with dynamic BCA simulation and experimental validation.

PubMed

Huang, J; Loeffler, M; Muehle, U; Moeller, W; Mulders, J J L; Kwakman, L F Tz; Van Dorp, W F; Zschech, E

2018-01-01

A Ga focused ion beam (FIB) is often used in transmission electron microscopy (TEM) analysis sample preparation. In case of a crystalline Si sample, an amorphous near-surface layer is formed by the FIB process. In order to optimize the FIB recipe by minimizing the amorphization, it is important to predict the amorphous layer thickness from simulation. Molecular Dynamics (MD) simulation has been used to describe the amorphization, however, it is limited by computational power for a realistic FIB process simulation. On the other hand, Binary Collision Approximation (BCA) simulation is able and has been used to simulate ion-solid interaction process at a realistic scale. In this study, a Point Defect Density approach is introduced to a dynamic BCA simulation, considering dynamic ion-solid interactions. We used this method to predict the c-Si amorphization caused by FIB milling on Si. To validate the method, dedicated TEM studies are performed. It shows that the amorphous layer thickness predicted by the numerical simulation is consistent with the experimental data. In summary, the thickness of the near-surface Si amorphization layer caused by FIB milling can be well predicted using the Point Defect Density approach within the dynamic BCA model. Copyright © 2017 Elsevier B.V. All rights reserved.

Rupture Dynamics and Seismic Radiation on Rough Faults for Simulation-Based PSHA

NASA Astrophysics Data System (ADS)

Mai, P. M.; Galis, M.; Thingbaijam, K. K. S.; Vyas, J. C.; Dunham, E. M.

2017-12-01

Simulation-based ground-motion predictions may augment PSHA studies in data-poor regions or provide additional shaking estimations, incl. seismic waveforms, for critical facilities. Validation and calibration of such simulation approaches, based on observations and GMPE's, is important for engineering applications, while seismologists push to include the precise physics of the earthquake rupture process and seismic wave propagation in 3D heterogeneous Earth. Geological faults comprise both large-scale segmentation and small-scale roughness that determine the dynamics of the earthquake rupture process and its radiated seismic wavefield. We investigate how different parameterizations of fractal fault roughness affect the rupture evolution and resulting near-fault ground motions. Rupture incoherence induced by fault roughness generates realistic ω-2 decay for high-frequency displacement amplitude spectra. Waveform characteristics and GMPE-based comparisons corroborate that these rough-fault rupture simulations generate realistic synthetic seismogram for subsequent engineering application. Since dynamic rupture simulations are computationally expensive, we develop kinematic approximations that emulate the observed dynamics. Simplifying the rough-fault geometry, we find that perturbations in local moment tensor orientation are important, while perturbations in local source location are not. Thus, a planar fault can be assumed if the local strike, dip, and rake are maintained. The dynamic rake angle variations are anti-correlated with local dip angles. Based on a dynamically consistent Yoffe source-time function, we show that the seismic wavefield of the approximated kinematic rupture well reproduces the seismic radiation of the full dynamic source process. Our findings provide an innovative pseudo-dynamic source characterization that captures fault roughness effects on rupture dynamics. Including the correlations between kinematic source parameters, we present a new pseudo-dynamic rupture modeling approach for computing broadband ground-motion time-histories for simulation-based PSHA

Post-Flight Assessment of Low Density Supersonic Decelerator Flight Dynamics Test 2 Simulation

NASA Technical Reports Server (NTRS)

Dutta, Soumyo; Bowes, Angela L.; White, Joseph P.; Striepe, Scott A.; Queen, Eric M.; O'Farrel, Clara; Ivanov, Mark C.

2016-01-01

NASA's Low Density Supersonic Decelerator (LDSD) project conducted its second Supersonic Flight Dynamics Test (SFDT-2) on June 8, 2015. The Program to Optimize Simulated Trajectories II (POST2) was one of the flight dynamics tools used to simulate and predict the flight performance and was a major tool used in the post-flight assessment of the flight trajectory. This paper compares the simulation predictions with the reconstructed trajectory. Additionally, off-nominal conditions seen during flight are modeled in the simulation to reconcile the predictions with flight data. These analyses are beneficial to characterize the results of the flight test and to improve the simulation and targeting of the subsequent LDSD flights.

Novel Breast Cancer Therapeutics Based on Bacterial Cupredoxin

DTIC Science & Technology

2008-09-01

M. and Lim, C. (1999) Exploring the dynamic information content of a protein NMR structure: comparison of a molecular dynamics simulation with the...crowding has structural effects on the folded ensemble of polypeptides. energy landscape theory excluded volume effect molecular simulations protein... molecular simulations (51). Thermo- dynamic properties such as the radius of gyration (Rg), shape parameters ( and S) (11), and the fraction of native

Improved Pyrolysis Micro reactor Design via Computational Fluid Dynamics Simulations

DTIC Science & Technology

2017-05-23

Dynamics Simulations Ghanshyam L. Vaghjiani Air Force Research Laboratory (AFMC) AFRL/RQRS 1 Ara Drive Edwards AFB, CA 93524-7013 Air Force...Aerospace Systems Directorate Air Force Research Laboratory AFRL/RQRS 1 Ara Road Edwards AFB, CA 93524 *Email: ghanshyam.vaghjiani@us.af.mil IMPROVED...PYROLYSIS MICRO-REACTOR DESIGN VIA COMPUTATIONAL FLUID DYNAMICS SIMULATIONS Ghanshyam L. Vaghjiani* DISTRIBUTION A: Approved for public release

Combat Simulation Using Breach Computer Language

DTIC Science & Technology

1979-09-01

simulation and weapon system analysis computer language Two types of models were constructed: a stochastic duel and a dynamic engagement model The... duel model validates the BREACH approach by comparing results with mathematical solutions. The dynamic model shows the capability of the BREACH...BREACH 2 Background 2 The Language 3 Static Duel 4 Background and Methodology 4 Validation 5 Results 8 Tank Duel Simulation 8 Dynamic Assault Model

Control Performance, Aerodynamic Modeling, and Validation of Coupled Simulation Techniques for Guided Projectile Roll Dynamics

DTIC Science & Technology

2014-11-01

39–44) has been explored in depth in the literature. Of particular interest for this study are investigations into roll control. Isolating the...Control Performance, Aerodynamic Modeling, and Validation of Coupled Simulation Techniques for Guided Projectile Roll Dynamics by Jubaraj...Simulation Techniques for Guided Projectile Roll Dynamics Jubaraj Sahu, Frank Fresconi, and Karen R. Heavey Weapons and Materials Research

Free-Energy Profiles of Membrane Insertion of the M2 Transmembrane Peptide from Influenza A Virus

DTIC Science & Technology

2008-12-01

ABSTRACT The insertion of the M2 transmembrane peptide from influenza A virus into a membrane has been studied with molecular - dynamics simulations ...performed replica-exchange molecular - dynamics simulations with umbrella-sampling techniques to characterize the probability distribution and conformation...atomic- detailed molecular dynamics (MD) simulation techniques represent a valuable complementary methodology to inves- tigate membrane-insertion of

Study of the dynamics of poly(ethylene oxide) by combining molecular dynamic simulations and neutron scattering experiments

NASA Astrophysics Data System (ADS)

Brodeck, M.; Alvarez, F.; Arbe, A.; Juranyi, F.; Unruh, T.; Holderer, O.; Colmenero, J.; Richter, D.

2009-03-01

We performed quasielastic neutron scattering experiments and atomistic molecular dynamics simulations on a poly(ethylene oxide) (PEO) homopolymer system above the melting point. The excellent agreement found between both sets of data, together with a successful comparison with literature diffraction results, validates the condensed-phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field used to produce our dynamic runs and gives support to their further analysis. This provided direct information on magnitudes which are not accessible from experiments such as the radial probability distribution functions of specific atoms at different times and their moments. The results of our simulations on the H-motions and different experiments indicate that in the high-temperature range investigated the dynamics is Rouse-like for Q-values below ≈0.6 Å-1. We then addressed the single chain dynamic structure factor with the simulations. A mode analysis, not possible directly experimentally, reveals the limits of applicability of the Rouse model to PEO. We discuss the possible origins for the observed deviations.

Study of the dynamics of poly(ethylene oxide) by combining molecular dynamic simulations and neutron scattering experiments.

PubMed

Brodeck, M; Alvarez, F; Arbe, A; Juranyi, F; Unruh, T; Holderer, O; Colmenero, J; Richter, D

2009-03-07

We performed quasielastic neutron scattering experiments and atomistic molecular dynamics simulations on a poly(ethylene oxide) (PEO) homopolymer system above the melting point. The excellent agreement found between both sets of data, together with a successful comparison with literature diffraction results, validates the condensed-phase optimized molecular potentials for atomistic simulation studies (COMPASS) force field used to produce our dynamic runs and gives support to their further analysis. This provided direct information on magnitudes which are not accessible from experiments such as the radial probability distribution functions of specific atoms at different times and their moments. The results of our simulations on the H-motions and different experiments indicate that in the high-temperature range investigated the dynamics is Rouse-like for Q-values below approximately 0.6 A(-1). We then addressed the single chain dynamic structure factor with the simulations. A mode analysis, not possible directly experimentally, reveals the limits of applicability of the Rouse model to PEO. We discuss the possible origins for the observed deviations.

An intercomparison of GCM and RCM dynamical downscaling for characterizing the hydroclimatology of California and Nevada

NASA Astrophysics Data System (ADS)

Xu, Z.; Rhoades, A.; Johansen, H.; Ullrich, P. A.; Collins, W. D.

2017-12-01

Dynamical downscaling is widely used to properly characterize regional surface heterogeneities that shape the local hydroclimatology. However, the factors in dynamical downscaling, including the refinement of model horizontal resolution, large-scale forcing datasets and dynamical cores, have not been fully evaluated. Two cutting-edge global-to-regional downscaling methods are used to assess these, specifically the variable-resolution Community Earth System Model (VR-CESM) and the Weather Research & Forecasting (WRF) regional climate model, under different horizontal resolutions (28, 14, and 7 km). Two groups of WRF simulations are driven by either the NCEP reanalysis dataset (WRF_NCEP) or VR-CESM outputs (WRF_VRCESM) to evaluate the effects of the large-scale forcing datasets. The impacts of dynamical core are assessed by comparing the VR-CESM simulations to the coupled WRF_VRCESM simulations with the same physical parameterizations and similar grid domains. The simulated hydroclimatology (i.e., total precipitation, snow cover, snow water equivalent and surface temperature) are compared with the reference datasets. The large-scale forcing datasets are critical to the WRF simulations in more accurately simulating total precipitation, SWE and snow cover, but not surface temperature. Both the WRF and VR-CESM results highlight that no significant benefit is found in the simulated hydroclimatology by just increasing horizontal resolution refinement from 28 to 7 km. Simulated surface temperature is sensitive to the choice of dynamical core. WRF generally simulates higher temperatures than VR-CESM, alleviates the systematic cold bias of DJF temperatures over the California mountain region, but overestimates the JJA temperature in California's Central Valley.

Modelling and simulation of Space Station Freedom berthing dynamics and control

NASA Technical Reports Server (NTRS)

Cooper, Paul A.; Garrison, James L., Jr.; Montgomery, Raymond C.; Wu, Shih-Chin; Stockwell, Alan E.; Demeo, Martha E.

1994-01-01

A large-angle, flexible, multibody, dynamic modeling capability has been developed to help validate numerical simulations of the dynamic motion and control forces which occur during berthing of Space Station Freedom to the Shuttle Orbiter in the early assembly flights. This paper outlines the dynamics and control of the station, the attached Shuttle Remote Manipulator System, and the orbiter. The simulation tool developed for the analysis is described and the results of two simulations are presented. The first is a simulated maneuver from a gravity-gradient attitude to a torque equilibrium attitude using the station reaction control jets. The second simulation is the berthing of the station to the orbiter with the station control moment gyros actively maintaining an estimated torque equilibrium attitude. The influence of the elastic dynamic behavior of the station and of the Remote Manipulator System on the attitude control of the station/orbiter system during each maneuver was investigated. The flexibility of the station and the arm were found to have only a minor influence on the attitude control of the system during the maneuvers.

Simulating Vibrations in a Complex Loaded Structure

NASA Technical Reports Server (NTRS)

Cao, Tim T.

2005-01-01

The Dynamic Response Computation (DIRECT) computer program simulates vibrations induced in a complex structure by applied dynamic loads. Developed to enable rapid analysis of launch- and landing- induced vibrations and stresses in a space shuttle, DIRECT also can be used to analyze dynamic responses of other structures - for example, the response of a building to an earthquake, or the response of an oil-drilling platform and attached tanks to large ocean waves. For a space-shuttle simulation, the required input to DIRECT includes mathematical models of the space shuttle and its payloads, and a set of forcing functions that simulates launch and landing loads. DIRECT can accommodate multiple levels of payload attachment and substructure as well as nonlinear dynamic responses of structural interfaces. DIRECT combines the shuttle and payload models into a single structural model, to which the forcing functions are then applied. The resulting equations of motion are reduced to an optimum set and decoupled into a unique format for simulating dynamics. During the simulation, maximum vibrations, loads, and stresses are monitored and recorded for subsequent analysis to identify structural deficiencies in the shuttle and/or payloads.

Focused and Corrective Feedback Versus Structured and Supported Debriefing in a Simulation-Based Cardiac Arrest Team Training: A Pilot Randomized Controlled Study.

PubMed

Kim, Ji-Hoon; Kim, Young-Min; Park, Seong Heui; Ju, Eun A; Choi, Se Min; Hong, Tai Yong

2017-06-01

The aim of the study was to compare the educational impact of two postsimulation debriefing methods-focused and corrective feedback (FCF) versus Structured and Supported Debriefing (SSD)-on team dynamics in simulation-based cardiac arrest team training. This was a pilot randomized controlled study conducted at a simulation center. Fourth-year medical students were randomly assigned to the FCF or SSD group, with each team composed of six students and a confederate. Each team participated in two simulations and the assigned debriefing (FCF or SSD) sessions and then underwent a test simulation. Two trained raters blindly assessed all of the recorded simulations using checklists. The primary outcome was the improvement in team dynamics scores between baseline and test simulation. The secondary outcomes were improvements before and after training in team clinical performance scores, self-assessed comprehension of and confidence in cardiac arrest management and team dynamics, as well as evaluations of the postsimulation debriefing intervention. In total, 95 students participated [FCF (8 teams, n = 47) and SSD (8 teams, n = 48)]. The SSD team dynamics score during the test simulation was higher than at baseline [baseline: 74.5 (65.9-80.9), test: 85.0 (71.9-87.6), P = 0.035]. However, there were no differences in the improvement in the team dynamics or team clinical performance scores between the two groups (P = 0.328, respectively). There was no significant difference in improvement in team dynamics scores during the test simulation compared with baseline between the SSD and FCF groups in a simulation-based cardiac arrest team training in fourth-year Korean medical students.

Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis.

PubMed

Forrey, Christopher; Saylor, David M; Silverstein, Joshua S; Douglas, Jack F; Davis, Eric M; Elabd, Yossef A

2014-10-14

Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems.

Troubleshooting Instruction in Vocational-Technical Education Via Dynamic Simulation. Final Report.

ERIC Educational Resources Information Center

Finch, Curtis R.

This study was designed to examine the feasibility of using simulation as a means of teaching vocational-technical students to detect and identify malfunctions in selected electrical and mechanical systems. A dynamic simulator was employed which features interchangeable panels and logic that permits the simulation of electrical or mechanical…

Towards a comprehensive framework for cosimulation of dynamic models with an emphasis on time stepping

NASA Astrophysics Data System (ADS)

Hoepfer, Matthias

Over the last two decades, computer modeling and simulation have evolved as the tools of choice for the design and engineering of dynamic systems. With increased system complexities, modeling and simulation become essential enablers for the design of new systems. Some of the advantages that modeling and simulation-based system design allows for are the replacement of physical tests to ensure product performance, reliability and quality, the shortening of design cycles due to the reduced need for physical prototyping, the design for mission scenarios, the invoking of currently nonexisting technologies, and the reduction of technological and financial risks. Traditionally, dynamic systems are modeled in a monolithic way. Such monolithic models include all the data, relations and equations necessary to represent the underlying system. With increased complexity of these models, the monolithic model approach reaches certain limits regarding for example, model handling and maintenance. Furthermore, while the available computer power has been steadily increasing according to Moore's Law (a doubling in computational power every 10 years), the ever-increasing complexities of new models have negated the increased resources available. Lastly, modern systems and design processes are interdisciplinary, enforcing the necessity to make models more flexible to be able to incorporate different modeling and design approaches. The solution to bypassing the shortcomings of monolithic models is cosimulation. In a very general sense, co-simulation addresses the issue of linking together different dynamic sub-models to a model which represents the overall, integrated dynamic system. It is therefore an important enabler for the design of interdisciplinary, interconnected, highly complex dynamic systems. While a basic co-simulation setup can be very easy, complications can arise when sub-models display behaviors such as algebraic loops, singularities, or constraints. This work frames the co-simulation approach to modeling and simulation. It lays out the general approach to dynamic system co-simulation, and gives a comprehensive overview of what co-simulation is and what it is not. It creates a taxonomy of the requirements and limits of co-simulation, and the issues arising with co-simulating sub-models. Possible solutions towards resolving the stated problems are investigated to a certain depth. A particular focus is given to the issue of time stepping. It will be shown that for dynamic models, the selection of the simulation time step is a crucial issue with respect to computational expense, simulation accuracy, and error control. The reasons for this are discussed in depth, and a time stepping algorithm for co-simulation with unknown dynamic sub-models is proposed. Motivations and suggestions for the further treatment of selected issues are presented.

Microsecond Simulations of DNA and Ion Transport in Nanopores with Novel Ion-Ion and Ion-Nucleotides Effective Potentials

PubMed Central

De Biase, Pablo M.; Markosyan, Suren; Noskov, Sergei

2014-01-01

We developed a novel scheme based on the Grand-Canonical Monte-Carlo/Brownian Dynamics (GCMC/BD) simulations and have extended it to studies of ion currents across three nanopores with the potential for ssDNA sequencing: solid-state nanopore Si3N4, α-hemolysin, and E111N/M113Y/K147N mutant. To describe nucleotide-specific ion dynamics compatible with ssDNA coarse-grained model, we used the Inverse Monte-Carlo protocol, which maps the relevant ion-nucleotide distribution functions from an all-atom MD simulations. Combined with the previously developed simulation platform for Brownian Dynamic (BD) simulations of ion transport, it allows for microsecond- and millisecond-long simulations of ssDNA dynamics in nanopore with a conductance computation accuracy that equals or exceeds that of all-atom MD simulations. In spite of the simplifications, the protocol produces results that agree with the results of previous studies on ion conductance across open channels and provide direct correlations with experimentally measured blockade currents and ion conductances that have been estimated from all-atom MD simulations. PMID:24738152

Model structure identification for wastewater treatment simulation based on computational fluid dynamics.

PubMed

Alex, J; Kolisch, G; Krause, K

2002-01-01

The objective of this presented project is to use the results of an CFD simulation to automatically, systematically and reliably generate an appropriate model structure for simulation of the biological processes using CSTR activated sludge compartments. Models and dynamic simulation have become important tools for research but also increasingly for the design and optimisation of wastewater treatment plants. Besides the biological models several cases are reported about the application of computational fluid dynamics ICFD) to wastewater treatment plants. One aim of the presented method to derive model structures from CFD results is to exclude the influence of empirical structure selection to the result of dynamic simulations studies of WWTPs. The second application of the approach developed is the analysis of badly performing treatment plants where the suspicion arises that bad flow behaviour such as short cut flows is part of the problem. The method suggested requires as the first step the calculation of fluid dynamics of the biological treatment step at different loading situations by use of 3-dimensional CFD simulation. The result of this information is used to generate a suitable model structure for conventional dynamic simulation of the treatment plant by use of a number of CSTR modules with a pattern of exchange flows between the tanks automatically. The method is explained in detail and the application to the WWTP Wuppertal Buchenhofen is presented.

Use of multiple picosecond high-mass molecular dynamics simulations to predict crystallographic B-factors of folded globular proteins.

PubMed

Pang, Yuan-Ping

2016-09-01

Predicting crystallographic B-factors of a protein from a conventional molecular dynamics simulation is challenging, in part because the B-factors calculated through sampling the atomic positional fluctuations in a picosecond molecular dynamics simulation are unreliable, and the sampling of a longer simulation yields overly large root mean square deviations between calculated and experimental B-factors. This article reports improved B-factor prediction achieved by sampling the atomic positional fluctuations in multiple picosecond molecular dynamics simulations that use uniformly increased atomic masses by 100-fold to increase time resolution. Using the third immunoglobulin-binding domain of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as model systems, the B-factor root mean square deviations (mean ± standard error) of these proteins were 3.1 ± 0.2-9 ± 1 Å 2 for Cα and 7.3 ± 0.9-9.6 ± 0.2 Å 2 for Cγ, when the sampling was done for each of these proteins over 20 distinct, independent, and 50-picosecond high-mass molecular dynamics simulations with AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the atomic positional fluctuations in multiple picosecond high-mass molecular dynamics simulations may be conducive to a priori prediction of crystallographic B-factors of a folded globular protein.

From laws of inference to protein folding dynamics.

PubMed

Tseng, Chih-Yuan; Yu, Chun-Ping; Lee, H C

2010-08-01

Protein folding dynamics is one of major issues constantly investigated in the study of protein functions. The molecular dynamic (MD) simulation with the replica exchange method (REM) is a common theoretical approach considered. Yet a trade-off in applying the REM is that the dynamics toward the native configuration in the simulations seems lost. In this work, we show that given REM-MD simulation results, protein folding dynamics can be directly derived from laws of inference. The applicability of the resulting approach, the entropic folding dynamics, is illustrated by investigating a well-studied Trp-cage peptide. Our results are qualitatively comparable with those from other studies. The current studies suggest that the incorporation of laws of inference and physics brings in a comprehensive perspective on exploring the protein folding dynamics.

Applying Parallel Adaptive Methods with GeoFEST/PYRAMID to Simulate Earth Surface Crustal Dynamics

NASA Technical Reports Server (NTRS)

Norton, Charles D.; Lyzenga, Greg; Parker, Jay; Glasscoe, Margaret; Donnellan, Andrea; Li, Peggy

2006-01-01

This viewgraph presentation reviews the use Adaptive Mesh Refinement (AMR) in simulating the Crustal Dynamics of Earth's Surface. AMR simultaneously improves solution quality, time to solution, and computer memory requirements when compared to generating/running on a globally fine mesh. The use of AMR in simulating the dynamics of the Earth's Surface is spurred by future proposed NASA missions, such as InSAR for Earth surface deformation and other measurements. These missions will require support for large-scale adaptive numerical methods using AMR to model observations. AMR was chosen because it has been successful in computation fluid dynamics for predictive simulation of complex flows around complex structures.

Easy GROMACS: A Graphical User Interface for GROMACS Molecular Dynamics Simulation Package

NASA Astrophysics Data System (ADS)

Dizkirici, Ayten; Tekpinar, Mustafa

2015-03-01

GROMACS is a widely used molecular dynamics simulation package. Since it is a command driven program, it is difficult to use this program for molecular biologists, biochemists, new graduate students and undergraduate researchers who are interested in molecular dynamics simulations. To alleviate the problem for those researchers, we wrote a graphical user interface that simplifies protein preparation for a classical molecular dynamics simulation. Our program can work with various GROMACS versions and it can perform essential analyses of GROMACS trajectories as well as protein preparation. We named our open source program `Easy GROMACS'. Easy GROMACS can give researchers more time for scientific research instead of dealing with technical intricacies.

Insights from molecular dynamics simulations for computational protein design.

PubMed

Childers, Matthew Carter; Daggett, Valerie

2017-02-01

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures.

Insights from molecular dynamics simulations for computational protein design

PubMed Central

Childers, Matthew Carter; Daggett, Valerie

2017-01-01

A grand challenge in the field of structural biology is to design and engineer proteins that exhibit targeted functions. Although much success on this front has been achieved, design success rates remain low, an ever-present reminder of our limited understanding of the relationship between amino acid sequences and the structures they adopt. In addition to experimental techniques and rational design strategies, computational methods have been employed to aid in the design and engineering of proteins. Molecular dynamics (MD) is one such method that simulates the motions of proteins according to classical dynamics. Here, we review how insights into protein dynamics derived from MD simulations have influenced the design of proteins. One of the greatest strengths of MD is its capacity to reveal information beyond what is available in the static structures deposited in the Protein Data Bank. In this regard simulations can be used to directly guide protein design by providing atomistic details of the dynamic molecular interactions contributing to protein stability and function. MD simulations can also be used as a virtual screening tool to rank, select, identify, and assess potential designs. MD is uniquely poised to inform protein design efforts where the application requires realistic models of protein dynamics and atomic level descriptions of the relationship between dynamics and function. Here, we review cases where MD simulations was used to modulate protein stability and protein function by providing information regarding the conformation(s), conformational transitions, interactions, and dynamics that govern stability and function. In addition, we discuss cases where conformations from protein folding/unfolding simulations have been exploited for protein design, yielding novel outcomes that could not be obtained from static structures. PMID:28239489

Virtual Habitat -a dynamic simulation of closed life support systems -human model status

NASA Astrophysics Data System (ADS)

Markus Czupalla, M. Sc.; Zhukov, Anton; Hwang, Su-Au; Schnaitmann, Jonas

In order to optimize Life Support Systems on a system level, stability questions must be in-vestigated. To do so the exploration group of the Technical University of Munich (TUM) is developing the "Virtual Habitat" (V-HAB) dynamic LSS simulation software. V-HAB shall provide the possibility to conduct dynamic simulations of entire mission scenarios for any given LSS configuration. The Virtual Habitat simulation tool consists of four main modules: • Closed Environment Module (CEM) -monitoring of compounds in a closed environment • Crew Module (CM) -dynamic human simulation • P/C Systems Module (PCSM) -dynamic P/C subsystems • Plant Module (PM) -dynamic plant simulation The core module of the simulation is the dynamic and environment sensitive human module. Introduced in its basic version in 2008, the human module has been significantly updated since, increasing its capabilities and maturity significantly. In this paper three newly added human model subsystems (thermal regulation, digestion and schedule controller) are introduced touching also on the human stress subsystem which is cur-rently under development. Upon the introduction of these new subsystems, the integration of these into the overall V-HAB human model is discussed, highlighting the impact on the most important I/F. The overall human model capabilities shall further be summarized and presented based on meaningful test cases. In addition to the presentation of the results, the correlation strategy for the Virtual Habitat human model shall be introduced assessing the models current confidence level and giving an outlook on the future correlation strategy. Last but not least, the remaining V-HAB mod-ules shall be introduced shortly showing how the human model is integrated into the overall simulation.

Parallel Performance of Linear Solvers and Preconditioners

DTIC Science & Technology

2014-01-01

are produced by a discrete dislocation dynamics ( DDD ) simulation and change with each timestep of the DDD simulation as the dislocation structure...evolves. However, the coefficient—or stiffness matrix— remains constant during the DDD simulation and some expensive matrix factorizations only occur once...discrete dislocation dynamics ( DDD ) simulations. This can be achieved by coupling a DDD simulator for bulk material (Arsenlis et al., 2007) to a

Dynamical properties of magnetized two-dimensional one-component plasma

NASA Astrophysics Data System (ADS)

Dubey, Girija S.; Gumbs, Godfrey; Fessatidis, Vassilios

2018-05-01

Molecular dynamics simulation are used to examine the effect of a uniform perpendicular magnetic field on a two-dimensional interacting electron system. In this simulation we include the effect of the magnetic field classically through the Lorentz force. Both the Coulomb and the magnetic forces are included directly in the electron dynamics to study their combined effect on the dynamical properties of the 2D system. Results are presented for the velocity autocorrelation function and the diffusion constants in the presence and absence of an external magnetic field. Our simulation results clearly show that the external magnetic field has an effect on the dynamical properties of the system.

A comparison of East Asian summer monsoon simulations from CAM3.1 with three dynamic cores

NASA Astrophysics Data System (ADS)

Wei, Ting; Wang, Lanning; Dong, Wenjie; Dong, Min; Zhang, Jingyong

2011-12-01

This paper examines the sensitivity of CAM3.1 simulations of East Asian summer monsoon (EASM) to the choice of dynamic cores using three long-term simulations, one with each of the following cores: the Eulerian spectral transform method (EUL), semi-Lagrangian scheme (SLD) and finite volume approach (FV). Our results indicate that the dynamic cores significantly influence the simulated fields not only through dynamics, such as wind, but also through physical processes, such as precipitation. Generally speaking, SLD is superior to EUL and FV in simulating the climatological features of EASM and its interannual variability. The SLD version of the CAM model partially reduces its known deficiency in simulating the climatological features of East Asian summer precipitation. The strength and position of simulated western Pacific subtropical high (WPSH) and its ridge line compare more favourably with observations in SLD and FV than in EUL. They contribute to the intensification of the south-easterly along the south of WPSH and the vertical motion through the troposphere around 30° N, where the subtropical rain belt exists. Additionally, SLD simulates the scope of the westerly jet core over East Asia more realistically than the other two dynamic cores do. Considerable systematic errors of the seasonal migration of monsoon rain belt and water vapour flux exist in all of the three versions of CAM3.1 model, although it captures the broad northward shift of convection, and the simulated results share similarities. The interannual variation of EASM is found to be more accurate in SLD simulation, which reasonably reproduces the leading combined patterns of precipitation and 850-hPa winds in East Asia, as well as the 2.5- and 10-year periods of Li-Zeng EASM index. These results emphasise the importance of dynamic cores for the EASM simulation as distinct from the simulation's sensitivity to the physical parameterisations.

Cluster growth mechanisms in Lennard-Jones fluids: A comparison between molecular dynamics and Brownian dynamics simulations

NASA Astrophysics Data System (ADS)

Jung, Jiyun; Lee, Jumin; Kim, Jun Soo

2015-03-01

We present a simulation study on the mechanisms of a phase separation in dilute fluids of Lennard-Jones (LJ) particles as a model of self-interacting molecules. Molecular dynamics (MD) and Brownian dynamics (BD) simulations of the LJ fluids are employed to model the condensation of a liquid droplet in the vapor phase and the mesoscopic aggregation in the solution phase, respectively. With emphasis on the cluster growth at late times well beyond the nucleation stage, we find that the growth mechanisms can be qualitatively different: cluster diffusion and coalescence in the MD simulations and Ostwald ripening in the BD simulations. We also show that the rates of the cluster growth have distinct scaling behaviors during cluster growth. This work suggests that in the solution phase the random Brownian nature of the solute dynamics may lead to the Ostwald ripening that is qualitatively different from the cluster coalescence in the vapor phase.

Protocols for Molecular Dynamics Simulations of RNA Nanostructures.

PubMed

Kim, Taejin; Kasprzak, Wojciech K; Shapiro, Bruce A

2017-01-01

Molecular dynamics (MD) simulations have been used as one of the main research tools to study a wide range of biological systems and bridge the gap between X-ray crystallography or NMR structures and biological mechanism. In the field of RNA nanostructures, MD simulations have been used to fix steric clashes in computationally designed RNA nanostructures, characterize the dynamics, and investigate the interaction between RNA and other biomolecules such as delivery agents and membranes.In this chapter we present examples of computational protocols for molecular dynamics simulations in explicit and implicit solvent using the Amber Molecular Dynamics Package. We also show examples of post-simulation analysis steps and briefly mention selected tools beyond the Amber package. Limitations of the methods, tools, and protocols are also discussed. Most of the examples are illustrated for a small RNA duplex (helix), but the protocols are applicable to any nucleic acid structure, subject only to the computational speed and memory limitations of the hardware available to the user.

ChainMail based neural dynamics modeling of soft tissue deformation for surgical simulation.

PubMed

Zhang, Jinao; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-07-20

Realistic and real-time modeling and simulation of soft tissue deformation is a fundamental research issue in the field of surgical simulation. In this paper, a novel cellular neural network approach is presented for modeling and simulation of soft tissue deformation by combining neural dynamics of cellular neural network with ChainMail mechanism. The proposed method formulates the problem of elastic deformation into cellular neural network activities to avoid the complex computation of elasticity. The local position adjustments of ChainMail are incorporated into the cellular neural network as the local connectivity of cells, through which the dynamic behaviors of soft tissue deformation are transformed into the neural dynamics of cellular neural network. Experiments demonstrate that the proposed neural network approach is capable of modeling the soft tissues' nonlinear deformation and typical mechanical behaviors. The proposed method not only improves ChainMail's linear deformation with the nonlinear characteristics of neural dynamics but also enables the cellular neural network to follow the principle of continuum mechanics to simulate soft tissue deformation.

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

Noe, F; Diadone, Isabella; Lollmann, Marc

There is a gap between kinetic experiment and simulation in their views of the dynamics of complex biomolecular systems. Whereas experiments typically reveal only a few readily discernible exponential relaxations, simulations often indicate complex multistate behavior. Here, a theoretical framework is presented that reconciles these two approaches. The central concept is dynamical fingerprints which contain peaks at the time scales of the dynamical processes involved with amplitudes determined by the experimental observable. Fingerprints can be generated from both experimental and simulation data, and their comparison by matching peaks permits assignment of structural changes present in the simulation to experimentally observedmore » relaxation processes. The approach is applied here to a test case interpreting single molecule fluorescence correlation spectroscopy experiments on a set of fluorescent peptides with molecular dynamics simulations. The peptides exhibit complex kinetics shown to be consistent with the apparent simplicity of the experimental data. Moreover, the fingerprint approach can be used to design new experiments with site-specific labels that optimally probe specific dynamical processes in the molecule under investigation.« less

Is an intuitive convergence definition of molecular dynamics simulations solely based on the root mean square deviation possible?

PubMed

Knapp, B; Frantal, S; Cibena, M; Schreiner, W; Bauer, P

2011-08-01

Molecular dynamics is a commonly used technique in computational biology. One key issue of each molecular dynamics simulation is: When does this simulation reach equilibrium state? A widely used way to determine this is the visual and intuitive inspection of root mean square deviation (RMSD) plots of the simulation. Although this technique has been criticized several times, it is still often used. Therefore, we present a study proving that this method is not reliable at all. We conducted a survey with participants from the field in which we illustrated different RMSD plots to scientists in the field of molecular dynamics. These plots were randomized and repeated, using a statistical model and different variants of the plots. We show that there is no mutual consent about the point of equilibrium. The decisions are severely biased by different parameters. Therefore, we conclude that scientists should not discuss the equilibration of a molecular dynamics simulation on the basis of a RMSD plot.

Determination and Control of Optical and X-Ray Wave Fronts

NASA Technical Reports Server (NTRS)

Kim, Young K.

1997-01-01

A successful design of a space-based or ground optical system requires an iterative procedure which includes the kinematics and dynamics of the system in operating environment, control synthesis and verification. To facilitate the task of designing optical wave front control systems being developed at NASA/MSFC, a multi-discipline dynamics and control tool has been developed by utilizing TREETOPS, a multi-body dynamics and control simulation, NASTRAN and MATLAB. Dynamics and control models of STABLE and ARIS were developed for TREETOPS simulation, and their simulation results are documented in this report.

Mesoscopic modelling and simulation of soft matter.

PubMed

Schiller, Ulf D; Krüger, Timm; Henrich, Oliver

2017-12-20

The deformability of soft condensed matter often requires modelling of hydrodynamical aspects to gain quantitative understanding. This, however, requires specialised methods that can resolve the multiscale nature of soft matter systems. We review a number of the most popular simulation methods that have emerged, such as Langevin dynamics, dissipative particle dynamics, multi-particle collision dynamics, sometimes also referred to as stochastic rotation dynamics, and the lattice-Boltzmann method. We conclude this review with a short glance at current compute architectures for high-performance computing and community codes for soft matter simulation.

Molecular dynamics simulations: advances and applications

PubMed Central

Hospital, Adam; Goñi, Josep Ramon; Orozco, Modesto; Gelpí, Josep L

2015-01-01

Molecular dynamics simulations have evolved into a mature technique that can be used effectively to understand macromolecular structure-to-function relationships. Present simulation times are close to biologically relevant ones. Information gathered about the dynamic properties of macromolecules is rich enough to shift the usual paradigm of structural bioinformatics from studying single structures to analyze conformational ensembles. Here, we describe the foundations of molecular dynamics and the improvements made in the direction of getting such ensemble. Specific application of the technique to three main issues (allosteric regulation, docking, and structure refinement) is discussed. PMID:26604800

Simulations of Operation Dynamics of Different Type GaN Particle Sensors

PubMed Central

Gaubas, Eugenijus; Ceponis, Tomas; Kalesinskas, Vidas; Pavlov, Jevgenij; Vysniauskas, Juozas

2015-01-01

The operation dynamics of the capacitor-type and PIN diode type detectors based on GaN have been simulated using the dynamic and drift-diffusion models. The drift-diffusion current simulations have been implemented by employing the software package Synopsys TCAD Sentaurus. The monopolar and bipolar drift regimes have been analyzed by using dynamic models based on the Shockley-Ramo theorem. The carrier multiplication processes determined by impact ionization have been considered in order to compensate carrier lifetime reduction due to introduction of radiation defects into GaN detector material. PMID:25751080

Movement Characteristics Analysis and Dynamic Simulation of Collaborative Measuring Robot

NASA Astrophysics Data System (ADS)

guoqing, MA; li, LIU; zhenglin, YU; guohua, CAO; yanbin, ZHENG

2017-03-01

Human-machine collaboration is becoming increasingly more necessary, and so collaborative robot applications are also in high demand. We selected a UR10 robot as our research subject for this study. First, we applied D-H coordinate transformation of the robot to establish a link system, and we then used inverse transformation to solve the robot’s inverse kinematics and find all the joints. Use Lagrange method to analysis UR robot dynamics; use ADAMS multibody dynamics simulation software to dynamic simulation; verifying the correctness of the derived kinetic models.

System Dynamics Modeling for Supply Chain Information Sharing

NASA Astrophysics Data System (ADS)

Feng, Yang

In this paper, we try to use the method of system dynamics to model supply chain information sharing. Firstly, we determine the model boundaries, establish system dynamics model of supply chain before information sharing, analyze the model's simulation results under different changed parameters and suggest improvement proposal. Then, we establish system dynamics model of supply chain information sharing and make comparison and analysis on the two model's simulation results, to show the importance of information sharing in supply chain management. We wish that all these simulations would provide scientific supports for enterprise decision-making.

Dynamic Shade and Irradiance Simulation of Aquatic Landscapes and Watersheds

EPA Science Inventory

Penumbra is a landscape shade and irradiance simulation model that simulates how solar energy spatially and temporally interacts within dynamic ecosystems such as riparian zones, forests, and other terrain that cast topological shadows. Direct and indirect solar energy accumulate...

Dynamic extension of the Simulation Problem Analysis Kernel (SPANK)

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

Sowell, E.F.; Buhl, W.F.

1988-07-15

The Simulation Problem Analysis Kernel (SPANK) is an object-oriented simulation environment for general simulation purposes. Among its unique features is use of the directed graph as the primary data structure, rather than the matrix. This allows straightforward use of graph algorithms for matching variables and equations, and reducing the problem graph for efficient numerical solution. The original prototype implementation demonstrated the principles for systems of algebraic equations, allowing simulation of steady-state, nonlinear systems (Sowell 1986). This paper describes how the same principles can be extended to include dynamic objects, allowing simulation of general dynamic systems. The theory is developed andmore » an implementation is described. An example is taken from the field of building energy system simulation. 2 refs., 9 figs.« less

Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome.

PubMed

Šponer, Jiří; Banáš, Pavel; Jurečka, Petr; Zgarbová, Marie; Kührová, Petra; Havrila, Marek; Krepl, Miroslav; Stadlbauer, Petr; Otyepka, Michal

2014-05-15

We present a brief overview of explicit solvent molecular dynamics (MD) simulations of nucleic acids. We explain physical chemistry limitations of the simulations, namely, the molecular mechanics (MM) force field (FF) approximation and limited time scale. Further, we discuss relations and differences between simulations and experiments, compare standard and enhanced sampling simulations, discuss the role of starting structures, comment on different versions of nucleic acid FFs, and relate MM computations with contemporary quantum chemistry. Despite its limitations, we show that MD is a powerful technique for studying the structural dynamics of nucleic acids with a fast growing potential that substantially complements experimental results and aids their interpretation.

Open-source framework for power system transmission and distribution dynamics co-simulation

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

Huang, Renke; Fan, Rui; Daily, Jeff

The promise of the smart grid entails more interactions between the transmission and distribution networks, and there is an immediate need for tools to provide the comprehensive modelling and simulation required to integrate operations at both transmission and distribution levels. Existing electromagnetic transient simulators can perform simulations with integration of transmission and distribution systems, but the computational burden is high for large-scale system analysis. For transient stability analysis, currently there are only separate tools for simulating transient dynamics of the transmission and distribution systems. In this paper, we introduce an open source co-simulation framework “Framework for Network Co-Simulation” (FNCS), togethermore » with the decoupled simulation approach that links existing transmission and distribution dynamic simulators through FNCS. FNCS is a middleware interface and framework that manages the interaction and synchronization of the transmission and distribution simulators. Preliminary testing results show the validity and capability of the proposed open-source co-simulation framework and the decoupled co-simulation methodology.« less

Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.

PubMed

Dalby, Andrew; Shamsir, Mohd Shahir

2015-01-01

Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation.

Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.

PubMed Central

Dalby, Andrew; Shamsir, Mohd Shahir

2015-01-01

Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation. PMID:26539292

AceCloud: Molecular Dynamics Simulations in the Cloud.

PubMed

Harvey, M J; De Fabritiis, G

2015-05-26

We present AceCloud, an on-demand service for molecular dynamics simulations. AceCloud is designed to facilitate the secure execution of large ensembles of simulations on an external cloud computing service (currently Amazon Web Services). The AceCloud client, integrated into the ACEMD molecular dynamics package, provides an easy-to-use interface that abstracts all aspects of interaction with the cloud services. This gives the user the experience that all simulations are running on their local machine, minimizing the learning curve typically associated with the transition to using high performance computing services.

Development of a Computational Assay for the Estrogen Receptor

DTIC Science & Technology

2006-07-01

University Ashley Deline, Senior Thesis in chemistry, " Molecular Dynamic Simulations of a Glycoform and its Constituent Parts Related to Rheumatoid Arthritis...involves running a long molecular dynamics (MD) simulation of the uncoupled receptor in order to sample the protein’s unique conformations. The second...Receptor binding domain. * Performed several long molecular dynamics simulations (800 ps - 3 ns) on the ligand-ER system using ligands with known

New Finite Element/Multibody System Algorithm for Modeling Flexible Tracked Vehicles

DTIC Science & Technology

2011-08-01

U.S. Army RDECOM-TARDEC & 2 University of Illinois at Chicago ABSTRACT The dynamic simulation of multibody tracked vehicles offers engineers a...bodies. Then in a follow-on structural analysis, the loads from the multibody dynamic simulation are input to calculate strains and stresses within the...multibody dynamic simulation environment allowing for an integrated solution. In addition, a new formulation for the interaction between the rigid sprocket

In Silico Analyses of Substrate Interactions with Human Serum Paraoxonase 1

DTIC Science & Technology

2008-01-01

substrate interactions of HuPON1 remains elusive. In this study, we apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the...mod- eling; docking; molecular dynamics simulations ; binding free energy decomposition. 486 PROTEINS Published 2008 WILEY-LISS, INC. yThis article is a...apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the binding interactions of HuPON1 with representative substrates. The

Predictions of Crystal Structures from First Principles

DTIC Science & Technology

2007-06-01

RDX crystal in hoped that the problem could be resolved by the molecular dynamics simulations . The fully ab initio development of density functional... Molecular Dynamics Simulations of RDX i.e., without any use of experimental results (except that Crystal the geometry of monomers was derived from X-ray...applied in molecular dynamics simulations of the RDX system, due to its size, is intractable by any high-level ab crystal. We performed isothermal

A reduced basis method for molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Vincent-Finley, Rachel Elisabeth

In this dissertation, we develop a method for molecular simulation based on principal component analysis (PCA) of a molecular dynamics trajectory and least squares approximation of a potential energy function. Molecular dynamics (MD) simulation is a computational tool used to study molecular systems as they evolve through time. With respect to protein dynamics, local motions, such as bond stretching, occur within femtoseconds, while rigid body and large-scale motions, occur within a range of nanoseconds to seconds. To capture motion at all levels, time steps on the order of a femtosecond are employed when solving the equations of motion and simulations must continue long enough to capture the desired large-scale motion. To date, simulations of solvated proteins on the order of nanoseconds have been reported. It is typically the case that simulations of a few nanoseconds do not provide adequate information for the study of large-scale motions. Thus, the development of techniques that allow longer simulation times can advance the study of protein function and dynamics. In this dissertation we use principal component analysis (PCA) to identify the dominant characteristics of an MD trajectory and to represent the coordinates with respect to these characteristics. We augment PCA with an updating scheme based on a reduced representation of a molecule and consider equations of motion with respect to the reduced representation. We apply our method to butane and BPTI and compare the results to standard MD simulations of these molecules. Our results indicate that the molecular activity with respect to our simulation method is analogous to that observed in the standard MD simulation with simulations on the order of picoseconds.

Comparative Implementation of High Performance Computing for Power System Dynamic Simulations

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

Jin, Shuangshuang; Huang, Zhenyu; Diao, Ruisheng

Dynamic simulation for transient stability assessment is one of the most important, but intensive, computations for power system planning and operation. Present commercial software is mainly designed for sequential computation to run a single simulation, which is very time consuming with a single processer. The application of High Performance Computing (HPC) to dynamic simulations is very promising in accelerating the computing process by parallelizing its kernel algorithms while maintaining the same level of computation accuracy. This paper describes the comparative implementation of four parallel dynamic simulation schemes in two state-of-the-art HPC environments: Message Passing Interface (MPI) and Open Multi-Processing (OpenMP).more » These implementations serve to match the application with dedicated multi-processor computing hardware and maximize the utilization and benefits of HPC during the development process.« less

27ps DFT Molecular Dynamics Simulation of a-maltose: A Reduced Basis Set Study.

USDA-ARS?s Scientific Manuscript database

DFT molecular dynamics simulations are time intensive when carried out on carbohydrates such as alpha-maltose, requiring up to three or more weeks on a fast 16-processor computer to obtain just 5ps of constant energy dynamics. In a recent publication [1] forces for dynamics were generated from B3LY...

Implicit methods for efficient musculoskeletal simulation and optimal control

PubMed Central

van den Bogert, Antonie J.; Blana, Dimitra; Heinrich, Dieter

2011-01-01

The ordinary differential equations for musculoskeletal dynamics are often numerically stiff and highly nonlinear. Consequently, simulations require small time steps, and optimal control problems are slow to solve and have poor convergence. In this paper, we present an implicit formulation of musculoskeletal dynamics, which leads to new numerical methods for simulation and optimal control, with the expectation that we can mitigate some of these problems. A first order Rosenbrock method was developed for solving forward dynamic problems using the implicit formulation. It was used to perform real-time dynamic simulation of a complex shoulder arm system with extreme dynamic stiffness. Simulations had an RMS error of only 0.11 degrees in joint angles when running at real-time speed. For optimal control of musculoskeletal systems, a direct collocation method was developed for implicitly formulated models. The method was applied to predict gait with a prosthetic foot and ankle. Solutions were obtained in well under one hour of computation time and demonstrated how patients may adapt their gait to compensate for limitations of a specific prosthetic limb design. The optimal control method was also applied to a state estimation problem in sports biomechanics, where forces during skiing were estimated from noisy and incomplete kinematic data. Using a full musculoskeletal dynamics model for state estimation had the additional advantage that forward dynamic simulations, could be done with the same implicitly formulated model to simulate injuries and perturbation responses. While these methods are powerful and allow solution of previously intractable problems, there are still considerable numerical challenges, especially related to the convergence of gradient-based solvers. PMID:22102983

OSS: OSSOS Survey Simulator

NASA Astrophysics Data System (ADS)

Petit, J.-M.; Kavelaars, J. J.; Gladman, B.; Alexandersen, M.

2018-05-01

Comparing properties of discovered trans-Neptunian Objects (TNOs) with dynamical models is impossible due to the observational biases that exist in surveys. The OSSOS Survey Simulator takes an intrinsic orbital model (from, for example, the output of a dynamical Kuiper belt emplacement simulation) and applies the survey biases, so the biased simulated objects can be directly compared with real discoveries.

A Simulation Program for Dynamic Infrared (IR) Spectra

ERIC Educational Resources Information Center

Zoerb, Matthew C.; Harris, Charles B.

2013-01-01

A free program for the simulation of dynamic infrared (IR) spectra is presented. The program simulates the spectrum of two exchanging IR peaks based on simple input parameters. Larger systems can be simulated with minor modifications. The program is available as an executable program for PCs or can be run in MATLAB on any operating system. Source…

Exploring travelers' behavior in response to dynamic message signs (DMS) using a driving simulator.

DOT National Transportation Integrated Search

2013-10-01

This research studies the effectiveness of a dynamic message sign (DMS) using a driving : simulator. Over 100 subjects from different socio-economic and age groups were recruited to : drive the simulator under different traffic and driving conditions...

The sunspot databases of the Debrecen Observatory

NASA Astrophysics Data System (ADS)

Baranyi, Tünde; Gyori, Lajos; Ludmány, András

2015-08-01

We present the sunspot data bases and online tools available in the Debrecen Heliophysical Observatory: the DPD (Debrecen Photoheliographic Data, 1974 -), the SDD (SOHO/MDI-Debrecen Data, 1996-2010), the HMIDD (SDO/HMI-Debrecen Data, HMIDD, 2010-), the revised version of Greenwich Photoheliographic Data (GPR, 1874-1976) presented together with the Hungarian Historical Solar Drawings (HHSD, 1872-1919). These are the most detailed and reliable documentations of the sunspot activity in the relevant time intervals. They are very useful for studying sunspot group evolution on various time scales from hours to weeks. Time-dependent differences between the available long-term sunspot databases are investigated and cross-calibration factors are determined between them. This work has received funding from the European Community's Seventh Framework Programme (FP7/2012-2015) under grant agreement No. 284461 (eHEROES).

Gamma Ray Observatory (GRO) dynamics simulator requirements and mathematical specifications, revision 1

NASA Technical Reports Server (NTRS)

Harman, R.; Blejer, D.

1990-01-01

The requirements and mathematical specifications for the Gamma Ray Observatory (GRO) Dynamics Simulator are presented. The complete simulator system, which consists of the profie subsystem, simulation control and input/output subsystem, truth model subsystem, onboard computer model subsystem, and postprocessor, is described. The simulator will be used to evaluate and test the attitude determination and control models to be used on board GRO under conditions that simulate the expected in-flight environment.

High Fidelity, “Faster than Real-Time” Simulator for Predicting Power System Dynamic Behavior - Final Technical Report

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

Flueck, Alex

The “High Fidelity, Faster than Real­Time Simulator for Predicting Power System Dynamic Behavior” was designed and developed by Illinois Institute of Technology with critical contributions from Electrocon International, Argonne National Laboratory, Alstom Grid and McCoy Energy. Also essential to the project were our two utility partners: Commonwealth Edison and AltaLink. The project was a success due to several major breakthroughs in the area of large­scale power system dynamics simulation, including (1) a validated faster than real­ time simulation of both stable and unstable transient dynamics in a large­scale positive sequence transmission grid model, (2) a three­phase unbalanced simulation platform formore » modeling new grid devices, such as independently controlled single­phase static var compensators (SVCs), (3) the world’s first high fidelity three­phase unbalanced dynamics and protection simulator based on Electrocon’s CAPE program, and (4) a first­of­its­ kind implementation of a single­phase induction motor model with stall capability. The simulator results will aid power grid operators in their true time of need, when there is a significant risk of cascading outages. The simulator will accelerate performance and enhance accuracy of dynamics simulations, enabling operators to maintain reliability and steer clear of blackouts. In the long­term, the simulator will form the backbone of the newly conceived hybrid real­time protection and control architecture that will coordinate local controls, wide­area measurements, wide­area controls and advanced real­time prediction capabilities. The nation’s citizens will benefit in several ways, including (1) less down time from power outages due to the faster­than­real­time simulator’s predictive capability, (2) higher levels of reliability due to the detailed dynamics plus protection simulation capability, and (3) more resiliency due to the three­ phase unbalanced simulator’s ability to model three­phase and single­ phase networks and devices.« less

Thermalized Drude Oscillators with the LAMMPS Molecular Dynamics Simulator.

PubMed

Dequidt, Alain; Devémy, Julien; Pádua, Agílio A H

2016-01-25

LAMMPS is a very customizable molecular dynamics simulation software, which can be used to simulate a large diversity of systems. We introduce a new package for simulation of polarizable systems with LAMMPS using thermalized Drude oscillators. The implemented functionalities are described and are illustrated by examples. The implementation was validated by comparing simulation results with published data and using a reference software. Computational performance is also analyzed.

Computational Fluid Dynamics Demonstration of Rigid Bodies in Motion

NASA Technical Reports Server (NTRS)

Camarena, Ernesto; Vu, Bruce T.

2011-01-01

The Design Analysis Branch (NE-Ml) at the Kennedy Space Center has not had the ability to accurately couple Rigid Body Dynamics (RBD) and Computational Fluid Dynamics (CFD). OVERFLOW-D is a flow solver that has been developed by NASA to have the capability to analyze and simulate dynamic motions with up to six Degrees of Freedom (6-DOF). Two simulations were prepared over the course of the internship to demonstrate 6DOF motion of rigid bodies under aerodynamic loading. The geometries in the simulations were based on a conceptual Space Launch System (SLS). The first simulation that was prepared and computed was the motion of a Solid Rocket Booster (SRB) as it separates from its core stage. To reduce computational time during the development of the simulation, only half of the physical domain with respect to the symmetry plane was simulated. Then a full solution was prepared and computed. The second simulation was a model of the SLS as it departs from a launch pad under a 20 knot crosswind. This simulation was reduced to Two Dimensions (2D) to reduce both preparation and computation time. By allowing 2-DOF for translations and 1-DOF for rotation, the simulation predicted unrealistic rotation. The simulation was then constrained to only allow translations.

Use of dynamical downscaling to improve the simulation of Central U.S. warm season precipitation in CMIP5 models

NASA Astrophysics Data System (ADS)

Harding, Keith J.; Snyder, Peter K.; Liess, Stefan

2013-11-01

supporting exceptionally productive agricultural lands, the Central U.S. is susceptible to severe droughts and floods. Such precipitation extremes are expected to worsen with climate change. However, future projections are highly uncertain as global climate models (GCMs) generally fail to resolve precipitation extremes. In this study, we assess how well models from the Coupled Model Intercomparison Project Phase 5 (CMIP5) simulate summer means, variability, extremes, and the diurnal cycle of Central U.S. summer rainfall. Output from a subset of historical CMIP5 simulations are used to drive the Weather Research and Forecasting model to determine whether dynamical downscaling improves the representation of Central U.S. rainfall. We investigate which boundary conditions influence dynamically downscaled precipitation estimates and identify GCMs that can reasonably simulate precipitation when downscaled. The CMIP5 models simulate the seasonal mean and variability of summer rainfall reasonably well but fail to resolve extremes, the diurnal cycle, and the dynamic forcing of precipitation. Downscaling to 30 km improves these characteristics of precipitation, with the greatest improvement in the representation of extremes. Additionally, sizeable diurnal cycle improvements occur with higher (10 km) resolution and convective parameterization disabled, as the daily rainfall peak shifts 4 h closer to observations than 30 km resolution simulations. This lends greater confidence that the mechanisms responsible for producing rainfall are better simulated. Because dynamical downscaling can more accurately simulate these aspects of Central U.S. summer rainfall, policymakers can have added confidence in dynamically downscaled rainfall projections, allowing for more targeted adaptation and mitigation.

Molecular Dynamics Simulations to Determine the Structure and Dynamics of Hepatitis B Virus Capsid Bound to a Novel Anti-viral Drug.

PubMed

Watanabe, Go; Sato, Shunsuke; Iwadate, Mitsuo; Umeyama, Hideaki; Hayakawa, Michiyo; Murakami, Yoshiki; Yoneda, Shigetaka

2016-01-01

Hepatitis B virus (HBV) chronically infects millions of people worldwide and is a major cause of serious liver diseases, including liver cirrhosis and liver cancer. In our previous study, in silico screening was used to isolate new anti-viral compounds predicted to bind to the HBV capsid. Four of the isolated compounds have been reported to suppress the cellular multiplication of HBV experimentally. In the present study, molecular dynamics simulations of the HBV capsid were performed under rotational symmetry boundary conditions, to clarify how the structure and dynamics of the capsid are affected at the atomic level by the binding of one of the isolated compounds, C13. Two simulations of the free HBV capsid, two further simulations of the capsid-C13 complex, and one simulation of the capsid-AT-130 complex were performed. For statistical confidence, each set of simulations was repeated by five times, changing the simulation conditions. C13 continued to bind at the predicted binding site during the simulations, supporting the hypothesis that C13 is a capsid-binding compound. The structure and dynamics of the HBV capsid were greatly influenced by the binding and release of C13, and these effects were essentially identical to those seen for AT-130, indicating that C13 likely inhibits the function of the HBV capsid.

Faster protein folding using enhanced conformational sampling of molecular dynamics simulation.

PubMed

Kamberaj, Hiqmet

2018-05-01

In this study, we applied swarm particle-like molecular dynamics (SPMD) approach to enhance conformational sampling of replica exchange simulations. In particular, the approach showed significant improvement in sampling efficiency of conformational phase space when combined with replica exchange method (REM) in computer simulation of peptide/protein folding. First we introduce the augmented dynamical system of equations, and demonstrate the stability of the algorithm. Then, we illustrate the approach by using different fully atomistic and coarse-grained model systems, comparing them with the standard replica exchange method. In addition, we applied SPMD simulation to calculate the time correlation functions of the transitions in a two dimensional surface to demonstrate the enhancement of transition path sampling. Our results showed that folded structure can be obtained in a shorter simulation time using the new method when compared with non-augmented dynamical system. Typically, in less than 0.5 ns using replica exchange runs assuming that native folded structure is known and within simulation time scale of 40 ns in the case of blind structure prediction. Furthermore, the root mean square deviations from the reference structures were less than 2Å. To demonstrate the performance of new method, we also implemented three simulation protocols using CHARMM software. Comparisons are also performed with standard targeted molecular dynamics simulation method. Copyright © 2018 Elsevier Inc. All rights reserved.

SIMULATION OF SUMMER-TIME DIURNAL BACTERIAL DYNAMICS IN THE ATMOSPHERIC SURFACE LAYER

EPA Science Inventory

A model was prepared to simulate the observed concentration dynamics of culturable bacteria in the diurnal summer atmosphere at a Willamette River Valley, Oregon location. The meteorological and bacterial mechanisms included in a dynamic null-dimensional model with one-second tim...

A Direct, Quantitative Connection between Molecular Dynamics Simulations and Vibrational Probe Line Shapes.

PubMed

Xu, Rosalind J; Blasiak, Bartosz; Cho, Minhaeng; Layfield, Joshua P; Londergan, Casey H

2018-05-17

A quantitative connection between molecular dynamics simulations and vibrational spectroscopy of probe-labeled systems would enable direct translation of experimental data into structural and dynamical information. To constitute this connection, all-atom molecular dynamics (MD) simulations were performed for two SCN probe sites (solvent-exposed and buried) in a calmodulin-target peptide complex. Two frequency calculation approaches with substantial nonelectrostatic components, a quantum mechanics/molecular mechanics (QM/MM)-based technique and a solvatochromic fragment potential (SolEFP) approach, were used to simulate the infrared probe line shapes. While QM/MM results disagreed with experiment, SolEFP results matched experimental frequencies and line shapes and revealed the physical and dynamic bases for the observed spectroscopic behavior. The main determinant of the CN probe frequency is the exchange repulsion between the probe and its local structural neighbors, and there is a clear dynamic explanation for the relatively broad probe line shape observed at the "buried" probe site. This methodology should be widely applicable to vibrational probes in many environments.

Potential-based dynamical reweighting for Markov state models of protein dynamics.

PubMed

Weber, Jeffrey K; Pande, Vijay S

2015-06-09

As simulators attempt to replicate the dynamics of large cellular components in silico, problems related to sampling slow, glassy degrees of freedom in molecular systems will be amplified manyfold. It is tempting to augment simulation techniques with external biases to overcome such barriers with ease; biased simulations, however, offer little utility unless equilibrium properties of interest (both kinetic and thermodynamic) can be recovered from the data generated. In this Article, we present a general scheme that harnesses the power of Markov state models (MSMs) to extract equilibrium kinetic properties from molecular dynamics trajectories collected on biased potential energy surfaces. We first validate our reweighting protocol on a simple two-well potential, and we proceed to test our method on potential-biased simulations of the Trp-cage miniprotein. In both cases, we find that equilibrium populations, time scales, and dynamical processes are reliably reproduced as compared to gold standard, unbiased data sets. We go on to discuss the limitations of our dynamical reweighting approach, and we suggest auspicious target systems for further application.

Concerted Dynamic Motions of an FABP4 Model and Its Ligands Revealed by Microsecond Molecular Dynamics Simulations

PubMed Central

2015-01-01

In this work, we investigate the dynamic motions of fatty acid binding protein 4 (FABP4) in the absence and presence of a ligand by explicitly solvated all-atom molecular dynamics simulations. The dynamics of one ligand-free FABP4 and four ligand-bound FABP4s is compared via multiple 1.2 μs simulations. In our simulations, the protein interconverts between the open and closed states. Ligand-free FABP4 prefers the closed state, whereas ligand binding induces a conformational transition to the open state. Coupled with opening and closing of FABP4, the ligand adopts distinct binding modes, which are identified and compared with crystal structures. The concerted dynamics of protein and ligand suggests that there may exist multiple FABP4–ligand binding conformations. Thus, this work provides details about how ligand binding affects the conformational preference of FABP4 and how ligand binding is coupled with a conformational change of FABP4 at an atomic level. PMID:25231537

Concerted dynamic motions of an FABP4 model and its ligands revealed by microsecond molecular dynamics simulations.

PubMed

Li, Yan; Li, Xiang; Dong, Zigang

2014-10-14

In this work, we investigate the dynamic motions of fatty acid binding protein 4 (FABP4) in the absence and presence of a ligand by explicitly solvated all-atom molecular dynamics simulations. The dynamics of one ligand-free FABP4 and four ligand-bound FABP4s is compared via multiple 1.2 μs simulations. In our simulations, the protein interconverts between the open and closed states. Ligand-free FABP4 prefers the closed state, whereas ligand binding induces a conformational transition to the open state. Coupled with opening and closing of FABP4, the ligand adopts distinct binding modes, which are identified and compared with crystal structures. The concerted dynamics of protein and ligand suggests that there may exist multiple FABP4-ligand binding conformations. Thus, this work provides details about how ligand binding affects the conformational preference of FABP4 and how ligand binding is coupled with a conformational change of FABP4 at an atomic level.