Computer simulation of vehicle handling. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Computer simulation of vehicle handling. Final report. Volume I - summary report.

National Highway Traffic Safety Administration, Washington, D.C.

Operational hybrid computer simulation for vehicle handling studies. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Computer simulation study of liquid lithium at 470 and 843 K

Both structural and dynamical properties of 7Li at 470 and 843 K are studied by molecular dynamics simulation and the results are comapred with the available experimental data. Two effective interatomic potentials are used, i.e., a potential derived from the Ashcroft pseudopotential [Phys. Lett. 23, 48 (1966)] and a recently proposed potential deduced from the neutral pseudoatom method [J. Phys.: Condens. Matter 5, 4283 (1993)]. Although the shape of the two potential functions is very different, the majority of the properties calculated from them are very similar. The differences among the results using the two interaction models are carefully discussed.

Influence of the solvent on the self-assembly of a modified amyloid beta peptide fragment. II. NMR and computer simulation investigation

The conformation of a model peptide AAKLVFF based on a fragment of the amyloid beta peptide A beta 16-20, KLVFF, is investigated in methanol and water via solution NMR experiments and Molecular dynamics computer simulations. In previous work, we have shown that AAKLVFF forms peptide nanotubes in methanol and twisted fibrils in water. Chemical shift measurements were used to investigate the solubility of the peptide as a function of concentration in methanol and water. This enabled the determination of critical aggregation concentrations, The Solubility was lower in water. In dilute solution, diffusion coefficients revealed the presence of intermediate aggregates in concentrated solution, coexisting with NMR-silent larger aggregates, presumed to be beta-sheets. In water, diffusion coefficients did not change appreciably with concentration, indicating the presence mainly of monomers, coexisting with larger aggregates in more concentrated solution. Concentration-dependent chemical shift measurements indicated a folded conformation for the monomers/intermediate aggregates in dilute methanol, with unfolding at higher concentration. In water, an antiparallel arrangement of strands was indicated by certain ROESY peak correlations. The temperature-dependent solubility of AAKLVFF in methanol was well described by a van't Hoff analysis, providing a solubilization enthalpy and entropy. This pointed to the importance of solvophobic interactions in the self-assembly process. Molecular dynamics Simulations constrained by NOE values from NMR suggested disordered reverse turn structures for the monomer, with an antiparallel twisted conformation for dimers. To model the beta-sheet structures formed at higher concentration, possible model arrangements of strands into beta-sheets with parallel and antiparallel configurations and different stacking sequences were used as the basis for MD simulations; two particular arrangements of antiparallel beta-sheets were found to be stable, one being linear and twisted and the other twisted in two directions. These structures Were used to simulate Circular dichroism spectra. The roles of aromatic stacking interactions and charge transfer effects were also examined. Simulated spectra were found to be similar to those observed experimentally.(in water or methanol) which show a maximum at 215 or 218 nm due to pi-pi* interactions, when allowance is made for a 15-18 nm red-shift that may be due to light scattering effects.

Structure and viscoelasticity of an electrorheological fluid in oscillatory shear: computer simulation investigation

The three-dimensional molecular dynamics simulation method has been used to study the dynamic responses of an electrorheological (ER) fluid in oscillatory shear. The structure and related viscoelastic behaviour of the fluid are found to be sensitive to the amplitude of the strain. With the increase of the strain amplitude, the structure formed by the particles changes from isolated columns to sheet-like structures which may be perpendicular or parallel to the oscillating direction. Along with the structure evolution, the field-induced moduli decrease significantly with an increase in strain amplitude. The viscoelastic behaviour of the structures obtained in the cases of different strain amplitudes was examined in the linear response regime and an evident structure dependence of the moduli was found. The reason for this lies in the anisotropy of the arrangement of the particles in these structures. Short-range interactions between the particles cannot be neglected in determining the viscoelastic behaviour of ER fluids at small strain amplitude, especially for parallel sheets. The simulation results were compared with available experimental data and good agreement was reached for most of them.

Computer simulation study of equilibrium properties of magnetic dipolar fluids

Langevin dynamics simulations are used to investigate the equilibrium magnetization properties and structure of magnetic dipolar fluids. The influence of using different boundary conditions are systematically studied. Simulation results on the initial susceptibility and magnetization curves are compared with theoretical predictions. The effect of particle aggregation is discussed in detail by performing a cluster analysis of the microstructure.

Transport coefficients, Raman spectroscopy, and computer simulation of lithium salt solutions in an ionic liquid

Lithium salt solutions of Li(CF3SO2)(2)N, LiTFSI, in a room-temperature ionic liquid (RTIL), 1-butyl-2,3-dimethyl-imidazolium cation, BMMI, and the (CF3SO2)(2)N-, bis(trifluoromethanesulfonyl)imide anion, [BMMI][TFSI], were prepared in different concentrations. Thermal properties, density, viscosity, ionic conductivity, and self-diffusion coefficients were determined at different temperatures for pure [BMMI][TFSI] and the lithium solutions. Raman spectroscopy measurements and computer simulations were also carried out in order to understand the microscopic origin of the observed changes in transport coefficients. Slopes of Walden plots for conductivity and fluidity, and the ratio between the actual conductivity and the Nernst-Einstein estimate for conductivity, decrease with increasing LiTFSI content. All of these studies indicated the formation of aggregates of different chemical nature, as it is corroborated by the Raman spectra. In addition, molecular dynamics (MD) simulations showed that the coordination of Li+ by oxygen atoms of TFSI anions changes with Li+ concentration producing a remarkable change of the RTIL structure with a concomitant reduction of diffusion coefficients of all species in the solutions.

Two dimensional computer simulation of plasma immersion ion implantation

The biggest advantage of plasma immersion ion implantation (PIII) is the capability of treating objects with irregular geometry without complex manipulation of the target holder. The effectiveness of this approach relies on the uniformity of the incident ion dose. Unfortunately, perfect dose uniformity is usually difficult to achieve when treating samples of complex shape. The problems arise from the non-uniform plasma density and expansion of plasma sheath. A particle-in-cell computer simulation is used to study the time-dependent evolution of the plasma sheath surrounding two-dimensional objects during process of plasma immersion ion implantation. Before starting the implantation phase, steady-state nitrogen plasma is established inside the simulation volume by using ionization of gas precursor with primary electrons. The plasma self-consistently evolves to a non-uniform density distribution, which is used as initial density distribution for the implantation phase. As a result, we can obtain a more realistic description of the plasma sheath expansion and dynamics. Ion current density on the target, average impact energy, and trajectories of the implanted ions were calculated for three geometrical shapes. Large deviations from the uniform dose distribution have been observed for targets with irregular shapes. In addition, effect of secondary electron emission has been included in our simulation and no qualitative modifications to the sheath dynamics have been noticed. However, the energetic secondary electrons change drastically the plasma net balance and also pose significant X-ray hazard. Finally, an axial magnetic field has been added to the calculations and the possibility for magnetic insulation of secondary electrons has been proven.

Regulatory mechanism of the light-activable allosteric switch LOV-TAP for the control of DNA binding: a computer simulation study

The spatio-temporal control of gene expression is fundamental to elucidate cell proliferation and deregulation phenomena in living systems. Novel approaches based on light-sensitive multiprotein complexes have recently been devised, showing promising perspectives for the noninvasive and reversible modulation of the DNA-transcriptional activity in vivo. This has lately been demonstrated in a striking way through the generation of the artificial protein construct light-oxygen-voltage (LOV)-tryptophan-activated protein (TAP), in which the LOV-2-Jα photoswitch of phototropin1 from Avena sativa (AsLOV2-Jα) has been ligated to the tryptophan-repressor (TrpR) protein from Escherichia coli. Although tremendous progress has been achieved on the generation of such protein constructs, a detailed understanding of their functioning as opto-genetical tools is still in its infancy. Here, we elucidate the early stages of the light-induced regulatory mechanism of LOV-TAP at the molecular level, using the noninvasive molecular dynamics simulation technique. More specifically, we find that Cys450-FMN-adduct formation in the AsLOV2-Jα-binding pocket after photoexcitation induces the cleavage of the peripheral Jα-helix from the LOV core, causing a change of its polarity and electrostatic attraction of the photoswitch onto the DNA surface. This goes along with the flexibilization through unfolding of a hairpin-like helix-loop-helix region interlinking the AsLOV2-Jα- and TrpR-domains, ultimately enabling the condensation of LOV-TAP onto the DNA surface. By contrast, in the dark state the AsLOV2-Jα photoswitch remains inactive and exerts a repulsive electrostatic force on the DNA surface. This leads to a distortion of the hairpin region, which finally relieves its tension by causing the disruption of LOV-TAP from the DNA.

Computer simulation of glioma growth and morphology.

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.

Computer simulation of glioma growth and morphology.

Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.

High-resolution dynamic computer simulation analysis of the behavior of sample components with pI values outside the pH gradient established by carrier ampholyte CIEF

The behavior of sample components whose pI values are outside the pH gradient established by 101 hypothetical biprotic carrier ampholytes covering a pH 6-8 range was investigated by computer simulation under constant current conditions with concomitant constant electroosmosis toward the cathode. Data obtained with the sample being applied between zones of carrier ampholytes and on the anodic side of the carrier ampholytes were studied and found to evolve into zone structures comprising three regions between anolyte and catholyte. The focusing region with the pH gradient is bracketed by two isotachopheretic zone structures comprising selected sample and carrier components as isotachophoretic zones. The isotachophoretic structures electrophoretically migrate in opposite direction and their lengths increase with time due to the gradual isotachophoretic decay at the pH gradient edges. Due to electroosmosis, however, the overall pattern is being transported toward the cathode. Sample components whose pI values are outside the established pH gradient are demonstrated to form isotachophoretic zones behind the leading cation of the catholyte (components with pI values larger than 8) and the leading anion of the anolyte (components with pI values smaller than 6). Amphoteric compounds with appropriate pI values or nonamphoteric components can act as isotachophoretic spacer compounds between sample compounds or between the leader and the sample with the highest mobility. The simulation data obtained provide for the first time insight into the dynamics of amphoteric sample components that do not focus within the established pH gradient.

Dynamic high-resolution computer simulation of isotachophoretic enantiomer separation and zone stability

The development of electrophoretic computer models and their use for simulation of electrophoretic processes has increased significantly during the last few years. Recently, GENTRANS and SIMUL5 were extended with algorithms that describe chemical equilibria between solutes and a buffer additive in a fast 1:1 interaction process, an approach that enables simulation of the electrophoretic separation of enantiomers. For acidic cationic systems with sodium and H3 0(+) as leading and terminating components, respectively, acetic acid as counter component, charged weak bases as samples, and a neutral CD as chiral selector, the new codes were used to investigate the dynamics of isotachophoretic adjustment of enantiomers, enantiomer separation, boundaries between enantiomers and between an enantiomer and a buffer constituent of like charge, and zone stability. The impact of leader pH, selector concentration, free mobility of the weak base, mobilities of the formed complexes and complexation constants could thereby be elucidated. For selected examples with methadone enantiomers as analytes and (2-hydroxypropyl)-β-CD as selector, simulated zone patterns were found to compare well with those monitored experimentally in capillary setups with two conductivity detectors or an absorbance and a conductivity detector. Simulation represents an elegant way to provide insight into the formation of isotachophoretic boundaries and zone stability in presence of complexation equilibria in a hitherto inaccessible way.

Dynamic high-resolution computer simulation of electrophoretic enantiomer separations with neutral cyclodextrins as chiral selectors.

GENTRANS, a comprehensive one-dimensional dynamic simulator for electrophoretic separations and transport, was extended for handling electrokinetic chiral separations with a neutral ligand. The code can be employed to study the 1:1 interaction of monovalent weak and strong acids and bases with a single monovalent weak or strong acid or base additive, including a neutral cyclodextrin, under real experimental conditions. It is a tool to investigate the dynamics of chiral separations and to provide insight into the buffer systems used in chiral capillary zone electrophoresis (CZE) and chiral isotachophoresis. Analyte stacking across conductivity and buffer additive gradients, changes of additive concentration, buffer component concentration, pH, and conductivity across migrating sample zones and peaks, and the formation and migration of system peaks can thereby be investigated in a hitherto inaccessible way. For model systems with charged weak bases and neutral modified β-cyclodextrins at acidic pH, for which complexation constants, ionic mobilities, and mobilities of selector-analyte complexes have been determined by CZE, simulated and experimentally determined electropherograms and isotachopherograms are shown to be in good agreement. Simulation data reveal that CZE separations of cationic enantiomers performed in phosphate buffers at low pH occur behind a fast cationic migrating system peak that has a small impact on the buffer composition under which enantiomeric separation takes place.