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Sample records for additive all-atom force

  1. CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling

    PubMed Central

    Guvench, Olgun; Mallajosyula, Sairam S.; Raman, E. Prabhu; Hatcher, Elizabeth; Vanommeslaeghe, Kenno; Foster, Theresa J.; Jamison, Francis W.; MacKerell, Alexander D.

    2011-01-01

    Monosaccharide derivatives such as xylose, fucose, N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GlaNAc), glucuronic acid, iduronic acid, and N-acetylneuraminic acid (Neu5Ac) are important components of eukaryotic glycans. The present work details development of force-field parameters for these monosaccharides and their covalent connections to proteins via O-linkages to serine or threonine sidechains and via N-linkages to asparagine sidechains. The force field development protocol was designed to explicitly yield parameters that are compatible with the existing CHARMM additive force field for proteins, nucleic acids, lipids, carbohydrates, and small molecules. Therefore, when combined with previously developed parameters for pyranose and furanose monosaccharides, for glycosidic linkages between monosaccharides, and for proteins, the present set of parameters enables the molecular simulation of a wide variety of biologically-important molecules such as complex carbohydrates and glycoproteins. Parametrization included fitting to quantum mechanical (QM) geometries and conformational energies of model compounds, as well as to QM pair interaction energies and distances of model compounds with water. Parameters were validated in the context of crystals of relevant monosaccharides, as well NMR and/or x-ray crystallographic data on larger systems including oligomeric hyaluronan, sialyl Lewis X, O- and N-linked glycopeptides, and a lectin:sucrose complex. As the validated parameters are an extension of the CHARMM all-atom additive biomolecular force field, they further broaden the types of heterogeneous systems accessible with a consistently-developed force-field model. PMID:22125473

  2. CHARMM General Force Field (CGenFF): A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields

    PubMed Central

    Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.; MacKerell, A. D.

    2010-01-01

    The widely used CHARMM additive all-atom force field includes parameters for proteins, nucleic acids, lipids and carbohydrates. In the present paper an extension of the CHARMM force field to drug-like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug-like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present paper in the context of the model systems, pyrrolidine, and 3-phenoxymethylpyrrolidine will allow users to readily extend the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform “all-CHARMM” simulations on drug-target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems. PMID:19575467

  3. Impact of 2'-hydroxyl sampling on the conformational properties of RNA: update of the CHARMM all-atom additive force field for RNA.

    PubMed

    Denning, Elizabeth J; Priyakumar, U Deva; Nilsson, Lennart; Mackerell, Alexander D

    2011-07-15

    Here, we present an update of the CHARMM27 all-atom additive force field for nucleic acids that improves the treatment of RNA molecules. The original CHARMM27 force field parameters exhibit enhanced Watson-Crick base pair opening which is not consistent with experiment, whereas analysis of molecular dynamics (MD) simulations show the 2'-hydroxyl moiety to almost exclusively sample the O3' orientation. Quantum mechanical (QM) studies of RNA related model compounds indicate the energy minimum associated with the O3' orientation to be too favorable, consistent with the MD results. Optimization of the dihedral parameters dictating the energy of the 2'-hydroxyl proton targeting the QM data yielded several parameter sets, which sample both the base and O3' orientations of the 2'-hydroxyl to varying degrees. Selection of the final dihedral parameters was based on reproduction of hydration behavior as related to a survey of crystallographic data and better agreement with experimental NMR J-coupling values. Application of the model, designated CHARMM36, to a collection of canonical and noncanonical RNA molecules reveals overall improved agreement with a range of experimental observables as compared to CHARMM27. The results also indicate the sensitivity of the conformational heterogeneity of RNA to the orientation of the 2'-hydroxyl moiety and support a model whereby the 2'-hydroxyl can enhance the probability of conformational transitions in RNA.

  4. Simulation of lipid bilayer self-assembly using all-atom lipid force fields.

    PubMed

    Skjevik, Åge A; Madej, Benjamin D; Dickson, Callum J; Lin, Charles; Teigen, Knut; Walker, Ross C; Gould, Ian R

    2016-04-21

    In this manuscript we expand significantly on our earlier communication by investigating the bilayer self-assembly of eight different types of phospholipids in unbiased molecular dynamics (MD) simulations using three widely used all-atom lipid force fields. Irrespective of the underlying force field, the lipids are shown to spontaneously form stable lamellar bilayer structures within 1 microsecond, the majority of which display properties in satisfactory agreement with the experimental data. The lipids self-assemble via the same general mechanism, though at formation rates that differ both between lipid types, force fields and even repeats on the same lipid/force field combination. In addition to zwitterionic phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids, anionic phosphatidylserine (PS) and phosphatidylglycerol (PG) lipids are represented. To our knowledge this is the first time bilayer self-assembly of phospholipids with negatively charged head groups is demonstrated in all-atom MD simulations.

  5. A coarse-grained protein-protein potential derived from an all-atom force field.

    PubMed

    Basdevant, Nathalie; Borgis, Daniel; Ha-Duong, Tap

    2007-08-01

    In order to study protein-protein nonbonded interactions, we present the development of a new reduced protein model that represents each amino acid residue with one to three coarse grains, whose physical properties are derived in a consistent bottom-up procedure from the higher-resolution all-atom AMBER force field. The resulting potential energy function is pairwise additive and includes distinct van-der-Waals and Coulombic terms. The van-der-Waals effective interactions are deduced from preliminary molecular dynamics simulations of all possible amino acid homodimers. They are best represented by a soft 1/r6 repulsion and a Gaussian attraction, with parameters obeying Lorentz-Berthelot mixing rules. For the Coulombic interaction, coarse grain charges are optimized for each separate protein in order to best represent the all-atom electrostatic potential outside the protein core. This approach leaves the possibility of using any implicit solvent model to describe solvation effects and electrostatic screening. The coarse-grained force field is tested carefully for a small homodimeric complex, the magainin. It is shown to reproduce satisfactorily the specificity of the all-atom underlying potential, in particular within a PB/SA solvation model. The coarse-grained potential is applied to the redocking prediction of three different protein-protein complexes: the magainin dimer, the barnase-barstar, and the trypsin-BPTI complexes. It is shown to provide per se an efficient and discriminating scoring energy function for the protein-protein docking problem that remains pertinent at both the global and refinement stage. PMID:17616119

  6. A coarse-grained protein-protein potential derived from an all-atom force field.

    PubMed

    Basdevant, Nathalie; Borgis, Daniel; Ha-Duong, Tap

    2007-08-01

    In order to study protein-protein nonbonded interactions, we present the development of a new reduced protein model that represents each amino acid residue with one to three coarse grains, whose physical properties are derived in a consistent bottom-up procedure from the higher-resolution all-atom AMBER force field. The resulting potential energy function is pairwise additive and includes distinct van-der-Waals and Coulombic terms. The van-der-Waals effective interactions are deduced from preliminary molecular dynamics simulations of all possible amino acid homodimers. They are best represented by a soft 1/r6 repulsion and a Gaussian attraction, with parameters obeying Lorentz-Berthelot mixing rules. For the Coulombic interaction, coarse grain charges are optimized for each separate protein in order to best represent the all-atom electrostatic potential outside the protein core. This approach leaves the possibility of using any implicit solvent model to describe solvation effects and electrostatic screening. The coarse-grained force field is tested carefully for a small homodimeric complex, the magainin. It is shown to reproduce satisfactorily the specificity of the all-atom underlying potential, in particular within a PB/SA solvation model. The coarse-grained potential is applied to the redocking prediction of three different protein-protein complexes: the magainin dimer, the barnase-barstar, and the trypsin-BPTI complexes. It is shown to provide per se an efficient and discriminating scoring energy function for the protein-protein docking problem that remains pertinent at both the global and refinement stage.

  7. An all-atom force field developed for Zn₄O(RCO₂)₆ metal organic frameworks.

    PubMed

    Sun, Yingxin; Sun, Huai

    2014-03-01

    An all-atom force field is developed for metal organic frameworks Zn₄O(RCO₂)₆ by fitting to quantum mechanics data. Molecular simulations are conducted to validate the force field by calculating thermal expansion coefficients, crystal bulk and Young's moduli, power spectra, self-diffusion coefficients, and activation energies of self-diffusions for benzene and n-hexane. The calculated results are in good agreement with available experimental data. The proposed force field is suitable for simulations of adsorption or diffusion of organic molecules with flexible frameworks. PMID:24562858

  8. An All-Atom Force Field for Tertiary Structure Prediction of Helical Proteins

    PubMed Central

    Herges, T.; Wenzel, W.

    2004-01-01

    We have developed an all-atom free-energy force field (PFF01) for protein tertiary structure prediction. PFF01 is based on physical interactions and was parameterized using experimental structures of a family of proteins believed to span a wide variety of possible folds. It contains empirical, although sequence-independent terms for hydrogen bonding. Its solvent-accessible surface area solvent model was first fit to transfer energies of small peptides. The parameters of the solvent model were then further optimized to stabilize the native structure of a single protein, the autonomously folding villin headpiece, against competing low-energy decoys. Here we validate the force field for five nonhomologous helical proteins with 20–60 amino acids. For each protein, decoys with 2–3 Å backbone root mean-square deviation and correct experimental Cβ–Cβ distance constraints emerge as those with the lowest energy. PMID:15507688

  9. Examining the origins of the hydration force between lipid bilayers using all-atom simulations.

    PubMed

    Gentilcore, Anastasia N; Michaud-Agrawal, Naveen; Crozier, Paul S; Stevens, Mark J; Woolf, Thomas B

    2010-05-01

    Using 237 all-atom double bilayer simulations, we examined the thermodynamic and structural changes that occur as a phosphatidylcholine lipid bilayer stack is dehydrated. The simulated system represents a micropatch of lipid multilayer systems that are studied experimentally using surface force apparatus, atomic force microscopy and osmotic pressure studies. In these experiments, the hydration level of the system is varied, changing the separation between the bilayers, in order to understand the forces that the bilayers feel as they are brought together. These studies have found a curious, strongly repulsive force when the bilayers are very close to each other, which has been termed the "hydration force," though the origins of this force are not clearly understood. We computationally reproduce this repulsive, relatively free energy change as bilayers come together and make qualitative conclusions as to the enthalpic and entropic origins of the free energy change. This analysis is supported by data showing structural changes in the waters, lipids and salts that have also been seen in experimental work. Increases in solvent ordering as the bilayers are dehydrated are found to be essential in causing the repulsion as the bilayers come together.

  10. All-Atom Internal Coordinate Mechanics (ICM) Force Field for Hexopyranoses and Glycoproteins

    PubMed Central

    2016-01-01

    We present an extension of the all-atom internal-coordinate force field, ICMFF, that allows for simulation of heterogeneous systems including hexopyranose saccharides and glycan chains in addition to proteins. A library of standard glycan geometries containing α- and β-anomers of the most common hexapyranoses, i.e., d-galactose, d-glucose, d-mannose, d-xylose, l-fucose, N-acetylglucosamine, N-acetylgalactosamine, sialic, and glucuronic acids, is created based on the analysis of the saccharide structures reported in the Cambridge Structural Database. The new force field parameters include molecular electrostatic potential-derived partial atomic charges and the torsional parameters derived from quantum mechanical data for a collection of minimal molecular fragments and related molecules. The ϕ/ψ torsional parameters for different types of glycosidic linkages are developed using model compounds containing the key atoms in the full carbohydrates, i.e., glycosidic-linked tetrahydropyran–cyclohexane dimers. Target data for parameter optimization include two-dimensional energy surfaces corresponding to the ϕ/ψ glycosidic dihedral angles in the disaccharide analogues, as determined by quantum mechanical MP2/6-31G** single-point energies on HF/6-31G** optimized structures. To achieve better agreement with the observed geometries of glycosidic linkages, the bond angles at the O-linkage atoms are added to the internal variable set and the corresponding bond bending energy term is parametrized using quantum mechanical data. The resulting force field is validated on glycan chains of 1–12 residues from a set of high-resolution X-ray glycoprotein structures based on heavy atom root-mean-square deviations of the lowest-energy glycan conformations generated by the biased probability Monte Carlo (BPMC) molecular mechanics simulations from the native structures. The appropriate BPMC distributions for monosaccharide–monosaccharide and protein–glycan linkages are derived

  11. Refined OPLS all-atom force field for saturated phosphatidylcholine bilayers at full hydration.

    PubMed

    Maciejewski, Arkadiusz; Pasenkiewicz-Gierula, Marta; Cramariuc, Oana; Vattulainen, Ilpo; Rog, Tomasz

    2014-05-01

    We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA) force field. We chose DPPC as it is one of the most studied phospholipid species and thus has plenty of experimental data necessary for model validation, and it is also one of the highly important and abundant lipid types, e.g., in lung surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA force field; thus, there is a need to derive its bonding and nonbonding parameters for both the polar and nonpolar parts of the molecule. In the present study, we determined the parameters for torsion angles in the phosphatidylcholine and glycerol moieties and in the acyl chains, as well the partial atomic charges. In these calculations, we used three methods: (1) Hartree-Fock (HF), (2) second order Møller-Plesset perturbation theory (MP2), and (3) density functional theory (DFT). We also tested the effect of the polar environment by using the polarizable continuum model (PCM), and for acyl chains the van der Waals parameters were also adjusted. In effect, six parameter sets were generated and tested on a DPPC bilayer. Out of these six sets, only one was found to be able to satisfactorily reproduce experimental data for the lipid bilayer. The successful DPPC model was obtained from MP2 calculations in an implicit polar environment (PCM). PMID:24745688

  12. Refined OPLS all-atom force field for saturated phosphatidylcholine bilayers at full hydration.

    PubMed

    Maciejewski, Arkadiusz; Pasenkiewicz-Gierula, Marta; Cramariuc, Oana; Vattulainen, Ilpo; Rog, Tomasz

    2014-05-01

    We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA) force field. We chose DPPC as it is one of the most studied phospholipid species and thus has plenty of experimental data necessary for model validation, and it is also one of the highly important and abundant lipid types, e.g., in lung surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA force field; thus, there is a need to derive its bonding and nonbonding parameters for both the polar and nonpolar parts of the molecule. In the present study, we determined the parameters for torsion angles in the phosphatidylcholine and glycerol moieties and in the acyl chains, as well the partial atomic charges. In these calculations, we used three methods: (1) Hartree-Fock (HF), (2) second order Møller-Plesset perturbation theory (MP2), and (3) density functional theory (DFT). We also tested the effect of the polar environment by using the polarizable continuum model (PCM), and for acyl chains the van der Waals parameters were also adjusted. In effect, six parameter sets were generated and tested on a DPPC bilayer. Out of these six sets, only one was found to be able to satisfactorily reproduce experimental data for the lipid bilayer. The successful DPPC model was obtained from MP2 calculations in an implicit polar environment (PCM).

  13. All-atom polarizable force field for DNA based on the classical Drude oscillator model.

    PubMed

    Savelyev, Alexey; MacKerell, Alexander D

    2014-06-15

    Presented is a first generation atomistic force field (FF) for DNA in which electronic polarization is modeled based on the classical Drude oscillator formalism. The DNA model is based on parameters for small molecules representative of nucleic acids, including alkanes, ethers, dimethylphosphate, and the nucleic acid bases and empirical adjustment of key dihedral parameters associated with the phosphodiester backbone, glycosidic linkages, and sugar moiety of DNA. Our optimization strategy is based on achieving a compromise between satisfying the properties of the underlying model compounds in the gas phase targeting quantum mechanical (QM) data and reproducing a number of experimental properties of DNA duplexes in the condensed phase. The resulting Drude FF yields stable DNA duplexes on the 100-ns time scale and satisfactorily reproduce (1) the equilibrium between A and B forms of DNA and (2) transitions between the BI and BII substates of B form DNA. Consistency with the gas phase QM data for the model compounds is significantly better for the Drude model as compared to the CHARMM36 additive FF, which is suggested to be due to the improved response of the model to changes in the environment associated with the explicit inclusion of polarizability. Analysis of dipole moments associated with the nucleic acid bases shows the Drude model to have significantly larger values than those present in CHARMM36, with the dipoles of individual bases undergoing significant variations during the MD simulations. Additionally, the dipole moment of water was observed to be perturbed in the grooves of DNA. PMID:24752978

  14. Hierarchical atom type definitions and extensible all-atom force fields.

    PubMed

    Jin, Zhao; Yang, Chunwei; Cao, Fenglei; Li, Feng; Jing, Zhifeng; Chen, Long; Shen, Zhe; Xin, Liang; Tong, Sijia; Sun, Huai

    2016-03-15

    The extensibility of force field is a key to solve the missing parameter problem commonly found in force field applications. The extensibility of conventional force fields is traditionally managed in the parameterization procedure, which becomes impractical as the coverage of the force field increases above a threshold. A hierarchical atom-type definition (HAD) scheme is proposed to make extensible atom type definitions, which ensures that the force field developed based on the definitions are extensible. To demonstrate how HAD works and to prepare a foundation for future developments, two general force fields based on AMBER and DFF functional forms are parameterized for common organic molecules. The force field parameters are derived from the same set of quantum mechanical data and experimental liquid data using an automated parameterization tool, and validated by calculating molecular and liquid properties. The hydration free energies are calculated successfully by introducing a polarization scaling factor to the dispersion term between the solvent and solute molecules. © 2015 Wiley Periodicals, Inc.

  15. Derivation and Systematic Validation of a Refined All-Atom Force Field for Phosphatidylcholine Lipids

    PubMed Central

    2012-01-01

    An all-atomistic force field (FF) has been developed for fully saturated phospholipids. The parametrization has been largely based on high-level ab initio calculations in order to keep the empirical input to a minimum. Parameters for the lipid chains have been developed based on knowledge about bulk alkane liquids, for which thermodynamic and dynamic data are excellently reproduced. The FFs ability to simulate lipid bilayers in the liquid crystalline phase in a tensionless ensemble was tested in simulations of three lipids: 1,2-diauroyl-sn-glycero-3-phospocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dipalmitoyl-sn-glycero-3-phospcholine (DPPC). Computed areas and volumes per lipid, and three different kinds of bilayer thicknesses, have been investigated. Most importantly NMR order parameters and scattering form factors agree in an excellent manner with experimental data under a range of temperatures. Further, the compatibility with the AMBER FF for biomolecules as well as the ability to simulate bilayers in gel phase was demonstrated. Overall, the FF presented here provides the important balance between the hydrophilic and hydrophobic forces present in lipid bilayers and therefore can be used for more complicated studies of realistic biological membranes with protein insertions. PMID:22352995

  16. Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

    PubMed

    Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

    2014-10-16

    Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide-water and peptide-membrane interactions allow prediction of free energy minima at the bilayer-water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are -2.51, -4.28, and -5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are -0.83, -3.33, and -3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of the ensemble of

  17. In Silico Folding of a Three Helix Protein and Characterization of Its Free-Energy Landscape in an All-Atom Force Field

    NASA Astrophysics Data System (ADS)

    Herges, T.; Wenzel, W.

    2005-01-01

    We report the reproducible first-principles folding of the 40 amino-acid, three-helix headpiece of the HIV accessory protein in a recently developed all-atom free-energy force field. Six of 20 simulations using an adapted basin-hopping method converged to better than 3Å backbone rms deviation to the experimental structure. Using over 60 000 low-energy conformations of this protein, we constructed a decoy tree that completely characterizes its folding funnel.

  18. Additive empirical force field for hexopyranose monosaccharides

    PubMed Central

    Guvench, Olgun; Greene, Shannon N.; Kamath, Ganesh; Brady, John W.; Venable, Richard M.; Pastor, Richard W.; MacKerell, Alexander D.

    2010-01-01

    We present an all-atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all-atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the α- and β-anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas-phase and condensed-phase properties of small-molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute – water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc-pVTZ//MP2/6-31G(d) level of theory. Though not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well-reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids. PMID:18470966

  19. COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids

    PubMed Central

    2015-01-01

    We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions—which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)—quantitatively reproduced all of the “target” MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (PLoS Comput. Biol.2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP’s nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically

  20. Insight into the Properties of Cardiolipin Containing Bilayers from Molecular Dynamics Simulations, Using a Hybrid All-Atom/United-Atom Force Field.

    PubMed

    Aguayo, Daniel; González-Nilo, Fernando D; Chipot, Christophe

    2012-05-01

    Simulation of three models of cardiolipin (CL) containing membranes using a new set of parameters for tetramyristoyl and tetraoleoyl CLs has been developed in the framework of the united-atom CHARMM27-UA and the all-atom CHARMM36 force fields with the aim of performing molecular dynamics (MD) simulations of cardiolipin-containing mixed-lipid membranes. The new parameters use a hybrid representation of all-atom head groups in conjunction with implicit-hydrogen united-atom (UA) to describe the oleoyl and myristoyl chains of the CLs, in lieu of the fully atomistic description, thereby allowing longer simulations to be undertaken. The physicochemical properties of the bilayers were determined and compared with previously reported data. Furthermore, using tetramyristoyl CL mixed with POPG and POPE lipids, a mitochondrial membrane was simulated. The results presented here show the different behavior of the bilayers as a result of the lipid composition, where the length of the acyl chain and the conformation of the headgroup can be associated with the mitochondrial membrane properties. The new hybrid CL parameters prove to be well suited for the simulation of the molecular structure of CL-containing bilayers and can be extended to other lipid bilayers composed of CLs with different acyl chains or alternate head groups.

  1. Insight into the Properties of Cardiolipin Containing Bilayers from Molecular Dynamics Simulations, Using a Hybrid All-Atom/United-Atom Force Field.

    PubMed

    Aguayo, Daniel; González-Nilo, Fernando D; Chipot, Christophe

    2012-05-01

    Simulation of three models of cardiolipin (CL) containing membranes using a new set of parameters for tetramyristoyl and tetraoleoyl CLs has been developed in the framework of the united-atom CHARMM27-UA and the all-atom CHARMM36 force fields with the aim of performing molecular dynamics (MD) simulations of cardiolipin-containing mixed-lipid membranes. The new parameters use a hybrid representation of all-atom head groups in conjunction with implicit-hydrogen united-atom (UA) to describe the oleoyl and myristoyl chains of the CLs, in lieu of the fully atomistic description, thereby allowing longer simulations to be undertaken. The physicochemical properties of the bilayers were determined and compared with previously reported data. Furthermore, using tetramyristoyl CL mixed with POPG and POPE lipids, a mitochondrial membrane was simulated. The results presented here show the different behavior of the bilayers as a result of the lipid composition, where the length of the acyl chain and the conformation of the headgroup can be associated with the mitochondrial membrane properties. The new hybrid CL parameters prove to be well suited for the simulation of the molecular structure of CL-containing bilayers and can be extended to other lipid bilayers composed of CLs with different acyl chains or alternate head groups. PMID:26593668

  2. Ionic velocities in an ionic liquid under high electric fields using all-atom and coarse-grained force field molecular dynamics

    NASA Astrophysics Data System (ADS)

    Daily, John W.; Micci, Michael M.

    2009-09-01

    Molecular dynamics has been used to estimate ionic velocities and electrical conductivity in the ionic liquid 1-ethyl-3-methylimidazolium/tetraflouroborate (EMIM-BF4). Both an all-atom and coarse grained force fields were explored. The simulations were carried out at high electric fields where one might expect the Wien effect to become important in conventional electrolytes and that effect is observed. While the original Wilson theory used to explain the Wien effect in conventional electrolytes does not work well for ionic liquids, a minor modification of the theory allowed it to be used to qualitatively describe the data. The two coarse-graining methods were noisier as expected, but result in a significant savings in computational cost.

  3. Additive CHARMM force field for naturally occurring modified ribonucleotides.

    PubMed

    Xu, You; Vanommeslaeghe, Kenno; Aleksandrov, Alexey; MacKerell, Alexander D; Nilsson, Lennart

    2016-04-15

    More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs. PMID:26841080

  4. Additive CHARMM force field for naturally occurring modified ribonucleotides.

    PubMed

    Xu, You; Vanommeslaeghe, Kenno; Aleksandrov, Alexey; MacKerell, Alexander D; Nilsson, Lennart

    2016-04-15

    More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs.

  5. Parameterization of backbone flexibility in a coarse-grained force field for proteins (COFFDROP) derived from all-atom explicit-solvent molecular dynamics simulations of all possible two-residue peptides

    PubMed Central

    Frembgen-Kesner, Tamara; Andrews, Casey T.; Li, Shuxiang; Ngo, Nguyet Anh; Shubert, Scott A.; Jain, Aakash; Olayiwola, Oluwatoni; Weishaar, Mitch R.; Elcock, Adrian H.

    2015-01-01

    Recently, we reported the parameterization of a set of coarse-grained (CG) nonbonded potential functions, derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acid pairs, and designed for use in (implicit-solvent) Brownian dynamics (BD) simulations of proteins; this force field was named COFFDROP (COarse-grained Force Field for Dynamic Representations Of Proteins). Here, we describe the extension of COFFDROP to include bonded backbone terms derived from fitting to results of explicit-solvent MD simulations of all possible two-residue peptides containing the 20 standard amino acids, with histidine modeled in both its protonated and neutral forms. The iterative Boltzmann inversion (IBI) method was used to optimize new CG potential functions for backbone-related terms by attempting to reproduce angle, dihedral and distance probability distributions generated by the MD simulations. In a simple test of the transferability of the extended force field, the angle, dihedral and distance probability distributions obtained from BD simulations of 56 three-residue peptides were compared to results from corresponding explicit-solvent MD simulations. In a more challenging test of the COFFDROP force field, it was used to simulate eight intrinsically disordered proteins and was shown to quite accurately reproduce the experimental hydrodynamic radii (Rhydro), provided that the favorable nonbonded interactions of the force field were uniformly scaled downwards in magnitude. Overall, the results indicate that the COFFDROP force field is likely to find use in modeling the conformational behavior of intrinsically disordered proteins and multi-domain proteins connected by flexible linkers. PMID:26574429

  6. All-atom force field for molecular dynamics simulations on organotransition metal solids and liquids. Application to M(CO)(n) (M = Cr, Fe, Ni, Mo, Ru, or W) compounds.

    PubMed

    Bernardes, Carlos E S; Canongia Lopes, José N; Minas da Piedade, Manuel E

    2013-10-31

    A previously developed OPLS-based all-atom force field for organometallic compounds was extended to a series of first-, second-, and third-row transition metals based on the study of M(CO)(n) (M = Cr, Fe, Ni, Mo, Ru, or W) complexes. For materials that are solid at ambient temperature and pressure (M = Cr, Mo, W) the validation of the force field was based on reported structural data and on the standard molar enthalpies of sublimation at 298.15 K, experimentally determined by Calvet-drop microcalorimetry using samples corresponding to a specific and well-characterized crystalline phase: Δ(sub)H(m)° = 72.6 ± 0.3 kJ·mol(–1) for Cr(CO)(6), 73.4 ± 0.3 kJ·mol(–1) for Mo(CO)(6), and 77.8 ± 0.3 kJ·mol(–1) for W(CO)(6). For liquids, where problems of polymorphism or phase mixtures are absent, critically analyzed literature data were used. The force field was able to reproduce the volumetric properties of the test set (density and unit cell volume) with an average deviations smaller than 2% and the experimentally determined enthalpies of sublimation and vaporization with an accuracy better than 2.3 kJ·mol(–1). The Lennard-Jones (12-6) potential function parameters used to calculate the repulsive and dispersion contributions of the metals within the framework of the force field were found to be transferable between chromium, iron, and nickel (first row) and between molybdenum and ruthenium (second row). PMID:24079472

  7. All-atom Simulation of Amyloid Aggregates

    NASA Astrophysics Data System (ADS)

    Berhanu, Workalemahu M.; Alred, Erik J.; Bernhardt, Nathan A.; Hansmann, Ulrich H. E.

    Molecular simulations are now commonly used to complement experiments in the investigation of amyloid formation and their role in human diseases. While various simulations based on enhanced sampling techniques are used in amyloid formation simulations, this article will focus on those using standard atomistic simulations to evaluate the stability of fibril models. Such studies explore the limitations that arise from the choice of force field or polymorphism; and explore the stability of in vivo and in vitro forms of Aβ fibril aggregates, and the role of heterologous seeding as a link between different amyloid diseases.

  8. Additive CHARMM force field for naturally occurring modified ribonucleotides

    PubMed Central

    Xu, You; Vanommeslaeghe, Kenno; Aleksandrov, Alexey; MacKerell, Alexander D.

    2016-01-01

    More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all‐atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:26841080

  9. Nonlinearly Additive Forces in Multivalent Ligand Binding to a Single Protein Revealed with Force Spectroscopy

    SciTech Connect

    Ratto, T V; Rudd, R E; Langry, K C; Balhorn, R L; McElfresh, M W

    2005-07-15

    We present evidence of multivalent interactions between a single protein molecule and multiple carbohydrates at a pH where the protein can bind four ligands. The evidence is based not only on measurements of the force required to rupture the bonds formed between ConcanavalinA (ConA) and {alpha}-D-mannose, but also on an analysis of the polymer-extension force curves to infer the polymer architecture that binds the protein to the cantilever and the ligands to the substrate. We find that although the rupture forces for multiple carbohydrate connections to a single protein are larger than the rupture force for a single connection, they do not scale additively with increasing number. Specifically, the most common rupture forces are approximately 46, 66, and 85 pN, which we argue corresponds to 1, 2, and 3 ligands being pulled simultaneously from a single protein as corroborated by an analysis of the linkage architecture. As in our previous work polymer tethers allow us to discriminate between specific and non-specific binding. We analyze the binding configuration (i.e. serial versus parallel connections) through fitting the polymer stretching data with modified Worm-Like Chain (WLC) models that predict how the effective stiffness of the tethers is affected by multiple connections. This analysis establishes that the forces we measure are due to single proteins interacting with multiple ligands, the first force spectroscopy study that establishes single-molecule multivalent binding unambiguously.

  10. Extensive all-atom Monte Carlo sampling and QM/MM corrections in the SAMPL4 hydration free energy challenge.

    PubMed

    Genheden, Samuel; Cabedo Martinez, Ana I; Criddle, Michael P; Essex, Jonathan W

    2014-03-01

    We present our predictions for the SAMPL4 hydration free energy challenge. Extensive all-atom Monte Carlo simulations were employed to sample the compounds in explicit solvent. While the focus of our study was to demonstrate well-converged and reproducible free energies, we attempted to address the deficiencies in the general Amber force field force field with a simple QM/MM correction. We show that by using multiple independent simulations, including different starting configurations, and enhanced sampling with parallel tempering, we can obtain well converged hydration free energies. Additional analysis using dihedral angle distributions, torsion-root mean square deviation plots and thermodynamic cycles support this assertion. We obtain a mean absolute deviation of 1.7 kcal mol(-1) and a Kendall's τ of 0.65 compared with experiment. PMID:24488307

  11. Deriving Coarse-Grained Charges from All-Atom Systems: An Analytic Solution.

    PubMed

    McCullagh, Peter; Lake, Peter T; McCullagh, Martin

    2016-09-13

    An analytic method to assign optimal coarse-grained charges based on electrostatic potential matching is presented. This solution is the infinite size and density limit of grid-integration charge-fitting and is computationally more efficient by several orders of magnitude. The solution is also minimized with respect to coarse-grained positions which proves to be an extremely important step in reproducing the all-atom electrostatic potential. The joint optimal-charge optimal-position coarse-graining procedure is applied to a number of aggregating proteins using single-site per amino acid resolution. These models provide a good estimate of both the vacuum and Debye-Hückel screened all-atom electrostatic potentials in the vicinity and in the far-field of the protein. Additionally, these coarse-grained models are shown to approximate the all-atom dimerization electrostatic potential energy of 10 aggregating proteins with good accuracy.

  12. Resolution-Adapted All-Atomic and Coarse-Grained Model for Biomolecular Simulations.

    PubMed

    Shen, Lin; Hu, Hao

    2014-06-10

    We develop here an adaptive multiresolution method for the simulation of complex heterogeneous systems such as the protein molecules. The target molecular system is described with the atomistic structure while maintaining concurrently a mapping to the coarse-grained models. The theoretical model, or force field, used to describe the interactions between two sites is automatically adjusted in the simulation processes according to the interaction distance/strength. Therefore, all-atomic, coarse-grained, or mixed all-atomic and coarse-grained models would be used together to describe the interactions between a group of atoms and its surroundings. Because the choice of theory is made on the force field level while the sampling is always carried out in the atomic space, the new adaptive method preserves naturally the atomic structure and thermodynamic properties of the entire system throughout the simulation processes. The new method will be very useful in many biomolecular simulations where atomistic details are critically needed.

  13. Microtubule Elasticity: Connecting All-Atom Simulations with Continuum Mechanics

    NASA Astrophysics Data System (ADS)

    Sept, David; Mackintosh, Fred C.

    2010-01-01

    The mechanical properties of microtubules have been extensively studied using a wide range of biophysical techniques, seeking to understand the mechanics of these cylindrical polymers. Here we develop a method for connecting all-atom molecular dynamics simulations with continuum mechanics and show how this can be applied to understand microtubule mechanics. Our coarse-graining technique applied to the microscopic simulation system yields consistent predictions for the Young’s modulus and persistence length of microtubules, while clearly demonstrating how binding of the drug Taxol decreases the stiffness of microtubules. The techniques we develop should be widely applicable to other macromolecular systems.

  14. An all-atom simulation study of the ordering of liquid squalane near a solid surface

    NASA Astrophysics Data System (ADS)

    Tsige, Mesfin; Patnaik, Soumya S.

    2008-05-01

    An all-atom molecular dynamics study using the OPLS force field has been carried out to obtain new insights in to the orientation and ordering of liquid squalane near a solid surface. As observed in previous experiments, the squalane molecules closest to a SiO 2 substrate are found to be tightly bound with their molecular axis preferentially parallel to the interface. Unlike linear alkanes, the squalane molecules are also found to lie preferentially parallel to the liquid/vapor interface. The simulation results predict that the molecular plane orientation of the squalane molecules changes from mainly parallel to perpendicular to the substrate in going further away from the substrate.

  15. An effective all-atom potential for proteins

    PubMed Central

    Irbäck, Anders; Mitternacht, Simon; Mohanty, Sandipan

    2009-01-01

    We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed α/β protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49–67-residue systems with high statistical accuracy, using only modest computational resources by today's standards. PACS Codes: 87.14.E-, 87.15.A-, 87.15.Cc PMID:19356242

  16. Preformed template fluctuations promote fibril formation: Insights from lattice and all-atom models

    NASA Astrophysics Data System (ADS)

    Kouza, Maksim; Co, Nguyen Truong; Nguyen, Phuong H.; Kolinski, Andrzej; Li, Mai Suan

    2015-04-01

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

  17. Preformed template fluctuations promote fibril formation: Insights from lattice and all-atom models

    SciTech Connect

    Kouza, Maksim Kolinski, Andrzej; Co, Nguyen Truong; Nguyen, Phuong H.; Li, Mai Suan

    2015-04-14

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

  18. CHARMM additive and polarizable force fields for biophysics and computer-aided drug design

    PubMed Central

    Vanommeslaeghe, K.

    2014-01-01

    Background Molecular Mechanics (MM) is the method of choice for computational studies of biomolecular systems owing to its modest computational cost, which makes it possible to routinely perform molecular dynamics (MD) simulations on chemical systems of biophysical and biomedical relevance. Scope of Review As one of the main factors limiting the accuracy of MD results is the empirical force field used, the present paper offers a review of recent developments in the CHARMM additive force field, one of the most popular bimolecular force fields. Additionally, we present a detailed discussion of the CHARMM Drude polarizable force field, anticipating a growth in the importance and utilization of polarizable force fields in the near future. Throughout the discussion emphasis is placed on the force fields’ parametrization philosophy and methodology. Major Conclusions Recent improvements in the CHARMM additive force field are mostly related to newly found weaknesses in the previous generation of additive force fields. Beyond the additive approximation is the newly available CHARMM Drude polarizable force field, which allows for MD simulations of up to 1 microsecond on proteins, DNA, lipids and carbohydrates. General Significance Addressing the limitations ensures the reliability of the new CHARMM36 additive force field for the types of calculations that are presently coming into routine computational reach while the availability of the Drude polarizable force fields offers a model that is an inherently more accurate model of the underlying physical forces driving macromolecular structures and dynamics. PMID:25149274

  19. All-atom simulations of crowding effects on ubiquitin dynamics

    NASA Astrophysics Data System (ADS)

    Abriata, Luciano A.; Spiga, Enrico; Dal Peraro, Matteo

    2013-08-01

    It is well-known that crowded environments affect the stability of proteins, with strong biological and biotechnological implications; however, beyond this, crowding is also expected to affect the dynamic properties of proteins, an idea that is hard to probe experimentally. Here we report on a simulation study aimed at evaluating the effects of crowding on internal protein dynamics, based on fully all-atom descriptions of the protein, the solvent and the crowder. Our model system consists of ubiquitin, a protein whose dynamic features are closely related to its ability to bind to multiple partners, in a 325 g L-1 solution of glucose in water, a condition widely employed in in vitro studies of crowding effects. We observe a slight reduction in loop flexibility accompanied by a dramatic restriction of the conformational space explored in the timescale of the simulations (˜0.5 µs), indicating that crowding slows down collective motions and the rate of exploration of the conformational space. This effect is attributed to the extensive and long-lasting interactions observed between protein residues and glucose molecules throughout the entire protein surface. Potential implications of the observed effects are discussed.

  20. Analysis of Ligand-Receptor Association and Intermediate Transfer Rates in Multienzyme Nanostructures with All-Atom Brownian Dynamics Simulations.

    PubMed

    Roberts, Christopher C; Chang, Chia-En A

    2016-08-25

    We present the second-generation GeomBD Brownian dynamics software for determining interenzyme intermediate transfer rates and substrate association rates in biomolecular complexes. Substrate and intermediate association rates for a series of enzymes or biomolecules can be compared between the freely diffusing disorganized configuration and various colocalized or complexed arrangements for kinetic investigation of enhanced intermediate transfer. In addition, enzyme engineering techniques, such as synthetic protein conjugation, can be computationally modeled and analyzed to better understand changes in substrate association relative to native enzymes. Tools are provided to determine nonspecific ligand-receptor association residence times, and to visualize common sites of nonspecific association of substrates on receptor surfaces. To demonstrate features of the software, interenzyme intermediate substrate transfer rate constants are calculated and compared for all-atom models of DNA origami scaffold-bound bienzyme systems of glucose oxidase and horseradish peroxidase. Also, a DNA conjugated horseradish peroxidase enzyme was analyzed for its propensity to increase substrate association rates and substrate local residence times relative to the unmodified enzyme. We also demonstrate the rapid determination and visualization of common sites of nonspecific ligand-receptor association by using HIV-1 protease and an inhibitor, XK263. GeomBD2 accelerates simulations by precomputing van der Waals potential energy grids and electrostatic potential grid maps, and has a flexible and extensible support for all-atom and coarse-grained force fields. Simulation software is written in C++ and utilizes modern parallelization techniques for potential grid preparation and Brownian dynamics simulation processes. Analysis scripts, written in the Python scripting language, are provided for quantitative simulation analysis. GeomBD2 is applicable to the fields of biophysics, bioengineering

  1. A simple and transferable all-atom/coarse-grained hybrid model to study membrane processes.

    PubMed

    Genheden, Samuel; Essex, Jonathan W

    2015-10-13

    We present an efficient all-atom/coarse-grained hybrid model and apply it to membrane processes. This model is an extension of the all-atom/ELBA model applied previously to processes in water. Here, we improve the efficiency of the model by implementing a multiple-time step integrator that allows the atoms and the coarse-grained beads to be propagated at different timesteps. Furthermore, we fine-tune the interaction between the atoms and the coarse-grained beads by computing the potential of mean force of amino acid side chain analogs along the membrane normal and comparing to atomistic simulations. The model was independently validated on the calculation of small-molecule partition coefficients. Finally, we apply the model to membrane peptides. We studied the tilt angle of the Walp23 and Kalp23 helices in two different model membranes and the stability of the glycophorin A dimer. The model is efficient, accurate, and straightforward to use, as it does not require any extra interaction particles, layers of atomistic solvent molecules or tabulated potentials, thus offering a novel, simple approach to study membrane processes. PMID:26574264

  2. Benchmarking all-atom simulations using hydrogen exchange

    PubMed Central

    Skinner, John J.; Yu, Wookyung; Gichana, Elizabeth K.; Baxa, Michael C.; Hinshaw, James R.; Freed, Karl F.; Sosnick, Tobin R.

    2014-01-01

    Long-time molecular dynamics (MD) simulations are now able to fold small proteins reversibly to their native structures [Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) Science 334(6055):517–520]. These results indicate that modern force fields can reproduce the energy surface near the native structure. To test how well the force fields recapitulate the other regions of the energy surface, MD trajectories for a variant of protein G are compared with data from site-resolved hydrogen exchange (HX) and other biophysical measurements. Because HX monitors the breaking of individual H-bonds, this experimental technique identifies the stability and H-bond content of excited states, thus enabling quantitative comparison with the simulations. Contrary to experimental findings of a cooperative, all-or-none unfolding process, the simulated denatured state ensemble, on average, is highly collapsed with some transient or persistent native 2° structure. The MD trajectories of this protein G variant and other small proteins exhibit excessive intramolecular H-bonding even for the most expanded conformations, suggesting that the force fields require improvements in describing H-bonding and backbone hydration. Moreover, these comparisons provide a general protocol for validating the ability of simulations to accurately capture rare structural fluctuations. PMID:25349413

  3. All-atom crystal simulations of DNA and RNA duplexes

    PubMed Central

    Liu, Chunmei; Janowski, Pawel A.; Case, David A.

    2014-01-01

    Background Molecular dynamics simulations can complement experimental measures of structure and dynamics of biomolecules. The quality of such simulations can be tested by comparisons to models refined against experimental crystallographic data. Methods We report simulations of a DNA and RNA duplex in their crystalline environment. The calculations mimic the conditions for PDB entries 1D23 [d(CGATCGATCG)2] and 1RNA [(UUAUAUAUAUAUAA)2], and contain 8 unit cells, each with 4 copies of the Watson-Crick duplex; this yields in aggregate 64 µs of duplex sampling for DNA and 16 µs for RNA. Results The duplex structures conform much more closely to the average structure seen in the crystal than do structures extracted from a solution simulation with the same force field. Sequence-dependent variations in helical parameters, and in groove widths, are largely maintained in the crystal structure, but are smoothed out in solution. However, the integrity of the crystal lattice is slowly degraded in both simulations, with the result that the interfaces between chains become heterogeneous. This problem is more severe for the DNA crystal, which has fewer inter-chain hydrogen bond contacts than does the RNA crystal. Conclusions Crystal simulations using current force fields reproduce many features of observed crystal structures, but suffer from a gradual degradation of the integrity of the crystal lattice. General significance The results offer insights into force-field simulations that tests their ability to preserve weak interactions between chains, which will be of importance also in non-crystalline applications that involve binding and recognition. PMID:25255706

  4. An All-Atom Model of the Structure of Human Copper Transporter 1

    PubMed Central

    Sharikov, Yuriy; Greenberg, Jerry P.; Miller, Mark A.; Kouznetsova, Valentina L.; Larson, Christopher A.; Howell, Stephen B.

    2013-01-01

    Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells that also mediates uptake of the cancer chemotherapeutic agent cisplatin. A low resolution structure of hCTR1 determined by cryoelectron microscopy was recently published. Several protein structure simulation techniques were used to create an all-atom model of this important transporter using the low resolution structure as a starting point. The all-atom model provides new insights into the roles of specific residues of the N-terminal extracellular domain, the intracellular loop, and C-terminal region in metal ion transport. In particular, the model demonstrates that the central region of the pore contains four sets of methionine triads in the intramembranous region. The structure confirms that two triads of methionine residues delineate the intramembranous region of the transporter, and further identifies two additional methionine triads that are located in the extracellular N-terminal part of the transporter. Together, the four triads create a structure that promotes stepwise transport of metal ions into and then through the intramembranous channel of the transporter via transient thioether bonds to methionine residues. Putative copper-binding sites in the hCTR1 trimer were identified by a program developed by us for prediction of metal-binding sites. These sites correspond well with the known effects of mutations on the ability of the protein to transport copper and cisplatin. PMID:22569840

  5. DIGIT FORCE ADJUSTMENTS DURING FINGER ADDITION/REMOVAL IN MULTI-DIGIT PREHENSION

    PubMed Central

    Budgeon, Mark K.; Latash, Mark L.; Zatsiorsky, Vladimir M.

    2008-01-01

    We explored adjustments in multi-digit coordinated action on a hand-held object with finger addition and removal. The subjects (n= 7) kept a vertically oriented handle at rest using a prismatic grasp as if holding a glass of liquid and then either added one finger to the grasp—the index (I) or little (L) finger—or removed one finger. Three external torques were applied on the apparatus: clockwise, counterclockwise, and no torque. The individual digit forces and moments were recorded with 6-component sensors. The change in grasping force depended on the function of the manipulated finger, i.e. on whether the finger resisted external torque (torque agonist) or assisted it (torque antagonist). There was a significant increase of the grasping force when an antagonist was added or when an agonist was removed. These force increases were not necessary for slipping prevention: the normal forces prior to the manipulation were large enough to prevent slipping. All other finger manipulations exhibited no significant change in the grip force, except for the antagonist removal during the supination efforts (after removing the I finger the grasping force decreased). In contrast, the changes in the tangential force depended on the manipulated finger, not on the finger function with respect to external torque. There was a significant thumb force increase when the I finger was added or when the L finger was removed; opposite changes were seen when the L finger was added or the I finger was removed. The changes of the virtual finger (VF) tangential force were equal and opposite to the thumb tangential force alterations; these opposite changes caused changes in the moments these forces generated. The changes in the moments of the tangential forces were counterbalanced by the opposite changes in the moments of normal forces such that the total moment remained constant and the handle orientation was maintained. At the level of individual finger (IF) forces two strategies of error

  6. An Evolutionary Strategy for All-Atom Folding of the 60-Amino-Acid Bacterial Ribosomal Protein L20

    PubMed Central

    Schug, A.; Wenzel, W.

    2006-01-01

    We have investigated an evolutionary algorithm for de novo all-atom folding of the bacterial ribosomal protein L20. We report results of two simulations that converge to near-native conformations of this 60-amino-acid, four-helix protein. We observe a steady increase of “native content” in both simulated ensembles and a large number of near-native conformations in their final populations. We argue that these structures represent a significant fraction of the low-energy metastable conformations, which characterize the folding funnel of this protein. These data validate our all-atom free-energy force field PFF01 for tertiary structure prediction of a previously inaccessible structural family of proteins. We also compare folding simulations of the evolutionary algorithm with the basin-hopping technique for the Trp-cage protein. We find that the evolutionary algorithm generates a dynamic memory in the simulated population, which leads to faster overall convergence. PMID:16565067

  7. All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

    NASA Astrophysics Data System (ADS)

    Kim, Seung-Yeon; Kwak, Wooseop

    2014-12-01

    We perform simulations of the N-terminal 34-residue protein fragment PTH(1-34), consisting of 581 atoms, of the 84-residue human parathyroid hormone by using the all-atom ECEPP/3 force field and the Wang-Landau sampling method. Through a massive high-performance computation, the density of states and the partition function Z( T), as a continuous function of T, are obtained for PTH(1-34). From the continuous partition function Z( T), the partition function zeros of PTH(1-34) are evaluated for the first time. From both the specific heat and the partition function zeros, two characteristic transition temperatures are obtained for the all-atom protein PTH(1-34). The higher transition temperature T 1 and the lower transition temperature T 2 of PTH(1-34) can be interpreted as the collapse temperature T θ and the folding temperature T f , respectively.

  8. Local order parameters for use in driving homogeneous ice nucleation with all-atom models of water.

    PubMed

    Reinhardt, Aleks; Doye, Jonathan P K; Noya, Eva G; Vega, Carlos

    2012-11-21

    We present a local order parameter based on the standard Steinhardt-Ten Wolde approach that is capable both of tracking and of driving homogeneous ice nucleation in simulations of all-atom models of water. We demonstrate that it is capable of forcing the growth of ice nuclei in supercooled liquid water simulated using the TIP4P/2005 model using over-biassed umbrella sampling Monte Carlo simulations. However, even with such an order parameter, the dynamics of ice growth in deeply supercooled liquid water in all-atom models of water are shown to be very slow, and so the computation of free energy landscapes and nucleation rates remains extremely challenging.

  9. Accelerating All-Atom MD Simulations of Lipids Using a Modified Virtual-Sites Technique.

    PubMed

    Loubet, Bastien; Kopec, Wojciech; Khandelia, Himanshu

    2014-12-01

    We present two new implementations of the virtual sites technique which completely suppresses the degrees of freedom of the hydrogen atoms in a lipid bilayer allowing for an increased time step of 5 fs in all-atom simulations of the CHARMM36 force field. One of our approaches uses the derivation of the virtual sites used in GROMACS while the other uses a new definition of the virtual sites of the CH2 groups. Our methods is tested on a DPPC (no unsaturated chain), a POPC (one unsaturated chain), and a DOPC (two unsaturated chains) lipid bilayers. We calculate various physical properties of the membrane of our simulations with and without virtual sites and explain the differences and similarity observed. The best agreements are obtained for the GROMACS original virtual sites on the DOPC bilayer where we get an area per lipid of 67.3 ± 0.3 Å(2) without virtual sites and 67.6 ± 0.3 Å(2) with virtual sites. In conclusion the virtual-sites technique on lipid membranes is a powerful simulation tool, but it should be used with care. The procedure can be applied to other force fields and lipids in a straightforward manner.

  10. Improvement in topology measurement accuracy of atomic force microscope using additional sensor

    NASA Astrophysics Data System (ADS)

    Yoon, Yeomin; Jeong, Jiseong; Kim, Junsup; Park, Kyihwan

    2015-07-01

    The topology image of an atomic force microscope is obtained by picking up a controlled output of a force-feedback loop that is proportional to the height of a sample under the assumption that no dynamics in a z-axis actuator exist. However, the dynamic effects such as hysteresis and creep in a PZT driving z-axis actuator cannot be ignored. To solve this problem, a strain-gage sensor is used as an additional sensor, which enables measurement of the absolute displacement of a z-axis PZT nano scanner. The advantage of using an additional sensor is experimentally provided and validated in topology images.

  11. Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel.

    PubMed

    Li, Xianfeng; Murthy, N Sanjeeva; Becker, Matthew L; Latour, Robert A

    2016-06-24

    A multiscale modeling approach is presented for the efficient construction of an equilibrated all-atom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEG-chain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications.

  12. Additive manufacturing of a monolithic optical force sensor based on polarization modulation.

    PubMed

    Nierenberger, Mathieu; Lecler, Sylvain; Pfeiffer, Pierre; Geiskopf, François; Guilhem, Mathieu; Renaud, Pierre

    2015-08-01

    One of the specific interests of optical sensors is their compatibility with harsh environments. The polarization modulated force sensor we propose offers this advantage, in addition to low cost and ease of manufacturing thanks to its acrylate 3D printed monolithic design. All the polarization control is indeed achieved using the geometry of a single component making unnecessary future alignments. The complex geometry of the transducer is obtained thanks to the 3D printing process. This process and the resulting material optical properties are described. The sensor concept and the fabrication method are experimentally investigated. A monolithic force sensor in the required range of 20 N is exhibited for application in the field of MR-compatible robotics. The potentiality of 3D printing for optical application in the design of the force sensor is illustrated.

  13. Non-additivity of molecule-surface van der Waals potentials from force measurements

    NASA Astrophysics Data System (ADS)

    Tautz, Stefan

    2014-03-01

    Van der Waals (vdW) forces act ubiquitously in condensed matter. Their description as an inherently quantum mechanical phenomenon was developed for single atoms and homogeneous macroscopic bodies by London, Casimir, and Lifshitz. For intermediate-sized objects like organic molecules an atomistic description is required, but explicit first principles calculations are very difficult since correlations between many interacting electrons have to be considered. Hence, semi-empirical correction schemes are often used that simplify the vdW interaction to a sum over atom-pair potentials. A similar gap exists between successful measurements of vdW and Casimir forces for single atoms on the one hand and macroscopic bodies on the other, as comparable experiments for molecules are absent. I will present experiments in which long-range vdW potentials between a series of related molecules and a metal surface have been determined experimentally. The experiments rely on the extremely sensitive force detection of an atomic force microscope in combination with its molecular manipulation capabilities. The results allow us to confirm the asymptotic force law and to quantify the non-additive part of the vdW interaction which is particularly challenging for theory. In the present case, cooperative effects account for 10% of the total interaction. This effect is of general validity in molecules and thus relevant at the intersection of chemistry, physics, biology, and materials science.

  14. Resonant-pattern formation induced by additive noise in periodically forced reaction-diffusion systems

    NASA Astrophysics Data System (ADS)

    Wang, Hongli; Zhang, Ke; Ouyang, Qi

    2006-09-01

    We report frequency-locked resonant patterns induced by additive noise in periodically forced reaction-diffusion Brusselator model. In the regime of 2:1 frequency-locking and homogeneous oscillation, the introduction of additive noise, which is colored in time and white in space, generates and sustains resonant patterns of hexagons, stripes, and labyrinths which oscillate at half of the forcing frequency. Both the noise strength and the correlation time control the pattern formation. The system transits from homogeneous to hexagons, stripes, and to labyrinths successively as the noise strength is adjusted. Good frequency-locked patterns are only sustained by the colored noise and a finite time correlation is necessary. At the limit of white noise with zero temporal correlation, irregular patterns which are only nearly resonant come out as the noise strength is adjusted. The phenomenon induced by colored noise in the forced reaction-diffusion system is demonstrated to correspond to noise-induced Turing instability in the corresponding forced complex Ginzburg-Landau equation.

  15. Resonant-pattern formation induced by additive noise in periodically forced reaction-diffusion systems.

    PubMed

    Wang, Hongli; Zhang, Ke; Ouyang, Qi

    2006-09-01

    We report frequency-locked resonant patterns induced by additive noise in periodically forced reaction-diffusion Brusselator model. In the regime of 2:1 frequency-locking and homogeneous oscillation, the introduction of additive noise, which is colored in time and white in space, generates and sustains resonant patterns of hexagons, stripes, and labyrinths which oscillate at half of the forcing frequency. Both the noise strength and the correlation time control the pattern formation. The system transits from homogeneous to hexagons, stripes, and to labyrinths successively as the noise strength is adjusted. Good frequency-locked patterns are only sustained by the colored noise and a finite time correlation is necessary. At the limit of white noise with zero temporal correlation, irregular patterns which are only nearly resonant come out as the noise strength is adjusted. The phenomenon induced by colored noise in the forced reaction-diffusion system is demonstrated to correspond to noise-induced Turing instability in the corresponding forced complex Ginzburg-Landau equation. PMID:17025732

  16. Matching of additive and polarizable force fields for multiscale condensed phase simulations

    PubMed Central

    Baker, Christopher M.; Best, Robert B.

    2013-01-01

    Inclusion of electronic polarization effects is one of the key aspects in which the accuracy of current biomolecular force fields may be improved. The principal drawback of such approaches is the computational cost, which typically ranges from 3 – 10 times that of the equivalent additive model, and may be greater for more sophisticated treatments of polarization or other many-body effects. Here, we present a multiscale approach which may be used to enhance the sampling in simulations with polarizable models, by using the additive model as a tool to explore configuration space. We use a method based on information theory to determine the charges for an additive model that has optimal overlap with the polarizable one, and we demonstrate the feasibility of enhancing sampling via a hybrid replica exchange scheme for several model systems. An additional advantage is that, in the process, we obtain a systematic method for deriving charges for an additive model that will be the natural complement to its polarizable parent. The additive charges are found by an effective coarse-graining of the polarizable force field, rather than by ad hoc procedures. PMID:23997691

  17. A coarse-graining approach for molecular simulation that retains the dynamics of the all-atom reference system by implementing hydrodynamic interactions

    SciTech Connect

    Markutsya, Sergiy; Lamm, Monica H

    2014-11-07

    We report on a new approach for deriving coarse-grained intermolecular forces that retains the frictional contribution that is often discarded by conventional coarse-graining methods. The approach is tested for water and an aqueous glucose solution, and the results from the new implementation for coarse-grained molecular dynamics simulation show remarkable agreement with the dynamics obtained from reference all-atom simulations. The agreement between the structural properties observed in the coarse-grained and all-atom simulations is also preserved. We discuss how this approach may be applied broadly to any existing coarse-graining method where the coarse-grained models are rigorously derived from all-atom reference systems.

  18. Non-additivity of molecule-surface van der Waals potentials from force measurements

    PubMed Central

    Wagner, Christian; Fournier, Norman; Ruiz, Victor G.; Li, Chen; Müllen, Klaus; Rohlfing, Michael; Tkatchenko, Alexandre; Temirov, Ruslan; Tautz, F. Stefan

    2014-01-01

    Van der Waals (vdW) forces act ubiquitously in condensed matter. Despite being weak on an atomic level, they substantially influence molecular and biological systems due to their long range and system-size scaling. The difficulty to isolate and measure vdW forces on a single-molecule level causes our present understanding to be strongly theory based. Here we show measurements of the attractive potential between differently sized organic molecules and a metal surface using an atomic force microscope. Our choice of molecules and the large molecule-surface separation cause this attraction to be purely of vdW type. The experiment allows testing the asymptotic vdW force law and its validity range. We find a superlinear growth of the vdW attraction with molecular size, originating from the increased deconfinement of electrons in the molecules. Because such non-additive vdW contributions are not accounted for in most first-principles or empirical calculations, we suggest further development in that direction. PMID:25424490

  19. Non-additivity of molecule-surface van der Waals potentials from force measurements.

    PubMed

    Wagner, Christian; Fournier, Norman; Ruiz, Victor G; Li, Chen; Müllen, Klaus; Rohlfing, Michael; Tkatchenko, Alexandre; Temirov, Ruslan; Tautz, F Stefan

    2014-11-26

    Van der Waals (vdW) forces act ubiquitously in condensed matter. Despite being weak on an atomic level, they substantially influence molecular and biological systems due to their long range and system-size scaling. The difficulty to isolate and measure vdW forces on a single-molecule level causes our present understanding to be strongly theory based. Here we show measurements of the attractive potential between differently sized organic molecules and a metal surface using an atomic force microscope. Our choice of molecules and the large molecule-surface separation cause this attraction to be purely of vdW type. The experiment allows testing the asymptotic vdW force law and its validity range. We find a superlinear growth of the vdW attraction with molecular size, originating from the increased deconfinement of electrons in the molecules. Because such non-additive vdW contributions are not accounted for in most first-principles or empirical calculations, we suggest further development in that direction.

  20. The force-field derivation and application of explosive/additive interfaces

    NASA Astrophysics Data System (ADS)

    Long, Yao; Chen, Jun

    2016-10-01

    The inter-molecular force-field across RDX/(paraffin, fluoropolymer) interfaces are derived from first-principles calculated energies under the GGA+vdW functional. Based on the force-field, the polycrystal structures of mixture explosives are obtained, and a set of thermodynamic properties are calculated, including the elastic constants, thermal expansion coefficient, heat capacity, isothermal curve and the Hugoniot curve. The results are in good agreement with the available experiments, and provide a reasonable prediction about the properties of plastic bonded explosives. We find that the thermal expansion coefficient of a multi-component explosive is not only determined by the properties of the components, but is also affected by the thermal stress at the explosive/additive interfaces.

  1. Influence of Polarization on Carbohydrate Hydration: A Comparative Study Using Additive and Polarizable Force Fields.

    PubMed

    Pandey, Poonam; Mallajosyula, Sairam S

    2016-07-14

    Carbohydrates are known to closely modulate their surrounding solvent structures and influence solvation dynamics. Spectroscopic investigations studying far-IR regions (below 1000 cm(-1)) have observed spectral shifts in the libration band (around 600 cm(-1)) of water in the presence of monosaccharides and polysaccharides. In this paper, we use molecular dynamics simulations to gain atomistic insight into carbohydrate-water interactions and to specifically highlight the differences between additive (nonpolarizable) and polarizable simulations. A total of six monosaccharide systems, α and β anomers of glucose, galactose, and mannose, were studied using additive and polarizable Chemistry at HARvard Macromolecular Mechanics (CHARMM) carbohydrate force fields. Solvents were modeled using three additive water models TIP3P, TIP4P, and TIP5P in additive simulations and polarizable water model SWM4 in polarizable simulations. The presence of carbohydrate has a significant effect on the microscopic water structure, with the effects being pronounced for proximal water molecules. Notably, disruption of the tetrahedral arrangement of proximal water molecules was observed due to the formation of strong carbohydrate-water hydrogen bonds in both additive and polarizable simulations. However, the inclusion of polarization resulted in significant water-bridge occupancies, improved ordered water structures (tetrahedral order parameter), and longer carbohydrate-water H-bond correlations as compared to those for additive simulations. Additionally, polarizable simulations also allowed the calculation of power spectra from the dipole-dipole autocorrelation function, which corresponds to the IR spectra. From the power spectra, we could identify spectral signatures differentiating the proximal and bulk water structures, which could not be captured from additive simulations. PMID:27266974

  2. Influence of Additional Tensile Force on Springback of Tube Under Rotary Draw Bending

    NASA Astrophysics Data System (ADS)

    E, Daxin; Guan, Zhiping; Chen, Jisheng

    2012-11-01

    According to the characteristics of tube under rotary draw bending, the formulae were derived to calculate the springback angles of tubes subjected to combined bending and additional tension. Especially, as the neutral layer (NL) moves to the inner concave surface of the bend, the analytical values agree very well with the experimental results. The analysis shows that the additional tensile force causes the movement of the NL toward the bending center and makes the deformation behavior under rotary draw bending or numerically controlled (NC) bending different with that under pure bending, and also it could enlarge the springback angle if taking the movement of the NL into consideration. In some range, the springback angle would increase slightly with larger wall thickness/diameter ratio and decrease with wall thinning. The investigation could provide reference for the analysis of rotary draw bending, the design of NC tube bender and the related techniques.

  3. Note: vibration reduction control of an atomic force microscope using an additional cantilever.

    PubMed

    Kim, Chulsoo; Jung, Jongkyu; Park, Kyihwan

    2011-11-01

    Since an atomic force microscope is used to measure sub-nanometer level precision, it is sensitive to external vibration. If the vibration can be measured by using an additional sensor, we can obtain the vibration-free signal by subtracting the vibration signal from the signal containing the vibration. To achieve a highly effective vibration rejection ratio, it is important to decide where to locate the additional sensor. This is because the vibration measured at the sensing position should have the same phase as that of the vibration in the signal. Vibration reduction control using this electrical sensing method is verified through time domain analysis and topology images of a standard grid sample.

  4. Transferability and additivity of dihedral parameters in polarizable and nonpolarizable empirical force fields.

    PubMed

    Zgarbová, Marie; Rosnik, Andreana M; Luque, F Javier; Curutchet, Carles; Jurečka, Petr

    2015-09-30

    Recent advances in polarizable force fields have revealed that major reparameterization is necessary when the polarization energy is treated explicitly. This study is focused on the torsional parameters, which are crucial for the accurate description of conformational equilibria in biomolecules. In particular, attention is paid to the influence of polarization on the (i) transferability of dihedral terms between molecules, (ii) transferability between different environments, and (iii) additivity of dihedral energies. To this end, three polarizable force fields based on the induced point dipole model designed for use in AMBER are tested, including two recent ff02 reparameterizations. Attention is paid to the contributions due to short range interactions (1-2, 1-3, and 1-4) within the four atoms defining the dihedral angle. The results show that when short range 1-2 and 1-3 polarization interactions are omitted, as for instance in ff02, the 1-4 polarization contribution is rather small and unlikely to improve the description of the torsional energy. Conversely, when screened 1-2 and 1-3 interactions are included, the polarization contribution is sizeable and shows potential to improve the transferability of parameters between different molecules and environments as well as the additivity of dihedral terms. However, to reproduce intramolecular polarization effects accurately, further fine-tuning of the short range damping of polarization is necessary.

  5. Transferability and additivity of dihedral parameters in polarizable and nonpolarizable empirical force fields.

    PubMed

    Zgarbová, Marie; Rosnik, Andreana M; Luque, F Javier; Curutchet, Carles; Jurečka, Petr

    2015-09-30

    Recent advances in polarizable force fields have revealed that major reparameterization is necessary when the polarization energy is treated explicitly. This study is focused on the torsional parameters, which are crucial for the accurate description of conformational equilibria in biomolecules. In particular, attention is paid to the influence of polarization on the (i) transferability of dihedral terms between molecules, (ii) transferability between different environments, and (iii) additivity of dihedral energies. To this end, three polarizable force fields based on the induced point dipole model designed for use in AMBER are tested, including two recent ff02 reparameterizations. Attention is paid to the contributions due to short range interactions (1-2, 1-3, and 1-4) within the four atoms defining the dihedral angle. The results show that when short range 1-2 and 1-3 polarization interactions are omitted, as for instance in ff02, the 1-4 polarization contribution is rather small and unlikely to improve the description of the torsional energy. Conversely, when screened 1-2 and 1-3 interactions are included, the polarization contribution is sizeable and shows potential to improve the transferability of parameters between different molecules and environments as well as the additivity of dihedral terms. However, to reproduce intramolecular polarization effects accurately, further fine-tuning of the short range damping of polarization is necessary. PMID:26224547

  6. All-atom normal-mode analysis reveals an RNA-induced allostery in a bacteriophage coat protein

    NASA Astrophysics Data System (ADS)

    Dykeman, Eric C.; Twarock, Reidun

    2010-03-01

    Assembly of the T=3 bacteriophage MS2 is initiated by the binding of a 19 nucleotide RNA stem loop from within the phage genome to a symmetric coat protein dimer. This binding event effects a folding of the FG loop in one of the protein subunits of the dimer and results in the formation of an asymmetric dimer. Since both the symmetric and asymmetric forms of the dimer are needed for the assembly of the protein container, this allosteric switch plays an important role in the life cycle of the phage. We provide here details of an all-atom normal-mode analysis of this allosteric effect. The results suggest that asymmetric contacts between the A -duplex RNA phosphodiester backbone of the stem loop with the EF loop in one coat protein subunit results in an increased dynamic behavior of its FG loop. The four lowest-frequency modes, which encompass motions predominantly on the FG loops, account for over 90% of the increased dynamic behavior due to a localization of the vibrational pattern on a single FG loop. Finally, we show that an analysis of the allosteric effect using an elastic network model fails to predict this localization effect, highlighting the importance of using an all-atom full force field method for this problem.

  7. All-atom molecular dynamics studies of the full-length β-amyloid peptides

    NASA Astrophysics Data System (ADS)

    Luttmann, Edgar; Fels, Gregor

    2006-03-01

    β-Amyloid peptides are believed to play an essential role in Alzheimer's disease (AD), due to their sedimentation in the form of β-amyloid aggregates in the brain of AD-patients, and the in vitro neurotoxicity of oligomeric aggregates. The monomeric peptides come in different lengths of 39-43 residues, of which the 42 alloform seems to be most strongly associated with AD-symptoms. Structural information on these peptides to date comes from NMR studies in acidic solutions, organic solvents, or on shorter fragments of the peptide. In addition X-ray and solid-state NMR investigations of amyloid fibrils yield insight into the structure of the final aggregate and therefore define the endpoint of any conformational change of an Aβ-monomer along the aggregation process. The conformational changes necessary to connect the experimentally known conformations are not yet understood and this process is an active field of research. In this paper, we report results from all-atom molecular dynamics simulations based on experimental data from four different peptides of 40 amino acids and two peptides consisting of 42 amino acids. The simulations allow for the analysis of intramolecular interactions and the role of structural features. In particular, they show the appearance of β-turn in the region between amino acid 21 and 33, forming a hook-like shape as it is known to exist in the fibrillar Aβ-structures. This folding does not depend on the formation of a salt bridge between Asp-23 and Lys-28 but requires the Aβ(1-42) as such structure was not observed in the shorter system Aβ(1-40).

  8. Simulation of uphill/downhill running on a level treadmill using additional horizontal force.

    PubMed

    Gimenez, Philippe; Arnal, Pierrick J; Samozino, Pierre; Millet, Guillaume Y; Morin, Jean-Benoit

    2014-07-18

    Tilting treadmills allow a convenient study of biomechanics during uphill/downhill running, but they are not commonly available and there is even fewer tilting force-measuring treadmill. The aim of the present study was to compare uphill/downhill running on a treadmill (inclination of ± 8%) with running on a level treadmill using additional backward or forward pulling forces to simulate the effect of gravity. This comparison specifically focused on the energy cost of running, stride frequency (SF), electromyographic activity (EMG), leg and foot angles at foot strike, and ground impact shock. The main results are that SF, impact shock, and leg and foot angle parameters determined were very similar and significantly correlated between the two methods, the intercept and slope of the linear regression not differing significantly from zero and unity, respectively. The correlation of oxygen uptake (V̇O2) data between both methods was not significant during uphill running (r=0.42; P>0.05). V̇O2 data were correlated during downhill running (r=0.74; P<0.01) but there was a significant difference between the methods (bias=-2.51 ± 1.94 ml min(-1) kg(-1)). Linear regressions for EMG of vastus lateralis, biceps femoris, gastrocnemius lateralis, soleus and tibialis anterior were not different from the identity line but the systematic bias was elevated for this parameter. In conclusion, this method seems appropriate for the study of SF, leg and foot angle, impact shock parameters but is less applicable for physiological variables (EMG and energy cost) during uphill/downhill running when using a tilting force-measuring treadmill is not possible.

  9. Folding of proteins with an all-atom Go-model.

    PubMed

    Wu, L; Zhang, J; Qin, M; Liu, F; Wang, W

    2008-06-21

    The Go-like potential at a residual level has been successfully applied to the folding of proteins in many previous works. However, taking into consideration more detailed structural information in the atomic level, the definition of contacts used in these traditional Go-models may not be suitable for all-atom simulations. Here, in this work, we develop a rational definition of contacts considering the screening effect in the crowded intramolecular environment. In such a scheme, a large amount of screened atom pairs are excluded and the number of contacts is decreased compared to the case of the traditional definition. These contacts defined by such a new definition are compatible with the all-atom representation of protein structures. To verify the rationality of the new definition of contacts, the folding of proteins CI2 and SH3 is simulated by all-atom molecular dynamics simulations. A high folding cooperativity and good correlation of the simulated Phi-values with those obtained experimentally, especially for CI2, are found. This suggests that the all-atom Go-model is improved compared to the traditional Go-model. Based on the comparison of the Phi-values, the roles of side chains in the folding are discussed, and it is concluded that the side-chain structures are more important for local contacts in determining the transition state structures. Moreover, the relations between side chain and backbone orderings are also discussed.

  10. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  11. The additive effects of quinine on antidepressant drugs in the forced swimming test in mice.

    PubMed

    Guo, W Y; Todd, K G; Bourin, M; Hascoet, M

    1995-09-01

    The aim of this study was to investigate if quinine plus antidepressant drugs (ADS) leads to an additive effect in the forced swimming test. Quinine (0.125, 0.5 mg/kg) and ADS (subactive doses) were given IP 45 and 30 min, respectively, before the test. When combined with QUIN, all drugs that act via inhibition of 5-HT uptake (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine and fluvoxamine) significantly increased the swimming time of mice. Among trazodone, mianserin and iprindole (atypical ADS), only iprindole combined with quinine decreased the immobility (increased swimming) of the animals. The specific noradrenaline (NA) uptake inhibitors, desipramine and viloxazine, but not maprotiline, were also found to reduce the immobility time when pretreated with quinine. The mixed monoamine oxidase (MAO) inhibitor (pargyline) and MAO-A inhibitor (moclobemide) also shortened the period of immobility whereas the MAO-B inhibitor (nialamide) and the dopamine (DA) uptake inhibitor (bupropion) did not. Quinine's additive effects on several types of ADS is likely a result of blockade of potassium channels.

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

    PubMed Central

    2016-01-01

    Molecular dynamics (MD) simulations of ions (K+, Na+, Ca2+ 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. PMID:27118886

  13. Folding peptides and proteins with all-atom physics: methods and applications

    NASA Astrophysics Data System (ADS)

    Shell, M. Scott

    2008-03-01

    Computational methods offer powerful tools for investigating proteins and peptides at the molecular-level; however, it has proven challenging to reproduce the long time scale folding processes of these molecules at a level that is both faithful to the atomic driving forces and attainable with modern commodity cluster computing. Alternatively, the past decade has seen significant progress in using bioinformatics-based approaches to infer the three dimensional native structures of proteins, drawing upon extensive knowledge databases of known protein structures [1]. These methods work remarkably well when a homologous protein can be found to provide a structural template for a candidate sequence. However, in cases where homology to database proteins is low, where the folding pathway is of interest, or where conformational flexibility is substantial---as in many emerging protein and peptide technologies---bioinformatics methods perform poorly. There is therefore great interest in seeing purely physics-based approaches succeed. We discuss a purely physics-based, database-free folding method, relying on proper thermal sampling (replica exchange molecular dynamics) and molecular potential energy functions. In order to surmount the tremendous computational demands of all-atom folding simulations, our approach implements a conformational search strategy based on a putative protein folding mechanism called zipping and assembly [2-4]. That is, we explicitly seek out potential folding pathways inferred from short simulations, and iteratively pursue all such routes by coaxing a polypeptide chain along them. The method is called the Zipping and Assembly Method (ZAM) and it works in two parts: (1) the full polypeptide chain is broken into small fragments that are first simulated independently and then successively re-assembled into larger segments with further sampling, and (2) consistently stable structure in fragments is detected and locked into place, in order to avoid re

  14. Additive effects of clonidine and antidepressant drugs in the mouse forced-swimming test.

    PubMed

    Malinge, M; Bourin, M; Colombel, M C; Larousse, C

    1988-01-01

    In the mouse forced-swimming model, dose-dependent reversal of immobility was induced by the alpha-agonist clonidine given IP 30 min before testing. In addition, three preferential inhibitors of 5-HT uptake (citalopram, indalpine and fluvoxamine) had similar activity in the dose range 8-16 mg/kg as did the 5-HT1 agonist 8-OH-DPAT (1-4 mg/kg). Pretreatment with alpha-methyl-paratyrosine (100 mg/kg) did not prevent clonidine (1 mg/kg) action, suggesting that there was mediation by alpha post-junctional receptors. The effect of clonidine was unaltered by prazosin (2 mg/kg) and reversed by yohimbine (4 mg/kg) and 5-MeODMT (1 mg/kg), whereas it was potentiated by reserpine (2.5 mg/kg), methysergide (2 mg/kg) and ketanserin (8 mg/kg). Moreover, an ineffective dose of clonidine (0.06 mg/kg at 45 min pre-testing) made active subthreshold doses of various antidepressants (given at 30 min pre-testing): imipramine (4 mg/kg), amitriptyline (1 mg/kg), maprotiline (8 mg/kg), citalopram (2 mg/kg), indalpine, fluvoxamine and mianserin (4 mg/kg), viloxazine (2 mg/kg). Similar interactions were found with iprindole and nialamide (32 mg/kg), which were inactive alone up to 64 mg/kg, and 8-OH-DPAT (0.5 mg/kg) but not with major and minor tranquillizers. It is suggested that one effect of antidepressants might be the triggering of different relationships between alpha-2 and 5-HT mechanisms.

  15. Force.

    ERIC Educational Resources Information Center

    Gamble, Reed

    1989-01-01

    Discusses pupil misconceptions concerning forces. Summarizes some of Assessment of Performance Unit's findings on meaning of (1) force, (2) force and motion in one dimension and two dimensions, and (3) Newton's second law. (YP)

  16. Dynamic performance of duolayers at the air/water interface. 2. Mechanistic insights from all-atom simulations.

    PubMed

    Christofferson, Andrew J; Yiapanis, George; Leung, Andy H M; Prime, Emma L; Tran, Diana N H; Qiao, Greg G; Solomon, David H; Yarovsky, Irene

    2014-09-18

    The novel duolayer system, comprising a monolayer of ethylene glycol monooctadecyl ether (C18E1) and the water-soluble polymer poly(vinylpyrrolidone) (PVP), has been shown to resist forces such as wind stress to a greater degree than the C18E1 monolayer alone. This paper reports all-atom molecular dynamics simulations comparing the monolayer (C18E1 alone) and duolayer systems under an applied force parallel to the air/water interface. The simulations show that, due to the presence of PVP at the interface, the duolayer film exhibits an increase in chain tilt, ordering, and density, as well as a lower lateral velocity compared to the monolayer. These results provide a molecular rationale for the improved performance of the duolayer system under wind conditions, as well as an atomic-level explanation for the observed efficacy of the duolayer system as an evaporation suppressant, which may serve as a useful guide for future development for thin films where resistance to external perturbation is desirable.

  17. Changes in the nanoparticle aggregation rate due to the additional effect of electrostatic and magnetic forces on mass transport coefficients.

    PubMed

    Rosická, Dana; Sembera, Jan

    2013-01-01

    : The need may arise to be able to simulate the migration of groundwater nanoparticles through the ground. Transportation velocities of nanoparticles are different from that of water and depend on many processes that occur during migration. Unstable nanoparticles, such as zero-valent iron nanoparticles, are especially slowed down by aggregation between them. The aggregation occurs when attracting forces outweigh repulsive forces between the particles. In the case of iron nanoparticles that are used for remediation, magnetic forces between particles contribute to attractive forces and nanoparticles aggregate rapidly. This paper describes the addition of attractive magnetic forces and repulsive electrostatic forces between particles (by 'particle', we mean both single nanoparticles and created aggregates) into a basic model of aggregation which is commonly used. This model is created on the basis of the flow of particles in the proximity of observed particles that gives the rate of aggregation of the observed particle. By using a limit distance that has been described in our previous work, the flow of particles around one particle is observed in larger spacing between the particles. Attractive magnetic forces between particles draw the particles into closer proximity and result in aggregation. This model fits more closely with rapid aggregation which occurs between magnetic nanoparticles.

  18. Addition of Electrostatic Forces to EDEM with Applications to Triboelectrically Charged Particles

    NASA Technical Reports Server (NTRS)

    Hogue, Michael D.; Calle, Carlos; Curry, David

    2008-01-01

    Tribocharging of particles is common in many processes including fine powder handling and mixing, printer toner transport and dust extraction. In a lunar environment with its high vacuum and lack of water, electrostatic forces are an important factor to consider when designing and operating equipment. Dust mitigation and management is critical to safe and predictable performance of people and equipment. The extreme nature of lunar conditions makes it difficult and costly to carryout experiments on earth which are necessary to better understand how particles gather and transfer charge between each other and with equipment surfaces. DEM (Discrete Element Modeling) provides an excellent virtual laboratory for studying tribocharging of particles as well as for design of devices for dust mitigation and for other purposes related to handling and processing of lunar regolith. Theoretical and experimental work has been performed pursuant to incorporating screened Coulombic electrostatic forces into EDEM Tm, a commercial DEM software package. The DEM software is used to model the trajectories of large numbers of particles for industrial particulate handling and processing applications and can be coupled with other solvers and numerical models to calculate particle interaction with surrounding media and force fields. In this paper we will present overview of the theoretical calculations and experimental data and their comparison to the results of the DEM simulations. We will also discuss current plans to revise the DEM software with advanced electrodynamic and mechanical algorithms.

  19. All-atom molecular dynamics analysis of multi-peptide systems reproduces peptide solubility in line with experimental observations

    PubMed Central

    Kuroda, Yutaka; Suenaga, Atsushi; Sato, Yuji; Kosuda, Satoshi; Taiji, Makoto

    2016-01-01

    In order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 106 Å3 cubic boxes containing ~3 × 104 water molecules and 27 tetra-peptides regularly positioned at 23 Å from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any “artificial” hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y, and H formed large amorphous clusters, and those containing A, P, S, and T formed smaller ones. Tetra-peptides made of D, E, K, and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations. PMID:26817663

  20. All-Atom Molecular Dynamics of Virus Capsids as Drug Targets

    PubMed Central

    2016-01-01

    Virus capsids are protein shells that package the viral genome. Although their morphology and biological functions can vary markedly, capsids often play critical roles in regulating viral infection pathways. A detailed knowledge of virus capsids, including their dynamic structure, interactions with cellular factors, and the specific roles that they play in the replication cycle, is imperative for the development of antiviral therapeutics. The following Perspective introduces an emerging area of computational biology that focuses on the dynamics of virus capsids and capsid–protein assemblies, with particular emphasis on the effects of small-molecule drug binding on capsid structure, stability, and allosteric pathways. When performed at chemical detail, molecular dynamics simulations can reveal subtle changes in virus capsids induced by drug molecules a fraction of their size. Here, the current challenges of performing all-atom capsid–drug simulations are discussed, along with an outlook on the applicability of virus capsid simulations to reveal novel drug targets. PMID:27128262

  1. Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses.

    PubMed

    Hoang Man, Viet; Van-Oanh, Nguyen-Thi; Derreumaux, Philippe; Li, Mai Suan; Roland, Christopher; Sagui, Celeste; Nguyen, Phuong H

    2016-04-28

    Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use. However, considerably fewer studies are devoted to developing efficient methods to degrade or recycle such enhanced stability biomaterials. With this in mind, we carry out all-atom nonequilibrium molecular dynamics simulation, inspired by the recently developed mid-infrared free-electron laser pulse technology, to dissociate viruses. Adopting the poliovirus as a representative example, we find that the primary step in the dissociation process is due to the strong resonance between the amide I vibrational modes of the virus and the tuned laser frequencies. This process is determined by a balance between the formation and dissociation of the protein shell, reflecting the highly plasticity of the virus. Furthermore, our method should provide a feasible approach to simulate viruses, which is otherwise too expensive for conventional equilibrium all-atom simulations of such very large systems. Our work shows a proof of concept which may open a new, efficient way to cleave or to recycle virus-based materials, provide an extremely valuable tool for elucidating mechanical aspects of viruses, and may well play an important role in future fighting against virus-related diseases.

  2. Additive effect of lithium and clonidine with 5-HT1A agonists in the forced swimming test.

    PubMed

    Hascoet, M; Bourin, M; Khimake, S

    1994-03-01

    1. The aim of the present work was to demonstrate the possible additive effect of lithium and clonidine with 5-HT1a agonists in the forced swimming test. 2. Anti-depressant like effects of 5-HT1a agonists was investigated using forced swimming test. When administered alone, only 8-OH-DPAT reduced the immobility time in mice. 3. 5-HT1a agonists were then tested in combination with clonidine or lithium. Only gepirone and ipsapirone pretreated by either lithium or clonidine reduced immobility time in the forced swimming test. 4. The authors conclude that lithium and clonidine might be useful to predict antidepressant-like activity of new compounds.

  3. Variational Optimization of an All-Atom Implicit Solvent Force Field to Match Explicit Solvent Simulation Data.

    PubMed

    Bottaro, Sandro; Lindorff-Larsen, Kresten; Best, Robert B

    2013-12-10

    The development of accurate implicit solvation models with low computational cost is essential for addressing many large-scale biophysical problems. Here, we present an efficient solvation term based on a Gaussian solvent-exclusion model (EEF1) for simulations of proteins in aqueous environment, with the primary aim of having a good overlap with explicit solvent simulations, particularly for unfolded and disordered states - as would be needed for multiscale applications. In order to achieve this, we have used a recently proposed coarse-graining procedure based on minimization of an entropy-related objective function to train the model to reproduce the equilibrium distribution obtained from explicit water simulations. Via this methodology, we have optimized both a charge screening parameter and a backbone torsion term against explicit solvent simulations of an α-helical and a β-stranded peptide. The performance of the resulting effective energy function, termed EEF1-SB, is tested with respect to the properties of folded proteins, the folding of small peptides or fast-folding proteins, and NMR data for intrinsically disordered proteins. The results show that EEF1-SB provides a reasonable description of a wide range of systems, but its key advantage over other methods tested is that it captures very well the structure and dimension of disordered or weakly structured peptides. EEF1-SB is thus a computationally inexpensive (~ 10 times faster than Generalized-Born methods) and transferable approximation for treating solvent effects. PMID:24748852

  4. Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH

    NASA Astrophysics Data System (ADS)

    Wallace, Jason A.; Shen, Jana K.

    2012-11-01

    Recent development of constant pH molecular dynamics (CpHMD) methods has offered promise for adding pH-stat in molecular dynamics simulations. However, until now the working pH molecular dynamics (pHMD) implementations are dependent in part or whole on implicit-solvent models. Here we show that proper treatment of long-range electrostatics and maintaining charge neutrality of the system are critical for extending the continuous pHMD framework to the all-atom representation. The former is achieved here by adding forces to titration coordinates due to long-range electrostatics based on the generalized reaction field method, while the latter is made possible by a charge-leveling technique that couples proton titration with simultaneous ionization or neutralization of a co-ion in solution. We test the new method using the pH-replica-exchange CpHMD simulations of a series of aliphatic dicarboxylic acids with varying carbon chain length. The average absolute deviation from the experimental pKa values is merely 0.18 units. The results show that accounting for the forces due to extended electrostatics removes the large random noise in propagating titration coordinates, while maintaining charge neutrality of the system improves the accuracy in the calculated electrostatic interaction between ionizable sites. Thus, we believe that the way is paved for realizing pH-controlled all-atom molecular dynamics in the near future.

  5. Magnetic Force Microscopy Study of Zr2Co11 -Based Nanocrystalline Materials: Effect of Mo Addition

    DOE PAGES

    Yue, Lanping; Jin, Yunlong; Zhang, Wenyong; Sellmyer, David J.

    2015-01-01

    Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr2Co11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr16Co84-xMox(x=0, 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content (x≤1.5). he maximum energy product(BH)maxincreases with increasingxfrom 0.5 MGOe forx=0to a maximum value of 4.2 MGOe forx=1.5. he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shiftΦrmsvalue of 0.66° are observed for thex=1.5. he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample.« less

  6. Reduction of All-Atom Protein Folding Dynamics to One-Dimensional Diffusion.

    PubMed

    Zheng, Wenwei; Best, Robert B

    2015-12-10

    Theoretical models have often modeled protein folding dynamics as diffusion on a low-dimensional free energy surface, a remarkable simplification. However, the accuracy of such an approximation and the number of dimensions required were not clear. For all-atom folding simulations of ten small proteins in explicit solvent we show that the folding dynamics can indeed be accurately described as diffusion on just a single coordinate, the fraction of native contacts (Q). The diffusion models reproduce both folding rates, and finer details such as transition-path durations and diffusive propagators. The Q-averaged diffusion coefficients decrease with chain length, as anticipated from energy landscape theory. Although the Q-diffusion model does not capture transition-path durations for the protein NuG2, we show that this can be accomplished by designing an improved coordinate Qopt. Overall, one-dimensional diffusion on a suitable coordinate turns out to be a remarkably faithful model for the dynamics of the proteins considered.

  7. All-atom molecular dynamics simulation of a photosystem i/detergent complex.

    PubMed

    Harris, Bradley J; Cheng, Xiaolin; Frymier, Paul

    2014-10-01

    All-atom molecular dynamics (MD) simulation was used to investigate the solution structure and dynamics of the photosynthetic pigment-protein complex photosystem I (PSI) from Thermosynechococcus elongatus embedded in a toroidal belt of n-dodecyl-β-d-maltoside (DDM) detergent. Evaluation of root-mean-square deviations (RMSDs) relative to the known crystal structure show that the protein complex surrounded by DDM molecules is stable during the 200 ns simulation time, and root-mean-square fluctuation (RMSF) analysis indicates that regions of high local mobility correspond to solvent-exposed regions such as turns in the transmembrane α-helices and flexible loops on the stromal and lumenal faces. Comparing the protein-detergent complex to a pure detergent micelle, the detergent surrounding the PSI trimer is found to be less densely packed but with more ordered detergent tails, contrary to what is seen in most lipid bilayer models. We also investigated any functional implications for the observed conformational dynamics and protein-detergent interactions, discovering interesting structural changes in the psaL subunits associated with maintaining the trimeric structure of the protein. Importantly, we find that the docking of soluble electron mediators such as cytochrome c6 and ferredoxin to PSI is not significantly impacted by the solubilization of PSI in detergent.

  8. All-Atom Molecular Dynamics Simulation of Protein Translocation through an α-Hemolysin Nanopore.

    PubMed

    Di Marino, Daniele; Bonome, Emma Letizia; Tramontano, Anna; Chinappi, Mauro

    2015-08-01

    Nanopore sensing is attracting the attention of a large and varied scientific community. One of the main issues in nanopore sensing is how to associate the measured current signals to specific features of the molecule under investigation. This is particularly relevant when the translocating molecule is a protein and the pore is sufficiently narrow to necessarily involve unfolding of the translocating protein. Recent experimental results characterized the cotranslocational unfolding of Thioredoxin (Trx) passing through an α-hemolisin pore, providing evidence for the existence of a multistep process. In this study we report the results of all-atom molecular dynamics simulations of the same system. Our data indicate that Trx translocation involves two main barriers. The first one is an unfolding barrier associated with a translocation intermediate where the N-terminal region of Trx is stuck at the pore entrance in a conformation that strongly resembles the native one. After the abrupt unfolding of the N-terminal region, the Trx enters the α-hemolisin vestibule. During this stage, the constriction is occupied not only by the translocating residue but also by a hairpin-like structure forming a tangle in the constriction. The second barrier is associated with the disentangling of this region.

  9. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    SciTech Connect

    Andoh, Y.; Yoshii, N.; Yamada, A.; Kojima, H.; Mizutani, K.; Okazaki, S.; Fujimoto, K.; Nakagawa, A.; Nomoto, A.

    2014-10-28

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10{sup 6} all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  10. A real-time all-atom structural search engine for proteins.

    PubMed

    Gonzalez, Gabriel; Hannigan, Brett; DeGrado, William F

    2014-07-01

    Protein designers use a wide variety of software tools for de novo design, yet their repertoire still lacks a fast and interactive all-atom search engine. To solve this, we have built the Suns program: a real-time, atomic search engine integrated into the PyMOL molecular visualization system. Users build atomic-level structural search queries within PyMOL and receive a stream of search results aligned to their query within a few seconds. This instant feedback cycle enables a new "designability"-inspired approach to protein design where the designer searches for and interactively incorporates native-like fragments from proven protein structures. We demonstrate the use of Suns to interactively build protein motifs, tertiary interactions, and to identify scaffolds compatible with hot-spot residues. The official web site and installer are located at http://www.degradolab.org/suns/ and the source code is hosted at https://github.com/godotgildor/Suns (PyMOL plugin, BSD license), https://github.com/Gabriel439/suns-cmd (command line client, BSD license), and https://github.com/Gabriel439/suns-search (search engine server, GPLv2 license).

  11. ALMOST: an all atom molecular simulation toolkit for protein structure determination.

    PubMed

    Fu, Biao; Sahakyan, Aleksandr B; Camilloni, Carlo; Tartaglia, Gian Gaetano; Paci, Emanuele; Caflisch, Amedeo; Vendruscolo, Michele; Cavalli, Andrea

    2014-05-30

    Almost (all atom molecular simulation toolkit) is an open source computational package for structure determination and analysis of complex molecular systems including proteins, and nucleic acids. Almost has been designed with two primary goals: to provide tools for molecular structure determination using various types of experimental measurements as conformational restraints, and to provide methods for the analysis and assessment of structural and dynamical properties of complex molecular systems. The methods incorporated in Almost include the determination of structural and dynamical features of proteins using distance restraints derived from nuclear Overhauser effect measurements, orientational restraints obtained from residual dipolar couplings and the structural restraints from chemical shifts. Here, we present the first public release of Almost, highlight the key aspects of its computational design and discuss the main features currently implemented. Almost is available for the most common Unix-based operating systems, including Linux and Mac OS X. Almost is distributed free of charge under the GNU Public License, and is available both as a source code and as a binary executable from the project web site at http://www.open-almost.org. Interested users can follow and contribute to the further development of Almost on http://sourceforge.net/projects/almost.

  12. ALMOST: an all atom molecular simulation toolkit for protein structure determination.

    PubMed

    Fu, Biao; Sahakyan, Aleksandr B; Camilloni, Carlo; Tartaglia, Gian Gaetano; Paci, Emanuele; Caflisch, Amedeo; Vendruscolo, Michele; Cavalli, Andrea

    2014-05-30

    Almost (all atom molecular simulation toolkit) is an open source computational package for structure determination and analysis of complex molecular systems including proteins, and nucleic acids. Almost has been designed with two primary goals: to provide tools for molecular structure determination using various types of experimental measurements as conformational restraints, and to provide methods for the analysis and assessment of structural and dynamical properties of complex molecular systems. The methods incorporated in Almost include the determination of structural and dynamical features of proteins using distance restraints derived from nuclear Overhauser effect measurements, orientational restraints obtained from residual dipolar couplings and the structural restraints from chemical shifts. Here, we present the first public release of Almost, highlight the key aspects of its computational design and discuss the main features currently implemented. Almost is available for the most common Unix-based operating systems, including Linux and Mac OS X. Almost is distributed free of charge under the GNU Public License, and is available both as a source code and as a binary executable from the project web site at http://www.open-almost.org. Interested users can follow and contribute to the further development of Almost on http://sourceforge.net/projects/almost. PMID:24676684

  13. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    NASA Astrophysics Data System (ADS)

    Andoh, Y.; Yoshii, N.; Yamada, A.; Fujimoto, K.; Kojima, H.; Mizutani, K.; Nakagawa, A.; Nomoto, A.; Okazaki, S.

    2014-10-01

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 106 all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  14. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    NASA Astrophysics Data System (ADS)

    Zheng, Wenjun; Glenn, Paul

    2015-01-01

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  15. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    SciTech Connect

    Zheng, Wenjun Glenn, Paul

    2015-01-21

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  16. Effect of calcium and magnesium on phosphatidylserine membranes: experiments and all-atomic simulations.

    PubMed

    Martín-Molina, Alberto; Rodríguez-Beas, César; Faraudo, Jordi

    2012-05-01

    It is known that phosphatidylserine (PS(-)) lipids have a very similar affinity for Ca(2+) and Mg(2+) cations, as revealed by electrokinetic and stability experiments. However, despite this similar affinity, experimental evidence shows that the presence of Ca(2+) or Mg(2+) induces very different aggregation behavior for PS(-) liposomes as characterized by their fractal dimensions. Also, turbidity measurements confirm substantial differences in aggregation behavior depending on the presence of Ca(2+) or Mg(2+) cations. These puzzling results suggest that although these two cations have a similar affinity for PS(-) lipids, they induce substantial structural differences in lipid bilayers containing each of these cations. In other words, these cations have strong ion-specific effects on the structure of PS(-) membranes. This interpretation is supported by all-atomic molecular-dynamics simulations showing that Ca(2+) and Mg(2+) cations have different binding sites and induce different membrane hydration. We show that although both ions are incorporated deep into the hydrophilic region of the membrane, they have different positions and configurations at the membrane. Absorbed Ca(2+) cations present a peak at a distance ~2 nm from the center of the lipid bilayer, and their most probable binding configuration involves two oxygen atoms from each of the charged moieties of the PS molecule (phosphate and carboxyl groups). In contrast, the distribution of absorbed Mg(2+) cations has two different peaks, located a few angstroms before and after the Ca(2+) peak. The most probable configurations (corresponding to these two peaks) involve binding to two oxygen atoms from carboxyl groups (the most superficial binding peak) or two oxygen atoms from phosphate groups (the most internal peak). Moreover, simulations also show differences in the hydration structure of the membrane: we obtained a hydration of 7.5 and 9 water molecules per lipid in simulations with Ca(2+) and Mg(2

  17. All-atom semiclassical dynamics study of quantum coherence in photosynthetic Fenna-Matthews-Olson complex.

    PubMed

    Kim, Hyun Woo; Kelly, Aaron; Park, Jae Woo; Rhee, Young Min

    2012-07-18

    Although photosynthetic pigment-protein complexes are in noisy environments, recent experimental and theoretical results indicate that their excitation energy transfer (EET) can exhibit coherent characteristics for over hundreds of femtoseconds. Despite the almost universal observations of the coherence to some degree, questions still remain regarding the detailed role of the protein and the extent of high-temperature coherence. Here we adopt a theoretical method that incorporates an all-atom description of the photosynthetic complex within a semiclassical framework in order to study EET in the Fenna-Matthews-Olson complex. We observe that the vibrational modes of the chromophore tend to diminish the coherence at the ensemble level, yet much longer-lived coherences may be observed at the single-complex level. We also observe that coherent oscillations in the site populations also commence within tens of femtoseconds even when the system is initially prepared in a non-oscillatory stationary state. We show that the protein acts to maintain the electronic couplings among the system of embedded chromophores. We also investigate the extent to which the protein's electrostatic modulation that disperses the chromophore electronic energies may affect the coherence lifetime. Further, we observe that even though mutation-induced disruptions in the protein structure may change the coupling pattern, a relatively strong level of coupling and associated coherence in the dynamics still remain. Finally, we demonstrate that thermal fluctuations in the chromophore couplings induce some redundancy in the coherent energy-transfer pathway. Our results indicate that a description of both chromophore coupling strengths and their fluctuations is crucial to better understand coherent EET processes in photosynthetic systems. PMID:22708971

  18. RNABC: forward kinematics to reduce all-atom steric clashes in RNA backbone.

    PubMed

    Wang, Xueyi; Kapral, Gary; Murray, Laura; Richardson, David; Richardson, Jane; Snoeyink, Jack

    2008-01-01

    Although accurate details in RNA structure are of great importance for understanding RNA function, the backbone conformation is difficult to determine, and most existing RNA structures show serious steric clashes (>or= 0.4 A overlap) when hydrogen atoms are taken into account. We have developed a program called RNABC (RNA Backbone Correction) that performs local perturbations to search for alternative conformations that avoid those steric clashes or other local geometry problems. Its input is an all-atom coordinate file for an RNA crystal structure (usually from the MolProbity web service), with problem areas specified. RNABC rebuilds a suite (the unit from sugar to sugar) by anchoring the phosphorus and base positions, which are clearest in crystallographic electron density, and reconstructing the other atoms using forward kinematics. Geometric parameters are constrained within user-specified tolerance of canonical or original values, and torsion angles are constrained to ranges defined through empirical database analyses. Several optimizations reduce the time required to search the many possible conformations. The output results are clustered and presented to the user, who can choose whether to accept one of the alternative conformations. Two test evaluations show the effectiveness of RNABC, first on the S-motifs from 42 RNA structures, and second on the worst problem suites (clusters of bad clashes, or serious sugar pucker outliers) in 25 unrelated RNA structures. Among the 101 S-motifs, 88 had diagnosed problems, and RNABC produced clash-free conformations with acceptable geometry for 71 of those (about 80%). For the 154 worst problem suites, RNABC proposed alternative conformations for 72. All but 8 of those were judged acceptable after examining electron density (where available) and local conformation. Thus, even for these worst cases, nearly half the time RNABC suggested corrections suitable to initiate further crystallographic refinement. The program is

  19. MolProbity: all-atom structure validation for macromolecular crystallography

    SciTech Connect

    Chen, Vincent B.; Arendall, W. Bryan III; Headd, Jeffrey J.; Keedy, Daniel A.; Immormino, Robert M.; Kapral, Gary J.; Murray, Laura W.; Richardson, Jane S.; Richardson, David C.

    2010-01-01

    MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction. MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors’ contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database.

  20. Dissociation of a Dynamic Protein Complex Studied by All-Atom Molecular Simulations.

    PubMed

    Zhang, Liqun; Borthakur, Susmita; Buck, Matthias

    2016-02-23

    The process of protein complex dissociation remains to be understood at the atomic level of detail. Computers now allow microsecond timescale molecular-dynamics simulations, which make the visualization of such processes possible. Here, we investigated the dissociation process of the EphA2-SHIP2 SAM-SAM domain heterodimer complex using unrestrained all-atom molecular-dynamics simulations. Previous studies on this system have shown that alternate configurations are sampled, that their interconversion can be fast, and that the complex is dynamic by nature. Starting from different NMR-derived structures, mutants were designed to stabilize a subset of configurations by swapping ion pairs across the protein-protein interface. We focused on two mutants, K956D/D1235K and R957D/D1223R, with attenuated binding affinity compared with the wild-type proteins. In contrast to calculations on the wild-type complexes, the majority of simulations of these mutants showed protein dissociation within 2.4 μs. During the separation process, we observed domain rotation and pivoting as well as a translation and simultaneous rolling, typically to alternate and weaker binding interfaces. Several unsuccessful recapturing attempts occurred once the domains were moderately separated. An analysis of protein solvation suggests that the dissociation process correlates with a progressive loss of protein-protein contacts. Furthermore, an evaluation of internal protein dynamics using quasi-harmonic and order parameter analyses indicates that changes in protein internal motions are expected to contribute significantly to the thermodynamics of protein dissociation. Considering protein association as the reverse of the separation process, the initial role of charged/polar interactions is emphasized, followed by changes in protein and solvent dynamics. The trajectories show that protein separation does not follow a single distinct pathway, but suggest that the mechanism of dissociation is common in

  1. All-atom 3D structure prediction of transmembrane β-barrel proteins from sequences

    PubMed Central

    Hayat, Sikander; Sander, Chris; Marks, Debora S.

    2015-01-01

    Transmembrane β-barrels (TMBs) carry out major functions in substrate transport and protein biogenesis but experimental determination of their 3D structure is challenging. Encouraged by successful de novo 3D structure prediction of globular and α-helical membrane proteins from sequence alignments alone, we developed an approach to predict the 3D structure of TMBs. The approach combines the maximum-entropy evolutionary coupling method for predicting residue contacts (EVfold) with a machine-learning approach (boctopus2) for predicting β-strands in the barrel. In a blinded test for 19 TMB proteins of known structure that have a sufficient number of diverse homologous sequences available, this combined method (EVfold_bb) predicts hydrogen-bonded residue pairs between adjacent β-strands at an accuracy of ∼70%. This accuracy is sufficient for the generation of all-atom 3D models. In the transmembrane barrel region, the average 3D structure accuracy [template-modeling (TM) score] of top-ranked models is 0.54 (ranging from 0.36 to 0.85), with a higher (44%) number of residue pairs in correct strand–strand registration than in earlier methods (18%). Although the nonbarrel regions are predicted less accurately overall, the evolutionary couplings identify some highly constrained loop residues and, for FecA protein, the barrel including the structure of a plug domain can be accurately modeled (TM score = 0.68). Lower prediction accuracy tends to be associated with insufficient sequence information and we therefore expect increasing numbers of β-barrel families to become accessible to accurate 3D structure prediction as the number of available sequences increases. PMID:25858953

  2. Effect of calcium and magnesium on phosphatidylserine membranes: experiments and all-atomic simulations.

    PubMed

    Martín-Molina, Alberto; Rodríguez-Beas, César; Faraudo, Jordi

    2012-05-01

    It is known that phosphatidylserine (PS(-)) lipids have a very similar affinity for Ca(2+) and Mg(2+) cations, as revealed by electrokinetic and stability experiments. However, despite this similar affinity, experimental evidence shows that the presence of Ca(2+) or Mg(2+) induces very different aggregation behavior for PS(-) liposomes as characterized by their fractal dimensions. Also, turbidity measurements confirm substantial differences in aggregation behavior depending on the presence of Ca(2+) or Mg(2+) cations. These puzzling results suggest that although these two cations have a similar affinity for PS(-) lipids, they induce substantial structural differences in lipid bilayers containing each of these cations. In other words, these cations have strong ion-specific effects on the structure of PS(-) membranes. This interpretation is supported by all-atomic molecular-dynamics simulations showing that Ca(2+) and Mg(2+) cations have different binding sites and induce different membrane hydration. We show that although both ions are incorporated deep into the hydrophilic region of the membrane, they have different positions and configurations at the membrane. Absorbed Ca(2+) cations present a peak at a distance ~2 nm from the center of the lipid bilayer, and their most probable binding configuration involves two oxygen atoms from each of the charged moieties of the PS molecule (phosphate and carboxyl groups). In contrast, the distribution of absorbed Mg(2+) cations has two different peaks, located a few angstroms before and after the Ca(2+) peak. The most probable configurations (corresponding to these two peaks) involve binding to two oxygen atoms from carboxyl groups (the most superficial binding peak) or two oxygen atoms from phosphate groups (the most internal peak). Moreover, simulations also show differences in the hydration structure of the membrane: we obtained a hydration of 7.5 and 9 water molecules per lipid in simulations with Ca(2+) and Mg(2

  3. Effect of Calcium and Magnesium on Phosphatidylserine Membranes: Experiments and All-Atomic Simulations

    PubMed Central

    Martín-Molina, Alberto; Rodríguez-Beas, César; Faraudo, Jordi

    2012-01-01

    It is known that phosphatidylserine (PS−) lipids have a very similar affinity for Ca2+ and Mg2+ cations, as revealed by electrokinetic and stability experiments. However, despite this similar affinity, experimental evidence shows that the presence of Ca2+ or Mg2+ induces very different aggregation behavior for PS− liposomes as characterized by their fractal dimensions. Also, turbidity measurements confirm substantial differences in aggregation behavior depending on the presence of Ca2+ or Mg2+ cations. These puzzling results suggest that although these two cations have a similar affinity for PS− lipids, they induce substantial structural differences in lipid bilayers containing each of these cations. In other words, these cations have strong ion-specific effects on the structure of PS− membranes. This interpretation is supported by all-atomic molecular-dynamics simulations showing that Ca2+ and Mg2+ cations have different binding sites and induce different membrane hydration. We show that although both ions are incorporated deep into the hydrophilic region of the membrane, they have different positions and configurations at the membrane. Absorbed Ca2+ cations present a peak at a distance ∼2 nm from the center of the lipid bilayer, and their most probable binding configuration involves two oxygen atoms from each of the charged moieties of the PS molecule (phosphate and carboxyl groups). In contrast, the distribution of absorbed Mg2+ cations has two different peaks, located a few angstroms before and after the Ca2+ peak. The most probable configurations (corresponding to these two peaks) involve binding to two oxygen atoms from carboxyl groups (the most superficial binding peak) or two oxygen atoms from phosphate groups (the most internal peak). Moreover, simulations also show differences in the hydration structure of the membrane: we obtained a hydration of 7.5 and 9 water molecules per lipid in simulations with Ca2+ and Mg2+, respectively. PMID:22824273

  4. Optimization of the CHARMM additive force field for DNA: Improved treatment of the BI/BII conformational equilibrium.

    PubMed

    Hart, Katarina; Foloppe, Nicolas; Baker, Christopher M; Denning, Elizabeth J; Nilsson, Lennart; Mackerell, Alexander D

    2012-01-10

    The B-form of DNA can populate two different backbone conformations: BI and BII, defined by the difference between the torsion angles ε and ζ (BI = ε-ζ < 0 and BII = ε-ζ > 0). BI is the most populated state, but the population of the BII state, which is sequence dependent, is significant and accumulating evidence shows that BII affects the overall structure of DNA, and thus influences protein-DNA recognition. This work presents a reparametrization of the CHARMM27 additive nucleic acid force field to increase the sampling of the BII form in MD simulations of DNA. In addition, minor modifications of sugar puckering were introduced to facilitate sampling of the A form of DNA under the appropriate environmental conditions. Parameter optimization was guided by quantum mechanical data on model compounds, followed by calculations on several DNA duplexes in the condensed phase. The selected optimized parameters were then validated against a number of DNA duplexes, with the most extensive tests performed on the EcoRI dodecamer, including comparative calculations using the Amber Parm99bsc0 force field. The new CHARMM model better reproduces experimentally observed sampling of the BII conformation, including sampling as a function of sequence. In addition, the model reproduces the A form of the 1ZF1 duplex in 75 % ethanol, and yields a stable Z-DNA conformation of duplex (GTACGTAC) in its crystal environment. The resulting model, in combination with a recent reoptimization of the CHARMM27 force field for RNA, will be referred to as CHARMM36.

  5. Lessons Learned at the Idaho National Laboratory for the Entry into Force of the U.S. Additional Protocol

    SciTech Connect

    Jeffrey C. Joe; Shauna A. Hoiland

    2009-07-01

    For a number of years, the Idaho National Laboratory (INL) has been preparing for the entry into force of the U.S. Additional Protocol (AP). These preparations included attending training, participating in tabletop exercises, preparing draft declarations, developing INL-specific guidance documents, preparing for and hosting a mock complementary access visit, and preparing declarations for official submittal. All of these activities, the training materials, and software developed by other U.S. DOE national laboratories (PNNL, ORNL, LANL, and BNL) were very helpful in preparing for the entry into force of the AP. As with any endeavor of this size and complexity, however, there are always instances where even the best preparations and advanced planning do not anticipate every challenge. As the DOE's lead nuclear energy research and development facility, the INL faced many unique challenges. The majority of research conducted at the INL is nuclear fuel cycle related, most of which is not protected by the National Security Exclusion. This paper describes the lessons learned from the INL’s experience of preparing for the entry into force of the AP, specifically how translating and implementing general principles into actual activities proved to be one of many challenges, and provides general suggestions on how to respond effectively and efficiently to routine annual data calls and other AP requests.

  6. Dissociation of a Dynamic Protein Complex Studied by All-Atom Molecular Simulations.

    PubMed

    Zhang, Liqun; Borthakur, Susmita; Buck, Matthias

    2016-02-23

    The process of protein complex dissociation remains to be understood at the atomic level of detail. Computers now allow microsecond timescale molecular-dynamics simulations, which make the visualization of such processes possible. Here, we investigated the dissociation process of the EphA2-SHIP2 SAM-SAM domain heterodimer complex using unrestrained all-atom molecular-dynamics simulations. Previous studies on this system have shown that alternate configurations are sampled, that their interconversion can be fast, and that the complex is dynamic by nature. Starting from different NMR-derived structures, mutants were designed to stabilize a subset of configurations by swapping ion pairs across the protein-protein interface. We focused on two mutants, K956D/D1235K and R957D/D1223R, with attenuated binding affinity compared with the wild-type proteins. In contrast to calculations on the wild-type complexes, the majority of simulations of these mutants showed protein dissociation within 2.4 μs. During the separation process, we observed domain rotation and pivoting as well as a translation and simultaneous rolling, typically to alternate and weaker binding interfaces. Several unsuccessful recapturing attempts occurred once the domains were moderately separated. An analysis of protein solvation suggests that the dissociation process correlates with a progressive loss of protein-protein contacts. Furthermore, an evaluation of internal protein dynamics using quasi-harmonic and order parameter analyses indicates that changes in protein internal motions are expected to contribute significantly to the thermodynamics of protein dissociation. Considering protein association as the reverse of the separation process, the initial role of charged/polar interactions is emphasized, followed by changes in protein and solvent dynamics. The trajectories show that protein separation does not follow a single distinct pathway, but suggest that the mechanism of dissociation is common in

  7. Resonance scattering and radiation force calculations for an elastic cylinder using the translational addition theorem for cylindrical wave functions

    SciTech Connect

    Mitri, F. G.

    2015-09-15

    The standard Resonance Scattering Theory (RST) of plane waves is extended for the case of any two-dimensional (2D) arbitrarily-shaped monochromatic beam incident upon an elastic cylinder with arbitrary location using an exact methodology based on Graf’s translational addition theorem for the cylindrical wave functions. The analysis is exact as it does not require numerical integration procedures. The formulation is valid for any cylinder of finite size and material that is immersed in a nonviscous fluid. Partial-wave series expansions (PWSEs) for the incident, internal and scattered linear pressure fields are derived, and the analysis is further extended to obtain generalized expressions for the on-axis and off-axis acoustic radiation force components. The wave-fields are expressed using generalized PWSEs involving the beam-shape coefficients (BSCs) and the scattering coefficients of the cylinder. The off-axial BSCs are expressed analytically in terms of an infinite PWSE with emphasis on the translational offset distance d. Numerical computations are considered for a zeroth-order quasi-Gaussian beam chosen as an example to illustrate the analysis. Acoustic resonance scattering directivity diagrams are calculated by subtracting an appropriate background from the expression of the scattered pressure field. In addition, computations for the radiation force exerted on an elastic cylinder centered on the axis of wave propagation of the beam, and shifted off-axially are analyzed and discussed.

  8. Resonance scattering and radiation force calculations for an elastic cylinder using the translational addition theorem for cylindrical wave functions

    NASA Astrophysics Data System (ADS)

    Mitri, F. G.

    2015-09-01

    The standard Resonance Scattering Theory (RST) of plane waves is extended for the case of any two-dimensional (2D) arbitrarily-shaped monochromatic beam incident upon an elastic cylinder with arbitrary location using an exact methodology based on Graf's translational addition theorem for the cylindrical wave functions. The analysis is exact as it does not require numerical integration procedures. The formulation is valid for any cylinder of finite size and material that is immersed in a nonviscous fluid. Partial-wave series expansions (PWSEs) for the incident, internal and scattered linear pressure fields are derived, and the analysis is further extended to obtain generalized expressions for the on-axis and off-axis acoustic radiation force components. The wave-fields are expressed using generalized PWSEs involving the beam-shape coefficients (BSCs) and the scattering coefficients of the cylinder. The off-axial BSCs are expressed analytically in terms of an infinite PWSE with emphasis on the translational offset distance d. Numerical computations are considered for a zeroth-order quasi-Gaussian beam chosen as an example to illustrate the analysis. Acoustic resonance scattering directivity diagrams are calculated by subtracting an appropriate background from the expression of the scattered pressure field. In addition, computations for the radiation force exerted on an elastic cylinder centered on the axis of wave propagation of the beam, and shifted off-axially are analyzed and discussed.

  9. Relationship between population of the fibril-prone conformation in the monomeric state and oligomer formation times of peptides: Insights from all-atom simulations

    NASA Astrophysics Data System (ADS)

    Nam, Hoang Bao; Kouza, Maksim; Zung, Hoang; Li, Mai Suan

    2010-04-01

    Despite much progress in understanding the aggregation process of biomolecules, the factors that govern its rates have not been fully understood. This problem is of particular importance since many conformational diseases such as Alzheimer, Parkinson, and type-II diabetes are associated with the protein oligomerization. Having performed all-atom simulations with explicit water and various force fields for two short peptides KFFE and NNQQ, we show that their oligomer formation times are strongly correlated with the population of the fibril-prone conformation in the monomeric state. The larger the population the faster the aggregation process. Our result not only suggests that this quantity plays a key role in the self-assembly of polypeptide chains but also opens a new way to understand the fibrillogenesis of biomolecules at the monomeric level. The nature of oligomer ordering of NNQQ is studied in detail.

  10. Effects of Water Models on Binding Affinity: Evidence from All-Atom Simulation of Binding of Tamiflu to A/H5N1 Neuraminidase

    PubMed Central

    Nguyen, Trang Truc; Viet, Man Hoang

    2014-01-01

    The influence of water models SPC, SPC/E, TIP3P, and TIP4P on ligand binding affinity is examined by calculating the binding free energy ΔGbind of oseltamivir carboxylate (Tamiflu) to the wild type of glycoprotein neuraminidase from the pandemic A/H5N1 virus. ΔGbind is estimated by the Molecular Mechanic-Poisson Boltzmann Surface Area method and all-atom simulations with different combinations of these aqueous models and four force fields AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA/L. It is shown that there is no correlation between the binding free energy and the water density in the binding pocket in CHARMM. However, for three remaining force fields ΔGbind decays with increase of water density. SPC/E provides the lowest binding free energy for any force field, while the water effect is the most pronounced in CHARMM. In agreement with the popular GROMACS recommendation, the binding score obtained by combinations of AMBER-TIP3P, OPLS-TIP4P, and GROMOS-SPC is the most relevant to the experiments. For wild-type neuraminidase we have found that SPC is more suitable for CHARMM than TIP3P recommended by GROMACS for studying ligand binding. However, our study for three of its mutants reveals that TIP3P is presumably the best choice for CHARMM. PMID:24672329

  11. Bridging between NMA and Elastic Network Models: Preserving All-Atom Accuracy in Coarse-Grained Models

    PubMed Central

    Na, Hyuntae; Jernigan, Robert L.; Song, Guang

    2015-01-01

    Dynamics can provide deep insights into the functional mechanisms of proteins and protein complexes. For large protein complexes such as GroEL/GroES with more than 8,000 residues, obtaining a fine-grained all-atom description of its normal mode motions can be computationally prohibitive and is often unnecessary. For this reason, coarse-grained models have been used successfully. However, most existing coarse-grained models use extremely simple potentials to represent the interactions within the coarse-grained structures and as a result, the dynamics obtained for the coarse-grained structures may not always be fully realistic. There is a gap between the quality of the dynamics of the coarse-grained structures given by all-atom models and that by coarse-grained models. In this work, we resolve an important question in protein dynamics computations—how can we efficiently construct coarse-grained models whose description of the dynamics of the coarse-grained structures remains as accurate as that given by all-atom models? Our method takes advantage of the sparseness of the Hessian matrix and achieves a high efficiency with a novel iterative matrix projection approach. The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes. The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models. PMID:26473491

  12. Bridging between NMA and Elastic Network Models: Preserving All-Atom Accuracy in Coarse-Grained Models.

    PubMed

    Na, Hyuntae; Jernigan, Robert L; Song, Guang

    2015-10-01

    Dynamics can provide deep insights into the functional mechanisms of proteins and protein complexes. For large protein complexes such as GroEL/GroES with more than 8,000 residues, obtaining a fine-grained all-atom description of its normal mode motions can be computationally prohibitive and is often unnecessary. For this reason, coarse-grained models have been used successfully. However, most existing coarse-grained models use extremely simple potentials to represent the interactions within the coarse-grained structures and as a result, the dynamics obtained for the coarse-grained structures may not always be fully realistic. There is a gap between the quality of the dynamics of the coarse-grained structures given by all-atom models and that by coarse-grained models. In this work, we resolve an important question in protein dynamics computations--how can we efficiently construct coarse-grained models whose description of the dynamics of the coarse-grained structures remains as accurate as that given by all-atom models? Our method takes advantage of the sparseness of the Hessian matrix and achieves a high efficiency with a novel iterative matrix projection approach. The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes. The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models.

  13. All-atom molecular dynamics simulations of actin-myosin interactions: a comparative study of cardiac α myosin, β myosin, and fast skeletal muscle myosin.

    PubMed

    Li, Minghui; Zheng, Wenjun

    2013-11-26

    Myosins are a superfamily of actin-binding motor proteins with significant variations in kinetic properties (such as actin binding affinity) between different isoforms. It remains unknown how such kinetic variations arise from the structural and dynamic tuning of the actin-myosin interface at the amino acid residue level. To address this key issue, we have employed molecular modeling and simulations to investigate, with atomistic details, the isoform dependence of actin-myosin interactions in the rigor state. By combining electron microscopy-based docking with homology modeling, we have constructed three all-atom models for human cardiac α and β and rabbit fast skeletal muscle myosin in complex with three actin subunits in the rigor state. Starting from these models, we have performed extensive all-atom molecular dynamics (MD) simulations (total of 100 ns per system) and then used the MD trajectories to calculate actin-myosin binding free energies with contributions from both electrostatic and nonpolar forces. Our binding calculations are in good agreement with the experimental finding of isoform-dependent differences in actin binding affinity between these myosin isoforms. Such differences are traced to changes in actin-myosin electrostatic interactions (i.e., hydrogen bonds and salt bridges) that are highly dynamic and involve several flexible actin-binding loops. By partitioning the actin-myosin binding free energy to individual myosin residues, we have also identified key myosin residues involved in the actin-myosin interactions, some of which were previously validated experimentally or implicated in cardiomyopathy mutations, and the rest make promising targets for future mutational experiments. PMID:24224850

  14. Additive effects of glyburide and antidepressants in the forced swimming test: evidence for the involvement of potassium channel blockade.

    PubMed

    Guo, W; Todd, K; Bourin, M; Hascoet, M; Kouadio, F

    1996-08-01

    Evidence in the literature suggests that the modulatory effects of antidepressant drugs (ADS) on neuronal excitability, via the inhibition of K+ channels, may be the final common pathway of pharmacological action. Therefore, we tested the hypothesis that combining the ATP-sensitive K+ channel blocker glyburide with a variety of ADS would produce an additive effect and decrease the immobility time of mice in the forced swimming test (FST). Glyburide (GLY, IP, 30 and 50 mg/kg) and subactive doses of ADS were administered 45 and 30 min, respectively, prior to behavioral testing. Results showed that when combined with GLY, ADS whose main pharmacological effect is one of 5-HT uptake blockade (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine, and fluvoxamine) were more effective in decreasing the amount of time mice were immobile, than when these drugs were administered alone. Some noradrenaline uptake inhibiting ADS (desipramine and viloxazine, but not maprotiline) were also significantly more effective in decreasing immobility time when combined with GLY than when administered alone. Pretreatment with GLY was found to have no effect on the dopamine uptake inhibitor bupropion, and out of the atypical ADS tested (trazodone, mianserine and iprindole), only coadministration with iprindole decreased the immobility time. Only the specific MAO-A inhibitor moclobemide was observed to have an antiimmobility effect when combined with GLY. Neither MAO-B specific (RO 16 6491) nor mixed MAO inhibitors (nialamide and pargyline) interacted with GLY to produce antiimmobility effects. These results corroborate and extend our previous report of the ADS enhancing effects of quinine in the same behavioral model, and suggest that the additive effects of quinine and GLY on ADS in FST are a result of K+ channel blockade.

  15. Forced and natural carbonation of lime-based mortars with and without additives: Mineralogical and textural changes

    SciTech Connect

    Cultrone, G.

    2005-12-15

    We have studied the carbonation process in different types of mortars, with and without pozzolana or air-entraining additives, subject to a CO{sub 2}-rich atmosphere and compared the results with those of similar naturally carbonated mortars. We used X-ray diffraction technique to demonstrate that high CO{sub 2} concentrations favour a faster, more complete carbonation process with 8 days being sufficient to convert portlandite into 90 wt.% calcite. Full carbonation, however, is not reached during the life-span of the tests, not even in forced carbonation experiments. This could be due to at least one of the following phenomena: a premature drying of samples during carbonation reaction, the temperature at which the carbonation process was carried out or the reduction of pore volume occupied by newly formed calcite crystals. This last option seems to be the least probable. We observed a more prolific development of calcite crystals in the pores and fissures through which the carbonic anhydride flows. Under natural conditions, carbonation is much slower and similar levels are not reached for 6 months. These differences suggest that the carbonation process is influenced by the amount of CO{sub 2} used. Both the mineralogy and texture of mortars vary depending on the type of additive used but the speed of the portlandite-calcite transformation does not change significantly. Pozzolana produces hydraulic mortars although the quantity of calcium aluminosilicate crystals is low. The air-entraining agent significantly alters the texture of the mortars creating rounded pores and eliminating or reducing the drying cracks.

  16. Accurate and efficient loop selections by the DFIRE-based all-atom statistical potential.

    PubMed

    Zhang, Chi; Liu, Song; Zhou, Yaoqi

    2004-02-01

    The conformations of loops are determined by the water-mediated interactions between amino acid residues. Energy functions that describe the interactions can be derived either from physical principles (physical-based energy function) or statistical analysis of known protein structures (knowledge-based statistical potentials). It is commonly believed that statistical potentials are appropriate for coarse-grained representation of proteins but are not as accurate as physical-based potentials when atomic resolution is required. Several recent applications of physical-based energy functions to loop selections appear to support this view. In this article, we apply a recently developed DFIRE-based statistical potential to three different loop decoy sets (RAPPER, Jacobson, and Forrest-Woolf sets). Together with a rotamer library for side-chain optimization, the performance of DFIRE-based potential in the RAPPER decoy set (385 loop targets) is comparable to that of AMBER/GBSA for short loops (two to eight residues). The DFIRE is more accurate for longer loops (9 to 12 residues). Similar trend is observed when comparing DFIRE with another physical-based OPLS/SGB-NP energy function in the large Jacobson decoy set (788 loop targets). In the Forrest-Woolf decoy set for the loops of membrane proteins, the DFIRE potential performs substantially better than the combination of the CHARMM force field with several solvation models. The results suggest that a single-term DFIRE-statistical energy function can provide an accurate loop prediction at a fraction of computing cost required for more complicate physical-based energy functions. A Web server for academic users is established for loop selection at the softwares/services section of the Web site http://theory.med.buffalo.edu/.

  17. The equilibrium properties and folding kinetics of an all-atom Go model of the Trp-cage.

    PubMed

    Linhananta, Apichart; Boer, Jesse; MacKay, Ian

    2005-03-15

    The ultrafast-folding 20-residue Trp-cage protein is quickly becoming a new benchmark for molecular dynamics studies. Already several all-atom simulations have probed its equilibrium and kinetic properties. In this work an all-atom Go model is used to accurately represent the side-chain packing and native atomic contacts of the Trp-cage. The model reproduces the hallmark thermodynamics cooperativity of small proteins. Folding simulations observe that in the fast-folding dominant pathway, partial alpha-helical structure forms before hydrophobic core collapse. In the slow-folding secondary pathway, partial core collapse occurs before helical structure. The slow-folding rate of the secondary pathway is attributed to the loss of side-chain rotational freedom, due to the early core collapse, which impedes the helix formation. A major finding is the observation of a low-temperature kinetic intermediate stabilized by a salt bridge between residues Asp-9 and Arg-16. Similar observations [R. Zhou, Proc. Natl. Acad. Sci. U.S.A. 100, 13280 (2003)] were reported in a recent study using an all-atom model of the Trp-cage in explicit water, in which the salt-bridge stabilized intermediate was hypothesized to be the origin of the ultrafast-folding mechanism. A theoretical mutation that eliminates the Asp-9-Arg-16 salt bridge, but leaves the residues intact, is performed. Folding simulations of the mutant Trp-cage observe a two-state free-energy landscape with no kinetic intermediate and a significant decrease in the folding rate, in support of the hypothesis.

  18. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): time-resolved fluorescence measurements and all-atom molecular dynamics simulations.

    PubMed

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH3CONH2) and urea (NH2CONH2) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH3CONH2 + (1 - f)NH2CONH2] have been studied in a temperature range of 328-353 K which is ∼120-145 K above the measured glass transition temperatures (∼207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (∼70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α2) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems.

  19. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): Time-resolved fluorescence measurements and all-atom molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-01

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH3CONH2) and urea (NH2CONH2) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH3CONH2 + (1 - f)NH2CONH2] have been studied in a temperature range of 328-353 K which is ˜120-145 K above the measured glass transition temperatures (˜207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (˜70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α2) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems.

  20. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): Time-resolved fluorescence measurements and all-atom molecular dynamics simulations

    SciTech Connect

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH{sub 3}CONH{sub 2}) and urea (NH{sub 2}CONH{sub 2}) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH{sub 3}CONH{sub 2} + (1 − f)NH{sub 2}CONH{sub 2}] have been studied in a temperature range of 328-353 K which is ∼120-145 K above the measured glass transition temperatures (∼207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (∼70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α{sub 2}) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems.

  1. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): time-resolved fluorescence measurements and all-atom molecular dynamics simulations.

    PubMed

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH3CONH2) and urea (NH2CONH2) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH3CONH2 + (1 - f)NH2CONH2] have been studied in a temperature range of 328-353 K which is ∼120-145 K above the measured glass transition temperatures (∼207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (∼70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α2) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems. PMID:25612718

  2. All-Atom Structural Models of the Transmembrane Domains of Insulin and Type 1 Insulin-Like Growth Factor Receptors

    PubMed Central

    Mohammadiarani, Hossein; Vashisth, Harish

    2016-01-01

    The receptor tyrosine kinase superfamily comprises many cell-surface receptors including the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF1R) that are constitutively homodimeric transmembrane glycoproteins. Therefore, these receptors require ligand-triggered domain rearrangements rather than receptor dimerization for activation. Specifically, binding of peptide ligands to receptor ectodomains transduces signals across the transmembrane domains for trans-autophosphorylation in cytoplasmic kinase domains. The molecular details of these processes are poorly understood in part due to the absence of structures of full-length receptors. Using MD simulations and enhanced conformational sampling algorithms, we present all-atom structural models of peptides containing 51 residues from the transmembrane and juxtamembrane regions of IR and IGF1R. In our models, the transmembrane regions of both receptors adopt helical conformations with kinks at Pro961 (IR) and Pro941 (IGF1R), but the C-terminal residues corresponding to the juxtamembrane region of each receptor adopt unfolded and flexible conformations in IR as opposed to a helix in IGF1R. We also observe that the N-terminal residues in IR form a kinked-helix sitting at the membrane–solvent interface, while homologous residues in IGF1R are unfolded and flexible. These conformational differences result in a larger tilt-angle of the membrane-embedded helix in IGF1R in comparison to IR to compensate for interactions with water molecules at the membrane–solvent interfaces. Our metastable/stable states for the transmembrane domain of IR, observed in a lipid bilayer, are consistent with a known NMR structure of this domain determined in detergent micelles, and similar states in IGF1R are consistent with a previously reported model of the dimerized transmembrane domains of IGF1R. Our all-atom structural models suggest potentially unique structural organization of kinase domains in each receptor. PMID

  3. Effects of Bi-2212 addition on the levitation force properties of bulk MgB2 superconductors

    NASA Astrophysics Data System (ADS)

    Taylan Koparan, E.; Savaskan, B.; Guner, S. B.; Celik, S.

    2016-02-01

    We present a detailed investigation of the effects of Bi2Sr2Ca1Cu2O8+κ (Bi-2212) adding on the levitation force and magnetic properties of bulk MgB2 obtained by hot press method. The amount of Bi-2212 was varied between 0 and 10 wt% (0, 2, 4, 6, 10 wt%) of the total MgB2. Moreover, we present MgB2 bulk samples fabricated by using different production methods including hot pressing method to our knowledge. All samples were prepared by using elemental magnesium (Mg) powder, amorphous nano-boron (B) powder and Bi-2212 powder which are produced by hot press method. As a result of hot press process, compact pellet samples were manufactured. The vertical and lateral levitation force measurements were executed at the temperatures of 20, 24 and 28 K under zero-field-cooled (ZFC) and field-cooled (FC) regimes for samples with various adding levels. At 24 K and 28 K under ZFC regime, the 2 wt% Bi-2212 added sample exhibits a higher vertical levitation force than the pure sample. Bi-2212 added MgB2 samples compared to the pure sample have lower attractive force values in FC regime. The magnetic field dependence of the critical current density J c was calculated from the M-H loops for Bi-2212 added MgB2 samples. The 2 wt% Bi-2212 added sample has the best levitation and critical current density performance compared to other samples. The critical temperature ( T c ) has slightly dropped from 37.8 K for the pure MgB2 sample to 36.7 K for the 10 wt% of Bi-2212 added sample. The transition temperature slightly decreases when Bi-2212 adding level is increased.

  4. Effect of water on structure and dynamics of [BMIM][PF6] ionic liquid: An all-atom molecular dynamics simulation investigation.

    PubMed

    Sharma, Anirban; Ghorai, Pradip Kr

    2016-03-21

    Composition dependent structural and dynamical properties of aqueous hydrophobic 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) ionic liquid (IL) have been investigated by using all-atom molecular dynamics simulation. We observe that addition of water does not increase significant number of dissociated ions in the solution over the pure state. As a consequence, self-diffusion coefficient of the cation and anion is comparable to each other at all water concentration similar to that is observed for the pure state. Voronoi polyhedra analysis exhibits strong dependence on the local environment of IL concentration. Void and neck distributions in Voronoi tessellation are approximately Gaussian for pure IL but upon subsequent addition of water, we observe deviation from the Gaussian behaviour with an asymmetric broadening with long tail of exponential decay at large void radius, particularly at higher water concentrations. The increase in void space and neck size at higher water concentration facilitates ionic motion, thus, decreasing dynamical heterogeneity and IL reorientation time and increases self-diffusion coefficient significantly.

  5. Effect of water on structure and dynamics of [BMIM][PF6] ionic liquid: An all-atom molecular dynamics simulation investigation

    NASA Astrophysics Data System (ADS)

    Sharma, Anirban; Ghorai, Pradip Kr.

    2016-03-01

    Composition dependent structural and dynamical properties of aqueous hydrophobic 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) ionic liquid (IL) have been investigated by using all-atom molecular dynamics simulation. We observe that addition of water does not increase significant number of dissociated ions in the solution over the pure state. As a consequence, self-diffusion coefficient of the cation and anion is comparable to each other at all water concentration similar to that is observed for the pure state. Voronoi polyhedra analysis exhibits strong dependence on the local environment of IL concentration. Void and neck distributions in Voronoi tessellation are approximately Gaussian for pure IL but upon subsequent addition of water, we observe deviation from the Gaussian behaviour with an asymmetric broadening with long tail of exponential decay at large void radius, particularly at higher water concentrations. The increase in void space and neck size at higher water concentration facilitates ionic motion, thus, decreasing dynamical heterogeneity and IL reorientation time and increases self-diffusion coefficient significantly.

  6. Parallel inhibition of active force and relaxed fiber stiffness by caldesmon fragments at physiological ionic strength and temperature conditions: additional evidence that weak cross-bridge binding to actin is an essential intermediate for force generation.

    PubMed Central

    Kraft, T; Chalovich, J M; Yu, L C; Brenner, B

    1995-01-01

    Previously we showed that stiffness of relaxed fibers and active force generated in single skinned fibers of rabbit psoas muscle are inhibited in parallel by actin-binding fragments of caldesmon, an actin-associated protein of smooth muscle, under conditions in which a large fraction of cross-bridges is weakly attached to actin (ionic strength of 50 mM and temperature of 5 degrees C). These results suggested that weak cross-bridge attachment to actin is essential for force generation. The present study provides evidence that this is also true for physiological ionic strength (170 mM) at temperatures up to 30 degrees C, suggesting that weak cross-bridge binding to actin is generally required for force generation. In addition, we show that the inhibition of active force is not a result of changes in cross-bridge cycling kinetics but apparently results from selective inhibition of weak cross-bridge binding to actin. Together with our previous biochemical, mechanical, and structural studies, these findings support the proposal that weak cross-bridge attachment to actin is an essential intermediate on the path to force generation and are consistent with the concept that isometric force mainly results from an increase in strain of the attached cross-bridge as a result of a structural change associated with the transition from a weakly bound to a strongly bound actomyosin complex. This mechanism is different from the processes responsible for quick tension recovery that were proposed by Huxley and Simmons (Proposed mechanism of force generation in striated muscle. Nature. 233:533-538.) to represent the elementary mechanism of force generation. Images FIGURE 1 PMID:7647245

  7. PRIMO: A Transferable Coarse-grained Force Field for Proteins.

    PubMed

    Kar, Parimal; Gopal, Srinivasa Murthy; Cheng, Yi-Ming; Predeus, Alexander; Feig, Michael

    2013-08-13

    We describe here the PRIMO (PRotein Intermediate Model) force field, a physics-based fully transferable additive coarse-grained potential energy function that is compatible with an all-atom force field for multi-scale simulations. The energy function consists of standard molecular dynamics energy terms plus a hydrogen-bonding potential term and is mainly parameterized based on the CHARMM22/CMAP force field in a bottom-up fashion. The solvent is treated implicitly via the generalized Born model. The bonded interactions are either harmonic or distance-based spline interpolated potentials. These potentials are defined on the basis of all-atom molecular dynamics (MD) simulations of dipeptides with the CHARMM22/CMAP force field. The non-bonded parameters are tuned by matching conformational free energies of diverse set of conformations with that of CHARMM all-atom results. PRIMO is designed to provide a correct description of conformational distribution of the backbone (ϕ/ψ) and side chains (χ1) for all amino acids with a CMAP correction term. The CMAP potential in PRIMO is optimized based on the new CHARMM C36 CMAP. The resulting optimized force field has been applied in MD simulations of several proteins of 36-155 amino acids and shown that the root-mean-squared-deviation of the average structure from the corresponding crystallographic structure varies between 1.80 and 4.03 Å. PRIMO is shown to fold several small peptides to their native-like structures from extended conformations. These results suggest the applicability of the PRIMO force field in the study of protein structures in aqueous solution, structure predictions as well as ab initio folding of small peptides.

  8. Structure and function of photosystem I–[FeFe] hydrogenase protein fusions: An all-atom molecular dynamics study

    SciTech Connect

    Harris, Bradley J.; Cheng, Xiaolin; Frymier, Paul

    2015-12-15

    All-atom molecular dynamics (MD) simulation was used to study the solution dynamics and protein protein interactions of protein fusions of photosystem I (PSI) from Thermosynechococcus elongatus and an [FeFe]-hydrogenase (FeFe H2ase) from Clostridium pasteurianum, a unique complex capable of photocatalytic hydrogen production. This study involved fusions of these two proteins via dithiol linkers of different length including decanedithiol, octanedithiol, and hexanedithiol, for which experimental data had previously been obtained. Evaluation of root-mean-squared deviations (RMSDs) relative to the respective crystal structures of PSI and the FeFe H2ase shows that these fusion complexes approach stable equilibrium conformations during the MD simulations. Investigating protein mobility via root-mean-squared fluctuations (RMSFs) reveals that tethering via the shortest hexanedithiol linker results in increased atomic fluctuations of both PSI and the hydrogenase in these fusion complexes. Furthermore, evaluation of the inter- and intraprotein electron transfer distances in these fusion complexes indicates that the structural changes in the FeFe H2ase arising from ligation to PSI via the shortest hexanedithiol linker may hinder electron transport in the hydrogenase, thus providing a molecular level explanation for the observation that the medium-length octanedithiol linker gives the highest hydrogen production rate.

  9. Insights into the Tunnel Mechanism of Cholesteryl Ester Transfer Protein through All-atom Molecular Dynamics Simulations.

    PubMed

    Lei, Dongsheng; Rames, Matthew; Zhang, Xing; Zhang, Lei; Zhang, Shengli; Ren, Gang

    2016-07-01

    Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) transfer from the atheroprotective high density lipoprotein (HDL) cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy (EM) experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up a CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases. PMID:27143480

  10. Structure and function of photosystem I–[FeFe] hydrogenase protein fusions: An all-atom molecular dynamics study

    DOE PAGES

    Harris, Bradley J.; Cheng, Xiaolin; Frymier, Paul

    2015-12-15

    All-atom molecular dynamics (MD) simulation was used to study the solution dynamics and protein protein interactions of protein fusions of photosystem I (PSI) from Thermosynechococcus elongatus and an [FeFe]-hydrogenase (FeFe H2ase) from Clostridium pasteurianum, a unique complex capable of photocatalytic hydrogen production. This study involved fusions of these two proteins via dithiol linkers of different length including decanedithiol, octanedithiol, and hexanedithiol, for which experimental data had previously been obtained. Evaluation of root-mean-squared deviations (RMSDs) relative to the respective crystal structures of PSI and the FeFe H2ase shows that these fusion complexes approach stable equilibrium conformations during the MD simulations. Investigatingmore » protein mobility via root-mean-squared fluctuations (RMSFs) reveals that tethering via the shortest hexanedithiol linker results in increased atomic fluctuations of both PSI and the hydrogenase in these fusion complexes. Furthermore, evaluation of the inter- and intraprotein electron transfer distances in these fusion complexes indicates that the structural changes in the FeFe H2ase arising from ligation to PSI via the shortest hexanedithiol linker may hinder electron transport in the hydrogenase, thus providing a molecular level explanation for the observation that the medium-length octanedithiol linker gives the highest hydrogen production rate.« less

  11. Reproducible In-Silico Folding of a Four Helix 60 Amino Acid Protein in a Transferable All-Atom Forcefield

    NASA Astrophysics Data System (ADS)

    Schug, Alexander

    2005-03-01

    For predicting the protein tertiary structure one approach describes the native state of a protein as the global minimum of an appropiate free-energy forcefield. We have recently developed such a all-atom protein forcefield (PFF01). As major challenge remains the search for the global minimum for which we developed efficient methods. Using these we were able to predict the structure of helical proteins from different families ranging in size from 20 to 60 amino acids starting with random configurations. For the four helix 60 amino acid protein Bacterial Ribosomal Protein L20 (pdb code: 1GYZ) we used a simple client-master model for distributed computing. Starting from a set of random structures three phases of different folding simulations refined this set to a final one with 50 configurations. During this process the amount of native-like structures increased strongly. Six out of the ten structures best in energy approached the native structure within 5 åbackbone rmsd. The conformation with the lowest energy had a backbone rmsd value of 4.6 åtherefore correctly predicting the tertiary structure of 1GYZ.ReferencesA. Schug et al, Phys. Rev. Letters, 91:158102, 2003A. Schug et al, J. Am. Chem. Soc. (in press), 2004

  12. Insights into the Tunnel Mechanism of Cholesteryl Ester Transfer Protein through All-atom Molecular Dynamics Simulations*

    PubMed Central

    Lei, Dongsheng; Rames, Matthew; Zhang, Xing; Zhang, Lei; Zhang, Shengli; Ren, Gang

    2016-01-01

    Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) transfer from the atheroprotective high density lipoprotein (HDL) cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy (EM) experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up a CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases. PMID:27143480

  13. Additive effects of lithium and antidepressants in the forced swimming test: further evidence for involvement of the serotoninergic system.

    PubMed

    Nixon, M K; Hascoet, M; Bourin, M; Colombel, M C

    1994-06-01

    In the mouse forced swimming test (FST) pretreatment with a subactive dose of lithium (1 mEq/kg), given IP 45 min before the test, facilitated the antidepressant activity of iprindole, fluoxetine, and moclobemide (given IP 30 min before the test). These antidepressants (ADS) were not active alone in the FST in this study. Moreover, when subactive lithium was combined with a wide range of ADS, each given at subactive doses, those ADS with serotoninergic properties (e.g. imipramine, citalopram, paroxetine, fluoxetine, trazodone, mianserin, and moclobemide) significantly reduced immobility times. ADS acting primarily on noradrenaline (NA) or dopamine (DA) systems (desipramine, maprotiline, viloxazine, and bupropion) did not significantly decrease immobility when given in combination with lithium. This was also the case for RO 16 6491 [a reversible, B specific monoamine oxidase inhibitor (MAOI)], nialamide, and pargyline (both irreversible, mixed MAOIs). The anti-immobility effect of iprindole in combination with lithium suggests either a direct or indirect action on the serotonin (5HT) system by this ADS whose mechanism of action remains obscure. These results, using an animal behavioral model of depression and combining our present knowledge of the acute action of various ADS, support the hypothesis that the potentiation by lithium of ADS is via direct 5HT mechanisms, indirectly via a NA/5HT link, and/or by second messenger systems. Lithium may also facilitate the expression of antidepressant activity of ADS not active by themselves in the FST.

  14. Lessons learned during the training exercise for the entry into force of the U.S. additional protocol in the DOE complex

    SciTech Connect

    Boyer, Brian D

    2009-01-01

    In 2008 in anticipation of the United States bringing into force the Additional Protocol in early 2009 DOE/NNSA planned and executed training exercises in the conduct of Additional Protocol complementary access activities. Brookhaven National Laboratory and Los Alamos National Laboratory together produced the exercises designed to prepare the following types of DOE laboratories for complementary access - weapons laboratories, nuclear engineering laboratories, and science laboratories. This panel provides a forum to discuss and summarize the results and lessons learned from the 2008 exercise.

  15. Insights into activation and RNA binding of trp RNA-binding attenuation protein (TRAP) through all-atom simulations.

    PubMed

    Murtola, Teemu; Vattulainen, Ilpo; Falck, Emma

    2008-06-01

    Tryptophan biosynthesis in Bacillus stearothermophilus is regulated by a trp RNA binding attenuation protein (TRAP). It is a ring-shaped 11-mer of identical 74 residue subunits. Tryptophan binding pockets are located between adjacent subunits, and tryptophan binding activates TRAP to bind RNA. Here, we report results from all-atom molecular dynamics simulations of the system, complementing existing extensive experimental studies. We focus on two questions. First, we look at the activation mechanism, of which relatively little is known experimentally. We find that the absence of tryptophan allows larger motions close to the tryptophan binding site, and we see indication of a conformational change in the BC loop. However, complete deactivation seems to occur on much longer time scales than the 40 ns studied here. Second, we study the TRAP-RNA interactions. We look at the relative flexibilities of the different bases in the complex and analyze the hydrogen bonds between the protein and RNA. We also study the role of Lys37, Lys56, and Arg58, which have been experimentally identified as essential for RNA binding. Hydrophobic stacking of Lys37 with the nearby RNA base is confirmed, but we do not see direct hydrogen bonding between RNA and the other two residues, in contrast to the crystal structure. Rather, these residues seem to stabilize the RNA-binding surface, and their positive charge may also play a role in RNA binding. Simulations also indicate that TRAP is able to attract RNA nonspecifically, and the interactions are quantified in more detail using binding energy calculations. The formation of the final binding complex is a very slow process: within the simulation time scale of 40 ns, only two guanine bases become bound (and no others), indicating that the binding initiates at these positions. In general, our results are in good agreement with experimental studies, and provide atomic-scale insights into the processes. PMID:18186477

  16. Probing the Huntingtin 1-17 Membrane Anchor on a Phospholipid Bilayer by Using All-Atom Simulations

    PubMed Central

    Côté, Sébastien; Binette, Vincent; Salnikov, Evgeniy S.; Bechinger, Burkhard; Mousseau, Normand

    2015-01-01

    Mislocalization and aggregation of the huntingtin protein are related to Huntington’s disease. Its first exon—more specifically the first 17 amino acids (Htt17)—is crucial for the physiological and pathological functions of huntingtin. It regulates huntingtin’s activity through posttranslational modifications and serves as an anchor to membrane-containing organelles of the cell. Recently, structure and orientation of the Htt17 membrane anchor were determined using a combined solution and solid-state NMR approach. This prompted us to refine this model by investigating the dynamics and thermodynamics of this membrane anchor on a POPC bilayer using all-atom, explicit solvent molecular dynamics and Hamiltonian replica exchange. Our simulations are combined with various experimental measurements to generate a high-resolution atomistic model for the huntingtin Htt17 membrane anchor on a POPC bilayer. More precisely, we observe that the single α-helix structure is more stable in the phospholipid membrane than the NMR model obtained in the presence of dodecylphosphocholine detergent micelles. The resulting Htt17 monomer has its hydrophobic plane oriented parallel to the bilayer surface. Our results further unveil the key residues interacting with the membrane in terms of hydrogen bonds, salt-bridges, and nonpolar contributions. We also observe that Htt17 equilibrates at a well-defined insertion depth and that it perturbs the physical properties—order parameter, thickness, and area per lipid—of the bilayer in a manner that could favor its dimerization. Overall, our observations reinforce and refine the NMR measurements on the Htt17 membrane anchor segment of huntingtin that is of fundamental importance to its biological functions. PMID:25762330

  17. A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation

    PubMed Central

    Qin, Feng

    2015-01-01

    The transient receptor potential (TRP) channels act as key sensors of various chemical and physical stimuli in eukaryotic cells. Despite years of study, the molecular mechanisms of TRP channel activation remain unclear. To elucidate the structural, dynamic, and energetic basis of gating in TRPV1 (a founding member of the TRPV subfamily), we performed coarse-grained modeling and all-atom molecular dynamics (MD) simulation based on the recently solved high resolution structures of the open and closed form of TRPV1. Our coarse-grained normal mode analysis captures two key modes of collective motions involved in the TRPV1 gating transition, featuring a quaternary twist motion of the transmembrane domains (TMDs) relative to the intracellular domains (ICDs). Our transition pathway modeling predicts a sequence of structural movements that propagate from the ICDs to the TMDs via key interface domains (including the membrane proximal domain and the C-terminal domain), leading to sequential opening of the selectivity filter followed by the lower gate in the channel pore (confirmed by modeling conformational changes induced by the activation of ICDs). The above findings of coarse-grained modeling are robust to perturbation by lipids. Finally, our MD simulation of the ICD identifies key residues that contribute differently to the nonpolar energy of the open and closed state, and these residues are predicted to control the temperature sensitivity of TRPV1 gating. These computational predictions offer new insights to the mechanism for heat activation of TRPV1 gating, and will guide our future electrophysiology and mutagenesis studies. PMID:25918362

  18. New-generation amber united-atom force field.

    PubMed

    Yang, Lijiang; Tan, Chun-Hu; Hsieh, Meng-Juei; Wang, Junmei; Duan, Yong; Cieplak, Piotr; Caldwell, James; Kollman, Peter A; Luo, Ray

    2006-07-01

    We have developed a new-generation Amber united-atom force field for simulations involving highly demanding conformational sampling such as protein folding and protein-protein binding. In the new united-atom force field, all hydrogens on aliphatic carbons in all amino acids are united with carbons except those on Calpha. Our choice of explicit representation of all protein backbone atoms aims at minimizing perturbation to protein backbone conformational distributions and to simplify development of backbone torsion terms. Tests with dipeptides and solvated proteins show that our goal is achieved quite successfully. The new united-atom force field uses the same new RESP charging scheme based on B3LYP/cc-pVTZ//HF/6-31g** quantum mechanical calculations in the PCM continuum solvent as that in the Duan et al. force field. van der Waals parameters are empirically refitted starting from published values with respect to experimental solvation free energies of amino acid side-chain analogues. The suitability of mixing new point charges and van der Waals parameters with existing Amber covalent terms is tested on alanine dipeptide and is found to be reasonable. Parameters for all new torsion terms are refitted based on the new point charges and the van der Waals parameters. Molecular dynamics simulations of three small globular proteins in the explicit TIP3P solvent are performed to test the overall stability and accuracy of the new united-atom force field. Good agreements between the united-atom force field and the Duan et al. all-atom force field for both backbone and side-chain conformations are observed. In addition, the per-step efficiency of the new united-atom force field is demonstrated for simulations in the implicit generalized Born solvent. A speedup around two is observed over the Duan et al. all-atom force field for the three tested small proteins. Finally, the efficiency gain of the new united-atom force field in conformational sampling is further demonstrated

  19. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    PubMed

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

  20. A hierarchical coarse-grained (all-atom to all residue) approach to peptides (P1, P2) binding with a graphene sheet

    NASA Astrophysics Data System (ADS)

    Pandey, Ras; Kuang, Zhifeng; Farmer, Barry; Kim, Sang; Naik, Rajesh

    2012-02-01

    Recently, Kim et al. [1] have found that peptides P1: HSSYWYAFNNKT and P2: EPLQLKM bind selectively to graphene surfaces and edges respectively which are critical in modulating both the mechanical as well as electronic transport properties of graphene. Such distinctions in binding sites (edge versus surface) observed in electron micrographs were verified by computer simulation by an all-atomic model that captures the pi-pi bonding. We propose a hierarchical approach that involves input from the all-atom Molecular Dynamics (MD) study (with atomistic detail) into a coarse-grained Monte Carlo simulation to extend this study further to a larger scale. The binding energy of a free amino acid with the graphene sheet from all-atom simulation is used in the interaction parameter for the coarse-grained approach. Peptide chain executes its stochastic motion with the Metropolis algorithm. We investigate a number of local and global physical quantities and find that peptide P1 is likely to bind more strongly to graphene sheet than P2 and that it is anchored by three residues ^4Y^5W^6Y. [1] S.N. Kim et al J. Am. Chem. Soc. 133, 14480 (2011).

  1. An FFT-based method for modeling protein folding and binding under crowding: benchmarking on ellipsoidal and all-atom crowders.

    PubMed

    Qin, Sanbo; Zhou, Huan-Xiang

    2013-10-01

    It is now well recognized that macromolecular crowding can exert significant effects on protein folding and binding stability. In order to calculate such effects in direct simulations of proteins mixed with bystander macromolecules, the latter (referred to as crowders) are usually modeled as spheres and the proteins represented at a coarse-grained level. Our recently developed postprocessing approach allows the proteins to be represented at the all-atom level but, for computational efficiency, has only been implemented for spherical crowders. Modeling crowder molecules in cellular environments and in vitro experiments as spheres may distort their effects on protein stability. Here we present a new method that is capable for treating aspherical crowders. The idea, borrowed from protein-protein docking, is to calculate the excess chemical potential of the proteins in crowded solution by fast Fourier transform (FFT). As the first application, we studied the effects of ellipsoidal crowders on the folding and binding free energies of all-atom proteins, and found, in agreement with previous direct simulations with coarse-grained protein models, that the aspherical crowders exert greater stabilization effects than spherical crowders of the same volume. Moreover, as demonstrated here, the FFT-based method has the important property that its computational cost does not increase strongly even when the level of details in representing the crowders is increased all the way to all-atom, thus significantly accelerating realistic modeling of protein folding and binding in cell-like environments. PMID:24187527

  2. Investigating a link between all-atom model simulation and the Ising-based theory on the helix-coil transition. II. Nonstationary properties

    NASA Astrophysics Data System (ADS)

    Takano, Mitsunori; Nakamura, Hironori K.; Nagayama, Kuniaki; Suyama, Akira

    2003-06-01

    The all-atom and the Ising-based models have both played their own roles to help our understanding of helix-coil transition. In this study, we address to what degree these two theoretical models can be consistent with each other in the nonstationary regime, complementing the preceding equilibrium study. We conducted molecular dynamics simulations of an all-atom model polyalanine chain and Monte Carlo simulations of a corresponding kinetic Ising chain. Nonstationary properties of each model were characterized through power spectrum, Allan variance, and autocorrelation analyses regarding the time course of a system order parameter. A clear difference was indicated between the two models: the Ising-based model showed a Lorentzian spectrum in the frequency domain and a single exponential form in the time domain, whereas the all-atom model showed a 1/f spectrum and a stretched exponential form. The observed stretched exponential form is in agreement with a very recent T-jump experiment. The effect of viscous damping on helix-coil dynamics was also studied. A possible source of the observed difference between the two models is discussed by considering the potential energy landscape, and the idea of dynamical disorder was introduced into the original Glauber model in the hope of bridging the gap between the two models. Other possible sources, e.g., the limitations of the Ising framework and the validity of the Markovian dynamics assumption, are also discussed.

  3. Additional hemodynamic measurements with an esophageal Doppler monitor: a preliminary report of compliance, force, kinetic energy, and afterload in the clinical setting.

    PubMed

    Atlas, Glen; Brealey, David; Dhar, Sunil; Dikta, Gerhard; Singer, Meryvn

    2012-12-01

    The esophageal Doppler monitor (EDM) is a minimally-invasive hemodynamic device which evaluates both cardiac output (CO), and fluid status, by estimating stroke volume (SV) and calculating heart rate (HR). The measurement of these parameters is based upon a continuous and accurate approximation of distal thoracic aortic blood flow. Furthermore, the peak velocity (PV) and mean acceleration (MA), of aortic blood flow at this anatomic location, are also determined by the EDM. The purpose of this preliminary report is to examine additional clinical hemodynamic calculations of: compliance (C), kinetic energy (KE), force (F), and afterload (TSVR(i)). These data were derived using both velocity-based measurements, provided by the EDM, as well as other contemporaneous physiologic parameters. Data were obtained from anesthetized patients undergoing surgery or who were in a critical care unit. A graphical inspection of these measurements is presented and discussed with respect to each patient's clinical situation. When normalized to each of their initial values, F and KE both consistently demonstrated more discriminative power than either PV or MA. The EDM offers additional applications for hemodynamic monitoring. Further research regarding the accuracy, utility, and limitations of these parameters is therefore indicated.

  4. Competition among Li+, Na+, K+ and Rb+ Monovalent Ions for DNA in Molecular Dynamics Simulations using the Additive CHARMM36 and Drude Polarizable Force Fields

    PubMed Central

    Savelyev, Alexey; MacKerell, Alexander D.

    2015-01-01

    In the present study we report on interactions of and competition between monovalent ions for two DNA sequences in MD simulations. Efforts included the development and validation of parameters for interactions among the first-group monovalent cations, Li+, Na+, K+ and Rb+, and DNA in the Drude polarizable and additive CHARMM36 force fields (FF). The optimization process targeted gas-phase QM interaction energies of various model compounds with ions and osmotic pressures of bulk electrolyte solutions of chemically relevant ions. The optimized ionic parameters are validated against counterion condensation theory and buffer exchange-atomic emission spectroscopy measurements providing quantitative data on the competitive association of different monovalent ions with DNA. Comparison between experimental and MD simulation results demonstrates that, compared to the additive CHARMM36 model, the Drude FF provides an improved description of the general features of the ionic atmosphere around DNA and leads to closer agreement with experiment on the ionic competition within the ion atmosphere. Results indicate the importance of extended simulation systems on the order of 25 Å beyond the DNA surface to obtain proper convergence of ion distributions. PMID:25751286

  5. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

    DOE PAGES

    Lee, Jumin; Cheng, Xi; Swails, Jason M.; Yeom, Min Sun; Eastman, Peter K.; Lemkul, Justin A.; Wei, Shuai; Buckner, Joshua; Jeong, Jong Cheol; Qi, Yifei; et al

    2015-11-12

    Here we report that proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find themore » optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order parameters, and area compressibility modulus) obtained using the standard protocol used in CHARMM as well as from experiments. The optimal simulation protocol was then applied to the other five lipid simulations and resulted in excellent agreement between results from most simulation programs as well as with experimental data. AMBER compared least favorably with the expected membrane properties, which appears to be due to its use of the hard-truncation in the LJ potential versus a force-based switching function used to smooth the LJ potential as it approaches the cutoff distance. The optimal simulation protocol for each program has been implemented in CHARMM-GUI. This protocol is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules.« less

  6. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

    SciTech Connect

    Lee, Jumin; Cheng, Xi; Swails, Jason M.; Yeom, Min Sun; Eastman, Peter K.; Lemkul, Justin A.; Wei, Shuai; Buckner, Joshua; Jeong, Jong Cheol; Qi, Yifei; Jo, Sunhwan; Pande, Vijay S.; Case, David A.; Brooks, Charles L.; MacKerell, Alexander D.; Klauda, Jeffery B.; Im, Wonpil

    2015-11-12

    Here we report that proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find the optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order parameters, and area compressibility modulus) obtained using the standard protocol used in CHARMM as well as from experiments. The optimal simulation protocol was then applied to the other five lipid simulations and resulted in excellent agreement between results from most simulation programs as well as with experimental data. AMBER compared least favorably with the expected membrane properties, which appears to be due to its use of the hard-truncation in the LJ potential versus a force-based switching function used to smooth the LJ potential as it approaches the cutoff distance. The optimal simulation protocol for each program has been implemented in CHARMM-GUI. This protocol is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules.

  7. The relaxation of intrinsic compressive stress in complementary metal-oxide-semiconductor transistors by additional N ion implantation treatment with atomic force microscope-Raman stress extraction

    NASA Astrophysics Data System (ADS)

    Liao, M.-H.; Chen, C.-H.; Chang, L.-C.; Yang, C.; Kao, S.-C.

    2012-05-01

    Based on the stress extraction and measurement by atomic force microscope-Raman technique with the nanometer level space resolution, the high compressive stress about 550 MPa on the Si active region (OD) is observed for the current complementary metal-oxide-semiconductor (CMOS) transistor. During the thermal budget for the standard manufacture process of the current CMOS transistor, the difference of thermal expansion coefficients between Si and Shallow Trench Isolation (STI) oxide results in this high compressive stress in Si OD and further degrades the electron carrier mobility seriously. In order to relax this intrinsic processed compressive stress in Si OD and try to recover this performance loss, the novel process is proposed in this work in addition to the usage of one-side pad SiN layer. With this novel process of additional N-ion implantation (IMP) treatment in STI oxide, it can be found that the less compressive stress about 438 MPa in Si OD can be achieved by the smaller difference of thermal expansion coefficients between Si and N-doped SiO2 STI oxide. The formation of Si-N bonding in N-doped SiO2 STI region can be monitored by Fourier transform infrared spectroscopy spectra and thermal expansion coefficients for Si, SiO2, and SiN are 2.6 ppm/K, 0.4 ppm/K, and 2.87 ppm/K, respectively. The effective relaxation of intrinsic processed compressive stress in Si OD about 112 MPa (from 550 MPa to 438 MPa) by this proposed additional N IMP treatment contributes ˜14% electron carrier mobility enhancement/recovery. The experimental electrical data agree well with the theoretical piezoelectricity calculation for the strained-Si theory.

  8. The equilibrium properties and folding kinetics of an all-atom Go xAF model of the Trp-cage

    NASA Astrophysics Data System (ADS)

    Linhananta, Apichart; Boer, Jesse; MacKay, Ian

    2005-03-01

    The ultrafast-folding 20-residue Trp-cage protein is quickly becoming a new benchmark for molecular dynamics studies. Already several all-atom simulations have probed its equilibrium and kinetic properties. In this work an all-atom Go ¯ model is used to accurately represent the side-chain packing and native atomic contacts of the Trp-cage. The model reproduces the hallmark thermodynamics cooperativity of small proteins. Folding simulations observe that in the fast-folding dominant pathway, partial α-helical structure forms before hydrophobic core collapse. In the slow-folding secondary pathway, partial core collapse occurs before helical structure. The slow-folding rate of the secondary pathway is attributed to the loss of side-chain rotational freedom, due to the early core collapse, which impedes the helix formation. A major finding is the observation of a low-temperature kinetic intermediate stabilized by a salt bridge between residues Asp-9 and Arg-16. Similar observations [R. Zhou, Proc. Natl. Acad. Sci. U.S.A. 100, 13280 (2003)] were reported in a recent study using an all-atom model of the Trp-cage in explicit water, in which the salt-bridge stabilized intermediate was hypothesized to be the origin of the ultrafast-folding mechanism. A theoretical mutation that eliminates the Asp-9-Arg-16 salt bridge, but leaves the residues intact, is performed. Folding simulations of the mutant Trp-cage observe a two-state free-energy landscape with no kinetic intermediate and a significant decrease in the folding rate, in support of the hypothesis.

  9. Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation

    NASA Astrophysics Data System (ADS)

    Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

    2012-12-01

    We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

  10. Analysis of solvation structure and thermodynamics of ethane and propane in water by reference interaction site model theory using all-atom models

    NASA Astrophysics Data System (ADS)

    Cui, Qizhi; Smith, Vedene H.

    2001-08-01

    Following our previous paper on methane [Cui and Smith, J. Chem. Phys. 113, 10240 (2000)], we study the solvation structures and thermodynamics of ethane and propane in water at the infinite dilution limit by using the hypernetted chain closure reference interaction site model (HNC-RISM) theory with all-atom representations for solute molecules. At four thermodynamic states: temperature T=283.15, 298.15, 313.15, 328.15 K and the corresponding bulk water density ρ=0.9997, 0.9970, 0.9922, 0.9875 g cm-3, all the atomic solute-solvent radial distribution functions are obtained, and the corresponding running coordination numbers and the hydration free energies, energies, enthalpies, and entropies are calculated with the radial distribution functions as input. The hydration structures of ethane and propane are presented and analyzed at the atomic level in terms of the atomic solute-solvent radial distribution functions. With the optimized nonbonded potential parameters based on the CHARMM96 all-atom model for alkanes [Yin and Mackerell, J. Comput. Chem. 19, 334 (1998)], the ethane and propane hydration thermodynamic properties predicted by the HNC-RISM theory are improved in the specified temperature range (10-55 °C).

  11. Large-scale compensation of errors in pairwise-additive empirical force fields: comparison of AMBER intermolecular terms with rigorous DFT-SAPT calculations.

    PubMed

    Zgarbová, Marie; Otyepka, Michal; Sponer, Jirí; Hobza, Pavel; Jurecka, Petr

    2010-09-21

    The intermolecular interaction energy components for several molecular complexes were calculated using force fields available in the AMBER suite of programs and compared with Density Functional Theory-Symmetry Adapted Perturbation Theory (DFT-SAPT) values. The extent to which such comparison is meaningful is discussed. The comparability is shown to depend strongly on the intermolecular distance, which means that comparisons made at one distance only are of limited value. At large distances the coulombic and van der Waals 1/r(6) empirical terms correspond fairly well with the DFT-SAPT electrostatics and dispersion terms, respectively. At the onset of electronic overlap the empirical values deviate from the reference values considerably. However, the errors in the force fields tend to cancel out in a systematic manner at equilibrium distances. Thus, the overall performance of the force fields displays errors an order of magnitude smaller than those of the individual interaction energy components. The repulsive 1/r(12) component of the van der Waals expression seems to be responsible for a significant part of the deviation of the force field results from the reference values. We suggest that further improvement of the force fields for intermolecular interactions would require replacement of the nonphysical 1/r(12) term by an exponential function. Dispersion anisotropy and its effects are discussed. Our analysis is intended to show that although comparing the empirical and non-empirical interaction energy components is in general problematic, it might bring insights useful for the construction of new force fields. Our results are relevant to often performed force-field-based interaction energy decompositions.

  12. Molecular modeling of the binding modes of the Iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches

    PubMed Central

    Mozolewska, Magdalena A.; Krupa, Paweł; Scheraga, Harold A.; Liwo, Adam

    2015-01-01

    The Iron sulfur protein 1 (Isu1) from yeast, and the J-type co-chaperone Jac1, are part of a huge ATP-dependent system, and both interact with Hsp70 chaperones. Interaction of Isu1 and Jac1 is a part of the iron-sulfur cluster biogenesis system in mitochondria. In this study, the structure and dynamics of the yeast Isu1-Jac1 complex has been modeled. First, the complete structure of Isu1 was obtained by homology modeling using the I-TASSER server and YASARA software and thereafter tested for stability in the all-atom force field AMBER. Then, the known experimental structure of Jac1 was adopted to obtain initial models of the Isu1-Jac1 complex by using the ZDOCK server for global and local docking and the AutoDock software for local docking. Three most probable models were subsequently subjected to the coarse-grained molecular dynamics simulations with the UNRES force field to obtain the final structures of the complex. In the most probable model, Isu1 binds to the left face of the “Γ” shaped Jac1 molecule by the β-sheet section of Isu1. Residues L105, L109, and Y163 of Jac1 have been assessed by mutation studies to be essential for binding (Ciesielski et al., J. Mol. Biol. 2012, 417, 1–12). These residues were also found, by UNRES/MD simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N95, T98, P102, H112, V159, L167 and A170 of Jac1, not yet tested experimentally, were also found important in binding. PMID:25973573

  13. Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches.

    PubMed

    Mozolewska, Magdalena A; Krupa, Paweł; Scheraga, Harold A; Liwo, Adam

    2015-08-01

    The iron-sulfur protein 1 (Isu1) and the J-type co-chaperone Jac1 from yeast are part of a huge ATP-dependent system, and both interact with Hsp70 chaperones. Interaction of Isu1 and Jac1 is a part of the iron-sulfur cluster biogenesis system in mitochondria. In this study, the structure and dynamics of the yeast Isu1-Jac1 complex has been modeled. First, the complete structure of Isu1 was obtained by homology modeling using the I-TASSER server and YASARA software and thereafter tested for stability in the all-atom force field AMBER. Then, the known experimental structure of Jac1 was adopted to obtain initial models of the Isu1-Jac1 complex by using the ZDOCK server for global and local docking and the AutoDock software for local docking. Three most probable models were subsequently subjected to the coarse-grained molecular dynamics simulations with the UNRES force field to obtain the final structures of the complex. In the most probable model, Isu1 binds to the left face of the Γ-shaped Jac1 molecule by the β-sheet section of Isu1. Residues L105 , L109 , and Y163 of Jac1 have been assessed by mutation studies to be essential for binding (Ciesielski et al., J Mol Biol 2012; 417:1-12). These residues were also found, by UNRES/molecular dynamics simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N(95), T(98), P(102), H(112), V(159), L(167), and A(170) of Jac1, not yet tested experimentally, were also found to be important in binding.

  14. 77 FR 9251 - Designation of a Class of Employees for Addition to the Special Exposure Cohort

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-16

    ... designate a class of employees from the Linde Ceramics Plant in Tonawanda, New York, as an addition to the... addition to the SEC: All Atomic Weapons Employees who worked in any area at the Linde Ceramics Plant...

  15. C6 Coefficients and Dipole Polarizabilities for All Atoms and Many Ions in Rows 1-6 of the Periodic Table.

    PubMed

    Gould, Tim; Bučko, Tomáš

    2016-08-01

    Using time-dependent density functional theory (TDDFT) with exchange kernels, we calculate and test imaginary frequency-dependent dipole polarizabilities for all atoms and many ions in rows 1-6 of the periodic table. These are then integrated over frequency to produce C6 coefficients. Results are presented under different models: straight TDDFT calculations using two different kernels; "benchmark" TDDFT calculations corrected by more accurate quantum chemical and experimental data; and "benchmark" TDDFT with frozen orbital anions. Parametrizations are presented for 411+ atoms and ions, allowing results to be easily used by other researchers. A curious relationship, C6,XY ∝ [αX(0)αY(0)](0.73), is found between C6 coefficients and static polarizabilities α(0). The relationship C6,XY = 2C6,XC6,Y/[(αX/αY)C6,Y + (αY/αX)C6,X] is tested and found to work well (<5% errors) in ∼80% of the cases, but can break down badly (>30% errors) in a small fraction of cases. PMID:27304856

  16. Large-scale relativistic calculations of ionization energies and total binding energies of all atoms and positive atomic ions with nuclear charge Z = 1-110

    NASA Astrophysics Data System (ADS)

    Kramida, Alexander; Froese Fischer, Charlotte; Reader, Joseph; Indelicato, Paul

    2015-05-01

    The latest versions of advanced multiconfiguration Dirac-Fock atomic codes, MCDFGME and Grasp2K, are used to calculate ionization energies (IE) and total binding energies of all atomic systems. Comparison with experiment and other benchmark data shows an excellent accuracy achieved in these calculations for H-, He-, and Li-like ions. In particular, our results for H-like ions with Z >2, obtained with the MCDFGME code, are the most accurate available today. For multi-electron ions, we combine the accurate single-configuration MCDFGME calculations with the correlation-difference energy (difference between the multiconfiguration and single-configuration total energies) calculated with Grasp2K. This approach results in a dramatically improved agreement of calculated IEs with experiment (less than 0.7 eV on average) for all systems, excluding those involving open f-shells. The most probable ground states are found for most systems, leaving questionable only about 100 out of total 6105 considered systems.

  17. All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics

    PubMed Central

    Woo, Sun Young; Lee, Hwankyu

    2016-01-01

    Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect. PMID:26926570

  18. C6 Coefficients and Dipole Polarizabilities for All Atoms and Many Ions in Rows 1-6 of the Periodic Table.

    PubMed

    Gould, Tim; Bučko, Tomáš

    2016-08-01

    Using time-dependent density functional theory (TDDFT) with exchange kernels, we calculate and test imaginary frequency-dependent dipole polarizabilities for all atoms and many ions in rows 1-6 of the periodic table. These are then integrated over frequency to produce C6 coefficients. Results are presented under different models: straight TDDFT calculations using two different kernels; "benchmark" TDDFT calculations corrected by more accurate quantum chemical and experimental data; and "benchmark" TDDFT with frozen orbital anions. Parametrizations are presented for 411+ atoms and ions, allowing results to be easily used by other researchers. A curious relationship, C6,XY ∝ [αX(0)αY(0)](0.73), is found between C6 coefficients and static polarizabilities α(0). The relationship C6,XY = 2C6,XC6,Y/[(αX/αY)C6,Y + (αY/αX)C6,X] is tested and found to work well (<5% errors) in ∼80% of the cases, but can break down badly (>30% errors) in a small fraction of cases.

  19. Energetics of nonpolar and polar compounds in cationic, anionic, and nonionic micelles studied by all-atom molecular dynamics simulation combined with a theory of solutions.

    PubMed

    Date, Atsushi; Ishizuka, Ryosuke; Matubayasi, Nobuyuki

    2016-05-21

    Energetic analysis was conducted for nonpolar and polar solutes bound in a cationic micelle of dodecyl trimethyl ammonium bromide (DTAB), an anionic micelle of sodium dodecyl sulfate (SDS), and a nonionic micelle of tetraethylene glycol monododecyl ether (Brij30). All-atom molecular dynamics simulation was performed, and the free energies of binding the solutes in the hydrophobic-core and headgroup regions of the micelles were computed using the energy-representation method. It was found in all the micelles examined that aromatic naphthalene is preferably located more outward than aliphatic propane and that the polar solutes are localized at the interface of the hydrophobic and hydrophilic regions. The roles of the surfactant and water were then elucidated by decomposing the free energy into the contributions from the respective species. Water was observed to play a decisive role in determining the binding location of the solute, while the surfactant was found to be more important for the overall stabilization of the solute within the micelle. The effects of attractive and repulsive interactions of the solute with the surfactant and water were further examined, and their competition was analyzed in connection with the preferable location of the solute in the micellar system.

  20. Putative membrane lytic sites of P-type and S-type cardiotoxins from snake venoms as probed by all-atom molecular dynamics simulations.

    PubMed

    Gorai, Biswajit; Karthikeyan, Muthusamy; Sivaraman, Thirunavukkarasu

    2016-10-01

    Cardiotoxins (CTXs) belonging to the three-finger toxin superfamily of snake venoms are one of principal toxic components and the protein toxins exhibit membrane lytic activities when the venoms are injected into victims. In the present study, complex formations between CTX VI (a P-type CTX from Naja atra) and CTX1 (an S-type CTX from Naja naja) on zwitterionic POPC bilayers (a major lipid component of cell membranes) have been studied in near physiological conditions for a total dynamic time scale of 1.35 μs using all-atom molecular dynamics (MD) simulations. Comprehensive analyses of the MD data revealed that residues such as Leu1, Lys2, Tyr11, Lys31, Asp57 and Arg58 of CTX VI, and Ala16, Lys30 and Arg58 of CTX1 were crucial for establishing interactions with the POPC bilayer. Moreover, loop I, along with globular head and loop II of CTX VI, and loop II of CTX1 were found to be the structural regions chiefly governing complex formation of the respective proteins with POPC. Rationalizations for the differential binding modes of CTXs and implications of the findings for designing small molecular inhibitors to the toxins are also discussed. Graphical Abstract Binding modes of a P-type CTX and an S-type CTX towards the POPC bilayer. PMID:27628673

  1. Free energetics of carbon nanotube association in aqueous inorganic NaI salt solutions: Temperature effects using all-atom molecular dynamics simulations.

    PubMed

    Ou, Shu-Ching; Cui, Di; Wezowicz, Matthew; Taufer, Michela; Patel, Sandeep

    2015-06-15

    In this study, we examine the temperature dependence of free energetics of nanotube association using graphical processing unit-enabled all-atom molecular dynamics simulations (FEN ZI) with two (10,10) single-walled carbon nanotubes in 3 m NaI aqueous salt solution. Results suggest that the free energy, enthalpy and entropy changes for the association process are all reduced at the high temperature, in agreement with previous investigations using other hydrophobes. Via the decomposition of free energy into individual components, we found that solvent contribution (including water, anion, and cation contributions) is correlated with the spatial distribution of the corresponding species and is influenced distinctly by the temperature. We studied the spatial distribution and the structure of the solvent in different regions: intertube, intratube and the bulk solvent. By calculating the fluctuation of coarse-grained tube-solvent surfaces, we found that tube-water interfacial fluctuation exhibits the strongest temperature dependence. By taking ions to be a solvent-like medium in the absence of water, tube-anion interfacial fluctuation shows similar but weaker dependence on temperature, while tube-cation interfacial fluctuation shows no dependence in general. These characteristics are discussed via the malleability of their corresponding solvation shells relative to the nanotube surface. Hydrogen bonding profiles and tetrahedrality of water arrangement are also computed to compare the structure of solvent in the solvent bulk and intertube region. The hydrophobic confinement induces a relatively lower concentration environment in the intertube region, therefore causing different intertube solvent structures which depend on the tube separation. This study is relevant in the continuing discourse on hydrophobic interactions (as they impact generally a broad class of phenomena in biology, biochemistry, and materials science and soft condensed matter research), and

  2. Free energetics of carbon nanotube association in aqueous inorganic NaI salt solutions: Temperature effects using all-atom molecular dynamics simulations.

    PubMed

    Ou, Shu-Ching; Cui, Di; Wezowicz, Matthew; Taufer, Michela; Patel, Sandeep

    2015-06-15

    In this study, we examine the temperature dependence of free energetics of nanotube association using graphical processing unit-enabled all-atom molecular dynamics simulations (FEN ZI) with two (10,10) single-walled carbon nanotubes in 3 m NaI aqueous salt solution. Results suggest that the free energy, enthalpy and entropy changes for the association process are all reduced at the high temperature, in agreement with previous investigations using other hydrophobes. Via the decomposition of free energy into individual components, we found that solvent contribution (including water, anion, and cation contributions) is correlated with the spatial distribution of the corresponding species and is influenced distinctly by the temperature. We studied the spatial distribution and the structure of the solvent in different regions: intertube, intratube and the bulk solvent. By calculating the fluctuation of coarse-grained tube-solvent surfaces, we found that tube-water interfacial fluctuation exhibits the strongest temperature dependence. By taking ions to be a solvent-like medium in the absence of water, tube-anion interfacial fluctuation shows similar but weaker dependence on temperature, while tube-cation interfacial fluctuation shows no dependence in general. These characteristics are discussed via the malleability of their corresponding solvation shells relative to the nanotube surface. Hydrogen bonding profiles and tetrahedrality of water arrangement are also computed to compare the structure of solvent in the solvent bulk and intertube region. The hydrophobic confinement induces a relatively lower concentration environment in the intertube region, therefore causing different intertube solvent structures which depend on the tube separation. This study is relevant in the continuing discourse on hydrophobic interactions (as they impact generally a broad class of phenomena in biology, biochemistry, and materials science and soft condensed matter research), and

  3. Free Energetics of Carbon Nanotube Association in Aqueous Inorganic NaI Salt Solutions: Temperature Effects using All-Atom Molecular Dynamics Simulations

    PubMed Central

    Ou, Shu-Ching; Cui, Di; Wezowicz, Matthew; Taufer, Michela; Patel, Sandeep

    2015-01-01

    In this study we examine the temperature dependence of free energetics of nanotube association by using GPU-enabled all-atom molecular dynamics simulations (FEN ZI) with two (10,10) single-walled carbon nanotubes in 3 m NaI aqueous salt solution. Results suggest that the free energy, enthalpy and entropy changes for the association process are all reduced at the high temperature, in agreement with previous investigations using other hydrophobes. Via the decomposition of free energy into individual components, we found that solvent contribution (including water, anion and cation contributions) is correlated with the spatial distribution of the corresponding species and is influenced distinctly by the temperature. We studied the spatial distribution and the structure of the solvent in different regions: intertube, intra-tube and the bulk solvent. By calculating the fluctuation of coarse-grained tube-solvent surfaces, we found that tube-water interfacial fluctuation exhibits the strongest temperature dependence. By taking ions to be a solvent-like medium in the absence of water, tube-anion interfacial fluctuation also shows similar but weaker dependence on temperature, while tube-cation interfacial fluctuation shows no dependence in general. These characteristics are discussed via the malleability of their corresponding solvation shells relative to the nanotube surface. Hydrogen bonding profiles and tetrahedrality of water arrangement are also computed to compare the structure of solvent in the solvent bulk and intertube region. The hydrophobic confinement induces a relatively lower concentration environment in the intertube region, therefore causing different intertube solvent structures which depend on the tube separation. This study is relevant in the continuing discourse on hydrophobic interactions (as they impact generally a broad class of phenomena in biology, biochemistry, and materials science and soft condensed matter research), and interpretations of

  4. Balancing the Interactions of Ions, Water, and DNA in the Drude Polarizable Force Field

    PubMed Central

    2015-01-01

    Recently we presented a first-generation all-atom Drude polarizable force field for DNA based on the classical Drude oscillator model, focusing on optimization of key dihedral angles followed by extensive validation of the force field parameters. Presently, we describe the procedure for balancing the electrostatic interactions between ions, water, and DNA as required for development of the Drude force field for DNA. The proper balance of these interactions is shown to impact DNA stability and subtler conformational properties, including the conformational equilibrium between the BI and BII states, and the A and B forms of DNA. The parametrization efforts were simultaneously guided by gas-phase quantum mechanics (QM) data on small model compounds and condensed-phase experimental data on the hydration and osmotic properties of biologically relevant ions and their solutions, as well as theoretical predictions for ionic distribution around DNA oligomer. In addition, fine-tuning of the internal base parameters was performed to obtain the final DNA model. Notably, the Drude model is shown to more accurately reproduce counterion condensation theory predictions of DNA charge neutralization by the condensed ions as compared to the CHARMM36 additive DNA force field, indicating an improved physical description of the forces dictating the ionic solvation of DNA due to the explicit treatment of electronic polarizability. In combination with the polarizable DNA force field, the availability of Drude polarizable parameters for proteins, lipids, and carbohydrates will allow for simulation studies of heterogeneous biological systems. PMID:24874104

  5. Balancing the interactions of ions, water, and DNA in the Drude polarizable force field.

    PubMed

    Savelyev, Alexey; MacKerell, Alexander D

    2014-06-19

    Recently we presented a first-generation all-atom Drude polarizable force field for DNA based on the classical Drude oscillator model, focusing on optimization of key dihedral angles followed by extensive validation of the force field parameters. Presently, we describe the procedure for balancing the electrostatic interactions between ions, water, and DNA as required for development of the Drude force field for DNA. The proper balance of these interactions is shown to impact DNA stability and subtler conformational properties, including the conformational equilibrium between the BI and BII states, and the A and B forms of DNA. The parametrization efforts were simultaneously guided by gas-phase quantum mechanics (QM) data on small model compounds and condensed-phase experimental data on the hydration and osmotic properties of biologically relevant ions and their solutions, as well as theoretical predictions for ionic distribution around DNA oligomer. In addition, fine-tuning of the internal base parameters was performed to obtain the final DNA model. Notably, the Drude model is shown to more accurately reproduce counterion condensation theory predictions of DNA charge neutralization by the condensed ions as compared to the CHARMM36 additive DNA force field, indicating an improved physical description of the forces dictating the ionic solvation of DNA due to the explicit treatment of electronic polarizability. In combination with the polarizable DNA force field, the availability of Drude polarizable parameters for proteins, lipids, and carbohydrates will allow for simulation studies of heterogeneous biological systems. PMID:24874104

  6. Surface Tension of Organic Liquids Using the OPLS/AA Force Field.

    PubMed

    Zubillaga, Rafael A; Labastida, Ariana; Cruz, Bibiana; Martínez, Juan Carlos; Sánchez, Enrique; Alejandre, José

    2013-03-12

    Molecular dynamics simulations are performed to obtain the surface tension of 61 organic liquids using the OPLS/AA (all-atom optimized potential for liquid simulations). The force field parameters are the same as those recently used (Caleman et al. J. Chem. Theory Comput.2012, 8, 61) to determine several thermodynamic properties of 146 organic liquids. The correct evaluation of surface tension using slab simulations of liquids requires one to properly take into account the long-range interactions (Trukhymchuk and Alejandre J. Chem. Phys.1999, 111, 8510). In addition, the liquid density from slab simulations has to be the same as that obtained in liquid simulations at constant temperature and pressure. The new results of surface tensions from this work improve those reported by Caleman et al. The OPLS/AA force field gives good surface tensions compared with experimental data for most of the systems studied in this work, although it was developed to simulate liquids. PMID:26587622

  7. Surface Tension of Organic Liquids Using the OPLS/AA Force Field.

    PubMed

    Zubillaga, Rafael A; Labastida, Ariana; Cruz, Bibiana; Martínez, Juan Carlos; Sánchez, Enrique; Alejandre, José

    2013-03-12

    Molecular dynamics simulations are performed to obtain the surface tension of 61 organic liquids using the OPLS/AA (all-atom optimized potential for liquid simulations). The force field parameters are the same as those recently used (Caleman et al. J. Chem. Theory Comput.2012, 8, 61) to determine several thermodynamic properties of 146 organic liquids. The correct evaluation of surface tension using slab simulations of liquids requires one to properly take into account the long-range interactions (Trukhymchuk and Alejandre J. Chem. Phys.1999, 111, 8510). In addition, the liquid density from slab simulations has to be the same as that obtained in liquid simulations at constant temperature and pressure. The new results of surface tensions from this work improve those reported by Caleman et al. The OPLS/AA force field gives good surface tensions compared with experimental data for most of the systems studied in this work, although it was developed to simulate liquids.

  8. NGSI student activities in open source information analysis in support of the training program of the U.S. DOE laboratories for the entry into force of the additional protocol

    SciTech Connect

    Sandoval, M Analisa; Uribe, Eva C; Sandoval, Marisa N; Boyer, Brian D; Stevens, Rebecca S

    2009-01-01

    In 2008 a joint team from Los Alamos National Laboratory (LANL) and Brookhaven National Laboratory (BNL) consisting of specialists in training of IAEA inspectors in the use of complementary access activities formulated a training program to prepare the U.S. Doe laboratories for the entry into force of the Additional Protocol. As a major part of the support of the activity, LANL summer interns provided open source information analysis to the LANL-BNL mock inspection team. They were a part of the Next Generation Safeguards Initiative's (NGSI) summer intern program aimed at producing the next generation of safeguards specialists. This paper describes how they used open source information to 'backstop' the LANL-BNL team's effort to construct meaningful Additional Protocol Complementary Access training scenarios for each of the three DOE laboratories, Lawrence Livermore National Laboratory, Idaho National Laboratory, and Oak Ridge National Laboratory.

  9. A Critical Comparison of Biomembrane Force Fields: Structure and Dynamics of Model DMPC, POPC, and POPE Bilayers.

    PubMed

    Pluhackova, Kristyna; Kirsch, Sonja A; Han, Jing; Sun, Liping; Jiang, Zhenyan; Unruh, Tobias; Böckmann, Rainer A

    2016-04-28

    Atomistic molecular dynamics simulations have become an important source of information for the structure and dynamics of biomembranes at molecular detail difficult to access in experiments. A number of force fields for lipid membrane simulations have been derived in the past; the choice of the most suitable force field is, however, frequently hampered by the availability of parameters for specific lipids. Additionally, the comparison of different quantities among force fields is often aggravated by varying simulation parameters. Here, we compare four atomistic lipid force fields, namely, the united-atom GROMOS54a7 and the all-atom force fields CHARMM36, Slipids, and Lipid14, for a broad range of structural and dynamical properties of saturated and monounsaturated phosphatidylcholine bilayers (DMPC and POPC) as well as for monounsaturated phosphatidylethanolamine bilayers (POPE). Additionally, the ability of the different force fields to describe the gel-liquid crystalline phase transition is compared and their computational efficiency estimated. Moreover, membrane properties like the water flux across the lipid bilayer and lipid acyl chain protrusion probabilities are compared.

  10. Crossflow force transducer. [LMFBR

    SciTech Connect

    Mulcahy, T M

    1982-05-01

    A force transducer for measuring lift and drag coefficients for a circular cylinder in turbulent water flow is presented. In addition to describing the actual design and construction of the strain-gauged force- ring based transducer, requirements for obtained valid fluid force test data are discussed, and pertinent flow test experience is related.

  11. 77 FR 15759 - Final Effect of Designation of a Class of Employees for Addition to the Special Exposure Cohort

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-16

    ... Ceramics Plant in Tonawanda, New York, as an addition to the Special Exposure Cohort (SEC) under the Energy... to the SEC: All Atomic Weapons Employees who worked in any area at the Linde Ceramics Plant...

  12. Dimerization of Amino Acid Side Chains: Lessons from the Comparison of Different Force Fields.

    PubMed

    de Jong, Djurre H; Periole, Xavier; Marrink, Siewert J

    2012-03-13

    The interactions between amino acid side chains govern protein secondary, tertiary, and quaternary structure formation. For molecular modeling approaches to be able to realistically describe these phenomena, the underlying force fields have to represent these interactions as accurately as possible. Here, we compare the side chain-side chain interactions for a number of commonly used force fields, namely the all-atom OPLS, the united-atom GROMOS, and the coarse-grain MARTINI force field. We do so by calculating the dimerization free energies between selected pairs of side chains and structural characterization of their binding modes. To mimic both polar and nonpolar environments, the simulations are performed in water, n-octanol, and decane. In general, reasonable correlations are found between all three force fields, with deviations on the order of 1 kT in aqueous solvent. In apolar solvent, however, significantly larger differences are found, especially for charged amino acid pairs between the OPLS and GROMOS force fields, and for polar interactions in the MARTINI force field in comparison to the higher resolution models. Interestingly, even in cases where the dimerization free energies are similar, the binding mode may differ substantially between the force fields. This was found to be especially the case for aromatic residues. In addition to the inter-force-field comparison, we compared the various force fields to a knowledge-based potential. The two independent approaches show good correlation in aqueous solvent with an exception of aromatic residues for which the interaction strength is lower in the knowledge-based potentials.

  13. 75 FR 44966 - Designation of a Class of Employees for Addition to the Special Exposure Cohort

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    ... York, as an addition to the Special Exposure Cohort (SEC) under the Energy Employees Occupational... class of employees as an addition to the SEC: All Atomic Weapons Employer employees who worked at the... publish a notice in the Federal Register reporting the addition of this class to the SEC or the result...

  14. Nanonet Force Microscopy for Measuring Cell Forces.

    PubMed

    Sheets, Kevin; Wang, Ji; Zhao, Wei; Kapania, Rakesh; Nain, Amrinder S

    2016-07-12

    The influence of physical forces exerted by or felt by cells on cell shape, migration, and cytoskeleton arrangement is now widely acknowledged and hypothesized to occur due to modulation of cellular inside-out forces in response to changes in the external fibrous environment (outside-in). Our previous work using the non-electrospinning Spinneret-based Tunable Engineered Parameters' suspended fibers has revealed that cells are able to sense and respond to changes in fiber curvature and structural stiffness as evidenced by alterations to focal adhesion cluster lengths. Here, we present the development and application of a suspended nanonet platform for measuring C2C12 mouse myoblast forces attached to fibers of three diameters (250, 400, and 800 nm) representing a wide range of structural stiffness (3-50 nN/μm). The nanonet force microscopy platform measures cell adhesion forces in response to symmetric and asymmetric external perturbation in single and cyclic modes. We find that contractility-based, inside-out forces are evenly distributed at the edges of the cell, and that forces are dependent on fiber structural stiffness. Additionally, external perturbation in symmetric and asymmetric modes biases cell-fiber failure location without affecting the outside-in forces of cell-fiber adhesion. We then extend the platform to measure forces of (1) cell-cell junctions, (2) single cells undergoing cyclic perturbation in the presence of drugs, and (3) cancerous single-cells transitioning from a blebbing to a pseudopodial morphology. PMID:27410747

  15. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  16. Relativistic Linear Restoring Force

    ERIC Educational Resources Information Center

    Clark, D.; Franklin, J.; Mann, N.

    2012-01-01

    We consider two different forms for a relativistic version of a linear restoring force. The pair comes from taking Hooke's law to be the force appearing on the right-hand side of the relativistic expressions: d"p"/d"t" or d"p"/d["tau"]. Either formulation recovers Hooke's law in the non-relativistic limit. In addition to these two forces, we…

  17. Force-Measuring Clamps

    NASA Technical Reports Server (NTRS)

    Nunnelee, Mark

    2003-01-01

    Force-measuring clamps have been invented to facilitate and simplify the task of measuring the forces or pressures applied to clamped parts. There is a critical need to measure clamping forces or pressures in some applications for example, while bonding sensors to substrates or while clamping any sensitive or delicate parts. Many manufacturers of adhesives and sensors recommend clamping at specific pressures while bonding sensors or during adhesive bonding between parts in general. In the absence of a force-measuring clamp, measurement of clamping force can be cumbersome at best because of the need for additional load sensors and load-indicating equipment. One prior method of measuring clamping force involved the use of load washers or miniature load cells in combination with external power sources and load-indicating equipment. Calibrated spring clamps have also been used. Load washers and miniature load cells constitute additional clamped parts in load paths and can add to the destabilizing effects of loading mechanisms. Spring clamps can lose calibration quickly through weakening of the springs and are limited to the maximum forces that the springs can apply. The basic principle of a force-measuring clamp can be implemented on a clamp of almost any size and can enable measurement of a force of almost any magnitude. No external equipment is needed because the component(s) for transducing the clamping force and the circuitry for supplying power, conditioning the output of the transducers, and displaying the measurement value are all housed on the clamp. In other words, a force-measuring clamp is a complete force-application and force-measurement system all in one package. The advantage of unitary packaging of such a system is that it becomes possible to apply the desired clamping force or pressure with precision and ease.

  18. Nuclear forces

    SciTech Connect

    Machleidt, R.

    2013-06-10

    These lectures present an introduction into the theory of nuclear forces. We focus mainly on the modern approach, in which the forces between nucleons emerge from low-energy QCD via chiral effective field theory.

  19. Labor Force

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2012

    2012-01-01

    The labor force is the number of people ages 16 or older who are either working or looking for work. It does not include active-duty military personnel or the institutionalized population, such as prison inmates. Determining the size of the labor force is a way of determining how big the economy can get. The size of the labor force depends on two…

  20. 75 FR 44966 - Designation of a Class of Employees for Addition to the Special Exposure Cohort

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    ..., as an addition to the Special Exposure Cohort (SEC) under the Energy Employees Occupational Illness... employees as an addition to the SEC: All Atomic Weapons Employer employees who worked at BWX Technologies... class to the SEC or the result of any provision by Congress regarding the decision by HHS to add...

  1. 77 FR 64996 - Designation of a Class of Employees for Addition to the Special Exposure Cohort

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-24

    ... the Special Exposure Cohort (SEC) under the Energy Employees Occupational Illness Compensation Program... an addition to the SEC: All Atomic Weapons Employees who worked for the Ventron Corporation at its... publish a notice in the Federal Register reporting the addition of this class to the SEC or the result...

  2. A Generic Force Field for Protein Coarse-Grained Molecular Dynamics Simulation

    PubMed Central

    Gu, Junfeng; Bai, Fang; Li, Honglin; Wang, Xicheng

    2012-01-01

    Coarse-grained (CG) force fields have become promising tools for studies of protein behavior, but the balance of speed and accuracy is still a challenge in the research of protein coarse graining methodology. In this work, 20 CG beads have been designed based on the structures of amino acid residues, with which an amino acid can be represented by one or two beads, and a CG solvent model with five water molecules was adopted to ensure the consistence with the protein CG beads. The internal interactions in protein were classified according to the types of the interacting CG beads, and adequate potential functions were chosen and systematically parameterized to fit the energy distributions. The proposed CG force field has been tested on eight proteins, and each protein was simulated for 1000 ns. Even without any extra structure knowledge of the simulated proteins, the Cα root mean square deviations (RMSDs) with respect to their experimental structures are close to those of relatively short time all atom molecular dynamics simulations. However, our coarse grained force field will require further refinement to improve agreement with and persistence of native-like structures. In addition, the root mean square fluctuations (RMSFs) relative to the average structures derived from the simulations show that the conformational fluctuations of the proteins can be sampled. PMID:23203075

  3. Optimization of the OPLS-AA Force Field for Long Hydrocarbons.

    PubMed

    Siu, Shirley W I; Pluhackova, Kristyna; Böckmann, Rainer A

    2012-04-10

    The all-atom optimized potentials for liquid simulations (OPLS-AA) force field is a popular force field for simulating biomolecules. However, the current OPLS parameters for hydrocarbons developed using short alkanes cannot reproduce the liquid properties of long alkanes in molecular dynamics simulations. Therefore, the extension of OPLS-AA to (phospho)lipid molecules required for the study of biological membranes was hampered in the past. Here, we optimized the OPLS-AA force field for both short and long hydrocarbons. Following the framework of the OPLS-AA parametrization, we refined the torsional parameters for hydrocarbons by fitting to the gas-phase ab initio energy profiles calculated at the accurate MP2/aug-cc-pVTZ theory level. Additionally, the depth of the Lennard-Jones potential for methylene hydrogen atoms was adjusted to reproduce the densities and the heats of vaporization of alkanes and alkenes of different lengths. Optimization of partial charges finally allowed to reproduce the gel-to-liquid-phase transition temperature for pentadecane and solvation free energies. It is shown that the optimized parameter set (L-OPLS) yields improved hydrocarbon diffusion coefficients, viscosities, and gauche-trans ratios. Moreover, its applicability for lipid bilayer simulations is shown for a GMO bilayer in its liquid-crystalline phase.

  4. Phosphazene additives

    DOEpatents

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  5. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  6. One Force

    NASA Astrophysics Data System (ADS)

    Kotas, Ronald R.

    2002-04-01

    There is only one entity that can extend force and couple through space; and it should be apparent that Electromagnetism is that entity. In the cases of the nuclear strong force and the nuclear weak force, this is the same fundamental Electromagnetism manifesting itself in two different ways in the nucleus. It remains the same basic Electromagnetism. On the other hand, General Relativity fails to produce force at a distance, fails the Cavendish experiment, and does not allow an apple to fall to the ground. The result shows there is only Electromagnetism that functions through physical nature providing gravity, actions in the nucleus, as well as all other physical actions universally, including Gravity and Gravitation. There are many direct proofs of this, the same proofs as in NUCLEAR QUANTUM GRAVITATION. In contrast, General Relativity plainly relies on fallacy abstract and incoherent proofs; proofs which have now been mostly disproved. In the past it was deemed necessary by some to have an "ether" to propagate Electromagnetic waves. The fallacy concept of time space needs "space distortions" in order to cause gravity. However, Electromagnetic gravity does not have this problem. Clearly there is only ONE FORCE that causes Gravity, Electromagnetism, the Nuclear Strong Force, and the Nuclear Weak Force, and that ONE FORCE is Electromagnetism.

  7. Labor Force

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2010

    2010-01-01

    The labor force is the number of people aged 16 or older who are either working or looking for work. It does not include active-duty military personnel or institutionalized people, such as prison inmates. Quantifying this total supply of labor is a way of determining how big the economy can get. Labor force participation rates vary significantly…

  8. Acoustic force mapping in a hybrid acoustic-optical micromanipulation device supporting high resolution optical imaging† †Electronic supplementary information (ESI) available: Additional information about 1D model calculations for a piezoelectric transducer. See DOI: 10.1039/c6lc00182c Click here for additional data file.

    PubMed Central

    McDougall, Craig; MacDonald, Michael Peter; Ritsch-Marte, Monika

    2016-01-01

    Many applications in the life-sciences demand non-contact manipulation tools for forceful but nevertheless delicate handling of various types of sample. Moreover, the system should support high-resolution optical imaging. Here we present a hybrid acoustic/optical manipulation system which utilizes a transparent transducer, making it compatible with high-NA imaging in a microfluidic environment. The powerful acoustic trapping within a layered resonator, which is suitable for highly parallel particle handling, is complemented by the flexibility and selectivity of holographic optical tweezers, with the specimens being under high quality optical monitoring at all times. The dual acoustic/optical nature of the system lends itself to optically measure the exact acoustic force map, by means of direct force measurements on an optically trapped particle. For applications with (ultra-)high demand on the precision of the force measurements, the position of the objective used for the high-NA imaging may have significant influence on the acoustic force map in the probe chamber. We have characterized this influence experimentally and the findings were confirmed by model simulations. We show that it is possible to design the chamber and to choose the operating point in such a way as to avoid perturbations due to the objective lens. Moreover, we found that measuring the electrical impedance of the transducer provides an easy indicator for the acoustic resonances. PMID:27025398

  9. Traceable periodic force calibration

    NASA Astrophysics Data System (ADS)

    Schlegel, Ch; Kieckenap, G.; Glöckner, B.; Buß, A.; Kumme, R.

    2012-06-01

    A procedure for dynamic force calibration using sinusoidal excitations of force transducers is described. The method is based on a sinusoidal excitation of force transducers equipped with an additional top mass excited with an electrodynamic shaker system. The acting dynamic force can in this way be determined according to Newton's law as mass times acceleration, whereby the acceleration is measured on the surface of the top mass with the aid of laser interferometers. The dynamic sensitivity, which is the ratio of the electrical output signal of the force transducer and the acting dynamic force, is the main point of interest of such a dynamic calibration. In addition to the sensitivity, the parameter stiffness and damping of the transducer can also be determined. The first part of the paper outlines a mathematical model to describe the dynamic behaviour of a transducer. This is followed by a presentation of the traceability of the measured quantities involved and their uncertainties. The paper finishes with an example calibration of a 25 kN strain gauge force transducer.

  10. Force sensor

    DOEpatents

    Grahn, A.R.

    1993-05-11

    A force sensor and related method for determining force components is described. The force sensor includes a deformable medium having a contact surface against which a force can be applied, a signal generator for generating signals that travel through the deformable medium to the contact surface, a signal receptor for receiving the signal reflected from the contact surface, a generation controller, a reception controller, and a force determination apparatus. The signal generator has one or more signal generation regions for generating the signals. The generation controller selects and activates the signal generation regions. The signal receptor has one or more signal reception regions for receiving signals and for generating detections signals in response thereto. The reception controller selects signal reception regions and detects the detection signals. The force determination apparatus measures signal transit time by timing activation and detection and, optionally, determines force components for selected cross-field intersections. The timer which times by activation and detection can be any means for measuring signal transit time. A cross-field intersection is defined by the overlap of a signal generation region and a signal reception region.

  11. Force sensor

    DOEpatents

    Grahn, Allen R.

    1993-01-01

    A force sensor and related method for determining force components. The force sensor includes a deformable medium having a contact surface against which a force can be applied, a signal generator for generating signals that travel through the deformable medium to the contact surface, a signal receptor for receiving the signal reflected from the contact surface, a generation controller, a reception controller, and a force determination apparatus. The signal generator has one or more signal generation regions for generating the signals. The generation controller selects and activates the signal generation regions. The signal receptor has one or more signal reception regions for receiving signals and for generating detections signals in response thereto. The reception controller selects signal reception regions and detects the detection signals. The force determination apparatus measures signal transit time by timing activation and detection and, optionally, determines force components for selected cross-field intersections. The timer which times by activation and detection can be any means for measuring signal transit time. A cross-field intersection is defined by the overlap of a signal generation region and a signal reception region.

  12. Combination of the CHARMM27 force field with united-atom lipid force fields.

    PubMed

    Sapay, Nicolas; Tieleman, D Peter

    2011-05-01

    Computer simulations offer a valuable way to study membrane systems, from simple lipid bilayers to large transmembrane protein complexes and lipid-nucleic acid complexes for drug delivery. Their accuracy depends on the quality of the force field parameters used to describe the components of a particular system. We have implemented the widely used CHARMM22 and CHARMM27 force fields in the GROMACS simulation package to (i) combine the CHARMM22 protein force field with two sets of united-atom lipids parameters; (ii) allow comparisons of the lipid CHARMM27 force field with other lipid force fields or lipid-protein force field combinations. Our tests do not show any particular issue with the combination of the all-atom CHARMM22 force field with united-atoms lipid parameters, although pertinent experimental data are lacking to assess the quality of the lipid-protein interactions. The conversion utilities allow automatic generation of GROMACS simulation files with CHARMM nucleic acids and protein parameters and topologies, starting from pdb files using the standard GROMACS pdb2gmx method. CMAP is currently not implemented.

  13. Vacuum force

    NASA Astrophysics Data System (ADS)

    Han, Yongquan

    2015-03-01

    To study on vacuum force, we must clear what is vacuum, vacuum is a space do not have any air and also ray. There is not exist an absolute the vacuum of space. The vacuum of space is relative, so that the vacuum force is relative. There is a certain that vacuum vacuum space exists. In fact, the vacuum space is relative, if the two spaces compared to the existence of relative vacuum, there must exist a vacuum force, and the direction of the vacuum force point to the vacuum region. Any object rotates and radiates. Rotate bend radiate- centripetal, gravity produced, relative gravity; non gravity is the vacuum force. Gravity is centripetal, is a trend that the objects who attracted wants to Centripetal, or have been do Centripetal movement. Any object moves, so gravity makes the object curve movement, that is to say, the radiation range curve movement must be in the gravitational objects, gravity must be existed in non vacuum region, and make the object who is in the region of do curve movement (for example: The earth moves around the sun), or final attracted in the form gravitational objects, and keep relatively static with attract object. (for example: objects on the earth moves but can't reach the first cosmic speed).

  14. Causal reasoning with forces

    PubMed Central

    Wolff, Phillip; Barbey, Aron K.

    2015-01-01

    Causal composition allows people to generate new causal relations by combining existing causal knowledge. We introduce a new computational model of such reasoning, the force theory, which holds that people compose causal relations by simulating the processes that join forces in the world, and compare this theory with the mental model theory (Khemlani et al., 2014) and the causal model theory (Sloman et al., 2009), which explain causal composition on the basis of mental models and structural equations, respectively. In one experiment, the force theory was uniquely able to account for people's ability to compose causal relationships from complex animations of real-world events. In three additional experiments, the force theory did as well as or better than the other two theories in explaining the causal compositions people generated from linguistically presented causal relations. Implications for causal learning and the hierarchical structure of causal knowledge are discussed. PMID:25653611

  15. Extension of the LOPLS-AA Force Field for Alcohols, Esters, and Monoolein Bilayers and its Validation by Neutron Scattering Experiments.

    PubMed

    Pluhackova, Kristyna; Morhenn, Humphrey; Lautner, Lisa; Lohstroh, Wiebke; Nemkovski, Kirill S; Unruh, Tobias; Böckmann, Rainer A

    2015-12-10

    The recently presented LOPLS-AA all-atom force field for long hydrocarbon chains, based on the OPLS-AA force field, was extended to alcohols, esters, and glyceryl monooleate (GMO) lipids as a model lipid. Dihedral angles were fitted against high level ab initio calculations, and ester charges were increased to improve their hydration properties. Additionally, the ester Lennard-Jones parameters were readjusted to reproduce experimental liquid bulk properties, densities, and heats of vaporization. This extension enabled the setup of LOPLS-AA parameters for GMO molecules. The properties of the lipid force field were tested for the liquid-crystalline phase of a GMO bilayer. The obtained area per lipid for GMO is in good agreement with experiment. Additionally, the lipid dynamics on the subpicosecond to the nanosecond time scale is in excellent agreement with results from time-of-flight (TOF) quasielastic neutron scattering (QENS) experiments on a multilamellar monoolein system, enabling here for the first time the critical evaluation of the short-time dynamics obtained from a molecular dynamics simulation of a membrane system. PMID:26537654

  16. Extension of the LOPLS-AA Force Field for Alcohols, Esters, and Monoolein Bilayers and its Validation by Neutron Scattering Experiments.

    PubMed

    Pluhackova, Kristyna; Morhenn, Humphrey; Lautner, Lisa; Lohstroh, Wiebke; Nemkovski, Kirill S; Unruh, Tobias; Böckmann, Rainer A

    2015-12-10

    The recently presented LOPLS-AA all-atom force field for long hydrocarbon chains, based on the OPLS-AA force field, was extended to alcohols, esters, and glyceryl monooleate (GMO) lipids as a model lipid. Dihedral angles were fitted against high level ab initio calculations, and ester charges were increased to improve their hydration properties. Additionally, the ester Lennard-Jones parameters were readjusted to reproduce experimental liquid bulk properties, densities, and heats of vaporization. This extension enabled the setup of LOPLS-AA parameters for GMO molecules. The properties of the lipid force field were tested for the liquid-crystalline phase of a GMO bilayer. The obtained area per lipid for GMO is in good agreement with experiment. Additionally, the lipid dynamics on the subpicosecond to the nanosecond time scale is in excellent agreement with results from time-of-flight (TOF) quasielastic neutron scattering (QENS) experiments on a multilamellar monoolein system, enabling here for the first time the critical evaluation of the short-time dynamics obtained from a molecular dynamics simulation of a membrane system.

  17. Strategic forces

    SciTech Connect

    Not Available

    1990-10-01

    The Air Force now plans to retain the Minuteman II and III missile force through fiscal year 2008. Introduced about 25 years ago, these missiles have served as a nuclear deterrence for longer than initially envisioned. Over the extended lives of the systems, questions have arisen over their continued reliability and operational effectiveness, particularly the Minuteman II system. Limited flight testing, due to a shortage of test missiles, and reduced reliability caused by age-related deterioration of guidance computers and propulsion motors are two factors undermining confidence in the Minuteman II. GAO believes that the Minuteman II could be retired before 1998 as presently contemplated under an assumption of a Strategic Arms Reduction Talks agreement. An alternative would be to reinstate the Air Force's plans to replace deteriorated missile components and acquire the assets needed to resume flight testing at rates necessary to restore and sustain confidence in the system's performance through fiscal year 2008. However, on the basis of current test schedules, GAO is concerned that components to test the missile's warheads will be depleted by about 1999.

  18. Carbohydrate force fields

    PubMed Central

    Foley, B. Lachele; Tessier, Matthew B.; Woods, Robert J.

    2014-01-01

    Carbohydrates present a special set of challenges to the generation of force fields. First, the tertiary structures of monosaccharides are complex merely by virtue of their exceptionally high number of chiral centers. In addition, their electronic characteristics lead to molecular geometries and electrostatic landscapes that can be challenging to predict and model. The monosaccharide units can also interconnect in many ways, resulting in a large number of possible oligosaccharides and polysaccharides, both linear and branched. These larger structures contain a number of rotatable bonds, meaning they potentially sample an enormous conformational space. This article briefly reviews the history of carbohydrate force fields, examining and comparing their challenges, forms, philosophies, and development strategies. Then it presents a survey of recent uses of these force fields, noting trends, strengths, deficiencies, and possible directions for future expansion. PMID:25530813

  19. Surgical force detection probe

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Roberts, Paul; Scott, Charles; Prass, Richard

    1991-01-01

    The development progress of a precision electro-mechanical instrument which allows the detection and documentation of the forces and moment applied to human tissue during surgery (under actual operation room conditions), is reported. The pen-shaped prototype probe which measures 1/2 inch in diameter and 7 inches in length was fabricated using an aerodynamic balance. The aerodynamic balance, a standard wind tunnel force and moment sensing transducer, measures the forces and the moments transmitted through the surgeon's hand to the human tissue during surgery. The prototype probe which was fabricated as a development tool was tested successfully. The final version of the surgical force detection probe will be designed based on additional laboratory tests in order to establish the full scale loads. It is expected that the final product will require a simplified aerodynamic balance with two or three force components and one moment component with lighter full scale loads. A signal conditioner was fabricated to process and display the outputs from the prototype probe. This unit will be interfaced with a PC-based data system to provide automatic data acquisition, data processing, and graphics display. The expected overall accuracy of the probe is better than one percent full scale.

  20. Radiative Forcing by Contrails

    NASA Technical Reports Server (NTRS)

    Meerkoetter, R.; Schumann, U.; Doelling, D. R.; Nakajima, T.; Tsushima, Y.

    1999-01-01

    A parametric study of the instantaneous radiative impact of contrails is presented using three different radiative transfer models for a series of model atmospheres and cloud parameters. Contrails are treated as geometrically and optically thin plane parallel homogeneous cirrus layers in a static atmospheres The ice water content is varied as a function of ambient temperature. The model atmospheres include tropical, mid-latitude, and subarctic summer and winter atmospheres Optically thin contrails cause a positive net forcing at top of the atmosphere. At the surface the radiative forcing is negative during daytime. The forcing increases with the optical depth and the amount of contrail cover. At the top of the atmosphere a mean contrail cover of 0.1% with average optical depth of 0.2 to 0.5 causes about 0.01 to 0.03 W/m(exp 2)a daily mean instantaneous radiative forcing. Contrails cool the surface during the day and heat the surface during the night, and hence reduce the daily temperature amplitude The net effect depends strongly on the daily variation of contrail cloud cover. The indirect radiative forcing due to particle changes in natural cirrus clouds may be of the same magnitude as the direct one due to additional cover.

  1. 78 FR 3897 - Final Effect of Designation of a Class of Employees for Addition to the Special Exposure Cohort

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-17

    ... Cohort AGENCY: National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control... notice concerning the final effect of the HHS decision to designate a class of employees from the Nuclear... employees as an addition to the SEC: All Atomic Weapons Employees who worked at the facility owned...

  2. Performance of different force fields in force probe simulations.

    PubMed

    Schlesier, Thomas; Diezemann, Gregor

    2013-02-14

    We present detailed force probe molecular dynamic simulations of mechanically interlocked dimeric calix[4]arene-catenanes, comparing the results obtained using three different commonly used force fields (GROMOS G53a5, OPLS-AA, and AMBER GAFF). The model system is well characterized as a two-state system consisting of a closed compact and an elongated structure. Both states are stabilized by a different hydrogen-bond network, and complete separation of the dimer is prevented by the mechanical lock of the entangled aliphatic loops. The system shows fully reversible rebinding meaning that after bond rupture the system rejoins when the external force is relaxed. We present a detailed study of quantities determined in simulations using a force ramp, like the rupture force and rejoin force distributions. Additionally, we analyze the dynamics of the hydrogen-bond network. We find that the results obtained from using the different force fields qualitatively agree in the sense that always the fully reversible behavior is found. The details, like the mean rupture forces, however, do depend on the particular force field. Some of the differences observed can be traced back to differences in the strength of the hydrogen-bond networks.

  3. Current Status of Protein Force Fields for Molecular Dynamics

    PubMed Central

    Lopes, Pedro E.M.; Guvench, Olgun

    2015-01-01

    Summary The current status of classical force fields for proteins is reviewed. These include additive force fields as well as the latest developments in the Drude and AMOEBA polarizable force fields. Parametrization strategies developed specifically for the Drude force field are described and compared with the additive CHARMM36 force field. Results from molecular simulations of proteins and small peptides are summarized to illustrate the performance of the Drude and AMOEBA force fields. PMID:25330958

  4. Current status of protein force fields for molecular dynamics simulations.

    PubMed

    Lopes, Pedro E M; Guvench, Olgun; MacKerell, Alexander D

    2015-01-01

    The current status of classical force fields for proteins is reviewed. These include additive force fields as well as the latest developments in the Drude and AMOEBA polarizable force fields. Parametrization strategies developed specifically for the Drude force field are described and compared with the additive CHARMM36 force field. Results from molecular simulations of proteins and small peptides are summarized to illustrate the performance of the Drude and AMOEBA force fields.

  5. 75 FR 31769 - Procurement List Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... . SUPPLEMENTARY INFORMATION: Additions On 4/9/2010 (75 FR 18164-18165), the Committee for Purchase From People Who... Force, FA3020 82 CONS LGC, Sheppard AFB, TX. Barry S. Lineback, Director, Business Operations....

  6. 78 FR 4133 - Procurement List; Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-18

    ... . SUPPLEMENTARY INFORMATION: Addition On 11/9/2012 (77 FR 67343-67344), the Committee for Purchase From People Who...: Lakeview Center, Inc., Pensacola, FL. Contracting Activity: Dept of the Air Force, FA5004 354 CONS...

  7. 75 FR 75461 - Procurement List; Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ... . SUPPLEMENTARY INFORMATION: Additions On 10/8/2010 (75 FR 62370), the Committee for Purchase From People Who Are... Center, Inc., Pensacola, FL. Contracting Activity: Dept of the Air Force, FA2823 96 CONS MSC, Eglin...

  8. Communication: Multiple atomistic force fields in a single enhanced sampling simulation

    SciTech Connect

    Hoang Viet, Man; Derreumaux, Philippe; Nguyen, Phuong H.

    2015-07-14

    The main concerns of biomolecular dynamics simulations are the convergence of the conformational sampling and the dependence of the results on the force fields. While the first issue can be addressed by employing enhanced sampling techniques such as simulated tempering or replica exchange molecular dynamics, repeating these simulations with different force fields is very time consuming. Here, we propose an automatic method that includes different force fields into a single advanced sampling simulation. Conformational sampling using three all-atom force fields is enhanced by simulated tempering and by formulating the weight parameters of the simulated tempering method in terms of the energy fluctuations, the system is able to perform random walk in both temperature and force field spaces. The method is first demonstrated on a 1D system and then validated by the folding of the 10-residue chignolin peptide in explicit water.

  9. Communication: Multiple atomistic force fields in a single enhanced sampling simulation.

    PubMed

    Hoang Viet, Man; Derreumaux, Philippe; Nguyen, Phuong H

    2015-07-14

    The main concerns of biomolecular dynamics simulations are the convergence of the conformational sampling and the dependence of the results on the force fields. While the first issue can be addressed by employing enhanced sampling techniques such as simulated tempering or replica exchange molecular dynamics, repeating these simulations with different force fields is very time consuming. Here, we propose an automatic method that includes different force fields into a single advanced sampling simulation. Conformational sampling using three all-atom force fields is enhanced by simulated tempering and by formulating the weight parameters of the simulated tempering method in terms of the energy fluctuations, the system is able to perform random walk in both temperature and force field spaces. The method is first demonstrated on a 1D system and then validated by the folding of the 10-residue chignolin peptide in explicit water.

  10. Multistage Force Amplification of Piezoelectric Stacks

    NASA Technical Reports Server (NTRS)

    Xu, Tian-Bing (Inventor); Siochi, Emilie J. (Inventor); Zuo, Lei (Inventor); Jiang, Xiaoning (Inventor); Kang, Jin Ho (Inventor)

    2015-01-01

    Embodiments of the disclosure include an apparatus and methods for using a piezoelectric device, that includes an outer flextensional casing, a first cell and a last cell serially coupled to each other and coupled to the outer flextensional casing such that each cell having a flextensional cell structure and each cell receives an input force and provides an output force that is amplified based on the input force. The apparatus further includes a piezoelectric stack coupled to each cell such that the piezoelectric stack of each cell provides piezoelectric energy based on the output force for each cell. Further, the last cell receives an input force that is the output force from the first cell and the last cell provides an output apparatus force In addition, the piezoelectric energy harvested is based on the output apparatus force. Moreover, the apparatus provides displacement based on the output apparatus force.

  11. The swim force as a body force

    NASA Astrophysics Data System (ADS)

    Yan, Wen; Brady, John

    2015-11-01

    Net (as opposed to random) motion of active matter results from an average swim (or propulsive) force. It is shown that the average swim force acts like a body force - an internal body force [Yan and Brady, Soft Matter, DOI:10.1039/C5SM01318F]. As a result, the particle-pressure exerted on a container wall is the sum of the swim pressure [Takatori et al., Phys. Rev. Lett., 2014, 113, 028103] and the `weight' of the active particles. A continuum mechanical description is possible when variations occur on scales larger than the run length of the active particles and gives a Boltzmann-like distribution from a balance of the swim force and the swim pressure. Active particles may also display `action at a distance' and accumulate adjacent to (or be depleted from) a boundary without any external forces. In the momentum balance for the suspension - the mixture of active particles plus fluid - only external body forces appear.

  12. Benchmarking of Force Fields for Molecule-Membrane Interactions.

    PubMed

    Paloncýová, Markéta; Fabre, Gabin; DeVane, Russell H; Trouillas, Patrick; Berka, Karel; Otyepka, Michal

    2014-09-01

    Studies of drug-membrane interactions witness an ever-growing interest, as penetration, accumulation, and positioning of drugs play a crucial role in drug delivery and metabolism in human body. Molecular dynamics simulations complement nicely experimental measurements and provide us with new insight into drug-membrane interactions; however, the quality of the theoretical data dramatically depends on the quality of the force field used. We calculated the free energy profiles of 11 molecules through a model dimyristoylphosphatidylcholine (DMPC) membrane bilayer using five force fields, namely Berger, Slipids, CHARMM36, GAFFlipids, and GROMOS 43A1-S3. For the sake of comparison, we also employed the semicontinuous tool COSMOmic. High correlation was observed between theoretical and experimental partition coefficients (log K). Partition coefficients calculated by all-atomic force fields (Slipids, CHARMM36, and GAFFlipids) and COSMOmic differed by less than 0.75 log units from the experiment and Slipids emerged as the best performing force field. This work provides the following recommendations (i) for a global, systematic and high throughput thermodynamic evaluations (e.g., log K) of drugs COSMOmic is a tool of choice due to low computational costs; (ii) for studies of the hydrophilic molecules CHARMM36 should be considered; and (iii) for studies of more complex systems, taking into account all pros and cons, Slipids is the force field of choice.

  13. Molecular dynamics simulations data of the twenty encoded amino acids in different force fields.

    PubMed

    Vitalini, F; Noé, F; Keller, B G

    2016-06-01

    We present extensive all-atom Molecular Dynamics (MD) simulation data of the twenty encoded amino acids in explicit water, simulated with different force fields. The termini of the amino acids have been capped to ensure that the dynamics of the Φ and ψ torsion angles are analogues to the dynamics within a peptide chain. We use representatives of each of the four major force field families: AMBER ff-99SBILDN [1], AMBER ff-03 [2], OPLS-AA/L [3], CHARMM27 [4] and GROMOS43a1 [5], [6]. Our data represents a library and test bed for method development for MD simulations and for force fields development. Part of the data set has been previously used for comparison of the dynamic properties of force fields (Vitalini et al., 2015) [7] and for the construction of peptide basis functions for the variational approach to molecular kinetics [8].

  14. Molecular dynamics simulations data of the twenty encoded amino acids in different force fields.

    PubMed

    Vitalini, F; Noé, F; Keller, B G

    2016-06-01

    We present extensive all-atom Molecular Dynamics (MD) simulation data of the twenty encoded amino acids in explicit water, simulated with different force fields. The termini of the amino acids have been capped to ensure that the dynamics of the Φ and ψ torsion angles are analogues to the dynamics within a peptide chain. We use representatives of each of the four major force field families: AMBER ff-99SBILDN [1], AMBER ff-03 [2], OPLS-AA/L [3], CHARMM27 [4] and GROMOS43a1 [5], [6]. Our data represents a library and test bed for method development for MD simulations and for force fields development. Part of the data set has been previously used for comparison of the dynamic properties of force fields (Vitalini et al., 2015) [7] and for the construction of peptide basis functions for the variational approach to molecular kinetics [8]. PMID:27054161

  15. Molecular dynamics simulations data of the twenty encoded amino acids in different force fields

    PubMed Central

    Vitalini, F.; Noé, F.; Keller, B.G.

    2016-01-01

    We present extensive all-atom Molecular Dynamics (MD) simulation data of the twenty encoded amino acids in explicit water, simulated with different force fields. The termini of the amino acids have been capped to ensure that the dynamics of the Φ and ψ torsion angles are analogues to the dynamics within a peptide chain. We use representatives of each of the four major force field families: AMBER ff-99SBILDN [1], AMBER ff-03 [2], OPLS-AA/L [3], CHARMM27 [4] and GROMOS43a1 [5], [6]. Our data represents a library and test bed for method development for MD simulations and for force fields development. Part of the data set has been previously used for comparison of the dynamic properties of force fields (Vitalini et al., 2015) [7] and for the construction of peptide basis functions for the variational approach to molecular kinetics [8]. PMID:27054161

  16. Theoretical models for surface forces and adhesion and their measurement using atomic force microscopy.

    PubMed

    Leite, Fabio L; Bueno, Carolina C; Da Róz, Alessandra L; Ziemath, Ervino C; Oliveira, Osvaldo N

    2012-10-08

    The increasing importance of studies on soft matter and their impact on new technologies, including those associated with nanotechnology, has brought intermolecular and surface forces to the forefront of physics and materials science, for these are the prevailing forces in micro and nanosystems. With experimental methods such as the atomic force spectroscopy (AFS), it is now possible to measure these forces accurately, in addition to providing information on local material properties such as elasticity, hardness and adhesion. This review provides the theoretical and experimental background of afs, adhesion forces, intermolecular interactions and surface forces in air, vacuum and in solution.

  17. Theoretical Models for Surface Forces and Adhesion and Their Measurement Using Atomic Force Microscopy

    PubMed Central

    Leite, Fabio L.; Bueno, Carolina C.; Da Róz, Alessandra L.; Ziemath, Ervino C.; Oliveira, Osvaldo N.

    2012-01-01

    The increasing importance of studies on soft matter and their impact on new technologies, including those associated with nanotechnology, has brought intermolecular and surface forces to the forefront of physics and materials science, for these are the prevailing forces in micro and nanosystems. With experimental methods such as the atomic force spectroscopy (AFS), it is now possible to measure these forces accurately, in addition to providing information on local material properties such as elasticity, hardness and adhesion. This review provides the theoretical and experimental background of AFS, adhesion forces, intermolecular interactions and surface forces in air, vacuum and in solution. PMID:23202925

  18. Calibration of frictional forces in atomic force microscopy

    SciTech Connect

    Ogletree, D.F.; Carpick, R.W.; Salmeron, M.

    1996-09-01

    The atomic force microscope can provide information on the atomic-level frictional properties of surfaces, but reproducible quantitative measurements are difficult to obtain. Parameters that are either unknown or difficult to precisely measure include the normal and lateral cantilever force constants (particularly with microfabricated cantilevers), the tip height, the deflection sensor response, and the tip structure and composition at the tip-surface contact. We present an {ital in} {ital situ} experimental procedure to determine the response of a cantilever to lateral forces in terms of its normal force response. This procedure is quite general. It will work with any type of deflection sensor and does not require the knowledge or direct measurement of the lever dimensions or the tip height. In addition, the shape of the tip apex can be determined. We also discuss a number of specific issues related to force and friction measurements using optical lever deflection sensing. We present experimental results on the lateral force response of commercially available V-shaped cantilevers. Our results are consistent with estimates of lever mechanical properties using continuum elasticity theory. {copyright} {ital 1996 American Institute of Physics.}

  19. Training program to prepare the U.S. DOE laboratories for the entry into force of the protocol additional to the agreement between the United States of America and the International Atomic Energy Agency for the application of safeguards in the United

    SciTech Connect

    Boyer, Brian David; Stevens, Rebecca C; Uribe, Eva C; Sandoval, M Analisa; Valente, John N; Valente, John U; Jo, Jae H; Sellen, Joana

    2009-01-01

    In 2008, a joint team from Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL) consisting of specialists in training IAEA inspectors in the use of complementary access activities formulated a training program to prepare the U.S DOE laboratories for the entry into force of the U.S. Additional Protocol. Since the U.S. Additional Protocol would allow for IAEA access to the DOE laboratories under the aegis of complementary access activities, the DOE laboratories would need to prepare for such visits. The goal of the training was to ensure that the DOE laboratories would successfully host an IAEA complementary access. In doing so, the labs must be able to provide the IAEA with the information that the IAEA would need to resolve its questions about the U.S. Declaration and declared activities at the lab, and also protect certain equities, as provided under the U.S. Additional Protocol Article 1.b and c. which set forth a 'National Security Exclusion.' This 'NSE' states that the AP provisions apply within the United States 'excluding only instances where its application would result in access by the Agency to activities with direct national security significance to the United States or to location or information associated with such activities.' These activities are referred to collectively as DNSS-direct national security significance. Furthermore, the U.S. has a specific right to employ managed access, without prejudice to the right under Article 1.b, in connection with activities of DNSS. The provisions in Articles 1.b and 1.c are unique to the U.S. AP, and are additional to the more general right, under Article 7, to use managed access to protect from disclosure proprietary and/or proliferation-sensitive information, and to meet safety and security requirements, that is incorporated directly from the Model Additional Protocol. The BNL-LANL team performed training at Lawrence Livermore National Laboratory, Idaho National Laboratory, and Oak

  20. Predicting transcription factor specificity with all-atom models.

    PubMed

    Jamal Rahi, Sahand; Virnau, Peter; Mirny, Leonid A; Kardar, Mehran

    2008-11-01

    The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites, rather than an ab initio approach. Here, we examine the possibility of using structure-based energy calculations that require no knowledge of bound sites but rather start with the structure of a protein-DNA complex. We study the PurR Escherichia coli TF, and explore to which extent atomistic models of protein-DNA complexes can be used to distinguish between cognate and noncognate DNA sites. Particular emphasis is placed on systematic evaluation of this approach by comparing its performance with bioinformatic methods, by testing it against random decoys and sites of homologous TFs. We also examine a set of experimental mutations in both DNA and the protein. Using our explicit estimates of energy, we show that the specificity for PurR is dominated by direct protein-DNA interactions, and weakly influenced by bending of DNA.

  1. Beyond Modeling: All-Atom Olfactory Receptor Model Simulations

    PubMed Central

    Lai, Peter C.; Crasto, Chiquito J.

    2012-01-01

    Olfactory receptors (ORs) are a type of GTP-binding protein-coupled receptor (GPCR). These receptors are responsible for mediating the sense of smell through their interaction with odor ligands. OR-odorant interactions marks the first step in the process that leads to olfaction. Computational studies on model OR structures can generate focused and novel hypotheses for further bench investigation by providing a view of these interactions at the molecular level beyond inferences that are drawn merely from static docking. Here we have shown the specific advantages of simulating the dynamic environment associated with OR-odorant interactions. We present a rigorous protocol which ranges from the creation of a computationally derived model of an olfactory receptor to simulating the interactions between an OR and an odorant molecule. Given the ubiquitous occurrence of GPCRs in the membranes of cells, we anticipate that our OR-developed methodology will serve as a model for the computational structural biology of all GPCRs. PMID:22563330

  2. Finger Forces in Clarinet Playing

    PubMed Central

    Hofmann, Alex; Goebl, Werner

    2016-01-01

    Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17) and professional clarinettists (N = 6) were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 × 2 × 2 design (register: low–high; tempo: slow–fast, dynamics: soft–loud). There was an additional condition controlled by the experimenter, which determined the expression levels (low–high) of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions). The melody was performed in three tempo conditions (slow, medium, fast) in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (Fmean) and peak force (Fmax) were calculated. The overall finger forces were low (Fmean = 1.17 N, Fmax = 3.05 N) compared to those on other musical instruments (e.g., guitar). Participants applied the largest finger forces during the high expression level performance conditions (Fmean = 1.21 N). For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (Fmean = 0.54 N). Such sensor instruments provide useful insights into player

  3. Additive-free digital microfluidics.

    PubMed

    Freire, Sergio L S; Tanner, Brendan

    2013-07-16

    Digital microfluidics, a technique for manipulation of droplets, is becoming increasingly important for the development of miniaturized platforms for laboratory processes. Despite the enthusiasm, droplet motion is frequently hindered by the desorption of proteins or other analytes to surfaces. Current approaches to minimize this unwanted surface fouling involve the addition of extra species to the droplet or its surroundings, which might be problematic depending on the droplet content. Here, a new strategy is introduced to move droplets containing cells and other analytes on solid substrates, without extra moieties; in particular, droplets with bovine serum albumin could be moved at a concentration 2000 times higher than previously reported (without additives). This capability is achieved by using a soot-based superamphiphobic surface combined with a new device geometry, which favors droplet rolling. Contrasting with electrowetting, wetting forces are not required for droplet motion.

  4. Automatic molecular structure perception for the universal force field.

    PubMed

    Artemova, Svetlana; Jaillet, Léonard; Redon, Stephane

    2016-05-15

    The Universal Force Field (UFF) is a classical force field applicable to almost all atom types of the periodic table. Such a flexibility makes this force field a potential good candidate for simulations involving a large spectrum of systems and, indeed, UFF has been applied to various families of molecules. Unfortunately, initializing UFF, that is, performing molecular structure perception to determine which parameters should be used to compute the UFF energy and forces, appears to be a difficult problem. Although many perception methods exist, they mostly focus on organic molecules, and are thus not well-adapted to the diversity of systems potentially considered with UFF. In this article, we propose an automatic perception method for initializing UFF that includes the identification of the system's connectivity, the assignment of bond orders as well as UFF atom types. This perception scheme is proposed as a self-contained UFF implementation integrated in a new module for the SAMSON software platform for computational nanoscience (http://www.samson-connect.net). We validate both the automatic perception method and the UFF implementation on a series of benchmarks. PMID:26927616

  5. Systematic procedure to parametrize force fields for molecular fluids.

    PubMed

    Salas, Frank José; Méndez-Maldonado, G Arlette; Núñez-Rojas, Edgar; Aguilar-Pineda, Gabriel Eloy; Domínguez, Hector; Alejandre, José

    2015-02-10

    A new strategy to develop force fields for molecular fluids is presented. The intermolecular parameters are fitted to reproduce experimental values of target properties at ambient conditions and also the critical temperature. The partial charges are chosen to match the dielectric constant. The Lennard-Jones parameters, εii and σii, are fitted to reproduce the surface tension at the vapor-liquid interface and the liquid density, respectively. The choice of those properties allows obtaining systematically the final parameters using a small number of simulations. It is shown that the use of surface tension as a target property is better than the choice of heat of vaporization. The method is applied to molecules, from all atoms to a coarse-grained level, such as pyridine, dichloromethane, methanol, and 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) at different temperatures and pressures. The heat of vaporization, radial distribution functions, and self-diffusion coeficient are also calculated.

  6. Ab initio based force field and molecular dynamics simulations of crystalline TATB.

    PubMed

    Gee, Richard H; Roszak, Szczepan; Balasubramanian, Krishnan; Fried, Laurence E

    2004-04-15

    An all-atom force field for 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is presented. The classical intermolecular interaction potential for TATB is based on single-point energies determined from high-level ab initio calculations of TATB dimers. The newly developed potential function is used to examine bulk crystalline TATB via molecular dynamics simulations. The isobaric thermal expansion and isothermal compression under hydrostatic pressures obtained from the molecular dynamics simulations are in good agreement with experiment. The calculated volume-temperature expansion is almost one dimensional along the c crystallographic axis, whereas under compression, all three unit cell axes participate, albeit unequally. PMID:15267608

  7. Force propagation and force generation in cells.

    PubMed

    Jonas, Oliver; Duschl, Claus

    2010-09-01

    Determining how forces are produced by and propagated through the cytoskeleton (CSK) of the cell is of great interest as dynamic processes of the CSK are intimately correlated with many molecular signaling pathways. We are presenting a novel approach for integrating measurements on cell elasticity, transcellular force propagation, and cellular force generation to obtain a comprehensive description of dynamic and mechanical properties of the CSK under force loading. This approach uses a combination of scanning force microscopy (SFM) and Total Internal Reflection Fluorescence (TIRF) microscopy. We apply well-defined loading schemes onto the apical cell membrane of fibroblasts using the SFM and simultaneously use TIRF microscopy to image the topography of the basal cell membrane. The locally distinct changes of shape and depth of the cytoskeletal imprints onto the basal membrane are interpreted as results of force propagation through the cytoplasm. This observation provides evidence for the tensegrity model and demonstrates the usefulness of our approach that does not depend on potentially disturbing marker compounds. We confirm that the actin network greatly determines cell stiffness and represents the substrate that mediates force transduction through the cytoplasm of the cell. The latter is an essential feature of tensegrity. Most importantly, our new finding that, both intact actin and microtubule networks are required for enabling the cell to produce work, can only be understood within the framework of the tensegrity model. We also provide, for the first time, a direct measurement of the cell's mechanical power output under compression at two femtowatts. PMID:20607861

  8. Oblique view of east side mechanical additions and south side ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Oblique view of east side mechanical additions and south side of 1955 addition, facing northwest. - Albrook Air Force Station, Dispensary, East side of Canfield Avenue, Balboa, Former Panama Canal Zone, CZ

  9. The Mouse Forced Swim Test

    PubMed Central

    Can, Adem; Dao, David T.; Arad, Michal; Terrillion, Chantelle E.; Piantadosi, Sean C.; Gould, Todd D.

    2012-01-01

    The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed. PMID:22314943

  10. The mouse forced swim test.

    PubMed

    Can, Adem; Dao, David T; Arad, Michal; Terrillion, Chantelle E; Piantadosi, Sean C; Gould, Todd D

    2012-01-29

    The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed.

  11. Detailed Per-residue Energetic Analysis Explains the Driving Force for Microtubule Disassembly

    PubMed Central

    Ayoub, Ahmed T.; Klobukowski, Mariusz; Tuszynski, Jack A.

    2015-01-01

    Microtubules are long filamentous hollow cylinders whose surfaces form lattice structures of αβ-tubulin heterodimers. They perform multiple physiological roles in eukaryotic cells and are targets for therapeutic interventions. In our study, we carried out all-atom molecular dynamics simulations for arbitrarily long microtubules that have either GDP or GTP molecules in the E-site of β-tubulin. A detailed energy balance of the MM/GBSA inter-dimer interaction energy per residue contributing to the overall lateral and longitudinal structural stability was performed. The obtained results identified the key residues and tubulin domains according to their energetic contributions. They also identified the molecular forces that drive microtubule disassembly. At the tip of the plus end of the microtubule, the uneven distribution of longitudinal interaction energies within a protofilament generates a torque that bends tubulin outwardly with respect to the cylinder's axis causing disassembly. In the presence of GTP, this torque is opposed by lateral interactions that prevent outward curling, thus stabilizing the whole microtubule. Once GTP hydrolysis reaches the tip of the microtubule (lateral cap), lateral interactions become much weaker, allowing tubulin dimers to bend outwards, causing disassembly. The role of magnesium in the process of outward curling has also been demonstrated. This study also showed that the microtubule seam is the most energetically labile inter-dimer interface and could serve as a trigger point for disassembly. Based on a detailed balance of the energetic contributions per amino acid residue in the microtubule, numerous other analyses could be performed to give additional insights into the properties of microtubule dynamic instability. PMID:26030285

  12. Aerodynamic Lifting Force.

    ERIC Educational Resources Information Center

    Weltner, Klaus

    1990-01-01

    Describes some experiments showing both qualitatively and quantitatively that aerodynamic lift is a reaction force. Demonstrates reaction forces caused by the acceleration of an airstream and the deflection of an airstream. Provides pictures of demonstration apparatus and mathematical expressions. (YP)

  13. Microprocessor controlled force actuator

    NASA Technical Reports Server (NTRS)

    Zimmerman, D. C.; Inman, D. J.; Horner, G. C.

    1986-01-01

    The mechanical and electrical design of a prototype force actuator for vibration control of large space structures (LSS) is described. The force actuator is an electromagnetic system that produces a force by reacting against a proof-mass. The actuator has two colocated sensors, a digital microcontroller, and a power amplifier. The total weight of actuator is .998 kg. The actuator has a steady state force output of approximately 2.75 N from approximately 2 Hz to well beyond 1000 Hz.

  14. Fluid force transducer

    DOEpatents

    Jendrzejczyk, Joseph A.

    1982-01-01

    An electrical fluid force transducer for measuring the magnitude and direction of fluid forces caused by lateral fluid flow, includes a movable sleeve which is deflectable in response to the movement of fluid, and a rod fixed to the sleeve to translate forces applied to the sleeve to strain gauges attached to the rod, the strain gauges being connected in a bridge circuit arrangement enabling generation of a signal output indicative of the magnitude and direction of the force applied to the sleeve.

  15. Submolecular Resolution Imaging of Molecules by Atomic Force Microscopy: The Influence of the Electrostatic Force.

    PubMed

    van der Lit, Joost; Di Cicco, Francesca; Hapala, Prokop; Jelinek, Pavel; Swart, Ingmar

    2016-03-01

    The forces governing the contrast in submolecular resolution imaging of molecules with atomic force microscopy (AFM) have recently become a topic of intense debate. Here, we show that the electrostatic force is essential to understand the contrast in atomically resolved AFM images of polar molecules. Specifically, we image strongly polarized molecules with negatively and positively charged tips. A contrast inversion is observed above the polar groups. By taking into account the electrostatic forces between tip and molecule, the observed contrast differences can be reproduced using a molecular mechanics model. In addition, we analyze the height dependence of the various force components contributing to the high-resolution AFM contrast.

  16. Submolecular Resolution Imaging of Molecules by Atomic Force Microscopy: The Influence of the Electrostatic Force

    NASA Astrophysics Data System (ADS)

    van der Lit, Joost; Di Cicco, Francesca; Hapala, Prokop; Jelinek, Pavel; Swart, Ingmar

    2016-03-01

    The forces governing the contrast in submolecular resolution imaging of molecules with atomic force microscopy (AFM) have recently become a topic of intense debate. Here, we show that the electrostatic force is essential to understand the contrast in atomically resolved AFM images of polar molecules. Specifically, we image strongly polarized molecules with negatively and positively charged tips. A contrast inversion is observed above the polar groups. By taking into account the electrostatic forces between tip and molecule, the observed contrast differences can be reproduced using a molecular mechanics model. In addition, we analyze the height dependence of the various force components contributing to the high-resolution AFM contrast.

  17. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  18. Forces in General Relativity

    ERIC Educational Resources Information Center

    Ridgely, Charles T.

    2010-01-01

    Many textbooks dealing with general relativity do not demonstrate the derivation of forces in enough detail. The analyses presented herein demonstrate straightforward methods for computing forces by way of general relativity. Covariant divergence of the stress-energy-momentum tensor is used to derive a general expression of the force experienced…

  19. Turkish Students' Force Meanings

    ERIC Educational Resources Information Center

    Menekse, Muhsin; Clark, Douglas B.; Ozdemir, Gokhan; D'angelo, Cynthia; Scheligh, Sharon

    2009-01-01

    What are Turkish pre, elementary, middle, and high school students' force ideas? And, how do Turkish students' non-normative force ideas differ or be similar to the well-known force misconceptions reported in the literature? Students have false and persistent beliefs about the physical world and they struggle with challenging misconceptions based…

  20. Debunking Coriolis Force Myths

    ERIC Educational Resources Information Center

    Shakur, Asif

    2014-01-01

    Much has been written and debated about the Coriolis force. Unfortunately, this has done little to demystify the paradoxes surrounding this fictitious force invoked by an observer in a rotating frame of reference. It is the purpose of this article to make another valiant attempt to slay the dragon of the Coriolis force! This will be done without…

  1. Cutting Force Control Applying Sensorless Cutting Force Monitoring Method

    NASA Astrophysics Data System (ADS)

    Kurihara, Daisuke; Kakinuma, Yasuhiro; Katsura, Seiichiro

    Intelligent machine tools require the functions of high-accurate process monitoring and adaptive control to fit the optimum process condition in each workpieces. For realizing these functions, the various techniques to monitor the cutting process and control it using additional sensors have been proposed and widely studied. Authors propose the sensorless cutting force control method using parallel disturbance observer. The performance of our proposed method is evaluated through simulation and experiments using a linear motor driving table.

  2. Efficacy of climate forcings

    NASA Astrophysics Data System (ADS)

    Hansen, J.; Sato, M.; Ruedy, R.; Nazarenko, L.; Lacis, A.; Schmidt, G. A.; Russell, G.; Aleinov, I.; Bauer, M.; Bauer, S.; Bell, N.; Cairns, B.; Canuto, V.; Chandler, M.; Cheng, Y.; Del Genio, A.; Faluvegi, G.; Fleming, E.; Friend, A.; Hall, T.; Jackman, C.; Kelley, M.; Kiang, N.; Koch, D.; Lean, J.; Lerner, J.; Lo, K.; Menon, S.; Miller, R.; Minnis, P.; Novakov, T.; Oinas, V.; Perlwitz, Ja.; Perlwitz, Ju.; Rind, D.; Romanou, A.; Shindell, D.; Stone, P.; Sun, S.; Tausnev, N.; Thresher, D.; Wielicki, B.; Wong, T.; Yao, M.; Zhang, S.

    2005-09-01

    We use a global climate model to compare the effectiveness of many climate forcing agents for producing climate change. We find a substantial range in the "efficacy" of different forcings, where the efficacy is the global temperature response per unit forcing relative to the response to CO2 forcing. Anthropogenic CH4 has efficacy ˜110%, which increases to ˜145% when its indirect effects on stratospheric H2O and tropospheric O3 are included, yielding an effective climate forcing of ˜0.8 W/m2 for the period 1750-2000 and making CH4 the largest anthropogenic climate forcing other than CO2. Black carbon (BC) aerosols from biomass burning have a calculated efficacy ˜58%, while fossil fuel BC has an efficacy ˜78%. Accounting for forcing efficacies and for indirect effects via snow albedo and cloud changes, we find that fossil fuel soot, defined as BC + OC (organic carbon), has a net positive forcing while biomass burning BC + OC has a negative forcing. We show that replacement of the traditional instantaneous and adjusted forcings, Fi and Fa, with an easily computed alternative, Fs, yields a better predictor of climate change, i.e., its efficacies are closer to unity. Fs is inferred from flux and temperature changes in a fixed-ocean model run. There is remarkable congruence in the spatial distribution of climate change, normalized to the same forcing Fs, for most climate forcing agents, suggesting that the global forcing has more relevance to regional climate change than may have been anticipated. Increasing greenhouse gases intensify the Hadley circulation in our model, increasing rainfall in the Intertropical Convergence Zone (ITCZ), Eastern United States, and East Asia, while intensifying dry conditions in the subtropics including the Southwest United States, the Mediterranean region, the Middle East, and an expanding Sahel. These features survive in model simulations that use all estimated forcings for the period 1880-2000. Responses to localized forcings, such

  3. Cell adhesion force microscopy

    PubMed Central

    Sagvolden, G.; Giaever, I.; Pettersen, E. O.; Feder, J.

    1999-01-01

    The adhesion forces of cervical carcinoma cells in tissue culture were measured by using the manipulation force microscope, a novel atomic force microscope. The forces were studied as a function of time and temperature for cells cultured on hydrophilic and hydrophobic polystyrene substrates with preadsorbed proteins. The cells attached faster and stronger at 37°C than at 23°C and better on hydrophilic than on hydrophobic substrates, even though proteins adsorb much better to the hydrophobic substrates. Because cell adhesion serves to control several stages in the cell cycle, we anticipate that the manipulation force microscope can help clarify some cell-adhesion related issues. PMID:9892657

  4. Force reflecting hand controller for manipulator teleoperation

    NASA Technical Reports Server (NTRS)

    Bryfogle, Mark D.

    1991-01-01

    A force reflecting hand controller based upon a six degree of freedom fully parallel mechanism, often termed a Stewart Platform, has been designed, constructed, and tested as an integrated system with a slave robot manipulator test bed. A force reflecting hand controller comprises a kinesthetic device capable of transmitting position and orientation commands to a slave robot manipulator while simultaneously representing the environmental interaction forces of the slave manipulator back to the operator through actuators driving the hand controller mechanism. The Stewart Platform was chosen as a novel approach to improve force reflecting teleoperation because of its inherently high ratio of load generation capability to system mass content and the correspondingly high dynamic bandwidth. An additional novelty of the program was to implement closed loop force and torque control about the hand controller mechanism by equipping the handgrip with a six degree of freedom force and torque measuring cell. The mechanical, electrical, computer, and control systems are discussed and system tests are presented.

  5. Force reflecting hand controller for manipulator teleoperation

    NASA Astrophysics Data System (ADS)

    Bryfogle, Mark D.

    1991-12-01

    A force reflecting hand controller based upon a six degree of freedom fully parallel mechanism, often termed a Stewart Platform, has been designed, constructed, and tested as an integrated system with a slave robot manipulator test bed. A force reflecting hand controller comprises a kinesthetic device capable of transmitting position and orientation commands to a slave robot manipulator while simultaneously representing the environmental interaction forces of the slave manipulator back to the operator through actuators driving the hand controller mechanism. The Stewart Platform was chosen as a novel approach to improve force reflecting teleoperation because of its inherently high ratio of load generation capability to system mass content and the correspondingly high dynamic bandwidth. An additional novelty of the program was to implement closed loop force and torque control about the hand controller mechanism by equipping the handgrip with a six degree of freedom force and torque measuring cell. The mechanical, electrical, computer, and control systems are discussed and system tests are presented.

  6. Entropic force between biomembranes

    NASA Astrophysics Data System (ADS)

    Li, Long; Song, Fan

    2016-08-01

    Undulation force, an entropic force, stems from thermally excited fluctuations, and plays a key role in the essential interactions between neighboring surfaces of objects. Although the characteristics of the undulation force have been widely studied theoretically and experimentally, the distance dependence of the force, which constitutes its most fundamental characteristic, remains poorly understood. In this paper, first, we obtain a novel expression for the undulation force by employing elasticity and statistical mechanics and prove it to be in good agreement with existing experimental results. Second, we clearly demonstrate that the two representative forms of the undulation force proposed by Helfrich and Freund were respectively the upper and lower bounds of the present expression when the separation between membranes is sufficiently small, which was intrinsically different from the existing results where Helfrich's and Freund's forms of the undulation force were only suitable for the intermediate and small separations. The investigations show that only in a sufficiently small separation does Helfrich's result stand for the undulation force with a large wave number and Freund's result express the force with a small wave number. Finally, a critical acting distance of the undulation force, beyond which the entropic force will rapidly decay approaching zero, is presented.

  7. Feasibility of measuring antigen-antibody interaction forces using a scanning force microscope.

    PubMed

    Stuart, J K; Hlady, V

    1999-08-31

    The molecular affinity scanning force microscopy (MASFM) described in this study was developed in an effort to test the possibility of antigen-antibody binding measurement using force-separation distance profiles. The MASFM configuration was comprised of a spherical glass bead as an MASFM probe, to which the fluorescein antigen has been covalently attached, and a silicon dioxide-based substrate, to which the antifluorescyl IgG antibody was covalently bound. The bead was glued to the tip of a commercial SFM cantilever. Adhesion forces have been measured between two different specific antigen-antibody pairs and between nonspecific surfaces bearing only glycidoxypropylsilane immobilization chemistry. In force-separation (F-s) measurements, nonspecific forces displayed relatively few force discontinuities and mean adhesion forces lower than those found for specific antigen-antibody measurements. Force-separation profiles measured between specific antigen-antibody pairs showed many discontinuities and had higher mean forces. Positive controls revealed that the mean forces were slightly reduced by the addition of free ligand. The magnitude of mean forces did not correlate with the respective activation enthalpies of the proteins, as would be expected. At lower force values the force histograms for the specific pairs and for positive controls were indistinguishable. None of the force-separation data sets could fit a Poisson discrete-force model. This statistical analysis showed a large relative contribution from nonspecific interactions. It is concluded that the use of the large sphere as an SFM probe is counterproductive: while the large sphere does sample a larger number of specific interactions during each measurement, it also samples at the same time a large proportion of nonspecific forces. The presence of the nonspecific force contributions is likely due to the deformation of the polymerized GPS spacer layer which is thought to be delaminated from the surface upon

  8. Forces in molecules.

    PubMed

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another?

  9. Forces in molecules.

    PubMed

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  10. Force Limited Vibration Testing

    NASA Technical Reports Server (NTRS)

    Scharton, Terry; Chang, Kurng Y.

    2005-01-01

    This slide presentation reviews the concept and applications of Force Limited Vibration Testing. The goal of vibration testing of aerospace hardware is to identify problems that would result in flight failures. The commonly used aerospace vibration tests uses artificially high shaker forces and responses at the resonance frequencies of the test item. It has become common to limit the acceleration responses in the test to those predicted for the flight. This requires an analysis of the acceleration response, and requires placing accelerometers on the test item. With the advent of piezoelectric gages it has become possible to improve vibration testing. The basic equations have are reviewed. Force limits are analogous and complementary to the acceleration specifications used in conventional vibration testing. Just as the acceleration specification is the frequency spectrum envelope of the in-flight acceleration at the interface between the test item and flight mounting structure, the force limit is the envelope of the in-flight force at the interface . In force limited vibration tests, both the acceleration and force specifications are needed, and the force specification is generally based on and proportional to the acceleration specification. Therefore, force limiting does not compensate for errors in the development of the acceleration specification, e.g., too much conservatism or the lack thereof. These errors will carry over into the force specification. Since in-flight vibratory force data are scarce, force limits are often derived from coupled system analyses and impedance information obtained from measurements or finite element models (FEM). Fortunately, data on the interface forces between systems and components are now available from system acoustic and vibration tests of development test models and from a few flight experiments. Semi-empirical methods of predicting force limits are currently being developed on the basis of the limited flight and system test

  11. Photoacoustic radiation force on a microbubble.

    PubMed

    Erkol, Hakan; Aytac-Kipergil, Esra; Unlu, Mehmet Burcin

    2014-08-01

    We investigate the radiation force on a microbubble due to the photoacoustic wave which is generated by using a pulsed laser. In particular, we focus on the dependence of pulsed laser parameters on the radiation force. In order to do so, we first obtain a new and comprehensive analytical solution to the photoacoustic wave equation based on the Fourier transform for various absorption profiles. Then, we write an expression of the radiation force containing explicit laser parameters, pulse duration, and beamwidth of the laser. Furthermore, we calculate the primary radiation force acting on a microbubble. We show that laser parameters and the position of the microbubble relative to a photoacoustic source have a considerable effect on the primary radiation force. By means of recent developments in laser technologies that render tunability of pulse duration and repetition frequency possible, an adjustable radiation force can be applied to microbubbles. High spatial control of applied force is ensured on account of smaller focal spots achievable by focused optics. In this context, conventional piezoelectric acoustic source applications could be surpassed. In addition, it is possible to increase the radiation force by making source wavelength with the absorption peak of absorber concurrent. The application of photoacoustic radiation force can open a cache of opportunities such as manipulation of microbubbles used as contrast agents and as carrier vehicles for drugs and genes with a desired force along with in vivo applications. PMID:25215814

  12. Magnus force in superfluids and superconductors

    SciTech Connect

    Sonin, E.B. |

    1997-01-01

    The forces on the vortex, transverse to its velocity, are considered. In addition to the superfluid Magnus force from the condensate (superfluid component), there are transverse forces from thermal quasiparticles and external fields violating the Galilean invariance. The forces between quasiparticles and the vortex originate from interference of quasiparticles with trajectories on the left and on the right from the vortex like similar forces for electrons interacting with the thin magnetic-flux tube (the Aharonov-Bohm effect). These forces are derived for phonons from the equations of superfluid hydrodynamics, and for BCS quasiparticles from the Bogolyubov{endash}de Gennes equations. The effect of external fields breaking Galilean invariance is analyzed for vortices in the two-dimensional Josephson junction array. The symmetry analysis of the classical equations for the array shows that the total transverse force on the vortex vanishes. Therefore the Hall effect which is linear in the transverse force is absent also. This means that the Magnus force from the superfluid component {ital exactly} cancels with the transverse force from the external fields. The results of other approaches are also brought together for discussion. {copyright} {ital 1997} {ital The American Physical Society}

  13. Photoacoustic radiation force on a microbubble

    NASA Astrophysics Data System (ADS)

    Erkol, Hakan; Aytac-Kipergil, Esra; Unlu, Mehmet Burcin

    2014-08-01

    We investigate the radiation force on a microbubble due to the photoacoustic wave which is generated by using a pulsed laser. In particular, we focus on the dependence of pulsed laser parameters on the radiation force. In order to do so, we first obtain a new and comprehensive analytical solution to the photoacoustic wave equation based on the Fourier transform for various absorption profiles. Then, we write an expression of the radiation force containing explicit laser parameters, pulse duration, and beamwidth of the laser. Furthermore, we calculate the primary radiation force acting on a microbubble. We show that laser parameters and the position of the microbubble relative to a photoacoustic source have a considerable effect on the primary radiation force. By means of recent developments in laser technologies that render tunability of pulse duration and repetition frequency possible, an adjustable radiation force can be applied to microbubbles. High spatial control of applied force is ensured on account of smaller focal spots achievable by focused optics. In this context, conventional piezoelectric acoustic source applications could be surpassed. In addition, it is possible to increase the radiation force by making source wavelength with the absorption peak of absorber concurrent. The application of photoacoustic radiation force can open a cache of opportunities such as manipulation of microbubbles used as contrast agents and as carrier vehicles for drugs and genes with a desired force along with in vivo applications.

  14. 76 FR 60809 - Procurement List; Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... . SUPPLEMENTARY INFORMATION: Additions On 7/1/2011 (76 FR 38641-38642) and 8/5/2011 (76 FR 47565-47566), the... Institute, Inc., San Antonio, TX. Contracting Activity: Dept of the Air Force, FA4830 23 CONS CC, Moody...

  15. 78 FR 16476 - Procurement List Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ...: Additions On 1/18/2013 (78 FR 4133-4134), the Committee for Purchase From People Who Are Blind or Severely...., San Antonio, TX. Contracting Activity: Dept Of The Air Force, FA4621 22 CONS LGC, McConnell AFB,...

  16. 77 FR 2962 - Procurement List Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-20

    ...@AbilityOne.gov . SUPPLEMENTARY INFORMATION: Additions On 11/14/2011 (76 FR 70423-70424) and 11/18/2011 (76 FR 71554), the Committee for Purchase From People Who Are Blind or Severely Disabled published... Activity: Dept. of the Air Force, FA2860 11 Cons Lgc, Andrews AFB, MD. Barry S. Lineback,...

  17. Coulomb force as an entropic force

    SciTech Connect

    Wang Tower

    2010-05-15

    Motivated by Verlinde's theory of entropic gravity, we give a tentative explanation to the Coulomb's law with an entropic force. When trying to do this, we find the equipartition rule should be extended to charges and the concept of temperature should be reinterpreted. If one accepts the holographic principle as well as our generalizations and reinterpretations, then Coulomb's law, the Poisson equation, and the Maxwell equations can be derived smoothly. Our attempt can be regarded as a new way to unify the electromagnetic force with gravity, from the entropic origin. Possibly some of our postulates are related to the D-brane picture of black hole thermodynamics.

  18. Coulomb force as an entropic force

    NASA Astrophysics Data System (ADS)

    Wang, Tower

    2010-05-01

    Motivated by Verlinde’s theory of entropic gravity, we give a tentative explanation to the Coulomb’s law with an entropic force. When trying to do this, we find the equipartition rule should be extended to charges and the concept of temperature should be reinterpreted. If one accepts the holographic principle as well as our generalizations and reinterpretations, then Coulomb’s law, the Poisson equation, and the Maxwell equations can be derived smoothly. Our attempt can be regarded as a new way to unify the electromagnetic force with gravity, from the entropic origin. Possibly some of our postulates are related to the D-brane picture of black hole thermodynamics.

  19. Quantum Fictitious Forces

    NASA Astrophysics Data System (ADS)

    Białynicki-Birula, I.; Cirone, M. A.; Dahl, J. P.; Seligman, T. H.; Straub, F.; Schleich, W. P.

    2003-09-01

    We present Heisenberg's equation of motion for the radial variable of a free non-relativistic particle in D dimensions. The resulting radial force consists of three contributions: (i) the quantum fictitious force which is either attractive or repulsive depending on the number of dimensions, (ii) a singular quantum force located at the origin, and (iii) the centrifugal force associated with non-vanishing angular momentum. Moreover, we use Heisenberg's uncertainty relation to introduce a lower bound for the kinetic energy of an ensemble of neutral particles. This bound is quadratic in the number of atoms and can be traced back to the repulsive quantum fictitious potential. All three forces arise for a free particle: “Force without force”.

  20. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Fletcher, James C. (Inventor); Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1992-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  1. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1993-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of the additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  2. Nonlinear nonresonant forces by radio-frequency waves in plasmas

    SciTech Connect

    Gao Zhe; Fisch, Nathaniel J.; Qin, Hong; Myra, J. R.

    2007-08-15

    Nonresonant forces by applied rf waves in plasmas are analyzed. Along the background dc magnetic field, the force arises from the gradient of the ponderomotive potential. Only when the dc magnetic field is straight, however, is this parallel force completely consistent with that from the single particle picture, where the ponderomotive force depends on the gradients of rf fields only. Across the dc magnetic field, besides the ponderomotive force from the particle picture, additional Reynolds stress and polarization stress contribute to the total force. For waves with frequency much lower than the cyclotron frequency, the perpendicular forces from the particle and fluid pictures can have opposite signs. In plasmas with a symmetry angle (e.g., toroidal systems), nonresonant forces cannot drive net flow or current in the flux surface, but the radial force may influence macroscopic behavior of plasma. Moreover, nonresonant forces may drive flow or current in linear plasmas or in a localized region of toroidal plasmas.

  3. Effective Forces Between Colloidal Particles

    NASA Technical Reports Server (NTRS)

    Tehver, Riina; Banavar, Jayanth R.; Koplik, Joel

    1999-01-01

    Colloidal suspensions have proven to be excellent model systems for the study of condensed matter and its phase behavior. Many of the properties of colloidal suspensions can be investigated with a systematic variation of the characteristics of the systems and, in addition, the energy, length and time scales associated with them allow for experimental probing of otherwise inaccessible regimes. The latter property also makes colloidal systems vulnerable to external influences such as gravity. Experiments performed in micro-ravity by Chaikin and Russell have been invaluable in extracting the true behavior of the systems without an external field. Weitz and Pusey intend to use mixtures of colloidal particles with additives such as polymers to induce aggregation and form weak, tenuous, highly disordered fractal structures that would be stable in the absence of gravitational forces. When dispersed in a polarizable medium, colloidal particles can ionize, emitting counterions into the solution. The standard interaction potential in these charged colloidal suspensions was first obtained by Derjaguin, Landau, Verwey and Overbeek. The DLVO potential is obtained in the mean-field linearized Poisson-Boltzmann approximation and thus has limited applicability. For more precise calculations, we have used ab initio density functional theory. In our model, colloidal particles are charged hard spheres, the counterions are described by a continuum density field and the solvent is treated as a homogeneous medium with a specified dielectric constant. We calculate the effective forces between charged colloidal particles by integrating over the solvent and counterion degrees of freedom, taking into account the direct interactions between the particles as well as particle-counterion, counterion-counterion Coulomb, counterion entropic and correlation contributions. We obtain the effective interaction potential between charged colloidal particles in different configurations. We evaluate two

  4. Debunking Coriolis Force Myths

    NASA Astrophysics Data System (ADS)

    Shakur, Asif

    2014-11-01

    Much has been written and debated about the Coriolis force.1-8 Unfortunately, this has done little to demystify the paradoxes surrounding this fictitious force invoked by an observer in a rotating frame of reference. It is the purpose of this article to make another valiant attempt to slay the dragon of the Coriolis force! This will be done without unleashing the usual mathematical apparatus, which we believe is more of a hindrance than a help.

  5. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  6. Food Additives and Hyperkinesis

    ERIC Educational Resources Information Center

    Wender, Ester H.

    1977-01-01

    The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

  7. Smog control fuel additives

    SciTech Connect

    Lundby, W.

    1993-06-29

    A method is described of controlling, reducing or eliminating, ozone and related smog resulting from photochemical reactions between ozone and automotive or industrial gases comprising the addition of iodine or compounds of iodine to hydrocarbon-base fuels prior to or during combustion in an amount of about 1 part iodine per 240 to 10,000,000 parts fuel, by weight, to be accomplished by: (a) the addition of these inhibitors during or after the refining or manufacturing process of liquid fuels; (b) the production of these inhibitors for addition into fuel tanks, such as automotive or industrial tanks; or (c) the addition of these inhibitors into combustion chambers of equipment utilizing solid fuels for the purpose of reducing ozone.

  8. Electrodynamic force law controversy.

    PubMed

    Graneau, P; Graneau, N

    2001-05-01

    Cavalleri et al. [Phys. Rev. E 52, 2505 (1998); Eur. J. Phys. 17, 205 (1996)] have attempted to resolve the electrodynamic force law controversy. This attempt to prove the validity of either the Ampère or Lorentz force law by theory and experiment has revealed only that the two are equivalent when predicting the force on part of a circuit due to the current in the complete circuit. However, in our analysis of internal stresses, only Ampère's force law agrees with experiment. PMID:11415053

  9. Finger Forces in Clarinet Playing.

    PubMed

    Hofmann, Alex; Goebl, Werner

    2016-01-01

    Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17) and professional clarinettists (N = 6) were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 × 2 × 2 design (register: low-high; tempo: slow-fast, dynamics: soft-loud). There was an additional condition controlled by the experimenter, which determined the expression levels (low-high) of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions). The melody was performed in three tempo conditions (slow, medium, fast) in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (F mean ) and peak force (F max ) were calculated. The overall finger forces were low (F mean = 1.17 N, F max = 3.05 N) compared to those on other musical instruments (e.g., guitar). Participants applied the largest finger forces during the high expression level performance conditions (F mean = 1.21 N). For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (F mean = 0.54 N). Such sensor instruments provide useful insights into player

  10. Finger Forces in Clarinet Playing.

    PubMed

    Hofmann, Alex; Goebl, Werner

    2016-01-01

    Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17) and professional clarinettists (N = 6) were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 × 2 × 2 design (register: low-high; tempo: slow-fast, dynamics: soft-loud). There was an additional condition controlled by the experimenter, which determined the expression levels (low-high) of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions). The melody was performed in three tempo conditions (slow, medium, fast) in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (F mean ) and peak force (F max ) were calculated. The overall finger forces were low (F mean = 1.17 N, F max = 3.05 N) compared to those on other musical instruments (e.g., guitar). Participants applied the largest finger forces during the high expression level performance conditions (F mean = 1.21 N). For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (F mean = 0.54 N). Such sensor instruments provide useful insights into player

  11. Inhomogeneous radiative forcing of homogeneous greenhouse gases

    NASA Astrophysics Data System (ADS)

    Huang, Yi; Tan, Xiaoxiao; Xia, Yan

    2016-03-01

    Radiative forcing of a homogeneous greenhouse gas (HGG) can be very inhomogeneous because the forcing is dependent on other atmospheric and surface variables. In the case of doubling CO2, the monthly mean instantaneous forcing at the top of the atmosphere is found to vary geographically and temporally from positive to negative values, with the range (-2.5-5.1 W m-2) being more than 3 times the magnitude of the global mean value (2.3 W m-2). The vertical temperature change across the atmospheric column (temperature lapse rate) is found to be the best single predictor for explaining forcing variation. In addition, the masking effects of clouds and water vapor also contribute to forcing inhomogeneity. A regression model that predicts forcing from geophysical variables is constructed. This model can explain more than 90% of the variance of the forcing. Applying this model to analyzing the forcing variation in the Climate Model Intercomparison Project Phase 5 models, we find that intermodel discrepancy in CO2 forcing caused by model climatology leads to considerable discrepancy in their projected change in poleward energy transport.

  12. Cutaneous mechanisms of isometric ankle force control.

    PubMed

    Choi, Julia T; Lundbye-Jensen, Jesper; Leukel, Christian; Nielsen, Jens Bo

    2013-07-01

    The sense of force is critical in the control of movement and posture. Multiple factors influence our perception of exerted force, including inputs from cutaneous afferents, muscle afferents and central commands. Here, we studied the influence of cutaneous feedback on the control of ankle force output. We used repetitive electrical stimulation of the superficial peroneal (foot dorsum) and medial plantar nerves (foot sole) to disrupt cutaneous afferent input in 8 healthy subjects. We measured the effects of repetitive nerve stimulation on (1) tactile thresholds, (2) performance in an ankle force-matching and (3) an ankle position-matching task. Additional force-matching experiments were done to compare the effects of transient versus continuous stimulation in 6 subjects and to determine the effects of foot anesthesia using lidocaine in another 6 subjects. The results showed that stimulation decreased cutaneous sensory function as evidenced by increased touch threshold. Absolute dorsiflexion force error increased without visual feedback during peroneal nerve stimulation. This was not a general effect of stimulation because force error did not increase during plantar nerve stimulation. The effects of transient stimulation on force error were greater when compared to continuous stimulation and lidocaine injection. Position-matching performance was unaffected by peroneal nerve or plantar nerve stimulation. Our results show that cutaneous feedback plays a role in the control of force output at the ankle joint. Understanding how the nervous system normally uses cutaneous feedback in motor control will help us identify which functional aspects are impaired in aging and neurological diseases.

  13. Climate forcings and feedbacks

    NASA Technical Reports Server (NTRS)

    Hansen, James

    1993-01-01

    Global temperature has increased significantly during the past century. Understanding the causes of observed global temperature change is impossible in the absence of adequate monitoring of changes in global climate forcings and radiative feedbacks. Climate forcings are changes imposed on the planet's energy balance, such as change of incoming sunlight or a human-induced change of surface properties due to deforestation. Radiative feedbacks are radiative changes induced by climate change, such as alteration of cloud properties or the extent of sea ice. Monitoring of global climate forcings and feedbacks, if sufficiently precise and long-term, can provide a very strong constraint on interpretation of observed temperature change. Such monitoring is essential to eliminate uncertainties about the relative importance of various climate change mechanisms including tropospheric sulfate aerosols from burning of coal and oil smoke from slash and burn agriculture, changes of solar irradiance changes of several greenhouse gases, and many other mechanisms. The considerable variability of observed temperature, together with evidence that a substantial portion of this variability is unforced indicates that observations of climate forcings and feedbacks must be continued for decades. Since the climate system responds to the time integral of the forcing, a further requirement is that the observations be carried out continuously. However, precise observations of forcings and feedbacks will also be able to provide valuable conclusions on shorter time scales. For example, knowledge of the climate forcing by increasing CFC's relative to the forcing by changing ozone is important to policymakers, as is information on the forcing by CO2 relative to the forcing by sulfate aerosols. It will also be possible to obtain valuable tests of climate models on short time scales, if there is precise monitoring of all forcings and feedbacks during and after events such as a large volcanic eruption

  14. Force distribution in a semiflexible loop

    NASA Astrophysics Data System (ADS)

    Waters, James T.; Kim, Harold D.

    2016-04-01

    Loops undergoing thermal fluctuations are prevalent in nature. Ringlike or cross-linked polymers, cyclic macromolecules, and protein-mediated DNA loops all belong to this category. Stability of these molecules are generally described in terms of free energy, an average quantity, but it may also be impacted by local fluctuating forces acting within these systems. The full distribution of these forces can thus give us insights into mechanochemistry beyond the predictive capability of thermodynamics. In this paper, we study the force exerted by an inextensible semiflexible polymer constrained in a looped state. By using a simulation method termed "phase-space sampling," we generate the equilibrium distribution of chain conformations in both position and momentum space. We compute the constraint forces between the two ends of the loop in this chain ensemble using Lagrangian mechanics, and show that the mean of these forces is equal to the thermodynamic force. By analyzing kinetic and potential contributions to the forces, we find that the mean force acts in the direction of increasing extension not because of bending stress, but in spite of it. Furthermore, we obtain a distribution of constraint forces as a function of chain length, extension, and stiffness. Notably, increasing contour length decreases the average force, but the additional freedom allows fluctuations in the constraint force to increase. The force distribution is asymmetric and falls off less sharply than a Gaussian distribution. Our work exemplifies a system where large-amplitude fluctuations occur in a way unforeseen by a purely thermodynamic framework, and offers computational tools useful for efficient, unbiased simulation of a constrained system.

  15. Additive Manufacturing Infrared Inspection

    NASA Technical Reports Server (NTRS)

    Gaddy, Darrell

    2014-01-01

    Additive manufacturing is a rapid prototyping technology that allows parts to be built in a series of thin layers from plastic, ceramics, and metallics. Metallic additive manufacturing is an emerging form of rapid prototyping that allows complex structures to be built using various metallic powders. Significant time and cost savings have also been observed using the metallic additive manufacturing compared with traditional techniques. Development of the metallic additive manufacturing technology has advanced significantly over the last decade, although many of the techniques to inspect parts made from these processes have not advanced significantly or have limitations. Several external geometry inspection techniques exist such as Coordinate Measurement Machines (CMM), Laser Scanners, Structured Light Scanning Systems, or even traditional calipers and gages. All of the aforementioned techniques are limited to external geometry and contours or must use a contact probe to inspect limited internal dimensions. This presentation will document the development of a process for real-time dimensional inspection technique and digital quality record of the additive manufacturing process using Infrared camera imaging and processing techniques.

  16. Elementary Particles and Forces.

    ERIC Educational Resources Information Center

    Quigg, Chris

    1985-01-01

    Discusses subatomic particles (quarks, leptons, and others) revealed by higher accelerator energies. A connection between forces at this subatomic level has been established, and prospects are good for a description of forces that encompass binding atomic nuclei. Colors, fundamental interactions, screening, camouflage, electroweak symmetry, and…

  17. Polarizable force fields.

    PubMed

    Antila, Hanne S; Salonen, Emppu

    2013-01-01

    This chapter provides an overview of the most common methods for including an explicit description of electronic polarization in molecular mechanics force fields: the induced point dipole, shell, and fluctuating charge models. The importance of including polarization effects in biomolecular simulations is discussed, and some of the most important achievements in the development of polarizable biomolecular force fields to date are highlighted.

  18. Forces in yeast flocculation.

    PubMed

    El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Vincent, Stéphane P; Abellán Flos, Marta; Hols, Pascal; Lipke, Peter N; Dufrêne, Yves F

    2015-02-01

    In the baker's yeast Saccharomyces cerevisiae, cell-cell adhesion ("flocculation") is conferred by a family of lectin-like proteins known as the flocculin (Flo) proteins. Knowledge of the adhesive and mechanical properties of flocculins is important for understanding the mechanisms of yeast adhesion, and may help controlling yeast behaviour in biotechnology. We use single-molecule and single-cell atomic force microscopy (AFM) to explore the nanoscale forces engaged in yeast flocculation, focusing on the role of Flo1 as a prototype of flocculins. Using AFM tips labelled with mannose, we detect single flocculins on Flo1-expressing cells, showing they are widely exposed on the cell surface. When subjected to force, individual Flo1 proteins display two distinct force responses, i.e. weak lectin binding forces and strong unfolding forces reflecting the force-induced extension of hydrophobic tandem repeats. We demonstrate that cell-cell adhesion bonds also involve multiple weak lectin interactions together with strong unfolding forces, both associated with Flo1 molecules. Single-molecule and single-cell data correlate with microscale cell adhesion behaviour, suggesting strongly that Flo1 mechanics is critical for yeast flocculation. These results favour a model in which not only weak lectin-sugar interactions are involved in yeast flocculation but also strong hydrophobic interactions resulting from protein unfolding.

  19. Forces in yeast flocculation

    NASA Astrophysics Data System (ADS)

    El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Vincent, Stéphane P.; Abellán Flos, Marta; Hols, Pascal; Lipke, Peter N.; Dufrêne, Yves F.

    2015-01-01

    In the baker's yeast Saccharomyces cerevisiae, cell-cell adhesion (``flocculation'') is conferred by a family of lectin-like proteins known as the flocculin (Flo) proteins. Knowledge of the adhesive and mechanical properties of flocculins is important for understanding the mechanisms of yeast adhesion, and may help controlling yeast behaviour in biotechnology. We use single-molecule and single-cell atomic force microscopy (AFM) to explore the nanoscale forces engaged in yeast flocculation, focusing on the role of Flo1 as a prototype of flocculins. Using AFM tips labelled with mannose, we detect single flocculins on Flo1-expressing cells, showing they are widely exposed on the cell surface. When subjected to force, individual Flo1 proteins display two distinct force responses, i.e. weak lectin binding forces and strong unfolding forces reflecting the force-induced extension of hydrophobic tandem repeats. We demonstrate that cell-cell adhesion bonds also involve multiple weak lectin interactions together with strong unfolding forces, both associated with Flo1 molecules. Single-molecule and single-cell data correlate with microscale cell adhesion behaviour, suggesting strongly that Flo1 mechanics is critical for yeast flocculation. These results favour a model in which not only weak lectin-sugar interactions are involved in yeast flocculation but also strong hydrophobic interactions resulting from protein unfolding.

  20. Force Concept Inventory.

    ERIC Educational Resources Information Center

    Hestenes, David; And Others

    1992-01-01

    Reports the rationale, design, validation, and uses of the "Force Concept Inventory," an instrument to assess the students' beliefs on force. Includes results and implications of two studies that compared the inventory with the "Mechanics Baseline." Includes a copy of the instrument. (MDH)

  1. SCM-Forcing Data

    DOE Data Explorer

    Xie, Shaocheng; Tang,Shuaiqi; Zhang,Yunyan; Zhang,Minghua

    2016-07-01

    Single-Column Model (SCM) Forcing Data are derived from the ARM facility observational data using the constrained variational analysis approach (Zhang and Lin 1997 and Zhang et al., 2001). The resulting products include both the large-scale forcing terms and the evaluation fields, which can be used for driving the SCMs and Cloud Resolving Models (CRMs) and validating model simulations.

  2. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamine, containing phenylethvnvl groups and various ratios of phthalic anhydride and 4-phenylethynviphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pvrrolidinone to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  3. A controlled-force laser interference profilometer

    NASA Astrophysics Data System (ADS)

    Yang, Bo; Chang, Suping; Xie, Tiebang; Pan, Wen

    2011-12-01

    This paper presents a controlled-force laser interference surface measuring system, which can achieve high-precision surface profile measurements in a large range. The key technology of the system is the controlled-force laser interference displacement sensor based on Michelson interference principle. The system operates in micro-force by the voice coil motor (VCM) which alters the measuring contact force in real time and reduces the scratches caused by the stylus tip on the surfaces of the tested samples. The position of the stylus can also be changed, which avoids the damage of the system when the stylus scans across high steps or deep grooves. The optical and mechanical principles of the displacement sensor, the realization method of controllable measuring force and photoelectric signal processing are discussed in this paper. Additionally, this paper introduces the two-dimensional stage used for high precision scanner, and presents primitive experimental results.

  4. Lorentz force velocimetry.

    PubMed

    Thess, A; Votyakov, E V; Kolesnikov, Y

    2006-04-28

    We describe a noncontact technique for velocity measurement in electrically conducting fluids. The technique, which we term Lorentz force velocimetry (LFV), is based on exposing the fluid to a magnetic field and measuring the drag force acting upon the magnetic field lines. Two series of measurements are reported, one in which the force is determined through the angular velocity of a rotary magnet system and one in which the force on a fixed magnet system is measured directly. Both experiments confirm that the measured signal is a linear function of the flow velocity. We then derive the scaling law that relates the force on a localized distribution of magnetized material to the velocity of an electrically conducting fluid. This law shows that LFV, if properly designed, has a wide range of potential applications in metallurgy, semiconductor crystal growth, and glass manufacturing. PMID:16712237

  5. Conservative entropic forces

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    2011-10-01

    Entropic forces have recently attracted considerable attention as ways to reformulate, retrodict, and perhaps even "explain" classical Newtonian gravity from a rather specific thermodynamic perspective. In this article I point out that if one wishes to reformulate classical Newtonian gravity in terms of an entropic force, then the fact that Newtonian gravity is described by a conservative force places significant constraints on the form of the entropy and temperature functions. (These constraints also apply to entropic reinterpretations of electromagnetism, and indeed to any conservative force derivable from a potential.) The constraints I will establish are sufficient to present real and significant problems for any reasonable variant of Verlinde's entropic gravity proposal, though for technical reasons the constraints established herein do not directly impact on either Jacobson'sor Padmanabhan's versions of entropic gravity. In an attempt to resolve these issues, I will extend the usual notion of entropic force to multiple heat baths with multiple "temperatures" and multiple "entropies".

  6. Biomolecular interactions measured by atomic force microscopy.

    PubMed

    Willemsen, O H; Snel, M M; Cambi, A; Greve, J; De Grooth, B G; Figdor, C G

    2000-12-01

    Atomic force microscopy (AFM) is nowadays frequently applied to determine interaction forces between biological molecules. Starting with the detection of the first discrete unbinding forces between ligands and receptors by AFM only several years ago, measurements have become more and more quantitative. At the same time, theories have been developed to describe and understand the dynamics of the unbinding process and experimental techniques have been refined to verify this theory. In addition, the detection of molecular recognition forces has been exploited to map and image the location of binding sites. In this review we discuss the important contributions that have led to the development of this field. In addition, we emphasize the potential of chemically well-defined surface modification techniques to further improve reproducible measurements by AFM. This increased reproducibility will pave the way for a better understanding of molecular interactions in cell biology.

  7. Multifunctional fuel additives

    SciTech Connect

    Baillargeon, D.J.; Cardis, A.B.; Heck, D.B.

    1991-03-26

    This paper discusses a composition comprising a major amount of a liquid hydrocarbyl fuel and a minor low-temperature flow properties improving amount of an additive product of the reaction of a suitable diol and product of a benzophenone tetracarboxylic dianhydride and a long-chain hydrocarbyl aminoalcohol.

  8. Biobased lubricant additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fully biobased lubricants are those formulated using all biobased ingredients, i.e. biobased base oils and biobased additives. Such formulations provide the maximum environmental, safety, and economic benefits expected from a biobased product. Currently, there are a number of biobased base oils that...

  9. Sensing Current and Forces with SPM

    SciTech Connect

    Park, Jeong Y.; Maier, Sabine; Hendriksen, Bas; Salmeron, Miquel

    2010-07-02

    Atomic force microscopy (AFM) and scanning tunneling microscopy (STM) are well established techniques to image surfaces and to probe material properties at the atomic and molecular scale. In this review, we show hybrid combinations of AFM and STM that bring together the best of two worlds: the simultaneous detection of atomic scale forces and conduction properties. We illustrate with several examples how the detection of forces during STM and the detection of currents during AFM can give valuable additional information of the nanoscale material properties.

  10. Turbomachinery rotor forces

    NASA Technical Reports Server (NTRS)

    Arndt, Norbert

    1988-01-01

    The fluid-induced forces, both steady and unsteady, acting upon an impeller of a centrifugal pump, and impeller blade-diffuser vane interaction in centrifugal pumps with vaned radial diffusers were evaluated experimentally and theoretically. Knowledge of the steady and unsteady forces, and the associated rotordynamic coefficients are required to effectively model the rotor dynamics of the High Pressure Fuel Turbopump (HPFTP) of the Space Shuttle Main Engine (SSME). These forces and rotordynamic coefficients were investigated using different impellers in combination with volutes and vaned diffusers, and axial inducers. These rotor forces are global. Local forces and pressures are also important in impeller-diffuser interaction, for they may cause cavitation damage and even vane failures. Thus, in a separate investigation, impeller wake, and impeller blade and diffuser vane pressure measurements were made. The nature of the rotordynamic forces is discussed, the experimental facility is described, and the measurements of unsteady forces and pressure are reported together with a brief and incomplete attempt to calculate these flows.

  11. OOTW Force Design Tools

    SciTech Connect

    Bell, R.E.; Hartley, D.S.III; Packard, S.L.

    1999-05-01

    This report documents refined requirements for tools to aid the process of force design in Operations Other Than War (OOTWs). It recommends actions for the creation of one tool and work on other tools relating to mission planning. It also identifies the governmental agencies and commands with interests in each tool, from whom should come the user advisory groups overseeing the respective tool development activities. The understanding of OOTWs and their analytical support requirements has matured to the point where action can be taken in three areas: force design, collaborative analysis, and impact analysis. While the nature of the action and the length of time before complete results can be expected depends on the area, in each case the action should begin immediately. Force design for OOTWs is not a technically difficult process. Like force design for combat operations, it is a process of matching the capabilities of forces against the specified and implied tasks of the operation, considering the constraints of logistics, transport and force availabilities. However, there is a critical difference that restricts the usefulness of combat force design tools for OOTWs: the combat tools are built to infer non-combat capability requirements from combat capability requirements and cannot reverse the direction of the inference, as is required for OOTWs. Recently, OOTWs have played a larger role in force assessment, system effectiveness and tradeoff analysis, and concept and doctrine development and analysis. In the first Quadrennial Defense Review (QDR), each of the Services created its own OOTW force design tool. Unfortunately, the tools address different parts of the problem and do not coordinate the use of competing capabilities. These tools satisfied the immediate requirements of the QDR, but do not provide a long-term cost-effective solution.

  12. Manual discrimination of force

    NASA Technical Reports Server (NTRS)

    Pang, Xiao-Dong; Tan, HONG-Z.; Durlach, Nathaniel I.

    1991-01-01

    Optimal design of human-machine interfaces for teleoperators and virtual-environment systems which involve the tactual and kinesthetic modalities requires knowledge of the human's resolving power in these modalities. The resolution of the interface should be appropriately matched to that of the human operator. We report some preliminary results on the ability of the human hand to distinguish small differences in force under a variety of conditions. Experiments were conducted on force discrimination with the thumb pushing an interface that exerts a constant force over the pushing distance and the index finger pressing against a fixed support. The dependence of the sensitivity index d' on force increment can be fit by a straight line through the origin and the just-noticeable difference (JND) in force can thus be described by the inverse of the slope of this line. The receiver operating characteristic (ROC) was measured by varying the a priori probabilities of the two alternatives, reference force and reference force plus an increment, in one-interval, two-alternative, forced-choice experiments. When plotted on normal deviate coordinates, the ROC's were roughly straight lines of unit slope, thus supporting the assumption of equal-variance normal distributions and the use of the conventional d' measure. The JND was roughly 6-8 percent for reference force ranging from 2.5 to 10 newtons, pushing distance from 5 to 30 mm, and initial finger-span from 45 to 125 mm. Also, the JND remained the same when the subjects were instructed to change the average speed of pushing from 23 to 153 mm/sec. The pushing was terminated by reaching either a wall or a well, and the JND's were essentially the same in both cases.

  13. Stable dynamics in forced systems with sufficiently high/low forcing frequency.

    PubMed

    Bartuccelli, M; Gentile, G; Wright, J A

    2016-08-01

    We consider parametrically forced Hamiltonian systems with one-and-a-half degrees of freedom and study the stability of the dynamics when the frequency of the forcing is relatively high or low. We show that, provided the frequency is sufficiently high, Kolmogorov-Arnold-Moser (KAM) theorem may be applied even when the forcing amplitude is far away from the perturbation regime. A similar result is obtained for sufficiently low frequency, but in that case we need the amplitude of the forcing to be not too large; however, we are still able to consider amplitudes which are outside of the perturbation regime. In addition, we find numerically that the dynamics may be stable even when the forcing amplitude is very large, well beyond the range of validity of the analytical results, provided the frequency of the forcing is taken correspondingly low. PMID:27586604

  14. Stable dynamics in forced systems with sufficiently high/low forcing frequency

    NASA Astrophysics Data System (ADS)

    Bartuccelli, M.; Gentile, G.; Wright, J. A.

    2016-08-01

    We consider parametrically forced Hamiltonian systems with one-and-a-half degrees of freedom and study the stability of the dynamics when the frequency of the forcing is relatively high or low. We show that, provided the frequency is sufficiently high, Kolmogorov-Arnold-Moser (KAM) theorem may be applied even when the forcing amplitude is far away from the perturbation regime. A similar result is obtained for sufficiently low frequency, but in that case we need the amplitude of the forcing to be not too large; however, we are still able to consider amplitudes which are outside of the perturbation regime. In addition, we find numerically that the dynamics may be stable even when the forcing amplitude is very large, well beyond the range of validity of the analytical results, provided the frequency of the forcing is taken correspondingly low.

  15. Vinyl capped addition polyimides

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D. (Inventor); Malarik, Diane C. (Inventor); Delvigs, Peter (Inventor)

    1991-01-01

    Polyimide resins (PMR) are generally useful where high strength and temperature capabilities are required (at temperatures up to about 700 F). Polyimide resins are particularly useful in applications such as jet engine compressor components, for example, blades, vanes, air seals, air splitters, and engine casing parts. Aromatic vinyl capped addition polyimides are obtained by reacting a diamine, an ester of tetracarboxylic acid, and an aromatic vinyl compound. Low void materials with improved oxidative stability when exposed to 700 F air may be fabricated as fiber reinforced high molecular weight capped polyimide composites. The aromatic vinyl capped polyimides are provided with a more aromatic nature and are more thermally stable than highly aliphatic, norbornenyl-type end-capped polyimides employed in PMR resins. The substitution of aromatic vinyl end-caps for norbornenyl end-caps in addition polyimides results in polymers with improved oxidative stability.

  16. Tackifier for addition polyimides

    NASA Technical Reports Server (NTRS)

    Butler, J. M.; St.clair, T. L.

    1980-01-01

    A modification to the addition polyimide, LaRC-160, was prepared to improve tack and drape and increase prepeg out-time. The essentially solventless, high viscosity laminating resin is synthesized from low cost liquid monomers. The modified version takes advantage of a reactive, liquid plasticizer which is used in place of solvent and helps solve a major problem of maintaining good prepeg tack and drape, or the ability of the prepeg to adhere to adjacent plies and conform to a desired shape during the lay up process. This alternate solventless approach allows both longer life of the polymer prepeg and the processing of low void laminates. This approach appears to be applicable to all addition polyimide systems.

  17. Electrophilic addition of astatine

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Nhan, D.D.; Huan, N.K.

    1988-03-01

    It has been shown for the first time that astatine is capable of undergoing addition reactions to unsaturated hydrocarbons. A new compound of astatine, viz., ethylene astatohydrin, has been obtained, and its retention numbers of squalane, Apiezon, and tricresyl phosphate have been found. The influence of various factors on the formation of ethylene astatohydrin has been studied. It has been concluded on the basis of the results obtained that the univalent cations of astatine in an acidic medium is protonated hypoastatous acid.

  18. Verbal regulation of grip force in preschoolers.

    PubMed

    Haishi, Koichi; Okuzumi, Hideyuki; Kokubun, Mitsuru; Komatsu, Ayumi; Kitajima, Yoshio; Hosobuchi, Tomio

    2009-04-01

    The purpose of this study was to clarify the developmental processes in verbal regulation by preschool children. Participants were 152 typically developing children (74 boys, 78 girls) between 4 and 6 years of age (M = 5.3, SD = .8), and 30 healthy adults (15 men, 15 women) between 19 and 26 years of age (M = 20.8, SD = 1.4). In Exp. 1, the task was to regulate grip force based on quantitative instruction which implies using a scale for regulation. Participants were required to produce a half-grip force of the maximum (Task 1). In Exp. 2, the task was grip-force regulation based on nonquantitative instruction. The participants were asked to respond with a slightly weaker grip force than the maximum (Task 2) and then a further weaker grip force (Task 3) than that used on Task 2. The regulation rates produced the extent of regulation and suggest regulation by quantitative instruction may develop earlier than by nonquantitative instruction. Also, precise grip-force regulation based on the semantic aspect of instruction may be difficult for young children. The developmental changes in the rate of performance especially observed in children of 4 to 6 years indicate that the tendency to use too much grip force disappears during this preschool period. In addition, too little grip force in regulation may reflect the developmental process toward fine grasping movements. PMID:19544959

  19. Force dynamics in fixed-ratio schedules.

    PubMed

    Pinkston, Jonathan W; McBee, Lindsey N

    2014-03-01

    Fixed-ratio schedules are widely used in behavioral research. Although fixed-ratio schedules often conjure up relationships to work and effort, little is known about effort-related measures in these schedules. Early research had shown that force and effort of operant behavior vary systematically during the execution of ratio schedules, and the goal of the present study was to revisit early research on force dynamics in fixed-ratio schedules. Four rats earned sucrose by pressing an isometric force transducer. Presses produced sucrose after ten or twenty responses. In general, the force of responses increased then decreased systematically across the ratio. The possibility that decreases in force during ratio execution was due to a trade-off with the differential reinforcement of short inter-response times (IRT) was investigated in an additional condition where sucrose was made available according to a tandem fixed-ratio 19 inter-response (IRT)> t schedule. The tandem IRT requirement did not eliminate decreasing trends in force across the ratio; unexpectedly, the tandem requirement did eliminate increases in force early in the ratio, which may reflect sequence-level organization operating in the control of force dynamics. PMID:24315798

  20. Dilatonic Entropic Force

    NASA Astrophysics Data System (ADS)

    Sakalli, I.

    2011-08-01

    We show in detail that the entropic force of the static spherically symmetric spacetimes with unusual asymptotics can be calculated through the Verlinde's arguments. We introduce three different holographic screen candidates, which are first employed thoroughly by Myung and Kim [Phys. Rev. D 81, 105012 (2010)] for Schwarzschild black hole solutions, in order to identify the entropic force arising between a charged dilaton black hole and a test particle. The significance of the dilaton parameter on the entropic force is highlighted, and shown graphically.

  1. Functional Generalized Additive Models.

    PubMed

    McLean, Mathew W; Hooker, Giles; Staicu, Ana-Maria; Scheipl, Fabian; Ruppert, David

    2014-01-01

    We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.

  2. Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase

    SciTech Connect

    Smith, Dayle MA; Xiong, Yijia; Straatsma, TP; Rosso, Kevin M.; Squier, Thomas C.

    2012-05-09

    Classical molecular force-field parameters describing the structure and motion of metal clusters in [NiFe] hydrogenase enzymes can be used to compare the dynamics and thermodynamics of [NiFe] under different oxidation, protonation, and ligation circumstances. Using density functional theory (DFT) calculations of small model clusters representative of the active site and the proximal, medial, and distal Fe/S metal centers and their attached protein side chains, we have calculated classical force-field parameters for [NiFe] in reduced and oxidized states, including internal coordinates, force constants, and atom-centered charges. Derived force constants revealed that cysteinate ligands bound to the metal ions are more flexible in the Ni-B active site, which has a bridging hydroxide ligand, than in the Ni-C active site, which has a bridging hydride. Ten nanosecond all-atom, explicit-solvent MD simulations of [NiFe] hydrogenase in oxidized and reduced catalytic states established the stability of the derived force-field parameters in terms of C{alpha} and metal cluster fluctuations. Average active site structures from the protein MD simulations are consistent with [NiFe] structures from the Protein Data Bank, suggesting that the derived force-field parameters are transferrable to other hydrogenases beyond the structure used for testing. A comparison of experimental H{sub 2}-production rates demonstrated a relationship between cysteinate side chain rotation and activity, justifying the use of a fully dynamic model of [NiFe] metal cluster motion.

  3. 3. Northwest side and southwest rear of addition. View to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Northwest side and southwest rear of addition. View to east. - Offutt Air Force Base, Looking Glass Airborne Command Post, Aerospace Ground Equipment (AGE) Storage Facility, Far Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

  4. 5. General interior overview of addition. View to south. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. General interior overview of addition. View to south. - Offutt Air Force Base, Looking Glass Airborne Command Post, Aerospace Ground Equipment (AGE) Storage Facility, Far Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

  5. 6. General interior overview of addition. View to northwest. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. General interior overview of addition. View to northwest. - Offutt Air Force Base, Looking Glass Airborne Command Post, Aerospace Ground Equipment (AGE) Storage Facility, Far Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

  6. 2. Southeast side of addition. View to northwest. Offutt ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Southeast side of addition. View to northwest. - Offutt Air Force Base, Looking Glass Airborne Command Post, Aerospace Ground Equipment (AGE) Storage Facility, Far Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

  7. View of southwest corner showing ell addition and carport, facing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of southwest corner showing ell addition and carport, facing northeast. - Albrook Air Force Station, Field Officer's Quarters, West side of Dargue Avenue Circle, Balboa, Former Panama Canal Zone, CZ

  8. 78. SAC control center aboveground addition partial first floor plan, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    78. SAC control center aboveground addition partial first floor plan, drawing number AW30-02-09, dated 15 October, 1962 - Offutt Air Force Base, Strategic Air Command Headquarters & Command Center, Headquarters Building, 901 SAC Boulevard, Bellevue, Sarpy County, NE

  9. Interior view of addition pharmacy showing dutch door and security ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Interior view of addition pharmacy showing dutch door and security ceiling grate, facing north. - Albrook Air Force Station, Dispensary, East side of Canfield Avenue, Balboa, Former Panama Canal Zone, CZ

  10. Forces in Motion.

    ERIC Educational Resources Information Center

    Goodsell, David; And Others

    1995-01-01

    Describes an activity to give students experience with the variables and forces impacting a moving body on an inclined plane by observing a ball as it rolls down an inclined PVC pipe of fixed length. Includes a student worksheet. (MKR)

  11. Metamaterials enhancing optical forces

    NASA Astrophysics Data System (ADS)

    Ginis, Vincent; Tassin, Philippe; Soukoulis, Costas M.; Veretennicoff, Irina

    2014-05-01

    The interaction between light and matter involves not only an energy transfer, but also the transfer of linear momentum. In everyday life applications this linear momentum of light is too small to play any significant role. However, in nanoscale dimensions, the associated optical forces start to play an increasingly important role. These forces are, e.g., large enough for exiting experiments in the fields of cavity-optomechanics, laser cooling and optical trapping of small particles. Recently, it has been suggested that optical gradient forces can also be employed for all-optical actuation in micro- and nanophotonic systems. The typical setup consists of two slab waveguides positioned in each others vicinity such that they are coupled through the interaction of the evanescent tails. Although the gradient forces between these waveguides can be enhanced considerably using electromagnetic resonators or slow-light techniques, the resulting displacements remain relatively small. In this contribution, we present an alternative approach to enhance optical gradient forces between waveguides using a combination of transformation optics and metamaterials. Our design starts from the observation that gradient forces exponentially decay with the separation distance between the waveguides. Therefore, we employ transformation optics to annihilate the apparent distance for light between the waveguides. Analytical calculations confirm that the resulting forces indeed increase when such an annihilating cladding is inserted. Subsequently, we discuss the metamaterial implementation of this annihilating medium. Such lensing media automatically translate into anisotropic metamaterials with negative components in the permittivity and permeability tensors. Our full-wave numerical simulations show that the overall amplification is highly limited by the loss-tangent of the metamaterial cladding. However, as this cladding only needs to operate in the near-field for a specific polarization

  12. Strategic forces briefing

    SciTech Connect

    Bing, G.; Chrzanowski, P.; May, M.; Nordyke, M.

    1989-04-06

    The Strategic Forces Briefing'' is our attempt, accomplished over the past several months, to outline and highlight the more significant strategic force issues that must be addressed in the near future. Some issues are recurrent: the need for an effective modernized Triad and a constant concern for force survivability. Some issues derive from arms control: the Strategic Arms Reduction Talks (SALT) are sufficiently advanced to set broad numerical limits on forces, but not so constraining as to preclude choices among weapon systems and deployment modes. Finally, a new administration faced with serious budgetary problems must strive for the most effective strategic forces limited dollars can buy and support. A review of strategic forces logically begins with consideration of the missions the forces are charged with. We begin the briefing with a short review of targeting policy and implementation within the constraints of available unclassified information. We then review each element of the Triad with sections on SLBMs, ICBMs, and Air-Breathing (bomber and cruise missile) systems. A short section at the end deals with the potential impact of strategic defense on offensive force planning. We consider ABM, ASAT, and air defense; but we do not attempt to address the technical issues of strategic defense per se. The final section gives a brief overview of the tritium supply problem. We conclude with a summary of recommendations that emerge from our review. The results of calculation on the effectiveness of various weapon systems as a function of cost that are presented in the briefing are by Paul Chrzanowski.

  13. Force-Measuring Clamp

    NASA Technical Reports Server (NTRS)

    Nunnelee, Mark (Inventor)

    2004-01-01

    A precision clamp that accurately measures force over a wide range of conditions is described. Using a full bridge or other strain gage configuration. the elastic deformation of the clamp is measured or detected by the strain gages. Thc strain gages transmit a signal that corresponds to the degree of stress upon the clamp. Thc strain gage signal is converted to a numeric display. Calibration is achieved by ero and span potentiometers which enable accurate measurements by the force-measuring clamp.

  14. Volcanic forcing in decadal forecasts

    NASA Astrophysics Data System (ADS)

    Ménégoz, Martin; Doblas-Reyes, Francisco; Guemas, Virginie; Asif, Muhammad; Prodhomme, chloe

    2016-04-01

    Volcanic eruptions can significantly impact the climate system, by injecting large amounts of particles into the stratosphere. By reflecting backward the solar radiation, these particles cool the troposphere, and by absorbing the longwave radiation, they warm the stratosphere. As a consequence of this radiative forcing, the global mean surface temperature can decrease by several tenths of degrees. However, large eruptions are also associated to a complex dynamical response of the climate system that is particularly tricky do understand regarding the low number of available observations. Observations seem to show an increase of the positive phases of the Northern Atlantic Oscillation (NAO) the two winters following large eruptions, associated to positive temperature anomalies over the Eurasian continent. The summers following large eruptions are generally particularly cold, especially over the continents of the Northern Hemisphere. Overall, it is really challenging to forecast the climate response to large eruptions, as it is both modulated by, and superimposed to the climate background conditions, largely driven themselves by internal variability at seasonal to decadal scales. This work describes the additional skill of a forecast system used for seasonal and decadal predictions when it includes observed volcanic forcing over the last decades. An idealized volcanic forcing that could be used for real-time forecasts is also evaluated. This work consists in a base for forecasts that will be performed in the context of the next large volcanic eruption.

  15. Optical ``Bernoulli'' forces

    NASA Astrophysics Data System (ADS)

    Movassagh, Ramis; Johnson, Steven

    2015-03-01

    By Bernoulli's law, an increase in the relative speed of a fluid around a body is accompanies by a decrease in the pressure. Therefore, a rotating body in a fluid stream experiences a force perpendicular to the motion of the fluid because of the unequal relative speed of the fluid across its surface. It is well known that light has a constant speed irrespective of the relative motion. Does a rotating body immersed in a stream of photons experience a Bernoulli-like force? We show that, indeed, a rotating dielectric cylinder experiences such a lateral force from an electromagnetic wave. In fact, the sign of the lateral force is the same as that of the fluid-mechanical analogue as long as the electric susceptibility is positive (ɛ >ɛ0), but for negative-susceptibility materials (e.g. metals) we show that the lateral force is in the opposite direction. Because these results are derived from a classical electromagnetic scattering problem, Mie-resonance enhancements that occur in other scattering phenomena also enhance the lateral force. [This talk is based on Phys. Rev. A 88, 023829 (2013).] Supported in part by the U.S. Army Research Office under contract W911NF-13-D-0001.

  16. The Missing Climate Forcing

    NASA Astrophysics Data System (ADS)

    Hansen, J.; Sato, M.; Lacis, A.; Ruedy, R.

    1997-02-01

    Observed climate change is consistent with radiative forcings on several time scales for which the dominant forcings are known, ranging from the few years after a large volcanic eruption to glacial-to-interglacial changes. In the period with most detailed data, 1979 to the present, climate observations contain clear signatures of both natural and anthropogenic forcings. But in the full period since the industrial revolution began, global warming is only about half of that expected due to the principal forcing, increasing greenhouse gases. The direct radiative effect of anthropogenic aerosols contributes only little towards resolving this discrepancy. Unforced climate variability is an unlikely explanation. We argue on the basis of several lines of indirect evidence that aerosol effects on clouds have caused a large negative forcing, at least -1 Wm-2, which has substantially offset greenhouse warming. The tasks of observing this forcing and determining the microphysical mechanisms at its basis are exceptionally difficult, but they are essential for the prognosis of future climate change.

  17. Van der Waals Forces

    NASA Astrophysics Data System (ADS)

    Parsegian, V. Adrian

    2006-03-01

    This should prove to be the definitive work explaining van der Waals forces, how to calculate them and take account of their impact under any circumstances and conditions. These weak intermolecular forces are of truly pervasive impact, and biologists, chemists, physicists and engineers will profit greatly from the thorough grounding in these fundamental forces that this book offers. Parsegian has organized his book at three successive levels of mathematical sophistication, to satisfy the needs and interests of readers at all levels of preparation. The Prelude and Level 1 are intended to give everyone an overview in words and pictures of the modern theory of van der Waals forces. Level 2 gives the formulae and a wide range of algorithms to let readers compute the van der Waals forces under virtually any physical or physiological conditions. Level 3 offers a rigorous basic formulation of the theory. Author is among the most highly respected biophysicists Van der Waals forces are significant for a wide range of questions and problems in the life sciences, chemistry, physics, and engineering, ranging up to the macro level No other book that develops the subject vigorously, and this book also makes the subject intuitively accessible to students who had not previously been mathematically sophisticated enough to calculate them

  18. Evaluation of intermolecular forces in a circulating system.

    PubMed

    Guo, Qiuquan; Liu, Mei; Yang, Jun

    2011-11-01

    Intercellular interactions, which are mediated by a variety of complex intercellular molecules through the processes of formation and dissociation of molecular bonds, play a critical role in regulating cellular functions in biological systems. Various approaches are applied to evaluate intercellular or molecular bonding forces. To quantify the intermolecular interaction forces, flow chamber has become a meaningful technique as it can ultimately mimic the cellular microenvironment in vivo under physiological flow conditions. Hydrodynamic forces are usually used to predict the intercellular forces down to the single molecular level. However, results show that only using hydrodynamic force will overestimate up to 30% of the receptor-ligand strength when the non-specific forces such as Derjaguin-Landau-Verway-Overbeek (DLVO) forces become un-neglected. Due to the nature of high ion concentration in the physiological condition, electrostatic force is largely screened which will cause DLVO force unbalanced. In this study, we propose to take account of the DLVO force, including van der Waals (VDW) force and electrostatic force, to predict the intermolecular forces of a cell doublet and cell-substrate model in a circulating system. Results also show that the DLVO force has a nonlinear effect as the cell-cell or cell-substrate distance changes. In addition, we used the framework of high accuracy hydrodynamic theories proved in colloidal systems. It is concluded that DLVO force could not be ignored in quantitative studies of molecular interaction forces in circulating system. More accurate prediction of intercellular forces needs to take account of both hydrodynamic force and DLVO force.

  19. Forced wetting and hydrodynamic assist

    NASA Astrophysics Data System (ADS)

    Blake, Terence D.; Fernandez-Toledano, Juan-Carlos; Doyen, Guillaume; De Coninck, Joël

    2015-11-01

    Wetting is a prerequisite for coating a uniform layer of liquid onto a solid. Wetting failure and air entrainment set the ultimate limit to coating speed. It is well known in the coating art that this limit can be postponed by manipulating the coating flow to generate what has been termed "hydrodynamic assist," but the underlying mechanism is unclear. Experiments have shown that the conditions that postpone air entrainment also reduce the apparent dynamic contact angle, suggesting a direct link, but how the flow might affect the contact angle remains to be established. Here, we use molecular dynamics to compare the outcome of steady forced wetting with previous results for the spontaneous spreading of liquid drops and apply the molecular-kinetic theory of dynamic wetting to rationalize our findings and place them on a quantitative footing. The forced wetting simulations reveal significant slip at the solid-liquid interface and details of the flow immediately adjacent to the moving contact line. Our results confirm that the local, microscopic contact angle is dependent not simply only on the velocity of wetting but also on the nature of the flow that drives it. In particular, they support an earlier suggestion that during forced wetting, an intense shear stress in the vicinity of the contact line can assist surface tension forces in promoting dynamic wetting, thus reducing the velocity-dependence of the contact angle. Hydrodynamic assist then appears as a natural consequence of wetting that emerges when the contact line is driven by a strong and highly confined flow. Our theoretical approach also provides a self-consistent model of molecular slip at the solid-liquid interface that enables its magnitude to be estimated from dynamic contact angle measurements. In addition, the model predicts how hydrodynamic assist and slip may be influenced by liquid viscosity and solid-liquid interactions.

  20. Performance Boosting Additive

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Mainstream Engineering Corporation was awarded Phase I and Phase II contracts from Goddard Space Flight Center's Small Business Innovation Research (SBIR) program in early 1990. With support from the SBIR program, Mainstream Engineering Corporation has developed a unique low cost additive, QwikBoost (TM), that increases the performance of air conditioners, heat pumps, refrigerators, and freezers. Because of the energy and environmental benefits of QwikBoost, Mainstream received the Tibbetts Award at a White House Ceremony on October 16, 1997. QwikBoost was introduced at the 1998 International Air Conditioning, Heating, and Refrigeration Exposition. QwikBoost is packaged in a handy 3-ounce can (pressurized with R-134a) and will be available for automotive air conditioning systems in summer 1998.

  1. Sewage sludge additive

    NASA Technical Reports Server (NTRS)

    Kalvinskas, J. J.; Mueller, W. A.; Ingham, J. D. (Inventor)

    1980-01-01

    The additive is for a raw sewage treatment process of the type where settling tanks are used for the purpose of permitting the suspended matter in the raw sewage to be settled as well as to permit adsorption of the dissolved contaminants in the water of the sewage. The sludge, which settles down to the bottom of the settling tank is extracted, pyrolyzed and activated to form activated carbon and ash which is mixed with the sewage prior to its introduction into the settling tank. The sludge does not provide all of the activated carbon and ash required for adequate treatment of the raw sewage. It is necessary to add carbon to the process and instead of expensive commercial carbon, coal is used to provide the carbon supplement.

  2. Perspectives on Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Bourell, David L.

    2016-07-01

    Additive manufacturing (AM) has skyrocketed in visibility commercially and in the public sector. This article describes the development of this field from early layered manufacturing approaches of photosculpture, topography, and material deposition. Certain precursors to modern AM processes are also briefly described. The growth of the field over the last 30 years is presented. Included is the standard delineation of AM technologies into seven broad categories. The economics of AM part generation is considered, and the impacts of the economics on application sectors are described. On the basis of current trends, the future outlook will include a convergence of AM fabricators, mass-produced AM fabricators, enabling of topology optimization designs, and specialization in the AM legal arena. Long-term developments with huge impact are organ printing and volume-based printing.

  3. Sarks as additional fermions

    NASA Astrophysics Data System (ADS)

    Agrawal, Jyoti; Frampton, Paul H.; Jack Ng, Y.; Nishino, Hitoshi; Yasuda, Osamu

    1991-03-01

    An extension of the standard model is proposed. The gauge group is SU(2) X ⊗ SU(3) C ⊗ SU(2) S ⊗ U(1) Q, where all gauge symmetries are unbroken. The colour and electric charge are combined with SU(2) S which becomes strongly coupled at approximately 500 GeV and binds preons to form fermionic and vector bound states. The usual quarks and leptons are singlets under SU(2) X but additional fermions, called sarks. transform under it and the electroweak group. The present model explains why no more than three light quark-lepton families can exist. Neutral sark baryons, called narks, are candidates for the cosmological dark matter having the characteristics designed for WIMPS. Further phenomenological implications of sarks are analyzed i including electron-positron annihilation. Z 0 decay, flavor-changing neutral currents. baryon-number non-conservation, sarkonium and the neutron electric dipole moment.

  4. Feedback Control of Floor Reaction Force Based on Force-Reflecting-Type Multilateral Control

    NASA Astrophysics Data System (ADS)

    Nagase, Kazuki; Katsura, Seiichiro

    Real-world haptics is being studied not only for improving feedback on real-world haptic information in teleoperation but also for developing key technologies for future human support. For the remote operating of systems at distant places, haptic information is required in addition to visual information. The haptic information around a work environment can be the floor reaction force, which can be obtained using a movement-type haptic device. The floor reaction force from the environment that the mobile haptic device touches is fed back accurately to the operator. First, this paper proposes a general force-reflecting-type multilateral control. Second, this paper extends the control to feedback control of the floor reaction force by using force-reflecting-type multilateral control and a novel haptic device employing a biped robot with a slave system. The position response of a master system is transformed to a leg tip position command for the biped-type haptic device. In addition, the floor reaction force determined by the biped-type haptic device is fed back to the master system. The proposed method can determine the force feedback to the sole of the foot, which is not possible with a conventional stationary system. As a result, the floor reaction force from a large area can be obtained, and the operability of the control system is improved by using the proposed system.

  5. Backbone Additivity in the Transfer Model of Protein Solvation

    SciTech Connect

    Hu, Char Y.; Kokubo, Hironori; Lynch, Gillian C.; Bolen, D Wayne; Pettitt, Bernard M.

    2010-05-01

    The transfer model implying additivity of the peptide backbone free energy of transfer is computationally tested. Molecular dynamics simulations are used to determine the extent of change in transfer free energy (ΔGtr) with increase in chain length of oligoglycine with capped end groups. Solvation free energies of oligoglycine models of varying lengths in pure water and in the osmolyte solutions, 2M urea and 2M trimethylamine N-oxide (TMAO), were calculated from simulations of all atom models, and ΔGtr values for peptide backbone transfer from water to the osmolyte solutions were determined. The results show that the transfer free energies change linearly with increasing chain length, demonstrating the principle of additivity, and provide values in reasonable agreement with experiment. The peptide backbone transfer free energy contributions arise from van der Waals interactions in the case of transfer to urea, but from electrostatics on transfer to TMAO solution. The simulations used here allow for the calculation of the solvation and transfer free energy of longer oligoglycine models to be evaluated than is currently possible through experiment. The peptide backbone unit computed transfer free energy of –54 cal/mol/Mcompares quite favorably with –43 cal/mol/M determined experimentally.

  6. Lenz's Law: Feel the Force.

    ERIC Educational Resources Information Center

    Sawicki, Charles A.

    1996-01-01

    Describes a simple, inexpensive system that allows students to have hands-on contact with simple experiments involving forces generated by induced currents. Discusses the use of a dynamic force sensor in making quantitative measurements of the forces generated. (JRH)

  7. Piezoresistive cantilever force-clamp system

    NASA Astrophysics Data System (ADS)

    Park, Sung-Jin; Petzold, Bryan C.; Goodman, Miriam B.; Pruitt, Beth L.

    2011-04-01

    We present a microelectromechanical device-based tool, namely, a force-clamp system that sets or "clamps" the scaled force and can apply designed loading profiles (e.g., constant, sinusoidal) of a desired magnitude. The system implements a piezoresistive cantilever as a force sensor and the built-in capacitive sensor of a piezoelectric actuator as a displacement sensor, such that sample indentation depth can be directly calculated from the force and displacement signals. A programmable real-time controller operating at 100 kHz feedback calculates the driving voltage of the actuator. The system has two distinct modes: a force-clamp mode that controls the force applied to a sample and a displacement-clamp mode that controls the moving distance of the actuator. We demonstrate that the system has a large dynamic range (sub-nN up to tens of μN force and nm up to tens of μm displacement) in both air and water, and excellent dynamic response (fast response time, <2 ms and large bandwidth, 1 Hz up to 1 kHz). In addition, the system has been specifically designed to be integrated with other instruments such as a microscope with patch-clamp electronics. We demonstrate the capabilities of the system by using it to calibrate the stiffness and sensitivity of an electrostatic actuator and to measure the mechanics of a living, freely moving Caenorhabditis elegans nematode.

  8. Piezoresistive cantilever force-clamp system

    SciTech Connect

    Park, Sung-Jin; Petzold, Bryan C.; Pruitt, Beth L.; Goodman, Miriam B.

    2011-04-15

    We present a microelectromechanical device-based tool, namely, a force-clamp system that sets or ''clamps'' the scaled force and can apply designed loading profiles (e.g., constant, sinusoidal) of a desired magnitude. The system implements a piezoresistive cantilever as a force sensor and the built-in capacitive sensor of a piezoelectric actuator as a displacement sensor, such that sample indentation depth can be directly calculated from the force and displacement signals. A programmable real-time controller operating at 100 kHz feedback calculates the driving voltage of the actuator. The system has two distinct modes: a force-clamp mode that controls the force applied to a sample and a displacement-clamp mode that controls the moving distance of the actuator. We demonstrate that the system has a large dynamic range (sub-nN up to tens of {mu}N force and nm up to tens of {mu}m displacement) in both air and water, and excellent dynamic response (fast response time, <2 ms and large bandwidth, 1 Hz up to 1 kHz). In addition, the system has been specifically designed to be integrated with other instruments such as a microscope with patch-clamp electronics. We demonstrate the capabilities of the system by using it to calibrate the stiffness and sensitivity of an electrostatic actuator and to measure the mechanics of a living, freely moving Caenorhabditis elegans nematode.

  9. Detecting chameleons through Casimir force measurements

    SciTech Connect

    Brax, Philippe; Davis, Anne-Christine; Shaw, Douglas; Mota, David F.

    2007-12-15

    The best laboratory constraints on strongly coupled chameleon fields come not from tests of gravity per se but from precision measurements of the Casimir force. The chameleonic force between two nearby bodies is more akin to a Casimir-like force than a gravitational one: The chameleon force behaves as an inverse power of the distance of separation between the surfaces of two bodies, just as the Casimir force does. Additionally, experimental tests of gravity often employ a thin metallic sheet to shield electrostatic forces; however, this sheet masks any detectable signal due to the presence of a strongly coupled chameleon field. As a result of this shielding, experiments that are designed to specifically test the behavior of gravity are often unable to place any constraint on chameleon fields with a strong coupling to matter. Casimir force measurements do not employ a physical electrostatic shield and as such are able to put tighter constraints on the properties of chameleons fields with a strong matter coupling than tests of gravity. Motivated by this, we perform a full investigation on the possibility of testing chameleon models with both present and future Casimir experiments. We find that present-day measurements are not able to detect the chameleon. However, future experiments have a strong possibility of detecting or rule out a whole class of chameleon models.

  10. Impulsive Enzymes: A New Force in Mechanobiology

    PubMed Central

    Butler, Peter J.; Dey, Krishna K.; Sen, Ayusman

    2015-01-01

    We review studies that quantify newly discovered forces from single enzymatic reactions. These forces arise from the conversion of chemical energy to kinetic energy, which can be harnessed to direct diffusion of the enzyme up a concentration gradient of substrate, a novel phenomenon of molecular chemotaxis. When immobilized, enzymes can move fluid around them and perform directional pumping in microfluidic chambers. Because of the extensive array of enzymes in biological cells, we also develop three new hypotheses: that enzymatic self diffusion can assist in organizing signaling pathways in cells, can assist in pumping of fluid in cells, and can impose biologically significant forces on organelles, which will be manifested as stochastic motion not explained by thermal forces or myosin II. Such mechanochemical phenomena open up new directions in research in mechanobiology in which all enzymes, in addition to their primary function as catalysts for reactions, may have secondary functions as initiators of mechanosensitive transduction pathways. PMID:26019728

  11. Additive lattice kirigami

    PubMed Central

    Castle, Toen; Sussman, Daniel M.; Tanis, Michael; Kamien, Randall D.

    2016-01-01

    Kirigami uses bending, folding, cutting, and pasting to create complex three-dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes. PMID:27679822

  12. Additive lattice kirigami

    PubMed Central

    Castle, Toen; Sussman, Daniel M.; Tanis, Michael; Kamien, Randall D.

    2016-01-01

    Kirigami uses bending, folding, cutting, and pasting to create complex three-dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes.

  13. Dynamic force matching: A method for constructing dynamical coarse-grained models with realistic time dependence

    SciTech Connect

    Davtyan, Aram; Dama, James F.; Voth, Gregory A.; Andersen, Hans C.

    2015-04-21

    Coarse-grained (CG) models of molecular systems, with fewer mechanical degrees of freedom than an all-atom model, are used extensively in chemical physics. It is generally accepted that a coarse-grained model that accurately describes equilibrium structural properties (as a result of having a well constructed CG potential energy function) does not necessarily exhibit appropriate dynamical behavior when simulated using conservative Hamiltonian dynamics for the CG degrees of freedom on the CG potential energy surface. Attempts to develop accurate CG dynamic models usually focus on replacing Hamiltonian motion by stochastic but Markovian dynamics on that surface, such as Langevin or Brownian dynamics. However, depending on the nature of the system and the extent of the coarse-graining, a Markovian dynamics for the CG degrees of freedom may not be appropriate. In this paper, we consider the problem of constructing dynamic CG models within the context of the Multi-Scale Coarse-graining (MS-CG) method of Voth and coworkers. We propose a method of converting a MS-CG model into a dynamic CG model by adding degrees of freedom to it in the form of a small number of fictitious particles that interact with the CG degrees of freedom in simple ways and that are subject to Langevin forces. The dynamic models are members of a class of nonlinear systems interacting with special heat baths that were studied by Zwanzig [J. Stat. Phys. 9, 215 (1973)]. The properties of the fictitious particles can be inferred from analysis of the dynamics of all-atom simulations of the system of interest. This is analogous to the fact that the MS-CG method generates the CG potential from analysis of equilibrium structures observed in all-atom simulation data. The dynamic models generate a non-Markovian dynamics for the CG degrees of freedom, but they can be easily simulated using standard molecular dynamics programs. We present tests of this method on a series of simple examples that demonstrate that

  14. Dynamic force matching: A method for constructing dynamical coarse-grained models with realistic time dependence

    NASA Astrophysics Data System (ADS)

    Davtyan, Aram; Dama, James F.; Voth, Gregory A.; Andersen, Hans C.

    2015-04-01

    Coarse-grained (CG) models of molecular systems, with fewer mechanical degrees of freedom than an all-atom model, are used extensively in chemical physics. It is generally accepted that a coarse-grained model that accurately describes equilibrium structural properties (as a result of having a well constructed CG potential energy function) does not necessarily exhibit appropriate dynamical behavior when simulated using conservative Hamiltonian dynamics for the CG degrees of freedom on the CG potential energy surface. Attempts to develop accurate CG dynamic models usually focus on replacing Hamiltonian motion by stochastic but Markovian dynamics on that surface, such as Langevin or Brownian dynamics. However, depending on the nature of the system and the extent of the coarse-graining, a Markovian dynamics for the CG degrees of freedom may not be appropriate. In this paper, we consider the problem of constructing dynamic CG models within the context of the Multi-Scale Coarse-graining (MS-CG) method of Voth and coworkers. We propose a method of converting a MS-CG model into a dynamic CG model by adding degrees of freedom to it in the form of a small number of fictitious particles that interact with the CG degrees of freedom in simple ways and that are subject to Langevin forces. The dynamic models are members of a class of nonlinear systems interacting with special heat baths that were studied by Zwanzig [J. Stat. Phys. 9, 215 (1973)]. The properties of the fictitious particles can be inferred from analysis of the dynamics of all-atom simulations of the system of interest. This is analogous to the fact that the MS-CG method generates the CG potential from analysis of equilibrium structures observed in all-atom simulation data. The dynamic models generate a non-Markovian dynamics for the CG degrees of freedom, but they can be easily simulated using standard molecular dynamics programs. We present tests of this method on a series of simple examples that demonstrate that

  15. Parameterization and optimization of the menthol force field for molecular dynamics simulations.

    PubMed

    Jasik, Mateusz; Szefczyk, Borys

    2016-10-01

    Menthol's various biological properties render it a useful component for medical and cosmetological applications, while its three centers of asymmetry mean that it can be used in a range of organic reactions. Menthol-substituted ionic liquids (ILs) have been found to exhibit promising antimicrobial and antielectrostatic properties, as well as being useful in organic catalysis and biochemical studies. However, so far, a force field designed and validated specifically for the menthol molecule has not been constructed. In the present work, the validation and optimization of force field parameters with regard to the ability to reproduce the macroscopic properties of menthol is presented. The set of optimized potentials for liquid simulations all atom (OPLS-AA) compatible parameters was tested and carefully tuned. The refinement of parameters included fitting of partial atomic charges, optimization of Lennard-Jones parameters, and recalculation of the dihedral angle parameters needed to reproduce quantum energy profiles. To validate the force field, a variety of physicochemical properties were calculated for liquid menthol. Both thermodynamic and kinetic properties were taken into account, including density, surface tension, enthalpy of vaporization, and shear viscosity. The obtained force field was proven to accurately reproduce the properties of the investigated compound while being fully compatible with the OPLS-AA force field. PMID:27604277

  16. Parameterization and optimization of the menthol force field for molecular dynamics simulations.

    PubMed

    Jasik, Mateusz; Szefczyk, Borys

    2016-10-01

    Menthol's various biological properties render it a useful component for medical and cosmetological applications, while its three centers of asymmetry mean that it can be used in a range of organic reactions. Menthol-substituted ionic liquids (ILs) have been found to exhibit promising antimicrobial and antielectrostatic properties, as well as being useful in organic catalysis and biochemical studies. However, so far, a force field designed and validated specifically for the menthol molecule has not been constructed. In the present work, the validation and optimization of force field parameters with regard to the ability to reproduce the macroscopic properties of menthol is presented. The set of optimized potentials for liquid simulations all atom (OPLS-AA) compatible parameters was tested and carefully tuned. The refinement of parameters included fitting of partial atomic charges, optimization of Lennard-Jones parameters, and recalculation of the dihedral angle parameters needed to reproduce quantum energy profiles. To validate the force field, a variety of physicochemical properties were calculated for liquid menthol. Both thermodynamic and kinetic properties were taken into account, including density, surface tension, enthalpy of vaporization, and shear viscosity. The obtained force field was proven to accurately reproduce the properties of the investigated compound while being fully compatible with the OPLS-AA force field.

  17. Rectified Forces in Rubidium

    NASA Astrophysics Data System (ADS)

    Grove, Timothy Todd

    The forces exerted on a three-level atom by a bichromatic standing-wave field are investigated. A theoretical analysis shows that the standing-wave dipole force can be rectified, i.e., maintain its sign over many optical wavelengths. Three systems in particular are studied: the lambda, the vee, and the cascade. Experimental results for the rubidium 5S --> 5P --> 5D cascade system are used to confirm the theory. The nearly coincident transition wavelengths for this system (780.0 nm and 776.0 nm) provide potential wells repeating at the beat wavelength (71 μm) which can accumulate laser cooled atoms. This force may have future applications in forming deep neutral atom traps as well as in the creation of new elements for atom optics. Two-color, two-photon spectroscopy of the 5D_{5/2}<=vel using the same cascade system (5S --> 5P --> 5D) was also performed.

  18. Linear force device

    NASA Technical Reports Server (NTRS)

    Clancy, John P.

    1988-01-01

    The object of the invention is to provide a mechanical force actuator which is lightweight and manipulatable and utilizes linear motion for push or pull forces while maintaining a constant overall length. The mechanical force producing mechanism comprises a linear actuator mechanism and a linear motion shaft mounted parallel to one another. The linear motion shaft is connected to a stationary or fixed housing and to a movable housing where the movable housing is mechanically actuated through actuator mechanism by either manual means or motor means. The housings are adapted to releasably receive a variety of jaw or pulling elements adapted for clamping or prying action. The stationary housing is adapted to be pivotally mounted to permit an angular position of the housing to allow the tool to adapt to skewed interfaces. The actuator mechanisms is operated by a gear train to obtain linear motion of the actuator mechanism.

  19. [Forced spirometry procedure].

    PubMed

    Cortés Aguilera, Antonio Javier

    2008-11-01

    Forced spirometry consists in a complementary test which is carried out in a health office in a workplace in order to determine the lung capacity of workers exposed to determined professional risks or those susceptible to determined working conditions which could lead to the development of respiratory problems. This test has been developed based on health vigilance laws under Article 22 of the Law for Prevention of Risks in the Workplace and requires that the technician, a nurse in a workplace, who performs it have some knowledge and skills regarding its use, following the norms for forced spirometry set by the Spanish Association for Pneumatology and Thoracic Surgery (SEPAR). PMID:19203116

  20. Radiative Forcing of Climate Change

    SciTech Connect

    Ramaswamy, V.; Boucher, Olivier; Haigh, J.; Hauglustaine, D.; Haywood, J.; Myhre, G.; Nakajima, Takahito; Shi, Guangyu; Solomon, S.; Betts, Robert E.; Charlson, R.; Chuang, C. C.; Daniel, J. S.; Del Genio, Anthony D.; Feichter, J.; Fuglestvedt, J.; Forster, P. M.; Ghan, Steven J.; Jones, A.; Kiehl, J. T.; Koch, D.; Land, C.; Lean, J.; Lohmann, Ulrike; Minschwaner, K.; Penner, Joyce E.; Roberts, D. L.; Rodhe, H.; Roelofs, G.-J.; Rotstayn, Leon D.; Schneider, T. L.; Schumann, U.; Schwartz, Stephen E.; Schwartzkopf, M. D.; Shine, K. P.; Smith, Steven J.; Stevenson, D. S.; Stordal, F.; Tegen, I.; van Dorland, R.; Zhang, Y.; Srinivasan, J.; Joos, Fortunat

    2001-10-01

    Chapter 6 of the IPCC Third Assessment Report Climate Change 2001: The Scientific Basis. Sections include: Executive Summary 6.1 Radiative Forcing 6.2 Forcing-Response Relationship 6.3 Well-Mixed Greenhouse Gases 6.4 Stratospheric Ozone 6.5 Radiative Forcing By Tropospheric Ozone 6.6 Indirect Forcings due to Chemistry 6.7 The Direct Radiative Forcing of Tropospheric Aerosols 6.8 The Indirect Radiative Forcing of Tropospheric Aerosols 6.9 Stratospheric Aerosols 6.10 Land-use Change (Surface Albedo Effect) 6.11 Solar Forcing of Climate 6.12 Global Warming Potentials hydrocarbons 6.13 Global Mean Radiative Forcings 6.14 The Geographical Distribution of the Radiative Forcings 6.15 Time Evolution of Radiative Forcings Appendix 6.1 Elements of Radiative Forcing Concept References.

  1. Lorentz force particle analyzer

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Thess, André; Moreau, René; Tan, Yanqing; Dai, Shangjun; Tao, Zhen; Yang, Wenzhi; Wang, Bo

    2016-07-01

    A new contactless technique is presented for the detection of micron-sized insulating particles in the flow of an electrically conducting fluid. A transverse magnetic field brakes this flow and tends to become entrained in the flow direction by a Lorentz force, whose reaction force on the magnetic-field-generating system can be measured. The presence of insulating particles suspended in the fluid produce changes in this Lorentz force, generating pulses in it; these pulses enable the particles to be counted and sized. A two-dimensional numerical model that employs a moving mesh method demonstrates the measurement principle when such a particle is present. Two prototypes and a three-dimensional numerical model are used to demonstrate the feasibility of a Lorentz force particle analyzer (LFPA). The findings of this study conclude that such an LFPA, which offers contactless and on-line quantitative measurements, can be applied to an extensive range of applications. These applications include measurements of the cleanliness of high-temperature and aggressive molten metal, such as aluminum and steel alloys, and the clean manufacturing of semiconductors.

  2. The Force of Ideas

    ERIC Educational Resources Information Center

    Ascher, Carol

    2005-01-01

    "The Force of Ideas" describes a little-known aspect of both educational history and Viennese psychoanalysis during the interwar years: the movement for psychoanalytic pedagogy. The author traces her father's own story, beginning with his application to the Vienna Psychoanalytic Society for training as a psychoanalytic pedagogue, as a way to…

  3. Force limited vibration testing

    NASA Technical Reports Server (NTRS)

    Scharton, Terry D.

    1991-01-01

    A new method of conducting lab vibration tests of spacecraft equipment was developed to more closely simulate the vibration environment experienced when the spacecraft is launched on a rocket. The improved tests are tailored to identify equipment design and workmanship problems without inducing artificial failures that would not have occurred at launch. These new, less destructive types of vibration tests are essential to JPL's protoflight test approach in which lab testing is conducted using the flight equipment, often one of a kind, to save time and money. In conventional vibration tests, only the input vibratory motion is specified; the feedback, or reaction force, between the test item and the vibration machine is ignored. Most test failures occur when the test item goes into resonance, and the reaction force becomes very large. It has long been recognized that the large reaction force is a test artifact which does not occur with the lightweight, flexible mounting structures characteristic of spacecraft and space vehicles. In new vibration tests, both the motion and the force provided to the test item by the vibration machine are controlled, so that the vibration ride experienced by the test item is as in flight.

  4. Measuring Your Force

    ERIC Educational Resources Information Center

    Gee, David E.

    2005-01-01

    This article talks about the force behind education leaders. With all the challenges facing public education today, it is difficult to remain focused and to remember why one chartered this particular leadership course. Perhaps someone respected encouraged one to take this path long ago. Perhaps this kind of service to the nation and its future…

  5. Unification of Fundamental Forces

    NASA Astrophysics Data System (ADS)

    Salam, Abdus; Taylor, Foreword by John C.

    2005-10-01

    Foreword John C. Taylor; 1. Unification of fundamental forces Abdus Salam; 2. History unfolding: an introduction to the two 1968 lectures by W. Heisenberg and P. A. M. Dirac Abdus Salam; 3. Theory, criticism, and a philosophy Werner Heisenberg; 4. Methods in theoretical physics Paul Adrian Maurice Dirac.

  6. The Dynamic Force Table

    ERIC Educational Resources Information Center

    Geddes, John B.; Black, Kelly

    2008-01-01

    We examine an experimental apparatus that is used to motivate the connections between the basic properties of vectors, potential functions, systems of nonlinear equations, and Newton's method for nonlinear systems of equations. The apparatus is an adaptation of a force table where we remove the center-pin and allow the center-ring to move freely.…

  7. Perpendicular-Force Latch

    NASA Technical Reports Server (NTRS)

    Mattei, John P.; Buck, Peter A.; Williams, Michael D.

    1990-01-01

    Latching mechanism simultaneously applies force in two perpendicular directions to install or remove electronic-equipment modules. Used to simplify installation and removal of modular equipment where movement restricted by protective clothing as in hazardous environments or where installation and removal to be performed by robots or remote manipulators. Concept adaptable to hydraulic, pneumatic, and mechanical systems.

  8. Direct Aerosol Forcing Uncertainty

    DOE Data Explorer

    Mccomiskey, Allison

    2008-01-15

    Understanding sources of uncertainty in aerosol direct radiative forcing (DRF), the difference in a given radiative flux component with and without aerosol, is essential to quantifying changes in Earth's radiation budget. We examine the uncertainty in DRF due to measurement uncertainty in the quantities on which it depends: aerosol optical depth, single scattering albedo, asymmetry parameter, solar geometry, and surface albedo. Direct radiative forcing at the top of the atmosphere and at the surface as well as sensitivities, the changes in DRF in response to unit changes in individual aerosol or surface properties, are calculated at three locations representing distinct aerosol types and radiative environments. The uncertainty in DRF associated with a given property is computed as the product of the sensitivity and typical measurement uncertainty in the respective aerosol or surface property. Sensitivity and uncertainty values permit estimation of total uncertainty in calculated DRF and identification of properties that most limit accuracy in estimating forcing. Total uncertainties in modeled local diurnally averaged forcing range from 0.2 to 1.3 W m-2 (42 to 20%) depending on location (from tropical to polar sites), solar zenith angle, surface reflectance, aerosol type, and aerosol optical depth. The largest contributor to total uncertainty in DRF is usually single scattering albedo; however decreasing measurement uncertainties for any property would increase accuracy in DRF. Comparison of two radiative transfer models suggests the contribution of modeling error is small compared to the total uncertainty although comparable to uncertainty arising from some individual properties.

  9. Lattice model for amyloid peptides: OPEP force field parametrization and applications to the nucleus size of Alzheimer's peptides.

    PubMed

    Tran, Thanh Thuy; Nguyen, Phuong H; Derreumaux, Philippe

    2016-05-28

    Coarse-grained protein lattice models approximate atomistic details and keep the essential interactions. They are, therefore, suitable for capturing generic features of protein folding and amyloid formation at low computational cost. As our aim is to study the critical nucleus sizes of two experimentally well-characterized peptide fragments Aβ16-22 and Aβ37-42 of the full length Aβ1-42 Alzheimer's peptide, it is important that simulations with the lattice model reproduce all-atom simulations. In this study, we present a comprehensive force field parameterization based on the OPEP (Optimized Potential for Efficient protein structure Prediction) force field for an on-lattice protein model, which incorporates explicitly the formation of hydrogen bonds and directions of side-chains. Our bottom-up approach starts with the determination of the best lattice force parameters for the Aβ16-22 dimer by fitting its equilibrium parallel and anti-parallel β-sheet populations to all-atom simulation results. Surprisingly, the calibrated force field is transferable to the trimer of Aβ16-22 and the dimer and trimer of Aβ37-42. Encouraged by this finding, we characterized the free energy landscapes of the two decamers. The dominant structure of the Aβ16-22 decamer matches the microcrystal structure. Pushing the simulations for aggregates between 4-mer and 12-mer suggests a nucleus size for fibril formation of 10 chains. In contrast, the Aβ37-42 decamer is largely disordered with mixed by parallel and antiparallel chains, suggesting that the nucleus size is >10 peptides. Our refined force field coupled to this on-lattice model should provide useful insights into the critical nucleation number associated with neurodegenerative diseases. PMID:27250331

  10. Lattice model for amyloid peptides: OPEP force field parametrization and applications to the nucleus size of Alzheimer's peptides

    NASA Astrophysics Data System (ADS)

    Tran, Thanh Thuy; Nguyen, Phuong H.; Derreumaux, Philippe

    2016-05-01

    Coarse-grained protein lattice models approximate atomistic details and keep the essential interactions. They are, therefore, suitable for capturing generic features of protein folding and amyloid formation at low computational cost. As our aim is to study the critical nucleus sizes of two experimentally well-characterized peptide fragments Aβ16-22 and Aβ37-42 of the full length Aβ1-42 Alzheimer's peptide, it is important that simulations with the lattice model reproduce all-atom simulations. In this study, we present a comprehensive force field parameterization based on the OPEP (Optimized Potential for Efficient protein structure Prediction) force field for an on-lattice protein model, which incorporates explicitly the formation of hydrogen bonds and directions of side-chains. Our bottom-up approach starts with the determination of the best lattice force parameters for the Aβ16-22 dimer by fitting its equilibrium parallel and anti-parallel β-sheet populations to all-atom simulation results. Surprisingly, the calibrated force field is transferable to the trimer of Aβ16-22 and the dimer and trimer of Aβ37-42. Encouraged by this finding, we characterized the free energy landscapes of the two decamers. The dominant structure of the Aβ16-22 decamer matches the microcrystal structure. Pushing the simulations for aggregates between 4-mer and 12-mer suggests a nucleus size for fibril formation of 10 chains. In contrast, the Aβ37-42 decamer is largely disordered with mixed by parallel and antiparallel chains, suggesting that the nucleus size is >10 peptides. Our refined force field coupled to this on-lattice model should provide useful insights into the critical nucleation number associated with neurodegenerative diseases.

  11. Chiral drag force

    NASA Astrophysics Data System (ADS)

    Rajagopal, Krishna; Sadofyev, Andrey V.

    2015-10-01

    We provide a holographic evaluation of novel contributions to the drag force acting on a heavy quark moving through strongly interacting plasma. The new contributions are chiral in the sense that they act in opposite directions in plasmas containing an excess of left- or right-handed quarks. The new contributions are proportional to the coefficient of the axial anomaly, and in this sense also are chiral. These new contributions to the drag force act either parallel to or antiparallel to an external magnetic field or to the vorticity of the fluid plasma. In all these respects, these contributions to the drag force felt by a heavy quark are analogous to the chiral magnetic effect (CME) on light quarks. However, the new contribution to the drag force is independent of the electric charge of the heavy quark and is the same for heavy quarks and antiquarks, meaning that these novel effects do not in fact contribute to the CME current. We show that although the chiral drag force can be non-vanishing for heavy quarks that are at rest in the local fluid rest frame, it does vanish for heavy quarks that are at rest in a suitably chosen frame. In this frame, the heavy quark at rest sees counterpropagating momentum and charge currents, both proportional to the axial anomaly coefficient, but feels no drag force. This provides strong concrete evidence for the absence of dissipation in chiral transport, something that has been predicted previously via consideration of symmetries. Along the way to our principal results, we provide a general calculation of the corrections to the drag force due to the presence of gradients in the flowing fluid in the presence of a nonzero chemical potential. We close with a consequence of our result that is at least in principle observable in heavy ion collisions, namely an anticorrelation between the direction of the CME current for light quarks in a given event and the direction of the kick given to the momentum of all the heavy quarks and

  12. Amplification of actin polymerization forces

    PubMed Central

    Dmitrieff, Serge; Nédélec, François

    2016-01-01

    The actin cytoskeleton drives many essential processes in vivo, using molecular motors and actin assembly as force generators. We discuss here the propagation of forces caused by actin polymerization, highlighting simple configurations where the force developed by the network can exceed the sum of the polymerization forces from all filaments. PMID:27002174

  13. Mechanical design and force calibration of dual-axis micromechanical probe for friction force microscopy

    SciTech Connect

    Fukuzawa, Kenji; Terada, Satoshi; Shikida, Mitsuhiro; Amakawa, Hiroaki; Zhang, Hedong; Mitsuya, Yasunaga

    2007-02-01

    A dual-axis micromechanical probe that combines a double cantilever and torsion beams is presented. This probe can reduce the mechanical cross-talk between the lateral and vertical force detections. In addition, dual-axis forces can be detected by measuring the dual-axis displacement of the probe end using the optical lever-based method used in conventional friction force microscopes (FFMs). In this paper, the mechanical design of the probe, the details of the fabrication method, FFM performance, and calibration of the friction force are discussed. The mechanical design and the microfabrication method for probes that can provide a force resolution of the order of 1 nN without mechanical cross-talk are presented. Calibration of the lateral force signal is possible by using the relationship between the lateral force and the piezodisplacement at the onset of the probe scanning. The micromechanical probe enables simultaneous and independent detection of atomic and friction forces. This leads to accurate investigation of nanotribological phenomena and visualization of the distribution of the friction properties, which helps the identification of the material properties.

  14. 10 CFR 1049.6 - Exercise of arrest authority-Use of non-deadly force.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Exercise of arrest authority-Use of non-deadly force. 1049... OF FORCE BY PROTECTIVE FORCE OFFICERS OF THE STRATEGIC PETROLEUM RESERVE § 1049.6 Exercise of arrest... for additional guidance on the use of non-deadly force in the exercise of arrest authority,...

  15. 10 CFR 1049.6 - Exercise of arrest authority-Use of non-deadly force.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Exercise of arrest authority-Use of non-deadly force. 1049... OF FORCE BY PROTECTIVE FORCE OFFICERS OF THE STRATEGIC PETROLEUM RESERVE § 1049.6 Exercise of arrest... for additional guidance on the use of non-deadly force in the exercise of arrest authority,...

  16. 10 CFR 1049.6 - Exercise of arrest authority-Use of non-deadly force.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Exercise of arrest authority-Use of non-deadly force. 1049... OF FORCE BY PROTECTIVE FORCE OFFICERS OF THE STRATEGIC PETROLEUM RESERVE § 1049.6 Exercise of arrest... for additional guidance on the use of non-deadly force in the exercise of arrest authority,...

  17. 10 CFR 1049.6 - Exercise of arrest authority-Use of non-deadly force.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Exercise of arrest authority-Use of non-deadly force. 1049... OF FORCE BY PROTECTIVE FORCE OFFICERS OF THE STRATEGIC PETROLEUM RESERVE § 1049.6 Exercise of arrest... for additional guidance on the use of non-deadly force in the exercise of arrest authority,...

  18. 10 CFR 1049.6 - Exercise of arrest authority-Use of non-deadly force.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Exercise of arrest authority-Use of non-deadly force. 1049... OF FORCE BY PROTECTIVE FORCE OFFICERS OF THE STRATEGIC PETROLEUM RESERVE § 1049.6 Exercise of arrest... for additional guidance on the use of non-deadly force in the exercise of arrest authority,...

  19. 20. Photographic copy of an asconstructed site plan for additions ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Photographic copy of an as-constructed site plan for additions to North Base: Job No. A(8-1), Military Construction, Materiel Command Flight Test Base, Muroc, California; Additional Construction, Location Plan, Sheet No. 2, October 1943. Reproduced from the holdings of the National Archives, Pacific Southwest Region - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

  20. Retention force measurement of telescopic crowns.

    PubMed

    Bayer, Stefan; Stark, Helmut; Mues, Sebastian; Keilig, Ludger; Schrader, Anja; Enkling, Norbert

    2010-10-01

    This study deals with the determination of the retentive force between primary and secondary telescopic crowns under clinical conditions. Forty-three combined fixed-removable prostheses with a total of 140 double crowns were used for retention force measurement of the telescopic crowns prior to cementation. The crowns had a preparation of 1-2°. A specifically designed measuring device was used. The retentive forces were measured with and without lubrication by a saliva substitute. The measured values were analyzed according to the type of tooth (incisors, canines, premolars, and molars). Additionally, a comparison between lubricated and unlubricated telescopic crowns was done. As maximum retention force value 29.98 N was recorded with a telescopic crown on a molar, while the minimum of 0.08 N was found with a specimen on a canine. The median value of retention force of all telescopic crowns reached 1.93 N with an interquartile distance of 4.35 N. No statistically significant difference between lubricated and unlubricated specimens was found. The results indicate that retention force values of telescopic crowns, measured in clinical practice, are often much lower than those cited in the literature. The measurements also show a wide range. Whether this proves to be a problem for the patient's quality of life or not can however only be established by a comparison of the presented results with a follow-up study involving measurement of intraoral retention and determination by e.g. oral health impact profile.

  1. Some punishing effects of response-force.

    PubMed

    Miller, L K

    1970-03-01

    The present experiment explored the punishing effect of different response-force requirements by means of a two-operant design analogous to a two-component chain schedule. The first component of the chain required a lever pull through 0.25 in. (0.64 cm) at 1 lb (4.45 N) of force. The second component required a lever pull through an additional 0.75 in. (1.90 cm) with the force varied between sessions from 1 lb to 50 lb (4.45 N to 223 N). Completion of the second component of the chain was reinforced after variable intervals averaging 1 min. The average rate of first-component response decreased as the force requirement for second-component responses was increased. This rate reduction did not appear to be due to increased response duration, "fatigue", or differing rates of reinforcement. If the force requirement for the second-component response is viewed as a consequence for the first-component response, then the results of the experiment show that a high force requirement is a punisher. PMID:16811439

  2. Probing adhesion forces at the molecular scale

    SciTech Connect

    Thomas, R.C.; Houston, J.E.; Michalske, T.A.

    1996-12-31

    Measurements of adhesion forces at the molecular scale, such as those discussed here, are necessary to understand macroscopic boundary-layer behavior such as adhesion, friction, wear, lubrication, and many other important phenomena. The authors` recent interfacial force microscopy (IFM) studies have provided detailed information about the mechanical response of both self-assembled monolayer (SAM) films and the underlying substrates. In addition, they recently demonstrated that the IFM is useful for studying the chemical nature of such films. In this talk, the authors discuss a new method for studying surface interactions and chemical reactions using the IFM. To quantitatively measure the work of adhesion and bond energies between two organic thin films, they modify both a Au substrate and a Au probe with self-assembling organomercaptan molecules having either the same or different end groups (-CH{sub 3}, -NH{sub 2}, and -COOH), and then analyze the force-versus-displacement curves (force profiles) that result from the approach to contact of the two surfaces. Their results show that the magnitude of the adhesive forces measured between methyl-methyl interactions are in excellent agreement with van der Waals calculations using Lifshitz theory and previous experimentally determined values. Moreover, the measured peak adhesive forces scale as expected for van der Waals, hydrogen-bonding, and acid-base interactions.

  3. Finding forced trends in oceanic oxygen

    NASA Astrophysics Data System (ADS)

    Long, Matthew C.; Deutsch, Curtis; Ito, Taka

    2016-02-01

    Anthropogenically forced trends in oceanic dissolved oxygen are evaluated in Earth system models in the context of natural variability. A large ensemble of a single Earth system model is used to clearly identify the forced component of change in interior oxygen distributions and to evaluate the magnitude of this signal relative to noise generated by internal climate variability. The time of emergence of forced trends is quantified on the basis of anomalies in oxygen concentrations and trends. We find that the forced signal should already be evident in the southern Indian Ocean and parts of the eastern tropical Pacific and Atlantic basins; widespread detection of forced deoxygenation is possible by 2030-2040. In addition to considering spatially discrete metrics of detection, we evaluate the similarity of the spatial structures associated with natural variability and the forced trend. Outside of the subtropics, these patterns are not wholly distinct on the isopycnal surfaces considered, and therefore, this approach does not provide significantly advanced detection. Our results clearly demonstrate the strong impact of natural climate variability on interior oxygen distributions, providing an important context for interpreting observations.

  4. Investigation of Calibrating Force Transducer Using Sinusoidal Force

    SciTech Connect

    Zhang Li; Wang Yu; Zhang Lizhe

    2010-05-28

    Sinusoidal force calibration method was studied several years before at Physikalisch-Technische Bundesanstalt (PTB). A similar dynamic force calibration system is developed at Changcheng Institute of Metrology and Measurement (CIMM). It uses electro-dynamic shakers to generate dynamic force in the range from 1 N to 20 kN, and heterodyne laser interferometers are used for acceleration measurement. The force transducer to be calibrated is mounted on the shaker, and a mass block is screwed on the top of force transducer, the sinusoidal forces realized by accelerated load masses are traceable to acceleration and mass according to the force definition. The methods of determining Spatial-dependent acceleration on mass block and measuring the end mass of force transducer in dynamic force calibration are discussed in this paper.

  5. Dark Forces At The Tevatron

    DOE PAGES

    Buckley, Matt; Fileviez Perez, Pavel; Hooper, Dan; Neil, Ethan

    2011-08-19

    A simple explanation of the W + dijet excess recently reported by the CDF collaboration involves the introduction of a new gauge boson with sizable couplings to quarks, but with no or highly suppressed couplings to leptons. Anomaly-free theories which include such a leptophobic gauge boson must also include additional particle content, which may include a stable and otherwise viable candidate for dark matter. Based on the couplings and mass of the Z` required to generate the CDF excess, we predict such a dark matter candidate to possess an elastic scattering cross section with nucleons on the order of σmore » ~ 10-40 cm2, providing a natural explanation for the signals reported by the CoGeNT and DAMA/LIBRA collaborations. In this light, CDF may be observing the gauge boson responsible for the force which mediates the interactions between the dark and visible matter of our universe.« less

  6. Dark Forces At The Tevatron

    SciTech Connect

    Buckley, Matt; Fileviez Perez, Pavel; Hooper, Dan; Neil, Ethan

    2011-08-19

    A simple explanation of the W + dijet excess recently reported by the CDF collaboration involves the introduction of a new gauge boson with sizable couplings to quarks, but with no or highly suppressed couplings to leptons. Anomaly-free theories which include such a leptophobic gauge boson must also include additional particle content, which may include a stable and otherwise viable candidate for dark matter. Based on the couplings and mass of the Z` required to generate the CDF excess, we predict such a dark matter candidate to possess an elastic scattering cross section with nucleons on the order of σ ~ 10-40 cm2, providing a natural explanation for the signals reported by the CoGeNT and DAMA/LIBRA collaborations. In this light, CDF may be observing the gauge boson responsible for the force which mediates the interactions between the dark and visible matter of our universe.

  7. Force Feedback Joystick

    NASA Technical Reports Server (NTRS)

    1997-01-01

    I-FORCE, a computer peripheral from Immersion Corporation, was derived from virtual environment and human factors research at the Advanced Displays and Spatial Perception Laboratory at Ames Research Center in collaboration with Stanford University Center for Design Research. Entrepreneur Louis Rosenberg, a former Stanford researcher, now president of Immersion, collaborated with Dr. Bernard Adelstein at Ames on studies of perception in virtual reality. The result was an inexpensive way to incorporate motors and a sophisticated microprocessor into joysticks and other game controllers. These devices can emulate the feel of a car on the skid, a crashing plane, the bounce of a ball, compressed springs, or other physical phenomenon. The first products incorporating I-FORCE technology include CH- Products' line of FlightStick and CombatStick controllers.

  8. Suicide and Forced Marriage

    PubMed Central

    Pridmore, Saxby; Walter, Garry

    2013-01-01

    Background: The prevailing view that the vast majority of those who complete suicide have an underlying psychiatric disorder has been recently challenged by research on the contribution of “predicaments”, in the absence of mental illness, to suicide. In this paper, we sought data to support the notion that forced marriage may lead to suicide without the presence of psychiatric disorder. Methods: Historical records, newspapers, and the electronic media were searched for examples. Results: Two examples from ancient times and six from the last hundred years were located and described. Conclusion: These cases suggest that forced marriage may lead to suicide and complements earlier findings that loss of fortune, health, liberty, and reputation may lead to suicide in the absence of mental disorder. PMID:23983577

  9. Forces Driving Chaperone Action.

    PubMed

    Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C A

    2016-07-14

    It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client's affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

  10. Force Modulator System

    SciTech Connect

    Redmond Clark

    2009-04-30

    Many metal parts manufacturers use large metal presses to shape sheet metal into finished products like car body parts, jet wing and fuselage surfaces, etc. These metal presses take sheet metal and - with enormous force - reshape the metal into a fully formed part in a manner of seconds. Although highly efficient, the forces involved in forming metal parts also damage the press itself, limit the metals used in part production, slow press operations and, when not properly controlled, cause the manufacture of large volumes of defective metal parts. To date, the metal-forming industry has not been able to develop a metal-holding technology that allows full control of press forces during the part forming process. This is of particular importance in the automotive lightweighting efforts under way in the US automotive manufacturing marketplace. Metalforming Controls Technology Inc. (MC2) has developed a patented press control system called the Force Modulator that has the ability to control these press forces, allowing a breakthrough in stamping process control. The technology includes a series of hydraulic cylinders that provide controlled tonnage at all points in the forming process. At the same time, the unique cylinder design allows for the generation of very high levels of clamping forces (very high tonnages) in very small spaces; a requirement for forming medium and large panels out of HSS and AHSS. Successful production application of these systems testing at multiple stamping operations - including Ford and Chrysler - has validated the capabilities and economic benefits of the system. Although this technology has been adopted in a number of stamping operations, one of the primary barriers to faster adoption and application of this technology in HSS projects is system cost. The cost issue has surfaced because the systems currently in use are built for each individual die as a custom application, thus driving higher tooling costs. This project proposed to better

  11. Air Force seal activities

    NASA Astrophysics Data System (ADS)

    Mayhew, Ellen R.

    1994-07-01

    Seal technology development is an important part of the Air Force's participation in the Integrated High Performance Turbine Engine Technology (IHPTET) initiative, the joint DOD, NASA, ARPA, and industry endeavor to double turbine engine capabilities by the turn of the century. Significant performance and efficiency improvements can be obtained through reducing internal flow system leakage, but seal environment requirements continue to become more extreme as the engine thermodynamic cycles advance towards these IHPTET goals. Brush seal technology continues to be pursued by the Air Force to reduce leakage at the required conditions. Likewise, challenges in engine mainshaft air/oil seals are also being addressed. Counter-rotating intershaft applications within the IHPTET initiative involve very high rubbing velocities. This viewgraph presentation briefly describes past and current seal research and development programs and gives a summary of seal applications in demonstrator and developmental engine testing.

  12. Ultrasensitive hysteretic force sensing with parametric nonlinear oscillators.

    PubMed

    Papariello, Luca; Zilberberg, Oded; Eichler, Alexander; Chitra, R

    2016-08-01

    We propose a method for linear detection of weak forces using parametrically driven nonlinear resonators. The method is based on a peculiar feature in the response of the resonator to a near resonant periodic external force. This feature stems from a complex interplay among the parametric drive, external force, and nonlinearities. For weak parametric drive, the response exhibits the standard Duffing-like single jump hysteresis. For stronger drive amplitudes, we find a qualitatively new double jump hysteresis which arises from stable solutions generated by the cubic Duffing nonlinearity. The additional jump exists only if the external force is present and the frequency at which it occurs depends linearly on the amplitude of the external force, permitting a straightforward ultrasensitive detection of weak forces. With state-of-the-art nanomechanical resonators, our scheme should permit force detection in the attonewton range. PMID:27627292

  13. Ultrasensitive hysteretic force sensing with parametric nonlinear oscillators

    NASA Astrophysics Data System (ADS)

    Papariello, Luca; Zilberberg, Oded; Eichler, Alexander; Chitra, R.

    2016-08-01

    We propose a method for linear detection of weak forces using parametrically driven nonlinear resonators. The method is based on a peculiar feature in the response of the resonator to a near resonant periodic external force. This feature stems from a complex interplay among the parametric drive, external force, and nonlinearities. For weak parametric drive, the response exhibits the standard Duffing-like single jump hysteresis. For stronger drive amplitudes, we find a qualitatively new double jump hysteresis which arises from stable solutions generated by the cubic Duffing nonlinearity. The additional jump exists only if the external force is present and the frequency at which it occurs depends linearly on the amplitude of the external force, permitting a straightforward ultrasensitive detection of weak forces. With state-of-the-art nanomechanical resonators, our scheme should permit force detection in the attonewton range.

  14. Recent Developments and Applications of the CHARMM force fields.

    PubMed

    Zhu, Xiao; Lopes, Pedro E M; Mackerell, Alexander D

    2012-01-01

    Empirical force fields commonly used to describe the condensed phase properties of complex systems such as biological macromolecules are continuously being updated. Improvements in quantum mechanical (QM) methods used to generate target data, availability of new experimental target data, incorporation of new classes of compounds and new theoretical developments (eg. polarizable methods) make force-field development a dynamic domain of research. Accordingly, a number of improvements and extensions of the CHARMM force fields have occurred over the years. The objective of the present review is to provide an up-to-date overview of the CHARMM force fields. A limited presentation on the historical aspects of force fields will be given, including underlying methodologies and principles, along with a brief description of the strategies used for parameter development. This is followed by information on the CHARMM additive and polarizable force fields, including examples of recent applications of those force fields.

  15. Ultrasonic Force Microscopies

    NASA Astrophysics Data System (ADS)

    Kolosov, Oleg; Briggs, Andrew

    Ultrasonic Force Microscopy, or UFM, allows combination of two apparently mutually exclusive requirements for the nanomechanical probe—high stiffness for the efficient indentation and high mechanical compliance that brings force sensitivity. Somewhat inventively, UFM allows to combine these two virtues in the same cantilever by using indention of the sample at high frequency, when cantilever is very rigid, but detecting the result of this indention at much lower frequency. That is made possible due to the extreme nonlinearity of the nanoscale tip-surface junction force-distance dependence, that acts as "mechanical diode" detecting ultrasound in AFM. After introducing UFM principles, we discuss features of experimental UFM implementation, and the theory of contrast in this mode, progressing to quantitative measurements of contact stiffness. A variety of UFM applications ranging from semiconductor quantum nanostructures, graphene, very large scale integrated circuits, and reinforced ceramics to polymer composites and biological materials is presented via comprehensive imaging gallery accompanied by the guidance for the optimal UFM measurements of these materials. We also address effects of adhesion and topography on the elasticity imaging and the approaches for reducing artifacts connected with these effects. This is complemented by another extremely useful feature of UFM—ultrasound induced superlubricity that allows damage free imaging of materials ranging from stiff solid state devices and graphene to biological materials. Finally, we proceed to the exploration of time-resolved nanoscale phenomena using nonlinear mixing of multiple vibration frequencies in ultrasonic AFM—Heterodyne Force Microscopy, or HFM, that also include mixing of ultrasonic vibration with other periodic physical excitations, eg. electrical, photothermal, etc. Significant section of the chapter analyzes the ability of UFM and HFM to detect subsurface mechanical inhomogeneities, as well as

  16. ``Force,'' ontology, and language

    NASA Astrophysics Data System (ADS)

    Brookes, David T.; Etkina, Eugenia

    2009-06-01

    We introduce a linguistic framework through which one can interpret systematically students’ understanding of and reasoning about force and motion. Some researchers have suggested that students have robust misconceptions or alternative frameworks grounded in everyday experience. Others have pointed out the inconsistency of students’ responses and presented a phenomenological explanation for what is observed, namely, knowledge in pieces. We wish to present a view that builds on and unifies aspects of this prior research. Our argument is that many students’ difficulties with force and motion are primarily due to a combination of linguistic and ontological difficulties. It is possible that students are primarily engaged in trying to define and categorize the meaning of the term “force” as spoken about by physicists. We found that this process of negotiation of meaning is remarkably similar to that engaged in by physicists in history. In this paper we will describe a study of the historical record that reveals an analogous process of meaning negotiation, spanning multiple centuries. Using methods from cognitive linguistics and systemic functional grammar, we will present an analysis of the force and motion literature, focusing on prior studies with interview data. We will then discuss the implications of our findings for physics instruction.

  17. Force Fluctuations and Correlations

    NASA Astrophysics Data System (ADS)

    Behringer, Robert

    1998-03-01

    Granular materials exhibit a rich array of dynamic and static phenomena which are only partly understood. Here, I focus on fluctuations in kinetic properties and in forces for slowly sheared granular materials. We have carried out a series of experiments in both 2D and in 3D. For 2D, we use a novel apparatus which allows us to quantify the forces, positions and orientations associated with individual grains. For slow to moderate shear rates, we find rate independence except for small random deviations which are associated with very long time changes in the system. The system evolves to a nearly steady average flow profile in which the velocity falls off approximately exponentially with distance from the shearing surface. The particle rotation shows systematic oscillations near the shearing surface. Velocity profiles show a complicated non-gaussian structure. Force measurements in both the 2D and 3D system are approximately exponentially distributed, but there are also some systematic deviations. Companion calculations by S. Schoellmann, S. Luding and H. Herrmann capture a number of these features. The experimental work has been carried out partially at Duke and partially at the E.S.P.C.I. Paris in collaboration with D. Howell, B. Miller, S. Tennakoon, and C. Veje.

  18. The task force process

    SciTech Connect

    Applegate, J.S.

    1995-01-31

    This paper focuses on the unique aspects of the Fernald Citizens Task Force process that have contributed to a largely successful public participation effort at Fernald. The Fernald Citizens Task Force passed quickly by many procedural issues. Instead, the Task Force concentrated on (a) educating itself about the site, its problems, and possible solutions, and (b) choosing a directed way to approach its mandate: To make recommendations on several {open_quotes}big picture{close_quotes} issues, including future use of the site, cleanup levels, waste disposition, and cleanup priorities. This paper presents the approach used at Fernald for establishing and running a focused site-specific advisory board, the key issues that have been faced, and how these issues were resolved. The success of Fernald in establishing a strong and functioning site-specific advisory board serves as a useful model for other DOE facilities, although the Fernald model is just one of many approaches that can be taken. However, the approach presented here has worked extremely well for Fernald.

  19. Modified entropic force

    SciTech Connect

    Gao Changjun

    2010-04-15

    The theory of statistical thermodynamics tells us the equipartition law of energy does not hold in the limit of very low temperatures. It is found the Debye model is very successful in explaining the experimental results for most of the solid objects. Motivated by this fact, we modify the entropic force formula which is proposed very recently. Since the Unruh temperature is proportional to the strength of the gravitational field, so the modified entropic force formula is an extension of the Newtonian gravity to the weak field. On the contrary, general relativity extends Newtonian gravity to the strong field case. Corresponding to Debye temperature, there exists a Debye acceleration g{sub D}. It is found the Debye acceleration is g{sub D}=10{sup -15} N kg{sup -1}. This acceleration is very much smaller than the gravitational acceleration 10{sup -4} N kg{sup -1} which is felt by Neptune and the gravitational acceleration 10{sup -10} N kg{sup -1} felt by the Sun. Therefore, the modified entropic force can be very well approximated by the Newtonian gravity in the Solar System and in the Galaxy. With this Debye acceleration, we find the current cosmic speeding up can be explained without invoking any kind of dark energy.

  20. Fidelity imaging for atomic force microscopy

    SciTech Connect

    Ghosal, Sayan Salapaka, Murti

    2015-01-05

    Atomic force microscopy is widely employed for imaging material at the nanoscale. However, real-time measures on image reliability are lacking in contemporary atomic force microscopy literature. In this article, we present a real-time technique that provides an image of fidelity for a high bandwidth dynamic mode imaging scheme. The fidelity images define channels that allow the user to have additional authority over the choice of decision threshold that facilitates where the emphasis is desired, on discovering most true features on the sample with the possible detection of high number of false features, or emphasizing minimizing instances of false detections. Simulation and experimental results demonstrate the effectiveness of fidelity imaging.

  1. Higher-order force gradient symplectic algorithms

    NASA Astrophysics Data System (ADS)

    Chin, Siu A.; Kidwell, Donald W.

    2000-12-01

    We show that a recently discovered fourth order symplectic algorithm, which requires one evaluation of force gradient in addition to three evaluations of the force, when iterated to higher order, yielded algorithms that are far superior to similarly iterated higher order algorithms based on the standard Forest-Ruth algorithm. We gauge the accuracy of each algorithm by comparing the step-size independent error functions associated with energy conservation and the rotation of the Laplace-Runge-Lenz vector when solving a highly eccentric Kepler problem. For orders 6, 8, 10, and 12, the new algorithms are approximately a factor of 103, 104, 104, and 105 better.

  2. Mechanical Response of Silk Crystalline Units from Force-Distribution Analysis

    PubMed Central

    Xiao, Senbo; Stacklies, Wolfram; Cetinkaya, Murat; Markert, Bernd; Gräter, Frauke

    2009-01-01

    The outstanding mechanical toughness of silk fibers is thought to be caused by embedded crystalline units acting as cross links of silk proteins in the fiber. Here, we examine the robustness of these highly ordered β-sheet structures by molecular dynamics simulations and finite element analysis. Structural parameters and stress-strain relationships of four different models, from spider and Bombyx mori silk peptides, in antiparallel and parallel arrangement, were determined and found to be in good agreement with x-ray diffraction data. Rupture forces exceed those of any previously examined globular protein many times over, with spider silk (poly-alanine) slightly outperforming Bombyx mori silk ((Gly-Ala)n). All-atom force distribution analysis reveals both intrasheet hydrogen-bonding and intersheet side-chain interactions to contribute to stability to similar extent. In combination with finite element analysis of simplified β-sheet skeletons, we could ascribe the distinct force distribution pattern of the antiparallel and parallel silk crystalline units to the difference in hydrogen-bond geometry, featuring an in-line or zigzag arrangement, respectively. Hydrogen-bond strength was higher in antiparallel models, and ultimately resulted in higher stiffness of the crystal, compensating the effect of the mechanically disadvantageous in-line hydrogen-bond geometry. Atomistic and coarse-grained force distribution patterns can thus explain differences in mechanical response of silk crystals, opening up the road to predict full fiber mechanics. PMID:19450471

  3. Finger force perception during ipsilateral and contralateral force matching tasks

    PubMed Central

    Park, Woo-Hyung; Leonard, Charles T.; Li, Sheng

    2010-01-01

    The aims of the present study were to compare matching performance between ipsilateral and contralateral finger force matching tasks and to examine the effect of handedness on finger force perception. Eleven subjects were instructed to produce reference forces by an instructed finger (index – I or little – L finger) and to reproduce the same amount force by the same or a different finger within the hand (i.e., ipsilateral matching task), or by a finger of the other hand (i.e., contralateral matching task). The results of the ipsilateral and contralateral tasks in the present study commonly showed that 1) the reference and matching forces were matched closely when the two forces were produced by the same or homologous finger(s) such as I/I task; 2) the weaker little finger underestimated the magnitude of reference force of the index finger (I/L task), even with the higher level of effort (relative force), but the two forces were matched when considering total finger forces; 3) the stronger index finger closely matched the reference force of the little finger with the lower level of relative force (i.e., L/I task); 4) when considering the constant errors, I/L tasks showed an underestimation and L/I tasks showed an overestimation compared to I/I tasks. There was no handedness effect during ipsilateral tasks. During the contralateral task, the dominant hand overestimated the force of the non-dominant hand, while the non-dominant hand attempted to match the absolute force of the dominant hand. The overall results support the notion that the absolute, rather than relative, finger force is perceived and reproduced during ipsilateral and contralateral finger force matching tasks, indicating the uniqueness of finger force perception. PMID:18488212

  4. Multiple stepwise pattern for potential of mean force in unfolding the thrombin binding aptamer in complex with Sr2+

    NASA Astrophysics Data System (ADS)

    Yang, Changwon; Jang, Soonmin; Pak, Youngshang

    2011-12-01

    Using all-atom molecular dynamics simulation in conjunction with umbrella sampling, we obtained the unfolding free energy and the force extension profiles of the thrombin binding DNA aptamer (15-TBA) in complex with Sr2+ (Protein Data Bank code: 1RDE). The resulting potential of mean force (PMF) displays a multiple stepwise pattern with distinct plateau regions. The detailed analysis of the simulation result indicated that each plateau was created by the interplay of the metal ion interacting with self-arranging guanine bases and the successive uptakes of water molecules. The current PMF simulation provides a quantitative description of the unfolding process of 15-TBA DNA driven by stretching and gives molecular insight on its detailed changes of base pair interactions in the presence of the metal cation.

  5. Transformation of the dihedral corrective map for D-amino residues using the CHARMM force field

    NASA Astrophysics Data System (ADS)

    Turpin, Eleanor R.; Hirst, Jonathan D.

    2012-08-01

    Molecular dynamics simulations in explicit solvent were performed on two peptides and two proteins containing D-amino residues, using three implementations of the CHARMM22 all-atom force field: (a) with the standard CMAP corrective term, (b) neglecting the correction entirely and (c) using a transformation of the CMAP grid (φ, ψ) → (-φ, -ψ) for the D-amino residues. The transformed map led to sampling of conformations which are closest to the X-ray crystallographic structures for D-amino residues and the standard CMAP correction destabilises D-amino secondary structure. Thus, the transformation of the CMAP term is needed to simulate proteins and peptides containing D-amino residues correctly.

  6. 76 FR 11307 - Small Business Information Security Task Force

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-01

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS... scope requirements for the Task Force with specific questions of Identity Theft, Privacy, and Government Contracting information. Additionally, resource and staffing issues to support the work of the Task Force...

  7. Potential of mean force of association of large hydrophobic particles: toward the nanoscale limit.

    PubMed

    Makowski, Mariusz; Czaplewski, Cezary; Liwo, Adam; Scheraga, Harold A

    2010-01-21

    The potentials of mean force (PMFs) were determined, in both water with the TIP3P water model and in vacuo, for systems involving formation of nonpolar dimers composed of bicyclooctane, adamantane (both an all-atom model and a sphere with the radius of 3.4 A representing adamantane), and fullerene, respectively. A series of umbrella-sampling molecular dynamics simulations with the AMBER force field were carried out for each pair under both environmental conditions. The PMFs were calculated by using the weighted histogram analysis method. The results were compared with our previously determined PMF for neopentane. The shape of the PMFs for dimers of all four nonpolar molecules is characteristic of hydrophobic interactions with contact and solvent-separated minima and desolvation maxima. The positions of all these minima and maxima change with the size of the nonpolar molecule; for larger molecules they shift toward larger distances. Comparison of the PMFs of the bicyclooctane, adamantane, and fullerene dimers in water and in vacuo shows that hydrophobic interactions in each dimer are different from that for the dimer of neopentane. Interactions in the bicyclooctane, adamantane, and fullerene dimers are stronger in vacuo than in water. These dimers cannot be treated as classical, spherical, hydrophobic objects. The solvent contribution to the PMF was also computed by subtracting the PMF determined in vacuo from that in explicit solvent. The solvent contribution to the PMFs of bicyclooctane, adamantane, and fullerene is positive, as opposed to that of neopentane. The water molecules in the first solvation sphere of both adamantane and neopentane dimers are more ordered as compared to bulk water, with their dipole moments pointing away from the surface of the dimers. The average number of hydrogen bonds per water molecule in the first hydration shell of adamantane is smaller compared to that in bulk water, but this shell is thicker for all-atom adamantane than for

  8. Quantification of Staphylococcus aureus adhesion forces on various dental restorative materials using atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Merghni, Abderrahmen; Kammoun, Dorra; Hentati, Hajer; Janel, Sébastien; Popoff, Michka; Lafont, Frank; Aouni, Mahjoub; Mastouri, Maha

    2016-08-01

    In the oral cavity dental restorative biomaterials can act as a reservoir for infection with opportunistic Staphylococcus aureus pathogen, which can lead to the occurrence of secondary caries and treatment failures. Our aim was to evaluate the adhesion forces by S. aureus on four dental restorative biomaterials and to correlate this finding to differences in specific surface characteristics. Additionally, the influence of salivary conditioning films in exerted adhesion forces was investigated. The substrate hydrophobicity was measured by goniometer and the surface free energy was calculated using the equilibrium advancing contact angle values of water, formamide, and diiodomethane on the tested surfaces. The surface roughness was determined using atomic force microscope (AFM). Additionally, cell force spectroscopy was achieved to quantify the forces that drive cell-substrate interactions. S. aureus bacterium exerted a considerable adhesion forces on various dental restorative materials, which decreased in the presence of saliva conditioning film. The influence of the surface roughness and free energy in initial adhesion appears to be more important than the effect of hydrophobicity, either in presence or absence of saliva coating. Hence, control of surface properties of dental restorative biomaterials is of crucial importance in preventing the attachment and subsequent the biofilm formation.

  9. Air Force construction automation/robotics

    NASA Technical Reports Server (NTRS)

    Nease, AL; Dusseault, Christopher

    1994-01-01

    The Air Force has several unique requirements that are being met through the development of construction robotic technology. The missions associated with these requirements place construction/repair equipment operators in potentially harmful situations. Additionally, force reductions require that human resources be leveraged to the maximum extent possible and that more stringent construction repair requirements push for increased automation. To solve these problems, the U.S. Air Force is undertaking a research and development effort at Tyndall AFB, FL to develop robotic teleoperation, telerobotics, robotic vehicle communications, automated damage assessment, vehicle navigation, mission/vehicle task control architecture, and associated computing environment. The ultimate goal is the fielding of robotic repair capability operating at the level of supervised autonomy. The authors of this paper will discuss current and planned efforts in construction/repair, explosive ordnance disposal, hazardous waste cleanup, fire fighting, and space construction.

  10. Atomic Force Microscope

    SciTech Connect

    Day, R.D.; Russell, P.E.

    1988-12-01

    The Atomic Force Microscope (AFM) is a recently developed instrument that has achieved atomic resolution imaging of both conducting and non- conducting surfaces. Because the AFM is in the early stages of development, and because of the difficulty of building the instrument, it is currently in use in fewer than ten laboratories worldwide. It promises to be a valuable tool for obtaining information about engineering surfaces and aiding the .study of precision fabrication processes. This paper gives an overview of AFM technology and presents plans to build an instrument designed to look at engineering surfaces.

  11. Causal Entropic Forces

    NASA Astrophysics Data System (ADS)

    Wissner-Gross, A. D.; Freer, C. E.

    2013-04-01

    Recent advances in fields ranging from cosmology to computer science have hinted at a possible deep connection between intelligence and entropy maximization, but no formal physical relationship between them has yet been established. Here, we explicitly propose a first step toward such a relationship in the form of a causal generalization of entropic forces that we find can cause two defining behaviors of the human “cognitive niche”—tool use and social cooperation—to spontaneously emerge in simple physical systems. Our results suggest a potentially general thermodynamic model of adaptive behavior as a nonequilibrium process in open systems.

  12. Turbulent forced diffusion flames

    SciTech Connect

    Arpaci, V.S.; Li, C.Y.

    1995-07-01

    It is the purpose of this study to introduce a turbulent microscale appropriate for forced diffusion flames and to propose models for fuel consumption and skin friction in terms of this scale. The study consists of four sections. Following the introduction, Section 2 recapitulates the laminar theories of reacting boundary layers in terms of dimensional arguments and proposes models for fuel consumption and skin friction. Section 3 extends these arguments by introducing a microscale appropriate for turbulent flames and, in terms of this scale, develops models for fuel consumption and skin friction, correlates the experimental data on skin friction, and Section 4 concludes the study.

  13. Radiative forcing of climate

    NASA Technical Reports Server (NTRS)

    Ramanswamy, V.; Shine, Keith; Leovy, Conway; Wang, Wei-Chyung; Rodhe, Henning; Wuebbles, Donald J.; Ding, M.; Lelieveld, Joseph; Edmonds, Jae A.; Mccormick, M. Patrick

    1991-01-01

    An update of the scientific discussions presented in Chapter 2 of the Intergovernmental Panel on Climate Change (IPCC) report is presented. The update discusses the atmospheric radiative and chemical species of significance for climate change. There are two major objectives of the present update. The first is an extension of the discussion on the Global Warming Potentials (GWP's), including a reevaluation in view of the updates in the lifetimes of the radiatively active species. The second important objective is to underscore major developments in the radiative forcing of climate due to the observed stratospheric ozone losses occurring between 1979 and 1990.

  14. 75 FR 81591 - U.S. Air Force Scientific Advisory Board Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ... of the Air Force. In addition, the SAB will discuss and reach a consensus on the results of the Air Force Research Laboratory Science and Technology FY11 Review. Pursuant to 5 U.S.C. 552b, as amended,...

  15. Influence of maglev force relaxation on the forces of bulk HTSC subjected to different lateral displacements above the NdFeB guideway

    NASA Astrophysics Data System (ADS)

    Qin, Yujie; Hou, Xiaojing

    2011-02-01

    This paper studied the influence of maglev force relaxation on the force (both levitation and guidance forces) of bulk high-temperature superconductor (HTSC) subjected to different lateral displacements above a NdFeB guideway. Firstly, the maglev forces relaxation property of bulk HTSC above the permanent-magnet guideway (PMG) was studied experimentally, then the levitation and guidance forces were measured by SCML-2 measurement system synchronously at different lateral displacements, some times later(after relaxation), the forces were measured again as the same way. Compared to the two measured results, it was found that the change of the levitation force was larger compared to the case without relaxation, while the change of the guidance force was smaller. In addition, the rate of change of levitation force and guidance force was different for different maximum lateral displacements. This work provided a scientific analysis for the practical application of the bulk HTS.

  16. Forces stabilizing proteins.

    PubMed

    Nick Pace, C; Scholtz, J Martin; Grimsley, Gerald R

    2014-06-27

    The goal of this article is to summarize what has been learned about the major forces stabilizing proteins since the late 1980s when site-directed mutagenesis became possible. The following conclusions are derived from experimental studies of hydrophobic and hydrogen bonding variants. (1) Based on studies of 138 hydrophobic interaction variants in 11 proteins, burying a -CH2- group on folding contributes 1.1±0.5 kcal/mol to protein stability. (2) The burial of non-polar side chains contributes to protein stability in two ways: first, a term that depends on the removal of the side chains from water and, more importantly, the enhanced London dispersion forces that result from the tight packing in the protein interior. (3) Based on studies of 151 hydrogen bonding variants in 15 proteins, forming a hydrogen bond on folding contributes 1.1±0.8 kcal/mol to protein stability. (4) The contribution of hydrogen bonds to protein stability is strongly context dependent. (5) Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. (6) Polar group burial can make a favorable contribution to protein stability even if the polar group is not hydrogen bonded. (7) Hydrophobic interactions and hydrogen bonds both make large contributions to protein stability.

  17. Magnetic force microscopy

    PubMed Central

    Passeri, Daniele; Dong, Chunhua; Reggente, Melania; Angeloni, Livia; Barteri, Mario; Scaramuzzo, Francesca A; De Angelis, Francesca; Marinelli, Fiorenzo; Antonelli, Flavia; Rinaldi, Federica; Marianecci, Carlotta; Carafa, Maria; Sorbo, Angela; Sordi, Daniela; Arends, Isabel WCE; Rossi, Marco

    2014-01-01

    Magnetic force microscopy (MFM) is an atomic force microscopy (AFM) based technique in which an AFM tip with a magnetic coating is used to probe local magnetic fields with the typical AFM spatial resolution, thus allowing one to acquire images reflecting the local magnetic properties of the samples at the nanoscale. Being a well established tool for the characterization of magnetic recording media, superconductors and magnetic nanomaterials, MFM is finding constantly increasing application in the study of magnetic properties of materials and systems of biological and biomedical interest. After reviewing these latter applications, three case studies are presented in which MFM is used to characterize: (i) magnetoferritin synthesized using apoferritin as molecular reactor; (ii) magnetic nanoparticles loaded niosomes to be used as nanocarriers for drug delivery; (iii) leukemic cells labeled using folic acid-coated core-shell superparamagnetic nanoparticles in order to exploit the presence of folate receptors on the cell membrane surface. In these examples, MFM data are quantitatively analyzed evidencing the limits of the simple analytical models currently used. Provided that suitable models are used to simulate the MFM response, MFM can be used to evaluate the magnetic momentum of the core of magnetoferritin, the iron entrapment efficiency in single vesicles, or the uptake of magnetic nanoparticles into cells. PMID:25050758

  18. Pairing forces in nuclei

    SciTech Connect

    Chasman, R.R.

    1996-12-31

    In this contribution, the author mentions some features of pairing forces that are unique to nuclei and cover some areas of major interest in nuclear structure research, that involve pairing. At the level of most nuclear structure studies, nuclei are treated as consisting of two kinds of fermions (protons and neutrons) in a valence space with rather few levels. These features give rise to unique aspects of pairing forces in nuclei: (1) n-p pairing in T = 0 as well as the usual T = 1 pairing that is characteristic of like fermions; (2) a need to correct pairing calculations for the (1/N) effects that can typically be neglected in superconducting solids. An issue of current concern is the nature of the pairing interaction: several recent studies suggest a need for a density dependent form of the pairing interaction. There is a good deal of feedback between the questions of accurate calculations of pairing interactions and the form and magnitude of the pairing interaction. Finally, the authors discuss some many-body wave functions that are a generalization of the BCS wave function form, and apply them to a calculation of energy level spacings in superdeformed rotational bands.

  19. Forces Stabilizing Proteins

    PubMed Central

    Pace, C. Nick; Scholtz, J. Martin; Grimsley, Gerald R.

    2014-01-01

    The goal of this article is to summarize what has been learned about the major forces stabilizing proteins since the late 1980s when site-directed mutagenesis became possible. The following conclusions are derived from experimental studies of hydrophobic and hydrogen bonding variants. 1. Based on studies of 138 hydrophobic interaction variants in 11 proteins, burying a –CH2– group on folding contributes 1.1 ± 0.5 kcal/mol to protein stability. 2. The burial of nonpolar side chains contributes to protein stability in two ways: first, a term that depends on the removal of the side chains from water and, more importantly, the enhanced London dispersion forces that result from the tight packing in the protein interior. 3. Based on studies of 151 hydrogen bonding variants in 15 proteins, forming a hydrogen bond on folding contributes 1.1 ± 0.8 kcal/mol to protein stability. 4. The contribution of hydrogen bonds to protein stability is strongly context dependent. 5. Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. 6. Polar group burial can make a favorable contribution to protein stability even if the polar group is not hydrogen bonded. 7. Hydrophobic interactions and hydrogen bonds both make large contributions to protein stability. PMID:24846139

  20. Environmental Crack Driving Force

    NASA Astrophysics Data System (ADS)

    Hall, M. M.

    2013-03-01

    The effect of environment on the crack driving force is considered, first by assuming quasistatic extension of a stationary crack and second, by use of stress corrosion cracking (SCC) crack growth rate models developed previously by this author and developed further here. A quasistatic thermodynamic energy balance approach, of the Griffith-Irwin type, is used to develop stationary crack threshold expressions, tilde{J}_c , which represent the conjoint mechanical and electrochemical conditions, below which stationary cracks are stable. Expressions for the electrochemical crack driving force (CDF) were derived using an analysis that is analogous to that used by Irwin to derive his "strain energy release rate," G, which Rice showed as being equivalent to his mechanical CDF, J. The derivations show that electrochemical CDFs both for active path dissolution (APD) and hydrogen embrittlement (HE) mechanisms of SCC are simply proportional to Tafel's electrochemical anodic and cathodic overpotentials, η a and η c, respectively. Phenomenological SCC models based on the kinetics of APD and HE crack growth are used to derive expressions for the kinetic threshold, J scc, below which crack growth cannot be sustained. These models show how independent mechanical and environmental CDFs may act together to drive SCC crack advance. Development of a user-friendly computational tool for calculating Tafel's overpotentials is advocated.

  1. Force normalization in paraplegics.

    PubMed

    Serra-Añó, P; García-Massó, X; Pellicer, M; González, L-M; López-Pascual, J; Giner-Pascual, M; Toca-Herrera, J L

    2012-06-01

    The principal aim of our study was the determination of the effectiveness of a standardized ratio, allometric scaling model and a gamma function model in normalizing the isometric torque data of spinal cord patients and healthy subjects. For this purpose we studied a sample of 21 healthy males and 23 spinal cord injury males. The experiment consisted of the measurement of the force of the upper limb movement executed by all the subjects. We also determined anthropometric variables with dual-energy x-ray absorptiometry. The experimental data were analyzed with 3 force normalization methods. Our results indicate that the most important confounding variable was the fat free mass of the dominant upper limb (r>0.36, p<0.05). With the standardization by body mass and allometric scaling model, the normalized torque was influenced by body size variables. However, the normalized torque by the gamma function model was independent of body size measures. Paraplegics were weaker (p<0.05) in extension movements when the data were normalized by the gamma function model. In summary, this study shows that the gamma function model with fat free mass of the dominant upper limb was more effective than the standardized ratio in removing the influence of body size variables. PMID:22377940

  2. Forced emigration, favourable outcomes.

    PubMed

    Pearn, J

    2001-10-01

    The discipline of public health and preventive medicine in Australia and New Zealand had its genesis in the advocacy of 18th and 19th century military pioneers. Military (Royal Navy and British Army) surgeons were posted to Australia as part of their non-discretionary duty. Civilian doctors emigrated variously for adventure, escapism and gold fever. One group, a particularly influential group disproportionate to their numbers, came in one sense as forced emigrants because of chronic respiratory disease in general, and tuberculosis in particular. Tuberculosis was an occupational hazard of 19th century medical and surgical practice throughout western Europe. This paper analyses six examples of such emigration which had, perhaps unforeseen at the time, significant results in the advancement of public health. Such emigration was in one sense voluntary, but in another was forced upon the victims in their quest for personal survival. In Australia, such medical individuals became leading advocates and successful catalysts for change in such diverse fields as social welfare, public health, the preventive aspects of medical practice, child health, nutrition and medical education. A number of such public health pioneers today have no physical memorials; but their influence is to be seen in the ethos of medical practice in Australia and New Zealand today. Their memory is further perpetuated in the names of Australian native wildflowers and trees that symbolise not only a healthy environment but the long-term investment, accrued with interest, of the institution of public health measures for which their advocacy achieved much success.

  3. Force reflecting hand controller

    NASA Technical Reports Server (NTRS)

    Mcaffee, Douglas A. (Inventor); Snow, Edward R. (Inventor); Townsend, William T. (Inventor)

    1993-01-01

    A universal input device for interfacing a human operator with a slave machine such as a robot or the like includes a plurality of serially connected mechanical links extending from a base. A handgrip is connected to the mechanical links distal from the base such that a human operator may grasp the handgrip and control the position thereof relative to the base through the mechanical links. A plurality of rotary joints is arranged to connect the mechanical links together to provide at least three translational degrees of freedom and at least three rotational degrees of freedom of motion of the handgrip relative to the base. A cable and pulley assembly for each joint is connected to a corresponding motor for transmitting forces from the slave machine to the handgrip to provide kinesthetic feedback to the operator and for producing control signals that may be transmitted from the handgrip to the slave machine. The device gives excellent kinesthetic feedback, high-fidelity force/torque feedback, a kinematically simple structure, mechanically decoupled motion in all six degrees of freedom, and zero backlash. The device also has a much larger work envelope, greater stiffness and responsiveness, smaller stowage volume, and better overlap of the human operator's range of motion than previous designs.

  4. Force reflecting hand controller

    NASA Astrophysics Data System (ADS)

    McAffee, Douglas A.; Snow, Edward R.; Townsend, William T.

    1993-03-01

    A universal input device for interfacing a human operator with a slave machine such as a robot or the like includes a plurality of serially connected mechanical links extending from a base. A handgrip is connected to the mechanical links distal from the base such that a human operator may grasp the handgrip and control the position thereof relative to the base through the mechanical links. A plurality of rotary joints is arranged to connect the mechanical links together to provide at least three translational degrees of freedom and at least three rotational degrees of freedom of motion of the handgrip relative to the base. A cable and pulley assembly for each joint is connected to a corresponding motor for transmitting forces from the slave machine to the handgrip to provide kinesthetic feedback to the operator and for producing control signals that may be transmitted from the handgrip to the slave machine. The device gives excellent kinesthetic feedback, high-fidelity force/torque feedback, a kinematically simple structure, mechanically decoupled motion in all six degrees of freedom, and zero backlash. The device also has a much larger work envelope, greater stiffness and responsiveness, smaller stowage volume, and better overlap of the human operator's range of motion than previous designs.

  5. High-Resolution Traction Force Microscopy

    PubMed Central

    Plotnikov, Sergey V.; Sabass, Benedikt; Schwarz, Ulrich S.; Waterman, Clare M.

    2015-01-01

    Cellular forces generated by the actomyosin cytoskeleton and transmitted to the extracellular matrix (ECM) through discrete, integrin-based protein assemblies, that is, focal adhesions, are critical to developmental morphogenesis and tissue homeostasis, as well as disease progression in cancer. However, quantitative mapping of these forces has been difficult since there has been no experimental technique to visualize nanonewton forces at submicrometer spatial resolution. Here, we provide detailed protocols for measuring cellular forces exerted on two-dimensional elastic substrates with a high-resolution traction force microscopy (TFM) method. We describe fabrication of polyacrylamide substrates labeled with multiple colors of fiducial markers, functionalization of the substrates with ECM proteins, setting up the experiment, and imaging procedures. In addition, we provide the theoretical background of traction reconstruction and experimental considerations important to design a high-resolution TFM experiment. We describe the implementation of a new algorithm for processing of images of fiducial markers that are taken below the surface of the substrate, which significantly improves data quality. We demonstrate the application of the algorithm and explain how to choose a regularization parameter for suppression of the measurement error. A brief discussion of different ways to visualize and analyze the results serves to illustrate possible uses of high-resolution TFM in biomedical research. PMID:24974038

  6. Force-Field Parameter Fitter

    SciTech Connect

    2015-05-27

    ParFit is a flexible and extendable framework and library of classes for fitting force-field parameters to data from high-level ab-initio calculations on the basis of deterministic and stochastic algorithms. Currently, the code is fitting MM3 and Merck force-field parameters but could easily extend to other force-field types.

  7. Proximal arm kinematics affect grip force-load force coordination.

    PubMed

    Vermillion, Billy C; Lum, Peter S; Lee, Sang Wook

    2015-10-01

    During object manipulation, grip force is coordinated with load force, which is primarily determined by object kinematics. Proximal arm kinematics may affect grip force control, as proximal segment motion could affect control of distal hand muscles via biomechanical and/or neural pathways. The aim of this study was to investigate the impact of proximal kinematics on grip force modulation during object manipulation. Fifteen subjects performed three vertical lifting tasks that involved distinct proximal kinematics (elbow/shoulder), but resulted in similar end-point (hand) trajectories. While temporal coordination of grip and load forces remained similar across the tasks, proximal kinematics significantly affected the grip force-to-load force ratio (P = 0.042), intrinsic finger muscle activation (P = 0.045), and flexor-extensor ratio (P < 0.001). Biomechanical coupling between extrinsic hand muscles and the elbow joint cannot fully explain the observed changes, as task-related changes in intrinsic hand muscle activation were greater than in extrinsic hand muscles. Rather, between-task variation in grip force (highest during task 3) appears to contrast to that in shoulder joint velocity/acceleration (lowest during task 3). These results suggest that complex neural coupling between the distal and proximal upper extremity musculature may affect grip force control during movements, also indicated by task-related changes in intermuscular coherence of muscle pairs, including intrinsic finger muscles. Furthermore, examination of the fingertip force showed that the human motor system may attempt to reduce variability in task-relevant motor output (grip force-to-load force ratio), while allowing larger fluctuations in output less relevant to task goal (shear force-to-grip force ratio). PMID:26289460

  8. Proximal arm kinematics affect grip force-load force coordination

    PubMed Central

    Vermillion, Billy C.; Lum, Peter S.

    2015-01-01

    During object manipulation, grip force is coordinated with load force, which is primarily determined by object kinematics. Proximal arm kinematics may affect grip force control, as proximal segment motion could affect control of distal hand muscles via biomechanical and/or neural pathways. The aim of this study was to investigate the impact of proximal kinematics on grip force modulation during object manipulation. Fifteen subjects performed three vertical lifting tasks that involved distinct proximal kinematics (elbow/shoulder), but resulted in similar end-point (hand) trajectories. While temporal coordination of grip and load forces remained similar across the tasks, proximal kinematics significantly affected the grip force-to-load force ratio (P = 0.042), intrinsic finger muscle activation (P = 0.045), and flexor-extensor ratio (P < 0.001). Biomechanical coupling between extrinsic hand muscles and the elbow joint cannot fully explain the observed changes, as task-related changes in intrinsic hand muscle activation were greater than in extrinsic hand muscles. Rather, between-task variation in grip force (highest during task 3) appears to contrast to that in shoulder joint velocity/acceleration (lowest during task 3). These results suggest that complex neural coupling between the distal and proximal upper extremity musculature may affect grip force control during movements, also indicated by task-related changes in intermuscular coherence of muscle pairs, including intrinsic finger muscles. Furthermore, examination of the fingertip force showed that the human motor system may attempt to reduce variability in task-relevant motor output (grip force-to-load force ratio), while allowing larger fluctuations in output less relevant to task goal (shear force-to-grip force ratio). PMID:26289460

  9. Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors.

    PubMed

    Mosayebi, Majid; Louis, Ard A; Doye, Jonathan P K; Ouldridge, Thomas E

    2015-12-22

    The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced rupture of short DNA duplexes, a system that has been given new importance by recently designed force sensors and nanotechnological devices. We argue that rupture must be understood as an activated process, where the duplex state is metastable and the strands will separate in a finite time that depends on the duplex length and the force applied. Thus, the critical shearing force required to rupture a duplex depends strongly on the time scale of observation. We use simple models of DNA to show that this approach naturally captures the observed dependence of the force required to rupture a duplex within a given time on duplex length. In particular, this critical force is zero for the shortest duplexes, before rising sharply and then plateauing in the long length limit. The prevailing approach, based on identifying when the presence of each additional base pair within the duplex is thermodynamically unfavorable rather than allowing for metastability, does not predict a time-scale-dependent critical force and does not naturally incorporate a critical force of zero for the shortest duplexes. We demonstrate that our findings have important consequences for the behavior of a new force-sensing nanodevice, which operates in a mixed mode that interpolates between shearing and unzipping. At a fixed time scale and duplex length, the critical force exhibits a sigmoidal dependence on the fraction of the duplex that is subject to shearing.

  10. Force interactions between magnetite, silica, and bentonite studied with atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Dobryden, I.; Potapova, E.; Holmgren, A.; Weber, H.; Hedlund, J.; Almqvist, N.

    2015-04-01

    Iron ore pellets consist of variety of mineral particles and are an important refined product used in steel manufacturing. Production of high-quality pellets requires good understanding of interactions between different constituents, such as magnetite, gangue residues, bentonite, and additives. Much research has been reported on magnetite, silica, and bentonite surface properties and their effect on pellet strength but more scant with a focus on a fundamental particle-particle interaction. To probe such particle interaction, atomic force microscopy (AFM) using colloidal probe technique has proven to be a suitable tool. In this work, the measurements were performed between magnetite-magnetite, bentonite-magnetite, silica-bentonite, and silica-magnetite particles in 1 mM CaCl2 solution at various pH values. The interaction character, i.e., repulsion or attraction, was determined by measuring and analyzing AFM force curves. The observed quantitative changes in interaction forces were in good agreement with the measured zeta-potentials for the particles at the same experimental conditions. Particle aggregation was studied by measuring the adhesion force. Absolute values of adhesion forces for different systems could not be compared due to the difference in particle size and contact geometry. Therefore, the relative change of adhesion force between pH 6 and 10 was used for comparison. The adhesion force decreased for the magnetite-magnetite and bentonite-silica systems and slightly increased for the magnetite-bentonite system at pH 10 as compared to pH 6, whereas a pronounced decrease in adhesion force was observed in the magnetite-silica system. Thus, the presence of silica particles on the magnetite surface could have a negative impact on the interaction between magnetite and bentonite in balling due to the reduction of the adhesion force.

  11. Parallel computation with the force

    NASA Technical Reports Server (NTRS)

    Jordan, H. F.

    1985-01-01

    A methodology, called the force, supports the construction of programs to be executed in parallel by a force of processes. The number of processes in the force is unspecified, but potentially very large. The force idea is embodied in a set of macros which produce multiproceossor FORTRAN code and has been studied on two shared memory multiprocessors of fairly different character. The method has simplified the writing of highly parallel programs within a limited class of parallel algorithms and is being extended to cover a broader class. The individual parallel constructs which comprise the force methodology are discussed. Of central concern are their semantics, implementation on different architectures and performance implications.

  12. Updates on Force Limiting Improvements

    NASA Technical Reports Server (NTRS)

    Kolaini, Ali R.; Scharton, Terry

    2013-01-01

    The following conventional force limiting methods currently practiced in deriving force limiting specifications assume one-dimensional translation source and load apparent masses: Simple TDOF model; Semi-empirical force limits; Apparent mass, etc.; Impedance method. Uncorrelated motion of the mounting points for components mounted on panels and correlated, but out-of-phase, motions of the support structures are important and should be considered in deriving force limiting specifications. In this presentation "rock-n-roll" motions of the components supported by panels, which leads to a more realistic force limiting specifications are discussed.

  13. Can Strained Hydrocarbons Be "Forced" To Be Stable?

    PubMed

    Stauch, Tim; Günther, Benjamin; Dreuw, Andreas

    2016-09-15

    Many strained hydrocarbons are prone to isomerization, dimerization, and trimerization under normal laboratory conditions. Here we investigate a method to stabilize angle-strained cycloalkynes by applying a mechanical pulling force to the carbon atoms adjacent to the triple bond, which partially linearizes the C≡C-C bond angles. We discuss various methods of applying such pulling forces, including photoswitches and incorporation into additional strained macrocycles. We use the computational JEDI (Judgement of Energy DIstribution) analysis to quantify the distribution of energy in strained cycloheptyne and judge the change in stability upon application of an external force via isodesmic and homodesmotic reactions. We find that cycloheptyne can indeed be stabilized by external forces. However, the force generated by photoswitches during isomerization is too low to lead to a significant stabilization of the molecule. Hence, stronger forces are needed, which can be achieved by incorporating cycloheptyne into a second strained macrocycle. PMID:27580048

  14. Forced to be right.

    PubMed

    Trout, J D

    2014-05-01

    In "Forced to be Free", Neil Levy surveys the raft of documented decision-making biases that humans are heir to, and advances several bold proposals designed to enhance the patient's judgment. Gratefully, Levy is moved by the psychological research on judgment and decision-making that documents people's inaccuracy when identifying courses of action will best promote their subjective well-being. But Levy is quick to favour the patient's present preferences, to ensure they get "final say" about their treatment. I urge the opposite inclination, raising doubts about whether the patient's "present preferences" are the best expression of their "final say". When there is adequate evidence that people, by their own lights, overemphasize their present preferences about the future, we should carefully depreciate those preferences, in effect biasing them to make the right decision by their own lights.

  15. [Galileo and centrifugal force].

    PubMed

    Vilain, Christiane

    This work intends to focus on Galileo's study of what is now called "centrifugal force," within the framework of the Second Day of his Dialogo written in 1632, rather than on the previously published commentaries on the topic. Galileo proposes three geometrical demonstrations in order to prove that gravity will always overcome centrifugalforce, and that the potential rotation of the Earth, whatever its speed, cannot in any case project objects beyond it. Each of these demonstrations must consequently contain an error and it has seemed to us that the first one had not been understood up until now. Our analysis offers an opportunity to return to Galileo's geometrical representation of dynamical questions; actually, we get an insight into the sophistication of Galileo's practices more than into his mistakes. Our second point, concerning the historiography of the problem, shows an evolution from anachronic critics to more contextual considerations, in the course of the second half of the twentieth century. PMID:25029818

  16. Silicon force sensor

    DOEpatents

    Galambos, Paul C.; Crenshaw, Thomas B.; Nishida, Erik E.; Burnett, Damon J.; Lantz, Jeffrey W.

    2016-07-05

    The various technologies presented herein relate to a sensor for measurement of high forces and/or high load shock rate(s), whereby the sensor utilizes silicon as the sensing element. A plate of Si can have a thinned region formed therein on which can be formed a number of traces operating as a Wheatstone bridge. The brittle Si can be incorporated into a layered structure comprising ductile and/or compliant materials. The sensor can have a washer-like configuration which can be incorporated into a nut and bolt configuration, whereby tightening of the nut and bolt can facilitate application of a compressive preload upon the sensor. Upon application of an impact load on the bolt, the compressive load on the sensor can be reduced (e.g., moves towards zero-load), however the magnitude of the preload can be such that the load on the sensor does not translate to tensile stress being applied to the sensor.

  17. [Galileo and centrifugal force].

    PubMed

    Vilain, Christiane

    This work intends to focus on Galileo's study of what is now called "centrifugal force," within the framework of the Second Day of his Dialogo written in 1632, rather than on the previously published commentaries on the topic. Galileo proposes three geometrical demonstrations in order to prove that gravity will always overcome centrifugalforce, and that the potential rotation of the Earth, whatever its speed, cannot in any case project objects beyond it. Each of these demonstrations must consequently contain an error and it has seemed to us that the first one had not been understood up until now. Our analysis offers an opportunity to return to Galileo's geometrical representation of dynamical questions; actually, we get an insight into the sophistication of Galileo's practices more than into his mistakes. Our second point, concerning the historiography of the problem, shows an evolution from anachronic critics to more contextual considerations, in the course of the second half of the twentieth century.

  18. Force Limit System

    NASA Technical Reports Server (NTRS)

    Pawlik, Ralph; Krause, David; Bremenour, Frank

    2011-01-01

    The Force Limit System (FLS) was developed to protect test specimens from inadvertent overload. The load limit value is fully adjustable by the operator and works independently of the test system control as a mechanical (non-electrical) device. When a test specimen is loaded via an electromechanical or hydraulic test system, a chance of an overload condition exists. An overload applied to a specimen could result in irreparable damage to the specimen and/or fixturing. The FLS restricts the maximum load that an actuator can apply to a test specimen. When testing limited-run test articles or using very expensive fixtures, the use of such a device is highly recommended. Test setups typically use electronic peak protection, which can be the source of overload due to malfunctioning components or the inability to react quickly enough to load spikes. The FLS works independently of the electronic overload protection.

  19. Forced Migration: Refugee Populations

    PubMed Central

    Boyle, Joyceen S.

    2015-01-01

    Undocumented migration is a global phenomenon that manifests in various contexts. This article describes the impact of the movement of large numbers of people in several African countries, producing a unique type of migrant—the refugee. We describe issues that refugee movements create on fragile health care systems, situations that precipitate refugee movements, certain human rights violations that are of particular concern such as gender based violence (GBV) and child soldiers, and lastly, implications for nursing practice and policy. We use examples from several countries in Sub-Saharan Africa, including the Democratic Republic of the Congo, Rwanda, Liberia, Sierra Leone, and Mozambique. Drawing on key documents from the United Nations High Commissioner for Refugees, current literature, as well as the international experience of the authors, this article presents an overview of forced migration and discusses opportunities for nurses to impact research, practice and policy related to refugee health. PMID:25645484

  20. Force protection: today's reality.

    PubMed

    Torgerson, Ron

    2004-11-11

    Most US infrastructure and major chemical manufacturing facilities as well as their supporting utility systems are inherently vulnerable to a terrorist attack. Force protection is a military and civilian term used to protect personnel and critical facilities and assets against would-be aggressors or terrorists. The war on terrorism is a 200-300-year war. Terrorist attacks on US soil could become as common-place as in the State of Israel. It is very easy to penetrate infrastructure or plants as evidenced by vulnerability assessments performed for states, cities, plants, and military facilities by Versar and others around the country. Chemical, biological, radiological, nuclear, and explosive weapons can be readily used to attack facilities in the US. This paper will explain some of those vulnerabilities, outline the current DoD standard as it relates to vulnerability assessments, and explain how this may be used in commercial applications to deter potential aggressors.

  1. Comparison between static maximal force and handbrake pulling force.

    PubMed

    Chateauroux, E; Wang, X

    2012-01-01

    The measurement of maximum pulling force is important not only for specifying force limit of industrial workers but also for designing controls requiring high force. This paper presents a comparison between maximal static handbrake pulling force (FST) and force exerted during normal handbrake pulling task (FDY). These forces were measured for different handle locations and subject characteristics. Participants were asked to pull a handbrake on an adjustable car mock-up as they would do when parking their own car, then to exert a force as high as possible on the pulled handbrake. Hand pulling forces were measured using a six-axes force sensor. 5 fixed handbrake positions were tested as well as a neutral handbrake position defined by the subject. FST and FDY were significantly correlated. Both were found to be dependent on handbrake position, age and gender. As expected, women and older subjects exerted lower forces. FST was significantly higher than FDY. The ratio FmR (FDY divided by FST) was also analyzed. Women showed higher FmR than men meaning that the task required a higher amount of muscle capability for women. FmR was also influenced by handbrake location. These data will be useful for handbrake design.

  2. Normal Force and Drag Force in Magnetorheological Finishing

    SciTech Connect

    Miao, C.; Shafrir, S.N.; Lambropoulos, J.C.; Jacobs, S.D.

    2010-01-13

    The material removal in magnetorheological finishing (MRF) is known to be controlled by shear stress, tau, which equals drag force, Fd, divided by spot area, As. However, it is unclear how the normal force, Fn, affects the material removal in MRF and how the measured ratio of drag force to normal force Fd/Fn, equivalent to coefficient of friction, is related to material removal. This work studies, for the first time for MRF, the normal force and the measured ratio Fd/Fn as a function of material mechanical properties. Experimental data were obtained by taking spots on a variety of materials including optical glasses and hard ceramics with a spot-taking machine (STM). Drag force and normal force were measured with a dual load cell. Drag force decreases linearly with increasing material hardness. In contrast, normal force increases with hardness for glasses, saturating at high hardness values for ceramics. Volumetric removal rate decreases with normal force across all materials. The measured ratio Fd/Fn shows a strong negative linear correlation with material hardness. Hard materials exhibit a low “coefficient of friction”. The volumetric removal rate increases with the measured ratio Fd/Fn which is also correlated with shear stress, indicating that the measured ratio Fd/Fn is a useful measure of material removal in MRF.

  3. Flow mechanotransduction regulates traction forces, intercellular forces, and adherens junctions

    PubMed Central

    Ting, Lucas H.; Jahn, Jessica R.; Jung, Joon I.; Shuman, Benjamin R.; Feghhi, Shirin; Han, Sangyoon J.; Rodriguez, Marita L.

    2012-01-01

    Endothelial cells respond to fluid shear stress through mechanotransduction responses that affect their cytoskeleton and cell-cell contacts. Here, endothelial cells were grown as monolayers on arrays of microposts and exposed to laminar or disturbed flow to examine the relationship among traction forces, intercellular forces, and cell-cell junctions. Cells under laminar flow had traction forces that were higher than those under static conditions, whereas cells under disturbed flow had lower traction forces. The response in adhesion junction assembly matched closely with changes in traction forces since adherens junctions were larger in size for laminar flow and smaller for disturbed flow. Treating the cells with calyculin-A to increase myosin phosphorylation and traction forces caused an increase in adherens junction size, whereas Y-27362 cause a decrease in their size. Since tugging forces across cell-cell junctions can promote junctional assembly, we developed a novel approach to measure intercellular forces and found that these forces were higher for laminar flow than for static or disturbed flow. The size of adherens junctions and tight junctions matched closely with intercellular forces for these flow conditions. These results indicate that laminar flow can increase cytoskeletal tension while disturbed flow decreases cytoskeletal tension. Consequently, we found that changes in cytoskeletal tension in response to shear flow conditions can affect intercellular tension, which in turn regulates the assembly of cell-cell junctions. PMID:22447948

  4. Microphotonic Forces from Superfluid Flow

    NASA Astrophysics Data System (ADS)

    McAuslan, D. L.; Harris, G. I.; Baker, C.; Sachkou, Y.; He, X.; Sheridan, E.; Bowen, W. P.

    2016-04-01

    In cavity optomechanics, radiation pressure and photothermal forces are widely utilized to cool and control micromechanical motion, with applications ranging from precision sensing and quantum information to fundamental science. Here, we realize an alternative approach to optical forcing based on superfluid flow and evaporation in response to optical heating. We demonstrate optical forcing of the motion of a cryogenic microtoroidal resonator at a level of 1.46 nN, roughly 1 order of magnitude larger than the radiation pressure force. We use this force to feedback cool the motion of a microtoroid mechanical mode to 137 mK. The photoconvective forces we demonstrate here provide a new tool for high bandwidth control of mechanical motion in cryogenic conditions, while the ability to apply forces remotely, combined with the persistence of flow in superfluids, offers the prospect for new applications.

  5. Force feedback in limb lengthening.

    PubMed

    Wee, Jinyong; Rahman, Tariq; Seliktar, Rahamim; Akins, Robert; Levine, David; Richardson, Dean; Dodge, George R; Thabet, Ahmed M; Holmes, Lauren; Mackenzie, William G

    2010-01-01

    A new variable-rate distraction system using a motorized distractor driven by feedback from the distraction force was designed. The distractor was mounted on a unilateral fixator and attached to the tibiae of 6 sheep that underwent distraction osteogenesis. The sheep were divided equally into 3 groups. In group 1, the forces were recorded but were not used to drive the lengthening rate. In group 2, force feedback was used and the desired distraction force level was set to 300 N and the initial rate was 1 mm/day. Group 3 also underwent force feedback with the desired force limit at 300 N, but the rate change was initiated earlier, at 200 N. The distraction force was recorded at 15 second intervals throughout the distraction phase and stored onboard the distractor.

  6. Force oscillations simulating breathing maneuvers do not prevent force adaptation.

    PubMed

    Pascoe, Chris; Jiao, Yuekan; Seow, Chun Y; Paré, Peter D; Bossé, Ynuk

    2012-07-01

    Airway inflammation in patients with asthma exposes the airway smooth muscle (ASM) to a variety of spasmogens. These spasmogens increase ASM tone, which can lead to force adaptation. Length oscillations of ASM, which occur in vivo due to breathing maneuvers, can attenuate force adaptation. However, in the presence of tone, the force oscillations required to achieve these length oscillations may be unphysiologic (i.e., magnitude greater than the ones achieved due to the swings in transpulmonary pressure required for breathing). In the present study, we applied force oscillations simulating the tension oscillations experienced by the wall of a fourth-generation airway during tidal breathing with or without deep inspirations (DI) to ASM. The goal was to investigate whether force adaptation occurs in conditions mimicking breathing maneuvers. Tone was induced by carbachol (average, 20 nM), and the force-generating capacity of the ASM was assessed at 5-minute intervals before and after carbachol administration using electrical field stimulations (EFS). The results show that force oscillations applied before the introduction of tone had a small effect on the force produced by EFS (declined to 96.8% [P > 0.05] and 92.3% [P < 0.05] with and without DI, respectively). The tone induced by carbachol transiently decreased after a DI and declined significantly (P < 0.05) due to tidal breathing oscillations (25%). These force oscillations did not prevent force adaptation (gain of force of 11.2 ± 2.2 versus 13.5 ± 2.7 and 11.2 ± 3.0% in static versus dynamic conditions with or without DI, respectively). The lack of effect of simulated breathing maneuvers on force adaptation suggests that this gain in ASM force may occur in vivo and could contribute to the development of airway hyperresponsiveness. PMID:22323367

  7. Chin force in violin playing.

    PubMed

    Obata, Satoshi; Kinoshita, Hiroshi

    2012-06-01

    Force generated between the left mandible of violinists and the chinrest of the violin was examined using a force-sensing chinrest developed in this study. A strain-gauge force sensor was built, and it was fixed between the violin's top plate and a chin cup. Fifteen professional/amateur violinists held the violin statically, played musical scales with different sound properties and sounding techniques, as well as an excerpt from a Max Bruch concerto. Peak and mean forces were evaluated for each task. In a separate experiment, lateral movement of the lower teeth due to different levels of voluntary chin force exertion was measured. Static holding forces observed were 15 and 22 N with and without the help of the left hand, respectively. Peak force increased from 16 N at soft dynamics to 20 N at strong dynamics during scales. The force further increased to 29 N with the use of vibrato technique and 35 N during shifts. Tempo and hand position did not affect the force. Playing a Bruch concerto induced a mean peak force of 52 N, ranging from 31 to 82 N among the violinists. The developed force-sensing chinrest could accurately record the generated chin force. Typical chin force to stabilize the violin during ordinary musical performance was less than 30 N, but it could momentarily exceed 50 N when technically demanding musical pieces were performed. The lateral shift of the mandible was fairly small (<0.4 mm) even with high chin-force exertion, possibly due to clenching of the molars.

  8. Chin force in violin playing.

    PubMed

    Obata, Satoshi; Kinoshita, Hiroshi

    2012-06-01

    Force generated between the left mandible of violinists and the chinrest of the violin was examined using a force-sensing chinrest developed in this study. A strain-gauge force sensor was built, and it was fixed between the violin's top plate and a chin cup. Fifteen professional/amateur violinists held the violin statically, played musical scales with different sound properties and sounding techniques, as well as an excerpt from a Max Bruch concerto. Peak and mean forces were evaluated for each task. In a separate experiment, lateral movement of the lower teeth due to different levels of voluntary chin force exertion was measured. Static holding forces observed were 15 and 22 N with and without the help of the left hand, respectively. Peak force increased from 16 N at soft dynamics to 20 N at strong dynamics during scales. The force further increased to 29 N with the use of vibrato technique and 35 N during shifts. Tempo and hand position did not affect the force. Playing a Bruch concerto induced a mean peak force of 52 N, ranging from 31 to 82 N among the violinists. The developed force-sensing chinrest could accurately record the generated chin force. Typical chin force to stabilize the violin during ordinary musical performance was less than 30 N, but it could momentarily exceed 50 N when technically demanding musical pieces were performed. The lateral shift of the mandible was fairly small (<0.4 mm) even with high chin-force exertion, possibly due to clenching of the molars. PMID:21952980

  9. Coordination of contact forces during multifinger static prehension.

    PubMed

    Martin, Joel R; Latash, Mark L; Zatsiorsky, Vladimir M

    2011-05-01

    This study investigated the effects of modifying contact finger forces in one direction-normal or tangential-on the entire set of the contact forces, while statically holding an object. Subjects grasped a handle instrumented with finger force-moment sensors, maintained it at rest in the air, and then slowly: (1) increased the grasping force, (2) tried to spread fingers apart, and (3) tried to squeeze fingers together. Analysis was mostly performed at the virtual finger (VF) level (the VF is an imaginable finger that generates the same force and moment as the four fingers combined). For all three tasks there were statistically significant changes in the VF normal and tangential forces. For finger spreading/squeezing the tangential force neutral point was located between the index and middle fingers. We conclude that the internal forces are regulated as a whole, including adjustments in both normal and tangential force, instead of only a subset of forces (normal or tangential). The effects of such factors as EFFORT and TORQUE were additive; their interaction was not statistically significant, thus supporting the principle of superposition in human prehension. PMID:21576716

  10. Coordination of Contact Forces During Multifinger Static Prehension

    PubMed Central

    Martin, Joel R.; Latash, Mark L.

    2011-01-01

    This study investigated the effects of modifying contact finger forces in one direction—normal or tangential—on the entire set of the contact forces, while statically holding an object. Subjects grasped a handle instrumented with finger force-moment sensors, maintained it at rest in the air, and then slowly: (1) increased the grasping force, (2) tried to spread fingers apart, and (3) tried to squeeze fingers together. Analysis was mostly performed at the virtual finger (VF) level (the VF is an imaginable finger that generates the same force and moment as the four fingers combined). For all three tasks there were statistically significant changes in the VF normal and tangential forces. For finger spreading/squeezing the tangential force neutral point was located between the index and middle fingers. We conclude that the internal forces are regulated as a whole, including adjustments in both normal and tangential force, instead of only a subset of forces (normal or tangential). The effects of such factors as EFFORT and TORQUE were additive; their interaction was not statistically significant, thus supporting the principle of superposition in human prehension. PMID:21576716

  11. Incorporation of additives into polymers

    DOEpatents

    McCleskey, T. Mark; Yates, Matthew Z.

    2003-07-29

    There has been invented a method for incorporating additives into polymers comprising: (a) forming an aqueous or alcohol-based colloidal system of the polymer; (b) emulsifying the colloidal system with a compressed fluid; and (c) contacting the colloidal polymer with the additive in the presence of the compressed fluid. The colloidal polymer can be contacted with the additive by having the additive in the compressed fluid used for emulsification or by adding the additive to the colloidal system before or after emulsification with the compressed fluid. The invention process can be carried out either as a batch process or as a continuous on-line process.

  12. [Patch-testing methods: additional specialised or additional series].

    PubMed

    Cleenewerck, M-B

    2009-01-01

    The tests in the European standard battery must occasionally be supplemented by specialised or additional batteries, particularly where the contact allergy is thought to be of occupational origin. These additional batteries cover all allergens associated with various professional activities (hairdressing, baking, dentistry, printing, etc.) and with different classes of materials and chemical products (glue, plastic, rubber...). These additional tests may also include personal items used by patients on a daily basis such as cosmetics, shoes, plants, textiles and so on.

  13. Additive manufacturing of optical components

    NASA Astrophysics Data System (ADS)

    Heinrich, Andreas; Rank, Manuel; Maillard, Philippe; Suckow, Anne; Bauckhage, Yannick; Rößler, Patrick; Lang, Johannes; Shariff, Fatin; Pekrul, Sven

    2016-08-01

    The development of additive manufacturing methods has enlarged rapidly in recent years. Thereby, the work mainly focuses on the realization of mechanical components, but the additive manufacturing technology offers a high potential in the field of optics as well. Owing to new design possibilities, completely new solutions are possible. This article briefly reviews and compares the most important additive manufacturing methods for polymer optics. Additionally, it points out the characteristics of additive manufactured polymer optics. Thereby, surface quality is of crucial importance. In order to improve it, appropriate post-processing steps are necessary (e.g. robot polishing or coating), which will be discussed. An essential part of this paper deals with various additive manufactured optical components and their use, especially in optical systems for shape metrology (e.g. borehole sensor, tilt sensor, freeform surface sensor, fisheye lens). The examples should demonstrate the potentials and limitations of optical components produced by additive manufacturing.

  14. Estimation of ligand efficacies of metabotropic glutamate receptors from conformational forces obtained from molecular dynamics simulations.

    PubMed

    Lakkaraju, Sirish Kaushik; Xue, Fengtian; Faden, Alan I; MacKerell, Alexander D

    2013-06-24

    Group 1 metabotropic glutamate receptors (mGluR) are G-protein coupled receptors with a large bilobate extracellular ligand binding region (LBR) that resembles a Venus fly trap. Closing of this LBR in the presence of a ligand is associated with the activation of the receptor. From conformational sampling of the LBR-ligand complexes using all-atom molecular dynamics (MD) simulations, we characterized the conformational minima related to the hinge like motion associated with the LBR closing/opening in the presence of known agonists and antagonists. By applying a harmonic restraint on the LBR, we also determined the conformational forces generated by the different ligands. The change in the location of the minima and the conformational forces were used to quantify the efficacies of the ligands. This analysis shows that efficacies can be estimated from the forces of a single conformation of the receptor, indicating the potential of MD simulations as an efficient and useful technique to quantify efficacies, thereby facilitating the rational design of mGluR agonists and antagonists.

  15. CHARMM force field parameters for simulation of reactive intermediates in native and thio-substituted ribozymes.

    PubMed

    Mayaan, Evelyn; Moser, Adam; MacKerell, Alexander D; York, Darrin M

    2007-01-30

    Force field parameters specifically optimized for residues important in the study of RNA catalysis are derived from density-functional calculations, in a fashion consistent with the CHARMM27 all-atom empirical force field. Parameters are presented for residues that model reactive RNA intermediates and transition state analogs, thio-substituted phosphates and phosphoranes, and bound Mg(2+) and di-metal bridge complexes. Target data was generated via density-functional calculations at the B3LYP/6-311++G(3df,2p)// B3LYP/6-31++G(d,p) level. Partial atomic charges were initially derived from CHelpG electrostatic potential fitting and subsequently adjusted to be consistent with the CHARMM27 charges. Lennard-Jones parameters were determined to reproduce interaction energies with water molecules. Bond, angle, and torsion parameters were derived from the density-functional calculations and renormalized to maintain compatibility with the existing CHARMM27 parameters for standard residues. The extension of the CHARMM27 force field parameters for the nonstandard biological residues presented here will have considerable use in simulations of ribozymes, including the study of freeze-trapped catalytic intermediates, metal ion binding and occupation, and thio effects.

  16. Numerical study of the hydrodynamic drag force in atomic force microscopy measurements undertaken in fluids.

    PubMed

    Méndez-Méndez, J V; Alonso-Rasgado, M T; Faria, E Correia; Flores-Johnson, E A; Snook, R D

    2014-11-01

    When atomic force microscopy (AFM) is employed for in vivo study of immersed biological samples, the fluid medium presents additional complexities, not least of which is the hydrodynamic drag force due to viscous friction of the cantilever with the liquid. This force should be considered when interpreting experimental results and any calculated material properties. In this paper, a numerical model is presented to study the influence of the drag force on experimental data obtained from AFM measurements using computational fluid dynamics (CFD) simulation. The model provides quantification of the drag force in AFM measurements of soft specimens in fluids. The numerical predictions were compared with experimental data obtained using AFM with a V-shaped cantilever fitted with a pyramidal tip. Tip velocities ranging from 1.05 to 105 μm/s were employed in water, polyethylene glycol and glycerol with the platform approaching from a distance of 6000 nm. The model was also compared with an existing analytical model. Good agreement was observed between numerical results, experiments and analytical predictions. Accurate predictions were obtained without the need for extrapolation of experimental data. In addition, the model can be employed over the range of tip geometries and velocities typically utilized in AFM measurements.

  17. Classical force field for hydrofluorocarbon molecular simulations. Application to the study of gas solubility in poly(vinylidene fluoride).

    PubMed

    Lachet, V; Teuler, J-M; Rousseau, B

    2015-01-01

    A classical all-atoms force field for molecular simulations of hydrofluorocarbons (HFCs) has been developed. Lennard-Jones force centers plus point charges are used to represent dispersion-repulsion and electrostatic interactions. Parametrization of this force field has been performed iteratively using three target properties of pentafluorobutane: the quantum energy of an isolated molecule, the dielectric constant in the liquid phase, and the compressed liquid density. The accuracy and transferability of this new force field has been demonstrated through the simulation of different thermophysical properties of several fluorinated compounds, showing significant improvements compared to existing models. This new force field has been applied to study solubilities of several gases in poly(vinylidene fluoride) (PVDF) above the melting temperature of this polymer. The solubility of CH4, CO2, H2S, H2, N2, O2, and H2O at infinite dilution has been computed using test particle insertions in the course of a NpT hybrid Monte Carlo simulation. For CH4, CO2, and their mixtures, some calculations beyond the Henry regime have also been performed using hybrid Monte Carlo simulations in the osmotic ensemble, allowing both swelling and solubility determination. An ideal mixing behavior is observed, with identical solubility coefficients in the mixtures and in pure gas systems.

  18. Comparison between empirical protein force fields for the simulation of the adsorption behavior of structured LK peptides on functionalized surfaces.

    PubMed

    Collier, Galen; Vellore, Nadeem A; Yancey, Jeremy A; Stuart, Steven J; Latour, Robert A

    2012-12-01

    All-atom empirical molecular mechanics protein force fields, which have been developed to represent the energetics of peptide folding behavior in aqueous solution, have not been parameterized for protein interactions with solid material surfaces. As a result, their applicability for representing the adsorption behavior of proteins with functionalized material surfaces should not be assumed. To address this issue, we conducted replica-exchange molecular dynamics simulations of the adsorption behavior of structured peptides to functionalized surfaces using three protein force fields that are widely used for the simulation of peptide adsorption behavior: CHARMM22, AMBER94, and OPLS-AA. Simulation results for peptide structure both in solution and when adsorbed to the surfaces were compared to experimental results for similar peptide-surface systems to provide a means of evaluating and comparing the performance of these three force fields for this type of application. Substantial differences in both solution and adsorbed peptide conformations were found amongst these three force fields, with the CHARMM22 force field found to most closely match experimental results.

  19. Probing cellular traction forces with magnetic nanowires and microfabricated force sensor arrays.

    PubMed

    Lin, Yi-Chia; Kramer, Corinne M; Chen, Christopher S; Reich, Daniel H

    2012-02-24

    In this paper, the use of magnetic nanowires for the study of cellular response to force is demonstrated. High-aspect ratio Ni rods with diameter 300 nm and lengths up to 20 μm were bound to or internalized by pulmonary artery smooth muscle cells (SMCs) cultured on arrays of flexible micropost force sensors. Forces and torques were applied to the cells by driving the nanowires with AC magnetic fields in the frequency range 0.1-10 Hz, and the changes in cellular contractile forces were recorded with the microposts. These local stimulations yield global force reinforcement of the cells' traction forces, but this contractile reinforcement can be effectively suppressed upon addition of a calcium channel blocker, ruthenium red, suggesting the role of calcium channels in the mechanical response. The responsiveness of the SMCs to actuation depends on the frequency of the applied stimulation. These results show that the combination of magnetic nanoparticles and micropatterned, flexible substrates can provide new approaches to the study of cellular mechanotransduction.

  20. Probing cellular traction forces with magnetic nanowires and microfabricated force sensor arrays

    NASA Astrophysics Data System (ADS)

    Lin, Yi-Chia; Kramer, Corinne M.; Chen, Christopher S.; Reich, Daniel H.

    2012-02-01

    In this paper, the use of magnetic nanowires for the study of cellular response to force is demonstrated. High-aspect ratio Ni rods with diameter 300 nm and lengths up to 20 μm were bound to or internalized by pulmonary artery smooth muscle cells (SMCs) cultured on arrays of flexible micropost force sensors. Forces and torques were applied to the cells by driving the nanowires with AC magnetic fields in the frequency range 0.1-10 Hz, and the changes in cellular contractile forces were recorded with the microposts. These local stimulations yield global force reinforcement of the cells’ traction forces, but this contractile reinforcement can be effectively suppressed upon addition of a calcium channel blocker, ruthenium red, suggesting the role of calcium channels in the mechanical response. The responsiveness of the SMCs to actuation depends on the frequency of the applied stimulation. These results show that the combination of magnetic nanoparticles and micropatterned, flexible substrates can provide new approaches to the study of cellular mechanotransduction.

  1. Mapping interaction forces with the atomic force microscope.

    PubMed Central

    Radmacher, M; Cleveland, J P; Fritz, M; Hansma, H G; Hansma, P K

    1994-01-01

    Force curves were recorded as the sample was raster-scanned under the tip. This opens new opportunities for imaging with the atomic force microscope: several characteristics of the samples can be measured simultaneously, for example, topography, adhesion forces, elasticity, van der Waals, and electrostatic interactions. The new opportunities are illustrated by images of several characteristics of thin metal films, aggregates of lysozyme, and single molecules of DNA. Images FIGURE 1 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:8075349

  2. Variability of a "force signature" during windmill softball pitching and relationship between discrete force variables and pitch velocity.

    PubMed

    Nimphius, Sophia; McGuigan, Michael R; Suchomel, Timothy J; Newton, Robert U

    2016-06-01

    This study assessed reliability of discrete ground reaction force (GRF) variables over multiple pitching trials, investigated the relationships between discrete GRF variables and pitch velocity (PV) and assessed the variability of the "force signature" or continuous force-time curve during the pitching motion of windmill softball pitchers. Intraclass correlation coefficient (ICC) for all discrete variables was high (0.86-0.99) while the coefficient of variance (CV) was low (1.4-5.2%). Two discrete variables were significantly correlated to PV; second vertical peak force (r(5)=0.81, p=0.03) and time between peak forces (r(5)=-0.79; p=0.03). High ICCs and low CVs support the reliability of discrete GRF and PV variables over multiple trials and significant correlations indicate there is a relationship between the ability to produce force and the timing of this force production with PV. The mean of all pitchers' curve-average standard deviation of their continuous force-time curves demonstrated low variability (CV=4.4%) indicating a repeatable and identifiable "force signature" pattern during this motion. As such, the continuous force-time curve in addition to discrete GRF variables should be examined in future research as a potential method to monitor or explain changes in pitching performance.

  3. An Integrated Higgs Force Theory

    NASA Astrophysics Data System (ADS)

    Colella, Antonio

    2016-03-01

    An Integrated Higgs force theory (IHFT) was based on 2 key requirement amplifications: a matter particle/Higgs force was one and inseparable; a matter particle/Higgs force bidirectionally condensed/evaporated from/to super force. These were basis of 5 theories: particle creation, baryogenesis, superpartner/quark decays, spontaneous symmetry breaking, and stellar black holes. Our universe's 129 matter/force particles contained 64 supersymmetric Higgs particles; 9 transient matter particles/Higgs forces decayed to 8 permanent matter particles/Higgs forces; mass was given to a matter particle by its Higgs force and gravitons; and sum of 8 Higgs force energies of 8 permanent matter particles was dark energy. An IHFT's essence is the intimate physical relationships between 8 theories. These theories are independent because physicists in one theory worked independently of physicists in the other seven. An IHFT's premise is without sacrificing their integrities, 8 independent existing theories are replaced by 8 interrelated amplified theories. Requirement amplifications provide interfaces between the 8 theories. Intimate relationships between 8 theories including the above 5 and string, Higgs forces, and Super Universe are described. The sorting category selected was F. PARTICLES AND FIELDS (e.g., F1 Higgs Physics, F10 Alternative Beyond the Standard Model Physics, F11 Dark Sector Theories and Searches, and F12 Particle Cosmology).

  4. The labor force of the future.

    PubMed

    Norwood, J L

    1987-07-01

    In the decades ahead, the US labor force will reflect changes in the industrial structure, with declines in some manufacturing industries and expansion in service industries. The services sector is so diverse that the jobs within it cannot be categorized as either high wage or low wage. The service-producing sector employs 85% of professional specialty workers in the US. In general, information on compensation trends indicates that greater increases in compensation have occurred for workers in service-producing as opposed to goods-producing industries. The increase in service sector jobs has created opportunities for women to enter the labor force and, at present, 5 out of 6 women work in this sector compared to fewer than 2 out of 3 men. Productivity growth rates in the service-producing industries vary substantially and are strongly affected by the business cycle. Central to employment opportunities in the years ahead will be the effect of new technology. To date, the aggregate effect of new technology has been increased employment and higher living standards. Although retraining programs should be in place, the scenario of a huge technology-created labor surplus seems unlikely. In fact, a more likely problem is a shortage of labor resulting from earlier labor force withdrawal and demographic aging of the population. Those in the 25-54-year age group will represent a larger share of the labor force in the years ahead. In addition, blacks are expected to account for 20% of the labor force growth in the next decade. Finally, given increasing labor force participation rates among mothers, employers may have to provide more flexible work schedules, assistance with day care, and more attractive benefits packages. PMID:12314853

  5. Theory of Casimir Forces without the Proximity-Force Approximation.

    PubMed

    Lapas, Luciano C; Pérez-Madrid, Agustín; Rubí, J Miguel

    2016-03-18

    We analyze both the attractive and repulsive Casimir-Lifshitz forces recently reported in experimental investigations. By using a kinetic approach, we obtain the Casimir forces from the power absorbed by the materials. We consider collective material excitations through a set of relaxation times distributed in frequency according to a log-normal function. A generalized expression for these forces for arbitrary values of temperature is obtained. We compare our results with experimental measurements and conclude that the model goes beyond the proximity-force approximation. PMID:27035293

  6. Automated force controller for amplitude modulation atomic force microscopy.

    PubMed

    Miyagi, Atsushi; Scheuring, Simon

    2016-05-01

    Atomic Force Microscopy (AFM) is widely used in physics, chemistry, and biology to analyze the topography of a sample at nanometer resolution. Controlling precisely the force applied by the AFM tip to the sample is a prerequisite for faithful and reproducible imaging. In amplitude modulation (oscillating) mode AFM, the applied force depends on the free and the setpoint amplitudes of the cantilever oscillation. Therefore, for keeping the applied force constant, not only the setpoint amplitude but also the free amplitude must be kept constant. While the AFM user defines the setpoint amplitude, the free amplitude is typically subject to uncontrollable drift, and hence, unfortunately, the real applied force is permanently drifting during an experiment. This is particularly harmful in biological sciences where increased force destroys the soft biological matter. Here, we have developed a strategy and an electronic circuit that analyzes permanently the free amplitude of oscillation and readjusts the excitation to maintain the free amplitude constant. As a consequence, the real applied force is permanently and automatically controlled with picoNewton precision. With this circuit associated to a high-speed AFM, we illustrate the power of the development through imaging over long-duration and at various forces. The development is applicable for all AFMs and will widen the applicability of AFM to a larger range of samples and to a larger range of (non-specialist) users. Furthermore, from controlled force imaging experiments, the interaction strength between biomolecules can be analyzed. PMID:27250433

  7. The Effect of Increasing Inertia upon Vertical Ground Reaction Forces during Locomotion

    NASA Technical Reports Server (NTRS)

    DeWitt, John K.; Hagan, R. Donald; Cromwell, Ronita L.

    2007-01-01

    The addition of inertia to exercising astronauts could increase ground reaction forces and potentially provide a greater health benefit. However, conflicting results have been reported regarding the adaptations to additional mass (inertia) without additional net weight (gravitational force) during locomotion. We examined the effect of increasing inertia while maintaining net gravitational force on vertical ground reaction forces and kinematics during walking and running. Vertical ground reaction force was measured for ten healthy adults (5 male/5 female) during walking (1.34 m/s) and running (3.13 m/s) using a force-measuring treadmill. Subjects completed locomotion at normal weight and mass, and at 10, 20, 30, and 40% of added inertial force. The added gravitational force was relieved with overhead suspension, so that the net force between the subject and treadmill at rest remained equal to 100% body weight. Peak vertical impact forces and loading rates increased with increased inertia during walking, and decreased during running. As inertia increased, peak vertical propulsive forces decreased during walking and did not change during running. Stride time increased during walking and running, and contact time increased during running. Vertical ground reaction force production and adaptations in gait kinematics were different between walking and running. The increased inertial forces were utilized independently from gravitational forces by the motor control system when determining coordination strategies.

  8. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  9. Enantioselective Michael addition of water.

    PubMed

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-02-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry.

  10. Gasoline additives, emissions, and performance

    SciTech Connect

    1995-12-31

    The papers included in this publication deal with the influence of fuel, additive, and hardware changes on a variety of vehicle performance characteristics. Advanced techniques for measuring these performance parameters are also described. Contents include: Fleet test evaluation of gasoline additives for intake valve and combustion chamber deposit clean up; A technique for evaluating octane requirement additives in modern engines on dynamometer test stands; A fleet test of two additive technologies comparing their effects on tailpipe emissions; Investigation into the vehicle exhaust emissions of high percentage ethanol blends; Variability in hydrocarbon speciation measurements at low emission (ULEV) levels; and more.

  11. Elementary Implantable Force Sensor

    PubMed Central

    Wachs, Rebecca A.; Ellstein, David; Drazan, John; Healey, Colleen P.; Uhl, Richard L.; Connor, Kenneth A.

    2014-01-01

    Implementing implantable sensors which are robust enough to maintain long term functionality inside the body remains a significant challenge. The ideal implantable sensing system is one which is simple and robust; free from batteries, telemetry, and complex electronics. We have developed an elementary implantable sensor for orthopaedic smart implants. The sensor requires no telemetry and no batteries to communicate wirelessly. It has no on-board signal conditioning electronics. The sensor itself has no electrical connections and thus does not require a hermetic package. The sensor is an elementary L-C resonator which can function as a simple force transducer by using a solid dielectric material of known stiffness between two parallel Archimedean coils. The operating characteristics of the sensors are predicted using a simplified, lumped circuit model. We have demonstrated sensor functionality both in air and in saline. Our preliminary data indicate that the sensor can be reasonably well modeled as a lumped circuit to predict its response to loading. PMID:24883335

  12. Tunneling magnetic force microscopy

    NASA Technical Reports Server (NTRS)

    Burke, Edward R.; Gomez, Romel D.; Adly, Amr A.; Mayergoyz, Isaak D.

    1993-01-01

    We have developed a powerful new tool for studying the magnetic patterns on magnetic recording media. This was accomplished by modifying a conventional scanning tunneling microscope. The fine-wire probe that is used to image surface topography was replaced with a flexible magnetic probe. Images obtained with these probes reveal both the surface topography and the magnetic structure. We have made a thorough theoretical analysis of the interaction between the probe and the magnetic fields emanating from a typical recorded surface. Quantitative data about the constituent magnetic fields can then be obtained. We have employed these techniques in studies of two of the most important issues of magnetic record: data overwrite and maximizing data-density. These studies have shown: (1) overwritten data can be retrieved under certain conditions; and (2) improvements in data-density will require new magnetic materials. In the course of these studies we have developed new techniques to analyze magnetic fields of recorded media. These studies are both theoretical and experimental and combined with the use of our magnetic force scanning tunneling microscope should lead to further breakthroughs in the field of magnetic recording.

  13. Maximum bow force revisited.

    PubMed

    Mores, Robert

    2016-08-01

    Schelleng [J. Acoust. Soc. Am. 53, 26-41 (1973)], Askenfelt [J. Acoust. Soc. Am. 86, 503-516 (1989)], Schumacher [J. Acoust. Soc. Am. 96, 1985-1998 (1994)], and Schoonderwaldt, Guettler, and Askenfelt [Acta Acust. Acust. 94, 604-622 (2008)] formulated-in different ways-how the maximum bow force relates to bow velocity, bow-bridge distance, string impedance, and friction coefficients. Issues of uncertainty are how to account for friction or for the rotational admittance of the strings. Related measurements at the respective transitions between regimes of Helmholtz motion and non-Helmholtz motion employ a variety of bowing machines and stringed instruments. The related findings include all necessary parameters except the friction coefficients, leaving the underlying models unconfirmed. Here, a bowing pendulum has been constructed which allows precise measurement of relevant bowing parameters, including the friction coefficients. Two cellos are measured across all strings for three different bow-bridge distances. The empirical data suggest that-taking the diverse elements of existing models as options-Schelleng's model combined with Schumacher's velocity term yields the best fit. Furthermore, the pendulum employs a bow driving mechanism with adaptive impedance which discloses that mentioned regimes are stable and transitions between them sometimes require a hysteresis on related parameters. PMID:27586745

  14. Forced air heater

    SciTech Connect

    Livezey, D.J.

    1980-09-23

    An air heating chamber is supported to project into a stove through an opening provided in the rear wall of the stove by a mounting plate mounted to the exterior of the stove rear wall. The mounting plate which forms the exterior end wall of the heating chamber, includes laterally spaced heating chamber inlet and outlet openings. A blower is detachably mounted to the exterior of the mounting plate in registration with the heating chamber inlet opening to deliver cool forced air into the heating chamber. After circulating therethrough, the air exits the heating chamber through the outlet opening and flows into a hot air manifold, which is also detachably mounted to the exterior of the mounting plate. The manifold includes an upwardly extending inlet chamber with a hot air inlet at its lower end aligned with the heating chamber outlet opening. A horizontal outlet chamber is attached to the top end of the inlet chamber to extend laterally along the back of the stove. Hot air outlets are provided at each end of the manifold outlet chamber to discharge the heated air horizontally over the top and towards the front of the stove.

  15. Deep atomic force microscopy

    SciTech Connect

    Barnard, H.; Drake, B.; Randall, C.; Hansma, P. K.

    2013-12-15

    The Atomic Force Microscope (AFM) possesses several desirable imaging features including the ability to produce height profiles as well as two-dimensional images, in fluid or air, at high resolution. AFM has been used to study a vast selection of samples on the scale of angstroms to micrometers. However, current AFMs cannot access samples with vertical topography of the order of 100 μm or greater. Research efforts have produced AFM scanners capable of vertical motion greater than 100 μm, but commercially available probe tip lengths are still typically less than 10 μm high. Even the longest probe tips are below 100 μm and even at this range are problematic. In this paper, we present a method to hand-fabricate “Deep AFM” probes with tips of the order of 100 μm and longer so that AFM can be used to image samples with large scale vertical topography, such as fractured bone samples.

  16. 19. Photographic copy of an asconstructed site plan for additions ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Photographic copy of an as-constructed site plan for additions to North Base: Job No. Muroc A(511), Military Construction, Third District Region, San Bernardino, California; Muroc Bombing Range, Muroc Lake, Calif; Additional Temporary Construction, Materiel Center Flight Test Base, Location Grading & Paving Plan, Sheet No. 1 of 21, March 1943. Reproduced from the holdings of the National Archives, Pacific Southwest Region - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

  17. 18. Photographic copy of site plan for additions to North ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Photographic copy of site plan for additions to North Base: Job No. Muroc A(511), Military Construction, Third District Region, San Bernardino, California; Muroc Bombing Range, Muroc Lake, Calif; Additional Temporary Construction, Materiel Center Flight Test Base, Location Plan, February 1943. Reproduced from the holdings of the National Archives, Pacific Southwest Region - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

  18. Force Limited Vibration Testing Monograph

    NASA Technical Reports Server (NTRS)

    Scharton, Terry D.

    1997-01-01

    The practice of limiting the shaker force in vibration tests was investigated at the NASA Jet Propulsion Laboratory (JPL) in 1990 after the mechanical failure of an aerospace component during a vibration test. Now force limiting is used in almost every major vibration test at JPL and in many vibration tests at NASA Goddard Space Flight Center (GSFC) and at many aerospace contractors. The basic ideas behind force limiting have been in the literature for several decades, but the piezo-electric force transducers necessary to conveniently implement force limiting have been available only in the last decade. In 1993, funding was obtained from the NASA headquarters Office of Chief Engineer to develop and document the technology needed to establish force limited vibration testing as a standard approach available to all NASA centers and aerospace contractors. This monograph is the final report on that effort and discusses the history, theory, and applications of the method in some detail.

  19. 1. Northeast front and southeast side of original section. Addition ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Northeast front and southeast side of original section. Addition to rear view to west. - Offutt Air Force Base, Looking Glass Airborne Command Post, Aerospace Ground Equipment (AGE) Storage Facility, Far Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

  20. Computer Maintenance Operations Center (CMOC), additional computer support equipment ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Computer Maintenance Operations Center (CMOC), additional computer support equipment - Beale Air Force Base, Perimeter Acquisition Vehicle Entry Phased-Array Warning System, Techinical Equipment Building, End of Spencer Paul Road, north of Warren Shingle Road (14th Street), Marysville, Yuba County, CA

  1. The Physics Force presents The Physics Circus

    NASA Astrophysics Data System (ADS)

    Dahlberg, E. Dan

    2015-03-01

    The Physics Force of the University of Minnesota is an outreach program developed with the goal to show students and the public Science is Fun, Science is Interesting, and Science is Understandable. The program grew from a rather small effort by three high school physics teachers and two University of Minnesota staff members. In the almost three decades since its humble beginnings of 100 attendees in a year, it has grown to an average attendance of over 36,000 annually. In the last three years alone, about 110,000 Minnesotans have seen a performance of The Physics Circus which is roughly 2% of the population of the state. In addition to the performances in Minnesota, The Force performed two years at Disney's Epcot Center, was featured on Newton's Apple, and made appearances on the very successful German TV science show, the Knoff-Hoff Show. I will begin the talk with some of our motivation to develop The Physics Force arising from the current ``scientific state'' of our society and then provide more information on The Force including both some history and examples taken from our Physics Circus.

  2. Interparticle Forces Underlying Nanoparticle Self-Assemblies.

    PubMed

    Luo, Dan; Yan, Cong; Wang, Tie

    2015-12-01

    Studies on the self-assembly of nanoparticles have been a hot topic in nanotechnology for decades and still remain relevant for the present and future due to their tunable collective properties as well as their remarkable applications to a wide range of fields. The novel properties of nanoparticle assemblies arise from their internal interactions and assemblies with the desired architecture key to constructing novel nanodevices. Therefore, a comprehensive understanding of the interparticle forces of nanoparticle self-assemblies is a pre-requisite to the design and control of the assembly processes, so as to fabricate the ideal nanomaterial and nanoproducts. Here, different categories of interparticle forces are classified and discussed according to their origins, behaviors and functions during the assembly processes, and the induced collective properties of the corresponding nanoparticle assemblies. Common interparticle forces, such as van der Waals forces, electrostatic interactions, electromagnetic dipole-dipole interactions, hydrogen bonds, solvophonic interactions, and depletion interactions are discussed in detail. In addition, new categories of assembly principles are summarized and introduced. These are termed template-mediated interactions and shape-complementary interactions. A deep understanding of the interactions inside self-assembled nanoparticles, and a broader perspective for the future synthesis and fabrication of these promising nanomaterials is provided.

  3. Force fluctuation in a semiflexible loop

    NASA Astrophysics Data System (ADS)

    Waters, James; Kim, Harold; Harold Kim Team

    DNA-binding proteins can regulate genetic expression by holding two sites in close proximity, forming a closed loop. Such complexes may require strong bending of DNA segments on the order of one persistence length or less. Both this elastic bending and the thermal fluctuations of the DNA molecule are necessary to describe the resulting behavior. To explore this problem, we consider a discrete model of a wormlike chain, kept in the fixed extension ensemble. By using a novel method to sample conformations in both position and momentum space, we can obtain a distribution of constraint forces as a function of chain length, extension, and flexibility. Our coarse-grained model allows us to explore the space of these parameters more efficiently than a detailed molecular dynamics approach. We find that increasing contour length decreases average force by relieving bending stress, but that the additional freedom allows fluctuations in the constraint force to increase. This implies that the probability of large forces may go up even as the mean goes down, impacting the lifetime of such bound states in a way unforeseen by purely equilibrium methods.

  4. Sensing mode atomic force microscope

    DOEpatents

    Hough, Paul V. C.; Wang, Chengpu

    2006-08-22

    An atomic force microscope is described having a cantilever comprising a base and a probe tip on an end opposite the base; a cantilever drive device connected to the base; a magnetic material coupled to the probe tip, such that when an incrementally increasing magnetic field is applied to the magnetic material an incrementally increasing force will be applied to the probe tip; a moveable specimen base; and a controller constructed to obtain a profile height of a specimen at a point based upon a contact between the probe tip and a specimen, and measure an adhesion force between the probe tip and the specimen by, under control of a program, incrementally increasing an amount of a magnetic field until a release force, sufficient to break the contact, is applied. An imaging method for atomic force microscopy involving measuring a specimen profile height and adhesion force at multiple points within an area and concurrently displaying the profile and adhesion force for each of the points is also described. A microscope controller is also described and is constructed to, for a group of points, calculate a specimen height at a point based upon a cantilever deflection, a cantilever base position and a specimen piezo position; calculate an adhesion force between a probe tip and a specimen at the point by causing an incrementally increasing force to be applied to the probe tip until the probe tip separates from a specimen; and move the probe tip to a new point in the group.

  5. Sensing mode atomic force microscope

    DOEpatents

    Hough, Paul V.; Wang, Chengpu

    2004-11-16

    An atomic force microscope is described having a cantilever comprising a base and a probe tip on an end opposite the base; a cantilever drive device connected to the base; a magnetic material coupled to the probe tip, such that when an incrementally increasing magnetic field is applied to the magnetic material an incrementally increasing force will be applied to the probe tip; a moveable specimen base; and a controller constructed to obtain a profile height of a specimen at a point based upon a contact between the probe tip and a specimen, and measure an adhesion force between the probe tip and the specimen by, under control of a program, incrementally increasing an amount of a magnetic field until a release force, sufficient to break the contact, is applied. An imaging method for atomic force microscopy involving measuring a specimen profile height and adhesion force at multiple points within an area and concurrently displaying the profile and adhesion force for each of the points is also described. A microscope controller is also described and is constructed to, for a group of points, calculate a specimen height at a point based upon a cantilever deflection, a cantilever base position and a specimen piezo position; calculate an adhesion force between a probe tip and a specimen at the point by causing an incrementally increasing force to be applied to the probe tip until the probe tip separates from a specimen; and move the probe tip to a new point in the group.

  6. Coriolis Force on Your Arms

    NASA Astrophysics Data System (ADS)

    Johns, Robert

    2003-12-01

    The Coriolis force is a sideward force that acts on a rotating object as it moves toward or away from the center of rotation. It is important to long-range artillery and the formation of tornados, but we seldom experience this force on a human scale, unless we play on a merry-go-round or similar apparatus. This note describes a simple activity that lets us see the effect of the Coriolis force on our outstretched arms as they fall down to our sides while we rotate.

  7. Force As A Momentum Current

    SciTech Connect

    Munera, Hector A.

    2010-07-28

    Advantages of a neo-Cartesian approach to classical mechanics are noted. If conservation of linear momentum is the fundamental principle, Newton's three laws become theorems. A minor paradox in static Newtonian mechanics is identified, and solved by reinterpreting force as a current of momentum. Contact force plays the role of a mere midwife in the exchange of momentum; however, force cannot be eliminated from physics because it provides the numerical value for momentum current. In this sense, in a neo-Cartesian formulation of mechanics the concept of force becomes strengthened rather than weakened.

  8. Force As A Momentum Current

    NASA Astrophysics Data System (ADS)

    Múnera, Héctor A.

    2010-07-01

    Advantages of a neo-Cartesian approach to classical mechanics are noted. If conservation of linear momentum is the fundamental principle, Newton's three laws become theorems. A minor paradox in static Newtonian mechanics is identified, and solved by reinterpreting force as a current of momentum. Contact force plays the role of a mere midwife in the exchange of momentum; however, force cannot be eliminated from physics because it provides the numerical value for momentum current. In this sense, in a neo-Cartesian formulation of mechanics the concept of force becomes strengthened rather than weakened.

  9. Rational design of solution additives for the prevention of protein aggregation.

    PubMed

    Baynes, Brian M; Trout, Bernhardt L

    2004-09-01

    We have developed a statistical-mechanical model of the effect of solution additives on protein association reactions. This model incorporates solvent radial distribution functions obtained from all-atom molecular dynamics simulations of particular proteins into simple models of protein interactions. In this way, the effects of additives can be computed along the entire association/dissociation reaction coordinate. We used the model to test our hypothesis that a class of large solution additives, which we term "neutral crowders," can slow protein association and dissociation by being preferentially excluded from protein-protein encounter complexes, in a manner analogous to osmotic stress. The magnitude of this proposed "gap effect" was probed for two simple model systems: the association of two spheres and the association of two planes. Our results suggest that for a protein of 20 A radius, an 8 A additive can increase the free energy barrier for association and dissociation by as much as 3-6 kcal/mol. Because the proposed gap effect is present only for reactions involving multiple molecules, it can be exploited to develop novel additives that affect protein association reactions although having little or no effect on unimolecular reactions such as protein folding. This idea has many potential applications in areas such as the stabilization of proteins against aggregation during folding and in pharmaceutical formulations.

  10. Adding Value to Force Diagrams: Representing Relative Force Magnitudes

    ERIC Educational Resources Information Center

    Wendel, Paul

    2011-01-01

    Nearly all physics instructors recognize the instructional value of force diagrams, and this journal has published several collections of exercises to improve student skill in this area. Yet some instructors worry that too few students perceive the conceptual and problem-solving utility of force diagrams, and over recent years a rich variety of…

  11. Magnetic force and optical force sensing with ultrathin silicon resonator

    NASA Astrophysics Data System (ADS)

    Ono, Takahito; Esashi, Masayoshi

    2003-12-01

    In this article, we demonstrated magnetic and optical force measurements using an ultrathin silicon cantilever down to 20 nm or 50 nm in thickness. The cantilever was heated in an ultrahigh vacuum for enhancing the Q factor and a magnetic particle was mounted at the end of the cantilever using a manipulator. The vibration was measured by a laser Doppler vibrometer and its signal was fed to an opposed metal electrode for electrostatic self-oscillation. An application of a magnetic field with a coil exerted a force to the magnetic material, which results in the change of the resonant frequency. However, the change in the mechanical properties of the cantilever, due to mechanical instability and temperature variation, drifts the resonance peak. Force balancing between the magnetic force and an electrostatic force in the opposite phase can minimize the vibration amplitude. From the electrostatic force at the minimum point, the exerted force can be estimated. A magnetic moment of 4×10-20 J/T was measured by this method. The same technique was also applied to measure the optical force of ˜10-17 N, impinging on the cantilever by a laser diode.

  12. Color Addition and Subtraction Apps

    ERIC Educational Resources Information Center

    Ruiz, Frances; Ruiz, Michael J.

    2015-01-01

    Color addition and subtraction apps in HTML5 have been developed for students as an online hands-on experience so that they can more easily master principles introduced through traditional classroom demonstrations. The evolution of the additive RGB color model is traced through the early IBM color adapters so that students can proceed step by step…

  13. Implication of radiative forcing distribution for energy transport

    NASA Astrophysics Data System (ADS)

    Huang, Yi

    2016-04-01

    Radiative forcing of a homogeneous greenhouse gas can be very inhomogeneous because the forcing is dependent on other atmospheric and surface variables. In the case of doubling CO2, the mean instantaneous forcing at the top of the atmosphere is found to vary geographically and temporally from positive to negative values, with the range being more than three times the magnitude of the global mean value. The vertical temperature change across the atmospheric column (temperature lapse rate) is found to be the best single predictor for explaining forcing variation. In addition, the masking effects of clouds and water vapor also contribute to forcing inhomogeneity. A regression model that predicts forcing from geophysical variables is constructed. This model can explain more than 90% of the variance of the forcing. Applying this model to analyzing the forcing variation in the CMIP5 models, we find that inter-model discrepancy in CO2 forcing caused by model climatology leads to considerable discrepancy in their projected change in poleward energy transport.

  14. Grip-load force coordination in cerebellar patients.

    PubMed

    Serrien, D J; Wiesendanger, M

    1999-09-01

    The study examined the anticipatory grip force modulations to load force changes during a drawer-opening task. An impact force was induced by a mechanical stop which abruptly arrested movement of the pulling hand. In performing this task, normal subjects generated a typical grip force profile characterized by an initial force impulse related to drawer movement onset, followed by a ramp-like grip force increase prior to the impending load perturbation. Finally, a reactive response was triggered by the impact. In patients with bilateral cerebellar dysfunction, the drawer-opening task was performed with an alternative control strategy. During pulling, grip force was increased to a high (overestimated) default level. The latter suggests that cerebellar patients were unable to adjust and to scale precisely the grip force according to the load force. In addition, the latency between impact and reactive activity was prolonged in the patients, suggesting an impaired cerebellar transmission of the long-latency responses. In conclusion, these data demonstrate the involvement of cerebellar circuits in both proactive and reactive mechanisms in view of predictable load perturbations during manipulative behavior. PMID:10473743

  15. Bacterial adhesion force quantification by fluidic force microscopy

    NASA Astrophysics Data System (ADS)

    Potthoff, Eva; Ossola, Dario; Zambelli, Tomaso; Vorholt, Julia A.

    2015-02-01

    Quantification of detachment forces between bacteria and substrates facilitates the understanding of the bacterial adhesion process that affects cell physiology and survival. Here, we present a method that allows for serial, single bacterial cell force spectroscopy by combining the force control of atomic force microscopy with microfluidics. Reversible bacterial cell immobilization under physiological conditions on the pyramidal tip of a microchanneled cantilever is achieved by underpressure. Using the fluidic force microscopy technology (FluidFM), we achieve immobilization forces greater than those of state-of-the-art cell-cantilever binding as demonstrated by the detachment of Escherichia coli from polydopamine with recorded forces between 4 and 8 nN for many cells. The contact time and setpoint dependence of the adhesion forces of E. coli and Streptococcus pyogenes, as well as the sequential detachment of bacteria out of a chain, are shown, revealing distinct force patterns in the detachment curves. This study demonstrates the potential of the FluidFM technology for quantitative bacterial adhesion measurements of cell-substrate and cell-cell interactions that are relevant in biofilms and infection biology.Quantification of detachment forces between bacteria and substrates facilitates the understanding of the bacterial adhesion process that affects cell physiology and survival. Here, we present a method that allows for serial, single bacterial cell force spectroscopy by combining the force control of atomic force microscopy with microfluidics. Reversible bacterial cell immobilization under physiological conditions on the pyramidal tip of a microchanneled cantilever is achieved by underpressure. Using the fluidic force microscopy technology (FluidFM), we achieve immobilization forces greater than those of state-of-the-art cell-cantilever binding as demonstrated by the detachment of Escherichia coli from polydopamine with recorded forces between 4 and 8 nN for many

  16. Atomic Force Microscope Operation

    NASA Technical Reports Server (NTRS)

    2008-01-01

    [figure removed for brevity, see original site] Click on image for animation (large file)

    This animation is a scientific illustration of the operation of NASA's Phoenix Mars Lander's Atomic Force Microscope, or AFM. The AFM is part of Phoenix's Microscopy, Electrochemistry, and Conductivity Analyzer, or MECA.

    The AFM is used to image the smallest Martian particles using a very sharp tip at the end of one of eight beams.

    The beam of the AFM is set into vibration and brought up to the surface of a micromachined silicon substrate. The substrate has etched in it a series of pits, 5 micrometers deep, designed to hold the Martian dust particles.

    The microscope then maps the shape of particles in three dimensions by scanning them with the tip.

    At the end of the animation is a 3D representation of the AFM image of a particle that was part of a sample informally called 'Sorceress.' The sample was delivered to the AFM on the 38th Martian day, or sol, of the mission (July 2, 2008).

    The image shows four round pits, only 5 microns in depth, that were micromachined into the silicon substrate.

    A Martian particle only one micrometer, or one millionth of a meter, across is held in the upper left pit.

    The rounded particle shown at the highest magnification ever seen from another world is a particle of the dust that cloaks Mars. Such dust particles color the Martian sky pink, feed storms that regularly envelop the planet and produce Mars' distinctive red soil.

    The AFM was developed by a Swiss-led consortium, with Imperial College London producing the silicon substrate that holds sampled particles.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  17. Probabilistic sampling of protein conformations: new hope for brute force?

    PubMed

    Feldman, Howard J; Hogue, Christopher W V

    2002-01-01

    Protein structure prediction from sequence alone by "brute force" random methods is a computationally expensive problem. Estimates have suggested that it could take all the computers in the world longer than the age of the universe to compute the structure of a single 200-residue protein. Here we investigate the use of a faster version of our FOLDTRAJ probabilistic all-atom protein-structure-sampling algorithm. We have improved the method so that it is now over twenty times faster than originally reported, and capable of rapidly sampling conformational space without lattices. It uses geometrical constraints and a Leonard-Jones type potential for self-avoidance. We have also implemented a novel method to add secondary structure-prediction information to make protein-like amounts of secondary structure in sampled structures. In a set of 100,000 probabilistic conformers of 1VII, 1ENH, and 1PMC generated, the structures with smallest Calpha RMSD from native are 3.95, 5.12, and 5.95A, respectively. Expanding this test to a set of 17 distinct protein folds, we find that all-helical structures are "hit" by brute force more frequently than beta or mixed structures. For small helical proteins or very small non-helical ones, this approach should have a "hit" close enough to detect with a good scoring function in a pool of several million conformers. By fitting the distribution of RMSDs from the native state of each of the 17 sets of conformers to the extreme value distribution, we are able to estimate the size of conformational space for each. With a 0.5A RMSD cutoff, the number of conformers is roughly 2N where N is the number of residues in the protein. This is smaller than previous estimates, indicating an average of only two possible conformations per residue when sterics are accounted for. Our method reduces the effective number of conformations available at each residue by probabilistic bias, without requiring any particular discretization of residue conformational

  18. Atomic Force Microscope Mediated Chromatography

    NASA Technical Reports Server (NTRS)

    Anderson, Mark S.

    2013-01-01

    sliding plate system, consisting of two flat surfaces, one of which has a recessed channel. A fluid flow is produced by axially sliding one plate past another, where the fluid has mechanical shear forces imposed at each point along the channel length. The shear-induced flow rates are very reproducible, and do not have pressure or voltage gradient limitations. SDC opens up a new range of enhanced separation kinetics by permitting the sample confinement with submicron dimensions. Small, highly confined liquid is advantageous for chromatographic separation because the separation rate is known to scale according to the square of the confined sample diameter. In addition, because shear-driven flows are not limited by fluid velocity, shear-driven liquid chromatography may provide up to 100,000 plate efficiency.

  19. Nanopatterning by atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Tang, Qian

    fabricated nanostructures via anodic nanooxidation and force nanolithography. In addition, we characterized the protein patterns with AFM by adsorption of a protein surfaces with different adsorption properties, and discussed the mechanism of the protein adsorption on these surfaces.

  20. Radiative forcing and climate response

    NASA Astrophysics Data System (ADS)

    Hansen, J.; Sato, M.; Ruedy, R.

    1997-03-01

    We examine the sensitivity of a climate model to a wide range of radiative forcings, including changes of solar irradiance, atmospheric CO2, O3, CFCs, clouds, aerosols, surface albedo, and a "ghost" forcing introduced at arbitrary heights, latitudes, longitudes, seasons, and times of day. We show that, in general, the climate response, specifically the global mean temperature change, is sensitive to the altitude, latitude, and nature of the forcing; that is, the response to a given forcing can vary by 50% or more depending upon characteristics of the forcing other than its magnitude measured in watts per square meter. The consistency of the response among different forcings is higher, within 20% or better, for most of the globally distributed forcings suspected of influencing global mean temperature in the past century, but exceptions occur for certain changes of ozone or absorbing aerosols, for which the climate response is less well behaved. In all cases the physical basis for the variations of the response can be understood. The principal mechanisms involve alterations of lapse rate and decrease (increase) of large-scale cloud cover in layers that are preferentially heated (cooled). Although the magnitude of these effects must be model-dependent, the existence and sense of the mechanisms appear to be reasonable. Overall, we reaffirm the value of the radiative forcing concept for predicting climate response and for comparative studies of different forcings; indeed, the present results can help improve the accuracy of such analyses and define error estimates. Our results also emphasize the need for measurements having the specificity and precision needed to define poorly known forcings such as absorbing aerosols and ozone change. Available data on aerosol single scatter albedo imply that anthropogenic aerosols cause less cooling than has commonly been assumed. However, negative forcing due to the net ozone change since 1979 appears to have counterbalanced 30

  1. Dynein arms are strain-dependent direction-switching force generators.

    PubMed

    Shingyoji, Chikako; Nakano, Izumi; Inoue, Yuichi; Higuchi, Hideo

    2015-08-01

    Dynein is a minus-end-directed motor that can generate (forward) force to move along the microtubule toward its minus end. In addition, axonemal dyneins were reported to oscillate in the generation of forward force, and cytoplasmic dynein is observed to generate bidirectional forces in response to defined chemical states. Both dyneins can also respond to mechanically applied force. To test whether axonemal dynein can switch direction of force generation, we measured force using an optical trap and UV-photolysis of caged ATP. We observed that isolated dynein could repeatedly generate force in both directions along the microtubule. Bidirectional force was also observed for dynein arms that are still attached on the doublet microtubules. Axonemal dynein generated force to move backward (∼ 4 pN) as well as forward (5-6 pN) along microtubules. Furthermore, backward force could be stimulated by plus-end directed external force applied to axonemal dynein before ATP application. The results show that axonemal dynein is unique exhibiting multiple modes of force generation including backward and forward force, oscillatory force and slow, repetitive bidirectional force. The results also demonstrate that mechanical strain is important for switching the directionality of force generation in axonemal dyneins.

  2. Exotic nuclei and nuclear forces

    NASA Astrophysics Data System (ADS)

    Otsuka, Takaharu

    2013-01-01

    I overview new aspects of the structure of exotic nuclei as compared to stable nuclei, focusing on several characteristic effects of nuclear forces. The shell structure of nuclei has been proposed by Mayer and Jensen, and has been considered to be kept valid basically for all nuclei, with well-known magic numbers, 2, 8, 20, 28, 50, …. Nuclear forces were shown, very recently, to change this paradigm. It will be presented that the evolution of shell structure occurs in various ways as more neutrons and/or protons are added, and I will present basic points of this shell evolution in terms of the monopole interaction of nuclear forces. I will discuss three types of nuclear forces. The first one is the tensor force. The tensor force is one of the most fundamental nuclear forces, but its first-order effect on the shell structure has been clarified only recently in studies on exotic nuclei. The tensor force can change the spin-orbit splitting depending on the occupation of specific orbits. This results in changes of the shell structure in many nuclei, and consequently some of Mayer-Jensen's magic numbers are lost and new ones emerge, in certain nuclei. This mechanism can be understood in an intuitive way, meaning that the effect is general and robust. The second type of nuclear forces is central force. I will show a general but unknown property of the central force in the shell-model Hamiltonian that can describe nuclear properties in a good agreement with experiment. I will then demonstrate how it can be incorporated into a simple model of the central force, and will discuss how this force works in the shell evolution. Actually, by combining this central force with the tensor force, one can understand and foresee how the same proton-neutron interaction drives the shell evolution, for examples such as Sn/Sb isotopes, N = 20 nuclei and Ni/Cu isotopes. The distribution of single-particle strength is discussed also in comparison to (e,e‧p) experiment on 48Ca. The shell

  3. Color Addition and Subtraction Apps

    NASA Astrophysics Data System (ADS)

    Ruiz, Frances; Ruiz, Michael J.

    2015-10-01

    Color addition and subtraction apps in HTML5 have been developed for students as an online hands-on experience so that they can more easily master principles introduced through traditional classroom demonstrations. The evolution of the additive RGB color model is traced through the early IBM color adapters so that students can proceed step by step in understanding mathematical representations of RGB color. Finally, color addition and subtraction are presented for the X11 colors from web design to illustrate yet another real-life application of color mixing.

  4. How Does Force Affect Motion?

    ERIC Educational Resources Information Center

    Darling, Gerald

    2012-01-01

    Whether playing soccer at recess, walking to lunch, or sitting at their desk, children encounter forces every moment of their lives. The connection between force and motion is absolutely amazing to children, so anyone working with them better be prepared for the battery of tough questions they ask: "What made the ball move that way? Why does a…

  5. Low-closing-force seal

    NASA Technical Reports Server (NTRS)

    Bergquist, L. E.

    1973-01-01

    Compress soft, inert metal gasket between cone and corresponding socket to attach tubes to vessels containing gas samples. Technique effects seals with minimum of applied force and does not contaminate contents. Seal is formed when port connector is pushed firmly into its socket. Gold washer is deformed and forced to flow into imperfections in surfaces.

  6. Minorities in the Armed Forces

    ERIC Educational Resources Information Center

    Griggs, Anthony

    1973-01-01

    Summarizes the findings of the Congressional Black Caucus and the specially formed task force; reports that high ranking officers have pledged to attack racial discrimination; and describes an association of minority officers whose purpose is to enhance the image of the armed forces within the minority community. (Author/JM)

  7. Force optimized recoil control system

    NASA Astrophysics Data System (ADS)

    Townsend, P. E.; Radkiewicz, R. J.; Gartner, R. F.

    1982-05-01

    Reduction of the recoil force of high rate of fire automatic guns was proven effective. This system will allow consideration of more powerful guns for use in both helicopter and armored personnel carrier applications. By substituting the large shock loads of firing guns with a nearly constant force, both vibration and fatigue problems that prevent mounting of powerful automatic guns is eliminated.

  8. Pseudo force acting between bodies

    NASA Astrophysics Data System (ADS)

    Baruah, Abhinav Ray; Deva, Anish; Sarma, Arun

    It has been shown that a non-contact force acts between two macroscopic physical objects held close together, which is not associated with the gravitational and electrostatic force. An experiment was conducted with objects of different mass, material and geometry to find the magnitude and properties of this apparent or pseudo force. The order of magnitude was found to be 10-5 and it remained constant for all types of objects while only the coefficient increased as the distance between the objects reduced. It only started acting at small distances and failed to make a body move if it experienced static friction from any contact surface. The nature of the force was found to be attractive as well as repulsive. Due to gravitation being a solely attractive force, it was eliminated as a possible reason for the pseudo force. The experiment was performed twice, once by grounding the apparatus and then again without grounding. The order of the force remained the same for both cases. As the test objects were held by hand, they were grounded through the human body. Also, none of the objects used were in contact with each other for the duration of this work, preventing any contact electrification. Due to these factors, the force was not considered electrostatic in nature.

  9. The Forced Hard Spring Equation

    ERIC Educational Resources Information Center

    Fay, Temple H.

    2006-01-01

    Through numerical investigations, various examples of the Duffing type forced spring equation with epsilon positive, are studied. Since [epsilon] is positive, all solutions to the associated homogeneous equation are periodic and the same is true with the forcing applied. The damped equation exhibits steady state trajectories with the interesting…

  10. Grasp force control in telemanipulation

    NASA Technical Reports Server (NTRS)

    Wiker, Steven F.; Duffie, Neil A.

    1992-01-01

    This paper presents two experiments which focus upon the issue of grasp force control in telemanipulation. The first experiment examines the ability to control and stabilize master-controller grasp force during a 30-s compensatory tracking task under different levels of master controller digit mass, friction, and backlash. The second experiment explores the potential for substituting tactile feedback in lieu of direct force-feedback to gage and control remote grasp force. Results show that subjects were better able to control force when mass and friction levels were increased. Even when perceptual gains between tactile and direct force feedback displays were matched, force reflection produced better grasp control. The lack of backlash effects and improvements in performance with direct force reflection in comparison to tactile feedback are attributable to reflexive short-loop adjustment of grasp tension afforded by the muscle's length-tension control system. The criterion of acceptable operator performance, dependent upon both the quality of the transmission of control commands and feedback, and the response of the remote device, is discussed.

  11. Simplified Relativistic Force Transformation Equation.

    ERIC Educational Resources Information Center

    Stewart, Benjamin U.

    1979-01-01

    A simplified relativistic force transformation equation is derived and then used to obtain the equation for the electromagnetic forces on a charged particle, calculate the electromagnetic fields due to a point charge with constant velocity, transform electromagnetic fields in general, derive the Biot-Savart law, and relate it to Coulomb's law.…

  12. Measuring Forces of Bacterial Biofilms on Substrates

    NASA Astrophysics Data System (ADS)

    Cooley, Benjamin; Gordon, Vernita

    2010-10-01

    Biofilms are multicellular aggregates of microorganisms with distinct gene expression and often complex spatial structure. Understanding the forces exerted by bacterial biofilms on their substrates could help in understanding damage they cause in industrial settings and to living tissue in biofilm infections. Here we propose a series of experiments to study the forces between biofilms and substrates using rheological and micro-rheological techniques. Polystyrene tracer beads embedded in agar gels can be mapped over the course of biofilm development, and these timelapse motions will show the strain in the substrate. Meanwhile, measurements of the Brownian motion of selected tracer beads can yield information about the microstructure of the agar. For instance, the extent of the Brownian motion will be increased if the agar is stretched apart or broken down. Additionally, tracers in the biofilms themselves would permit the study of the rheology of the biofilms throughout their development.

  13. Force-controlled lifting of molecular wires

    NASA Astrophysics Data System (ADS)

    Fournier, N.; Wagner, C.; Weiss, C.; Temirov, R.; Tautz, F. S.

    2011-07-01

    Lifting a single molecular wire off the surface with a combined frequency-modulated atomic force and tunneling microscope it is possible to monitor the evolution of both the wire configuration and the contacts simultaneously with the transport conductance experiment. In particular, critical points where individual bonds to the surface are broken and instabilities where the wire is prone to change its contact configuration can be identified in the force gradient and dissipation responses of the junction. This additional mechanical information can be used to unambiguously determine the conductance of a true molecular wire, that is, of a molecule that is contacted via a pointlike “crocodile clip” to each of the electrodes but is otherwise free.

  14. Friction forces on atoms after acceleration

    SciTech Connect

    Intravaia, Francesco; Mkrtchian, Vanik E.; Buhmann, Stefan Yoshi; Scheel, Stefan; Dalvit, Diego A. R.; Henkel, Carsten

    2015-05-12

    The aim of this study is to revisit the calculation of atom–surface quantum friction in the quantum field theory formulation put forward by Barton (2010 New J. Phys. 12 113045). We show that the power dissipated into field excitations and the associated friction force depend on how the atom is boosted from being initially at rest to a configuration in which it is moving at constant velocity (v) parallel to the planar interface. In addition, we point out that there is a subtle cancellation between the one-photon and part of the two-photon dissipating power, resulting in a leading order contribution to the frictional power which goes as v4. These results are also confirmed by an alternative calculation of the average radiation force, which scales as v3.

  15. Management of change through force field analysis.

    PubMed

    Baulcomb, Jean Sandra

    2003-07-01

    Today's NHS is rapidly changing, placing more emphasis on the managerial responsibilities of ward managers. Managing change is seen as being skilled at creating, acquiring and transferring knowledge to reflect new knowledge and insights. Defining core concepts is often difficult and requires the drawing on models/theories of change for guidance. Guidance from Lewin's (1951) force field analysis demonstrates the complexities of the change process and how driving and resisting forces were incorporated within the planning and implementation phases. Findings outline the benefits of a small scale change for staff, patients and the organization when successfully used to introduce a change of shift pattern within a progressively busy haematology day unit, in order to meet service demands without additional funding. Conclusions have been drawn in relation to the process and recommendations for practice made to further enhance care delivery within the unit. PMID:12801382

  16. Friction forces on atoms after acceleration

    DOE PAGES

    Intravaia, Francesco; Mkrtchian, Vanik E.; Buhmann, Stefan Yoshi; Scheel, Stefan; Dalvit, Diego A. R.; Henkel, Carsten

    2015-05-12

    The aim of this study is to revisit the calculation of atom–surface quantum friction in the quantum field theory formulation put forward by Barton (2010 New J. Phys. 12 113045). We show that the power dissipated into field excitations and the associated friction force depend on how the atom is boosted from being initially at rest to a configuration in which it is moving at constant velocity (v) parallel to the planar interface. In addition, we point out that there is a subtle cancellation between the one-photon and part of the two-photon dissipating power, resulting in a leading order contributionmore » to the frictional power which goes as v4. These results are also confirmed by an alternative calculation of the average radiation force, which scales as v3.« less

  17. Measurement and analysis of forces in grinding of silicon nitride

    SciTech Connect

    Jahanmir, S.; Hwang, T.; Whitenton, E.P.; Job, L.S.; Evans, C.J.

    1995-12-31

    Using an instrumented surface grinder, the two components of grinding forces (normal and tangential) were measured for different types of silicon nitride ceramics. The influences of grinding parameters, such as down feed and table speed, and grinding fluids on forces were determined. In addition to these measurements, the specific grinding energy defined as the energy per unit volume of removed material was calculated. This parameter and the measured forces were then analyzed to determine possible correlations with mechanical properties of the silicon nitrides. It was found that, in general, the grinding forces and the specific grinding energy increase with the hardness. Both the grinding forces and the specific grinding energy were influenced by the grinding fluid and the grinding parameters. The implication of these results on the mechanisms of material removal in grinding of silicon nitride and the possible tribological effects are discussed.

  18. Recent Investments by NASA's National Force Measurement Technology Capability

    NASA Technical Reports Server (NTRS)

    Commo, Sean A.; Ponder, Jonathan D.

    2016-01-01

    The National Force Measurement Technology Capability (NFMTC) is a nationwide partnership established in 2008 and sponsored by NASA's Aeronautics Evaluation and Test Capabilities (AETC) project to maintain and further develop force measurement capabilities. The NFMTC focuses on force measurement in wind tunnels and provides operational support in addition to conducting balance research. Based on force measurement capability challenges, strategic investments into research tasks are designed to meet the experimental requirements of current and future aerospace research programs and projects. This paper highlights recent and force measurement investments into several areas including recapitalizing the strain-gage balance inventory, developing balance best practices, improving calibration and facility capabilities, and researching potential technologies to advance balance capabilities.

  19. Direct Cytoskeleton Forces Cause Membrane Softening in Red Blood Cells

    PubMed Central

    Rodríguez-García, Ruddi; López-Montero, Iván; Mell, Michael; Egea, Gustavo; Gov, Nir S.; Monroy, Francisco

    2015-01-01

    Erythrocytes are flexible cells specialized in the systemic transport of oxygen in vertebrates. This physiological function is connected to their outstanding ability to deform in passing through narrow capillaries. In recent years, there has been an influx of experimental evidence of enhanced cell-shape fluctuations related to metabolically driven activity of the erythroid membrane skeleton. However, no direct observation of the active cytoskeleton forces has yet been reported to our knowledge. Here, we show experimental evidence of the presence of temporally correlated forces superposed over the thermal fluctuations of the erythrocyte membrane. These forces are ATP-dependent and drive enhanced flickering motions in human erythrocytes. Theoretical analyses provide support for a direct force exerted on the membrane by the cytoskeleton nodes as pulses of well-defined average duration. In addition, such metabolically regulated active forces cause global membrane softening, a mechanical attribute related to the functional erythroid deformability. PMID:26083919

  20. Detecting the gravitational sensitivity of Paramecium caudatum using magnetic forces

    NASA Astrophysics Data System (ADS)

    Guevorkian, Karine; Valles, James M., Jr.

    2006-03-01

    Under normal conditions, Paramecium cells regulate their swimming speed in response to the pN level mechanical force of gravity. This regulation, known as gravikinesis, is more pronounced when the external force is increased by methods such as centrifugation. Here we present a novel technique that simulates gravity fields using the interactions between strong inhomogeneous magnetic fields and cells. We are able to achieve variable gravities spanning from 10xg to -8xg; where g is earth's gravity. Our experiments show that the swimming speed regulation of Paramecium caudatum to magnetically simulated gravity is a true physiological response. In addition, they reveal a maximum propulsion force for paramecia. This advance establishes a general technique for applying continuously variable forces to cells or cell populations suitable for exploring their force transduction mechanisms.