COordinated Responsive Arrays of Surface-Linked polymer islands (CORALS) allow for the creation o... more COordinated Responsive Arrays of Surface-Linked polymer islands (CORALS) allow for the creation of molecular surfaces with novel and switchable properties. Critical components of CORALs are the uniformly distributed islands of densely grafted polymer chains (nanoislands) separated by regions of bare surface. The grafting footprint and separation distances of nanoislands are comparable to that of the constituent polymer chains themselves. Herein, we characterize the structural features of the nanoislands and semiflexible polymers within to better understand this critical constituent of CORALs. We observe different characteristics of grafted semiflexible polymers depending on the polymer island’s size and distance from the center of the island. Specifically, the characteristics of the chains at the island periphery are similar to isolated tethered polymer chains (full flexible chains), while chains in the center of the island experience the neighbor effect such as chains in the classi...
Molecular dynamics simulations were used to study the structural perturbations of lipids surround... more Molecular dynamics simulations were used to study the structural perturbations of lipids surrounding transmembrane ion channel forming helices/helical bundles and the movement of water within the pores of the ion-channels/bundles. Specifically, helical monomers to hexameric helical bundles embedded in palmitoyl-oleoyl-phosphatidyl-choline (POPC) lipid bilayer were studied. Two amphipathic α-helices with the sequence Ac-(LSLLLSL) 3 -NH 2 (LS2), and Ac-(LSSLLSL) 3 -NH 2 (LS3), which are known to form ion channels, were used. To investigate the surrounding lipid environment, we examined the hydrophobic mismatch, acyl chain order parameter profiles, lipid head-to-tail vector projection on the membrane surface, and the lipid headgroup vector projection. We find that the lipid structure is perturbed within approximately two lipid solvation shells from the protein bundle for each system (~15.0 A). Beyond two lipid “solvation” shells bulk lipid bilayer properties were observed in all systems. To understand water flow, we enumerated each time a water molecule enters or exited the channel, which allowed us to calculate the number of water crossing events and their rates, and the residence time of water in the channel. We correlate the rate of water crossing with the structural properties of these ion channels and find that the movements of water are predominantly governed by the packing and pore diameter, rather than the topology of each peptide or the pore (hydrophobic or hydrophilic). We show that the crossing events of water fit quantitatively to a stochastic process and that water molecules are traveling diffusively through the pores. These lipid and water findings can be used for understanding the environment within and around ion channels. Furthermore, these findings can benefit various research areas such as rational design of novel therapeutics, in which the drug interacts with membranes and transmembrane proteins to enhance the efficacy or reduce off-target effects.
The concept of CoOrdinated Responsive Arrays of surface Linked islands (polymer CORALs) is introd... more The concept of CoOrdinated Responsive Arrays of surface Linked islands (polymer CORALs) is introduced. This study targets a responsive system capable of revealing or covering the substrate surface in response to environmental changes in a reversible way. A convenient method of fabrication of polymer CORALs is proposed. It is based on microphase separation that occurs in thin films of supramolecular assemblies of block copolymers with reactive blocks. Such blocks form nanometer-size domains that may serve as anchors for surfacelinked polymer islands. Two characteristics of the islands are critically important for the switching function: high grafting density within the islands and small lateral separation that allows interactions between polymer chains grafted to neighboring islands. This combination permits complete coverage of the substrate surface upon exposure to a good solvent (relaxed state). In a weak solvent, the chains collapse within the islands thus revealing the substrate (compact state). The morphology of the CORALs in both states and some details of switching process were studied with atomic force microscopy, grazing incidence small angle scattering, and coarse grained molecular dynamic simulations.
A key component to the success of multiscale modeling approaches is the ability to switch between... more A key component to the success of multiscale modeling approaches is the ability to switch between molecular representations involving different levels of detail. In particular, the transition from a coarse to a fine representation is challenging because it requires the creation of information. To address this challenge, an algorithm is presented to fill in the detail when a coarse grain representation of a molecular system is replaced by an atomistic representation. The algorithm consists of minimization on the Lie group SO(3) for every coarse grain site, using the components of the atomistic force field that operate between atoms belonging to different coarse grain sites. This method is maximally efficient because the optimization is done at the coarse level using frozen atomistic library structures corresponding to each kind of coarse grain unit. The algorithm can be applied to any system since its input requirements are simply the force fields and molecular structures of both levels. The role of the algorithm in dual-resolution multiscale simulation methodology is discussed, and the efficacy of the algorithm is demonstrated through its implementation to liquid dodecane.
Functionalized single-walled carbon nanotubes (SWNTs) are widely applied in biomedical science. T... more Functionalized single-walled carbon nanotubes (SWNTs) are widely applied in biomedical science. To understand the interaction between SWNTs and biological systems, various studies have attempted to use coarsegrained molecular dynamics (CGMD). However, there is limited validation of the existing CG models of SWNTs. Here, we present CG models for both pristine and carboxylated SWNTs which are validated against experimental dispersion data. In addition, we present the first ever DLVO analysis of the colloidal stability of parallel SWNTs and establish that the solvent-induced repulsion between fullerenes, which is not considered in DLVO theory, is crucial to obtain a correct physical picture of SWNT dispersibility. The results presented here provide physical insight into the colloidal stability of SWNTs and can be applied to large-scale MD studies of biological systems.
Coupling between the inner and outer leaflets of a bilayer plays an important role in biomembrane... more Coupling between the inner and outer leaflets of a bilayer plays an important role in biomembrane function, particularly in inducing and registering rafts across leaflets for various cellular signals. However, mechanisms of raft registration remain elusive and several alternatives have been proposed, ranging from electrostatic coupling to chain interdigitation, cholesterol flip-flop and compositioncurvature coupling. A general mechanism has been suggested by recent experiments with mixtures of polymer amphiphiles that exhibit domain registration upon ligand-induced segregation. Here, using coarse grained molecular dynamics (CGMD) simulations that are rooted in atomistics, we show that raft registration arises spontaneously in bilayers with a calcium-or ligand-crosslinked ordered phase segregating from a liquid disordered phase. When rafts are not registered, a thickness mismatch between phases induces a ''bump'' in the apposing liquid phase leaflet, and it appears that the associated localized curvature change guides rafts together and stabilizes the registered state. The absence of explicit charge in the model and the fact that domain size modulates the strength of transmembrane coupling demonstrate that collective interactions are sufficient for raft registration.
We discuss three topologically different methods for calculating the surface tension between a fl... more We discuss three topologically different methods for calculating the surface tension between a flat solid and a liquid from theoretical and computer simulation viewpoints. The first method, commonly used in experiments, measures the contact angle at which a static droplet of liquid rests on a solid surface. We present a new analysis algorithm for this method and explore the effects of line tension on the contact angle. The second method, commonly used computer simulations, uses the pressure tensor through the virial in a system where a thick, infinitely extended slab of liquid rests on a solid surface. The third method, which is original to this paper and is closest to the thermodynamic definition of surface tension, applies to a spherical solid in contact with liquid in which the flat solid is recovered by extrapolating the sphere radius to infinity. We find that the second and third methods agree with each other, while the first method systematically underestimates surface tension values.
Normal mode analysis (NMA) is applied in a molecular-dynamics simulation of liquid CS2, modeled w... more Normal mode analysis (NMA) is applied in a molecular-dynamics simulation of liquid CS2, modeled with a potential including internal degrees of freedom. The entire supercooled liquid range, from the glass transition at 100 K to melting at 165 K, and the normal liquid from 165 to 293 K, are studied at P=1 atm. The normal modes of the liquid are classified as translation parallel (trans-∥) and perpendicular (trans-⊥) to the molecular axis, rotation, symmetric stretch, antisymmetric stretch, and bend. The configuration-averaged density of states, 〈ρ(ω)〉, with both stable and unstable modes, is correspondingly decomposed into separate contributions 〈ργ(ω)〉, with γ=trans-∥, etc. The trans-∥, trans-⊥, and rotational velocity correlation functions, and diffusion constants Dγ, are shown to be calculable from the same NMA techniques previously developed for atoms, so long as the appropriate 〈ργ(ω)〉 is used. Agreement between NMA theory and simulation is extremely good for the trans-⊥ velocity...
International journal of engineering research & technology (Ahmedabad), 2014
Polyphosphazenes, because of their unique properties, have generated many opportunities to explor... more Polyphosphazenes, because of their unique properties, have generated many opportunities to explore a variety of applications. These applications include areas such as biomedical research (e.g. drug delivery) and material science (e.g. fire-resistant polymers). Phosphazenes potentially have more variations then benzene analogues because of different substitution patterns. Here we present A computational study of the chemical modifications to a group of cyclic phosphazenes mainly hexachlorophosphazene (PNCl2)3. This study focuses on the relative energies of reactivity of hexachlorophosphazene to understand their geometry and the complexes they likely form. We compare diols, amino alcohols, and diamines with a carbon linker of 1-7 atoms. These heteroatom chains are attached to a single phosphorus atom or adjoining phosphorus atoms to form ring structures of geminal, vicinal (cis), and vicinal (trans) moieties. We find that the reactivities of "heteroatom caps" are predicted t...
Journal of organic and biomolecular simulations, 2014
We present a computational study of the effect of chemical modifications of the meta and para sub... more We present a computational study of the effect of chemical modifications of the meta and para substituents in the coordinating pendant arm of a modified 1,4,7,10-tetraazacyclododecane-N, N', N″, N‴-tetraamide (DOTAM) ligand on the Chemical Exchange Saturation Transfer (CEST) signal. Magnetic Resonance Imaging (MRI) is currently one of the most widely used techniques available. MRI has led to a new class of pharmaceuticals termed "imagining" or "contrast" agents. These agents usually work by incorporating lanthanide metals such as Gadolinium (Gd) and Europium (Eu). This allows the contrast agents to take advantage of the paramagnetic properties of the metals, which in turn enhances the signal detectable by MRI. The effect of simple electron-withdrawing (e.g., nitro) and electron-donating (e.g., methyl) substituents chemically attached to a modified chelate arm (pendant arm) is quantified by charge transfer interactions in the coordinated water-chelate system c...
N,N'-Dialkylimidazolium ionic liquids (ILs) show promise as non-derivatizing 'green' ... more N,N'-Dialkylimidazolium ionic liquids (ILs) show promise as non-derivatizing 'green' solvents for the dissolution and processing of cellulose. To better understand how these ILs solvate this and other polysaccharides at the molecular level, we have performed molecular dynamics (MD) simulations of neat 1-n-butyl-3-methylimidazolium chloride ([C 4 mim]Cl) at 298, 313, 333, 343, 353, 363, and 373 K, as well as 5 and 10 wt% cellobiose solutions in [C 4 mim]Cl at 363 K. Static, dynamic, and thermodynamic quantities have been derived from the collected data. Our findings agree well with experimental data from various sources. In particular, analysis of structural features and hydrogen bonding patterns between [C 4 mim]Cl and cellobiose are consistent with results from NMR relaxation studies which indicate that the IL Cl" ions interact with the carbohydrate OH groups in a ∼ 1:1 ratio.
A computationally efficient coarse grain model designed to closely mimic specific phospholipids i... more A computationally efficient coarse grain model designed to closely mimic specific phospholipids is used to study a number of phospholipid systems to demonstrate its strengths and weaknesses. A study of a membrane containing an anesthetic, halothane, illustrates the ...
We present the results of coarse grained molecular dynamics simulation using a charge free model ... more We present the results of coarse grained molecular dynamics simulation using a charge free model that is able to capture different regions of the morphological phase diagram of charged diblock copolymers. Specifically, we were able to reproduce many phases of the poly(acrylic acid)-(1,4)-polybutadiene (PAA-PBA) diblock copolymer, Ca(2+) and water systems as a function of pH and calcium concentration with short-range LJ type potentials. The morphologies observed range from bilayers to cylinders to spherical micelles. Such polyanionic/cationic amphiphiles in water typically present multiple challenges for molecular simulations, particularly due to the many charge interactions that are long ranged and computationally costly. Further, it is precisely these interactions that are thought to modulate large amphiphile assemblies of interest such as lipid rafts. However, our model is able to reproduce different morphologies due to pH and with or without the addition of Ca(2+) as well as the lateral phase segregation and the domain registration observed in neutral and charged diblock copolymer mixtures. The results suggest that the overall effect of charges is a local structural rearrangement that renormalizes the steric repulsion between the headgroups. This simple model, which is devoid of charges, is able to reproduce the complex phase diagram and can be used to investigate collective phenomena in these charged systems such as domain formation and registration or colocalization of lipid rafts across bilayer leaflets.
COordinated Responsive Arrays of Surface-Linked polymer islands (CORALS) allow for the creation o... more COordinated Responsive Arrays of Surface-Linked polymer islands (CORALS) allow for the creation of molecular surfaces with novel and switchable properties. Critical components of CORALs are the uniformly distributed islands of densely grafted polymer chains (nanoislands) separated by regions of bare surface. The grafting footprint and separation distances of nanoislands are comparable to that of the constituent polymer chains themselves. Herein, we characterize the structural features of the nanoislands and semiflexible polymers within to better understand this critical constituent of CORALs. We observe different characteristics of grafted semiflexible polymers depending on the polymer island’s size and distance from the center of the island. Specifically, the characteristics of the chains at the island periphery are similar to isolated tethered polymer chains (full flexible chains), while chains in the center of the island experience the neighbor effect such as chains in the classi...
Molecular dynamics simulations were used to study the structural perturbations of lipids surround... more Molecular dynamics simulations were used to study the structural perturbations of lipids surrounding transmembrane ion channel forming helices/helical bundles and the movement of water within the pores of the ion-channels/bundles. Specifically, helical monomers to hexameric helical bundles embedded in palmitoyl-oleoyl-phosphatidyl-choline (POPC) lipid bilayer were studied. Two amphipathic α-helices with the sequence Ac-(LSLLLSL) 3 -NH 2 (LS2), and Ac-(LSSLLSL) 3 -NH 2 (LS3), which are known to form ion channels, were used. To investigate the surrounding lipid environment, we examined the hydrophobic mismatch, acyl chain order parameter profiles, lipid head-to-tail vector projection on the membrane surface, and the lipid headgroup vector projection. We find that the lipid structure is perturbed within approximately two lipid solvation shells from the protein bundle for each system (~15.0 A). Beyond two lipid “solvation” shells bulk lipid bilayer properties were observed in all systems. To understand water flow, we enumerated each time a water molecule enters or exited the channel, which allowed us to calculate the number of water crossing events and their rates, and the residence time of water in the channel. We correlate the rate of water crossing with the structural properties of these ion channels and find that the movements of water are predominantly governed by the packing and pore diameter, rather than the topology of each peptide or the pore (hydrophobic or hydrophilic). We show that the crossing events of water fit quantitatively to a stochastic process and that water molecules are traveling diffusively through the pores. These lipid and water findings can be used for understanding the environment within and around ion channels. Furthermore, these findings can benefit various research areas such as rational design of novel therapeutics, in which the drug interacts with membranes and transmembrane proteins to enhance the efficacy or reduce off-target effects.
The concept of CoOrdinated Responsive Arrays of surface Linked islands (polymer CORALs) is introd... more The concept of CoOrdinated Responsive Arrays of surface Linked islands (polymer CORALs) is introduced. This study targets a responsive system capable of revealing or covering the substrate surface in response to environmental changes in a reversible way. A convenient method of fabrication of polymer CORALs is proposed. It is based on microphase separation that occurs in thin films of supramolecular assemblies of block copolymers with reactive blocks. Such blocks form nanometer-size domains that may serve as anchors for surfacelinked polymer islands. Two characteristics of the islands are critically important for the switching function: high grafting density within the islands and small lateral separation that allows interactions between polymer chains grafted to neighboring islands. This combination permits complete coverage of the substrate surface upon exposure to a good solvent (relaxed state). In a weak solvent, the chains collapse within the islands thus revealing the substrate (compact state). The morphology of the CORALs in both states and some details of switching process were studied with atomic force microscopy, grazing incidence small angle scattering, and coarse grained molecular dynamic simulations.
A key component to the success of multiscale modeling approaches is the ability to switch between... more A key component to the success of multiscale modeling approaches is the ability to switch between molecular representations involving different levels of detail. In particular, the transition from a coarse to a fine representation is challenging because it requires the creation of information. To address this challenge, an algorithm is presented to fill in the detail when a coarse grain representation of a molecular system is replaced by an atomistic representation. The algorithm consists of minimization on the Lie group SO(3) for every coarse grain site, using the components of the atomistic force field that operate between atoms belonging to different coarse grain sites. This method is maximally efficient because the optimization is done at the coarse level using frozen atomistic library structures corresponding to each kind of coarse grain unit. The algorithm can be applied to any system since its input requirements are simply the force fields and molecular structures of both levels. The role of the algorithm in dual-resolution multiscale simulation methodology is discussed, and the efficacy of the algorithm is demonstrated through its implementation to liquid dodecane.
Functionalized single-walled carbon nanotubes (SWNTs) are widely applied in biomedical science. T... more Functionalized single-walled carbon nanotubes (SWNTs) are widely applied in biomedical science. To understand the interaction between SWNTs and biological systems, various studies have attempted to use coarsegrained molecular dynamics (CGMD). However, there is limited validation of the existing CG models of SWNTs. Here, we present CG models for both pristine and carboxylated SWNTs which are validated against experimental dispersion data. In addition, we present the first ever DLVO analysis of the colloidal stability of parallel SWNTs and establish that the solvent-induced repulsion between fullerenes, which is not considered in DLVO theory, is crucial to obtain a correct physical picture of SWNT dispersibility. The results presented here provide physical insight into the colloidal stability of SWNTs and can be applied to large-scale MD studies of biological systems.
Coupling between the inner and outer leaflets of a bilayer plays an important role in biomembrane... more Coupling between the inner and outer leaflets of a bilayer plays an important role in biomembrane function, particularly in inducing and registering rafts across leaflets for various cellular signals. However, mechanisms of raft registration remain elusive and several alternatives have been proposed, ranging from electrostatic coupling to chain interdigitation, cholesterol flip-flop and compositioncurvature coupling. A general mechanism has been suggested by recent experiments with mixtures of polymer amphiphiles that exhibit domain registration upon ligand-induced segregation. Here, using coarse grained molecular dynamics (CGMD) simulations that are rooted in atomistics, we show that raft registration arises spontaneously in bilayers with a calcium-or ligand-crosslinked ordered phase segregating from a liquid disordered phase. When rafts are not registered, a thickness mismatch between phases induces a ''bump'' in the apposing liquid phase leaflet, and it appears that the associated localized curvature change guides rafts together and stabilizes the registered state. The absence of explicit charge in the model and the fact that domain size modulates the strength of transmembrane coupling demonstrate that collective interactions are sufficient for raft registration.
We discuss three topologically different methods for calculating the surface tension between a fl... more We discuss three topologically different methods for calculating the surface tension between a flat solid and a liquid from theoretical and computer simulation viewpoints. The first method, commonly used in experiments, measures the contact angle at which a static droplet of liquid rests on a solid surface. We present a new analysis algorithm for this method and explore the effects of line tension on the contact angle. The second method, commonly used computer simulations, uses the pressure tensor through the virial in a system where a thick, infinitely extended slab of liquid rests on a solid surface. The third method, which is original to this paper and is closest to the thermodynamic definition of surface tension, applies to a spherical solid in contact with liquid in which the flat solid is recovered by extrapolating the sphere radius to infinity. We find that the second and third methods agree with each other, while the first method systematically underestimates surface tension values.
Normal mode analysis (NMA) is applied in a molecular-dynamics simulation of liquid CS2, modeled w... more Normal mode analysis (NMA) is applied in a molecular-dynamics simulation of liquid CS2, modeled with a potential including internal degrees of freedom. The entire supercooled liquid range, from the glass transition at 100 K to melting at 165 K, and the normal liquid from 165 to 293 K, are studied at P=1 atm. The normal modes of the liquid are classified as translation parallel (trans-∥) and perpendicular (trans-⊥) to the molecular axis, rotation, symmetric stretch, antisymmetric stretch, and bend. The configuration-averaged density of states, 〈ρ(ω)〉, with both stable and unstable modes, is correspondingly decomposed into separate contributions 〈ργ(ω)〉, with γ=trans-∥, etc. The trans-∥, trans-⊥, and rotational velocity correlation functions, and diffusion constants Dγ, are shown to be calculable from the same NMA techniques previously developed for atoms, so long as the appropriate 〈ργ(ω)〉 is used. Agreement between NMA theory and simulation is extremely good for the trans-⊥ velocity...
International journal of engineering research & technology (Ahmedabad), 2014
Polyphosphazenes, because of their unique properties, have generated many opportunities to explor... more Polyphosphazenes, because of their unique properties, have generated many opportunities to explore a variety of applications. These applications include areas such as biomedical research (e.g. drug delivery) and material science (e.g. fire-resistant polymers). Phosphazenes potentially have more variations then benzene analogues because of different substitution patterns. Here we present A computational study of the chemical modifications to a group of cyclic phosphazenes mainly hexachlorophosphazene (PNCl2)3. This study focuses on the relative energies of reactivity of hexachlorophosphazene to understand their geometry and the complexes they likely form. We compare diols, amino alcohols, and diamines with a carbon linker of 1-7 atoms. These heteroatom chains are attached to a single phosphorus atom or adjoining phosphorus atoms to form ring structures of geminal, vicinal (cis), and vicinal (trans) moieties. We find that the reactivities of "heteroatom caps" are predicted t...
Journal of organic and biomolecular simulations, 2014
We present a computational study of the effect of chemical modifications of the meta and para sub... more We present a computational study of the effect of chemical modifications of the meta and para substituents in the coordinating pendant arm of a modified 1,4,7,10-tetraazacyclododecane-N, N', N″, N‴-tetraamide (DOTAM) ligand on the Chemical Exchange Saturation Transfer (CEST) signal. Magnetic Resonance Imaging (MRI) is currently one of the most widely used techniques available. MRI has led to a new class of pharmaceuticals termed "imagining" or "contrast" agents. These agents usually work by incorporating lanthanide metals such as Gadolinium (Gd) and Europium (Eu). This allows the contrast agents to take advantage of the paramagnetic properties of the metals, which in turn enhances the signal detectable by MRI. The effect of simple electron-withdrawing (e.g., nitro) and electron-donating (e.g., methyl) substituents chemically attached to a modified chelate arm (pendant arm) is quantified by charge transfer interactions in the coordinated water-chelate system c...
N,N'-Dialkylimidazolium ionic liquids (ILs) show promise as non-derivatizing 'green' ... more N,N'-Dialkylimidazolium ionic liquids (ILs) show promise as non-derivatizing 'green' solvents for the dissolution and processing of cellulose. To better understand how these ILs solvate this and other polysaccharides at the molecular level, we have performed molecular dynamics (MD) simulations of neat 1-n-butyl-3-methylimidazolium chloride ([C 4 mim]Cl) at 298, 313, 333, 343, 353, 363, and 373 K, as well as 5 and 10 wt% cellobiose solutions in [C 4 mim]Cl at 363 K. Static, dynamic, and thermodynamic quantities have been derived from the collected data. Our findings agree well with experimental data from various sources. In particular, analysis of structural features and hydrogen bonding patterns between [C 4 mim]Cl and cellobiose are consistent with results from NMR relaxation studies which indicate that the IL Cl" ions interact with the carbohydrate OH groups in a ∼ 1:1 ratio.
A computationally efficient coarse grain model designed to closely mimic specific phospholipids i... more A computationally efficient coarse grain model designed to closely mimic specific phospholipids is used to study a number of phospholipid systems to demonstrate its strengths and weaknesses. A study of a membrane containing an anesthetic, halothane, illustrates the ...
We present the results of coarse grained molecular dynamics simulation using a charge free model ... more We present the results of coarse grained molecular dynamics simulation using a charge free model that is able to capture different regions of the morphological phase diagram of charged diblock copolymers. Specifically, we were able to reproduce many phases of the poly(acrylic acid)-(1,4)-polybutadiene (PAA-PBA) diblock copolymer, Ca(2+) and water systems as a function of pH and calcium concentration with short-range LJ type potentials. The morphologies observed range from bilayers to cylinders to spherical micelles. Such polyanionic/cationic amphiphiles in water typically present multiple challenges for molecular simulations, particularly due to the many charge interactions that are long ranged and computationally costly. Further, it is precisely these interactions that are thought to modulate large amphiphile assemblies of interest such as lipid rafts. However, our model is able to reproduce different morphologies due to pH and with or without the addition of Ca(2+) as well as the lateral phase segregation and the domain registration observed in neutral and charged diblock copolymer mixtures. The results suggest that the overall effect of charges is a local structural rearrangement that renormalizes the steric repulsion between the headgroups. This simple model, which is devoid of charges, is able to reproduce the complex phase diagram and can be used to investigate collective phenomena in these charged systems such as domain formation and registration or colocalization of lipid rafts across bilayer leaflets.
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Papers by Preston Moore