Search

While the bulk structure of vapor-deposited glasses has been extensively studied, structure at buried interfaces has received little attention, despite being important for organic electronic applications. To learn about glass structure at buried interfaces, we study the structure of vapor-deposited glasses of the organic semiconductor DSA-Ph (1,4-di-[4-( N , N -diphenyl)amino]styrylbenzene) as a function of film thickness; the structure is probed with grazing incidence X-ray scattering. We deposit on silicon and gold substrates and span a film thickness range of 10-600 nm. Our experiments demonstrate that interfacial molecular packing in vapor-deposited glasses of DSA-Ph is more disordered compared to the bulk. At a deposition temperature near room temperature, we estimate ∼8 nm near the substrate can have modified molecular packing. Molecular dynamics simulations of a coarse-grained representation of DSA-Ph reveal a similar length scale. In both the simulations and the experiments, deposition temperature controls glass structure beyond this interfacial layer of a few nanometers.

Polyelectrolyte brushes provide wear protection and lubrication in many technical, medical, physiological, and biological applications. Wear resistance and low friction are attributed to counterion osmotic pressure and the hydration layer surrounding the charged polymer segments. However, the presence of multivalent counterions in solution can strongly affect the interchain interactions and structural properties of brush layers. We evaluated the lubrication properties of polystyrene sulfonate brush layers sliding against each other in aqueous solutions containing increasing concentrations of counterions. The presence of multivalent ions (Y 3+ , Ca 2+ , Ba 2+ ), even at minute concentrations, markedly increases the friction forces between brush layers owing to electrostatic bridging and brush collapse. Our results suggest that the lubricating properties of polyelectrolyte brushes in multivalent solution are hindered relative to those in monovalent solution., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Polyelectrolyte molecules of opposite charge are known to form stable complexes in solution. Depending on the system conditions, such complexes can be solid or liquid. The latter are known as complex coacervates, and they appear as a second liquid phase in equilibrium with a polymer-dilute aqueous phase. This work considers the complexation between poly(glutamic acid) and poly(lysine), which is of particular interest because it enables examination of the role of chirality in ionic complexation, without changes to the overall chemical composition. Systematic atomic-level simulations are carried out for chains of poly(glutamic acid) and poly(lysine) with varying combinations of chirality along the backbone. Achiral chains form unstructured complexes. In contrast, homochiral chains lead to formation of stable β-sheets between molecules of opposite charge, and experiments indicate that β-sheet formation is correlated with the formation of solid precipitates. Changes in chirality along the peptide backbone are found to cause "kinks" in the β-sheets. These are energetically unfavorable and result in irregular structures that are more difficult to pack together. Taken together, these results provide new insights that may be of use for the development of simple yet strong bioinspired materials consisting of β-rich domains and amorphous regions.

Technological applications of liquid crystals have generally relied on control of molecular orientation at a surface or an interface. Such control has been achieved through topography, chemistry and the adsorption of monolayers or surfactants. The role of the substrate or interface has been to impart order over visible length scales and to confine the liquid crystal in a device. Here, we report results from a computational study of a liquid-crystal-based system in which the opposite is true: the liquid crystal is used to impart order on the interfacial arrangement of a surfactant. Recent experiments on macroscopic interfaces have hinted that an interfacial coupling between bulk liquid crystal and surfactant can lead to a two-dimensional phase separation of the surfactant at the interface, but have not had the resolution to measure the structure of the resulting phases. To enhance that coupling, we consider the limit of nanodroplets, the interfaces of which are decorated with surfactant molecules that promote local perpendicular orientation of mesogens within the droplet. In the absence of surfactant, mesogens at the interface are all parallel to that interface. As the droplet is cooled, the mesogens undergo a transition from a disordered (isotropic) to an ordered (nematic or smectic) liquid-crystal phase. As this happens, mesogens within the droplet cause a transition of the surfactant at the interface, which forms new ordered nanophases with morphologies dependent on surfactant concentration. Such nanophases are reminiscent of those encountered in block copolymers, and include circular, striped and worm-like patterns.

A continuum theory is used to study the interactions between nanoparticles suspended in nematic liquid crystals. The free energy functional that describes the system is minimized using an Euler-Lagrange approach and an unsymmetric radial basis function method. It is shown that nanoparticle liquid-crystal mediated interactions can be controlled over a large range of magnitudes through changes of the anchoring energy and the particle diameter. The results presented in this work serve to reconcile past discrepancies between theoretical predictions and experimental observations, and suggest intriguing possibilities for directed nanoparticle self-assembly in liquid crystalline media., (© 2012 American Chemical Society)

The structural evolution of surface gratings on a glassy material is investigated by means of molecular simulations. The gratings provide a means to probe surface diffusion in the vicinity of the glass transition temperature. A theory by Mullins [J. Appl. Phys. 30, 77 (1959)] is used to extract qu-antitative measures of surface diffusivity that rely on calculation of grating amplitude as a function of time. The simulations are implemented in the context of a model binary glass mixture [S. S. Ashwin and S. Sastry, J. Phys.: Condens. Matter 15, S1253 (2003)]. We find that surface diffusion is faster than bulk diffusion by several orders of magnitude, consistent with recent experimental data for an organic glass former. The diffusivities extracted by the grating-decay approach are consistent with those estimated on the basis of mean-squared particle displacements. The grating-decay approach, however, is more efficient than traditional techniques based on Einstein's diffusion equation. Grating decay is also more versatile and is shown to be applicable in a variety of sample geometries., (© 2011 American Institute of Physics.)

We present a coarse grain representation for Gaussian chains in the presence of hard surfaces. Whereas a Gaussian chain in the bulk can be represented by a bead-spring model with a quadratic potential between adjacent beads, the presence of a surface reduces the number of allowed chain configurations and modifies the effective potential between the beads. We derive the corrected potentials for several surface geometries: a single wall, two parallel walls (slit), and a spherical or cylindrical object (nanoparticle). Those potentials can be used in any model that includes a Gaussian chain, regardless of the simulation method. As an illustration, we consider a coarse grain model of a polymeric melt and, using Monte Carlo simulations, we compute the density profiles for (i) a melt confined in a slit and (ii) a melt in the vicinity of a nanoparticle. The case of a polymeric solution confined within a slit is also addressed, and the proposed approach is shown to yield results in qualitative agreement with those obtained with field-theoretic simulations.

DNA hybridization plays a central role in biology and, increasingly, in materials science. Yet, there is no precedent for examining the pathways by which specific single-stranded DNA sequences interact to assemble into a double helix. A detailed model of DNA is adopted in this work to examine such pathways and to determine the role of sequence, if any, on DNA hybridization. Transition path sampling simulations reveal that DNA rehybridization is prompted by a distinct nucleation event involving molecular sites with approximately four bases pairing with partners slightly offset from those involved in ideal duplexation. Nucleation is promoted in regions with repetitive base pair sequence motifs, which yield multiple possibilities for finding complementary base partners. Repetitive sequences follow a nonspecific pathway to renaturation consistent with a molecular "slithering" mechanism, whereas random sequences favor a restrictive pathway involving the formation of key base pairs before renaturation fully ensues.

A growing body of experimental evidence indicates that the interaction between amyloid beta peptide and lipid bilayer membranes plays an important role in the development of Alzheimer disease. Recent experimental evidence also suggests that trehalose, a simple disaccharide, reduces the toxicity of amyloid beta peptide. Molecular simulations are used to examine the effect of trehalose on the conformational stability of amyloid beta peptide in aqueous solution and its effect on the interaction between amyloid beta peptide and a model phospholipid bilayer membrane. It is found that, in aqueous solution, the peptide exhibits a random coil conformation but, in the presence of trehalose, it adopts an alpha helical conformation. It is then shown that the insertion of amyloid beta peptide into a membrane is more favorable when the peptide is folded into an alpha-helix than in a random coil conformation, thereby suggesting that trehalose promotes the insertion of alpha-helical amyloid beta into biological membranes.

A mesoscale model of DNA is presented (3SPN.1), extending the scheme previously developed by our group. Each nucleotide is mapped onto three interaction sites. Solvent is accounted for implicitly through a medium-effective dielectric constant and electrostatic interactions are treated at the level of Debye-Hückel theory. The force field includes a weak, solvent-induced attraction, which helps mediate the renaturation of DNA. Model parameterization is accomplished through replica exchange molecular dynamics simulations of short oligonucleotide sequences over a range of composition and chain length. The model describes the melting temperature of DNA as a function of composition as well as ionic strength, and is consistent with heat capacity profiles from experiments. The dependence of persistence length on ionic strength is also captured by the force field. The proposed model is used to examine the renaturation of DNA. It is found that a typical renaturation event occurs through a nucleation step, whereby an interplay between repulsive electrostatic interactions and colloidal-like attractions allows the system to undergo a series of rearrangements before complete molecular reassociation occurs.

The renaturation/denaturation of DNA oligonucleotides is characterized in the context of expanded ensemble (EXE) and transition path sampling (TPS) simulations. Free energy profiles have been determined from EXE for DNA sequences of varying composition, chain length, and ionic strength. TPS simulations within a Langevin dynamics formalism have been carried out to obtain further information of the transition state for renaturation. Simulation results reveal that free energy profiles are strikingly similar for the various DNA sequences considered in this work. Taking intact double-stranded DNA to have an extent of reaction ξ = 1.0, the maximum of the free energy profile appears at ξ≈0.15, corresponding to ∼2 base pairs. In terms of chain length, the free energy barrier of longer oligonucleotides (30 versus 15 base pairs) is higher and slightly narrower, due to increased sharpness associated with the transition. Low ionic strength tends to decrease free energy barriers, whereby increasing strand rigidity facilitates reassociation. Two mechanisms for DNA reassociation emerge from our analysis of the transition state ensemble. Repetitive sequences tend to reassociate through a non-specific pathway involving molecular slithering. In contrast, random sequences associate through a more restrictive pathway involving the formation of specific contacts, which then leads to overall molecular zippering. In both random and repetitive sequences, the distribution of contacts suggests that nucleation is favored for sites located within the middle region of the chain. The prevalent extent of reaction for the transition state is ξ≈0.25, and the critical size of the nucleus as obtained from our analysis involves ∼4 base pairs.

Long polyglutamine chains have been associated with a number of neurodegenerative diseases. These include Huntington's disease, where expanded polyglutamine (PolyQ) sequences longer than 36 residues are correlated with the onset of symptoms. In this paper we study the folding pathway of a 54-residue PolyQ chain into a beta-helical structure. Transition path sampling Monte Carlo simulations are used to generate unbiased reactive pathways between unfolded configurations and the folded beta-helical structure of the polyglutamine chain. The folding process is examined in both explicit water and an implicit solvent. Both models reveal that the formation of a few critical contacts is necessary and sufficient for the molecule to fold. Once the primary contacts are formed, the fate of the protein is sealed and it is largely committed to fold. We find that, consistent with emerging hypotheses about PolyQ aggregation, a stable beta-helical structure could serve as the nucleus for subsequent polymerization of amyloid fibrils. Our results indicate that PolyQ sequences shorter than 36 residues cannot form that nucleus, and it is also shown that specific mutations inferred from an analysis of the simulated folding pathway exacerbate its stability.

Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here, we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome.

The free energy surfaces of a wide variety of systems encountered in physics, chemistry, and biology are characterized by the existence of deep minima separated by numerous barriers. One of the central aims of recent research in computational chemistry and physics has been to determine how transitions occur between deep local minima on rugged free energy landscapes, and transition path sampling (TPS) Monte-Carlo methods have emerged as an effective means for numerical investigation of such transitions. Many of the shortcomings of TPS-like approaches generally stem from their high computational demands. Two new algorithms are presented in this work that improve the efficiency of TPS simulations. The first algorithm uses biased shooting moves to render the sampling of reactive trajectories more efficient. The second algorithm is shown to substantially improve the accuracy of the transition state ensemble by introducing a subset of local transition path simulations in the transition state. The system considered in this work consists of a two-dimensional rough energy surface that is representative of numerous systems encountered in applications. When taken together, these algorithms provide gains in efficiency of over two orders of magnitude when compared to traditional TPS simulations.

A high-flux backscattering spectrometer and a time-of-flight disk chopper spectrometer are used to probe the molecular mobility of model freeze-dried phospholipid liposomes at a range of temperatures surrounding the main melting transition. Using specific deuteration, quasielastic neutron scattering provides evidence that, in contrast to the hydrocarbon chains, the headgroups of the phospholipid molecules do not exhibit a sharp melting transition. The onset of motion in the tails is located at temperatures far below the calorimetric transition. Long-range motion is achieved through the onset of whole-lipid translation at the melting temperature. Atomistic simulations are performed on a multibilayer model at conditions corresponding to the scattering experiments. The model provides a good description of the dynamics of the system, with predictions of the scattering functions that agree with experimental results. The analysis of both experimental data and results of simulations supports a picture of a gradual melting of the heterogeneous hydrophobic domain, with part of the chains spanning increasingly larger volumes and part of them remaining effectively immobile until the thermodynamic phase transition occurs.

A Monte Carlo simulation method is presented for simulation of phase transitions, with emphasis on the study of crystallization. The method relies on a random walk in order parameter Phi(q(N)) space to calculate a free energy profile between the two coexisting phases. The energy and volume data generated over the course of the simulation are subsequently reweighed to identify the precise conditions for phase coexistence. The usefulness of the method is demonstrated in the context of crystallization of a purely repulsive Lennard-Jones system. A systematic analysis of precritical and critical nuclei as a function of supercooling reveals a gradual change from a bcc to a fcc structure inside the crystalline nucleus as it grows at large degrees of supercooling. The method is generally applicable and is expected to find applications in systems for which two or more coexisting phases can be distinguished through one or more order parameters.

In this paper a new algorithm is presented that improves the efficiency of Wang and Landau algorithm or density of states (DOS) Monte Carlo simulations by employing rejected states. The algorithm is shown to have a performance superior to that of the original Wang-Landau [F. Wang and D. P. Landau, Phys. Rev. Lett. 86, 2050 (2001)] algorithm and the more recent configurational temperature DOS algorithm. The performance of the method is illustrated in the context of results for the Lennard-Jones fluid.

Expanded ensemble density-of-states simulations and a connectivity altering algorithm are used to investigate the effective interactions that arise between nanoparticles suspended in polymer solutions. Our calculations with systems of long polymeric chains reveal oscillations in the effective polymer-induced interactions between the particles, even at low concentrations. The range of these interactions is considerably longer than originally anticipated, and their origin is traced back to the chain-end effects and density fluctuations that were absent in previous treatments of these systems.

We analyze the response of a nematic liquid-crystal film, confined between parallel walls, to the presence of nanoscopic particles adsorbed at the walls. This is done for a variety of patterns of adsorption (random and periodic) and operational conditions of the system that can be controlled in experimental liquid-crystal-based devices. We compute simulated optical textures and the total optical output of the sensor between crossed polars, as well as the correlation function for the liquid-crystal tensor order parameter; we use these observables to discuss the gradual destruction of the original uniform orientation. For large concentrations of particles adsorbed in random patterns, the liquid crystal at the center of the sensor adopts a multidomain state, characterized by a small correlation length of the tensor order parameter, and also by a loss of optical anisotropy under observation through crossed polars. In contrast, for particles adsorbed in periodic patterns, the nematic at the center of the cell can remain in a monodomain orientation state, provided the patterns in opposite walls are synchronized.

Recent experiments indicate that liquid crystals can be used to optically report the presence of biomolecules adsorbed at solid surfaces. In this work, numerical simulations are used to investigate the effects of biological molecules, modeled as spherical particles, on the structure and dynamics of nematic ordering. In the absence of adsorbed particles, a nematic in contact with a substrate adopts a uniform orientational order, imposed by the boundary conditions at this surface. It is found that the relaxation to this uniform state is slowed down by the presence of a small number of adsorbed particles. However, beyond a critical concentration of adsorbed particles, the liquid crystal ceases to exhibit uniform orientational order at long times. At this concentration, the domain growth is characterized by a first regime where the average nematic domain size LD obeys the scaling law LDt approximately t1/2; at long times, a slow dynamics regime is attained for which LD tends to a finite value corresponding to a metastable state with a disordered texture. The results of simulations are consistent with experimental observations., (2005 American Institute of Physics.)

The conformation and dynamics of a single DNA molecule undergoing oscillatory pressure-driven flow in microfluidic channels is studied using Brownian dynamics simulations, accounting for hydrodynamic interactions between segments in the bulk and between the chain and the walls. Oscillatory flow provides a scenario under which the polymers may remain in the channel for an indefinite amount of time as they are stretched and migrate away from the channel walls. We show that by controlling the chain length, flow rate and oscillatory flow frequency, we are able to manipulate the chain extension and the chain migration from the channel walls. The chain stretch and the chain depletion layer thickness near the wall are found to increase as the Weissenberg number increases and as the oscillatory frequency decreases.

The conformation and diffusion of a single DNA molecule confined between two parallel plates are examined using both single molecule experiments and Brownian dynamics simulations accounting for hydrodynamic interactions. The degree of chain stretching and the diffusivity are characterized as a function of the chain confinement and the channel geometry. Good agreement is found between the simulations, experiments, and scaling theory predictions.

The structure of polymers in the vicinity of spherical colloids is investigated by Monte Carlo simulations and integral equation theory. Polymers are represented by a simple bead-spring model; only repulsive Lennard-Jones interactions are taken into account. Using advanced trial moves that alter chain connectivity, depletion and packing effects are analyzed as a function of chain length and density, both at the bond and the chain level. Chain ends segregate to the colloidal surface and polymer bonds orient parallel to it. In the dilute regime, the polymer chain length governs the range of depletion and has a negligible influence on monomer packing in dense polymer melts. Polymers adopt an ellipsoidal shape, with the larger axis parallel to the surface of the particle, as they approach larger colloids. The dimensions are perturbed within the range of the depletion layer.

The hydration of Na-saturated Wyoming-type montmorillonite is investigated by Monte Carlo simulations at constant stress in the NP(zz)T ensemble and at constant chemical potential in the microVT ensemble, at the sedimentary basin temperature of 353 K and pressure of 625 bar, equivalent to 2-4 km depth. The simulations use procedures established in Chavez-Paez et al. [J. Chem. Phys. 114, 1405 (2001)]. At these conditions, simulations predict a single stable form of 1,2-water layer Na-montmorillonite, containing 164.38 mg/g or 53.37 molecules/layer of adsorbed water and having a spacing of 12.72 A. The corresponding density is 0.32 g/ml. Sodium ions are coordinated with six molecules of water separated 2.30-2.33 A. Water molecules are closer to the central interlayer plane and the spacing is larger than that at 300 K and 1 bar. The interlayer configuration consists of two symmetrical layers of oriented water molecules 1.038 A from the central plane, with the hydrogen atoms in two outermost layers, 3.826 A apart, and the sodium ions on the central plane located between the water layers. The interlayer configuration can be considered to be a stable two-layer intermediate between the one- and two-layer hydrates. Our simulations do not predict formation of other hydrates of Na-montmorillonite at 353 K and 615 bar., ((c) 2004 American Institute of Physics)

This Letter investigates the defect structures that arise between two colloidal spheres immersed in a nematic liquid crystal. Molecular simulations and a dynamic field theory are employed to arrive at molecular-level and mesoscopic descriptions of the systems of interest. At large separations, each sphere is surrounded by a Saturn ring defect. However, at short separations both theory and simulation predict that a third disclination ring appears in between the spheres, in a plane normal to the Saturn rings. This feature gives rise to an effective binding of the particles. The structures predicted by field theory and molecular simulations are consistent with each other.

Insertion of spherical particles into a uniform nematic liquid crystal gives rise to the formation of topological defects. In the present work, we investigate how a spherical particle accompanied by its topological defects interacts with neighboring disclination lines. We perform two- and three-dimensional dynamic simulations to analyze the effect of a particle on the annihilation process of two disclination lines. The dynamics of the liquid crystal is described by a time-dependent evolution equation on the symmetric traceless order parameter that includes some of the salient features of liquid crystalline materials: excluded volume effects, or equivalently, short-range order elasticity and long-range order elasticity. At the surface of the particle, the liquid crystal is assumed to exhibit strong homeotropic anchoring. The particle is located between two disclination lines of topological charges +1/2 and -1/2. Two-dimensional simulations indicate that the topological defects bound to the particle mediate an interaction between the two disclination lines which increases the attraction between them. This result is confirmed by three-dimensional simulations that provide a complete description of the director field and of the order parameter around the particle. These simulations indicate that a spherical particle between two disclination lines can be surrounded by a Saturn ring, and suggest that the dynamic behavior of disclination lines could be used to report the structure of a defect around the particle.

The effects of confinement on the director field configurations are studied for a spherical particle immersed in a nematic liquid crystal. The liquid crystal is confined in a cylindrical geometry and the particle is located on the axis of symmetry. A finite element method is used to minimize the Frank free energy for various sizes of the system. The liquid crystal is assumed to possess strong anchoring at all the surfaces in the system. Two structures are examined for strong homeotropic anchoring at the surface of the particle: configuration with a Saturn ring disclination line and configuration with a satellite point defect (hedgehog defect). It is shown that the equilibrium locations of the Saturn ring and of the hedgehog point defect change with confinement. It is also found that confinement induces an increase in the elastic free energy that differs substantially with the type of topological defect under consideration. In particular, the evaluation of the total free energy that includes an approximate contribution for the core defect shows that, for micrometer-sized particles in confined systems, the Saturn ring configuration appears to be more stable than the hedgehog defect. This result is in contrast to the bulk situation, where the hedgehog is more stable than the Saturn ring, and it helps explain recent experimental observations of Saturn ring defects around confined micrometer-sized solid particles.

The low-temperature phase coexistence of size-asymmetric primitive model electrolyte solutions has been investigated by means of Monte Carlo simulations. Binodal curves and critical parameters are reported as a function of size ratio lambda = sigma(+)/sigma(-) in the range 0.05 to 1. Both the critical temperature and the critical density are found to decrease as lambda decreases. These trends are in conflict with available theoretical predictions. For highly asymmetric systems, the depression of the critical parameters is accompanied by the formation of large chainlike and ringlike structures, thereby giving rise to considerable finite-size effects.

Properties such as the glass transition temperature ( T(g)) and the diffusion coefficient of ultrathin polymeric films are shown to depend on the dimensions of the system. In this work, a hard-sphere molecular dynamics methodology has been applied to simulate such systems. We investigate the influence that substrates have on the behavior of thin polymer films; we report evidence suggesting that, depending on the strength of substrate-polymer interactions, the glass transition temperature for a thin film can be significantly lower or higher than that of the bulk.

Lyophilization and vacuum- or spray-drying are some of the most useful techniques for preserving foods, agricultural products, and pharmaceuticals. Biological materials, however, can be irreversibly damaged during these treatments. Therefore, it is essential to design protective agents to preserve protein activity and cell viability. In this paper we examine the use of alpha, alpha-trehalose-borate systems as protectants for Lactobacillus acidophilus during freeze- and vacuum-drying. Trehalose was found to be an effective protectant for freeze-dried and vacuum-dried samples, and it is equivalent to a protective formulation which is in current industrial use. It is known from our previous work on enzymes that the presence of borate can dramatically enhance the protective ability of trehalose. In this work, the addition of trehalose-borate to bacterial concentrate greatly improves the recovery of viable cells after storage. This improvement was seen in freeze-dried samples stored at 37 degrees C as well as for vacuum-dried samples held at room temperature. A tailored buffering strategy was tested to counteract the high pH resulting from the addition of borate to the mixture. Use of citric or lactic acids in combination with ammonium hydroxide gave a protectant solution with high pH (resulting in effective crosslinking between trehalose and borate) but a dry product with reduced pH upon rehydration (conducive to cell survival). These results raise exciting possibilities for protection of more labile prokaryotic species as well as simple eukaryotes., (Copyright 2000 Academic Press.)

This review provides a discussion of recent techniques for simulation of phase equilibria of complex fluids. Monte Carlo methods are emphasized over molecular dynamics methods. We describe recent developments, such as the use of expanded-ensemble, tempering, or histogram reweighting techniques. Our discussion of such developments is aimed at a general audience and is intended to provide an overview of the main advantages and limitations of each particular technique. References are provided to allow interested readers to identify and trace back most recent applications of a particular simulation technique. We conclude with general guidelines regarding selection of suitable simulation methods for particular problems and systems of interest.

Purpose: The purpose of this work was to investigate the effects of trehalose and trehalose/sodium tetraborate mixtures on recovery of lactate dehydrogenase (LDH) activity following freeze-thawing and centrifugal vacuum-drying/rehydration. The storage stability of LDH under conditions of either high relative humidity or high temperature was also studied., Methods: LDH was prepared in buffered aqueous formulations containing trehalose alone and trehalose/"borate" mixtures. Enzymatic activity was measured immediately following freeze-thawing and vacuum-drying/rehydration processes, and also after vacuum-dried formulations were stored in either high humidity or high temperature environments. Also, glass transition temperatures (Tg) were measured for both freeze-dried and vacuum-dried formulations., Results: The Tg values of freeze-dried trehalose/borate mixtures are considerably higher than that of trehalose alone. Freezing and vacuum-drying LDH in the presence of 300 mM trehalose resulted in the recovery of 80% and 65% of the original activity, respectively. For vacuum-dried mixtures, boron concentrations below 1.2 mole boron/ mole trehalose had no effect on recovered LDH. After several weeks storage in either humid (100% relative humidity) or warm (45 degrees C) environments, vacuum-dried formulations that included trehalose and borate showed greater enzymatic activities than those prepared with trehalose alone. We attribute this stability to the formation of a chemical complex between trehalose and borate., Conclusions: The high Tg values of trehalose/borate mixtures offer several advantages over the use of trehalose alone. Most notable is the storage stability under conditions of high temperature and high relative humidity. In these cases, formulations that contain trehalose and borate are superior to those containing trehalose alone. These results have practical implications for long-term storage of biological materials.

Purpose: To address the lack of fundamental thermophysical data for trehalose and its aqueous systems by measuring equilibrium and non-equilibrium properties of such systems., Methods/results: Differential scanning calorimetry (DSC) and dynamic mechanical analysis were used to measure glass transition temperatures of trehalose and its solutions. X-ray diffractometry was used to verify the structure of amorphous trehalose. Controlled-stress rheometry was used to measure viscosity of several aqueous trehalose systems at ambient and sub-ambient temperatures. Over this temperature range, the density of these solutions was also measured with a vibrating tube densimeter. The equilibrium phase diagram of aqueous trehalose was determined by measuring the solubility and freezing point depression., Conclusions: Our solubility measurements, which have allowed long times for attainment of chemical equilibrium, are substantially different from those reported earlier that used different techniques. Our measurements of the glass transition temperature of trehalose are higher than reported values. A simple model for the glass transition is presented to describe our experimental observations.