Perfusion-based microfluidic device for three-dimensional dynamic primary human hepatocyte cell culture in the absence of biological or synthetic matrices or coagulants

We describe a perfusion-based microfluidic device for three-dimensional (3D) dynamic primary human hepatocyte cell culture. The microfluidic device was used to promote and maintain 3D tissue-like cellular morphology and cell-specific functionality of primary human hepatocytes by restoring membrane polarity and hepatocyte transport function in vitro without the addition of biological or synthetic matrices or coagulants. A unique feature of our dynamic cell culture device is the creation of a microenvironment, without the addition of biological or synthetic matrices or coagulants, that promotes the 3D organization of hepatocytes into cord-like structures that exhibit functional membrane polarity as evidenced by the expression of gap junctions and the formation of an extended, functionally active, bile canalicular network.     

Automatic identification of model reductions for discrete stochastic simulation

Multiple time scales in cellular chemical reaction systems present a challenge for the efficiency of stochastic simulation. Numerous model reductions have been proposed to accelerate the simulation of chemically reacting systems by exploiting time scale separation. However, these are often identified and deployed manually, requiring expert knowledge. This is time-consuming, prone to error, and opportunities for model reduction may be missed, particularly for large models. We propose an automatic model analysis algorithm using an adaptively weighted Petri net to dynamically identify opportunities for model reductions for both the stochastic simulation algorithm and tau-leaping simulation, with no requirement of expert knowledge input. Results are presented to demonstrate the utility and effectiveness of this approach.     

State-dependent biasing method for importance sampling in the weighted stochastic simulation algorithm

The weighted stochastic simulation algorithm (wSSA) was developed by Kuwahara and Mura [J. Chem. Phys. 129, 165101 (2008)] to efficiently estimate the probabilities of rare events in discrete stochastic systems. The wSSA uses importance sampling to enhance the statistical accuracy in the estimation of the probability of the rare event. The original algorithm biases the reaction selection step with a fixed importance sampling parameter. In this paper, we introduce a novel method where the biasing parameter is state-dependent. The new method features improved accuracy, efficiency, and robustness.     

Interaction of cationic surfactant and anionic polyelectrolytes in mixed aqueous solutions

Surfactant–polymer interactions in aqueous solutions have been studied using dynamic surface tension, polyelectrolyte titration, nephelometric turbidity, and dynamic light scattering. For the preparation of complexes, a technical cationic surfactant was used in combination with two poly(maleic acid-co-polymers) of similar structure but different hydrophobicity. The dynamic surface tensions of mixed solutions as functions of surfactant concentration at constant polyelectrolyte content, as well as changes in the surface activity due to the influence of polyanion at constant surfactant concentration are discussed in terms of a complex or aggregate formation in the bulk phase. The interaction of the surfactant with poly(maleic acid-alt-propene) (P-MS-P) and poly(maleic acid-alt--methylstyrene) (P-MS-MeSty), respectively, is strong in both cases and results in the formation of nanoparticles with properties depending on the composition of the corresponding mixture.     

Viscosity of aqueous micellar solutions of surfactants

The viscosity of aqueous micellar solutions of two long-chain surfactants, C₂₄H₄₃N₂ClO and C₂₁H₃₈NCl, is studied in a concentration range of 10^?4?C10^?2 mol/L and a temperature range of 20?C40°C. It is established that, in the region of critical micelle concentration, the viscosity is a nonmonotonic function of concentration and has minima and maxima.     

An error estimate for matrix equations

This paper proposes a new method for estimating the error in the solution of matrix equations. The estimate is based on the adjoint method in combination with small sample statistical theory. It can be implemented simply and is inexpensive to compute. Numerical examples are presented which illustrate the power and effectiveness of the new method.     

Novel tetrahydroisoquinoline based organocatalysts for asymmetric Diels–Alder reactions: insight into the catalytic mode using ROESY NMR and DFT studies

For the first time an organocatalyst bearing a secondary nitrogen within a cyclohexane ring has been evaluated in the asymmetric Diels–Alder reaction. This organocatalyst is also the first of its kind based on a (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline backbone. These catalysts were tested over a range of dienes and dienophiles and displayed promising chemical conversions of up to 100% with up to 64% ee with triflic acid as the cocatalyst. Density functional theory computational studies and 2D NMR spectroscopy were used to determine the structure of the intermediate iminium ion formed between the most efficient catalyst and cinnamaldehyde. The reaction profile for each of the four possibilities in this reaction were calculated and it was found that the iminium intermediate leading to the major product is higher in energy but kinetically preferred. The activation energies of all possible reaction paths were calculated and the results correlated with the observed products. These experiments revealed that the presence of both (E)- and (Z)-isomers of the cinnamaldehyde were contributing factors for the low enantioselectivity of the reaction products.     

Effect of reactant size on discrete stochastic chemical kinetics

This paper is aimed at understanding what happens to the propensity functions (rates) of bimolecular chemical reactions when the volume occupied by the reactant molecules is not negligible compared to the containing volume of the system. For simplicity our analysis focuses on a one-dimensional gas of N hard-rod molecules, each of length l. Assuming these molecules are distributed randomly and uniformly inside the real interval [0,L] in a nonoverlapping way, and that they have Maxwellian distributed velocities, the authors derive an expression for the probability that two rods will collide in the next infinitesimal time dt. This probability controls the rate of any chemical reaction whose occurrence is initiated by such a collision. The result turns out to be a simple generalization of the well-known result for the point molecule case l=0: the system volume L in the formula for the propensity function in the point molecule case gets replaced by the "free volume" L-Nl. They confirm the result in a series of one-dimensional molecular dynamics simulations. Some possible wider implications of this result are discussed.