Surface Characteristics of Poly(alkyl methacrylate)s from Molecular Dynamics Simulations Using All-Atom Force Field.

Molecular dynamics (MD) simulations of melt films of poly(alkyl methacrylate)s (PAMAs) with methyl, ethyl, and n-butyl substituents, respectively, have been performed using an all-atom model to investigate their surface and thin film properties. The applied all-atom force fields predict the bulk densities of PAMAs in good agreement with experiments. Moreover, predictions of the surface tensions of PMMA, PEMA, and Pn-BMA melts are in reasonably good agreement with experiments. The density profiles and orientational-order parameters of chain segments show atomic-scale characteristics in the air/polymer interfacial region. In the surface region, the backbone segments of PAMAs form a well-defined layer structure with the chain vectors oriented parallel to the surface, while the ester side-chains strongly segregate to the surface region and show perpendicular orientation to the surface, with the most pronounced surface segregation noted for Pn-BMA. Such surface segregations of chain segments make it difficult to apply a simple relationship between the cohesive energy density and the surface tension of polymers, for example, and should be taken into account in relating the surface/thin film characteristics to the bulk properties of polymers in general.

Critical phenomena and strategy ordering with hub centrality approach in the aspiration-based coordination game.

We study the coordination game with an aspiration-driven update rule in regular graphs and scale-free networks. We prove that the model coincides exactly with the Ising model and shows a phase transition at the critical selection noise when the aspiration level is zero. It is found that the critical selection noise decreases with clustering in random regular graphs. With a non-zero aspiration level, the model also exhibits a phase transition as long as the aspiration level is smaller than the degree of graphs. We also show that the critical exponents are independent of clustering and aspiration level to confirm that the coordination game belongs to the Ising universality class. As for scale-free networks, the effect of aspiration level on the order parameter at a low selection noise is examined. In model networks (the Barabási-Albert network and the Holme-Kim network), the order parameter abruptly decreases when the aspiration level is the same as the average degree of the network. In contrast, in real-world networks, the order parameter decreases gradually. We explain this difference by proposing the concepts of hub centrality and local hub. The histogram of hub centrality of real-world networks separates into two parts unlike model networks, and local hubs exist only in real-world networks. We conclude that the difference of network structures in model and real-world networks induces qualitatively different behavior in the coordination game.

Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial.

BACKGROUND: Telbivudine has been suggested to induce hepatitis B surface antigen (HBsAg) decline to the similar degree as pegylated interferon. We aimed to investigate whether telbivudine could further decrease HBsAg titer in patients who maintain undetectable serum hepatitis B virus (HBV) DNA after initial entecavir treatment. METHODS: In this open-label trial, patients who had serum HBsAg and HBV DNA levels ≥1,000 IU/mL and <60 IU/mL, respectively, following entecavir (0.5 mg/day) treatment for HBeAg-positive chronic hepatitis B were randomized to either switch treatment to telbivudine (600 mg/day, n = 47) or continue entecavir (n = 50) for 48 weeks. RESULTS: The baseline characteristics were comparable between groups including HBsAg levels (median, 3.41 log10 IU/mL). All patients had undetectable HBV DNA and normal alanine aminotransferase level. At week 48, the mean change in serum HBsAg levels was not significantly different between the telbivudine and entecavir groups (-0.03 log10 IU/mL vs. -0.05 log10 IU/mL; P = 0.57). No patient experienced HBsAg seroclearance or HBsAg decline >0.5 log10 IU/mL. Eleven patients (23.4%) in the telbivudine group, but none in the entecavir group, experienced virologic breakthrough (P < 0.001). Seven patients (14.9%) exhibited genotypic resistance mutations (M204I +/- L180M) during the virologic breakthrough. CONCLUSION: Sequential therapy with entecavir followed by telbivudine resulted in a high rate of virologic breakthrough and drug-resistance without any beneficial effect on HBsAg decline. These results do not support the use of low genetic barrier drugs as a switch treatment strategy in patients who achieve virologic response with high genetic barrier drugs. TRIAL REGISTRATION: NCT01595685 (date of trial registration: May 8, 2012).

Zwitterionic polymerization: a kinetic strategy for the controlled synthesis of cyclic polylactide.

The zwitterionic ring-opening polymerization of lactide initiated by N-heterocyclic carbenes generates cyclic polylactides with well-defined molecular weights between M(n) = 5000 and 30,000 g/mol with narrow polydispersities (M(w)/M(n) < or = 1.31). These zwitterionic polymerizations are extremely rapid (k(p) = 48.7 M(-1) s(-1)), but also exhibit exceptional control of molecular weight and molecular weight distribution. The unusual kinetic features of these zwitterionic polymerizations are illuminated with kinetic and mechanistic investigations, which implicate a mechanism that involves a slow initiation step (second order in [M]), a propagation step (first order in [M]) that is much faster than initiation (k(i) = 0.274 M(-2) s(-1)), cyclization (k(c) = 0.0575 s(-1)), and depropagation (k(d) = 0.208 s(-1)). Numerical and stochastic simulations of the kinetic data provide a kinetic rationale for the evolution of molecular weight with monomer conversion: the molecular weights increase with increasing monomer conversion, exhibit a nonzero intercept near 0% monomer conversion, and are relatively insensitive to the initial monomer-to-initiator ratio. The observed narrow molecular weight distributions are due to a high rate of propagation relative to cyclization and chain transfer. Kinetic simulations define the kinetic criteria under which the active zwitterions remain in solution; these simulations were substantiated by chain-extension experiments, which provide experimental evidence for chain extension of the zwitterions and reinitiation by the N-heterocyclic carbenes liberated upon macrocyclization. The kinetic model rationalizes some of the unique features of zwitterionic ring-opening polymerization and provides a useful mechanistic framework to optimize these polymerizations as a strategy to generate well-defined cyclic polyesters.

Effects of temperature and chemical modification on polymer Langmuir films.

We previously reported on a rheological study of Langmuir films of poly(tert-butyl methacrylate) (PtBMA), and this work describes further studies on this system. Here, surface pressure-area (Pi-A) isotherms and interfacial shear rheology experiments are performed to better understand the effects of two modifications: varying the temperature between 5 and 40 degrees C and introducing small amounts of carboxylic acid groups by partially hydrolyzing the polymer. Increased temperature produced isotherms with lower plateau surface pressures, Pip, and Pi values shifted to lower areas above Pip. Film properties transition from being primarily viscous to being dominated by elasticity as Pip is crossed for all temperatures studied, even as the value of Pip changes. Increasing the hydrolysis fraction leads to isotherms shifted to lower areas throughout the curve and higher Pip values. Both temperature variation and chemical modification are believed to affect the relative importance of polymer-polymer and polymer-subphase interactions.

Challenging nature's monopoly on the creation of well-defined nanoparticles.

Nature has selected and fine-tuned the physical and chemical properties of natural objects, such as size, shape, mechanical properties and surface chemistry, at the molecular level in order to modulate biological functions. A new particle fabrication process, particle replication in nonwetting templates (PRINT), has recently begun to attempt to emulate nature's ability to control those physical and chemical traits. The PRINT technology, which combines modern soft lithography with the unique properties of perfluoropolyether molds, enables the production of nanoparticles with unprecedented control of size, shape, chemical composition, deformability and surface functionality. This scalable 'top-down' fabrication process allows for the generation of well-defined nanostructures without the need for molecular assembly. The ability to flexibly engineer various matrix materials offers unique opportunities for the development of nanomedicines with desired functionality. The strength and versatility of PRINT makes it a powerful platform in nanomedicine for elucidating the role of physical and chemical properties of nanodelivery vehicles on the behavior and fate at the cellular, tissue and whole organism level. Utilizing the PRINT technology, we are generating well-defined nanomedicines with tailored properties for preclinical studies against a variety of human diseases.