Activity of microemulsion-based nanoparticles at the human bio-nano interface: concentration-dependent effects on thrombosis and hemolysis in whole blood

Background: Although microemulsion-based nanoparticles (MEs) may be useful for drug delivery or scavenging, these benefits must be balanced against potential nanotoxicological effects in biological tissue (bio-nano interface). We investigated the actions of assembled MEs and their individual components at the bio-nano interface of thrombosis and hemolysis in human blood. Methods: Oil-in-water MEs were synthesized using ethylbutyrate, sodium caprylate, and pluronic F-68 (ME4) or F-127 (ME6) in 0.9% NaCl_w/v. The effects of MEs or components on thrombosis were determined using thrombo-elastography, platelet contractile force, clot elastic modulus, and platelet counting. For hemolysis, ME or components were incubated with erythrocytes, centrifuged, and washed for measurement of free hemoglobin by spectroscopy. Results and conclusions: The mean particle diameters (polydispersity index) for ME6 and ME4 were 23.6 ± 2.5 nm (0.362) and 14.0 ± 1.0 nm (0.008), respectively. MEs (0, 0.03, 0.3, 3 mM) markedly reduced the thromboelastograph maximal amplitude in a concentration-dependent manner (49.0 ± 4.2, 39.0 ± 5.6, 15.0 ± 8.7, 3.8 ± 1.3 mm, respectively), an effect highly correlated (r2 = 0.94) with similar changes caused by pluronic surfactants (48.7 ± 10.9, 30.7 ± 15.8, 20.0 ± 11.3, 2.0 ± 0.5) alone. Neither oil nor sodium caprylate alone affected the thromboelastograph. The clot contractile force was reduced by ME (27.3 ± 11.1–6.7 ± 3.4 kdynes/cm², P = 0.02, n = 5) whereas the platelet population not affected (175 ± 28–182 ± 23 10⁶/ml, P = 0.12, n = 6). This data suggests that MEs reduced platelet activity due to associated pluronic surfactants, but caused minimal changes in protein function necessary for coagulation. Although pharmacological concentrations of sodium caprylate caused hemolysis (EC₅₀ = 213 mM), MEs and pluronic surfactants did not disrupt erythrocytes. Knowledge of nanoparticle activity and potential associated nanotoxicity at this bio-nano interface enables rational ME design for in vivo applications.     

Thermal diffusion of envelope solitons on anharmonic atomic chains

We study the motion of envelope solitons on anharmonic atomic chains in the presence of dissipation and thermal fluctuations. We consider the continuum limit of the discrete system and apply an adiabatic perturbation theory which yields a system of stochastic integro-differential equations for the collective variables of the ansatz for the perturbed envelope soliton. We derive the Fokker-Planck equation of this system and search for a statistically equivalent system of Langevin equations, which shares the same Fokker-Planck equation. We undertake an analytical analysis of the Langevin system and derive an expression for the variance of the soliton position Var[x _s ] which predicts a stronger than linear time dependence of Var[x _s ] (superdiffusion). We compare these results with simulations for the discrete system and find they agree well. We refer to recent studies where the diffusion of pulse solitons were found to exhibit a superdiffusive behaviour on longer time scales.Received: 28 June 2004, Published online: 26 November 2004PACS: 05.10.Gg Stochastic analysis methods - 05.45.Yv Solitons - 05.40.-a Fluctuation phenomena, random processes, noise, and Brownian motion - 05.50. + q Lattice theory and statistics     

Electronic transport properties of bismuth nanobridges through silicon-nitride membranes

The electronic transport through nanostructured bismuth nanobridges has been investigated at low temperatures (T<2 K) and in magnetic fields B up to 8.5 T. The samples show reproducible resistance fluctuations as a function of B, superimposed on a large magnetoresistance of up to 50%. In addition, time-dependent resistance fluctuations in zero magnetic field demonstrate the presence of bistable scatterers in the constriction region of our samples, which are described by two-level systems. Their dynamics are shown to be sensitive to subtle modifications of the static scatterer configuration in their vicinity, which cannot be detected in the sample magnetofingerprint.     

On Bayes and unbiased estimators of loss

We consider estimation of loss for generalized Bayes or pseudo-Bayes estimators of a multivariate normal mean vector, θ. In 3 and higher dimensions, the MLEX is UMVUE and minimax but is inadmissible. It is dominated by the James-Stein estimator and by many others. Johnstone (1988, On inadmissibility of some unbiased estimates of loss,Statistical Decision Theory and Related Topics, IV (eds. S. S. Gupta and J. O. Berger), Vol. 1, 361–379, Springer, New York) considered the estimation of loss for the usual estimatorX and the James-Stein estimator. He found improvements over the Stein unbiased estimator of risk. In this paper, for a generalized Bayes point estimator of θ, we compare generalized Bayes estimators to unbiased estimators of loss. We find, somewhat surprisingly, that the unbiased estimator often dominates the corresponding generalized Bayes estimator of loss for priors which give minimax estimators in the original point estimation problem. In particular, we give a class of priors for which the generalized Bayes estimator of θ is admissible and minimax but for which the unbiased estimator of loss dominates the generalized Bayes estimator of loss. We also give a general inadmissibility result for a generalized Bayes estimator of loss. Research supported by NSF Grant DMS-97-04524.