Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Neutral theory: the stability of forest biodiversity

The unified neutral theory of biodiversity and biogeography provides a dynamic null hypothesis for the assembly of natural communities. It is also useful for understanding the influence of speciation, extinction, dispersal and ecological drift on patterns of relative species abundance, species-area relationships and phylogeny. Clark and McLachlan argue that neutral drift is inconsistent with the palaeorecord of stability in fossil pollen assemblages of the Holocene forests of southern Canada. We show here that their analysis is based on a partial misunderstanding of neutral theory and that their data alone cannot unambiguously test its validity.     

Channel plasmon subwavelength waveguide components including interferometers and ring resonators

Photonic components are superior to electronic ones in terms of operational bandwidth, but the diffraction limit of light poses a significant challenge to the miniaturization and high-density integration of optical circuits. The main approach to circumvent this problem is to exploit the hybrid nature of surface plasmon polaritons (SPPs), which are light waves coupled to free electron oscillations in a metal that can be laterally confined below the diffraction limit using subwavelength metal structures. However, the simultaneous realization of strong confinement and a propagation loss sufficiently low for practical applications has long been out of reach. Channel SPP modes--channel plasmon polaritons (CPPs)--are electromagnetic waves that are bound to and propagate along the bottom of V-shaped grooves milled in a metal film. They are expected to exhibit useful subwavelength confinement, relatively low propagation loss, single-mode operation and efficient transmission around sharp bends. Our previous experiments showed that CPPs do exist and that they propagate over tens of micrometres along straight subwavelength grooves. Here we report the design, fabrication and characterization of CPP-based subwavelength waveguide components operating at telecom wavelengths: Y-splitters, Mach-Zehnder interferometers and waveguide-ring resonators. We demonstrate that CPP guides can indeed be used for large-angle bending and splitting of radiation, thereby enabling the realization of ultracompact plasmonic components and paving the way for a new class of integrated optical circuits.     

Reconfigurable combined forecasts in a non-stationary inflationary environment

This paper presents a composite method for non-stationary economic forecasts, incorporating reconfigurable exponential trend extraction and linear combinations of parabolic and spectral estimators for short-term prediction. The method automatically identifies the points of time series misalignment induced by sharp environmental changes. An application to the problem of hard currency exchange rate prediction in Russia is presented.     

Patterns of relative species abundance in rainforests and coral reefs

A formidable many-body problem in ecology is to understand the complex of factors controlling patterns of relative species abundance (RSA) in communities of interacting species. Unlike many problems in physics, the nature of the interactions in ecological communities is not completely known. Although most contemporary theories in ecology start with the basic premise that species interact, here we show that a theory in which all interspecific interactions are turned off leads to analytical results that are in agreement with RSA data from tropical forests and coral reefs. The assumption of non-interacting species leads to a sampling theory for the RSA that yields a simple approximation at large scales to the exact theory. Our results show that one can make significant theoretical progress in ecology by assuming that the effective interactions among species are weak in the stationary states in species-rich communities such as tropical forests and coral reefs.     

Neutral theory and relative species abundance in ecology

The theory of island biogeography asserts that an island or a local community approaches an equilibrium species richness as a result of the interplay between the immigration of species from the much larger metacommunity source area and local extinction of species on the island (local community). Hubbell generalized this neutral theory to explore the expected steady-state distribution of relative species abundance (RSA) in the local community under restricted immigration. Here we present a theoretical framework for the unified neutral theory of biodiversity and an analytical solution for the distribution of the RSA both in the metacommunity (Fisher's log series) and in the local community, where there are fewer rare species. Rare species are more extinction-prone, and once they go locally extinct, they take longer to re-immigrate than do common species. Contrary to recent assertions, we show that the analytical solution provides a better fit, with fewer free parameters, to the RSA distribution of tree species on Barro Colorado Island, Panama, than the lognormal distribution.     

The effect of tetrodotoxin on the synaptic and extrasynaptic membrane in frog skeletal muscle

Tetrodotoxin resistant sodium channels have been shown to operate in frog muscle membrane, which are responsible for local action potentials. These channels are located mainly in synaptic regions, and their distribution on the membrane is controlled by neurotrophic factors.     

Density dependence explains tree species abundance and diversity in tropical forests

The recurrent patterns in the commonness and rarity of species in ecological communities--the relative species abundance--have puzzled ecologists for more than half a century. Here we show that the framework of the current neutral theory in ecology can easily be generalized to incorporate symmetric density dependence. We can calculate precisely the strength of the rare-species advantage that is needed to explain a given RSA distribution. Previously, we demonstrated that a mechanism of dispersal limitation also fits RSA data well. Here we compare fits of the dispersal and density-dependence mechanisms for empirical RSA data on tree species in six New and Old World tropical forests and show that both mechanisms offer sufficient and independent explanations. We suggest that RSA data cannot by themselves be used to discriminate among these explanations of RSA patterns--empirical studies will be required to determine whether RSA patterns are due to one or the other mechanism, or to some combination of both.     

The effect of tetrodotoxin on the sypaptic and extrasynaptic membrane in frog skeletal muscle

Summary Tetrodotoxin resistant sodium channels have been shown to operate in frog muscle membrane, which are responsible for local action potentials. These channels are located mainly in synaptic regions, and their distribution on the membrane is controlled by neurotrophic factors.