The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model

BACKGROUND: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. RESULTS: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. CONCLUSIONS: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.Israel Cancer Research Fund (ICRF), Teva Pharmaceutical Industries Ltd

Breeding habitat loss reveals limited foraging flexibility and increases foraging effort in a colonial breeding seabird

Background: Habitat loss can force animals to relocate to new areas, where they would need to adjust to an unfamiliar resource landscape and find new breeding sites. Relocation may be costly and could compromise reproduction. Methods: Here, we explored how the Lesser black-backed gull (Larus fuscus), a colonial breeding seabird species with a wide ecological niche, responds to the loss of its breeding habitat. We investigated how individuals adjusted their foraging behaviour after relocating to another colony due to breeding site destruction, and whether there were any reproductive consequences in the first years after relocation. To this end, we compared offspring growth between resident individuals and individuals that recently relocated to the same colony due to breeding habitat loss. Using GPS-tracking, we further investigated the foraging behaviour of resident individuals in both colonies, as well as that of relocated individuals, as enhanced foraging effort could represent a potential driver of reproductive costs. Results: We found negative consequences of relocation for offspring development, which were apparent when brood demand was experimentally increased. Recently relocated gulls travelled further distances for foraging than residents, as they often visited more distant foraging sites used by residents breeding in their natal colony as well as new areas outside the home range of the residents in the colony where they settled. Conclusions: Our results imply that relocated individuals did not yet optimally adapt to the new food landscape, which was unexpected, given the social information on foraging locations that may have been available from resident neighbours in their new breeding colony. Even though the short-term reproductive costs were comparatively low, we show that generalist species, such as the Lesser black-backed gull, may be more vulnerable to habitat loss than expected. Long term studies are needed to investigate how long individuals are affected by their relocation in order to better assess potential population effects of (breeding) habitat loss

Universal knowledge-seeking agents for stochastic environments

We define an optimal Bayesian knowledge-seeking agent, KL-KSA, designed for countable hypothesis classes of stochastic environments and whose goal is to gather as much information about the unknown world as possible. Although this agent works for arbitrary countable classes and priors, we focus on the especially interesting case where all stochastic computable environments are considered and the prior is based on Solomonoff’s universal prior. Among other properties, we show that KL-KSA learns the true environment in the sense that it learns to predict the consequences of actions it does not take. We show that it does not consider noise to be information and avoids taking actions leading to inescapable traps. We also present a variety of toy experiments demonstrating that KL-KSA behaves according to expectation

The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model.

BACKGROUND: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. RESULTS: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. CONCLUSIONS: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.Israel Cancer Research Fund (ICRF), Teva Pharmaceutical Industries Ltd

Iron oxide nanoparticles for neuronal cell applications: uptake study and magnetic manipulations.

BACKGROUND: The ability to direct and manipulate neuronal cells has important potential in therapeutics and neural network studies. An emerging approach for remotely guiding cells is by incorporating magnetic nanoparticles (MNPs) into cells and transferring the cells into magnetic sensitive units. Recent developments offer exciting possibilities of magnetic manipulations of MNPs-loaded cells by external magnetic fields. In the present study, we evaluated and characterized uptake properties for optimal loading of cells by MNPs. We examined the interactions between MNPs of different cores and coatings, with primary neurons and neuron-like cells. RESULTS: We found that uncoated-maghemite iron oxide nanoparticles maximally interact and penetrate into cells with no cytotoxic effect. We observed that the cellular uptake of the MNPs depends on the time of incubation and the concentration of nanoparticles in the medium. The morphology patterns of the neuronal cells were not affected by MNPs uptake and neurons remained electrically active. We theoretically modeled magnetic fluxes and demonstrated experimentally the response of MNP-loaded cells to the magnetic fields affecting cell motility. Furthermore, we successfully directed neurite growth orientation along regeneration. CONCLUSIONS: Applying mechanical forces via magnetic mediators is a useful approach for biomedical applications. We have examined several types of MNPs and studied the uptake behavior optimized for magnetic neuronal manipulations.MM gratefully acknowledges the BINA Scholarship for Outstanding Graduate Students. The authors thank Michelle Katz for her help with the morphology measurements

Wireless Network Virtualization: Opportunities for Sharing in the 3.5 GHz Band

In this paper, we evaluate the opportunities that Wireless Network Virtualization (WNV) can bring for spectrum sharing by focusing on the regulatory framework that has been deployed by the Federal Communications Commission (FCC) for the 3.5GHz band. Pairing this regulatory approach with WNV permits us to present a sharing proposal where emphasis is made on increasing resource availability and providing flexible methods for negotiating for resource access. We include an economics framework that aims at presenting an additional perspective on the attainable outcomes of our sharing proposal. We find that by pairing regulatory flexibility with an enabling technology, within an appropriate economics context, we can increase resource access opportunities and enhance current sharing arrangements

Birds flee en mass from New Year’s Eve fireworks

Anthropogenic disturbances of wildlife, such as noise, human presence, hunting activity, and motor vehicles, are becoming an increasing concern in conservation biology. Fireworks are an important part of celebrations worldwide, and although humans often find fireworks spectacular, fireworks are probably perceived quite differently by wild animals. Behavioral responses to fireworks are difficult to study at night, and little is known about the negative effects fireworks may have on wildlife. Every year, thousands of tons of fireworks are lit by civilians on New Year’s Eve in the Netherlands. Using an operational weather radar, we quantified the reaction of birds to fireworks in 3 consecutive years. Thousands of birds took flight shortly after midnight, with high aerial movements lasting at least 45 min and peak densities measured at 500 m altitude. The highest densities were observed over grasslands and wetlands, including nature conservation sites, where thousands of waterfowl rest and feed. The Netherlands is the most important winter staging area for several species of waterfowl in Europe. We estimate that hundreds of thousands of birds in the Netherlands take flight due to fireworks. The spatial and temporal extent of disturbance is substantial, and potential consequences are discussed. Weather radar provides a unique opportunity to study the reaction of birds to fireworks, which has otherwise remained elusive