In vitro toxicity of nanoceria: effect of coating and stability in biofluids

Due to the increasing use of nanometric cerium oxide in applications, concerns about the toxicity of these particles have been raised and have resulted in a large number of investigations. We report here on the interactions between 7 nm anionically charged cerium oxide particles and living mammalian cells. By a modification of the particle coating including low-molecular weight ligands and polymers, two generic behaviors are compared: particles coated with citrate ions that precipitate in biofluids and particles coated with poly(acrylic acid) that are stable and remain nanometric. We find that nanoceria covered with both coating agents are taken up by mouse fibroblasts and localized into membrane-bound compartments. However, flow cytometry and electron microscopy reveal that as a result of their precipitation, citrate-coated particles interact more strongly with cells. At cerium concentration above 1 mM, only citrate-coated nanoceria (and not particles coated with poly(acrylic acid)) display toxicity and moderate genotoxicity. The results demonstrate that the control of the surface chemistry of the particles and its ability to prevent aggregation can affect the toxicity of nanomaterials.Comment: 33 pages 10 figures, accepted at Nanotoxicolog

Shape Transition in Artificial Tumors: From Smooth Buckles to Singular Creases

International audienceUsing swelling hydrogels, we study the evolution of a thin circular artificial tumor whose growth is confined at the periphery. When the volume of the outer proliferative ring increases, the tumor loses its initial symmetry and bifurcates towards an oscillatory shape. Depending on the geometrical and elastic parameters, we observe either a smooth large-wavelength undulation of the swelling layer or the formation of sharp creases at the free boundary. Our experimental results as well as previous observations from other studies are in very good agreement with a nonlinear poroelastic model

Evaluating Scalable Distributed Erlang for Scalability and Reliability

Large scale servers with hundreds of hosts and tens of thousands of cores are becoming common. To exploit these platforms software must be both scalable and reliable, and distributed actor languages like Erlang are a proven technology in this area. While distributed Erlang conceptually supports the engineering of large scale reliable systems, in practice it has some scalability limits that force developers to depart from the standard language mechanisms at scale. In earlier work we have explored these scalability limitations, and addressed them by providing a Scalable Distributed (SD) Erlang library that partitions the network of Erlang Virtual Machines (VMs) into scalable groups (s_groups). This paper presents the first systematic evaluation of SD Erlang s_groups and associated tools, and how they can be used. We present a comprehensive evaluation of the scalability and reliability of SD Erlang using three typical benchmarks and a case study. We demonstrate that s_groups improve the scalability of reliable and unreliable Erlang applications on up to 256 hosts (6,144 cores). We show that SD Erlang preserves the class-leading distributed Erlang reliability model, but scales far better than the standard model. We present a novel, systematic, and tool-supported approach for refactoring distributed Erlang applications into SD Erlang. We outline the new and improved monitoring, debugging and deployment tools for large scale SD Erlang applications. We demonstrate the scaling characteristics of key tools on systems comprising up to 10 K Erlang VMs

Coiling Instability of Multilamellar Membrane Tubes with Anchored Polymers

We study experimentally a coiling instability of cylindrical multilamellar stacks of phospholipid membranes, induced by polymers with hydrophobic anchors grafted along their hydrophilic backbone. Our system is unique in that coils form in the absence of both twist and adhesion. We interpret our experimental results in terms of a model in which local membrane curvature and polymer concentration are coupled. The model predicts the occurrence of maximally tight coils above a threshold polymer occupancy. A proper comparison between the model and experiment involved imaging of projections from simulated coiled tubes with maximal curvature and complicated torsions.Comment: 11 pages + 7 GIF figures + 10 JPEG figure

Improving the Network Scalability of Erlang

As the number of cores grows in commodity architectures so does the likelihood of failures. A distributed actor model potentially facilitates the development of reliable and scalable software on these architectures. Key components include lightweight processes which ‘share nothing’ and hence can fail independently. Erlang is not only increasingly widely used, but the underlying actor model has been a beacon for programming language design, influencing for example Scala, Clojure and Cloud Haskell. While the Erlang distributed actor model is inherently scalable, we demonstrate that it is limited by some pragmatic factors. We address two network scalability issues here: globally registered process names must be updated on every node (virtual machine) in the system, and any Erlang nodes that communicate maintain an active connection. That is, there is a fully connected O(n2) network of n nodes. We present the design, implementation, and initial evaluation of a conservative extension of Erlang — Scalable Distributed (SD) Erlang. SD Erlang partitions the global namespace and connection network using s_groups. An s_group is a set of nodes with its own process namespace and with a fully connected network within the s_group, but only individual connections outside it. As a node may belong to more than one s_group it is possible to construct arbitrary connection topologies like trees or rings. We present an operational semantics for the s_group functions, and outline the validation of conformance between the implementation and the semantics using the QuickCheck automatic testing tool. Our preliminary evaluation in comparison with distributed Erlang shows that SD Erlang dramatically improves network scalability even if the number of global operations is tiny (0.01%). Moreover, even in the absence of global operations the reduced connection maintenance overheads mean that SD Erlang scales better beyond 80 nodes (1920 cores)

Interactions between Magnetic Nanowires and Living Cells : Uptake, Toxicity and Degradation

We report on the uptake, toxicity and degradation of magnetic nanowires by NIH/3T3 mouse fibroblasts. Magnetic nanowires of diameters 200 nm and lengths comprised between 1 {\mu}m and 40 {\mu}m are fabricated by controlled assembly of iron oxide ({\gamma}-Fe2O3) nanoparticles. Using optical and electron microscopy, we show that after 24 h incubation the wires are internalized by the cells and located either in membrane-bound compartments or dispersed in the cytosol. Using fluorescence microscopy, the membrane-bound compartments were identified as late endosomal/lysosomal endosomes labeled with lysosomal associated membrane protein (Lamp1). Toxicity assays evaluating the mitochondrial activity, cell proliferation and production of reactive oxygen species show that the wires do not display acute short-term (< 100 h) toxicity towards the cells. Interestingly, the cells are able to degrade the wires and to transform them into smaller aggregates, even in short time periods (days). This degradation is likely to occur as a consequence of the internal structure of the wires, which is that of a non-covalently bound aggregate. We anticipate that this degradation should prevent long-term asbestos-like toxicity effects related to high aspect ratio morphologies and that these wires represent a promising class of nanomaterials for cell manipulation and microrheology.Comment: 21 pages 12 figure

Scaling Reliably: Improving the Scalability of the Erlang Distributed Actor Platform

Distributed actor languages are an effective means of constructing scalable reliable systems, and the Erlang programming language has a well-established and influential model. While the Erlang model conceptually provides reliable scalability, it has some inherent scalability limits and these force developers to depart from the model at scale. This article establishes the scalability limits of Erlang systems and reports the work of the EU RELEASE project to improve the scalability and understandability of the Erlang reliable distributed actor model. We systematically study the scalability limits of Erlang and then address the issues at the virtual machine, language, and tool levels. More specifically: (1) We have evolved the Erlang virtual machine so that it can work effectively in large-scale single-host multicore and NUMA architectures. We have made important changes and architectural improvements to the widely used Erlang/OTP release. (2) We have designed and implemented Scalable Distributed (SD) Erlang libraries to address language-level scalability issues and provided and validated a set of semantics for the new language constructs. (3) To make large Erlang systems easier to deploy, monitor, and debug, we have developed and made open source releases of five complementary tools, some specific to SD Erlang. Throughout the article we use two case studies to investigate the capabilities of our new technologies and tools: a distributed hash table based Orbit calculation and Ant Colony Optimisation (ACO). Chaos Monkey experiments show that two versions of ACO survive random process failure and hence that SD Erlang preserves the Erlang reliability model. While we report measurements on a range of NUMA and cluster architectures, the key scalability experiments are conducted on the Athos cluster with 256 hosts (6,144 cores). Even for programs with no global recovery data to maintain, SD Erlang partitions the network to reduce network traffic and hence improves performance of the Orbit and ACO benchmarks above 80 hosts. ACO measurements show that maintaining global recovery data dramatically limits scalability; however, scalability is recovered by partitioning the recovery data. We exceed the established scalability limits of distributed Erlang, and do not reach the limits of SD Erlang for these benchmarks at this scal