In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

The introduction of engineered nanostructured materials into a rapidly increasing number of industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of (consumer) products. The dynamic development of nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety.In this consensus document from a workshop on in-vitro cell systems for nanoparticle toxicity testing¹ an overview is given of the main issues concerning exposure to airborne nanoparticles, lung physiology, biological mechanisms of (adverse) action, in-vitro cell exposure systems, realistic tissue doses, risk assessment and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanoparticle toxicity. For the investigation of lung toxicity, a strong preference was expressed for air–liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they more closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. An important aspect, which is frequently overlooked, is the comparison of typically used in-vitro dose levels with realistic in-vivo nanoparticle doses in the lung. If we consider average ambient urban exposure and occupational exposure at 5 mg/m³ (maximum level allowed by Occupational Safety and Health Administration (OSHA)) as the boundaries of human exposure, the corresponding upper-limit range of nanoparticle flux delivered to the lung tissue is 3×10^?5–5×10^-3 μg/h/cm² of lung tissue and 2–300 particles/h/(epithelial) cell. This range can be easily matched and even exceeded by almost all currently available cell exposure systems.The consensus statement includes a set of recommendations for conducting in-vitro cell exposure studies with pulmonary cell systems and identifies urgent needs for future development. As these issues are crucial for the introduction of safe nanomaterials into the marketplace and the living environment, they deserve more attention and more interaction between biologists and aerosol scientists. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.     

Combinatorial approach to the growth of α-(Al1 − x,Crx)2 + δ(O1 − y,Ny)3 solid solution strengthened thin films by reactive r.f. magnetron sputtering

The design and synthesis of Al–Cr–O–N thin films in a metastable solid solution strengthened α-(Al_{1 − x},Cr_x)_{2 + δ}(O_{1 − y},N_y)₃ microstructure are described. The deposition experiments were carried out by reactive r.f. magnetron sputtering in an argon–oxygen–nitrogen atmosphere for the sputtering from a segmented target, composed of an Al half plate and a Cr half plate. The constitution, microstructure and Vickers micro hardness of the coatings are discussed in dependence of the deposition parameters and the elemental composition. The range of α-(Al_{1 − x},Cr_x)_{2 + δ}(O_{1 − y},N_y)₃ phase formation is shifted to higher Cr/(Al + Cr) ratios with increasing nitrogen gas flow. A γ-Al–Cr–O–N phase is formed at high total gas pressures and low Cr/(Al + Cr) ratios. The solid solution strengthening in the quaternary material system leads to a significant Vickers micro hardness increase compared to α-(Al_{1 − x},Cr_x)₂O₃ coatings deposited in the same PVD machine under corresponding process parameters. The α-(Al_{1 − x},Cr_x)_{2 + δ}(O_{1 − y},N_y)₃ thin films offer an additional restraint of the lattice by the incorporation of nitrogen and therefore higher Vickers micro hardness values are measured compared to the Al–Cr–O material system.     

Adaptive training of local reduced bases for unsteady incompressible Navier–Stokes flows

This report presents a numerical study of reduced‐order representations for simulating incompressible Navier–Stokes flows over a range of physical parameters. The reduced‐order representations combine ideas of approximation for nonlinear terms, of local bases, and of least‐squares residual minimization. To construct the local bases, temporal snapshots for different physical configurations are collected automatically until an error indicator is reduced below a user‐specified tolerance. An adaptive time‐integration scheme is also employed to accelerate the generation of snapshots as well as the simulations with the reduced‐order representations. The accuracy and efficiency of the different representations is compared with examples with parameter sweeps. Copyright © 2015 John Wiley & Sons, Ltd.     

Ultrasmall Integrin‐Targeted Silica Nanoparticles Modulate Signaling Events and Cellular Processes in a Concentration‐Dependent Manner

Cellular and molecular‐level interactions of nanoparticles with biological systems are a rapidly evolving field requiring an improved understanding of endocytic trafficking as the principal driver and regulator of signaling events and cellular responses. An understanding of these processes is vital to nanomedicine applications. Studies investigating the complex interplay of these processes and their relationship to targeted nanoparticles exploiting endocytic pathways are notably lacking. It is known that integrins traffic through the endosomal pathway and participate in diverse roles controlling signal transduction, cell migration, and proliferation. Here, it is shown that ultrasmall, nontoxic, core–shell silica nanoparticles (C‐dots), surface‐functionalized with cRGDY peptides, modestly activate integrin‐signaling pathways, in turn, promoting the enhancement of cellular functions. First, nanomolar concentrations, two orders of magnitude higher than clinical trial doses, internalize within αvβ3 integrin‐expressing melanoma and endothelial cells, predominantly through an integrin receptor‐dependent endocytic route. Second, integrin‐mediated activation of focal adhesion kinase (FAK) and downstream signaling pathways occurs, in turn, upregulating phosphorylated protein expression levels and promoting concentration‐dependent cellular migration and proliferative activity. Inhibiting FAK catalytic activity leads to decreased phosphorylation levels and cellular migration rates. These findings may inform the design of more effectively‐targeted nanomedicines and provide insights into endocytic regulation of signal transduction.     

A graph partitioning strategy for solving large-scale crew scheduling problems

Railway crew scheduling deals with generating driver duties for a given train timetable such that all work regulations are met and the resulting schedule has minimal cost. Typical problem instances in the freight railway industry require the generation of duties for thousands of drivers operating tens of thousands of trains per week. Due to short runtime requirements, common solution approaches decompose the optimization problem into smaller subproblems that are solved separately. Several studies have shown that the way of decomposing the problem significantly affects the solution quality. An overall best decomposition strategy for a freight railway crew scheduling problem, though, is not known. In this paper, we present general considerations on when to assign two scheduled train movements to separate subproblems (and when to rather assign them to the same subproblem) and deduct a graph partitioning based decomposition algorithm with several variations. Using a set of real-world problem instances from a major European railway freight carrier, we evaluate our strategy and benchmark the performance of the decomposition algorithm both against a common non-decomposition algorithm and a lower bound on the optimal solution schedule. The test runs show that our decomposition algorithm is capable of producing high-quality solution schedules while significantly cutting runtimes compared to the non-decomposition solution algorithm. We are following a ”greenfield” approach, where no information on previous schedules is needed. Hence, our approach is applicable to any railway crew scheduling setting, including network enlargement, integration of new customers, etc.     

Strain induced GdH2 precipitate in Mg–Gd based alloys

A new rectangle-shape GdH₂ precipitate was identified in Mg–Gd based alloys after mechanical polishing or compressive deformation. The precipitate was mainly distributed near the dendrite or grain boundaries where gadolinium element was segregated owing to non-equilibrium solidification. It is confirmed that hydrogen-containing medium, deformation and gadolinium segregation were the prerequisites to form GdH₂ precipitate. The amount of GdH₂ precipitate was mostly associated with deformation and the gadolinium content. A model was introduced to explain the formation mechanism of GdH₂ precipitate. The hydrogen in GdH₂ precipitate principally came from the outside medium. Moreover, the diffusion and transportation of hydrogen were improved by the movement of dislocation.     

Temperature of silicon wafers during in-line high-rate evaporation of aluminum

Knowing the substrate temperature during in-line high-rate Al deposition onto silicon solar cells is essential for understanding and improving the deposition process. We deposit 2 and 5 μm-thick aluminum layers at a dynamic deposition rate of 5 μm m/min onto 130 and 180 μm-thick, planar and pyramidally textured, p-type silicon wafers and measure the wafer temperature during the deposition. The temperature depends on the aluminum layer thickness, the wafer thickness, and the wafer emissivity. Two-dimensional finite-element simulations reproduce the measured peak temperatures with an accuracy of 3%.     

Vergleich des Abbrandverhaltens beim Rezyklieren von Aluminiumsp?nen und -briketts

At the processing of aluminium castings 3?C5 % swarf is arising. The fine material is transferred into the secondary aluminium metallurgy cycle. The melting process can be performed by using salt. Due to the high reactivity of the swarf, it is important that it has no contact to the surface. At the non-salt process different pumping systems can be used, but most of the companies do not have such devices. When the fine particles are charged directly on to the surface of the bath the losses of aluminium can be higher than 70 %. One possibility to avoid such enormous causalities is to briquette the fine material. In this paper the melting loss of aluminium swarf and briquettes is compared. Some practical trials have been done in a batch process with an induction furnace. In cooperation with the ATM Recyclingsystems GmbH some investigations concerning the behaviour of the aluminium swarf and briquettes at the melting process will be done.     

Vom Recht auf informationelle Selbstbestimmung zum Zensus 2011

Der Schutz des Rechts auf informationelle Selbstbestimmung erstreckt sich inzwischen auf fast alle Lebensbereiche, in denen Daten und Informationen über Bürgerinnen und Bürger eine Rolle spielen. Die Volksz?hlung des Jahres 2011 wirft die Frage nach dem Stand der Reichweite des Schutzbereiches der informationellen Selbstbestimmung jedoch erneut auf.