Scientific publications

Severe plastic deformation (strains > 100%) has been shown to create significant grain refinement in polycrystalline materials, leading to a nanometric equiaxed crystalline structure for such metals as aluminum, copper and nickel alloys. This process, termed continuous dynamic recrystallization, is governed by evolution of the dislocation structure, which creates new grain boundaries from dislocation walls. In the proposed model, plasticity occurs which firstly involves dislocation multiplication, leading to strain hardening limited by dynamic recovery. After a critical dislocation density is reached new grain boundaries are formed by condensation of walls of dislocations, creating a new stable configuration that is favored due to a reduction of the system free energy. This evolution of the microstructure continues to develop, with a consequent progressive decrease in the average grain diameter. The proposed model provides a quantitative prediction of the evolution of the average grain size, as well as the dislocation density, during continued plastic strain. The model can be calibrated by use of results from any experiment that involves large plastic deformation of metals, subject to negligible annealing effects. In this paper, the model has been calibrated, and consequently validated, through experiments on machining of Al 6061-T6.

A general asymptotic plane strain crack tip stress field is constructed for linear versions of neo-Hookean materials, which spans a wide variety of special cases including incompressible Mooney elastomers, the compressible Blatz-Ko elastomer, several cases of the Ogden constitutive law and a new result for a compressible linear neo-Hookean material. The nominal stress field has dominant terms that have a square root singularity with respect to the distance of material points from the crack tip in the undeformed reference configuration. At second order, there is a uniform tension parallel to the crack. The associated displacement field in plane strain at leading order has dependence proportional to the square root of the same coordinate. The relationship between the amplitude of the crack tip singularity (a stress intensity factor) and the plane strain energy release rate is outlined for the general linear material, with simplified relationships presented for notable special cases.

The phase field description for crack growth and fracture is an attractive alternative to numerical methods based on discrete representations of cracks, since the phase field methodology avoids the numerically challenging monitoring of the discontinuities introduced by the crack. In particular, for the simulation of complex crack growth topologies and application to coupled systems, e.g. with thermal or electrical fields, the phase field method has shown promise. However, an accurate prediction of the crack growth initiation is mandatory for a reliable simulation of crack trajectories both in terms of load history and the path followed through the material. In this work, we therefore investigate predictions of crack growth derived from the phase field method and compare them with established relations from fracture mechanics. To implement the phase field method for crack growth, a parallelized finite element method computer code using adaptive mesh refinement is developed and implemented. Results from it are presented. For these results, pre-existing cracks are introduced into the finite element model in two ways, including their representation as discrete discontinuities and as heterogeneities in the phase field order parameter.

While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth. We employed different models of M1 and M2 polarization: granulocyte-macrophage colony-stimulating factor/lipopolysaccharide (LPS)/interferon (IFN)-γ was used to generate primary human M1 cells and macrophage colony-stimulating factor (M-CSF)/interleukin (IL)-10 to differentiate M2 monocyte-derived macrophages (MDM). PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-γ and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø26 and 41 nm) and microparticles (Ø1.75 μm) was quantified. At the concentration used (50 μg/ml), silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human MDM compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue. In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but might also open up therapeutic perspectives allowing to specifically target M2 polarized macrophages.

Background: Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation. Methods: Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. Results: Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific T(H)2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. Conclusions: Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.

The development of safe engineered nanoparticles (NPs) requires a detailed understanding of their interaction mechanisms on a cellular level. Therefore, quantification of NP internalization is crucial to predict the potential impact of intracellular NP doses, providing essential information for risk assessment as well as for drug delivery applications. In this study, the internalization of 25 nm and 85 nm silica nanoparticles (SNPs) in alveolar type II cells (A549) was quantified by application of super-resolution STED (stimulated emission depletion) microscopy. Cells were exposed to equal particle number concentrations (9.2×1010 particles mL−1) of each particle size and the sedimentation of particles during exposure was taken into account. Microscopy images revealed that particles of both sizes entered the cells after 5 h incubation in serum supplemented and serum-free medium. According to the in vitro sedimentation, diffusion, and dosimetry (ISDD) model 20–27% of the particles sedimented. In comparison, 102-103 NPs per cell were detected intracellularly serum-containing medium. Furthermore, in the presence of serum, no cytotoxicity was induced by the SNPs. In serum-free medium, large agglomerates of both particle sizes covered the cells whereas only high concentrations (≥ 3.8 × 1012 particles mL−1) of the smaller particles induced cytotoxicity.

Different AlN nanostructures were synthesized by using chemical vapor condensation method. The raw materials were a mixture of Al and NH4Cl powder with different weight ratios as well as Cu and Mn powders, which were used as dopants. The effects of the source materials, dopants, and annealing on optical and structural properties of AlN nanostructures were investigated. Scanning electron microscopy results showed different nanostructures, including nanowires and nanoparticles with different sizes and morphologies. The photoluminescence spectroscopy of the samples was performed at room temperature. Photoluminescence spectra of the samples showed intense peaks in visible regions from undoped, Mn-doped, and Cu-doped samples. Due to the light emission from the samples at different wavelengths, these nanostructures can be used in optoelectronic devices.

In this work, we prepared thin films of aluminum oxide (Al2O3) with different thicknesses, using a wet chemical process. The Al2O3 nanoparticles with an average size of 40 nm were dispersed in water and deposited on soda glass substrates. The morphology of the resulting thin films was characterized by means of scanning electron microscopy. The optical properties of the thin films were studied by measuring reflectance and transmittance. A theoretical description of the reflection and transmission mechanism of the films was developed by measuring the thickness and spectral behavior of the refractive index. Numerical evaluations were used for modeling the optical spectra of the thin films of alumina. By fitting numerical curves to the experimental data, the extinction coefficient and refractive index were obtained. The dielectric constant and optical properties of the colloidal solution of the particles were also studied.

Intercellular communication is a fundamental process in the development and functioning of multicellular organisms. Recently, an essentially new type of intercellular communication, based on thin membrane channels between cells, has been reported. These structures, termed intercellular or tunnelling nanotubes (TNTs), permit the direct exchange of various components or signals (e.g., ions, proteins, or organelles) between non-adjacent cells at distances over 100 μm. Our studies revealed the presence of tunnelling nanotubes in microvascular endothelial cells (HMEC-1). The TNTs were studied with live cell imaging, environmental scanning electron microscopy (ESEM), and coherent anti-Stokes Raman scattering spectroscopy (CARS). Tunneling nanotubes showed marked persistence: the TNTs could connect cells over long distances (up to 150 μm) for several hours. Several cellular organelles were present in TNTs, such as lysosomes and mitochondria. Moreover, we could identify lipid droplets as a novel type of cargo in the TNTs. Under angiogenic conditions (VEGF treatment) the number of lipid droplets increased significantly. Arachidonic acid application not only increased the number of lipid droplets but also tripled the extent of TNT formation. Taken together, our results provide the first demonstration of lipid droplets as a cargo of TNTs and thereby open a new field in intercellular communication research.

Ideal cationic polymers for siRNA delivery could result in its enhanced cellular internalization, escape from endosomal degradation, and rapid release in cell cytoplasm, to facilitate knockdown of the target gene. In this study, we have investigated the ability of an in-house synthesized cationic polyrotaxane to bind siRNA into nanometric complexes. This polymer, which had earlier shown improved transfection of model siRNA (luciferase), was used to improve the cellular internalization of the siRNA molecule with therapeutic implications. In cellular assays, the polymer enhanced the knockdown of a gene involved in the pathogenesis of tuberculosis, when the nanocomplexes were compared with free siRNA. The efficacy and cellular non-toxicity of this polymer encourage its further exploitation in animal models of tuberculosis and other intracellular bacterial infections.