Scientific publications

In this paper we present a novel application of denoising by means of nonlinear diffusion filters (NDFs). NDFs have been successfully applied for image processing and computer vision areas, particularly in image denoising, smoothing, segmentation, and restoration. We apply two types of NDFs for the denoising of evoked responses in single-trials in a matrix form, the nonlinear isotropic and the anisotropic diffusion filters. We show that by means of NDFs we are able to denoise the evoked potentials resulting in a better extraction of physiologically relevant morphological features over the ongoing experiment. This technique offers the advantage of translation-invariance in comparison to other well-known methods, e.g., wavelet denoising based on maximally decimated filter banks, due to an adaptive diffusion feature. We compare the proposed technique with a wavelet denoising scheme that had been introduced before for evoked responses. It is concluded that NDFs represent a promising and useful approach in the denoising of event related potentials. Novel NDF applications of single-trials of auditory brain responses (ABRs) and the transcranial magnetic stimulation (TMS) evoked electroencephalographic responses denoising are presented in this paper.

A new class of materials for ultrasonic matching layers is presented. The materials consist of nanoscale cerium oxide particles in an epoxy functionalized organic inorganic hybrid polymer matrix. The cerium oxide agglomerates to particles with 20 nm diameters. The content of particles in the polymer matrix could be increased to 75 wt.% which corresponds to 37 vol.%. The most technical important piezoelectrical ceramics have an acoustic impedance of about 30 MRayl, to improve coupling into water or biological tissue with an acoustic impedance of about 1.5 MRayl a matching layer should have an acoustic impedance of about 6.8 MRayl. With a filling degree of 75 wt.% the new composite material reaches an acoustic impedance of 7 MRayl. The materials are synthesized by a hydrolytic condensation combined with polymerization. This way of synthesis allows the use of organic solvents to adjust the viscosity of the sol and the application of different coating techniques. Ultrasound transducers (100 MHz) were built to test the new matching layers and an increase of the voltage signal amplitude of about 100% could be detected.

Nanoscaled hydroxyapatite (n-HAp) was prepared by a wet chemical precipitation method, pressed to pellets and sintered at various temperatures between 900 and 1200°C. With input stoichiometries of Ca/P ratios between 1.4 and 2.0, compositions in the substoichiometric range of Ca/P between 1.45(1) and 1.62(3) were determined after preparation. After sintering, final values of the Ca/P ratio between 1.45(8) and 1.66(4) were found. Capacitances and dielectric losses were determined in the frequency range between 20 Hz and 1 MHz and dielectric constants calculated from the capacitances. Dependencies of the dielectric properties on the composition, as well as on sintering temperature and frequencies were investigated. The dielectric constants generally tend to increase with increasing Ca-content. Different behaviour was observed for low frequencies (below 103 Hz) and for compositions far from the stoichiometric point of hydroxyapatite (Ca/P: 1.67). Comparable results were found for dielectric losses.

Background: Investigations on pulmonary macrophages (MF) mostly focus on alveolar MF (AM) as a well-defined cell population. Characteristics of MF in the interstitium, referred to as lung interstitial MF (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods: Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results: IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MF populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion: AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MF in the inflammatory response.

Agglomeration of monodisperse thiol-stabilized gold particles with diameters of 6 nm, suspended in organic solvents, was induced by the cooling of the suspension. A sharp transition between the stable suspension and agglomeration resulted. The temperature of the transition depends on the concentration and the compatibility of the solvent. The morphology of the formed particle structures upon agglomeration implies that the used metal colloid can be described as a van der Waals-gas. The particles undergo phase transitions from a stable fluid phase to a metastable phase, in which nucleation and growth occur, or to an instable phase, in which spinodal decomposition occurs. The results will direct research on routes to nanostructured materials using nanoparticles as building blocks.

A reliable strategy is presented to combine the preparation of functional building blocks based on polymer beads decorated with luminescent nanocrystals (NCs) and their precise positioning onto suitable patterns by capillary assembly technique. In particular, a layer-by-layer (LbL) polyelectrolyte (PE) deposition procedure has been implemented to provide uniform NC coverage on PS beads, thus conveying the optical properties of luminescent nanocrystals to highly processable PS beads. The latter have then been integrated into patterned stamps by means of template-driven capillary assembly. Their selective positioning has been directed by means of pattern geometry. The use of luminescent (CdSe)ZnS NCs offers a direct optical probe to evaluate the efficiency of the positioning procedure on the substrate, enabling the extension of the method to a wide range of materials, i.e., NCs with different compositions and specific geometry-dependent properties. Moreover, the precise control over the pattern geometry and the micrometer accuracy in positioning achieved by capillary assembly make such functional patterned structures excellent candidates for integration into devices exploiting specific size-dependent NC properties.

The behaviour of materials is governed by their microstructures, whether they are naturally occurring or artificially designed. Engineered microstructures lead to materials with new and useful functions, but their real-world application requires scalable microstructuring methods for production. This review discusses several principles of fabrication and their scalability. Replication by imprint and multiplexed probes are obvious candidates for scale-up, but they limit the choice of materials. The assembly of interacting particles is a promising, scalable fabrication method. A wide range of materials can be obtained as particles which assemble into regular superstructures, but large-scale structuring at high precision and yield as yet remains a challenge.

Three synthetic routes to hydrophobic silica nanoparticles are compared in this paper. First, the established synthetic method based on the Stöber process was examined. Monodisperse colloidal silica particles with diameters of 15-25 nm were prepared via the hydrolysis of tetraethyl orthosilicate (TEOS) by aqueous ammonia in ethanol. The surfaces of these particles were rendered hydrophobic with octadecyltrimethoxysilane (ODTMS) after the reaction or, more conveniently, during the growth phase. Secondly, silica particles with diameters of 15-50 nm were prepared using a one-pot synthesis in which TEOS was hydrolyzed by an amino acid and the resulting particles were coated with ODTMS. Lastly a novel, direct approach to the synthesis of hydrophobic organosilica nanoparticles was developed using ODTMS as the single silica source. Hydrolysis of the ODTMS by aqueous ammonia in ethanol yielded monodisperse colloidal organosilica particles with diameters of 15-30 nm.

Gene therapy scientists have developed expression systems for therapeutic transgenes within patients, which must be seamlessly integrated into the patient's physiology by developing sophisticated control mechanisms to titrate expression levels of the transgenes into the therapeutic window. However, despite these efforts, gene-based medicine still faces security concerns related to the administration of the therapeutic transgene vector. Here, molecular tools developed for therapeutic transgene expression can readily be transferred to materials science to design a humanized drug depot that can be implanted into mice and enables the trigger-inducible release of a therapeutic protein in response to a small-molecule inducer. The drug depot is constructed by embedding the vascular endothelial growth factor (VEGF121) as model therapeutic protein into a hydrogel consisting of linear Polyacrylamide crosslinked with a homodimeric variant of the human FKbinding protein 12 (F M), originally developed for gene therapeutic applications, as well as with dimethylsuberimidate. Administrating increasing concentrations of the inducer molecule FK506 triggers the dissociation of FM thereby loosening the hydrogel structure and releasing the VEGF121 payload in a dose-adjustable manner. Subcutaneous implantation of the drug depot into mice and subsequent administration of the inducer by injection or by oral intake triggers the release of VEGF121 as monitored in the mouse serum. This study is the first demonstration of a stimuli-responsive hydrogel that can be used in mammals to release a therapeutic protein on demand by the application of a small-molecule stimulus. This trigger-inducible release is a starting point for the further development of externally controlled drug depots for patient-compliant administration of biopharmaceuticals. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthetic biology as the discipline of reconstructing natural and designing novel biological systems is gaining increasing impact in signaling science. This review article provides insight into synthetic approaches for analyzing and synthesizing signaling processes starting with strategies into how natural and pathological signaling pathways can be reconstructed in an evolutionary distant host to study their topology and function while avoiding interference with the original host background. In the second part we integrate synthetic strategies in the rewiring of signaling systems at the nucleic acid and protein level to reprogram cellular functions for biotechnological applications. The last part focuses on synthetic inter-cell and inter-species signaling devices and their integration into synthetic ecosystems to study fundamental mechanisms governing the co-existence of species. We finally address current bottlenecks in the (re-)design of signaling pathways and discuss future directions in signaling-related synthetic biology. © 2010 The Royal Society of Chemistry.