pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells

Chitosan has been extensively studied as a genetic drug delivery platform. However, its efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding strength of cargo with chitosan, we proposed including heparin as a competing polyanion in the polyplexes. We developed chitosan–heparin nanoparticles by a one-step process for the local delivery of oligonucleotides. The size of the polyplexes was dependent on the mass ratio of polycation to polyanion. The mechanism of oligonucleotide release was pH-dependent and associated with polyplex swelling and collapse of the polysaccharide network. Inclusion of heparin enhanced the oligonucleotide release from the chitosan-based polyplexes. Furthermore, heparin reduced the toxicity of polyplexes in the cultured cells. The cell uptake of chitosan–heparin polyplexes was equal to that of chitosan polyplexes, but heparin increased the transfection efficiency of the polyplexes two-fold. The application of chitosan–heparin small interfering RNA (siRNA) targeted to vascular endothelial growth factor (VEGF) silencing of ARPE-19 cells was 25% higher. Overall, chitosan–heparin polyplexes showed a significant improvement of gene release inside the cells, transfection, and gene silencing efficiency in vitro, suggesting that this fundamental strategy can further improve the transfection efficiency with application of non-viral vectors

Exactly solvable potentials of Calogero type for q-deformed Coxeter groups

We establish that by parameterizing the configuration space of a one-dimensional quantum system by polynomial invariants of q-deformed Coxeter groups it is possible to construct exactly solvable models of Calogero type. We adopt the previously introduced notion of solvability which consists of relating the Hamiltonian to finite dimensional representation spaces of a Lie algebra. We present explicitly the $G_2^q$-case for which we construct the potentials by means of suitable gauge transformations.Comment: 22 pages Late

Few-cycle laser driven reaction nanoscopy on aerosolized silica nanoparticles

Nanoparticles offer unique properties as photocatalysts with large surface areas. Under irradiation with light, the associated near-fields can induce, enhance, and control molecular adsorbate reactions on the nanoscale. So far, however, there is no simple method available to spatially resolve the near-field induced reaction yield on the surface of nanoparticles. Here we close this gap by introducing reaction nanoscopy based on three-dimensional momentum-resolved photoionization. The technique is demonstrated for the spatially selective proton generation in few-cycle laser-induced dissociative ionization of ethanol and water on SiO2 nanoparticles, resolving a pronounced variation across the particle surface. The results are modeled and reproduced qualitatively by electrostatic and quasi-classical mean-field Mie Monte-Carlo (M3C) calculations. Reaction nanoscopy is suited for a wide range of isolated nanosystems and can provide spatially resolved ultrafast reaction dynamics on nanoparticles, clusters, and droplets

Kriminalität von Aussiedlern: eine Bestandsaufnahme

"Das Bundesministerium des Innern hat die Forschungsgruppe des Bundesamtes für Migration und Flüchtlinge damit beauftragt, valide Zahlen zur Aussiedlerkriminalität zusammenzustellen und den Stand der Forschung aufzuarbeiten. Mit dem Working Paper wird eine Bestandsaufnahme vorgelegt, die sowohl die polizeiliche Kriminalitätsstatistik als auch die empirische Sozialforschung berücksichtigt. Dabei wird die Kriminalität von Aussiedlern mit der Kriminalität von einheimischen Deutschen und Nichtdeutschen verglichen. Die Befunde werden unter Berücksichtigung aller methodischen Forschungsprobleme eingehend beleuchtet. In Ergänzung dazu werden die selbstberichteten Gewalt- und Delinquenzerfahrungen von jugendlichen Aussiedlern anhand verschiedener Dunkelfelduntersuchungen analysiert. Die Ursachen und Risikofaktoren, die mit einer erhöhten Kriminalitätsrate einhergehen, werden dargelegt." (Autorenreferat

The individual relationship between atrial fibrillation sources from CARTOFINDER mapping and atrial cardiomyopathy: the catch me if you can trial

Background Targeting individual sources identified during atrial fibrillation (AF) has been used as an ablation strategy with varying results. Objective Aim of this study was to evaluate the relationship between regions of interest (ROIs) from CARTOFINDER (CF) mapping and atrial cardiomyopathy from late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR). Methods Twenty consecutive patients underwent index catheter ablation for persistent AF (PERS AF). Pre-processed LGE CMR images were merged with the results from CF mapping to visualize harboring regions for focal and rotational activities. Atrial cardiomyopathy was classified based on the four Utah stages. Results Procedural success was achieved in all patients (n = 20, 100%). LGE CMR revealed an intermediate amount of 21.41% ± 6.32% for LA fibrosis. ROIs were identified in all patients (mean no ROIs per patient n = 416.45 ± 204.57). A tendency towards a positive correlation between the total amount of atrial cardiomyopathy and the total number of ROIs per patient (regression coefficient, β = 10.86, p = .15) was observed. The degree of fibrosis and the presence of ROIs per segment showed no consistent spatial correlation (posterior: β = 0.36, p-value (p) = .24; anterior: β = −0.08, p = .54; lateral: β = 0.31, p = 39; septal: β = −0.12; p = .66; right PVs: β = 0.34, p = .27; left PVs: β = 0.07, p = .79; LAA: β = −0.91, p = .12). 12 months AF-free survival was 70% (n = 14) after ablation. Conclusion The presence of ROIs from CF mapping was not directly associated with the extent and location of fibrosis. Further studies evaluating the relationship between focal and rotational activity and atrial cardiomyopathy are mandatory

Few-cycle laser driven reaction nanoscopy on aerosolized silica nanoparticles

Nanoparticles offer unique properties as photocatalysts with large surface areas. Under irradiation with light, the associated near-fields can induce, enhance, and control molecular adsorbate reactions on the nanoscale. So far, however, there is no simple method available to spatially resolve the near-field induced reaction yield on the surface of nanoparticles. Here we close this gap by introducing reaction nanoscopy based on three-dimensional momentum-resolved photoionization. The technique is demonstrated for the spatially selective proton generation in few-cycle laser-induced dissociative ionization of ethanol and water on SiO2 nanoparticles, resolving a pronounced variation across the particle surface. The results are modeled and reproduced qualitatively by electrostatic and quasi-classical mean-field Mie Monte-Carlo (M3C) calculations. Reaction nanoscopy is suited for a wide range of isolated nanosystems and can provide spatially resolved ultrafast reaction dynamics on nanoparticles, clusters, and droplets

Targeted delivery of a vaccine protein to Langerhans cells in the human skin via the C-type lectin receptor Langerin

Human skin is a preferred vaccination site as it harbors multiple dendritic cell (DC) subsets, which display distinct C-type lectin receptors (CLR) that recognize pathogens. Antigens can be delivered to CLR by antibodies or ligands to boost antigen-specific immune responses. This concept has been established in mouse models but detailed insights into the functional consequences of antigen delivery to human skin DC in situ are sparse. In this study, we cloned and produced an anti-human Langerin antibody conjugated to the EBV nuclear antigen 1 (EBNA1). We confirmed specific binding of anti-Langerin-EBNA1 to Langerhans cells (LC). This novel LC-based vaccine was then compared to an existing anti-DEC-205-EBNA1 fusion protein by loading LC in epidermal cell suspensions before coculturing them with autologous T cells. After restimulation with EBNA1-peptides, we detected elevated levels of IFN-γ- and TNF-α-positive CD4+ T cells with both vaccines. When we injected the fusion proteins intradermally into human skin explants, emigrated skin DC targeted via DEC-205-induced cytokine production by T cells, whereas the Langerin-based vaccine failed to do so. In summary, we demonstrate that antibody-targeting approaches via the skin are promising vaccination strategies, however, further optimizations of vaccines are required to induce potent immune responses