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Solutions of Nafion® with an ion exchange capacity (IEC) of 0.91 meq g(-1), which are on the verge of the formation of SO(3)H nanoclusters, were spin coated on silicon (Si), glassy carbon (GC) and platinum/silicon (Pt/Si) substrates to form films of up to 256 nm thickness. Nanostructure of the films was studied using Doppler broadening of annihilation radiation (DBAR), positron annihilation lifetime (PAL), X-ray photoelectron spectroscopy (XPS), an atomic force microscope (AFM) and contact angle measurements. Contact angles as low as 10 degrees indicate that the surface of dry ultrathin Nafion® films on Si is highly hydrophilic. XPS data of 10 nm thick, ultrathin film on Si show that oxygen concentration is enhanced and the SO(3)H group concentration, in other words, IEC on the surface is much higher than other films. The S parameter measured by DBAR of an ultrathin Nafion® film on Si is much higher than that of the films on the other substrates. We consider that a large number of hydrophilic, reversed micelle like SO(3)H groups are on the surface of the ultrathin Nafion® film on Si but not on the surface of other films. Positrons implanted into the film are trapped by the SO(3)H clusters, annihilating with the electrons of oxygen and exhibit the high S parameter. The SO(3)H concentration on the surface of thin Nafion® films on GC and Pt/Si substrates may not be so high as the threshold for the formation of a large number of SO(3)H clusters. Positrons implanted into the films annihilate mostly with fluorine atoms, resulting in a low S parameter. The film-substrate interaction plays an essential role in nanostructuring of Nafion® thin films, which may also be the case for Nafion® on the catalysts of polymer electrolyte fuel cells.

To understand the relationship between surface morphology and proton conduction of polymer electrolyte thin films, perfluorinated ionomer Nafion® thin films were prepared on different substrates such as glassy carbon (GC), hydrophilic-GC (H-GC), and platinum (Pt) as models for the ionomer film within a catalyst layer. Atomic force microscopy coupled with an electrochemical (e-AFM) technique revealed that proton conduction decreased with film thickness; an abrupt decrease in proton conductance was observed when the film thickness was less than ca. 10 nm on GC substrates in addition to a significant change in surface morphology. Furthermore, thin films prepared on H-GC substrates with UV-ozone treatment exhibited higher proton conduction than those on untreated GC substrates. However, Pt substrates exhibited proton conduction comparable to that of GCs for films thicker than 20 nm; a decrease in proton conduction was observed at ∼5 nm thick film but was still much higher than for carbon substrates. These results indicate that the number of active proton-conductive pathways and/or the connectivity of the proton path network changed with film thickness. The surface morphology of thinner films was significantly affected by the film/substrate interface and was fundamentally different from that of the bulk thick membrane.

TFmiR is a freely available web server for deep and integrative analysis of combinatorial regulatory interactions between transcription factors, microRNAs and target genes that are involved in disease pathogenesis. Since the inner workings of cells rely on the correct functioning of an enormously complex system of activating and repressing interactions that can be perturbed in many ways, TFmiR helps to better elucidate cellular mechanisms at the molecular level from a network perspective. The provided topological and functional analyses promote TFmiR as a reliable systems biology tool for researchers across the life science communities. TFmiR web server is accessible through the following URL: http://service.bioinformatik.uni-saarland.de/tfmir.

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Variations of the free volume, O2 permeability, and structure of the Nafion membrane upon ion exchange of H+ with Na+ and K+ were studied. The free volume was quantified using the positron annihilation lifetime (PAL) technique, whereas the polymer structure was characterized by dynamic mechanical analysis (DMA), nanoindentation, and wide-angle X-ray diffraction (WAXD). It was found that the ion exchange significantly expands the free volume and at the same time decreases the O2 permeability. This is opposed to the simple free volume model in which the structure with less open volume is more amenable to lower permeability. Comparison of experimental data collected by different techniques revealed that not only the free volume but also the polymer stiffness plays an essential role in O2 permeation.

Mismatch-repair deficiency (MMR-D) is closely linked to hypermutation and accordingly, high immunogenicity. MMR-D-related tumors thus constitute ideal vaccination targets for both therapeutic and prophylactic approaches. Herein, the prophylactic and therapeutic impact of a cellular vaccine on tumor growth and tumor-immune microenvironment was studied in a murine MLH1 knockout mouse model. Prophylactic application of the lysate (+/- CpG ODN 1826) delayed tumor development, accompanied by increased levels of circulating T cell numbers. Therapeutic application of the vaccine prolonged overall survival (median time: 11.5 (lysate) and 12 weeks (lysate + CpG ODN) vs. 3 weeks (control group), respectively) along with reduced tumor burden, as confirmed by PET/CT imaging and immune stimulation (increased CD3CD8 T - and NK cell numbers, reduced levels of TIM-3 cells in both treatment groups). Coding microsatellite analysis of MMR-D-related target genes revealed increased mutational load upon vaccination (total mutation frequency within 28 genes: 28.6% vaccine groups vs. 14.9% control group, respectively). Reactive immune cells recognized autologous tumor cells, but also NK cells target YAC-1 in IFNγ ELISpot and, even more importantly, in functional kill assays. Assessment of tumor microenvironment revealed infiltration of CD8 T-cells and granulocytes, but also upregulation of immune checkpoint molecules (LAG-3, PD-L1). The present study is the first reporting results on a therapeutic cellular MMR-D vaccine. Vaccination-induced prolonged survival was achieved in a clinically-relevant mouse model for MMR-D-related diseases by long-term impairment of tumor growth and this could be attributed to re-activated immune responses.