Protein tau-3R/4R isoform ratio and phosphorylation regulates binding to microtubules and, when disturbed by aging or mutations, results in diverse tauopathies and in neurodegeneration. The underlying mechanisms were studied here in three transgenic mouse strains with identical genetic background, all expressing the tau-4R/2N isoform driven specifically in neurons by the thy1 gene promoter. Two strains, expressing human tau-4R/2N or mutant tau-4R/2N-P301L at similar, moderate levels, developed very different phenotypes. Tau-4R/2N mice became motor-impaired already around age 6-8 weeks, accompanied by axonopathy (dilatations, spheroids), but no tau aggregates, and surviving normally. In contrast, tau-P301L mice developed neurofibrillary tangles from age 6 months, without axonal dilatations and, despite only minor motor problems, all succumbing before the age of 13 months. The third strain, obtained by tau knock-out/knock-in (tau-KOKI), expressed normal levels of wild-type human tau-4R/2N replacing all mouse tau isoforms. Tau-KOKI mice survived normally with minor motor problems late in life and without any obvious pathology. Biochemically, a fraction of neuronal tau in aging tau-P301L mice was hyperphosphorylated concomitant with conformational changes and aggregation, but overall, tau-4R/2N was actually more phosphorylated than tau-P301L. Significantly, tau with changed conformation and with hyperphosphorylation colocalized in the same neurons in aging tau-P301L mice. Taken together, we conclude that excessive binding of tau-4R/2N as opposed to reduced binding of tau-P301L to microtubules is responsible for the development of axonopathy and tauopathy, respectively, in tau-4R/2N and tau-P301L mice and that the conformational change of tau-P301L is a major determinant in triggering the tauopathy.

If graphene is ever going to live up to the promises of future nanoelectronic devices, an easy and cheap route for mass production is an essential requirement. A way to extend the capabilities of plasma-enhanced chemical vapour deposition to the synthesis of freestanding few-layer graphene is presented. Micrometre-wide flakes consisting of four to six atomic layers of stacked graphene sheets have been synthesized by controlled recombination of carbon radicals in a microwave plasma. A simple and highly reproducible technique is essential, since the resulting flakes can be synthesized without the need for a catalyst on the surface of any substrate that withstands elevated temperatures up to 700• C. A thorough structural analysis of the flakes is performed with electron microscopy, x-ray diffraction, Raman spectroscopy and scanning tunnelling microscopy. The resulting graphene flakes are aligned vertically to the substrate surface and grow according to a three-step process, as revealed by the combined analysis of electron microscopy and x-ray photoelectron spectroscopy.

We describe a straightforward method for obtaining a precise value for the fractal dimension (selfaffine scaling exponent) of a surface, via scanning tunneling microscopy. It is applied to investigate ionbeam erosion of an iron film surface, providing strong support for the applicability of scaling theory to submicron erosion processes. A self-affine surface with scaling exponent H =0.53 ±0.02 is observed to develop.

Determination of the surface roughness by AFM is crucial to the study of particle fouling in nanofiltration. It is, however, very difficult to compare the different roughness values reported in the literature because of a lack in uniformity in the methods applied to determine surface roughness. AFM is used in both noncontact mode and tapping mode; moreover, the size of the scan area is highly variable. This study compares, for six different nanofiltration membranes (UTC-20, N30F, Desal 51HL, Desal 5DL, NTR7450, NF-PES-10), noncontact mode AFM with tapping mode AFM for several sizes of the scan area. Although the absolute roughness values are different for noncontact AFM and tapping mode AFM, no difference is found between the two modes of AFM in ranking the nanofiltration membranes with respect to their surface roughness. NTR 7450 and NF-PES-10 are the smoothest membranes, while the roughest surface can be found with Desal 51HL and Desal 5DL. UTC-20 and N30F are characterized by an intermediate roughness value. An increase in roughness with increasing scan area is observed for both AFM modes. Larger differences between the roughnesses of the membranes are obtained with tapping mode AFM because of the tapping of the tip on the surface. Phase imaging is an extension of tapping mode AFM, measuring the phase shift between the cantilever oscillation and the oscillation of the piezo driver. This phase shift reflects the interaction between the cantilever and the membrane surface. A comparison with contact angle measurements proves that a small phase shift corresponds to a large contact angle, representing a hydrophobic membrane surface.