Tau-dependent HDAC1 nuclear reduction is associated with altered VGluT1 expression

During AD pathology, Tau protein levels progressively increase from early pathological stages. Tau altered expression causes an unbalance of Tau subcellular localization in the cytosol and in the nuclear compartment leading to synaptic dysfunction, neuronal cell death and neurodegeneration as a consequence. Due to the relevant role of epigenetic remodellers in synaptic activity in physiology and in neurodegeneration, in particular of TRIM28 and HDAC1, we investigated the relationship between Tau and these epigenetic factors. By molecular, imaging and biochemical approaches, here we demonstrate that Tau altered expression in the neuronal cell line SH-SY5y does not alter TRIM28 and HDAC1 expression but it induces a subcellular reduction of HDAC1 in the nuclear compartment. Remarkably, HDAC1 reduced activity modulates the expression of synaptic genes in a way comparable to that observed by Tau increased levels. These results support a competitive relationship between Tau levels and HDAC1 subcellular localization and nuclear activity, indicating a possible mechanism mediating the alternative role of Tau in the pathological alteration of synaptic genes expression

Effect of alloying on the microstructure, phase stability, hardness and partitioning behavior of a new dual-superlattice nickel-based superalloy

A novel y-y'-y" dual-superlattice superalloy, with promising mechanical properties up to elevated temperatures was recently reported. The present work employs state of the art chemical and spatial characterization techniques to study the effect systematic additions of Mo, W and Fe and variations in Nb and Al contents have on the phase fraction, thermal stability, elemental partitioning and mechanical properties. Alloys were produced through arc melting followed by heat treatment. Multi-scale characterization techniques and hardness testing were employed to characterize their microstructure, thermal stability and mechanical properties. Alterations in such properties or in elemental partitioning behaviour were then explained through thermodynamic modelling. A modest addition of 1.8 at.% Mo had a strong effect on the microstructure and thermal stability: it minimized microstructural coarsening during heat treatments while not significantly decreasing the y' solvus temperature. A reduction of Nb by 0.6 at.%, strongly reduced the y" volume fraction, without affecting the y' volume fraction. The reduced precipitate fraction led to a significant reduction in alloy hardness. Fe, added to achieve better processability and reduced material cost, decreased the y' solvus temperature and caused rapid microstructural coarsening during heat treatments, without affecting alloy hardness. A reduction of Al by 0.4 at.%, reduced the y' volume fraction and the y' solvus temperature, also without affecting alloy hardness. The addition of 0.9 at.% W decreased the y' solvus temperature but increased both precipitate volume fractions. These data will be invaluable to optimize current alloy design and to inform future alloy design efforts

On the Effect of Nb on the Microstructure and Properties of Next Generation Polycrystalline Powder Metallurgy Ni-Based Superalloys

Abstract The effect of Nb on the properties and microstructure of two novel powder metallurgy (P/M) Ni-based superalloys was evaluated, and the results critically compared with the Rolls-Royce alloy RR1000. The Nb-containing alloy was found to exhibit improved tensile and creep properties as well as superior oxidation resistance compared with both RR1000 and the Nb-free variant tested. The beneficial effect of Nb on the tensile and creep properties was due to the microstructures obtained following the post-solution heat treatments, which led to a higher γ′ volume fraction and a finer tertiary γ′ distribution. In addition, an increase in the anti-phase-boundary energy of the γ′ phase is also expected with the addition of Nb, further contributing to the strength of the material. However, these modifications in the γ′ distribution detrimentally affect the dwell fatigue crack-growth behavior of the material, although this behavior can be improved through modified heat treatments. The oxidation resistance of the Nb-containing alloy was also enhanced as Nb is believed to accelerate the formation of a defect-free Cr2O3 scale. Overall, both developmental alloys, with and without the addition of Nb, were found to exhibit superior properties than RR1000.This work was supported by the Rolls-Royce/EPSRC Strategic Partnership under EP/H022309/1, EP/H500375/1 and EP/ M005607/1

Mechanical Properties and Microstructural Characterization of Aged Nickel-based Alloy 625 Weld Metal

The aim of this work was to evaluate the different phases formed during solidification and after thermal aging of the as-welded 625 nickel-based alloy, as well as the influence of microstructural changes on the mechanical properties. The experiments addressed aging temperatures of 650 and 950 A degrees C for 10, 100, and 200 hours. The samples were analyzed by electron microscopy, microanalysis, and X-ray diffraction in order to identify the secondary phases. Mechanical tests such as hardness, microhardness, and Charpy-V impact test were performed. Nondestructive ultrasonic inspection was also conducted to correlate the acquired signals with mechanical and microstructural properties. The results show that the alloy under study experienced microstructural changes when aged at 650 A degrees C. The aging was responsible by the dissolution of the Laves phase formed during the solidification and the appearance of gamma aEuro(3) phase within interdendritic region and fine carbides along the solidification grain boundaries. However, when it was aged at 950 A degrees C, the Laves phase was continuously dissolved and the excess Nb caused the precipitation of the delta-phase (Ni3Nb), which was intensified at 10 hours of aging, with subsequent dissolution for longer periods such as 200 hours. Even when subjected to significant microstructural changes, the mechanical properties, especially toughness, were not sensitive to the dissolution and/or precipitation of the secondary phases

Results of Aerosol Code Comparisons With Releases From ACE MCCI Tests

Results of aerosol release calculations by six groups from six countries are compared with the releases from ACE MCCI Test L6. The codes used for these calculations included: SOLGASMIX-PV, SOLGASMIX Reactor 1986, CORCON.UW, VANESA 1.01, and CORCON mod2.04/VANESA 1.01. Calculations were performed with the standard VANESA 1.01 code and with modifications to the VANESA code such as the inclusion of various zirconium-silica chemical reactions. Comparisons of results from these calculations were made with Test L6 release fractions for U, Zr, Si, the fission-product elements Te, Ba, Sr, Ce, La, Mo and control materials Ag, In, and Ru. Reasonable agreement was obtained between calculations and Test L6 results for the volatile elements Ag, In and Te. Calculated releases of the low volatility fission products ranged from within an order of magnitude to five orders of magnitude of Test L6 values. Releases were over and underestimated by calculations. Poorest agreements were obtained for Mo and Si

Results of aerosol code comparisons with releases from ACE MCCI tests

Results of aerosol release calculations by six groups from six countries are compared with the releases from ACE MCCI Test L6. The codes used for these calculations included: SOLGASMIX-PV, SOLGASMIX Reactor 1986, CORCON.UW, VANESA 1.01, and CORCON mod2.04/VANESA 1.01. Calculations were performed with the standard VANESA 1.01 code and with modifications to the VANESA code such as the inclusion of various zirconium-silica chemical reactions. Comparisons of results from these calculations were made with Test L6 release fractions for U, Zr, Si, the fission-product elements Te, Ba, Sr, Ce, La, Mo and control materials Ag, In, and Ru. Reasonable agreement was obtained between calculations and Test L6 results for the volatile elements Ag, In and Te. Calculated releases of the low volatility fission products ranged from within an order of magnitude to five orders of magnitude of Test L6 values. Releases were over and underestimated by calculations. Poorest agreements were obtained for Mo and Si

Research data supporting "Phase evolution in an Al0.5CrFeCoNiCu High Entropy Alloy"

These files provide the raw data for the paper by Jones et al. entitled “Phase evolution in an Al0.5CrFeCoNiCu High Entropy Alloy” (DOI: 10.1016/j.intermet.2015.12.001) Figure1.jpg - original image file for Figure 1as presented in the paper Figure2.zip - folder containing Figure 2 as presented in the paper and larger versions of each sub figure Figure3.zip - folder containing Figure 3 as presented in the paper along with the original EDX elemental distribution maps and corresponding secondary electron image Figure4.jpg - original image file for Figure 4 as presented in the paper Figure5.jpg - original image file for Figure 5 as presented in the paper Figure6.zip - folder containing Figure 6 as presented in the paper plus four comma separated variable (.csv) files with the raw X-ray diffraction data expressed as angle and intensity for the homogenised material and or material aged at 700, 800 and 900˚C. Figure7.zip - folder containing Figure 7 as presented in the paper and the underlying raw differential scanning calorimeter data in comma separated variable (.csv) format Figure8.jpg - original image file for Figure 5 as presented in the paperThis work is supported by the EPSRC [grant numbers EP/M005607/1 and EP/H022309/1]

Research data supporting "Phase evolution in an Al0.5CrFeCoNiCu High Entropy Alloy"

These files provide the raw data for the paper by Jones et al. entitled “Phase evolution in an Al0.5CrFeCoNiCu High Entropy Alloy” (DOI: 10.1016/j.intermet.2015.12.001) Figure1.jpg - original image file for Figure 1as presented in the paper Figure2.zip - folder containing Figure 2 as presented in the paper and larger versions of each sub figure Figure3.zip - folder containing Figure 3 as presented in the paper along with the original EDX elemental distribution maps and corresponding secondary electron image Figure4.jpg - original image file for Figure 4 as presented in the paper Figure5.jpg - original image file for Figure 5 as presented in the paper Figure6.zip - folder containing Figure 6 as presented in the paper plus four comma separated variable (.csv) files with the raw X-ray diffraction data expressed as angle and intensity for the homogenised material and or material aged at 700, 800 and 900˚C. Figure7.zip - folder containing Figure 7 as presented in the paper and the underlying raw differential scanning calorimeter data in comma separated variable (.csv) format Figure8.jpg - original image file for Figure 5 as presented in the paperThis work is supported by the EPSRC [grant numbers EP/M005607/1 and EP/H022309/1]