Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

Mechanism of generation of large(Ti,Nb,V)(C,N)-type precipitates in H13 + Nb tool steel

The characteristics and generation mechanism of（Ti,Nb,V）（C,N） precipitates larger than 2 μm in Nb-containing H13 bar steel were studied. The results show that two types of（Ti,Nb,V）（C,N） phases exist—a Ti-V-rich one and an Nb-rich one—in the form of single or complex precipitates. The sizes of the single Ti-V-rich（Ti,Nb,V）（C,N） precipitates are mostly within 5 to 10 μm, whereas the sizes of the single Nb-rich precipitates are mostly 2–5 μm. The complex precipitates are larger and contain an inner Ti-V-rich layer and an outer Nb-rich layer. The compositional distribution of（Ti,Nb,V）（C,N） is concentrated. The average composition of the single Ti-V-rich phase is（Ti_（0.511）V_（0.356）Nb_（0.133））（CxNy）, whereas that for the single Nb-rich phase is（Ti_（0.061）V_（0.263）Nb_（0.676））（C_xN_y）. The calculation results based on the Scheil–Gulliver model in the Thermo-Calc software combining with the thermal stability experiments show that the large phases precipitate during the solidification process. With the development of solidification, the Ti-V-rich phase precipitates first and becomes homogeneous during the subsequent temperature reduction and heat treatment processes. The Nb-rich phase appears later.

MULTI-SCALE AND MULTI-PHASE NANOCOMPOSITE CERAMIC TOOLS AND CUTTING PERFORMANCE

An advanced ceramic cutting tool material Al2O3/TiC/TiN （LTN） is developed by incorporation and dispersion of micro-scale TiC particle and nano-scale TiN particle in alumina matrix. With the optimal dispersing and fabricating technology, this multi-scale and multi-phase nanocomposite ceramic tool material can get both higher flexural strength and fracture toughness than that of A1203/TiC （LZ） ceramic tool material without nano-scale TiN particle, especially the fracture toughness can reach to 7.8 MPa . m^0.5. The nano-scale TiN can lead to the grain fining effect and promote the sintering process to get a higher density. The coexisting transgranular and intergranular fracture mode induced by micro-scale TiC and nano-scale TiN, and the homogeneous and densified microstructure can result in a remarkable strengthening and toughening effect. The cutting performance and wear mechanisms of the advanced multi-scale and multi-phase nanocomposite ceramic cutting tool are researched.

In-situ Fabricated TiB_2 Particle-whisker Synergistically Toughened Ti(C,N)-based Ceramic Cutting Tool Material

The mechanical properties of ceramic cutting tool materials can be modified by introducing proper content of nanoparticles or whiskers.However,the process of adding whiskers or nanoparticles has the disadvantages of high cost and health hazard as well as the agglomeration;although a new in-situ two-step sintering process can solve the above problems to some extent,yet the problems of low conversion ratio of the raw materials and the abnormal grain growth exist in this process.In this paper,an in-situ one-step synthesis technology is proposed,which means the growth of whiskers or nanoparticles and the sintering of the compact can be accomplished by one time in furnace.A kind of Ti（C,N）-based ceramic cutting tool material synergistically toughened by TiB_2 particles and whiskers is fabricated with this new process.The phase compositions,relationships between microstructure and mechanical properties as well as the toughening mechanisms are analyzed by means of X-ray diffraction（XRD）and scanning electron microscopy（SEM）.The composite which is sintered under a pressure of 32 MPa at a temperature of 1700℃in vacuum holding for 60 min can get the optimal mechanical properties.Its flexural strength,fracture toughness and Vickers hardness are 540 MPa,7.81 MPa·m（1/2）and 20.42 GPa,respectively.The composite has relatively high density,and the in-situ synthesized TiB_2 whiskers have good surface integrity,which is beneficial for the improvement of the fracture toughness.It is concluded that the main toughening mechanisms of the present composite are whiskers pulling-out and crack deflection induced by whiskers,crack bridging by whiskers/particles and multi-scale particles synergistically toughening.This study proposes an in-situ one-step synthesis technology which can be well used for fabricating particles and whiskers synergistically toughened ceramic tool materials.

Comparative study on local and global mechanical properties of bobbin tool and conventional friction stir welded 7085-T7452 aluminum thick plate

7085-T7452 plates with a thickness of 12 mm were welded by conventional single side and bobbin tool friction stir welding （SS-FSW and BB-FSW, respectively） at different welding parameters. The temperature distribution, microstructure evolution and mechanical properties of joints along the thickness direction were investigated, and digital image correlation （DIC） was utilized to evaluate quantitatively the deformation of different zones during tensile tests. The results indicated that heat-affected zone （HAZ）, the local softening region, was responsible for the early plastic deformation and also the fracture location for SS-FSW samples, while a rapid fracture was observed in weld nugget zone （WNZ） before yield behavior for all BB-FSW specimens. The ultimate tensile strength （UTS） of SS-FSW joints presented the highest value of 410 MPa, 82% of the base material, at a rotational speed of 300 rpm and welding speed of 60 mm/min, much higher than that of BB-FSW joints, with a joint efficiency of only 47%. This should be attributed to the Lazy S defect produced by a larger extent of heat input during the BB-FSW process, The whole joint exhibited a much higher elongation than the slices. Scanning electron microscopic （SEM） analysis of the fracture morphologies showed that joints failed through ductile fracture for SS-FSW and brittle fracture for BB-FSW.

Fatigue-creep interaction based on continuum damage mechanics for AISI H13 hot work tool steel at elevated temperatures

AISI H13 （4Cr5MoSiV1） is one of the commonly used materials for extrusion tool, and it suffers from fatigue-creep damage during the hot extrusion process. Stress-controlled fatigue and creep-fatigue interaction tests were carried out at 500℃ to investigate its damage evolution. The accumulated plastic strain was selected to define the damage variable due to its clear physical meaning. A new fatigue-creep interaction damage model was proposed on the basis of continuum damage mechanics. A new equivalent impulse density for fatigue-creep tests was proposed to incorporate the holding time effect by transforming creep impulse density into fatigue impulse density. The experimental results indicated that the damage model is able to describe the damage evolution under these working conditions.