Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration

The neuropathological hallmarks of Alzheimer's disease and other tauopathies include senile plaques and/or neurofibrillary tangles. Although mouse models have been created by overexpressing specific proteins including beta-amyloid precursor protein, presenilin and tau, no model has been generated by gene knockout. Phosphorylation of tau and other proteins on serine or threonine residues preceding proline seems to precede tangle formation and neurodegeneration in Alzheimer's disease. Notably, these phospho(Ser/Thr)-Pro motifs exist in two distinct conformations, whose conversion in some proteins is catalysed by the Pin1 prolyl isomerase. Pin1 activity can directly restore the conformation and function of phosphorylated tau or it can do so indirectly by promoting its dephosphorylation, which suggests that Pin1 is involved in neurodegeneration; however, genetic evidence is lacking. Here we show that Pin1 expression is inversely correlated with predicted neuronal vulnerability and actual neurofibrillary degeneration in Alzheimer's disease. Pin1 knockout in mice causes progressive age-dependent neuropathy characterized by motor and behavioural deficits, tau hyperphosphorylation, tau filament formation and neuronal degeneration. Thus, Pin1 is pivotal in protecting against age-dependent neurodegeneration, providing insight into the pathogenesis and treatment of Alzheimer's disease and other tauopathies.     

Experimental investigation on upstream-injection interaction with a scramjet cavity flameholder

The study has evaluated the coherent structures and the velocity field of gaseous transverse jet upstream of a scramjet flameholder in a supersonic turbulent flow. The high spatiotemporal resolution coherent structures of the jet plume/wakes and the cavity shear layer were obtained by utilizing the nanoparticle-based planar laser scattering technique. Compared to the no upstream injection case, the cavity shear layer downstream of the jet shows significant mass exchange with mainstream. The particle image veloc- imetry velocity field and the velocity profiles demonstrated that the interaction intensity of the cavity shear layer with the upstream injection is further enhanced as the injection stagnation pressure increases.     

Mechanism of brittle-ductile transition of a glass-ceramic rigid substrate

The hardness, elastic modulus, and scratch resistance of a glass-ceramic rigid substrate were measured by nanoindentation and nanoscratch, and the fracture toughness was measured by indentation using a Vickers indenter. The results show that the hardness and elastic modulus at a peak indentation depth of 200 nm are 9.04 and 94.70 GPa, respectively. These values reflect the properties of the glass-ceramic rigid substrate. The fracture toughness value of the glass-ceramic rigid substrate is 2.63 MPa·m1/2. The material removal mechanisms are seen to be directly related to normal force on the tip. The critical load and scratch depth estimated from the scratch depth profile after scratching and the friction profile are 268.60 mN and 335.10 nm, respectively. If the load and scratch depth are under the critical values, the glass-ceramic rigid substrate will undergo plastic flow rather than fracture. The formula of critical depth of cut described by Bifnao et al. is modified based on the difference of critical scratch depth     

Three-dimensional nonlinear flutter analysis of long-span suspension bridges during erection

In this work, the aerodynamic stability of the Yichang Suspension Bridge over Yangtze River during erection was determined by three-dimensional nonlinear flutter analysis, in which the nonlinearities of structural dynamic characteristics and aeroelastic forces caused by large deformation are fully considered. An interesting result obtained was that the bridge was more stable when the stiffening girders were erected in a non-symmetrical manner as opposed to the traditional symmetrical erection schedule. It was also found that the severe decrease in the aerodynamic stability was due to the nonlinear effects. Therefore, the nonlinear factors should be considered accurately in aerodynamic stability analysis of long-span suspension bridges during erection.     

Study on control strategy of CAN bus network based on event triggered mode

In order to reduce the load rate of CAN bus and improve the real-time performance of control system, CAN bus control system of a pure electric vehicle is studied. Communication messages of each node are optimized and redefined by sorting the message into three types: control message, status message and alarm message. Event triggered mode is added to the communication way of CAN bus, and the communication control strategy of the vehicle is made. It is proved that CAN bus load rate of control system is reduced after optimization, and the real-time performance of communication is improved effectively.     

Method to Identify Similarity and Dissimilarity between Systems Engineering and Neighboring Disciplines

1IntroductionSystems Engineering(SE)has been widelyused in many fields worldwide since WWII.Despite beingin use for nearly70years,there islittle consensus onthe definitionandscope of SE,and it is very difficult to answer the question“What is SE?”exactly…     

Studies on the developmental biology of sweet potato seed

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The design of a novel parallel haptic device

A novel haptic device which is characterized by large workspace, high rigidity, simple kinematics and easy construction is presented. This device is a parallel mechanism which is composed of a base plate, three sub-chains, and a mobile plate. Each sub-chain is attached to the base plate through a pin joint and to the top plate through a spherical joint. The sub-chain is derived from and kinematically equivalent to a pantograph linkage but is redesigned to solve the difficult problem of motor-fitting. The spherical joint is of the ball-in-socket type, but has much larger workspace than its regular counterpart. The kinematics is analyzed, and the inverse kinematics analysis is performed with a geometric approach. The complete workspace is readily obtained with the spherical coordinate system searching method. The optimal value of the cone angle of the spherical joint is shown to be 100°.     

Haversian bone-mimicking bioceramic scaffolds enhancing MSC-macrophage osteo-imunomodulation

The interaction between immune cells and bone forming cells plays a vital role in maintaining the homeostasis of the skeletal system, and is regulated by the three-dimensional structure of tissues. Whether the construction of biomaterials can activate or reproduce this spatial “cross-talk” between immune cells and bone forming cells in bone natural formation process is a prerequisite for successful fracture healing and bone regeneration. Herein, a bone marrow mesenchymal stem cells(MSCs)/macroph...     

Synergetic effect of multiple phases on hydrogen desorption kinetics and cycle durability in ball milled MgH2–PrF3–Al–Ni composite

A new Mg MgH₂–PrF₃–Al–Ni composite was prepared by ball milling under hydrogen atmosphere. After initial dehydrogenation and rehydrogenation, Pr₃Al₁₁, MgF₂, PrH₃ and Mg₂NiH₄ nanoparticles formed accompanying the main phase MgH₂. The hydrogen absorption-desorption properties were measured by using a Sieverts-type apparatus. The results showed that the Mg MgH₂–PrF₃–Al–Ni composi...