Galanin – 25 years with a multitalented neuropeptide

Galanin, a neuropeptide widely expressed in the central and peripheral nervous systems and in the endocrine system, has been shown to regulate numerous physiological and pathological processes through interactions with three G-protein-coupled receptors, GalR1 through GalR3. Over the past decade, some of the receptor subtype-specific effects have been elucidated through pharmacological studies using subtype selective ligands, as well as through molecular approaches involving knockout animals. In the present review, we summarize the current data which constitute the basis of targeting GalR1, GalR2 and GalR3 for the treatment of various human diseases and pathological conditions, including seizure, Alzheimer's disease, mood disorders, anxiety, alcohol intake in addiction, metabolic diseases, pain and solid tumors.     

斜拉桥索梁锚固结构疲劳试验模型设计优化

为了避免出现斜拉桥索梁锚固结构疲劳试验中辅助部分首先断裂的问题,在以往试验模型设计的基础上,考虑影响疲劳寿命的不同因素,建立了以模型的静力强度、位移、疲劳和断裂性能为模糊约束条件,以模型质量、疲劳和断裂寿命为多个目标的结构多目标优化设计模型.结合苏州南通长江公路大桥钢锚箱式索梁锚固结构足尺疲劳试验,验证了锚箱式索梁锚固结构设计的正确性,经过400万次加载而未破坏,且减少了模型用钢量.模型设计中提出的控制热点应力等措施切实可行.     

Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

In the present study we demonstrated that neurotoxin MPP⁺-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP⁺-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G₀/G₁ cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP⁺ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP⁺ and cell-cycle re-entry through retinoblastoma protein phosphorylation.     

Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)

The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.     

Characterization and Preparation of Bimetallic Nanoparticles

1 Results Bimetallic particles in the nanometer size range are of substantial interest due to their vast applications in catalysis[1].The synthesis of bimetallic nanoparticles with definite size with a well-control over their nanostructure remains a challenging problem.Thus there exists a great demand for both synthesis and atomic level characterization of nanostructure of bimetallic nanoparticles (NPs).With the recent advent of high-intensity tunable sources of X-rays,now available at synchrotron radia...     

Gerstewitz非线性标量化函数的性质及其在向量优化中的应用

【目的】对Gerstewitz非线性标量化函数的性质作进一步研究与应用。【方法】利用代数内部和向量闭包研究Gerstewitz非线性标量化函数的一些性质。【结果】给出了Gerstewitz非线性标量化函数的一些性质,进而利用这些性质建立了集值向量优化问题有效点和弱有效点的非线性标量化结果。【结论】将拓扑内部推广到代数内部情形,推广了Gerstewitz非线性标量化函数的一些性质与应用。
     

Ground demonstration system based on in-orbit assembly oriented manipulator flexible force control

To eliminate the load weight limit of carrier rockets and reduce the burden on support struc-tures,in-orbit assembly is a key technology to make design of scattering a large diameter telescope into submirror modules, which requires smooth operation of assembly robots, and flexible force con-trol technology is necessary.A ground demonstration system is presented for in-orbit assembly focu-sing on flexible force control.A six-dimensional force/torque sensor and its data acquisition system are used to compensate for gravity.For translation and rotation, an algorithm for flexible control is proposed.A ground transportation demonstration verifies accuracy and smoothness of flexible force control, and the transportation and assembly task is completed automatically.The proposed system is suitable for the development of in-orbit assembly robots.     

可持续城市设计的内涵、原则与维度

 可持续发展是世界范围内各国城市发展建设的基本共识,以可持续发展理论内涵为基础,通过分析可持续发展理论的研究进程和城市建设面临的困境,融合生态、绿色概念,总结出可持续城市设计的基本概念与原则,从生态环境、历史文化、空间形态、管控治理4个维度,提出具有实效性的可持续城市设计策略,指出城市建设未来的发展方向和城市研究的重难点问题,为中国城市的健康有序发展提供有益借鉴。     

Mechanical and corrosion properties of low-carbon steel prepared by friction stir processing

Low-carbon steel plates were successfully subjected to normal friction stir processing(NFSP) in air and submerged friction stir processing(SFSP) under water, and the microstructure, mechanical properties, and corrosion behavior of the NFSP and SFSP samples were investigated. Phase transformation and dynamic recrystallization resulted in fine-grained ferrite and martensite in the processed zone. The SFSP samples had smaller ferrites(5.1 μm), finer martensite laths(557 nm), and more uniform distribution of martensite compared to the NFSP samples. Compared to the base material(BM), the microhardness of the NFSP and SFSP samples increased by 19.8% and 27.1%, respectively because of the combined strengthening effects of grain refinement, phase transformation, and dislocation. The ultimate tensile strengths(UTSs) of the NFSP and SFSP samples increased by 27.1% and 38.7%, respectively. Grain refinement and martensite transformation also improved the electrochemical corrosion properties of the low-carbon steel. Overall, the SFSP samples had better mechanical properties and electrochemical corrosion resistance than the NFSP samples.     

Mechanical behavior of a near α titanium alloy under dynamic compression: Characterization and modeling

Dynamic compression tests under strain rates from 870 s^?1 to 2100 s^?1 were conducted for a near α Ti–8Al–1Mo–1V titanium alloy with equiaxed microstructure. Compression behavior, adiabatic shearing and band microstructure were investigated via characterization and calculation. The results demonstrate that all dynamic constitutive curves exhibited obvious stress fluctuation phenomenon with double increase-decrease changing stages at the primary stage of compression. The dislocation multiplication theory can be used to explain this phenomenon. After the stress fluctuation period, work hardening coexisted with the thermal softening, resulting in the slow hardening tendency in constitutive curves. J-C model was utilized to quantify the dynamic constitutive curves. The deviations between the predicted and experimental curves under high strain rates may be attributed to the over-consideration of thermal softening effect in J-C model. Adiabatic shearing band (ASB) began to form under the strain rate of 2100 s^?1. A total shearing strain of 8.1 within ASB achieved in 8.9 μs, corresponding to a local strain rate of about 9.1 × 10⁵ s^?1 and is over 430 times of the macro strain rate. Post annealing was conducted on ASB before EBSD characterization. Due to the static recrystallization during annealing, the α phase within ASB generally presented as ultra-fine grains less than 1 μm in diameter.