κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

A Metal-Free,Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells

Superoxide dismutase 1 (SOD1) is a metalloenzyme with high structural stability, but a lack of Cu and Zn ions decreases its stability and enhances the likelihood of misfolding, which is a pathological hallmark of amyotrophic lateral sclerosis (ALS). A growing body of evidence has demonstrated that misfolded SOD1 has prion-like properties such as transmissibility between cells and intracellular propagation of misfolding of natively folded SOD1. Recently, we found that SOD1 is misfolded in the cerebrospinal fluid of sporadic ALS patients, providing a route by which misfolded SOD1 spreads via the extracellular environment of the central nervous system. Unlike intracellular misfolded SOD1, it is unknown which extracellular misfolded species is most relevant to prion-like properties. Here, we determined a conformational feature of extracellular misfolded SOD1 that is linked to prion-like properties. Using culture media from motor neuron-like cells, NSC-34, extracellular misfolded wild-type, and four ALS-causing SOD1 mutants were characterized as a metal-free, disulfide oxidized form of SOD1 (apo-SOD1^S-S). Extracellular misfolded apo-SOD1^S-S exhibited cell-to-cell transmission from the culture medium to recipient cells as well as intracellular propagation of SOD1 misfolding in recipient cells. Furthermore, culture medium containing misfolded apo-SOD1^S-S exerted cytotoxicity to motor neuron-like cells, which was blocked by removal of misfolded apo-SOD1^S-S from the medium. We conclude that misfolded apo-SOD1^S-S is a primary extracellular species that is linked to prion-like properties.     

Progressive fracture processes around tunnel triggered by blast disturbances under biaxial compression with different lateral pressure coefficients

To investigate the progressive fracture processes around a tunnel triggered by static stress and dynamic disturbance, experiments and numerical simulations were performed. The results show that the spatial distributions of acoustic emission (AE) events become very different as lateral pressure coefficients change. The combined effect of static stress and dynamic disturbance causes the damage around the tunnel, and initial stress conditions control the damage morphology. The blast disturbance cannot fundamentally change the damaged area but will deepen the extent of damage and accelerate the failure speed. The more significant the difference between the vertical and horizontal stresses is, the higher the impact on the tunnel by the dynamic disturbance is. The AE activity recovers to a relatively stable state within a short time after the blast and conforms to power-law characteristics.     

热轧层流辊道内冷辊回水结构的优化改进

针对某热轧厂1 580 mm生产线精轧出口层流辊道内冷辊频繁发生操作侧轴承失效问题,对其原因进行了分析,同时核算了内冷辊受热轴向膨胀后操作侧轴承侧向间隙。结果表明:操作侧轴承侧向间隙满足使用要求,轴承失效和辊筒受热膨胀无关;操作侧轴承失效的直接原因是轴套制造精度低导致骨架油封失效、内冷辊高速旋转“吸水”效应,使冷却回水进入轴承座内部,进一步造成润滑不良进而造成轴承失效。为此,对内冷辊回水结构进行了优化改进:在操作侧轴承座端盖和水套之间增加法兰,延长轴套及安装轴套的轴头,在轴头和轴套之间增加O型密封圈。改进后两年的使用周期内没有发生过轴承失效故障。     

Optimum lateral extent of soil domain for dynamic SSI analysis of RC framed buildings on pile foundations

This article describes a novel approach for deciding optimal horizontal extent of soil domain to be used for finite element based numerical dynamic soil structure interaction (SSI) studies. SSI model for a 12 storied building frame, supported on pile foundation-soil system, is developed in the finite element based software framework, OpenSEES. Three different structure-foundation configurations are analyzed under different ground motion characteristics. Lateral extent of soil domain, along with the soil properties, were varied exhaustively for a particular structural configuration. Based on the reduction in the variation of acceleration response at different locations in the SSI system (quantified by normalized root mean square error, NRMSE), the optimum lateral extent of the soil domain is prescribed for various structural widths, soil types and peak ground acceleration levels of ground motion. Compared to the past studies, error estimation analysis shows that the relationships prescribed in the present study are credible and more inclusive of the various factors that influence SSI. These relationships can be readily applied for deciding upon the lateral extent of the soil domain for conducting precise SSI analysis with reduced computational time.     

波前传感器电铸镍层应力实时检测精度评估

目的 搭建电铸应力实时检测平台，评估其测量精度，并探明电化学沉积过程中镍层平均内应力的变化规律。方法 采用横向剪切波前传感器搭建电铸应力实时检测平台，通过测量在铸层应力作用下电铸基底弯曲的曲率半径，利用Stoney公式计算铸层平均应力。采用参考球面反射镜评估横向剪切波前传感器曲率半径的测量精度，并在0.5 A/dm2电流密度下进行电铸应力实时检测实验，对铸层平均应力测量极限进行评估，同时对检测误差进行分析。结果 横向波前传感器曲率半径测量精度为99.22%，在0.5 A/dm2电流密度下，所搭建的铸层应力实时检测平台可测量的最小厚度为5.1 μm，由曲率测量波动带来的应力检测误差为1.3 MPa。实验测得铸层平均应力随铸层厚度的增加而变大，当铸层厚度达到30 μm左右，铸层平均应力趋于稳定，应力大小为79.7 MPa。同时发现，当铸层厚度小于30 μm时，沿电铸基底长度方向的铸层平均应力明显大于宽度方向铸层平均应力，随铸层厚度的增加，两个方向的应力大小趋于等值。结论 采用横向剪切波前传感器搭建的电铸应力检测平台，能有效对铸层应力进行高精度的实时测量，为精密电铸过程中应力变化规律的研究提供了检测技术基础。