Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice’s survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.     

A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics

Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative disorders include Alzheimer’s and Parkinson’s disease. Although there are several medicines currently approved for managing neurodegenerative disorders, a large majority of them only help with associated symptoms. This lack of pathogenesis-targeting therapies is primarily due to the restrictive effects of the blood–brain barrier (BBB), which keeps close to 99% of all “foreign substances” out of the brain. Since their discovery, nanoparticles have been successfully used for targeted delivery into many organs, including the brain. This review briefly describes the pathophysiology of Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis, and their current management approaches. We then highlight the major challenges of brain-drug delivery, followed by the role of nanotherapeutics for the diagnosis and treatment of various neurological disorders.     

旋转导弹横向喷流/超声速来流干扰数值模拟

以旋转坐标系下Navier- Stokes方程为控制方程,用有限体积法、对称TVD格式和重叠网格技术对带有单股和两股横向喷流旋转导弹的喷流干扰流场进行了数值模拟,计算了喷流与来流、喷流与喷流之间的干扰情况。结果表明：两股喷流增强了与来流之间的干扰,喷流与喷流间也存在干扰;两种干扰影响使力放大因子较单股喷流高;旋转使喷口前的分离区形状改变;在背风面喷流时,旋转使喷流羽流发生周向偏转,影响喷流干扰力放大因子。     

迫弹横向脉冲控制飞行稳定性

为了研究迫弹利用脉冲发动机进行弹道修正而引起的飞行稳定性问题,分析了横向脉冲控制力及控制力矩,建立了有控弹道模型,在一定的假设条件下推导出脉冲作用段迫弹的攻角方程,讨论了脉冲作用段迫弹的飞行稳定性,给出了脉冲冲量大小及距质心作用距离的约束条件.研究表明,正常情况下,横向脉冲控制对迫弹的动稳定条件、追随稳定条件及共振不稳定条件没有影响,但需控制脉冲冲量大小和距质心作用距离,使得扰动引起的攻角增量幅值不超过允许的极限值,保证迫弹在脉冲作用后仍能稳定飞行.     

用脉宽式直接弹道侧向力的反导拦截弹复合控制方法

为提高反导拦截弹的机动性和敏捷性,对反导拦截弹采用脉宽式(PW)直接弹道侧向力 气动力复合控制方式的实现原理进行了设计,并提出了多模态控制策略.通过与纯气动控制方式的对比分析,验证了PW直接弹道侧向力 气动力复合控制方式及多模态控制方法的有效性.     

Role of Dorsomedial Hypothalamus GABAergic Neurons in Sleep–Wake States in Response to Changes in Ambient Temperature in Mice

Good sleep quality is essential for maintaining the body’s attention during wakefulness, which is easily affected by external factors such as an ambient temperature. However, the mechanism by which an ambient temperature influences sleep–wake behaviors remains unclear. The dorsomedial hypothalamus (DMH) has been reported to be involved in thermoregulation. It also receives projection from the preoptic area, which is an important region for sleep and energy homeostasis and the suprachiasmatic nucleus—a main control area of the clock rhythm. Therefore, we hypothesized that the DMH plays an important role in the regulation of sleep related to ambient temperatures. In this study, we found that cold exposure (24/20/16/12 °C) increased wakefulness and decreased non–rapid eye movement (NREM) sleep, while warm exposure (32/36/40/44 °C) increased NREM sleep and decreased wakefulness compared to 28 °C conditions in wild-type mice. Then, using non-specific and specific apoptosis, we found that lesions of whole DMH neurons and DMH γ–aminobutyric acid (GABA)-ergic neurons induced by caspase-3 virus aggravated the fluctuation of core body temperature after warm exposure and attenuated the change in sleep–wake behaviors during cold and warm exposure. However, chemogenetic activation or inhibition of DMH GABAergic neurons did not affect the sleep–wake cycle. Collectively, our findings reveal an essential role of DMH GABAergic neurons in the regulation of sleep–wake behaviors elicited by a change in ambient temperature.     

中厚煤层切顶卸压沿空留巷巷旁支护技术研究

根据切顶卸压沿空留巷巷旁支护技术特点,研究分析了工字钢(单体支柱)、双节U型钢和钢丝绳3种巷旁支护技术。深部中厚煤层留巷时,上述3种巷旁支护技术中工字钢偏向刚性,易被压弯;钢丝绳偏向柔性,留巷侧鼓包明显,变形量大;双节U型钢刚柔并济,通过纵向让压和侧向抗压技术优化,可达到服务年限长、留巷效果好的目的。实践表明:切顶卸压沿空留巷施工难度大,时间跨度长;选用双节U型钢巷旁支护技术是合理可行的,能够为深部开采中瓦斯、水害治理赢得时间。留巷侧巷帮变形量在留巷初期呈现显著变化状态,在支护器材回撤阶段呈现慢速变化状态,其余时段则呈现近似稳定状态(蠕变)。     

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。     

不同纵横均匀外压作用下环肋圆柱壳稳定性分析

环肋圆柱壳结构因其具有的诸多优点,而被广泛应用于工程实际,但随着钢材屈服极限的不断提高,其稳定性问题越来越成为保证结构强度的一个重要指标,因此有必要对其结构的稳定性进行详细的分析.在对受各向均匀外压和单向均匀外压作用下环肋圆柱壳稳定特性的了解、认识和重新分析的基础上,研究了不同纵横均匀外压作用下环肋圆柱壳的稳定特性,得出了不同纵横均匀外压作用下环肋圆柱壳的稳定特性的规律,并在理论分析的基础上绘制了不同纵横均匀外压作用下的环肋圆柱壳随几何参数变化的稳定性曲线,由稳定性曲线给出了能使材料充分得到利用的环肋圆柱壳几何参数的范围.所得到的一些结论不仅能进一步完善环肋圆柱壳的稳定性理论,而且对实际工程设计及计算具有指导意义.     

计及各种载荷时的外压元件设计——新版(2007)ASME Ⅷ-2介绍

对2007版ASMEⅧ-2提出的在各种载荷作用时的外压元件设计进行简要分析并介绍。