The Neurovascular Unit Dysfunction in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.     

Ambient and high-temperature thermal conductivity of thermal sprayed coatings

Aside from its importance as a design parameter for thermal barrier coatings, measuring thermal conductivity of thermal sprayed coatings itself provides a unique method to critically characterize the nature, quantity, and anisotropy of the defect morphologies in these splat-based coatings. In this paper, the authors present a systematic assessment of thermal conductivity of wide range using the flash diffusivity technique. For the case of plasma sprayed yttria-stabilized zirconia (YSZ), coatings obtained from wide-ranging initial powder morphologies as well as those fabricated under different particle states were characterized. Both in-plane and through-thickness properties were obtained. Other material systems that were considered include: metallic alloys and semiconductors of interests. Issues such as reproducibility and reliability in measurements were also considered and assessed. Finally, work in collaboration with the Oak Ridge National Laboratory (ORNL) for alternate approaches to characterization of thermal conductivity as well as high-temperature measurements was performed. This article was originally published inBuilding on 100 Years of Success, Proceedings of the 2006 International Thermal Spray Conference (Seattle, WA), May 15–18, 2006, B.R. Marple, M.M. Hyland, Y.-Ch. Lau, R.S. Lima, and J. Voyer, Ed., ASM International, Materials Park, OH, 2006.     

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.     

Electronic Theory of Thermodynamic Adhesion inMetal/Ceramic Systems

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熔融织构YBCO块样品的磁特性研究

对MTG区熔生长法,慢冷法,粉末熔融生长法这3种方法制备的熔融织构YBCO块样品进行了交流磁化率和磁阻的测量。根据实验结果计算了样品的钉扎势,并且发现3种方法制备的样品在150 mT外磁场下均显示出基本消除弱连接的特性;粉末融熔生长法所制样品中有较纯净123相和较好织构,质量最好。     

用WKB方法讨论透射系数和反射系数

本文用WKB近似方法讨论了势垒贯穿问题系数T和其透射反射系数R之和恒等为1,即满足恒等式T R=1,并进一步得出这一结论不仅适用于一般势垒贯穿而且在方势垒贯穿中也成立,最后讨论了势垒贯穿的几种极限情况,例如,h→0(即经典情况),势垒高度v→∞、v→0,势垒宽度a→∞、a→0,等几种特殊情况下的T及R的取值问题。     

Local‐scale Benefits of River Connectivity Restoration Planning Beyond Jurisdictional Boundaries

Conservation planning aims to optimize outcomes for select species or ecosystems by directing resources toward high‐return sites. The possibility that local benefits might be increased by directing resources beyond the focal area is rarely considered. We present a case study of restoring river connectivity for migratory fish of the Great Lakes Basin by removing dams and road crossings within municipal jurisdictions versus their broader watersheds. We found that greater river connectivity could often be achieved by considering both intra‐jurisdictional and extra‐jurisdictional barriers. Focusing on jurisdictional barriers alone generally forfeited <20% (median = 0%) of habitat gains for those who value solely habitat gains within the jurisdiction, but >75% (median = 100%) for planners who value larger‐scale habitat gains. Similarly, cost savings tended to be between ?50% and +50%, but in some cases were very negative. Our study underscores the local‐scale benefits of broadening restoration investments, especially for decision makers of the Great Lakes Basin and contributes to a discussion of appropriate and efficient scales of conservation planning. Copyright © 2017 John Wiley & Sons, Ltd.     

Free energy barrier for compact chains escaping from a small sphere

In this paper, the process of compact polymer chains escaping from a small sphere to a large one in the view of thermodynamics is investigated in detail based on the pruned-enriched-Rosenbluth method (PERM), which is quite efficient for the three-dimensional polymers on the simple-cubic lattice. In our simulation, three representative states of a polymer chain during the escaping process are studied, and some statistical properties of the chain size and the chain shape, such as mean-square radius of gyration per bond 〈S²〉/N and the shape factor 〈δ^∗〉 are investigated. Our aim is to illuminate how the size and shape of the compact chains change during the escaping process. The changes of 〈S²〉/N and 〈δ^∗〉 are not monotone and it is due to the fact that the chain should stretch itself in the escaping process. In the meantime, some thermodynamic properties are also calculated here. The hole is designed to be small enough to allow only one monomer at a time and it thus reduces the number of allowed chain conformations and breaks contacts between monomers at the beginning of the process. Additionally, we discuss the free energy barrier per bond H₂ − H₁ = ΔH of a compact chain, and here H₂ is the maximum free energy per bond during the process and H₁ is the minimum one when the compact chain is within the small sphere. Averaging free energy barrier over chain length N is convenient for the comparison with different chain lengths. ΔH as a function of chain length N and radius r₁ of the small sphere is also studied and our result shows that ΔH for longer chains is lower means that it is relatively easier for each bond in longer chains to surmount the free energy barrier to escape. Some discussions about the self-avoiding walk (SAW) and swollen chains are also made for the comparison, and our results also show that the restriction of the small sphere on the SAW and the swollen chains is more effective because of their relatively looser intrinsic structure.     

基于马尔可夫链的自适应性神经网络训练算法

提出一种基于马尔可夫链的自适应性神经网络训练方法,对传统的S型激励函数进行了改进,建立了自适应性的神经网络分类器。在假设样本中噪声服从于正态分布的情况下建立最大似然估计,通过后验概率建立马尔科夫链对样本进行训练,提高了神经网络训练速度。在轴承故障诊断中的测试结果表明,该算法可以迅速稳定地训练出神经网络,有效提高诊断的分类结果。