A novel adaptive sampling based methodology for feasible region identification of compute intensive models using artificial neural network

Identification of feasible region of operations in multivariate processes is a problem of interest in several fields. This is particularly challenging when the process model is black-box in nature and/or is computationally expensive, as analytical solutions are not available and the number of possible model evaluations is limited. An efficient methodology is required to identify samples where the model is evaluated for developing a computationally efficient surrogate model. In this work, an artificial neural network based surrogate model is proposed which is integrated with a statistical-based approach (Jack-knifing) to estimate the variance of the surrogate model prediction. This allows implementation of an adaptive sampling approach where new samples are identified close to the feasible region boundary or in regions of high prediction uncertainty. The proposed approach performs better than a previously published kriging based method for different dimensionality case studies.     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway

Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity.     

Understanding the asymmetric perceptions of smartphone security from security feature perspective: A comparative study

Smartphones are being used and relied on by people more than ever before. The open connectivity brings with it great convenience and leads to a variety of risks that cannot be overlooked. Smartphone vendors, security policy designers, and security application providers have put a variety of practical efforts to secure smartphones, and researchers have conducted extensive research on threat sources, security techniques, and user security behaviors. Regrettably, smartphone users do not pay enough attention to mobile security, making many efforts futile. This study identifies this gap between technology affordance and user requirements, and attempts to investigate the asymmetric perceptions toward security features between developers and users, between users and users, as well as between different security features. These asymmetric perceptions include perceptions of quality, perceptions of importance, and perceptions of satisfaction. After scoping the range of smartphone security features, this study conducts an improved Kano-based method and exhaustively analyzes the 245 collected samples using correspondence analysis and importance satisfaction analysis. The 14 security features of the smartphone are divided into four Kano quality types and the perceived quality differences between developers and users are compared. Correspondence analysis is utilized to capture the relationship between the perceived importance of security features across different groups of respondents, and results of importance-satisfaction analysis provide the basis for the developmental path and resource reallocation strategy of security features. This article offers new insights for researchers as well as practitioners of smartphone security.     

磁性硅铁载铜吸附Hg0动力学机制及密度泛函研究

采用粉末冶金法将纳米单质铜(Cu⁰)、硅铁(FeSi)、四氧化三铁硅涂层(Fe₃O₄@SiO₂)混合煅烧并制备出新型磁性硅铁载铜吸附剂MagFeSi-Cu⁰。实验研究不同烟气温度下MagFeSi-Cu⁰的汞吸附能力基础上,结合颗粒内扩散模型、准二阶动力学模型、Elovich模型及Bangham模型分析了MagFeSi-Cu⁰吸附Hg⁰过程的主要控制步骤。在此基础上,依据密度泛函理论(DFT)研究了不同反应温度下FeSi表面Cu⁰原子与Hg⁰原子的汞齐作用机制。研究结果表明,Bangham模型的拟合值与MagFeSi-Cu⁰汞吸附实验值拟合度最高,MagFeSi-Cu⁰表面痕量Hg⁰吸附由汞的外扩散和表面铜汞齐吸附共同控制;通过密度泛函计算,发现Cu⁰颗粒表面Cu-Hg齐吸附能为-0.534 eV,当烟气温度从80℃上升至200℃时,Hg⁰原子与单质Cu原子的吸附自由能从-22.47 kJ/mol下降至-13.96 kJ/mol,这些结果为深入了解Hg⁰在Cu(111)表面的反应机理提供了理论基础。     

Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

堆本体抗震试验动力相似关系推导与验证

为确保堆本体抗震试验中流体对流效应、脉冲效应和堆本体结构响应的准确性，需保证重力、流体与固体惯性力、结构弹性力和结构应变的相似性。本文从固体结构的振动方程、不可压牛顿流体的动力学方程、流固交界面的边界条件和环形柱体域内液体线性晃动的动力学公式出发，基于控制方程的量纲分析法，推导了考虑液体晃动效应的堆本体地震响应动力相似关系。基于上述相似关系建立了堆容器堆内构件和堆容器内自由液面流体域的缩尺模型，通过有限体积法分析堆容器堆内构件原型和缩尺模型中液体的晃动固有频率、晃动波高、压力以及液体晃动对堆容器支承裙的倾覆力矩。结果表明本文动力相似关系具有合理性和准确性，可用于堆本体缩尺模型的抗震试验研究。     

Research advances in residual thermal stress of ceramic/metal brazes

Brazing, as a common method of bonding ceramic and metal, has been applied in microelectronics, aerospace, machinery and other domains extensively. The residual thermal stress in the brazed joint has direct effects on the mechanical properties of the joint, so how to control the generation of residual thermal stress has become the vital point. In this paper, the methods of reducing residual thermal stress in the brazing process in recent years are reviewed. The generation and effects of residual thermal stress in the brazed joint are introduced. Besides, the methods of detecting residual thermal stress are discussed, and different methods of reducing residual thermal stress in brazed joints are also analyzed. Finally, the future development directions of reducing residual thermal stress in the brazed joint are proposed.     

Water vapor volatilization and oxidation induced surface cracking of environmental barrier coating systems: A numerical approach

A numerical model is developed for surface crack propagation in brittle ceramic coatings, aiming at the intrinsic failure of rare-earth silicate environmental barrier coating systems (EBCs) under combustion conditions in advanced gas turbines. The main features of progressive degradation of EBCs in such conditions are captured, including selective silica vaporization in the top coat due to exposure to water vapor, diffusion path-dependent bond coat oxidation, as well as crack propagation during cyclic thermal loading. In light of these features, user-defined subroutines are implemented in finite element analysis, where surface crack growth is simulated by node separation. Numerical results are validated by existing experimental data, in terms of monosilicate layer thickening, thermal oxide growth, and fracture behaviors. The experimentally observed quasi-linear oxidation in the early stage is also elucidated. Furthermore, it is suggested that surface crack undergoes rapid propagation in the late stage of extended thermal cycling in water vapor and leads to catastrophic failure, driven by both thermal mismatch and oxide growth stresses. The latter is identified as the dominant mechanism of penetration. Based on detailed analyses of failure mechanisms, the optimization strategy of EBCs composition is proposed, balancing the trade-off between mechanical compliance and erosion resistance.