Meta-Analysis of Methamphetamine Modulation on Amyloid Precursor Protein through HMGB1 in Alzheimer’s Disease

The deposition of amyloid-beta (Aβ) through the cleavage of amyloid-beta precursor protein (APP) is a biomarker of Alzheimer’s disease (AD). This study used QIAGEN Ingenuity Pathway Analysis (IPA) to conduct meta-analysis on the molecular mechanisms by which methamphetamine (METH) impacts AD through modulating the expression of APP. All the molecules affected by METH and APP were collected from the QIAGEN Knowledge Base (QKB); 78 overlapping molecules were identified. Upon simulation of METH exposure using the “Molecule Activity Predictor” feature, eight molecules were found to be affected by METH and exhibited activation relationships on APP expression at a confidence of p = 0.000453 (Z-score = 3.51, two-tailed). Core Analysis of these eight molecules identified High Mobility Group Box protein 1 (HMGB1) signaling pathway among the top 5 canonical pathways with most overlap with the 8-molecule dataset. Simulated METH exposure increased APP expression through HMGB1 at a confidence of p < 0.00001 (Z-score = 7.64, two-tailed). HMGB1 is a pathogenic hallmark in AD progression. It not only increases the production of inflammatory mediators, but also mediates the disruption of the blood-brain barrier. Our analyses suggest the involvement of HMGB1 signaling pathway in METH-induced modulation of APP as a potential casual factor of AD.     

基于GPS和WiFi的室内外定位系统的设计与实现

经济和科技高速发展的中国,基于GPS的定位技术和基于WiFi的定位技术已发展成熟。在有14亿人口的中国,人们的思想观念发生了巨大变化,人口老龄化越来越严重,老人和小孩等弱势群体走失事件频发。因此,借助定位技术缓解这种现象十分必要。借助定位信息,不仅可以缓解老人小孩走失问题,而且可以实现前签到等功能。定位技术的应用范围和发展前景非常广阔。     

APP软件性能效率研究

性能效率是APP软件的重要质量属性，但目前缺乏APP软件性能效率的通用模型。分析了APP软件的性能特征，基于ISO/IEC 25010标准提出了APP软件的性能效率模型，定义了APP软件性能效率的子特性和度量指标。基于提出的APP软件性能效率模型，通过实验对APP软件的性能效率进行了度量及相关分析。     

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.     

New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

The Amyloid Precursor Protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ) in Alzheimer’s disease (AD). However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y₆₈₂ mutation in the ₆₈₂YENPTY₆₈₇ domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS) on hippocampal tissue extracts of three month-old mice incubated with either the ₆₈₂YENPTY₆₈₇ peptide, its mutated form, ₆₈₂GENPTY₆₈₇ or its phosphorylated form, ₆₈₂pYENPTY₆₈₇. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc) and its Adaptor Protein 2 (AP-2). Overall our results consolidate and refine the importance of Y₆₈₂ in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.     

一种基于NFC的无源智能锁及其在配电网中的应用

针对配网柜体采用的传统机械锁具管理难度大、破解容易以及可追踪性差,无法满足现代电网快速发展的多样化需求等问题。该文研制了一种基于配电物联网架构的无源高可靠性智能电子锁。其内嵌安全芯片,采用近场通信(Near Field Communication,NFC)技术完成通信及取能,无需机械钥匙开锁,无需维护更换锁具电池,并配套开发了能够实时监测锁具状态、储存开锁信息的智能锁管理系统以及配合开锁APP使用的电子钥匙,分析了智能锁具的硬件设计及系统的应用流程。最后,通过实践应用表明,该套锁具系统在运维便捷、信息安全和科学管理方面具有明显效用。     

基于因子分析法的地区财政支出状况评价

以2012年我国财政支出数据为依据进行建模分析，并对我国目前各地财政支出状况给出科学的解释和说明。财政支出是一种经济行为，财政支出结构对于一个国家的经济发展起着至关重要的影响。运用因子分析法算出因子得分，对我国财政支出数据进行分析发现：我国各地区财政支出仍然相当不平衡，要实行财政转移以缩小各地财力差异。     

基于数字化、共享化背景下财务管理模式创新研究与实践

介绍了山东能源集团财务管理数字化转型的背景,阐述了该集团新型数字化、共享化财务管理模式的建设路径。通过不断探索财务理念和管理实践的创新,以及新型数字化和财务共享管理模式的建设,该集团实现了财务管理模式的转型升级,助力企业实现数字化、智慧化转型。     

智能网联汽车APP中控制模块的视觉设计与应用

目的研究智能网联汽车手机APP中控制模块的视觉设计与应用,强化视觉设计过程的合理性,为智能汽车HMI设计实践工作提供启示与借鉴。方法首先从用户体验的角度分析APP控制模块存在的视觉设计问题,主要是视觉结构单一、视觉层级混乱、视觉特征缺失,再从行为逻辑的角度思考视觉设计方法,"由面及点"地提出控制模块的视觉设计思路,并结合设计应用案例论证其可行性。结果从合理视觉布局、明确视觉层级和提炼视觉语言的角度提出APP控制模块的视觉设计思路。结论智能网联汽车APP控制模块的视觉设计应该重视行为逻辑的影响。从任务角度思考视觉布局、从行为逻辑的角度思考视觉层级、从行为特征的角度思考视觉语言,提高视觉设计工作的合理性,减少与交互设计工作脱节的现象,强化控制求助的高效性和安全性。     

基于内隐测量的APP交互流程可用性评估方法

目的 研究内隐测量用于交互流程评估的普遍方法，选取适合的参考指标建立评估标准，旨在提出一套完整且通用的评估策略。方法 以带有拍摄功能的宠物社交类APP为载体，提出两种不同的交互流程，建立交互原型，并提取两套原型中差异较大的流程进行对比实验，采用眼动仪收集被测的无意识行为，依据首次注视时间、兴趣区域注视率，注视点图等指标分析实验数据，并与外显测量结果相结合，衡量用户操作情况以及APP的交互性能。结果 根据实验和数据分析，得出以拍摄界面为主页是更适合宠物社交APP的交互方式。结论 内隐测量评估作为一种新兴的产品可用性评估方式，不仅在交互界面设计评估上得到了广泛的应用，还可作为产品交互流程的评估方法，并具有深度挖掘的意义。