A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

OBE-CDIO理念下“集成电路版图分析与设计”课程教学改革与探索

针对目前集成电路版图分析与设计课程存在教学方法老化、教学模式形式化等问题,本文以OBE-CDIO教育理念为指导,对”集成电路版图分析与设计”课程的课程教学模式、课程设计、项目式教学方式和课程考核方式等方面的改革进行有益的探索与实践。将工程教学认证中对学生的专业毕业要求作为制定教学目标的依据,将BB网络平台、ISO9001等现代化教学资源和质量标准融入课堂教学,采用OBE-CDIO能力教学理念指导课程设计,实现教学环节与考核环节的科学化与多元化,通过引入课程思政激发学生学习热情,树立社会主义核心价值观,全面地培养学生的综合版图分析与设计能力和素养。     

The role of microstructural evolution during spark plasma sintering on the soft magnetic and electronic properties of a CoFe–Al2O3 soft magnetic composite

Journal of Materials Science - For transformers and inductors to meet the world’s growing demand for electrical power, more efficient soft magnetic materials with high saturation magnetic...     

Mechanical Properties of Single-Layer Diamond Reinforced Poly(vinyl alcohol) Nanocomposites through Atomistic Simulation

Low-dimensional carbon nanostructures are ideal nanofillers to reinforce the mechanical performance of polymer nanocomposites due to their excellent mechanical properties. Through molecular dynamics simulations, the mechanical performance of poly(vinyl alchohol) (PVA) nanocomposites reinforced with a single-layer diamond – diamane is investigated. It is found the PVA/diamane exhibits similar interfacial strengths and pull-out characteristics with the PVA/bilayer-graphene counterpart. Specifically, when the nanofiller is fully embedded in the nanocomposite, it is unable to deform simultaneously with the PVA matrix due to the weak interfacial load transfer efficiency, thus the enhancement effect is not significant. In comparison, diamane can effectively promote the tensile properties of the nanocomposite when it has a laminated structure as it deforms simultaneously with the matrix. With this configuration, the interlayer sp³ bonds endows diamane with a much higher resistance under compression and shear tests, thus the nanocomposite can reach very high compressive and shear stress. Overall, enhancement on the mechanical interlocking at the interface as triggered by surface functionalization is only effective for the fully embedded nanofiller. This work provides a fundamental understanding of the mechanical properties of PVA nanocomposites reinforced by diamane, which can shed lights on the design and preparation of next generation high-performance nanocomposites.     

Hydrogeochemical Processes and Inverse Modeling for a Multilayer Aquifer System in the Yuaner Coal Mine,Huaibei Coalfield,China

Coal mining can dramatically change hydrogeological conditions and induce serious environmental problems. Fifty groundwater samples were collected from the main aquifers in the Yuaner coal mine (Anhui Province, China). The results show that the main hydrogeochemical processes in the mine include dissolution, precipitation, pyrite oxidation, desulfurization, and cation exchange. The Neogene porous aquifer is affected by groundwater flow conditions; its main hydrogeochemical processes are dissolution of carbonate minerals and gypsum, and cation exchange. The Permian coal measure’s fractured sandstone aquifer was confirmed to be controlled by the region’s geological structure; its main hydrogeochemical processes are desulfurization and cation exchange. The Carboniferous Taiyuan limestone aquifer was determined by both groundwater flow conditions and regional geological structure; its main hydrogeochemical processes are dissolution of carbonate minerals and gypsum, pyrite oxidation, and cation exchange. Additionally, hydrogeochemical inverse modeling of the groundwater flow path confirm the hydrochemistry results and principal component analysis.

     

Adaptive Synchronization-Based Approach for Finite-Time Parameters Identification of Genetic Regulatory Networks

Neural Processing Letters - This paper presents an approach to identify the unknown parameters of genetic regulatory network (GRN) in finite-time. The adaptive synchronization-based method is used...