Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

基于神经网络和遗传算法的锭子弹性管性能优化

为得到减振弹性管对下锭胆的支承弹性和锭子高速运动下的稳定性等性能的最优匹配效率,依据减振弹性管的等效抗弯刚度及底部等效刚度系数公式,利用MatLab数值分析软件构建弹性管抗弯刚度和底部挠度数学模型。首先,结合Isight优化软件基于径向基神经网络构建其近似模型,且使精度达到可接受水平,并以模型的关键结构参数弹性模量、螺距、槽宽、壁厚为设计变量,结合遗传算法对弹性管抗弯刚度和底部挠度进行多目标优化设计,得到Pareto最优解集和Pareto前沿图,确定出减振弹性管结构工艺参数的优化方案。通过对优化数据进行分析发现,该方案在保证减振弹性管弹性的同时,其底部振幅明显减弱。     

An experimental study of adaptive control for evolutionary algorithms

In this paper, we investigate how adaptive operator selection techniques are able to efficiently manage the balance between exploration and exploitation in an evolutionary algorithm, when solving combinatorial optimization problems. We introduce new high level reactive search strategies based on a generic algorithm's controller that is able to schedule the basic variation operators of the evolutionary algorithm, according to the observed state of the search. Our experiments on SAT instances show that reactive search strategies improve the performance of the solving algorithm.     

Digital Microfluidics for Manipulation and Analysis of a Single Cell

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical boundary of microchannels and microstructures, single cells are efficiently captured and analyzed, whereas electric forces sort and position single cells. Various microfluidic techniques have been exploited to manipulate single cells through hydrodynamic and electric forces. Digital microfluidics (DMF), the manipulation of individual droplets holding minute reagents and cells of interest by electric forces, has received more attention recently. Because of ease of fabrication, compactness and prospective automation, DMF has become a powerful approach for biological application. We review recent developments of various microfluidic chips for analysis of a single cell and for efficient genetic screening. In addition, perspectives to develop analysis of single cells based on DMF and emerging functionality with high throughput are discussed.     

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

多运营商高铁隧道移动网络覆盖方案

高铁移动网络覆盖是国内三大通信运营商的一个重点,而高铁隧道内移动网络覆盖更是运营商的一大难点痛点。文章根据我国中部省份某高铁线路覆盖规划实例,采用“设备+POI+泄漏电缆”模式,即三家运营商信号源设备通过同一POI(point of interface,多系统接入平台)接入,信号输出到泄漏电缆进行隧道覆盖,隧道口场坪站安装宽频切换天线对隧道外进行延伸覆盖,通过链路预算合理布置各运营商主设备信号源,从而实现隧道到室外的无缝覆盖。最后,根据已有成熟网络覆盖解决方案,对未来5G高铁隧道移动网络覆盖方案进行了探讨。     

基于SVM的煤与瓦斯突出预测模型及应用

为有效预测矿井内煤与瓦斯突出的危险程度,对其影响因素做了分析与探讨,分别构建了基于粒子群优化算法以及遗传算法支持向量机的煤与瓦斯突出预测模型,并且通过实例对两种模型预测的准确性进行了验证。分别利用单项以及综合指标、BP神经网络以及PSO-SVM模型、GA-SVM模型,对寺河煤矿二号井的突出区域进行预测比较。结果表明,PSO-SVM的预测模型不仅可以在小样本数据中预测出煤与瓦斯突出程度的大小,而且综合预测结果更加精确,其在解决矿井内煤与瓦斯突出的小样本数据中显示出更加强大、通用的性能。