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。     

A review of topic modeling methods

Topic modeling is a popular analytical tool for evaluating data. Numerous methods of topic modeling have been developed which consider many kinds of relationships and restrictions within datasets; however, these methods are not frequently employed. Instead many researchers gravitate to Latent Dirichlet Analysis, which although flexible and adaptive, is not always suited for modeling more complex data relationships. We present different topic modeling approaches capable of dealing with correlation between topics, the changes of topics over time, as well as the ability to handle short texts such as encountered in social media or sparse text data. We also briefly review the algorithms which are used to optimize and infer parameters in topic modeling, which is essential to producing meaningful results regardless of method. We believe this review will encourage more diversity when performing topic modeling and help determine what topic modeling method best suits the user needs.     

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.     

Questioning numerical integration methods for microsphere (and microplane) constitutive equations

In the last few years, more and more complex microsphere models have been proposed to predict the mechanical response of various polymers. Similarly than for microplane models, they consist in deriving a one-dimensional force vs. stretch equation and to integrate it over the unit sphere to obtain a three-dimensional constitutive equation. In this context, the focus of authors is laid on the physics of the one-dimensional relationship, but in most of the case the influence of the integration method on the prediction is not investigated.Here we compare three numerical integration schemes: a classical Gaussian scheme, a method based on a regular geometric meshing of the sphere, and an approach based on spherical harmonics. Depending on the method, the number of integration points may vary from 4 to 983,040! Considering simple quantities, i.e. principal (large) strain invariants, it is shown that the integration method must be carefully chosen. Depending on the quantities retained to described the one-dimensional equation and the required error, the performances of the three methods are discussed. Consequences on stress–strain prediction are illustrated with a directional version of the classical Mooney–Rivlin hyperelastic model. Finally, the paper closes with some advices for the development of new microsphere constitutive equations.     

Evolutionary collective behavior decomposition model for time series data mining

In this research, we propose a novel framework referred to as collective game behavior decomposition where complex collective behavior is assumed to be generated by aggregation of several groups of agents following different strategies and complexity emerges from collaboration and competition of individuals. The strategy of an agent is modeled by certain simple game theory models with limited information. Genetic algorithms are used to obtain the optimal collective behavior decomposition based on history data. The trained model can be used for collective behavior prediction. For modeling individual behavior, two simple games, the minority game and mixed game are investigated in experiments on the real-world stock prices and foreign-exchange rate. Experimental results are presented to show the effectiveness of the new proposed model.     

Hierarchical multi-reservoir optimization modeling for real-world complexity with application to the Three Gorges system

High dimensionality in real-world multi-reservoir systems greatly hinders the application and popularity of evolutionary algorithms, especially for systems with heterogeneous units. An efficient hierarchical optimization framework is presented for search space reduction, determining the best water distributions, not only between cascade reservoirs, but also among different types of hydropower units. The framework is applied to the Three Gorges Project (TGP) system and the results demonstrate that the difficulties of multi-reservoir optimization caused by high dimensionality can be effectively solved by the proposed hierarchical method. For the day studied, power output could be increased by 6.79 GWh using an optimal decision with the same amount of water actually used; while the same amount of power could be generated with 2.59 × 10⁷ m³ less water compared to the historical policy. The methodology proposed is general in that it can be used for other reservoir systems and other types of heterogeneous unit generators.     

Distributed wireless power transfer in sensor networks with multiple Mobile Chargers

We investigate the problem of efficient wireless power transfer in wireless sensor networks. In our approach, special mobile entities (called the Mobile Chargers) traverse the network and wirelessly replenish the energy of sensor nodes. In contrast to most current approaches, we envision methods that are distributed and use limited network information. We propose four new protocols for efficient charging, addressing key issues which we identify, most notably (i) what are good coordination procedures for the Mobile Chargers and (ii) what are good trajectories for the Mobile Chargers. Two of our protocols (DC, DCLK) perform distributed, limited network knowledge coordination and charging, while two others (CC, CCGK) perform centralized, global network knowledge coordination and charging. As detailed simulations demonstrate, one of our distributed protocols outperforms a known state of the art method, while its performance gets quite close to the performance of the powerful centralized global knowledge method.