New Insights into the Pathogenesis of Systemic Mastocytosis

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM.     

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

An Improved Immune Genetic Algorithm for Solving the Optimization Problems of Computer Communication Networks

1　IntroductionIndesigningacomputercommunicationnet work ,thenetworkaveragedelayisanimportantpa rameterinthenetworkperformance .Inthispaper,weonlyconsiderM /M/1networks,whichmeansthatthemessageprocessingtimeisaprobabilisticdensityfunctionwithnegativepower,thegroupar rivalandsendingisofPoissiondistributionwithasinglequeue .Supposethatthenetworktopologicalstructureandtheestimatesoftheexternaltrafficrequirementsaregiven ,howtoselecttheoptimalroutestobeusedbythecommunicatingnodesinthenetworksoast…     

一种抗NLOS的TDOA定位算法

本文提出了一种抗非视线传播(Non-Line-of-Sight)干扰的TDOA定位算法。该算法采用退火与遗传算法相结合的方式，在满足给定条件的空间内搜索源点坐标值。数值仿真表明，该算法具备抗NLOS干扰的能力，与传统TDOA算法相比，该算法无需知道各基站的非视线传播干扰分布，是一种实用有效的定位算法。     

27例乙型血友病患者Ⅸ因子基因突变研究

采用ＰＣＲ（聚合酶链反应）及ＧＡＷＴＳ（ＧｅｎｏｍｉｃＡｍｐｌｉｆｉｃａｔｉｏｎｗｉｔｈＴｒａｎｓｃｒｉｐｔｓＳｅｑｕｅｎｃｉｎｇ）技术，研究了江苏、湖北、山东、广东、福建、宁夏六省区２７例乙型血友病患者及其家系成员ＦⅨ（九因子）基因各２．２Ｋｂ　ＤＮＡ序列。在２ｌ例中发现２０种不同类型的突变。其中１２种是未曾报道的新突变。３８％的突变发生在ＣｐＧ二核苷致序列上，进一步证实了ＣｐＧ确系突变热点。同时检出６例女性为致病基因携带者。对开展基因产前诊断及优生优育等，具有重要意义。     

An integrated automatic test data generation system

The Godzilla automatic test data generator is an integrated collection of tools that implements a relatively new test data generation method—constraint-based testing—that is based on mutation analysis. Constraint-based testing integrates mutation analysis with several other testing techniques, including statement coverage, branch coverage, domain perturbation, and symbolic evaluation. Because Godzilla uses a rule-based approach to generate test data, it is easily extendible to allow new testing techniques to be integrated into the current system. This article describes the system that has been built to implement constraint-based testing. Godzilla's design emphasizes orthogonality and modularity, allowing relatively easy extensions. Godzilla's internal structure and algorithms are described with emphasis on internal structures of the system and the engineering problems that were solved during the implementation.Parts of this research were supported by Contract F30602-85-C-0255 through Rome Air Development Center while the author was a graduate student at the Georgia Institute of Technology.     

筛查基因突变的新技术——循环双脱氧指纹图谱法及其应用

建立了适用于大批量标本基因突变筛查的双脱氧指纹图谱法即ｄｄＦ。该技术民测定ＤＮＡ序列的双脱氧末端终止法及ＳＳＣＰ二者长处于一身，即只作一个双脱氧末端终止反应，然后将反应产物在与ＳＳＣＰ相同的电泳条件下进行聚丙烯酰胺凝胶电泳，这样有突变的样品不会漏检，阳性检出率高达１００％。     

采用混合搜索策略的阿奎拉优化算法

针对阿奎拉优化算法（AO）存在的不足,提出一种采用混合搜索策略的阿奎拉优化算法（HAO）。首先,利用动态调整函数平衡算法的全局探索与局部开发;其次,利用混沌自适应权重来增强算法的全局搜索能力、加快算法的收敛速度;最后,设计新的个体变异概率系数,采用改进型差分变异策略,利用适应度值较优个体引领群体中其他个体开展搜索活动,保持了种群的多样性,增强了算法跳出局部最优能力。通过八个基准测试函数和10个CEC2019测试函数,以及一个工程应用问题的数值实验仿真对所提算法进行实验验证。实验结果表明,所提算法的全局收敛速度和优化精度均得到了明显地改善,跳出局部最优的能力得到了增强。     

自适应变异粒子群优化算法及在新冠肺炎疫情传播预测中的应用

为克服粒子群算法容易陷入局部最优和全局寻优精度不高的缺点,通过对算法的局部寻优和全局寻优的特点进行分析,首先使用正态分布衰减策略改进惯性权重;同时基于算法运行的时间自适应采用不同的基于高斯分布及柯西分布的变异优化策略,解决全局搜索和局部开发能力的不平衡问题,实现了局部寻优和全局寻优的双重优化,满足了提高寻优速度和寻优精度的目的.为验证算法有效性及实用性,将改进算法用于预测新冠肺炎疫情传播情况.选取100天新冠肺炎疫情每日新确诊人数的数据,利用算法优化前馈神经网络的参数,使训练好的神经网络模型预测新冠肺炎疫情的性能提升.实验部分首先使用测试函数将改进的算法与其它五种算法进行对比,验证算法的良好性能,最后应用到神经网络完成新冠肺炎疫情传播预测.