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％。     

二进制分辨矩阵在连续属性约简中的研究

针对二进制分辨矩阵无法处理连续型数据,提出一种基于邻域的改进二进制分辨矩阵及其属性约简方法。实验结果表明,与先数据离散化,后属性约简的方法相比,利用文中方法提取出的特征属性的分类能力更高。     

邻域等价关系诱导的改进ID3决策树算法

经典ID3决策树算法适用于离散型数据分类,但用于连续处理时需要数据离散化容易导致信息损失。提出邻域等价关系从而诱导邻域ID3(NID3)决策树算法,NID3算法改进了ID3决策树算法,能够直接实施连续预测并获取更好的分类效果。在邻域决策系统中,挖掘一种邻域等价关系;基于邻域等价粒化,构建邻域信息度量;基于邻域信息增益,设计NID3决策树算法。实例分析与数据实验均表明,NID3算法具有连续数据分类预测有效性,在分类机器学习中优于ID3算法。     

A comparative study between dynamic adapted PSO and VNS for the vehicle routing problem with dynamic requests

Combinatorial optimization problems are usually modeled in a static fashion. In this kind of problems, all data are known in advance, i.e. before the optimization process has started. However, in practice, many problems are dynamic, and change while the optimization is in progress. For example, in the dynamic vehicle routing problem (DVRP), new orders arrive when the working day plan is in progress. In this case, routes must be reconfigured dynamically while executing the current simulation. The DVRP is an extension of a conventional routing problem, its main interest being the connection to many real word applications (repair services, courier mail services, dial-a-ride services, etc.). In this article, a DVRP is examined, and solving methods based on particle swarm optimization and variable neighborhood search paradigms are proposed. The performance of both approaches is evaluated using a new set of benchmarks that we introduce here as well as existing benchmarks in the literature. Finally, we measure the behavior of both methods in terms of dynamic adaptation.