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1.
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. 相似文献
2.
Margarita A. Sazonova Vasily V. Sinyov Anastasia I. Ryzhkova Marina D. Sazonova Tatiana V. Kirichenko Victoria A. Khotina Zukhra B. Khasanova Natalya A. Doroschuk Vasily P. Karagodin Alexander N. Orekhov Igor A. Sobenin 《International journal of molecular sciences》2021,22(2)
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. 相似文献
3.
An Improved Immune Genetic Algorithm for Solving the Optimization Problems of Computer Communication Networks 总被引:4,自引:0,他引:4
1 IntroductionIndesigningacomputercommunicationnet work ,thenetworkaveragedelayisanimportantpa rameterinthenetworkperformance .Inthispaper,weonlyconsiderM /M/1networks,whichmeansthatthemessageprocessingtimeisaprobabilisticdensityfunctionwithnegativepower,thegroupar rivalandsendingisofPoissiondistributionwithasinglequeue .Supposethatthenetworktopologicalstructureandtheestimatesoftheexternaltrafficrequirementsaregiven ,howtoselecttheoptimalroutestobeusedbythecommunicatingnodesinthenetworksoast… 相似文献
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27例乙型血友病患者Ⅸ因子基因突变研究 总被引:1,自引:0,他引:1
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。 相似文献
6.
王西文 《石油地球物理勘探》2007,42(3):362-361
《石油地球物理勘探》报道了我国石油地球物理勘探领域方法和技术的最新进展及所取得的成就,反映了我国石油地球物理勘探的科研水平和实际应用能力。面对我国新领域油气勘探的不断深入,石油地球物理勘探技术也不断地取得进步。2006年该刊共发表各类论文134篇,主要内容涉及7个方面:①野外地震采集技术;②地震资料处理方法和技术;③地震综合解释及油气预测方法和技术;④重磁电综合物探方法和技术;⑤测井技术应用;⑥地质研究;⑦专家综述和评述。 相似文献
7.
An integrated automatic test data generation system 总被引:3,自引:0,他引:3
A. Jefferson Offutt 《Journal of Systems Integration》1991,1(3-4):391-409
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. 相似文献
8.
筛查基因突变的新技术——循环双脱氧指纹图谱法及其应用 总被引:2,自引:0,他引:2
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%。 相似文献
9.
社会主义市场经济条件下企业经营者年薪制的建立,使经营者的收入与经营成果紧密相联,责权利一致,是现代企业制度的要求,体现了“按劳分配,多劳多得”的社会主义分配原则。企业在实行经营者年薪制时应明确基薪标准和效益收入,完善各项管理考核制度,建立起良好的激励机制。 相似文献
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