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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.
运用FLUENT数值模拟软件分析了平板集热器(倾角)变化对集热器传热特性的影响,保证其结构参数不变,通过对5组不同倾角(0°、30°、45°、60°、75°)的数值模型进行非稳态模拟,对模拟数据进行分析,得出了平板集热器不同倾角对集热器传热性能变化的影响。 相似文献
4.
Output feedback controller for polytopic systems exploiting the direct searching of the design space
This paper deals with the problem of designing a robust static output feedback controller for polytopic systems. The current research that tackled this problem is mainly based on LMI method, which is conservative by nature. In this paper, a novel approach is proposed, which considers the design space of the controller parameters and iteratively partitions the space to small simplexes. Then, by assessing the stability in each simplex, the solution space for design parameters is directly determined. It has been theoretically proved that, if there exists a feasible solution in the design space, the algorithm can find it. To validate the result of the proposed approach, comparative simulation examples are given to illustrate the performance of the design methodology as compared to those of previous approaches. 相似文献
6.
It is shown that, for the spectrum analysis of digital quasi-periodic signals, one must use a procedure based on approximating the sequence of data readouts by a first-order trigonometric polynomial with a varying frequency of its harmonic functions. 相似文献
7.
A method constructinq C~1 Piecewise quintic polynomial over a triangular grid to interpo-late function values and partial derivatives at vertices is presented in this paper.The set of precise poly-nomials of this method is discussed. 相似文献
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The distribution ratios of Fe and B between molten Fe–B alloy and molten Ag were measured at temperatures between 1573 and 1923 K. Also, distribution ratios of Fe and B between molten Fe–B–Csatd. alloys and molten Ag were measured at 1873 K. It was found that the excess Gibbs free energy of mixing in molten Fe–B and Fe–B–C alloys can be expressed by utilizing the Redlich–Kister polynomial. The activity curves of the elements in molten Fe–B alloy and Fe–B–C alloy were estimated. 相似文献