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61.
Esophageal cancer (EC) was an aggressive malignant neoplasm characterized by high morbidity and poor prognosis. Identifying the changes in DNA damage repair genes helps to better understand the mechanisms of carcinoma progression. In this study, by comparing EC samples and normal samples, we found a total of 132 DDR expression with a significant difference. Moreover, we revealed higher expression of POLN, PALB2, ATM, PER1, TOP3B and lower expression of HMGB1, UBE2B were correlated to longer OS in EC. In addition, a prognostic risk score based on 7 DDR gene expression (POLN, HMGB1, TOP3B, PER1, UBE2B, ATM, PALB2) was constructed for the prognosis of EC. Meanwhile, EC cancer samples were divided into 3 subtypes based on 132 DDR genes expressions. Clinical profile analysis showed cluster C1 and C2 showed a similar frequency of T2, which was remarked higher than that in cluster 3. Moreover, we found the immune cell inflation levels were significantly changed in different subtypes of EC. The infiltration levels of T cell CD8+, B cell and NK cells were greatly higher in cluster 2 than that in cluster 1 and cluster 3. The results showed T cell CD4+ infiltration levels were dramatically higher in cluster 1 than that in cluster 2 and cluster 3. Finally, we perform bioinformatics analysis of DEGs among 3 subtypes of EC and found DDR genes may be related to multiple signaling, such as Base excision repair, Cell cycle, Hedgehog signaling pathway, and Glycolysis/Gluconeogenesis. These results showed DDR genes may serve as new target for the prognosis of EC and prediction of the potential response of immune therapy in EC. 相似文献
62.
This paper mainly illustrates the Tree Seeds Algorithm (TSA) to tackle structural damage identification problem. The damage model is simulated by the alterations of both stiffness and mass parameters. The objective function is introduced by minimizing the differences between the measured and calculated acceleration data. To enhance the performance of the standard TSA, two modifications including the bare-bones Gaussian updated mechanism and the withering process are introduced. The modified algorithm is named after the BGTSA. In the numerical simulation part, the BGTSA is firstly used to make comparisons with several state-of-the-art algorithms on the CEC05. Secondly, the BGTSA is utilized to deal with the structural damage identification problem by optimizing the acceleration-based nonlinear objective function. Numerical experiments involving a simply supported beam and a truss are carried out to verify the effectiveness of the proposed algorithm. The final results show that with low amount of acceleration data, the BGTSA can acquire better identification results compared with other evolutionary algorithms. Therefore the proposed algorithm could be viewed as a potential tool to solve the structural damage identification problem. 相似文献
63.
Dr. Kun Yang Prof. Dr. Marc M. Greenberg 《Chembiochem : a European journal of chemical biology》2019,20(1):78-82
Abasic sites (AP) are produced 10 000 times per day in a single cell. Strand cleavage at AP is accelerated ≈100-fold within a nucleosome core particle (NCP) compared to free DNA. The lysine-rich N-terminal tails of histone proteins catalyze single-strand breaks through a mechanism used by base-excision-repair enzymes, despite the general dearth of glutamic acid, aspartic acid, and histidine—the amino acids that are typically responsible for deprotonation of Schiff base intermediates. Incorporating glutamic acid, aspartic acid, or histidine proximal to lysine residues in histone N-terminal tails increases AP reactivity as much as sixfold. The rate acceleration is due to more facile DNA cleavage of Schiff-base intermediates. These observations raise the possibility that histone proteins could have evolved to minimize the presence of histidine, glutamic acid, and aspartic acid in their lysine-rich N-terminal tails to guard against enhancing the toxic effects of DNA damage. 相似文献
64.
Hassan Ijaz Muhammad Zain-ul-abdein Waqas Saleem Muhammad Asad Tarek Mabrouki 《Machining Science and Technology》2018,22(3):522-542
Turning modeling and simulation of different metallic materials using the commercially available Finite Element (FE) softwares is getting prime importance because of saving of time and money in comparison to the costly experiments. Mostly, the numerical analysis of machining process considers a purely isotropic behavior of metallic materials; however, the literature shows that the elastic crystal anisotropy is present in most of the ‘so-called’ isotropic materials. In the present work, the elastic anisotropy is incorporated in the FE simulations along with the effect of grain size. A modified Johnson-Cook ductile material model based on coupled plasticity and damage evolution has been proposed to model the cutting process. The simulation results were compared with experimental data on the turning process of Aluminum alloy (AA2024). It was found that the elastic anisotropy influences the average cutting force up to 5% as compared to the isotropic models while the effect of grain size was more pronounced up to 20%. 相似文献
65.
针对地震发生后亟需对土石坝群体震害进行快速评估的问题,基于统计数据和MSA方法,提出了土石坝群体震害易损性分析方法。通过分析土石坝群体震害数据,对震损大坝进行等级划分,结合地震破坏损失比和破坏比建立土石坝地震易损性矩阵。并引入MSA方法,建立土石坝群体震害易损性评估模型,计算出四种烈度下易损性参数及易损性曲线和概率,为土石坝群体震害快速评估提供了依据。 相似文献
66.
ABSTRACTIn the present paper, the mechanical properties and the scratch failure mechanisms of Ni–P electroless coatings are described. The material microstructure was studied in as-deposited and annealed conditions through SEM and EDS analyses. Nanoindentation measurements on the coatings showed a remarkable hardening due to the crystallization and precipitation behaviour produced by annealing. The scratch tests, conducted by increasing the load during scratch, revealed the coating failure mechanisms in a broad range of applied stresses up to delamination. 相似文献
67.
Frontiers of Mechanical Engineering - Experimental and finite element research was conducted on the bolted interference fit of a single-lap laminated structure to reveal the damage propagation... 相似文献
68.
69.
Mingrui Duan Jenna Ulibarri Ke Jian Liu Peng Mao 《International journal of molecular sciences》2020,21(23)
Cisplatin is a chemotherapeutic drug used for the treatment of a number of cancers. The efficacy of cisplatin relies on its binding to DNA and the induction of cytotoxic DNA damage to kill cancer cells. Cisplatin-based therapy is best known for curing testicular cancer; however, treatment of other solid tumors with cisplatin has not been as successful. Pre-clinical and clinical studies have revealed nucleotide excision repair (NER) as a major resistance mechanism against cisplatin in tumor cells. NER is a versatile DNA repair system targeting a wide range of helix-distorting DNA damage. The NER pathway consists of multiple steps, including damage recognition, pre-incision complex assembly, dual incision, and repair synthesis. NER proteins can recognize cisplatin-induced DNA damage and remove the damage from the genome, thereby neutralizing the cytotoxicity of cisplatin and causing drug resistance. Here, we review the molecular mechanism by which NER repairs cisplatin damage, focusing on the recent development of genome-wide cisplatin damage mapping methods. We also discuss how the expression and somatic mutations of key NER genes affect the response of cancer cells to cisplatin. Finally, small molecules targeting NER factors provide important tools to manipulate NER capacity in cancer cells. The status of research on these inhibitors and their implications in cancer treatment will be discussed. 相似文献
70.
Joanna Jaskowiak Jolanta Kwasniewska Miriam Szurman-Zubrzycka Magdalena Rojek-Jelonek Paul B. Larsen Iwona Szarejko 《International journal of molecular sciences》2020,21(22)
ATR, a DNA damage signaling kinase, is required for cell cycle checkpoint regulation and detecting DNA damage caused by genotoxic factors including Al3+ ions. We analyzed the function of the HvATR gene in response to chemical clastogen-maleic acid hydrazide (MH). For this purpose, the Al-tolerant barley TILLING mutant hvatr.g was used. We described the effects of MH on the nuclear genome of hvatr.g mutant and its WT parent cv. “Sebastian”, showing that the genotoxic effect measured by TUNEL test and frequency of cells with micronuclei was much stronger in hvatr.g than in WT. MH caused a significant decrease in the mitotic activity of root cells in both genotypes, however this effect was significantly stronger in “Sebastian”. The impact of MH on the roots cell cycle, analyzed using flow cytometry, showed no differences between the mutant and WT. 相似文献