Artificial neural network (ANN) has wide applications such as data processing and classification. However, comparing with other classification methods, ANN needs enormous memory space and training time to build the model. This makes ANN infeasible in practical applications. In this paper, we try to integrate the ideas of human learning mechanism with the existing models of ANN. We propose an incremental neural network construction framework for unsupervised learning. In this framework, a neural network is incrementally constructed by the corresponding subnets with individual instances. First, a subnet maps the relation between inputs and outputs for an observed instance. Then, when combining multiple subnets, the neural network keeps the corresponding abilities to generate the same outputs with the same inputs. This makes the learning process unsupervised and inherent in this framework. In our experiment, Reuters-21578 was used as the dataset to show the effectiveness of the proposed method on text classification. The experimental results showed that our method can effectively classify texts with the best F1-measure of 92.5%. It also showed the learning algorithm can enhance the accuracy effectively and efficiently. This framework also validates scalability in terms of the network size, in which the training and testing times both showed a constant trend. This also validates the feasibility of the method for practical uses.
T315I mutation of Bcr-Abl in chronic myeloid leukemia (CML) leads to therapeutic resistance. It is known that Bcr-Abl transformation causes ROS-induced DNA damage, which can be exploited for anti-nucleotide treatment. We developed a small compound, JMF4073, which inhibits pyrimidylate kinases. Intriguingly, treatment of JMF4073 selectively eliminated WT-, but not T315I-, Bcr-Abl-transformed cells. We found that the higher level of cellular glutathione(GSH) in T315I-Bcr-Abl cells confers replication fork progression and sustains dTTP pool, leading to JMF4073 insusceptibility. Blocking mitochondrial pyruvate carrier (MPC) by UK-5099 reduced GSH and induced DNA replication stress in T315I-Bcr-Abl cells, thus increasing JMF4073 sensitivity in vitro and in vivo. We also observed the increases in glutamine flux to GSH production in T315I-Bcr-Abl cells, and reductive carboxylation of glutamate metabolism, together with mitochondrial dysfunction. The proteomic assay revealed the deficiencies in respiration complex I, II, and IV proteins in T315I-Bcr-Abl cells. Most interestingly, calcineurin inhibition remarkably elevated mitochondrial oxidative stress to cause cytotoxicity specifically in T315I-Bcr-Abl cells. Our results demonstrate the metabolic shift by T315I mutation of Bcr-Abl CML and provide the therapeutic options by co-targeting mitochondria and pyrimidylate kinases. Citation Format: Chang-Yu Huang, Yin-Hsuan Chung, Sheng-Yang Wu, Hsin-Yang Wang, Chih-Yu Lin, Tsung-Jung Yang, Jim-Ming Fang, Yu-Ju Chen, Chun-Mei Hu, Zee-Fen Chang. Co-targeting mitochondria and nucleotide metabolism in T315I-BCR-ABL myeloid leukemia for therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1602.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.