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A FIXED POINT THEOREM REVISITED
Kirk, W.A,Kang, B.G 대한수학회 1997 대한수학회지 Vol.34 No.2
In this paper we obtain an abstract formulation of a fixed point theorem for nonexpansive mappings. Our theorem is a non-metric version of Kirk's original theorem.
Novel Natural Product Modulators of Cancer Targets, Processes, and Phenotypes
( Kirk R. Gustafson ) 전남대학교 약품개발연구소 2016 약품개발연구지 Vol.25 No.-
The NCI`s Natural Products Repository contains>220,000 extracts from taxonomically diverse marine organisms, terrestrial palnts, and microbial isolates. These extracts represent a valuable source of chemical diversity for both phenotypic and molecularly targeted high-throughput screening applications. The Molecular Targets Laboratory has successfully combined assay development experience, high-throughput screening capabilities, and natural products chemistry expertise to evaluate these extracts. Assay-guided fractionation of active extracts has provided an array of bioactive compounds that span many different structural classes. Recently, the extracts of several marine invertebrate animals have provided new heterocyclic metabolites that block activation of the HIF-1a transcription factor. These compounds represent a new structural class of alkaloid comprised of novel fused ring systems and unusual heteroatom functionality. The structural elucidation challenges associated with these proton-deficient alkaloid structures will be highlighted, along with some spectroscopic and computational methods to help address these issues. Additional new metabolites that target MALT1 protease, B-Raf kinase, and other cancer-associated targets will be described. The combination of a large, diverse library of natural product samples and new cancer-related screening platforms, provides a valuable resource for discovery of novel compounds that can serve as biological probes or potential anticancer drug development leads.
DEVELOPMENT OF THE ALTERNATE PRESSURIZED THERMAL SHOCK RULE (10 CFR 50.61a) IN THE UNITED STATES
Kirk, Mark Korean Nuclear Society 2013 Nuclear Engineering and Technology Vol.45 No.3
In the early 1980s, attention focused on the possibility that pressurized thermal shock (PTS) events could challenge the integrity of a nuclear reactor pressure vessel (RPV) because operational experience suggested that overcooling events, while not common, did occur, and because the results of in-reactor materials surveillance programs showed that RPV steels and welds, particularly those having high copper content, experience a loss of toughness with time due to neutron irradiation embrittlement. These recognitions motivated analysis of PTS and the development of toughness limits for safe operation. It is now widely recognized that state of knowledge and data limitations from this time necessitated conservative treatment of several key parameters and models used in the probabilistic calculations that provided the technical of the PTS Rule, 10 CFR 50.61. To remove the unnecessary burden imposed by these conservatisms, and to improve the NRC's efficiency in processing exemption and license exemption requests, the NRC undertook the PTS re-evaluation project. This paper provides a synopsis of the results of that project, and the resulting Alternate PTS rule, 10 CFR 50.61a.
Effect of chromatin modifiers on the plasticity and immunogenicity of small-cell lung cancer
Kirk Nicole A.,Kim Kee-Beom,Park Kwon-Sik 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Tumor suppressor genes (TSGs) are often involved in maintaining homeostasis. Loss of tumor suppressor functions causes cellular plasticity that drives numerous types of cancer, including small-cell lung cancer (SCLC), an aggressive type of lung cancer. SCLC is largely driven by numerous loss-of-function mutations in TSGs, often in those encoding chromatin modifiers. These mutations present a therapeutic challenge because they are not directly actionable. Alternatively, understanding the resulting molecular changes may provide insight into tumor intervention strategies. We hypothesize that despite the heterogeneous genomic landscape in SCLC, the impacts of mutations in patient tumors are related to a few important pathways causing malignancy. Specifically, alterations in chromatin modifiers result in transcriptional dysregulation, driving mutant cells toward a highly plastic state that renders them immune evasive and highly metastatic. This review will highlight studies in which imbalance of chromatin modifiers with opposing functions led to loss of immune recognition markers, effectively masking tumor cells from the immune system. This review also discusses the role of chromatin modifiers in maintaining neuroendocrine characteristics and the role of aberrant transcriptional control in promoting epithelial-to-mesenchymal transition during tumor development and progression. While these pathways are thought to be disparate, we highlight that the pathways often share molecular drivers and mediators. Understanding the relationships among frequently altered chromatin modifiers will provide valuable insights into the molecular mechanisms of SCLC development and progression and therefore may reveal preventive and therapeutic vulnerabilities of SCLC and other cancers with similar mutations.
Comforting Fictions: The Tribute System, the Westphalian Order, and Sino-Korean Relations
Kirk W. Larsen 동아시아연구원 2013 Journal of East Asian Studies Vol.13 No.2
Observers and practitioners of Sino-Korean relations in both the pre- and post-nineteenth century have utilized powerful “comforting fictions” to describe and justify power asymmetry. In the prenineteenth- century period, the idea of the “tribute system” put a veneer of Confucian benevolence on what a closer examination reveals to have been unequal and coercive relations. Western proponents of the Westphalian system of sovereign equality saw the new norms of international relations as potentially liberating to Korea, a way to free Korea from the Chinese yoke. However, Westphalian equality, too, was a comforting fiction that masked the reality of imperialism—both formal and informal. The Qing empire played a heretofore neglected role in both types of unequal coercive relations between Korea and the outside world.