• Title/Summary/Keyword: targeting

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Gene Targeting in Mouse Embryos Mediated by recA and Modified Single-Stranded Oligonucleotides

  • Kang, Jee-Hyun;Won, Ji-Young;Heo, Soon-Young;Hosup Shim
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.193-193
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    • 2004
  • Gene targeting is an in situ manipulation of endogenous gene with precise manner by the introduction of exogenous DNA. The process of gene targeting involves a homologous recombination reaction between the targeted genomic sequence and an exogenous targeting vector. In elucidating the function of many genes, gene targeting has become the most important method of choice. (omitted)

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A Study on Methodology for Air Target Dynamic Targeting Applying Machine Learning (기계학습을 활용한 항공표적 긴급표적처리 발전방안 연구)

  • Kang, Junghyun;Yim, Dongsoon;Choi, Bongwan
    • Journal of the Korea Institute of Military Science and Technology
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    • v.22 no.4
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    • pp.555-566
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    • 2019
  • In order to prepare for the future warfare environment, which requires a faster operational tempo, it is necessary to utilize the fourth industrial revolution technology in the field of military operations. This study propose a methodology, 'machine learning based dynamic targeting', which can contribute to reduce required man-hour for dynamic targeting. Specifically, a decision tree algorithm is considered to apply to dynamic targeting process. The algorithm learns target prioritization patterns from JIPTL(Joint Integrated Prioritized Target List) which is the result of the deliberate targeting, and then learned algorithm rapidly(almost real-time) determines priorities for new targets that occur during ATO(Air Tasking Order) execution. An experiment is performed with artificially generated data to demonstrate the applicability of the methodology.

A Current Advance of Gene Targeting and Gene Trapping Methods As Tools of Making Transgenic Mice (형질전환생쥐의 제조 수단으로서 유전자 적중법 및 함정법의 개발 현황)

  • Kang, Hae-Mook
    • Development and Reproduction
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    • v.14 no.4
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    • pp.215-223
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    • 2010
  • The construction of transgenic mouse using embryonic stem (ES) cells has been crucial in the functional studies of gene on mouse genome. Gene knockout mice have been powerful for elucidating the function of genes as well as a research model for human diseases. Gene targeting and gene trapping mathods have been the representative technologies for making the knockout mice by using ES cells. Since the gene targeting and the gene trapping methods were independently developed about 20 years ago, it's efficiency and productivity has been improved with a advance of molecular biology. Conventional gene targeting method has been changes to high throughput conditional gene targeting. The combination of the advantage of gene targeting and gene tapping elements allows to extend a spectrum of gene trapping and to improve the efficiency of gene targeting. These advance should be able to produce the mutant with various phenotype to target a certain gene, and in postgenome era they have served as crucial research tools in understanding the functional study of whole genome in mouse.

Synthesis and Characterization of the Tumor Targeting Mitoxantrone-Insulin Conjugate

  • Liu, Wen-Sheng;Yuan-Huang;Zhang, Zhi-Rong
    • Archives of Pharmacal Research
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    • v.26 no.11
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    • pp.892-897
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    • 2003
  • Anticancer drugs have serious side effects arising from their poor malignant cells selectivity, Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at $37^{\circ}C$ within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1 % of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 $\mu g \cdot$ h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 1l9 h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes ($TI^c$) no larger than 0.3 besides good tumor targeting efficiency with $TI^c$ of 1.67. The results suggest the feasibility to promote the curative effect in ca.ncer chemotherapy by using insulin as the vector of anti-cancer drugs.

Targeting of Nuclear Encoded Proteins to Chloroplasts: a New Insight into the Mechanism

  • Lee, Yong-Jik;Kim, Yong-Woo;Pih, Kyeong-Tae;Hwang, Inhwan
    • Korean Journal of Plant Tissue Culture
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    • v.27 no.5
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    • pp.407-409
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    • 2000
  • Outer envelope membrane proteins of chloroplasts encoded by the nuclear genome are transported without the N-terminal transit peptide. Here, we investigated the targeting mechanism of AtOEP7, an Arabidopsis homolog of small outer envelope membrane proteins in vivo. AtOEP7 was expressed transiently in protoplasts or stably in transgenic plants as fusion proteins with GFP. In both cases AtOEP7:GFP was targeted to the outer envelope membrane when assayed under a fluorescent microscope or by Western blot analysis. Except the transmembrane domain, deletions of the N- or C-terminal regions of AtOEP7 did not affect targeting although a region closed to the C-terminal side of the transmembrane domain affected the targeting efficiency. Targeting experiments with various hybrid transmembrane mutants revealed that the amino acid sequence of the transmembrane domain determines the targeting specificity The targeting mechanism was further studied using a fusion protein, AtOEP7:NLS:GFP, that had a nuclear localization signal. AtOEP7:NLS:GFP was efficiently targeted to the chloroplast envelope despite the presence of the nuclear localization signal. Taken together, these results suggest that the transmembrane domain of AtOEP7 functions as the sole determinant of targeting specificity and that AtOEP7 may be associated with a cytosolic component during translocation to the chloroplast envelope membrane.

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Effect of FTY-720 on Pulmonary Fibrosis in Mice via the TGF-β1 Signaling Pathway and Autophagy

  • Yuying Jin;Weidong Liu;Ge Gao;Yilan Song;Hanye Liu;Liangchang Li;Jiaxu Zhou;Guanghai Yan;Hong Cui
    • Biomolecules & Therapeutics
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    • v.31 no.4
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    • pp.434-445
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    • 2023
  • We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

Targeting of Large-molecule Radiopharmaceuticals across the Blood-brain Barrier Using Endogenous Transport Systems

  • Lee, Hwa-Jeong
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.94-95
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    • 2002
  • Drug targeting to the central nervous system (CNS) is the limiting factor in CNS drug development because most of drug do not cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB) in vivo. One strategy for drug targeting to the brain is to use endogenous BBB transport systems. (omitted)

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Preparation and stability of N-terminal PEGylated Recombinant Human Epidermal Growth Factor

  • Na, Dong-Hee;Youn, Yu-Seok;Park, Chong-Jeon;Lee, Sang-Deuk;Lee, Kang-Choon
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.415.3-416
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    • 2002
  • To improve the stability of recombinant human epidermal growth factor (rhEGF) as therapeutic agent. the N-terminal PEGylated rhEGF (N-PEG-rhEGF) was prepared by site-specific bioconjugation and the stability was investigated in rat skin wound homogenates. Two different N-PEG-rhGEFs (N-PEG5K- and N-PEG20K-rhEGF) were successfully prepared with the yields of above 70%. The PEGylation site was directly confirmed by determining the molecular mass of Lys-C digested samples using MALDI- TOF MS. (omitted)

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The role of lipid binding for the targeting of synaptic proteins into synaptic vesicles

  • Jang, Deok-Jin;Park, Soo-Won;Kaang, Bong-Kiun
    • BMB Reports
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    • v.42 no.1
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    • pp.1-5
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    • 2009
  • Synaptic vesicles (SVs) are key structures for synaptic transmission in neurons. Numerous membrane-associated proteins are sorted from the Golgi complex to the axon and the presynaptic terminal. Protein-protein and protein-lipid interactions are involved with SV targeting in neurons. Interestingly, many SV proteins have lipid binding capability, primarily with either cholesterol or phosphoinositides (PIs). As examples, the major SV protein synaptophysin can bind to cholesterol, a major lipid component in SVs, while several other SV proteins, including synaptotagmin, can bind to PIs. Thus, lipid-protein binding plays a key role for the SV targeting of synaptic proteins. In addition, numerous SV proteins can be palmitoylated. Palmitoylation is thought to be another synaptic targeting signal. Here, we briefly describe the relationship between lipid binding and SV targeting.

A Research of Targeting Technique for Dynamic Objects with Neural Network and Robocode (Neural Network와 Robocode를 이용한 동적 객체에 대한 Targeting 기법의 연구)

  • Kim, Jung-Hoon;Lee, Jee-Hyong
    • Proceedings of the Korean Information Science Society Conference
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    • 2006.10b
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    • pp.218-222
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    • 2006
  • 우수한 능력의 인공지능 개체로 구성된 게임은 그렇지 못한 게임에 비해 더 나은 흥미를 사용자에게 제공할 수 있다. 미국 Valve사의 Half-Life, Counter-Strike 및 한국 Dragonfly사의 Special-Force와 같은 실시간 FPS 전투게임에서 상대편에 대한 검색 및 목표 화하는(Targeting) 기법은 인공개체의 전투력에 중요한 하나의 요소이다. 하지만 이 같은 경우의Targeting은 정적인 대상에 대한 것이 아니라 동적인 대상에 대한 것이므로 단순한 산술 계산으로는 실용적인 효과를 내기 힘들다. 본 논문에서는 Neural Network를 이용한 학습기법을 사용하여 동적인 개체에 대한 효과적인 Targeting기법을 제안한다. 제안한 기법은 매 순간 변화하는 상황정보와 Virtual bullet이라는 가상 미사일 개념을 활용하여 학습 Data를 모델링한 후 Neural Network로 학습시켜 효과적인 Targeting이 가능하도록 구현하였다. 제안한 기법은 Java기반의 탱크전투 시뮬레이션 Framework인 Robocode에 적용하여 그 성능을 평가하였다. 제안된 기법으로 제작된 Robot(Crystal 1.0)은 ‘2006 Robocode Korea Cup에서 우승을 차지하였다.

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