• Title/Summary/Keyword: molecular models

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Effects of Gas-surface Interaction Models on Spacecraft Aerodynamics

  • Khlopkov, Yuri Ivanovich;Chernyshev, Sergey Leonidovich;Myint, Zay Yar Myo;Khlopkov, Anton Yurievich
    • International Journal of Aeronautical and Space Sciences
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    • v.17 no.1
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    • pp.1-7
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    • 2016
  • The influence of boundary condition of the bodies with gas flows is one of the most important problems in high-altitude aerodynamics. In this paper presents the results of the calculation of aerodynamic characteristics of aerospace vehicle using Monte-Carlo method based on three different gas-surface interaction models - Maxwell model, Cercignani-Lampis-Lord (CLL) model and Lennard-Jones (LJ) potential. These models are very sensitive for force and moment coefficients of aerospace vehicle in the hypersonic free molecular flow. The models, method and results can be used for new generation aerospace vehicle design.

The Need for the Development of Pig Brain Tumor Disease Model using Genetic Engineering Techniques (유전자 조작기법을 통한 돼지 뇌종양 질환모델 개발의 필요성)

  • Hwang, Seon-Ung;Hyun, Sang-Hwan
    • Journal of Embryo Transfer
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    • v.31 no.1
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    • pp.97-107
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    • 2016
  • Although many diseases could be treated by the development of modern medicine, there are some incurable diseases including brain cancer, Alzheimer disease, etc. To study human brain cancer, various animal models were reported. Among these animal models, mouse models are valuable tools for understanding brain cancer characteristics. In spite of many mouse brain cancer models, it has been difficult to find a new target molecule for the treatment of brain cancer. One of the reasons is absence of large animal model which makes conducting preclinical trials. In this article, we review a recent study of molecular characteristics of human brain cancer, their genetic mutation and comparative analysis of the mouse brain cancer model. Finally, we suggest the need for development of large animal models using somatic cell nuclear transfer in translational research.

Mobilization of Photosystem II-Light Harvesting Complex II Supercomplexes during High Light Illumination and State Transitions

  • Nath, Krishna;Elizabeth, John;Poudyal, Roshan Sharma;Ko, Su Yeon;Lim, Woon Ki;Lee, Choon-Hwan
    • Rapid Communication in Photoscience
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    • v.2 no.1
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    • pp.18-23
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    • 2013
  • The photosystem II (PSII) light harvesting complex (LHC) consists of a variety of pigment protein complexes which are involved in structural organization and regulation of photosynthetic unit. These LHC proteins encoded by a group of Lhcb genes are essential for the structural integrity of PSII supercomplex, the channeling the excitation energy to the reaction center of PSII and its redistribution to photosystem I by state transitions. Numerous studies with the help of recent technological advancements have enabled a significant progress in our understanding on the structure of PSII-LHCII supercomplexes and their mobilization under various light conditions. Here, we present a mini-review on the latest concepts and models depicting the structure of PSII-LHCII supercomplexes and the role of Lhcb proteins in their supra-molecular organization. Also we will review on the current understandings and remaining problems involved in the mobilization of the supercomplexes during state transitions and during high light illumination for controlling light energy distribution between the two photosystems.

Evaluation of Therapeutic Efficacy using [18F]FP-CIT in 6-OHDA-induced Parkinson's Animal Model

  • Jang Woo Park;Yi Seul Choi;Dong Hyun Kim;Eun Sang Lee;Chan Woo Park;Hye Kyung Chung;Ran Ji Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.3-8
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    • 2023
  • Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.

Transcriptome Analysis of the Striatum of Electroacupuncture-treated Naïve and Ischemic Stroke Mice

  • Hong Ju Lee;Hwa Kyoung Shin;Ji-Hwan Kim;Byung Tae Choi
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.162-171
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    • 2024
  • Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

Nuclear Medicine Imaging Instrumentations for Molecular Imaging (분자영상 획득을 위한 핵의학 영상기기)

  • Chung, Yong-Hyun;Song, Tae-Yong;Choi, Yong
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.131-139
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    • 2004
  • Small animal models are extensively utilized in the study of biomedical sciences. Current animal experiments and analysis are largely restricted to in vitro measurements and need to sacrifice animals to perform tissue or molecular analysis. This prevents researchers from observing in vivo the natural evolution of the process under study. Imaging techniques can provide repeatedly in vivo anatomic and molecular information noninvasively. Small animal imaging systems have been developed to assess biological process in experimental animals and increasingly employed in the field of molecular imaging studies. This review outlines the current developments in nuclear medicine imaging instrumentations including fused multi-modality imaging systems for small animal imaging.

MicroSPECT and MicroPET Imaging of Small Animals for Drug Development

  • Jang, Beom-Su
    • Toxicological Research
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    • v.29 no.1
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    • pp.1-6
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    • 2013
  • The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

Quantitative Structure-Activity Relationships and Molecular Docking Studies of P56 LCK Inhibitors

  • Bharatham, Nagakumar;Bharatham, Kavitha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.27 no.2
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    • pp.266-272
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    • 2006
  • Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.

Synthesis of a squaric acid-derived molecular probe for near-infrared fluorescence and photoacoustic imaging

  • Jung Eun Park;Yong Dae Park;Jongho Jeon
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.6 no.2
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    • pp.177-181
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    • 2020
  • Dual-modality imaging strategy using near-infrared fluorescence (FLI) and photoacoustic imaging (PAI) demands a suitable probe to enable dual-modular signal production. Herein, we demonstrate a synthetic protocol of small molecular dye for dual-modular FLI and PAI. A condensation reaction between squaric acid and carboxypentyl benzoindolium, and followed by basic hydrolysis to give the benzoindole derived squaraine (BSQ) dye in 49% yield. Next, the carboxylic acid group of BSQ was further functionalized with N-hydroxysuccinimide or azide group for an efficient conjugation with a targeting biomolecule. BSQ showed a maximum fluorescent emission at around 680 nm and the photoacoustic signal reached a maximum intensity at 680-700 nm. Based on these results, we conclude that BSQ analogs will be useful probes for dual-modular (FLI/PAI) imaging studies in animal models.

QM and Pharmacophore based 3D-QSAR of MK886 Analogues against mPGES-1

  • Pasha, F.A.;Muddassar, M.;Jung, Hwan-Won;Yang, Beom-Seok;Lee, Cheol-Ju;Oh, Jung-Soo;Cho, Seung-Joo;Cho, Hoon
    • Bulletin of the Korean Chemical Society
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    • v.29 no.3
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    • pp.647-655
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    • 2008
  • Microsomal prostaglandin E2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q2 = 0.77, r2 = 0.97 and Rtestset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q2 = 0.90, r2 = 0.99. CoMSIA; q2 = 0.93, r2 = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity.