• Title/Summary/Keyword: Action Target 3

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Candidacidal Effects of Rev (11-20) Derived from HIV-1 Rev Protein

  • Lee, Juneyoung;Lee, Dong Hwan;Lee, Dong Gun
    • Molecules and Cells
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    • v.28 no.4
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    • pp.403-406
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    • 2009
  • Rev is an essential regulatory protein for HIV-1 replication. Rev (11-20) is known as the significant region regarding the function of a nuclear entry inhibitory signal (NIS) of Rev. In this study, anticandidal effects and mechanism of action of Rev (11-20) were investigated. The result exhibited that Rev (11-20) contained candidacidal activities. To understand target site(s) of Rev (11-20), the intracellular localization of the peptide was investigated. The result showed that Rev (11-20) rapidly accumulated in the fungal cell surface. The cell wall regeneration test also indicated that Rev (11-20) exerted its anticandidal activity to fungal plasma membrane rather than cell wall. The fluorescent study using 1,6-diphenyl-1,3,5-hexatriene (DPH) further confirmed the membrane-disruption mechanism(s) of Rev (11-20). The present study suggests that Rev (11-20) possesses significant potential regarding therapeutic agents for treating fungal diseases caused by Candida species in humans.

DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia

  • Kwon, Yong Sam;Son, Miwon
    • Biomolecules & Therapeutics
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    • v.21 no.3
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    • pp.181-189
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    • 2013
  • Motilitone$^{(R)}$ (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profile of DA-9701 is also preferable to that of other treatments.

ROV Manipulation from Observation and Exploration using Deep Reinforcement Learning

  • Jadhav, Yashashree Rajendra;Moon, Yong Seon
    • Journal of Advanced Research in Ocean Engineering
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    • v.3 no.3
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    • pp.136-148
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    • 2017
  • The paper presents dual arm ROV manipulation using deep reinforcement learning. The purpose of this underwater manipulator is to investigate and excavate natural resources in ocean, finding lost aircraft blackboxes and for performing other extremely dangerous tasks without endangering humans. This research work emphasizes on a self-learning approach using Deep Reinforcement Learning (DRL). DRL technique allows ROV to learn the policy of performing manipulation task directly, from raw image data. Our proposed architecture maps the visual inputs (images) to control actions (output) and get reward after each action, which allows an agent to learn manipulation skill through trial and error method. We have trained our network in simulation. The raw images and rewards are directly provided by our simple Lua simulator. Our simulator achieve accuracy by considering underwater dynamic environmental conditions. Major goal of this research is to provide a smart self-learning way to achieve manipulation in highly dynamic underwater environment. The results showed that a dual robotic arm trained for a 3DOF movement successfully achieved target reaching task in a 2D space by considering real environmental factor.

Action Mechanism of S-23142 on the PPIX Biosynthesis System of Spinacia oleracea L. Chloroplast (엽록체내 Protoporphyrin IX(PPIX) 생합성계에서 S-23142의 작용기구)

  • Kim, T.J.;Kim, J.S.;Cho, K.Y.;Yoshida, S.
    • Korean Journal of Weed Science
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    • v.14 no.1
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    • pp.1-7
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    • 1994
  • The effects of S-23142{N-(4-chloro-2-fluoro-5-propargyloxyphenyl)-3, 4, 5, 6-tetrahydrophtalimide}, on protoporphyrin IX(PPIX) biosynthesis in Spinacia oleracea L, leaf in vivo and in vitro condition were investigated by reversed-phase HPLC with fluorescence detector. The stroma and the membrane fraction of spinach chloroplast were isolated by osmotic regulation. The conversion of ${\delta}$-aminolevulinic acid(ALA) to PPIX occured more in the stroma than in the membrane fraction. It suggested that the enzymes that catalyse PPIX biosynthesis from ALA were localized in the stroma. Also, the synthesized PPIX content from ALA was completely inhibited by $10^{-8}M$ of S-23412 or $10^{-7}M$ of acifluorfen in the stroma but not in the membrane fractions. Therefore, these results suggested that the target site of S-23142 and acifluorfen may exist in the stroma fraction of spinach chloroplast.

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Condurango (Gonolobus condurango) Extract Activates Fas Receptor and Depolarizes Mitochondrial Membrane Potential to Induce ROS-dependent Apoptosis in Cancer Cells in vitro -CE-treatment on HeLa: a ROS-dependent mechanism-

  • Bishayee, Kausik;Mondal, Jesmin;Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.18 no.3
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    • pp.32-41
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    • 2015
  • Objectives: Condurango (Gonolobus condurango) extract is used by complementary and alternative medicine (CAM) practitioners as a traditional medicine, including homeopathy, mainly for the treatment of syphilis. Condurango bark extract is also known to reduce tumor volume, but the underlying molecular mechanisms still remain unclear. Methods: Using a cervical cancer cell line (HeLa) as our model, the molecular events behind condurango extract's (CE's) anticancer effect were investigated by using flow cytometry, immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Other included cell types were prostate cancer cells (PC3), transformed liver cells (WRL-68), and peripheral blood mononuclear cells (PBMCs). Results: Condurango extract (CE) was found to be cytotoxic against target cells, and this was significantly deactivated in the presence of N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), suggesting that its action could be mediated through ROS generation. CE caused an increase in the HeLa cell population containing deoxyribonucleic acid (DNA) damage at the G zero/Growth 1 (G0/G1) stage. Further, CE increased the tumor necrosis factor alpha ($TNF-{\alpha}$) and the fas receptor (FasR) levels both at the ribonucleic acid (RNA) and the protein levels, indicating that CE might have a cytotoxic mechanism of action. CE also triggered a sharp decrease in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) both at the RNA and the protein levels, a possible route to attenuation of B-cell lymphoma 2 (Bcl-2), and caused an opening of the mitochondrial membrane's permeability transition (MPT) pores, thus enhancing caspase activities. Conclusion: Overall, our results suggest possible pathways for CE mediated cytotoxicity in model cancer cells.

Identification of Alkylation-Sensitive Target Chaperone Proteins and Their Reactivity with Natural Products Containing Michael Acceptor

  • Liu, Xi-Wen;Sok, Dai-Eun
    • Archives of Pharmacal Research
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    • v.26 no.12
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    • pp.1047-1054
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    • 2003
  • Molecular chaperones have a crucial role in the folding of nascent polypeptides in endoplasmic reticulum. Some of them are known to be sensitive to the modification by electrophilic metabolites of organic pro-toxicants. In order to identify chaperone proteins sensitive to alkyators, ER extract was subjected to alkylation by 4-acetamido-4 -maleimidyl-stilbene-2,2 -disulfonate (AMS), and subsequent SDS-PAGE analyses. Protein spots, with molecular mass of 160, 100, 57 and 36 kDa, were found to be sensitive to AMS alkylation, and one abundant chaperon protein was identified to be protein disulfide isomerase (PDI) in comparison with the purified PDI. To see the reactivity of PDI with cysteine alkylators, the reduced form ($PDI_{red}$) of PDI was incubated with various alkylators containing Michael acceptor structure for 30 min at $38^{\circ}C$ at pH 6.3, and the remaining activity was determined by the insulin reduction assay. Iodoacetamide or N-ethylmaleimide at 0.1 mM remarkably inactivated $PDI_{red}$ with N-ethylmaleimide being more potent than iodoacetamide. A partial inactivation of $PDI_{oxid}$ was expressed by iodoacetamide, but not N-ethylmaleimide (NEM) at pH 6.3. Of Michael acceptor compounds tested, 1,4-benzoquinone ($IC_{50}, 15 \mu$ M) was the most potent, followed by 4-hydroxy-2-nonenal and 1,4-naphthoquinone. In contrast, 1,2-naphthoquinone, devoid of a remarkable inactivation action, was effective to cause the oxidative conversion of $PDI_{red}$ to $PDI_{oxid}$. Thus, the action of Michael acceptor compounds differed greatly depending on their structure. Based on these, it is proposed that POI, one of chaperone proteins in ER, could be susceptible to endogenous or xenobiotic Michael acceptor compounds in vivo system.

An Action Convergence Research to Improve Evaluation Index of Pneumonia Adequacy in Regional Public Hospital (지역거점 공공병원의 폐렴 적정성 평가 지표 개선을 위한 융복합 실행연구)

  • Eun Young Choi;Yoen-Im Park;Seung-Ju, Kang;Ja-Ok Kim
    • Journal of Digital Convergence
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    • v.21 no.1
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    • pp.19-27
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    • 2023
  • This is an implementation study towards the development of a strategy to improve the pneumonia adequacy evaluation index of regional public hospital and to confirm its effectiveness. One physician, eight nurses, one computer room staff, and one nursing professor working at a regional base public hospital located in N city participated in this study from March to October 2021. An implementation study was conducted based on the conceptual model of Zuber-Skerritt & Fletcher. The stages of planning, implementation, evaluation, and reflection were operated in two cycles, and the effectiveness was evaluated in the second and third quarters. Compared to the pneumonia adequacy evaluation index in 2019, all indicators reached 100% of the standard target in 2021. The results of this study therefore infer that to provide higher quality medical services in the future, it is necessary to apply medical quality improvement activities through practical research under multidisciplinary participation and cooperation and to review the applicability of clinical sites.

Comparison of Three Different Helmet Bolus Device for Total Scalp Irradiation (Total Scalp의 방사선 치료 시 Helmet Bolus 제작방법에 관한 연구)

  • Song, Yong-Min;Kim, Jong-Sik;Hong, Chae-Seon;Ju, Sang-Gyu;Park, Ju-Young;Park, Su-Yeon
    • The Journal of Korean Society for Radiation Therapy
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    • v.24 no.1
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    • pp.31-37
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    • 2012
  • Purpose: This study evaluated the usefulness of Helmet bolus device using Bolx-II, paraffin wax, solid thermoplastic material in total scalp irradiation. Materials and Methods: Using Rando phantom, we applied Bolx-II (Action Products, USA), paraffin wax (Densply, USA), solid thermoplastic material (Med-Tec, USA) on the whole scalp to make helmet bolus device. Computed tomography (GE, Ultra Light Speed16) images were acquired at 5 mm thickness. Then, we set up the optimum treatment plan and analyzed the variation in density of each bolus (Philips, Pinnacle). To evaluate the dose distribution, Dose-homogeneity index (DHI, $D_{90}/D_{10}$) and Conformity index (CI, $V_{95}/TV$) of Clinical Target Volume (CTV) using Dose-Volume Histogram (DVH) and $V_{20}$, $V_{30}$ of normal brain tissues. we assessed the efficiency of production process by measuring total time taken to produce. Thermoluminescent dosimeters (TLD) were used to verify the accuracy. Results: Density variation value of Bolx-II, paraffin wax, solid thermoplastic material turned out to be $0.952{\pm}0.13g/cm^3$, $0.842{\pm}0.17g/cm^3$, $0.908{\pm}0.24g/cm^3$, respectively. The DHI and CI of each helmet bolus device which used Bolx-II, paraffin wax, solid thermoplastic material were 0.89, 0.85, 0.77 and 0.86, 0.78, 0.74, respectively. The result of Bolx-II was the best. $V_{20}$ and $V_{30}$ of brain tissues were 11.50%, 10.80%, 10.07% and 7.62%, 7.40%, 7.31%, respectively. It took 30, 120, 90 minutes to produce. The measured TLD results were within ${\pm}7%$ of the planned values. Conclusion: The application of helmet bolus which used Bolx-II during total scalp irradiation not only improves homogeneity and conformity of Clinical Target Volume but also takes short time and the production method is simple. Thus, the helmet bolus which used Bolx-II is considered to be useful for the clinical trials.

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A Descriptive Research on Field Situation of Customized Modification for Vulnerable Single Elderly Home (사회취약 독거노인 주택의 맞춤형 개조 현장상황 기술 연구)

  • Lee, Yeun-Sook;Kim, Yun-Soo;Sung, Cho-Hee;Shin, Yoo-Jin;Cho, Won-Seob
    • Journal of the Korean housing association
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    • v.28 no.3
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    • pp.55-64
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    • 2017
  • Elderly population has increased rapidly and adjusting the environment is in demand to support their health. To improve the living environment of elderly, an appropriate plan for customized home modification is needed upon the personal contexts. The purpose of this study is to explain the sequence and to build an insight on customized home modification for vulnerable single elderly. It is a case study based on single target that includes 6 months of execution period deeply seeking the appropriate plan for implementation. The target is a male elderly aged 74 living in a single story detached house. The various research methods are applied in this study including exploratory, participatory, action and trade-off preference researches. The result shows that plan for home modification is complex outcome of interlocking uniqueness between residence environment and resident situation. If customized modification is targeted for residentially vulnerable social group, more sensitive approach aiming for the highest result is required due to financial constraint. To conclude, comprehensive understanding of overall circumstances of a dwelling, a resident and various stakeholder is essential throughout the process. Since the aging-in-place of elderly cannot be achieved without self-sustaining living environment, customized home modification should be a tool to meet housing suitability. It is important to strengthen the experts and future workforce with networks of local residents to share opinions and appropriate plans.

Anti-diabetic Effect and Mechanism of Korean Red Ginseng in C57BL/KsJ db/db Mice

  • Yuan, Hai-Dan;Shin, Eun-Jung;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.32 no.3
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    • pp.187-193
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    • 2008
  • The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.