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      • KCI등재

        김정은 체제 외교정책변화의 결정요인 분석: 대북제재와 국내정치 동학

        조현용 ( Jo Hyun-yong ),정기원 ( Jung Key-one ),김용호 ( Kim Yong-ho ) 국방대학교 안보문제연구소 2019 국방연구 Vol.62 No.4

        이 글은 2018년 정상회담을 계기로 나타난 김정은 외교정책 변화의 결정요인을 분석하고 있다. 보다 구체적으로 북한 외교정책의 변화를 대내외 변화에 대한 정치적 동학을 통해 규명함으로써 북한의 대내정치 과정에서 파생되는 정치변수들에 대한 분석 역시 한반도 비핵화를 둘러싼 국제정치적 동학 못지않게 중요한 작용을 하고 있음을 주장하고 있다. 독재체제의 정권유지와 경제발전에 대한 정치경제이론을 적용하여 이념 중립적 시각에서 정책변화의 동인을 추적하였으며 기존연구들이 간과해 온 국제환경과 국내정치 간의 상호작용 동학에 의한 변화라는 대안적 분석틀을 제시했다. 이 과정을 통해 도출된 외교정책변화의 핵심변수는 대외요인으로 ‘자원권력’, 국내정치요인으로 지도자의 ‘정치적 생존’과 ‘정치체제’로 나타났다. 김정은 정권의 외교정책변화는 경제제재에 의한 북중무역의 붕괴로 촉발된 것으로 분석되며, 내부적으로 지배연합에 대한 통제력 강화, 군부의 정치 영향력 축소, 제도적으로 당-국가체제 확립을 통한 국내정치적 필요라는 변수가 작용한 것으로 분석됐다. The article analyzes the determinants of North Korean foreign policy in the wake of the 2018 summit. The paper argues that his new foreign policy initiative was motivated by his perceived shortage in his co-optation resources resulted from Chinese active participation on international sanction. In particular, Chinese participation in the ban of coal export triggered his policy changes because North Korea’s export of coal has served as the key source of North Korea’s co-optation resource to maintain Kim’s political survival. In so doing, the paper focuses on the interaction between international environment and domestic politics, which previous studies have overlooked. This paper also identifies key variables of North Korea’s foreign policy changes, “resource power” as external factors, and the leader's “political survival” as domestic variable.

      • SCISCIESCOPUS

        Rhythmic Serotonin N-Acetyltransferase mRNA Degradation Is Essential for the Maintenance of Its Circadian Oscillation

        Kim, Tae-Don,Kim, Jong-So,Kim, Jong Heon,Myung, Jihwan,Chae, Hee-Don,Woo, Kyung-Chul,Jang, Sung Key,Koh, Duk-Su,Kim, Kyong-Tai American Society for Microbiology 2005 Molecular and cellular biology Vol.25 No.8

        <B>ABSTRACT</B><P>Serotonin <I>N</I>-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) is the key enzyme in melatonin synthesis regulated by circadian rhythm. To date, our understanding of the oscillatory mechanism of melatonin has been limited to autoregulatory transcriptional and posttranslational regulations of AANAT mRNA. In this study, we identify three proteins from pineal glands that associate with <I>cis</I>-acting elements within species-specific AANAT 3′ untranslated regions to mediate mRNA degradation. These proteins include heterogeneous nuclear ribonucleoprotein R (hnRNP R), hnRNP Q, and hnRNP L. Their RNA-destabilizing function was determined by RNA interference and overexpression approaches. Expression patterns of these factors in pineal glands display robust circadian rhythm. The enhanced levels detected after midnight correlate with an abrupt decline in AANAT mRNA level. A mathematical model for the AANAT mRNA profile and its experimental evidence with rat pinealocytes indicates that rhythmic AANAT mRNA degradation mediated by hnRNP R, hnRNP Q, and hnRNP L is a key process in the regulation of its circadian oscillation.</P>

      • KCI등재

        Suppression of Lipopolysaccharide-Induced Microglial Activation by a Benzothiazole Derivative

        Kim, Eun-A,Kim, Han-Wook,Ahn, Jee-Yin,Hahn, Hoh-Gyu,Kim, Key-Sun,Kim, Tae-Ue,Cho, Sung-Woo Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.1

        We previously reported that KHG21834, a benzothiazole derivative, attenuates the beta-amyloid (A${\beta}$)-induced degeneration of both cortical and mesencephalic neurons in vitro. Central nervous system inflammation mediated by activated microglia is a key event in the development of neurodegenerative disease. In this study, we show that KHG21834 suppresses inflammation-mediated cytokine upregulation. Specifically, KHG21834 induces significant reductions in the lipopolysaccharide-induced activation of microglia and production of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interlukin-1${\beta}$, nitric oxide, and inducible nitric oxide synthase. In addition, KHG21834 blocks the expression of mitogen-activated protein kinases, including ERK, p38 MAPK, JNK, and Akt. In vivo intracerebroventricular infusion of KHG21834 also leads to decreases the level of interleukin-1${\beta}$ and tumor necrosis factor-${\alpha}$ in brain. These results, in combination with our previous findings on A${\beta}$-induced degeneration, support the potential therapeutic efficacy of KHG21834 for the treatment of neurodegenerative disorders via the targeting of key glial activation pathways.

      • KCI등재
      • KCI등재
      • KCI등재

        Development of the Korean Developmental Screening Test for Infants and Children (K-DST)

        Chung, Hee Jung,Yang, Donghwa,Kim, Gun-Ha,Kim, Sung Koo,Kim, Seoung Woo,Kim, Young Key,Kim, Young Ah,Kim, Joon Sik,Kim, Jin Kyung,Kim, Cheongtag,Sung, In-Kyung,Shin, Son Moon,Oh, Kyung Ja,Yoo, Hee-Jeo The Korean Pediatric Society 2020 Clinical and Experimental Pediatrics (CEP) Vol.63 No.11

        Background: Most developmental screening tools in Korea are adopted from foreign tests. To ensure efficient screening of infants and children in Korea, a nationwide screening tool with high reliability and validity is needed. Purpose: This study aimed to independently develop, standardize, and validate the Korean Developmental Screening Test for Infants and Children (K-DST) for screening infants and children for neurodevelopmental disorders in Korea. Methods: The standardization and validation conducted in 2012-2014 of 3,284 subjects (4-71 months of age) resulted in the first edition of the K-DST. The restandardization and revalidation performed in 2015-2016 of 3.06 million attendees of the National Health Screening Program for Infants and Children resulted in the revised K-DST. We analyzed inter-item consistency and test-retest reliability for the reliability analysis. Regarding the validation of K-DST, we examined the construct validity, sensitivity and specificity, receiver operating characteristic curve analysis, and a criterion-related validity analysis. Results: We ultimately selected 8 questions in 6 developmental domains. For most age groups and each domain, internal consistency was 0.73-0.93 and test-retest reliability was 0.77-0.88. The revised K-DST had high discriminatory ability with a sensitivity of 0.833 and specificity of 0.979. The test supported construct validity by distinguishing between normal and neurodevelopmentally delayed groups. The language and cognition domain of the revised K-DST was highly correlated with the K-Bayley Scales of Infant Development-II's Mental Age Quotient (r=0.766, 0.739), while the gross and fine motor domains were highly correlated with Motor Age Quotient (r=0.695, 0.668), respectively. The Verbal Intelligence Quotient of Korean Wechsler Preschool and Primary Scales of Intelligence was highly correlated with the K-DST cognition and language domains (r=0.701, 0.770), as was the performance intelligence quotient with the fine motor domain (r=0.700). Conclusion: The K-DST is reliable and valid, suggesting its good potential as an effective screening tool for infants and children with neurodevelopmental disorders in Korea.

      • Direct Observation of Cooperative Protein Structural Dynamics of Homodimeric Hemoglobin from 100 ps to 10 ms with Pump–Probe X-ray Solution Scattering

        Kim, Kyung Hwan,Muniyappan, Srinivasan,Oang, Key Young,Kim, Jong Goo,Nozawa, Shunsuke,Sato, Tokushi,Koshihara, Shin-ya,Henning, Robert,Kosheleva, Irina,Ki, Hosung,Kim, Youngmin,Kim, Tae Wu,Kim, Jeongh American Chemical Society 2012 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.134 No.16

        <P/><P>Proteins serve as molecular machines in performing their biological functions, but the detailed structural transitions are difficult to observe in their native aqueous environments in real time. For example, despite extensive studies, the solution-phase structures of the intermediates along the allosteric pathways for the transitions between the relaxed (R) and tense (T) forms have been elusive. In this work, we employed picosecond X-ray solution scattering and novel structural analysis to track the details of the structural dynamics of wild-type homodimeric hemoglobin (HbI) from the clam <I>Scapharca inaequivalvis</I> and its F97Y mutant over a wide time range from 100 ps to 56.2 ms. From kinetic analysis of the measured time-resolved X-ray solution scattering data, we identified three structurally distinct intermediates (I<SUB>1</SUB>, I<SUB>2</SUB>, and I<SUB>3</SUB>) and their kinetic pathways common for both the wild type and the mutant. The data revealed that the singly liganded and unliganded forms of each intermediate share the same structure, providing direct evidence that the ligand photolysis of only a single subunit induces the same structural change as the complete photolysis of both subunits does. In addition, by applying novel structural analysis to the scattering data, we elucidated the detailed structural changes in the protein, including changes in the heme–heme distance, the quaternary rotation angle of subunits, and interfacial water gain/loss. The earliest, R-like I<SUB>1</SUB> intermediate is generated within 100 ps and transforms to the R-like I<SUB>2</SUB> intermediate with a time constant of 3.2 ± 0.2 ns. Subsequently, the late, T-like I<SUB>3</SUB> intermediate is formed via subunit rotation, a decrease in the heme–heme distance, and substantial gain of interfacial water and exhibits ligation-dependent formation kinetics with time constants of 730 ± 120 ns for the fully photolyzed form and 5.6 ± 0.8 μs for the partially photolyzed form. For the mutant, the overall kinetics are accelerated, and the formation of the T-like I<SUB>3</SUB> intermediate involves interfacial water loss (instead of water entry) and lacks the contraction of the heme–heme distance, thus underscoring the dramatic effect of the F97Y mutation. The ability to keep track of the detailed movements of the protein in aqueous solution in real time provides new insights into the protein structural dynamics.</P>

      • SCISCIESCOPUS

        Regulation of pyruvate kinase isozyme M2 is mediated by the ubiquitin-specific protease 20

        KIM, SO-RA,KIM, JIN-OCK,LIM, KEY-HWAN,YUN, JI-HYUN,HAN, INBO,BAEK, KWANG-HYUN Spandidos Publications 2015 International journal of oncology Vol.46 No.5

        <P>USP20, one of deubiquitinating enzymes (DUBs) belonging to the subfamily of ubiquitin-specific protease (USP), regulates ubiquitin-mediated protein degradation. So far, USP20 has been identified as a binding protein and a regulator of hypoxia-inducible factor (HIF)-1α, β-adrenergic receptor, and tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). In order to investigate other biological functions of USP20 with its novel substrates, we searched for putative substrates through two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. We found several putative substrates, some of which are related to cancer metabolism or neural disorders. Among these, the pyruvate kinase isoenzyme M2 (PKM2) had a high identity score. Most cancer cells contain a specific metabolic pathway, referred to as the Warburg effect. One well-known function of PKM2 is a main regulator in cancer metabolic pathways, and PKM2 promotes the Warburg effect and tumor growth. In addition, both PKM2 and HIF-1α upregulate the expression of target genes. From this evidence, it is expected that USP20 would be associated with the metabolic pathway through the regulation of PKM2 ubiquitination. Despite various roles of DUBs, the biological functions of USP20 in cellular mechanisms are poorly understood. Herein, we investigated the inter-action between PKM2 and USP20. Our results suggest a new molecular pathway in cancer metabolism through the regulation of PKM2.</P>

      • SCISCIESCOPUS

        In Vivo Evaluation of Angiogenic Activity and Its Correlation with Efficacy of Indirect Revascularization Surgery in Pediatric Moyamoya Disease

        Kim, Yong-il,Phi, Ji Hoon,Paeng, Jin Chul,Choi, Hongyoon,Kim, Seung-Ki,Lee, Yun-Sang,Kang, Keon Wook,Lee, Ji Yeoun,Jeong, Jae Min,Chung, June-Key,Lee, Dong Soo,Wang, Kyu-Chang Society of Nuclear Medicine 2014 The Journal of nuclear medicine Vol.55 No.9

        <P>Indirect revascularization is the most widely used treatment to induce angiogenesis in pediatric moyamoya disease (MMD). Molecular imaging methods targeted for angiogenesis have recently been developed. We performed angiogenesis imaging in indirect revascularization surgery for MMD to evaluate angiogenic activity and its correlation with treatment efficacy. <B>Methods:</B> Twelve patients with pediatric MMD were prospectively enrolled. Encephaloduroarteriosynangiosis surgery was conducted, and <SUP>68</SUP>Ga-Arg-Gly-Asp (RGD) PET was performed 3.7 ± 1.0 mo after surgery. Basal perfusion and stress perfusion (P<SUB>Str</SUB>) in the middle cerebral artery territory were evaluated by acetazolamide-stress brain perfusion SPECT using statistical probabilistic anatomic mapping, at preoperative, early postoperative, and long-term follow-up states. Angiogenic activity was assessed on the images in terms of maximal uptake ratio, volume of increased uptake, and uptake-volume product. <B>Results:</B> Basal perfusion and P<SUB>Str</SUB> were significantly improved after surgery. Increased angiogenic activity was observed in the revascularized area, mainly around the bony flap. Angiogenic activity gradually decreased with time and significantly correlated with the postoperative time interval (<I>P</I> = 0.0015 for maximal uptake ratio and 0.0069 for volume of increased uptake). It was estimated to normalize at 6.3 mo after surgery. Uptake-volume product was inversely correlated with P<SUB>Str</SUB> improvement at the early postoperative state (<I>r</I> = −0.5960, <I>P</I> = 0.0409) and also weakly correlated with P<SUB>Str</SUB> improvement at long-term follow-up (<I>r</I> = −0.5010, <I>P</I> = 0.1165). <B>Conclusion:</B> Angiogenesis PET imaging with <SUP>68</SUP>Ga-RGD was successfully used for the assessment of angiogenic activity in indirect revascularization surgery for MMD, and angiogenic activation measured at approximately 3.7 mo after surgery was inversely correlated with perfusion improvement. The assessment of angiogenic activity using <SUP>68</SUP>Ga-RGD PET is expected to be effective for evaluating the mechanism or efficacy of revascularization treatment.</P>

      • Total lesion glycolysis as the best 18F-FDG PET/CT parameter in differentiating intermediate–high risk adrenal incidentaloma

        Kim, Yong-il,Cheon, Gi Jeong,Paeng, Jin Chul,Cho, Jeong Yeon,Kang, Keon Wook,Chung, June-Key,Kim, Euishin Edmund,Lee, Dong Soo Wolters Kluwer Health | Lippincott Williams Wilkin 2014 Nuclear medicine communications Vol.35 No.6

        OBJECTIVE: Characterization of intermediate–high risk adrenal incidentaloma (AI) is important because biopsy or surgery should be performed to confirm the malignancy. We investigated which parameters of F-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) had an additive role in distinguishing malignancies in patients with incidental adrenal masses of intermediate–high risk. METHODS: From January 2008 to July 2013, 52 patients with a pathologically proven diagnosis of AI were retrospectively enrolled (age=56.4±12.7 years, M : F=34 : 18; benign : malignant=14 : 38). Volumetric parameters were size and volume according to combined CT, and metabolic parameters were peak standardized uptake value (SUVpeak), maximum SUV (SUVmax), mean SUV (SUVmean), and tumor-to-background ratio (SUVmax of adrenal mass/SUVmean of liver). Metabolovolumetric parameters of metabolic tumor volume and total lesion glycolysis (TLG, SUVmean×metabolic tumor volume) were also included and compared with the diagnostic value. In addition, the highest diagnostic parameters among volumetric and metabolic parameters were combined and compared in terms of diagnostic accuracy. RESULTS: Compared with benign adrenal adenoma, malignant lesions showed significantly higher values of all F-FDG PET/CT volumetric, metabolic, and metabolovolumetric parameters. Size showed the highest area under the curve (AUC) of 0.759 among the volumetric parameters, and SUVpeak showed the highest AUC of 0.853 among the metabolic parameters. Among all the PET/CT parameters, TLG showed the highest AUC of 0.900, with a sensitivity of 92.1% and specificity of 78.6% at a cutoff of 12.0. The combined value of size and SUVpeak showed lower diagnostic value than TLG. CONCLUSION: We found that TLG showed the best result in distinguishing intermediate–high risk AI among PET/CT parameters. TLG can be a useful PET/CT parameter for differential diagnosis of AI.

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