• Title/Summary/Keyword: Signal

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PDZ Domain-containing Proteins at Autotypic Junctions in Myelinating Schwann Cells (수초화 슈반세포 autotypic 세포연접의 PDZ 도메인 보유 단백질)

  • Han, Seongjohn;Park, Hyeongbin;Hong, Soomin;Lee, Donghyun;Choi, Maro;Cho, Jeongmok;Urm, Sang-Hwa;Jang, Won Hee;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.25 no.1
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    • pp.101-112
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    • 2015
  • A type of cell junction that is formed between different parts within the same cell is called autotypic cell junction. Autotypic junction proteins form tight junctions found between membrane lamellae of a cell, especially in myelinating glial cells. Some of them have postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains, which interact with the carboxyl (C)-terminal PDZ-binding motif of other proteins. PDZ domains are protein-protein interaction modules that play a role in protein complex assembly. The PDZ domain, which is widespread in bacteria, plants, yeast, metazoans, and Drosophila, allows the assembly of large multi-protein complexes. The multi-protein complexes act in intracellular signal transduction, protein targeting, and membrane polarization. The identified PDZ domain-containing proteins located at autotypic junctions include zonula occludens-1 (ZO-1), ZO-2, pals-1-associated tight junction protein (PATJ), multi-PDZ domain proteins (MUPPs), membrane-associated guanylate kinase inverted 2 (MAGI2), and protease-activated receptor (PAR)-3. PAR-3 interacts with atypical protein kinase C and PAR-6, forming a ternary complex, which plays an important role in the regulation of cell polarity. MAGI2 interacts with ${\alpha}$-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptor at excitatory synapses. PATJ is detected in paranodal loops associated with claudin-1. On the other hand, MUPP1 is found in mesaxons and Schmidt-Lanterman incisures with claudin-5. ZO-1, ZO-2, and PAR-3 are found at all three sites. Different distributions of PDZ domain-containing proteins affect the development of autotypic junctions. In this review, we will describe PDZ domain-containing proteins at autotypic tight junctions in myelinating Schwann cells and their roles.

Clinical Findings of Phenylketonuria Patients in Korea (페닐케톤뇨증의 임상적 고찰)

  • Shin, Ik Soon;Lee, Dong Hwan
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.12 no.1
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    • pp.14-22
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    • 2012
  • Objectives: This study was performed to review clinical manifestations of hyperphenylalaninemia patients in Korean. Methods: 178 cases of hyperphenyalaninemia were diagnosed at department of pediatrics, Soonchunhyang University Hospital from January, 1983 to August. We reviewed DNA analysis, MR imaging, EEG, radiography of the left hand and wrist, bone densitometry (BMD), IQ test of hyperphenyalaninemia patients. Results: Out of 178 cases, 161 cases were diagnosed classic phenylketonuria and 17 cases were diagnosed BH4 deficiency. 122 cases performed DNA analysis. R243Q (10.3%), Y204C (9.9%), and IVS4-1G>A (8.1%) mutations were predominant. 22 cases underwent MR imaging. Varying degrees of symmetrical high signal intensity were noted on T2-weighted sequences in the periventricular deep white matter of 15 cases. 23 cases were performed EEG. 12 cases (52.3%) showed abnormal pattern. EEG abnormalities showed in 11 cases. On lumbar BMD four of 11 cases (36%) showed reduced bone density of more than 1 S.D. in four of 11 cases, bone age was less than chronological age by at least one year. 18 cases were performed IQ test. Mean IQ scores was $84{\pm}21.6$. Among older than 15 years (9 cases), Mean IQ scores was $72{\pm}21.2$. PTPS deficiency was 14 cases, DHPR deficiency was 2 cases, and GTPCH deficiency was 1 case. Conclusion: We confirmed there were varieties of DNA mutations. And MR imaging and EEG were nonspecific in PKU patients. Older children showed lower IQ score. Low phenylalanine diet prevents brain damage in PKU patient. Not only first few years of life but also lifetime, Keeping low phenylalanine diet is important.

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The Effect of Acetylcholine on the Intracellular $Ca^{2+}$ Increase of the Mouse Early 2-cell Embryos (생쥐 초기 2-세포 배의 세포내 칼슘 증가에 미치는 Acetylcholine의 영향)

  • Yoon S. Y.;Kang D. W.;Bae I. H.
    • Journal of Embryo Transfer
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    • v.20 no.3
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    • pp.191-200
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    • 2005
  • Many studies have shown that the development of mouse early 2-cell embryos in vitro is related with the intracellular $Ca^{2+}$ changes. In ICR strain mouse, the development of embryos arrests at early 2-cell stage, but the arrested early 2-cell embryos can be rescued by the addition of $Ca^{2+}$-related materials. Acetylcholine (ACh) increases intracellular $Ca^{2+}$ concentration ([$Ca^{2+}$]i) via the mAChR-PLC-IP3 pathway in mouse oocytes. We examined whether ACh rescues 2-cell block in mouse. In early 2-cell embryos, ACh increased [$Ca^{2+}$]i in a dose-dependent manner (p<0.001), and had an effect on rescue of 2-cell block and embryonic development. To identify the signal pathway involved in ACh-induced rescue of 2-cell block, we first applied an agonist of ACh receptor (AChR). Like ACh, carbachol increased intracellular $Ca^{2+}$ concentration ([$Ca^{2+}$]i) and atropine, an antagonist of ACh receptor, blocked the ACh-induced $Ca^{2+}$ increase. In $Ca^{2+}$-free medium, ACh also increased [$Ca^{2+}$]i, indicating that $Ca^{2+}$ increased by ACh is mainly released from the intracellular $Ca^{2+}$ store. The ACh-induced $Ca^{2+}$ increase was blocked by PLC inhibitor (U73122), ryanodine receptor (RyR) antagonist (dantrolene), and CaM KII inhibitor (KN-93), but not by IP3R antagonists (xestospongin C). These results show that ACh increases intracellular $Ca^{2+}$ concentration via mAChR/PLC/RyR, and this contributes to the rescue of 2-cell block.

Estimation of river discharge using satellite-derived flow signals and artificial neural network model: application to imjin river (Satellite-derived flow 시그널 및 인공신경망 모형을 활용한 임진강 유역 유출량 산정)

  • Li, Li;Kim, Hyunglok;Jun, Kyungsoo;Choi, Minha
    • Journal of Korea Water Resources Association
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    • v.49 no.7
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    • pp.589-597
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    • 2016
  • In this study, we investigated the use of satellite-derived flow (SDF) signals and a data-based model for the estimation of outflow for the river reach where in situ measurements are either completely unavailable or are difficult to access for hydraulic and hydrology analysis such as the upper basin of Imjin River. It has been demonstrated by many studies that the SDF signals can be used as the river width estimates and the correlation between SDF signals and river width is related to the shape of cross sections. To extract the nonlinear relationship between SDF signals and river outflow, Artificial Neural Network (ANN) model with SDF signals as its inputs were applied for the computation of flow discharge at Imjin Bridge located in Imjin River. 15 pixels were considered to extract SDF signals and Partial Mutual Information (PMI) algorithm was applied to identify the most relevant input variables among 150 candidate SDF signals (including 0~10 day lagged observations). The estimated discharges by ANN model were compared with the measured ones at Imjin Bridge gauging station and correlation coefficients of the training and validation were 0.86 and 0.72, respectively. It was found that if the 1 day previous discharge at Imjin bridge is considered as an input variable for ANN model, the correlation coefficients were improved to 0.90 and 0.83, respectively. Based on the results in this study, SDF signals along with some local measured data can play an useful role in river flow estimation and especially in flood forecasting for data-scarce regions as it can simulate the peak discharge and peak time of flood events with satisfactory accuracy.

Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

Development of a Small Gamma Camera Using NaI(T1)-Position Sensitive Photomultiplier Tube for Breast Imaging (NaI (T1) 섬광결정과 위치민감형 광전자증배관을 이용한 유방암 진단용 소형 감마카메라 개발)

  • Kim, Jong-Ho;Choi, Yong;Kwon, Hong-Seong;Kim, Hee-Joung;Kim, Sang-Eun;Choe, Yearn-Seong;Lee, Kyung-Han;Kim, Moon-Hae;Joo, Koan-Sik;Kim, Byuug-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.4
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    • pp.365-373
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    • 1998
  • Purpose: The conventional gamma camera is not ideal for scintimammography because of its large detector size (${\sim}500mm$ in width) causing high cost and low image quality. We are developing a small gamma camera dedicated for breast imaging. Materials and Methods: The small gamma camera system consists of a NaI (T1) crystal ($60 mm{\times}60 mm{\times}6 mm$) coupled with a Hamamatsu R3941 Position Sensitive Photomultiplier Tube (PSPMT), a resister chain circuit, preamplifiers, nuclear instrument modules, an analog to digital converter and a personal computer for control and display. The PSPMT was read out using a standard resistive charge division which multiplexes the 34 cross wire anode channels into 4 signals ($X^+,\;X^-,\;Y^+,\;Y^-$). Those signals were individually amplified by four preamplifiers and then, shaped and amplified by amplifiers. The signals were discriminated ana digitized via triggering signal and used to localize the position of an event by applying the Anger logic. Results: The intrinsic sensitivity of the system was approximately 8,000 counts/sec/${\mu}Ci$. High quality flood and hole mask images were obtained. Breast phantom containing $2{\sim}7 mm$ diameter spheres was successfully imaged with a parallel hole collimator The image displayed accurate size and activity distribution over the imaging field of view Conclusion: We have succesfully developed a small gamma camera using NaI(T1)-PSPMT and nuclear Instrument modules. The small gamma camera developed in this study might improve the diagnostic accuracy of scintimammography by optimally imaging the breast.

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Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression with Radiolabeled 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in liver by Hydrodynamic-based Procedure (Hydrodynamic-based Procedure를 이용한 간에서의 HSV1-tk 발현 확인을 위한 방사표지 5-(2-iodovinyl)-2'-deoxyuridine (IVDU)의 영상연구)

  • Song, In-Ho;Lee, Tae-Sup;Kang, Joo-Hyun;Lee, Yong-Jin;Kim, Kwang-Il;An, Gwang-Il;Chung, Wee-Sup;Cheon, Gi-Jeong;Choi, Chang-Woon;Lim, Sang-Moo
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.5
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    • pp.468-477
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    • 2009
  • Purpose: Hydrodynamic-based procedure is a simple and effective gene delivery method to lead a high gene expression in liver tissue. Non-invasive imaging reporter gene system has been used widely with herpes simplex virus type 1 thymidine kinase (HSV1-tk) and its various substrates. In the present study, we investigated to image the expression of HSV1-tk gene with 5-(2-iodovinyD-2'-deoxyuridine (IVDU) in mouse liver by the hydrodynamicbased procedure. Materials and Methods: HSV1-tk or enhanced green fluorescence protein (EGFP) encoded plasmid DNA was transferred into the mouse liver by hydrodynaminc injection. At 24 h post-injection, RT-PCR, biodistribution, fluorescence imaging, nuclear imaging and digital wholebody autoradiography (DWBA) were performed to confirm transferred gene expression. Results: In RT-PCR assay using mRNA from the mouse liver, specific bands of HSV1-tk and EGFP gene were observed in HSV1-tk and EGFP expressing plasmid injected mouse, respectively. Higher uptake of radiolabeled IVDU was exhibited in liver of HSV1-tk gene transferred mouse by biodistribution study. In fluorescence imaging, the liver showed specific fluorescence signal in EGFP gene transferred mouse. Gamma-camera image and DWBA results showed that radiolabeled IVDU was accumulated in the liver of HSV1-tk gene transferred mouse. Conclusion: In this study, hydrodynamic-based procedure was effective in liver-specific gene delivery and it could be quantified with molecular imaging methods. Therefore, co-expression of HSV1-tk reporter gene and target gene by hydrodynamic-based procedure is expected to be a useful method for the evaluation of the target gene expression level with radiolabeled IVDU.

Effect of the Dose Reduction Applied Low Dose for PET/CT According to CT Attenuation Correction Method (PET/CT 저선량 적용 시 CT 감쇠보정법에 따른 피폭선량 저감효과)

  • Jung, Seung Woo;Kim, Hong Kyun;Kwon, Jae Beom;Park, Sung Wook;Kim, Myeong Jun;Sin, Yeong Man;Kim, Yeong Heon
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.127-133
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    • 2014
  • Purpose: Low dose of PET/CT is important because of Patient's X-ray exposure. The aim of this study was to evaluate the effectiveness of low-dose PET/ CT image through the CTAC and QAC of patient study and phantom study. Materials and Methods: We used the discovery 710 PET/CT (GE). We used the NEMA IEC body phantom for evaluating the PET data corrected by ultra-low dose CT attenuation correction method and NU2-94 phantom for uniformity. After injection of 70.78 MBq and 22.2 MBq of 18 F-FDG were done to each of phantom, PET/CT scans were obtained. PET data were reconstructed by using of CTAC of which dose was for the diagnosis CT and Q. AC of which was only for attenuation correction. Quantitative analysis was performed by use of horizontal profile and vertical profile. Reference data which were corrected by CTAC were compared to PET data which was corrected by the ultra-low dose. The relative error was assessed. Patients with over weighted and normal weight also underwent a PET/CT scans according to low dose protocol and standard dose protocol. Relative error and signal to noise ratio of SUV were analyzed. Results: In the results of phantom test, phantom PET data were corrected by CTAC and Q.AC and they were compared each other. The relative error of Q.AC profile was been calculated, and it was shown in graph. In patient studies, PET data for overweight patient and normal weight patient were reconstructed by CTAC and Q.AC under routine dose and ultra-low dose. When routine dose was used, the relative error was small. When high dose was used, the result of overweight patient was effectively corrected by Q.AC. Conclusion: In phantom study, CTAC method with 80 kVp and 10 mA was resulted in bead hardening artifact. PET data corrected by ultra- low dose CTAC was not quantified, but those by the same dose were quantified properly. In patients' cases, PET data of over weighted patient could be quantified by Q.AC method. Its relative difference was not significant. Q.AC method was proper attenuation correction method when ultra-low dose was used. As a result, it is expected that Q.AC is a good method in order to reduce patient's exposure dose.

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Abosrbed Dose Measurements and Phantom Image Ecaluation at Minimum CT Dose for Pediatric SPECT/CT Scan (소아 SPECT/CT 검사를 위한 최저조건에서의 피폭선량측정 및 팬텀의 영상평가)

  • Park, Chan Rok;Choi, Jin Wook;Cho, Seong Wook;Kim, Jin Eui
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.82-88
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    • 2014
  • Purpose: The purpose of study was to evaluate radiation dose for pediatric patients by changing tube voltage (kVp) and tube current (mA) at minimum conditions. By evaluating radiation dose, we want to provide dose reduction for pediatric patients and maintain good quality of SPECT/CT images. Materials and Methods: Discovery NM/CT 670 Scanne was used as SPECT/CT. Tube voltages are 80 and 100 kvP. Tube currents are 10, 15, 20, 25 mA. Using PMMA (Polymethyl methacrylate) Phantom, radiation dose which were calculated at center and peripheral dose and SNRD (Signal to Noise Ratio Dose) were evaluated. Using the CT performance phantom, spatial resolution was evaluated as the MTF (Modulation Transfer Function) graph. Jaszczak phantom was used for SPECT image evaluation by CNR (Contrast to Noise to Ratio). Results: Radiation dose using the PMMA phantom was higher peripheral dose than center dose about 7%. SNRD were 7.8, 8.2, 8.3, 8.8, 8.8, 9.9, 9.8, 9.6 for 80 kVp 10, 15, 20, 25 mA, 100 kVp 10, 15, 20, 25 mA. We can distinguish 35, 45, 70, 71, 52, 58, 90, 110 linepair for 80 kVp 10, 15, 20, 25 mA, 100 kVp 10, 15, 20, 25 mA at resolution with MTF. CNR of SPECT images using CT attenuation map were 57.8, 57.7, 57.1, 56.7, 56.6, 56.7, 56.7, 56.7% for 80 kVp 10, 15, 20, 25 mA, 100 kVp 10, 15, 20, 25 mA. Conclusion: In this study, radiation dose for pediatric patients showed decreased low dose condition. And SNRD value was similar in all condition. Resolution showed higher value at 100kVp than 80kVp. for CNR, there was no significant difference. we should take additional study to prove better quality and dose reduction.

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Regional Characteristics of Global Warming: Linear Projection for the Timing of Unprecedented Climate (지구온난화의 지역적 특성: 전례 없는 기후 시기에 대한 선형 전망)

  • SHIN, HO-JEONG;JANG, CHAN JOO
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.21 no.2
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    • pp.49-57
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    • 2016
  • Even if an external forcing that will drive a climate change is given uniformly over the globe, the corresponding climate change and the feedbacks by the climate system differ by region. Thus the detection of global warming signal has been made on a regional scale as well as on a global average against the internal variabilities and other noises involved in the climate change. The purpose of this study is to estimate a timing of unprecedented climate due to global warming and to analyze the regional differences in the estimated results. For this purpose, unlike previous studies that used climate simulation data, we used an observational dataset to estimate a magnitude of internal variability and a future temperature change. We calculated a linear trend in surface temperature using a historical temperature record from 1880 to 2014 and a magnitude of internal variability as the largest temperature displacement from the linear trend. A timing of unprecedented climate was defined as the first year when a predicted minimum temperature exceeds the maximum temperature record in a historical data and remains as such since then. Presumed that the linear trend and the maximum displacement will be maintained in the future, an unprecedented climate over the land would come within 200 years from now in the western area of Africa, the low latitudes including India and the southern part of Arabian Peninsula in Eurasia, the high latitudes including Greenland and the mid-western part of Canada in North America, the low latitudes including Amazon in South America, the areas surrounding the Ross Sea in Antarctica, and parts of East Asia including Korean Peninsula. On the other hand, an unprecedented climate would come later after 400 years in the high latitudes of Eurasia including the northern Europe, the middle and southern parts of North America including the U.S.A. and Mexico. For the ocean, an unprecedented climate would come within 200 years over the Indian Ocean, the middle latitudes of the North Atlantic and the South Atlantic, parts of the Southern Ocean, the Antarctic Ross Sea, and parts of the Arctic Sea. In the meantime, an unprecedented climate would come even after thousands of years over some other regions of ocean including the eastern tropical Pacific and the North Pacific middle latitudes where an internal variability is large. In summary, spatial pattern in timing of unprecedented climate are different for each continent. For the ocean, it is highly affected by large internal variability except for the high-latitude regions with a significant warming trend. As such, a timing of an unprecedented climate would not be uniform over the globe but considerably different by region. Our results suggest that it is necessary to consider an internal variability as well as a regional warming rate when planning a climate change mitigation and adaption policy.