Water quality forecasting can provide useful information for public health protection and support... more Water quality forecasting can provide useful information for public health protection and support water resources management. In order to forecast water quality more accurately, this paper proposes a novel hybrid model combining real-time data decomposition, fuzzy C-means clustering and bidirectional gated recurrent unit. Firstly, the original water quality data is decomposed into several subseries by empirical wavelet transform, and then, the decomposed subseries are recombined by fuzzy C-means clustering. Next, for each clustered series, bidirectional gated recurrent unit is applied to develop prediction model. Finally, the forecast result is obtained by the summation of the predictions for the subseries. The proposed forecast model is evaluated by the water quality data of Poyang Lake, China. Results show that the proposed forecast model provides highly accurate forecast result for all of the six water quality data: the average of MAPE of the forecast results for the six water quality datasets is 4.59% for 7 day ahead prediction. Furthermore, our model shows better forecast performance than the other models. Particularly, compared with the single BiGRU model, MAPE decreased by 32.86% in average. Results demonstrate that the proposed forecast model can be used effectively for water quality forecasting.
In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of P... more In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-γ (IFN-γ) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-γ treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-γ-mediated repression of T cell activation in vitro and enhances the anti-tumor activity of anti-PD-1 antibody in vivo when used in combination. Finally, transcriptomic analyses indicated that AX-0085 is highly specific in targeting the IFN-γ-pathway, thereby raising the possibility of applying this reagent in combination therapy with checkpoint inhibitor antibodies. It may be particularly relevant in cases in which PD-L1-mediated T cell exhaustion leads to immunoevasive phenotypes.
Hee Jung Lim1, Jusong Kim1, Chang-Hwan Park2, Sang A Lee3, Man Ryul Lee3, KyeSeong Kim2, Jaesang ... more Hee Jung Lim1, Jusong Kim1, Chang-Hwan Park2, Sang A Lee3, Man Ryul Lee3, KyeSeong Kim2, Jaesang Kim1, and Yun Soo Bae1 1Department of Life Sciences, Ewha Womans University, Seoul 120-750, Korea 2Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University, Seoul 133-791, Korea, 3Soonchunhyang Institute of Medi-bioscience, Soon Chun Hyang University, Cheonan, Korea
Reactive oxygen species (ROS) play important roles as second messengers in a wide array of cellul... more Reactive oxygen species (ROS) play important roles as second messengers in a wide array of cellular processes including differentiation of stem cells. We identified Nox4 as the major ROS-generating enzyme whose expression is induced during differentiation of embryoid body (EB) into cells of all three germ layers. The role of Nox4 was examined using induced pluripotent stem cells (iPSCs) generated from Nox4 knockout (Nox4−/−) mouse. Differentiation markers showed significantly reduced expression levels consistent with the importance of Nox4-generated ROS during this process. From transcriptomic analyses, we found insulin-like growth factor 2 (IGF2), a member of a gene family extensively involved in embryonic development, as one of the most down-regulated genes in Nox4−/− cells. Indeed, addition of IGF2 to culture partly restored the differentiation competence of Nox4−/− iPSCs. Our results reveal an important signaling axis mediated by ROS in control of crucial events during different...
Accurate forecasting of air pollutant concentration is of great importance since it is an essenti... more Accurate forecasting of air pollutant concentration is of great importance since it is an essential part of the early warning system. However, it still remains a challenge due to the limited information of emission source and high uncertainties of the dynamic processes. In order to improve the accuracy of air pollutant concentration forecast, this study proposes a novel hybrid model using clustering, feature selection, real-time decomposition by empirical wavelet transform, and deep learning neural network. First, all air pollutant time series are decomposed by empirical wavelet transform based on real-time decomposition, and subsets of output data are constructed by combining corresponding decomposed components. Second, each subset of output data is classified into several clusters by clustering algorithm, and then appropriate inputs are selected by feature selection method. Third, a deep learning-based predictor, which uses three dimensional convolutional neural network and bidirectional long short-term memory neural network, is applied to predict decomposition components of each cluster. Last, air pollutant concentration forecast for each monitoring station is obtained by reconstructing predicted values of all the decomposition components. PM2.5 concentration data of Beijing, China is used to validate and test our model. Results show that the proposed model outperforms other models used in this study. In our model, mean absolute percentage error for 1, 6, 10 h ahead PM2.5 concentration prediction is 4.03%, 6.87%, and 8.98%, respectively. These outcomes demonstrate that the proposed hybrid model is a powerful tool to provide highly accurate forecast for air pollutant concentration.
International Journal of Radiation Oncology*Biology*Physics, 2016
tumor histologies, data for gynecologic neoplasms is limited, often grouping patients with gyneco... more tumor histologies, data for gynecologic neoplasms is limited, often grouping patients with gynecologic primaries with multiple other histologies. Here we aim to exclusively study gynecologic histologies and, in doing so, provide a more focused characterization of their outcomes in the metastatic disease setting. Materials/Methods: A retrospective analysis was conducted of patients with metastatic gynecologic neoplasms whose lesions were first managed via site-directed radiotherapies at our institution between 2002 and 2014. Among the criteria for inclusion were pathologically confirmed neoplastic disease, pathologic (preferred) or radiologic evidence of Stage IV/M1 disease, limited metastatic burden of disease, and follow up imaging after the completion of radiation therapy to assess for control of disease and survival. Results: Twenty-nine patients met inclusion criteria, ranging from 42 to 85 years old at treatment onset, with a total of 34 lesions studied over a median follow up time of 13 months after treatment. Of these, 19 were endometrial in origin while 11 were ovarian. Major tumor histologies included adenocarcinoma (21), sarcoma (6), and squamous cell carcinoma (5). Prior to developing Stage IV disease, lesions were often treated definitively with surgery (32), chemotherapy (31), and/or external beam radiation therapy (22). Metachronous metastatic disease was most often first observed in the lungs (11), brain (10) and liver (7) with initial treatment mainly reliant on stereotactic techniques: SBRT (17) and SRS (9). A median biologically effective dose of 48 Gy (range: 11-132) was calculated using an alpha/beta ratio of ten. Median overall survival (OS), local control (LC), and time to distant failure (DF) were 18 (range: 1-141), 8 (range: 0-63), and 5 (range: 1-95) months, respectively, from the time of completing the initial course of radiation therapy. Distant failures most commonly involved the lung (18), liver (6), and brain (5). Histologyspecific parameters, the impact of definitive and adjuvant treatments prior to Stage IV diagnosis as well as subsequent to these initial radiotherapeutic interventions will also be presented. Conclusion: These results provide a glimpse into the benefits expected in managing gynecologic neoplastic disease with limited metastases and may help guide future studies or management of patients with advanced gynecologic malignancies.
We report that phytosphingosine, a sphingolipid found in many organisms and implicated in cellula... more We report that phytosphingosine, a sphingolipid found in many organisms and implicated in cellular signaling, promotes megakaryocytic differentiation of myeloid leukemia cells. Specifically, phytosphingosine induced several hallmark changes associated with megakaryopoiesis from K562 and HEL cells including cell cycle arrest, cell size increase and polyploidization. We also confirmed that cell type specific markers of megakaryocytes, CD41a and CD42b are induced by phytosphingosine. Phospholipids with highly similar structures were unable to induce similar changes, indicating that the activity of phytosphingosine is highly specific. Although phytosphingosine is known to activate p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis, the signaling mechanisms involved in megakaryopoiesis appear to be distinct. In sum, we present another model for dissecting molecular details of megakaryocytic differentiation which in large part remains obscure. [BMB Reports 2015; 48(12): 691-695]
We have previously reported that Ahnak-mediated TGFb signaling leads to down-regulation of c-Myc ... more We have previously reported that Ahnak-mediated TGFb signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak-/- MEF) show an increased level of c-Myc expression compared to wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2 and Klf4 (hereafter 3F) was significantly enhanced in Ahnak-/- MEF. Similar results were obtained when Ahnak-specific siRNA was applied to wild type MEF. Of note, expression of Ahnak was significantly induced during the formation of embryoid bodies (EB) from embryonic stem (ES) cells suggesting that Ahnak-mediated c-Myc inhibition is involved in EB formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak-/- MEF cells (Ahnak-/--iPSC-3...
To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and ove... more To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox re...
Journal of Tissue Engineering and Regenerative Medicine, 2012
In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl ph... more In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34 + haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia.
Water quality forecasting can provide useful information for public health protection and support... more Water quality forecasting can provide useful information for public health protection and support water resources management. In order to forecast water quality more accurately, this paper proposes a novel hybrid model combining real-time data decomposition, fuzzy C-means clustering and bidirectional gated recurrent unit. Firstly, the original water quality data is decomposed into several subseries by empirical wavelet transform, and then, the decomposed subseries are recombined by fuzzy C-means clustering. Next, for each clustered series, bidirectional gated recurrent unit is applied to develop prediction model. Finally, the forecast result is obtained by the summation of the predictions for the subseries. The proposed forecast model is evaluated by the water quality data of Poyang Lake, China. Results show that the proposed forecast model provides highly accurate forecast result for all of the six water quality data: the average of MAPE of the forecast results for the six water quality datasets is 4.59% for 7 day ahead prediction. Furthermore, our model shows better forecast performance than the other models. Particularly, compared with the single BiGRU model, MAPE decreased by 32.86% in average. Results demonstrate that the proposed forecast model can be used effectively for water quality forecasting.
In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of P... more In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-γ (IFN-γ) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-γ treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-γ-mediated repression of T cell activation in vitro and enhances the anti-tumor activity of anti-PD-1 antibody in vivo when used in combination. Finally, transcriptomic analyses indicated that AX-0085 is highly specific in targeting the IFN-γ-pathway, thereby raising the possibility of applying this reagent in combination therapy with checkpoint inhibitor antibodies. It may be particularly relevant in cases in which PD-L1-mediated T cell exhaustion leads to immunoevasive phenotypes.
Hee Jung Lim1, Jusong Kim1, Chang-Hwan Park2, Sang A Lee3, Man Ryul Lee3, KyeSeong Kim2, Jaesang ... more Hee Jung Lim1, Jusong Kim1, Chang-Hwan Park2, Sang A Lee3, Man Ryul Lee3, KyeSeong Kim2, Jaesang Kim1, and Yun Soo Bae1 1Department of Life Sciences, Ewha Womans University, Seoul 120-750, Korea 2Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University, Seoul 133-791, Korea, 3Soonchunhyang Institute of Medi-bioscience, Soon Chun Hyang University, Cheonan, Korea
Reactive oxygen species (ROS) play important roles as second messengers in a wide array of cellul... more Reactive oxygen species (ROS) play important roles as second messengers in a wide array of cellular processes including differentiation of stem cells. We identified Nox4 as the major ROS-generating enzyme whose expression is induced during differentiation of embryoid body (EB) into cells of all three germ layers. The role of Nox4 was examined using induced pluripotent stem cells (iPSCs) generated from Nox4 knockout (Nox4−/−) mouse. Differentiation markers showed significantly reduced expression levels consistent with the importance of Nox4-generated ROS during this process. From transcriptomic analyses, we found insulin-like growth factor 2 (IGF2), a member of a gene family extensively involved in embryonic development, as one of the most down-regulated genes in Nox4−/− cells. Indeed, addition of IGF2 to culture partly restored the differentiation competence of Nox4−/− iPSCs. Our results reveal an important signaling axis mediated by ROS in control of crucial events during different...
Accurate forecasting of air pollutant concentration is of great importance since it is an essenti... more Accurate forecasting of air pollutant concentration is of great importance since it is an essential part of the early warning system. However, it still remains a challenge due to the limited information of emission source and high uncertainties of the dynamic processes. In order to improve the accuracy of air pollutant concentration forecast, this study proposes a novel hybrid model using clustering, feature selection, real-time decomposition by empirical wavelet transform, and deep learning neural network. First, all air pollutant time series are decomposed by empirical wavelet transform based on real-time decomposition, and subsets of output data are constructed by combining corresponding decomposed components. Second, each subset of output data is classified into several clusters by clustering algorithm, and then appropriate inputs are selected by feature selection method. Third, a deep learning-based predictor, which uses three dimensional convolutional neural network and bidirectional long short-term memory neural network, is applied to predict decomposition components of each cluster. Last, air pollutant concentration forecast for each monitoring station is obtained by reconstructing predicted values of all the decomposition components. PM2.5 concentration data of Beijing, China is used to validate and test our model. Results show that the proposed model outperforms other models used in this study. In our model, mean absolute percentage error for 1, 6, 10 h ahead PM2.5 concentration prediction is 4.03%, 6.87%, and 8.98%, respectively. These outcomes demonstrate that the proposed hybrid model is a powerful tool to provide highly accurate forecast for air pollutant concentration.
International Journal of Radiation Oncology*Biology*Physics, 2016
tumor histologies, data for gynecologic neoplasms is limited, often grouping patients with gyneco... more tumor histologies, data for gynecologic neoplasms is limited, often grouping patients with gynecologic primaries with multiple other histologies. Here we aim to exclusively study gynecologic histologies and, in doing so, provide a more focused characterization of their outcomes in the metastatic disease setting. Materials/Methods: A retrospective analysis was conducted of patients with metastatic gynecologic neoplasms whose lesions were first managed via site-directed radiotherapies at our institution between 2002 and 2014. Among the criteria for inclusion were pathologically confirmed neoplastic disease, pathologic (preferred) or radiologic evidence of Stage IV/M1 disease, limited metastatic burden of disease, and follow up imaging after the completion of radiation therapy to assess for control of disease and survival. Results: Twenty-nine patients met inclusion criteria, ranging from 42 to 85 years old at treatment onset, with a total of 34 lesions studied over a median follow up time of 13 months after treatment. Of these, 19 were endometrial in origin while 11 were ovarian. Major tumor histologies included adenocarcinoma (21), sarcoma (6), and squamous cell carcinoma (5). Prior to developing Stage IV disease, lesions were often treated definitively with surgery (32), chemotherapy (31), and/or external beam radiation therapy (22). Metachronous metastatic disease was most often first observed in the lungs (11), brain (10) and liver (7) with initial treatment mainly reliant on stereotactic techniques: SBRT (17) and SRS (9). A median biologically effective dose of 48 Gy (range: 11-132) was calculated using an alpha/beta ratio of ten. Median overall survival (OS), local control (LC), and time to distant failure (DF) were 18 (range: 1-141), 8 (range: 0-63), and 5 (range: 1-95) months, respectively, from the time of completing the initial course of radiation therapy. Distant failures most commonly involved the lung (18), liver (6), and brain (5). Histologyspecific parameters, the impact of definitive and adjuvant treatments prior to Stage IV diagnosis as well as subsequent to these initial radiotherapeutic interventions will also be presented. Conclusion: These results provide a glimpse into the benefits expected in managing gynecologic neoplastic disease with limited metastases and may help guide future studies or management of patients with advanced gynecologic malignancies.
We report that phytosphingosine, a sphingolipid found in many organisms and implicated in cellula... more We report that phytosphingosine, a sphingolipid found in many organisms and implicated in cellular signaling, promotes megakaryocytic differentiation of myeloid leukemia cells. Specifically, phytosphingosine induced several hallmark changes associated with megakaryopoiesis from K562 and HEL cells including cell cycle arrest, cell size increase and polyploidization. We also confirmed that cell type specific markers of megakaryocytes, CD41a and CD42b are induced by phytosphingosine. Phospholipids with highly similar structures were unable to induce similar changes, indicating that the activity of phytosphingosine is highly specific. Although phytosphingosine is known to activate p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis, the signaling mechanisms involved in megakaryopoiesis appear to be distinct. In sum, we present another model for dissecting molecular details of megakaryocytic differentiation which in large part remains obscure. [BMB Reports 2015; 48(12): 691-695]
We have previously reported that Ahnak-mediated TGFb signaling leads to down-regulation of c-Myc ... more We have previously reported that Ahnak-mediated TGFb signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak-/- MEF) show an increased level of c-Myc expression compared to wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2 and Klf4 (hereafter 3F) was significantly enhanced in Ahnak-/- MEF. Similar results were obtained when Ahnak-specific siRNA was applied to wild type MEF. Of note, expression of Ahnak was significantly induced during the formation of embryoid bodies (EB) from embryonic stem (ES) cells suggesting that Ahnak-mediated c-Myc inhibition is involved in EB formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak-/- MEF cells (Ahnak-/--iPSC-3...
To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and ove... more To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox re...
Journal of Tissue Engineering and Regenerative Medicine, 2012
In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl ph... more In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34 + haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia.
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