33 results on '"So Young Kwon"'
Search Results
2. Editorial : Lymphatic system: organ specific functions in health and disease
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Koltowska, Kaska, Jakus, Zoltán, Hong, Young-Kwon, Kume, Tsutomu, Koltowska, Kaska, Jakus, Zoltán, Hong, Young-Kwon, and Kume, Tsutomu
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- 2023
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3. ABC-stacked multilayer graphene in holography
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Seo, Jeong-Won, Yuk, Taewon, Han, Young-Kwon, Sin, Sang-Jin, Seo, Jeong-Won, Yuk, Taewon, Han, Young-Kwon, and Sin, Sang-Jin
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A flat band can be studied an infinitely strong coupling, realized in a simple system. Therefore, its holographic realization should be interesting. Laia and Tong gave a realization of the flat band over the entire momentum region by introducing a particular boundary term. Here, we give a model with a flat band over a finite region of momentum space using a bulk interaction term instead of the boundary term. We find that the spectrum of our model is precisely analogous to that of the ABC stacked multilayer graphene. In the presence of the chemical potential, the flat band is bent in our holographic model, which is very close to the band deformation due to the spin-orbit
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- 2022
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4. Holographic Lieb lattice and gapping its Dirac band
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Han, Young-Kwon, Seo, Jeong-Won, Yuk, Taewon, Sin, Sang-Jin, Han, Young-Kwon, Seo, Jeong-Won, Yuk, Taewon, and Sin, Sang-Jin
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We first point out that the Laia-Tong model realizes the Lieb lattice in the holographic setup. It generates a flat band of sharp particle spectrum together with a Dirac band of unparticle spectrum. We then construct a model which opens a gap to the Dirac band so that one can realize a well-separated flat band, which can play the role of the hydrogen atom of strongly correlated systems. We then study the phase transition between the gapped and gapless phases analytically. We also made methodological progress to find a few other quantizations and we express the Green functions in any quantization in terms of that in the standard quantization., Comment: arXiv admin note: text overlap with arXiv:2012.04279 by other authors
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- 2022
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5. Subconjunctival Lymphatics Respond to VEGFC and Anti-Metabolites in Rabbit and Mouse Eyes.
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Lee, Jong Yeon, Lee, Jong Yeon, Wu, Jingyi, Liu, Yameng, Saraswathy, Sindhu, Zhou, Longfang, Bu, Qianwen, Su, Ying, Choi, Dongwon, Park, Eunkyung, Strohmaier, Clemens A, Weinreb, Robert N, Hong, Young-Kwon, Pan, Xiaojing, Huang, Alex S, Lee, Jong Yeon, Lee, Jong Yeon, Wu, Jingyi, Liu, Yameng, Saraswathy, Sindhu, Zhou, Longfang, Bu, Qianwen, Su, Ying, Choi, Dongwon, Park, Eunkyung, Strohmaier, Clemens A, Weinreb, Robert N, Hong, Young-Kwon, Pan, Xiaojing, and Huang, Alex S
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PurposeTo characterize and pharmacologically influence subconjunctival lymphatics in rabbit and mouse eyes.MethodsRabbits received subconjunctival injections of trypan blue or fixable fluorescent dextrans. Bleb-related outflow pathways were quantified. Immunofluorescence for vessel-specific markers (lymphatics [podoplanin and LYVE-1] and blood vessels [CD31]) were performed in native rabbit conjunctiva and after fixable fluorescent dextran injection. Vascular endothelial cell growth factor-C (VEGFC) was injected subconjunctivally in rabbits. mRNA and protein were assessed for the above markers using RT-PCR and Western blot. Alternatively, mouse studies used Prox1-tdTomato transgenic reporter mice. Subconjunctival injection conditions included: no injection, balanced salt solution (BSS), VEGFC, 5-fluorouracil (5FU) and two concentrations of mitomycin-C (MMC). Two mouse injection protocols (short and long) with different follow-up times and number of injections were performed. Mouse eyes were enucleated, flat mounts created, and subconjunctival branching and length assessed.ResultsRabbit eyes demonstrated clear bleb-related subconjunctival outflow pathways that were distinct from blood vessels and were without nasal/temporal predilection. Immunofluorescence against vessel-specific markers showed lymphatics and blood vessels in rabbit conjunctiva, and these lymphatics overlapped with bleb-related subconjunctival outflow pathways. Subconjunctival VEGFC increased lymphatic (P = 0.004-0.04) but not blood vessel (P = 0.77-0.84) mRNA or protein in rabbits. Prox1-tdTomato transgenic reporter mice demonstrated natively fluorescent lymphatics. Subconjunctival VEGFC increased murine lymphatic branching and length (P ≤ 0.001-0.004) while antimetabolites (P ≤ 0.001-0.043) did the opposite for the long protocol.DiscussionSubconjunctival lymphatics are pharmacologically responsive to both VEGFC and antimetabolites in two animal models studied using different methodologies. These re
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- 2022
6. Microalgal-based biochar in wastewater remediation: its synthesis, characterization and applications
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Law, Xin Ni, Cheah, Wai Yan, Chew, Kit Wayne, Ibrahim, Mohamad Faizal, Park, Young Kwon, Ho, Shih Hsin, Show, Pau Loke, Law, Xin Ni, Cheah, Wai Yan, Chew, Kit Wayne, Ibrahim, Mohamad Faizal, Park, Young Kwon, Ho, Shih Hsin, and Show, Pau Loke
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Microalgae are drawing attentions among researchers for their biorefinery use or value-added products. The high production rate of biomasses produced are attractive for conversion into volatile biochar. Torrefaction, pyrolysis and hydrothermal carbonization are the recommended thermochemical conversion techniques that could produce microalgal-based biochar with desirable physiochemical properties such as high surface area and pore volume, abundant surface functional groups, as well as functionality such as high adsorption capacity. The characterizations of the biochar significantly influence the mechanisms in adsorption of pollutants from wastewaters. Specific adsorption of the organic and inorganic pollutants from the effluent are reviewed to examine the adsorption capacity and efficiency of biochar derived from different microalgae species. Last but not least, future remarks over the challenges and improvements are discussed accordingly. Overall, this review would discuss the synthesis, characterization and application of the microalgal-based biochar in wastewater.
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- 2022
7. Microalgal-based biochar in wastewater remediation: its synthesis, characterization and applications
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Law, Xin Ni, Cheah, Wai Yan, Chew, Kit Wayne, Ibrahim, Mohamad Faizal, Park, Young Kwon, Ho, Shih Hsin, Show, Pau Loke, Law, Xin Ni, Cheah, Wai Yan, Chew, Kit Wayne, Ibrahim, Mohamad Faizal, Park, Young Kwon, Ho, Shih Hsin, and Show, Pau Loke
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Microalgae are drawing attentions among researchers for their biorefinery use or value-added products. The high production rate of biomasses produced are attractive for conversion into volatile biochar. Torrefaction, pyrolysis and hydrothermal carbonization are the recommended thermochemical conversion techniques that could produce microalgal-based biochar with desirable physiochemical properties such as high surface area and pore volume, abundant surface functional groups, as well as functionality such as high adsorption capacity. The characterizations of the biochar significantly influence the mechanisms in adsorption of pollutants from wastewaters. Specific adsorption of the organic and inorganic pollutants from the effluent are reviewed to examine the adsorption capacity and efficiency of biochar derived from different microalgae species. Last but not least, future remarks over the challenges and improvements are discussed accordingly. Overall, this review would discuss the synthesis, characterization and application of the microalgal-based biochar in wastewater.
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- 2022
8. Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.
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Choi, Dongwon, Choi, Dongwon, Park, Eunkyung, Yu, Roy P, Cooper, Michael N, Cho, Il-Taeg, Choi, Joshua, Yu, James, Zhao, Luping, Yum, Ji-Eun Irene, Yu, Jin Suh, Nakashima, Brandon, Lee, Sunju, Seong, Young Jin, Jiao, Wan, Koh, Chester J, Baluk, Peter, McDonald, Donald M, Saraswathy, Sindhu, Lee, Jong Y, Jeon, Noo Li, Zhang, Zhenqian, Huang, Alex S, Zhou, Bin, Wong, Alex K, Hong, Young-Kwon, Choi, Dongwon, Choi, Dongwon, Park, Eunkyung, Yu, Roy P, Cooper, Michael N, Cho, Il-Taeg, Choi, Joshua, Yu, James, Zhao, Luping, Yum, Ji-Eun Irene, Yu, Jin Suh, Nakashima, Brandon, Lee, Sunju, Seong, Young Jin, Jiao, Wan, Koh, Chester J, Baluk, Peter, McDonald, Donald M, Saraswathy, Sindhu, Lee, Jong Y, Jeon, Noo Li, Zhang, Zhenqian, Huang, Alex S, Zhou, Bin, Wong, Alex K, and Hong, Young-Kwon
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BackgroundMutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion.MethodsVarious mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration.ResultsPiezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouti
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- 2022
9. Progress, Barriers, and Prospects for Achieving a 'hydrogen Society' and Opportunities for Biochar Technology
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Igalavithana, Avanthi Deshani, You, Siming, Zhang, Lin, Shang, Jin, Lehmann, Johannes, Wang, Xiaonan, Zhu, Yong-Guan, Tsang, Daniel C. W., Park, Young-Kwon, Hou, Deyi, Ok, Yong Sik, Igalavithana, Avanthi Deshani, You, Siming, Zhang, Lin, Shang, Jin, Lehmann, Johannes, Wang, Xiaonan, Zhu, Yong-Guan, Tsang, Daniel C. W., Park, Young-Kwon, Hou, Deyi, and Ok, Yong Sik
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The concept of a "hydrogen (H2) society" is meant to serve as a greener alternative toward fossil fuel utilization and mitigating the climate crisis. However, major challenges concerning sustainability in the production of H2need to be resolved to fulfill the development of a hydrogen society. Climate change cannot be mitigated while fossil fuels remain the primary source of H2production. The use of excess renewable energy to produce H2can also be economically challenging; moreover, difficulties in storage and transportation could render a hydrogen society inviable. Biochar, as a renewable low-cost material, could be the key toward resolving these challenges, by serving as feedstock for steam gasification, as a catalyst or catalyst support for thermochemical or photochemical processes, or as an additive for biochemical processes. This study examines the plausibility of the concept of an "H2society" and the role of biochar in making this a reality. Biochar helps improve H2production, because it is an effective catalyst due to its high surface area, porosity, conductivity, and stability. Its high H2storage capacity could facilitate effective stationary storage and transportation. The role of biochar in an H2economy is becoming clearer; however, developing effective biochar-based materials for H2production and storage is necessary.
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- 2022
10. Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor-mediated lymphangiogenesis
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Furlong-Silva, Julio, Cross, Stephen D, Marriott, Amy E, Pionnier, Nicolas, Archer, John, Steven, Andrew, Merker, Stefan Schulte, Mack, Matthias, Hong, Young-Kwon, Taylor, Mark J, Turner, Joseph D, Furlong-Silva, Julio, Cross, Stephen D, Marriott, Amy E, Pionnier, Nicolas, Archer, John, Steven, Andrew, Merker, Stefan Schulte, Mack, Matthias, Hong, Young-Kwon, Taylor, Mark J, and Turner, Joseph D
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Lymphatic filariasis is the major global cause of nonhereditary lymphedema. We demonstrate that the filarial nematode Brugia malayi induced lymphatic remodeling and impaired lymphatic drainage following parasitism of limb lymphatics in a mouse model. Lymphatic insufficiency was associated with elevated circulating lymphangiogenic mediators, including vascular endothelial growth factor C. Lymphatic insufficiency was dependent on type 2 adaptive immunity, the interleukin-4 receptor, and recruitment of C-C chemokine receptor-2–positive monocytes and alternatively activated macrophages with a prolymphangiogenic phenotype. Oral treatments with second-generation tetracyclines improved lymphatic function, while other classes of antibiotic had no significant effect. Second-generation tetracyclines directly targeted lymphatic endothelial cell proliferation and modified type 2 prolymphangiogenic macrophage development. Doxycycline treatment impeded monocyte recruitment, inhibited polarization of alternatively activated macrophages, and suppressed T cell adaptive immune responses following infection. Our results determine a mechanism of action for the antimorbidity effects of doxycycline in filariasis and support clinical evaluation of second-generation tetracyclines as affordable, safe therapeutics for lymphedemas of chronic inflammatory origin.
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- 2021
11. Fast hydropyrolysis of biomass Conversion: A comparative review
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Oh, Shinyoung, Lee, Jechan, Lam, Su Shiung, Kwon, Eilhann E., Ha, Jeong-Myeong, Tsang, Daniel C.W., Ok, Yong Sik, Chen, Wei-Hsin, Park, Young-Kwon, Oh, Shinyoung, Lee, Jechan, Lam, Su Shiung, Kwon, Eilhann E., Ha, Jeong-Myeong, Tsang, Daniel C.W., Ok, Yong Sik, Chen, Wei-Hsin, and Park, Young-Kwon
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Recent studies show that fast hydropyrolysis (i.e., pyrolysis under hydrogen atmosphere operating at a rapid heating rate) is a promising technology for the conversion of biomass into liquid fuels (e.g., bio-oil and C4+ hydrocarbons). This pyrolysis approach is reported to be more effective than conventional fast pyrolysis in producing aromatic hydrocarbons and also lowering the oxygen content of the bio-oil obtained compared to hydrodeoxygenation (a common bio-oil upgrading method). Based on current literature, various non-catalytic and catalytic fast hydropyrolysis processes are reviewed and discussed. Efforts to combine fast hydropyrolysis and hydrotreatment process are also highlighted. Points to be considered for future research into fast hydropyrolysis and pending challenges are also discussed.
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- 2021
12. Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor-mediated lymphangiogenesis
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Furlong-Silva, Julio, Cross, Stephen D, Marriott, Amy E, Pionnier, Nicolas, Archer, John, Steven, Andrew, Merker, Stefan Schulte, Mack, Matthias, Hong, Young-Kwon, Taylor, Mark J, Turner, Joseph D, Furlong-Silva, Julio, Cross, Stephen D, Marriott, Amy E, Pionnier, Nicolas, Archer, John, Steven, Andrew, Merker, Stefan Schulte, Mack, Matthias, Hong, Young-Kwon, Taylor, Mark J, and Turner, Joseph D
- Abstract
Lymphatic filariasis is the major global cause of nonhereditary lymphedema. We demonstrate that the filarial nematode Brugia malayi induced lymphatic remodeling and impaired lymphatic drainage following parasitism of limb lymphatics in a mouse model. Lymphatic insufficiency was associated with elevated circulating lymphangiogenic mediators, including vascular endothelial growth factor C. Lymphatic insufficiency was dependent on type 2 adaptive immunity, the interleukin-4 receptor, and recruitment of C-C chemokine receptor-2–positive monocytes and alternatively activated macrophages with a prolymphangiogenic phenotype. Oral treatments with second-generation tetracyclines improved lymphatic function, while other classes of antibiotic had no significant effect. Second-generation tetracyclines directly targeted lymphatic endothelial cell proliferation and modified type 2 prolymphangiogenic macrophage development. Doxycycline treatment impeded monocyte recruitment, inhibited polarization of alternatively activated macrophages, and suppressed T cell adaptive immune responses following infection. Our results determine a mechanism of action for the antimorbidity effects of doxycycline in filariasis and support clinical evaluation of second-generation tetracyclines as affordable, safe therapeutics for lymphedemas of chronic inflammatory origin.
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- 2021
13. Lymphatic Proliferation Ameliorates Pulmonary Fibrosis after Lung Injury.
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Baluk, Peter, Baluk, Peter, Naikawadi, Ram P, Kim, Shineui, Rodriguez, Felipe, Choi, Dongwon, Hong, Young-Kwon, Wolters, Paul J, McDonald, Donald M, Baluk, Peter, Baluk, Peter, Naikawadi, Ram P, Kim, Shineui, Rodriguez, Felipe, Choi, Dongwon, Hong, Young-Kwon, Wolters, Paul J, and McDonald, Donald M
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Despite many reports about pulmonary blood vessels in lung fibrosis, the contribution of lymphatics to fibrosis is unknown. We examined the mechanism and consequences of lymphatic remodeling in mice with lung fibrosis after bleomycin injury or telomere dysfunction. Widespread lymphangiogenesis was observed after bleomycin treatment and in fibrotic lungs of prospero homeobox 1-enhanced green fluorescent protein (Prox1-EGFP) transgenic mice with telomere dysfunction. In loss-of-function studies, blocking antibodies revealed that lymphangiogenesis 14 days after bleomycin treatment was dependent on vascular endothelial growth factor (Vegf) receptor 3 signaling, but not on Vegf receptor 2. Vegfc gene and protein expression increased specifically. Extensive extravasated plasma, platelets, and macrophages at sites of lymphatic growth were potential sources of Vegfc. Lymphangiogenesis peaked at 14 to 28 days after bleomycin challenge, was accompanied by doubling of chemokine (C-C motif) ligand 21 in lung lymphatics and tertiary lymphoid organ formation, and then decreased as lung injury resolved by 56 days. In gain-of-function studies, expansion of the lung lymphatic network by transgenic overexpression of Vegfc in club cell secretory protein (CCSP)/VEGF-C mice reduced macrophage accumulation and fibrosis and accelerated recovery after bleomycin treatment. These findings suggest that lymphatics have an overall protective effect in lung injury and fibrosis and fit with a mechanism whereby lung lymphatic network expansion reduces lymph stasis and increases clearance of fluid and cells, including profibrotic macrophages.
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- 2020
14. Engineering pyrolysis biochar via single-step microwave steam activation for hazardous landfill leachate treatment
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Lam, Su Shiung, Yek, Peter Nai Yuh, Ok, Yong Sik, Chong, Chi Cheng, Liew, Rock Keey, Tsang, Daniel C.W., Park, Young-Kwon, Liu, Zhenling, Wong, Chee Swee, Peng, Wanxi, Lam, Su Shiung, Yek, Peter Nai Yuh, Ok, Yong Sik, Chong, Chi Cheng, Liew, Rock Keey, Tsang, Daniel C.W., Park, Young-Kwon, Liu, Zhenling, Wong, Chee Swee, and Peng, Wanxi
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Improving the sustainability and cost-effectiveness of biochar production is crucial to meet increased global market demand. Here, we developed a single-step microwave steam activation (STMSA) as a simplified yet efficient method to produce microwave activated biochar (MAB) from waste palm shell (WPS). The STMSA recorded a higher heating rate (70 °C/min) and higher conversion (45 wt%) of WPS into highly microporous MAB (micropore surface area of 679.22 m2/g) in contrast with the conventional heating approach (≤ 12−17 wt%). The MAB was then applied as biosorbent for hazardous landfill leachate (LL) treatment and the adsorption performance was compared with commercial activated carbon under different pH, adsorbent quantity, adsorbate concentrations, and contact times. The MAB demonstrated high adsorption capacity, achieving maximum adsorption efficiency at 595 mg/g and 65 % removal of chemical oxygen demand (COD) with 0.4 g/L of adsorbent amount under optimal acidic conditions (pH ≈ 2–3) after 24 h of contact time. The Freundlich isotherm and pseudo second-order kinetic models were well-fitted to explain the equilibrium adsorption and kinetics. The results indicate the viability of STMSA as a fast and efficient approach to produce activated biochar as a biosorbent for the treatment of hazardous landfill leachate.
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- 2020
15. YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis
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Cho, Hyunsoo, Kim, Jaeryung, Ahn, Ji Hoon, Hong, Young-Kwon, Mäkinen, Taija, Lim, Dae-Sik, Koh, Gou Young, Cho, Hyunsoo, Kim, Jaeryung, Ahn, Ji Hoon, Hong, Young-Kwon, Mäkinen, Taija, Lim, Dae-Sik, and Koh, Gou Young
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Rationale: The Hippo pathway governs cellular differentiation, morphogenesis, and homeostasis, but how it regulates these processes in lymphatic vessels is unknown. Objective: We aimed to reveal the role of the final effectors of the Hippo pathway, YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), in lymphatic endothelial cell (LEC) differentiation, morphogenesis, and homeostasis. Methods and Results: During mouse embryonic development, LEC-specific depletion of Yap/Taz disturbed both plexus patterning and valve initiation with upregulated Prox1 (prospero homeobox 1). Conversely, LEC-specific YAP/TAZ hyperactivation impaired lymphatic specification and restricted lymphatic sprouting with profoundly downregulated Prox1. Notably, lymphatic YAP/TAZ depletion or hyperactivation aggravated or attenuated pathological lymphangiogenesis in mouse cornea. Mechanistically, VEGF (vascular endothelial growth factor)-C activated canonical Hippo signaling pathway in LECs. Indeed, repression of PROX1 transcription by YAP/TAZ hyperactivation was mediated by recruitment of NuRD (nucleosome remodeling and histone deacetylase) complex and endogenous binding activity of TEAD (TEA domain family members) to the PROX1 promoter. Furthermore, YAP/TAZ hyperactivation enhanced MYC signaling and inhibited CDKN1C, leading to cell cycle dysregulation and aberrant proliferation. Conclusions: We find that YAP and TAZ play promoting roles in remodeling lymphatic plexus patterning and postnatal lymphatic valve maintenance by negatively regulating Prox1 expression. We further show that YAP and TAZ act as plastic regulators of lymphatic identity and define the Hippo signaling-mediated PROX1 transcriptional programing as a novel dynamic checkpoint underlying LEC plasticity and pathophysiology.
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- 2019
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16. Laminar flow downregulates Notch activity to promote lymphatic sprouting.
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Choi, Dongwon, Choi, Dongwon, Park, Eunkyung, Jung, Eunson, Seong, Young Jin, Yoo, Jaehyuk, Lee, Esak, Hong, Mingu, Lee, Sunju, Ishida, Hiroaki, Burford, James, Peti-Peterdi, Janos, Adams, Ralf H, Srikanth, Sonal, Gwack, Yousang, Chen, Christopher S, Vogel, Hans J, Koh, Chester J, Wong, Alex K, Hong, Young-Kwon, Choi, Dongwon, Choi, Dongwon, Park, Eunkyung, Jung, Eunson, Seong, Young Jin, Yoo, Jaehyuk, Lee, Esak, Hong, Mingu, Lee, Sunju, Ishida, Hiroaki, Burford, James, Peti-Peterdi, Janos, Adams, Ralf H, Srikanth, Sonal, Gwack, Yousang, Chen, Christopher S, Vogel, Hans J, Koh, Chester J, Wong, Alex K, and Hong, Young-Kwon
- Abstract
The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.
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- 2017
17. ORAI1 Activates Proliferation of Lymphatic Endothelial Cells in Response to Laminar Flow Through Krüppel-Like Factors 2 and 4.
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Choi, Dongwon, Choi, Dongwon, Park, Eunkyung, Jung, Eunson, Seong, Young Jin, Hong, Mingu, Lee, Sunju, Burford, James, Gyarmati, Georgina, Peti-Peterdi, Janos, Srikanth, Sonal, Gwack, Yousang, Koh, Chester J, Boriushkin, Evgenii, Hamik, Anne, Wong, Alex K, Hong, Young-Kwon, Choi, Dongwon, Choi, Dongwon, Park, Eunkyung, Jung, Eunson, Seong, Young Jin, Hong, Mingu, Lee, Sunju, Burford, James, Gyarmati, Georgina, Peti-Peterdi, Janos, Srikanth, Sonal, Gwack, Yousang, Koh, Chester J, Boriushkin, Evgenii, Hamik, Anne, Wong, Alex K, and Hong, Young-Kwon
- Abstract
RationaleLymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown.ObjectiveWe aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation.Methods and resultsPrimary endothelial cells from dermal blood and lymphatic vessels (blood vascular endothelial cells and lymphatic endothelial cells [LECs]) were exposed to low-rate steady laminar flow. Shear stress-induced molecular and cellular responses were defined and verified using various mutant mouse models. Steady laminar flow induced the classic shear stress responses commonly in blood vascular endothelial cells and LECs. Surprisingly, however, only LECs showed enhanced cell proliferation by regulating the vascular endothelial growth factor (VEGF)-A, VEGF-C, FGFR3, and p57/CDKN1C genes. As an early signal mediator, ORAI1, a pore subunit of the calcium release-activated calcium channel, was identified to induce the shear stress phenotypes and cell proliferation in LECs responding to the fluid flow. Mechanistically, ORAI1 induced upregulation of Krüppel-like factor (KLF)-2 and KLF4 in the flow-activated LECs, and the 2 KLF proteins cooperate to regulate VEGF-A, VEGF-C, FGFR3, and p57 by binding to the regulatory regions of the genes. Consistently, freshly isolated LECs from Orai1 knockout embryos displayed reduced expression of KLF2, KLF4, VEGF-A, VEGF-C, and FGFR3 and elevated expression of p57. Accordingly, mouse embryos deficient in Orai1, Klf2, or Klf4 showed a significantly reduced lymphatic density and impaired lymphatic development.ConclusionsOur study identified a molecular mechanism for laminar flow-activated LEC proliferation.
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- 2017
18. Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity.
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Yan, Kelley S, Yan, Kelley S, Gevaert, Olivier, Zheng, Grace XY, Anchang, Benedict, Probert, Christopher S, Larkin, Kathryn A, Davies, Paige S, Cheng, Zhuan-Fen, Kaddis, John S, Han, Arnold, Roelf, Kelly, Calderon, Ruben I, Cynn, Esther, Hu, Xiaoyi, Mandleywala, Komal, Wilhelmy, Julie, Grimes, Sue M, Corney, David C, Boutet, Stéphane C, Terry, Jessica M, Belgrader, Phillip, Ziraldo, Solongo B, Mikkelsen, Tarjei S, Wang, Fengchao, von Furstenberg, Richard J, Smith, Nicholas R, Chandrakesan, Parthasarathy, May, Randal, Chrissy, Mary Ann S, Jain, Rajan, Cartwright, Christine A, Niland, Joyce C, Hong, Young-Kwon, Carrington, Jill, Breault, David T, Epstein, Jonathan, Houchen, Courtney W, Lynch, John P, Martin, Martin G, Plevritis, Sylvia K, Curtis, Christina, Ji, Hanlee P, Li, Linheng, Henning, Susan J, Wong, Melissa H, Kuo, Calvin J, Yan, Kelley S, Yan, Kelley S, Gevaert, Olivier, Zheng, Grace XY, Anchang, Benedict, Probert, Christopher S, Larkin, Kathryn A, Davies, Paige S, Cheng, Zhuan-Fen, Kaddis, John S, Han, Arnold, Roelf, Kelly, Calderon, Ruben I, Cynn, Esther, Hu, Xiaoyi, Mandleywala, Komal, Wilhelmy, Julie, Grimes, Sue M, Corney, David C, Boutet, Stéphane C, Terry, Jessica M, Belgrader, Phillip, Ziraldo, Solongo B, Mikkelsen, Tarjei S, Wang, Fengchao, von Furstenberg, Richard J, Smith, Nicholas R, Chandrakesan, Parthasarathy, May, Randal, Chrissy, Mary Ann S, Jain, Rajan, Cartwright, Christine A, Niland, Joyce C, Hong, Young-Kwon, Carrington, Jill, Breault, David T, Epstein, Jonathan, Houchen, Courtney W, Lynch, John P, Martin, Martin G, Plevritis, Sylvia K, Curtis, Christina, Ji, Hanlee P, Li, Linheng, Henning, Susan J, Wong, Melissa H, and Kuo, Calvin J
- Abstract
Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5+ ISCs, the most well-defined ISC pool, but Bmi1-GFP+ cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP+ cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1+ cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo. Single-cell mRNA-seq revealed two subsets of Prox1-GFP+ cells, one of which resembled mature EE cells while the other displayed low-level EE gene expression but co-expressed tuft cell markers, Lgr5 and Ascl2, reminiscent of label-retaining secretory progenitors. Our data suggest that the EE lineage, including mature EE cells, comprises a reservoir of homeostatic and injury-inducible ISCs, extending our understanding of cellular plasticity and stemness.
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- 2017
19. West African monsoon decadal variability and surface-related forcings: Second West African Monsoon Modeling and Evaluation Project Experiment (WAMME II).
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Xue, Yongkang, Xue, Yongkang, De Sales, Fernando, Lau, William K-M, Boone, Aaron, Kim, Kyu-Myong, Mechoso, Carlos R, Wang, Guiling, Kucharski, Fred, Schiro, Kathleen, Hosaka, Masahiro, Li, Suosuo, Druyan, Leonard M, Seidou Sanda, Ibrah, Thiaw, Wassila, Zeng, Ning, Comer, Ruth E, Lim, Young-Kwon, Mahanama, Sarith, Song, Guoqiong, Gu, Yu, Hagos, Samson M, Chin, Mian, Schubert, Siegfried, Dirmeyer, Paul, Leung, L Ruby, Kalnay, Eugenia, Kitoh, Akio, Lu, Cheng-Hsuan, Mahowald, Natalie M, Zhang, Zhengqiu, Xue, Yongkang, Xue, Yongkang, De Sales, Fernando, Lau, William K-M, Boone, Aaron, Kim, Kyu-Myong, Mechoso, Carlos R, Wang, Guiling, Kucharski, Fred, Schiro, Kathleen, Hosaka, Masahiro, Li, Suosuo, Druyan, Leonard M, Seidou Sanda, Ibrah, Thiaw, Wassila, Zeng, Ning, Comer, Ruth E, Lim, Young-Kwon, Mahanama, Sarith, Song, Guoqiong, Gu, Yu, Hagos, Samson M, Chin, Mian, Schubert, Siegfried, Dirmeyer, Paul, Leung, L Ruby, Kalnay, Eugenia, Kitoh, Akio, Lu, Cheng-Hsuan, Mahowald, Natalie M, and Zhang, Zhengqiu
- Abstract
The second West African Monsoon Modeling and Evaluation Project Experiment (WAMME II) is designed to improve understanding of the possible roles and feedbacks of sea surface temperature (SST), land use land cover change (LULCC), and aerosols forcings in the Sahel climate system at seasonal to decadal scales. The project's strategy is to apply prescribed observationally based anomaly forcing, i.e., "idealized but realistic" forcing, in simulations by climate models. The goal is to assess these forcings' effects in producing/amplifying seasonal and decadal climate variability in the Sahel between the 1950s and the 1980s, which is selected to characterize the great drought period of the last century. This is the first multi-model experiment specifically designed to simultaneously evaluate such relative contributions. The WAMME II models have consistently demonstrated that SST forcing is a major contributor to the 20th century Sahel drought. Under the influence of the maximum possible SST forcing, the ensemble mean of WAMME II models can produce up to 60% of the precipitation difference during the period. The present paper also addresses the role of SSTs in triggering and maintaining the Sahel drought. In this regard, the consensus of WAMME II models is that both Indian and Pacific Ocean SSTs greatly contributed to the drought, with the former producing an anomalous displacement of the Intertropical Convergence Zone (ITCZ) before the WAM onset, and the latter mainly contributes to the summer WAM drought. The WAMME II models also show that the impact of LULCC forcing on the Sahel climate system is weaker than that of SST forcing, but still of first order magnitude. According to the results, under LULCC forcing the ensemble mean of WAMME II models can produces about 40% of the precipitation difference between the 1980s and the 1950s. The role of land surface processes in responding to and amplifying the drought is also identified. The results suggest that catastrophic con
- Published
- 2016
20. West African monsoon decadal variability and surface-related forcings: Second West African Monsoon Modeling and Evaluation Project Experiment (WAMME II).
- Author
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Xue, Yongkang, Xue, Yongkang, De Sales, Fernando, Lau, William K-M, Boone, Aaron, Kim, Kyu-Myong, Mechoso, Carlos R, Wang, Guiling, Kucharski, Fred, Schiro, Kathleen, Hosaka, Masahiro, Li, Suosuo, Druyan, Leonard M, Seidou Sanda, Ibrah, Thiaw, Wassila, Zeng, Ning, Comer, Ruth E, Lim, Young-Kwon, Mahanama, Sarith, Song, Guoqiong, Gu, Yu, Hagos, Samson M, Chin, Mian, Schubert, Siegfried, Dirmeyer, Paul, Leung, L Ruby, Kalnay, Eugenia, Kitoh, Akio, Lu, Cheng-Hsuan, Mahowald, Natalie M, Zhang, Zhengqiu, Xue, Yongkang, Xue, Yongkang, De Sales, Fernando, Lau, William K-M, Boone, Aaron, Kim, Kyu-Myong, Mechoso, Carlos R, Wang, Guiling, Kucharski, Fred, Schiro, Kathleen, Hosaka, Masahiro, Li, Suosuo, Druyan, Leonard M, Seidou Sanda, Ibrah, Thiaw, Wassila, Zeng, Ning, Comer, Ruth E, Lim, Young-Kwon, Mahanama, Sarith, Song, Guoqiong, Gu, Yu, Hagos, Samson M, Chin, Mian, Schubert, Siegfried, Dirmeyer, Paul, Leung, L Ruby, Kalnay, Eugenia, Kitoh, Akio, Lu, Cheng-Hsuan, Mahowald, Natalie M, and Zhang, Zhengqiu
- Abstract
The second West African Monsoon Modeling and Evaluation Project Experiment (WAMME II) is designed to improve understanding of the possible roles and feedbacks of sea surface temperature (SST), land use land cover change (LULCC), and aerosols forcings in the Sahel climate system at seasonal to decadal scales. The project's strategy is to apply prescribed observationally based anomaly forcing, i.e., "idealized but realistic" forcing, in simulations by climate models. The goal is to assess these forcings' effects in producing/amplifying seasonal and decadal climate variability in the Sahel between the 1950s and the 1980s, which is selected to characterize the great drought period of the last century. This is the first multi-model experiment specifically designed to simultaneously evaluate such relative contributions. The WAMME II models have consistently demonstrated that SST forcing is a major contributor to the 20th century Sahel drought. Under the influence of the maximum possible SST forcing, the ensemble mean of WAMME II models can produce up to 60% of the precipitation difference during the period. The present paper also addresses the role of SSTs in triggering and maintaining the Sahel drought. In this regard, the consensus of WAMME II models is that both Indian and Pacific Ocean SSTs greatly contributed to the drought, with the former producing an anomalous displacement of the Intertropical Convergence Zone (ITCZ) before the WAM onset, and the latter mainly contributes to the summer WAM drought. The WAMME II models also show that the impact of LULCC forcing on the Sahel climate system is weaker than that of SST forcing, but still of first order magnitude. According to the results, under LULCC forcing the ensemble mean of WAMME II models can produces about 40% of the precipitation difference between the 1980s and the 1950s. The role of land surface processes in responding to and amplifying the drought is also identified. The results suggest that catastrophic con
- Published
- 2016
21. Study of the Top-quark Pair Production in Association with a Bottom-quark Pair from Fast Simulations at the LHC
- Author
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Jo, Young Kwon, Choi, Su Yong, Kim, Tae Jeong, Roh, Youn Jung, Jo, Young Kwon, Choi, Su Yong, Kim, Tae Jeong, and Roh, Youn Jung
- Abstract
A large number of top quarks will be produced at the Large Hadron Collider (LHC) for Run II period. This will allow us to measure the rare processes from the top sector in great details. We present the study of the top-quark pair production in association with a bottom-quark pair (ttbb) from fast simulations for the Compact Muon Solenoid (CMS) experiment. The differential distributions of ttbb are compared with the top-quark pair production with two additional jets (ttjj) and with the production in association with the Higgs (ttH), where the Higgs decays to a bottom-quark pair. The significances of ttbb process in the dileptonic and semileptonic decay mode are calculated with the data corresponding to an integrated luminosity of 10 fb-1, which is foreseen to be collected in the early Run II period. This study will be an important input in searching for new physics beyond the standard model as well as in searching for ttH process where the Yukawa coupling with the top quark can be directly measured., Comment: 12 pages, 12 figures
- Published
- 2015
- Full Text
- View/download PDF
22. Study of the Top-quark Pair Production in Association with a Bottom-quark Pair from Fast Simulations at the LHC
- Author
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Jo, Young Kwon, Choi, Su Yong, Kim, Tae Jeong, Roh, Youn Jung, Jo, Young Kwon, Choi, Su Yong, Kim, Tae Jeong, and Roh, Youn Jung
- Abstract
A large number of top quarks will be produced at the Large Hadron Collider (LHC) for Run II period. This will allow us to measure the rare processes from the top sector in great details. We present the study of the top-quark pair production in association with a bottom-quark pair (ttbb) from fast simulations for the Compact Muon Solenoid (CMS) experiment. The differential distributions of ttbb are compared with the top-quark pair production with two additional jets (ttjj) and with the production in association with the Higgs (ttH), where the Higgs decays to a bottom-quark pair. The significances of ttbb process in the dileptonic and semileptonic decay mode are calculated with the data corresponding to an integrated luminosity of 10 fb-1, which is foreseen to be collected in the early Run II period. This study will be an important input in searching for new physics beyond the standard model as well as in searching for ttH process where the Yukawa coupling with the top quark can be directly measured., Comment: 12 pages, 12 figures
- Published
- 2015
- Full Text
- View/download PDF
23. Study of the Top-quark Pair Production in Association with a Bottom-quark Pair from Fast Simulations at the LHC
- Author
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Jo, Young Kwon, Choi, Su Yong, Kim, Tae Jeong, Roh, Youn Jung, Jo, Young Kwon, Choi, Su Yong, Kim, Tae Jeong, and Roh, Youn Jung
- Abstract
A large number of top quarks will be produced at the Large Hadron Collider (LHC) for Run II period. This will allow us to measure the rare processes from the top sector in great details. We present the study of the top-quark pair production in association with a bottom-quark pair (ttbb) from fast simulations for the Compact Muon Solenoid (CMS) experiment. The differential distributions of ttbb are compared with the top-quark pair production with two additional jets (ttjj) and with the production in association with the Higgs (ttH), where the Higgs decays to a bottom-quark pair. The significances of ttbb process in the dileptonic and semileptonic decay mode are calculated with the data corresponding to an integrated luminosity of 10 fb-1, which is foreseen to be collected in the early Run II period. This study will be an important input in searching for new physics beyond the standard model as well as in searching for ttH process where the Yukawa coupling with the top quark can be directly measured., Comment: 12 pages, 12 figures
- Published
- 2015
- Full Text
- View/download PDF
24. Hurricanes and Climate The U.S. Clivar Working Group on Hurricanes
- Author
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Walsh, Kevin J.E., Camargo, Suzana J., Vecchi, Gabriel A., Daloz, Anne Sophie, Elsner, James, Emanuel, Kerry, Horn, Michael, Lim, Young-Kwon, Roberts, Malcom, Patricola, Christina, Scoccimarro, Enrico, Sobel, Adam H., Strazzo, Sarah, Villarini, Gabrielle, Wehner, Michael, Zhao, Ming, Kossin, James P., LaRow, Tim, Oouchi, Kazuyoshi, Schubert, Sigfried, Wang, Hui, Bacmeister, Julio, Chang, Ping, Chauvin, Fabrice, Jablonowski, Christiane, Kumar, Arun, Murakami, Hiroyuki, Ose, Tomoaki, Reed, Kevin A., Saravanan, Ramalingam, Yamada, Yohei, Zarzycki, Colin M., Vidale, Pier Luigi, Jonas, Jefferey A., Henderson, Naomi, Walsh, Kevin J.E., Camargo, Suzana J., Vecchi, Gabriel A., Daloz, Anne Sophie, Elsner, James, Emanuel, Kerry, Horn, Michael, Lim, Young-Kwon, Roberts, Malcom, Patricola, Christina, Scoccimarro, Enrico, Sobel, Adam H., Strazzo, Sarah, Villarini, Gabrielle, Wehner, Michael, Zhao, Ming, Kossin, James P., LaRow, Tim, Oouchi, Kazuyoshi, Schubert, Sigfried, Wang, Hui, Bacmeister, Julio, Chang, Ping, Chauvin, Fabrice, Jablonowski, Christiane, Kumar, Arun, Murakami, Hiroyuki, Ose, Tomoaki, Reed, Kevin A., Saravanan, Ramalingam, Yamada, Yohei, Zarzycki, Colin M., Vidale, Pier Luigi, Jonas, Jefferey A., and Henderson, Naomi
- Abstract
While a quantitative climate theory of tropical cyclone formation remains elusive, considerable progress has been made recently in our ability to simulate tropical cyclone climatologies and to understand the relationship between climate and tropical cyclone formation. Climate models are now able to simulate a realistic rate of global tropical cyclone formation, although simulation of the Atlantic tropical cyclone climatology remains challenging unless horizontal resolutions finer than 50 km are employed. This article summarizes published research from the idealized experiments of the Hurricane Working Group of U.S. Climate and Ocean: Variability, Predictability and Change (CLIVAR). This work, combined with results from other model simulations, has strengthened relationships between tropical cyclone formation rates and climate variables such as midtropospheric vertical velocity, with decreased climatological vertical velocities leading to decreased tropical cyclone formation. Systematic differences are shown between experiments in which only sea surface temperature is increased compared with experiments where only atmospheric carbon dioxide is increased. Experiments where only carbon dioxide is increased are more likely to demonstrate a decrease in tropical cyclone numbers, similar to the decreases simulated by many climate models for a future, warmer climate. Experiments where the two effects are combined also show decreases in numbers, but these tend to be less for models that demonstrate a strong tropical cyclone response to increased sea surface temperatures. Further experiments are proposed that may improve our understanding of the relationship between climate and tropical cyclone formation, including experiments with two-way interaction between the ocean and the atmosphere and variations in atmospheric aerosols.
- Published
- 2015
25. Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity
- Author
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Park, Dae-Young, Lee, Junyeop, Park, Intae, Choi, Dongwon, Lee, Sunju, Song, Sukhyun, Hwang, Yoonha, Hong, Ki Yong, Nakaoka, Yoshikazu, Mäkinen, Taija, Kim, Pilhan, Alitalo, Kari, Hong, Young-Kwon, Koh, Gou Young, Park, Dae-Young, Lee, Junyeop, Park, Intae, Choi, Dongwon, Lee, Sunju, Song, Sukhyun, Hwang, Yoonha, Hong, Ki Yong, Nakaoka, Yoshikazu, Mäkinen, Taija, Kim, Pilhan, Alitalo, Kari, Hong, Young-Kwon, and Koh, Gou Young
- Abstract
Schlemm's canal (SC) is a specialized vascular structure in the eye that functions to drain aqueous humor from the intraocular chamber into systemic circulation. Dysfunction of SC has been proposed to Underlie increased aqueous humor outflow (AHO) resistance, which leads to elevated ocular pressure, a factor for glaucoma development in humans. Here, using lymphatic and blood vasculature reporter mice, we determined that SC, which originates from blood vessels during the postnatal period, acquires lymphatic identity through upregulation of prospero homeobox protein 1 (PROX1), the master regulator of lymphatic development. SC expressed lymphatic valve markers FOXC2 and integrin alpha(9) and exhibited continuous vascular endothelial-cadherin (VE-cadherin) junctions and basement membrane, similar to collecting lymphatics. SC notably lacked luminal valves and expression of the lymphatic endothelial cell markers podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Using an ocular puncture model, we determined that reduced AHO altered the fate of SC both during development and under pathologic conditions; however, alteration of VEGF-C/VEGFR3 signaling did not modulate SC integrity and identity. Intriguingly, PROX1 expression levels linearly correlated with SC functionality. For example, PROX1 expression was reduced or undetectable under pathogenic conditions and in deteriorated SCs. Collectively, our data indicate that PROX1 is an accurate and reliable biosensor of SC integrity and identity.
- Published
- 2014
- Full Text
- View/download PDF
26. A lymphatic defect causes ocular hypertension and glaucoma in mice
- Author
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Thomson, Benjamin R, Heinen, Stefan, Jeansson, Marie, Ghosh, Asish K, Fatima, Anees, Sung, Hoon-Ki, Onay, Tuncer, Chen, Hui, Yamaguchi, Shinji, Economides, Aris N, Flenniken, Ann, Gale, Nicholas W, Hong, Young-Kwon, Fawzi, Amani, Liu, Xiaorong, Kume, Tsutomu, Quaggin, Susan E, Thomson, Benjamin R, Heinen, Stefan, Jeansson, Marie, Ghosh, Asish K, Fatima, Anees, Sung, Hoon-Ki, Onay, Tuncer, Chen, Hui, Yamaguchi, Shinji, Economides, Aris N, Flenniken, Ann, Gale, Nicholas W, Hong, Young-Kwon, Fawzi, Amani, Liu, Xiaorong, Kume, Tsutomu, and Quaggin, Susan E
- Abstract
Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage is a major risk factor for the development of glaucoma. Here, we demonstrated that genetic disruption of the angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features of glaucoma, including retinal ganglion degeneration and vision loss. Eyes from mice with induced deletion of Angpt1 and Angpt2 (A1A2FloxWB mice) lacked drainage pathways in the corneal limbus, including Schlemm’s canal and lymphatic capillaries, which share expression of the PROX1, VEGFR3, and FOXC family of transcription factors. VEGFR3 and FOXCs have been linked to lymphatic disorders in patients, and FOXC1 has been linked to glaucoma. In contrast to blood endothelium, in which ANGPT2 is an antagonist of ANGPT1, we have shown that both ligands cooperate to regulate TIE2 in the lymphatic network of the eye. While A1A2FloxWB mice developed high IOP and glaucoma, expression of ANGPT1 or ANGPT2 alone was sufficient for ocular drainage. Furthermore, we demonstrated that loss of FOXC2 from lymphatics results in TIE2 downregulation, suggesting a mechanism for ocular defects in patients with FOXC mutations. These data reveal a pathogenetic and molecular basis for glaucoma and demonstrate the importance of angiopoietin ligand cooperation in the lymphatic endothelium.
- Published
- 2014
- Full Text
- View/download PDF
27. Preferential lymphatic growth in bronchus-associated lymphoid tissue in sustained lung inflammation.
- Author
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Baluk, Peter, Baluk, Peter, Adams, Alicia, Phillips, Keeley, Feng, Jennifer, Hong, Young-Kwon, Brown, Mary B, McDonald, Donald M, Baluk, Peter, Baluk, Peter, Adams, Alicia, Phillips, Keeley, Feng, Jennifer, Hong, Young-Kwon, Brown, Mary B, and McDonald, Donald M
- Abstract
Lymphatics proliferate, become enlarged, or regress in multiple inflammatory lung diseases in humans. Lymphatic growth and remodeling is known to occur in the mouse trachea in sustained inflammation, but whether intrapulmonary lymphatics exhibit similar plasticity is unknown. We examined the time course, distribution, and dependence on vascular endothelial growth factor receptor (VEGFR)-2/VEGFR-3 signaling of lung lymphatics in sustained inflammation. Lymphatics in mouse lungs were examined under baseline conditions and 3 to 28 days after Mycoplasma pulmonis infection, using prospero heomeobox 1-enhanced green fluorescence protein and VEGFR-3 as markers. Sprouting lymphangiogenesis was evident at 7 days. Lymphatic growth was restricted to regions of bronchus-associated lymphoid tissue (BALT), where VEGF-C-producing cells were scattered in T-cell zones. Expansion of lung lymphatics after infection was reduced 68% by blocking VEGFR-2, 83% by blocking VEGFR-3, and 99% by blocking both receptors. Inhibition of VEGFR-2/VEGFR-3 did not prevent the formation of BALT. Treatment of established infection with oxytetracycline caused BALT, but not the lymphatics, to regress. We conclude that robust lymphangiogenesis occurs in mouse lungs after M. pulmonis infection through a mechanism involving signaling of both VEGFR-2 and VEGFR-3. Expansion of the lymphatic network is restricted to regions of BALT, but lymphatics do not regress when BALT regresses after antibiotic treatment. The lung lymphatic network can thus expand in sustained inflammation, but the expansion is not as reversible as the accompanying inflammation.
- Published
- 2014
28. Web Based Monitoring in the CMS Experiment at CERN
- Author
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Badgett, William, Borrello, Laura, Chakaberia, Irakli, Gigi, Dominique, Jo, Young-Kwon, Lopez-Perez, Juan Antonio, Maeshima, Kaori, Maruyama, Sho, Patrick, James, Rapsevicius, Valdas, Soha, Aron, Sulmanas, Balys, Wan, Zongru, Badgett, William, Borrello, Laura, Chakaberia, Irakli, Gigi, Dominique, Jo, Young-Kwon, Lopez-Perez, Juan Antonio, Maeshima, Kaori, Maruyama, Sho, Patrick, James, Rapsevicius, Valdas, Soha, Aron, Sulmanas, Balys, and Wan, Zongru
- Abstract
The Compact Muon Solenoid (CMS) is a large and complex general purpose experiment at the CERN Large Hadron Collider (LHC), built and maintained by many collaborators from around the world. Efficient operation of the detector requires widespread and timely access to a broad range of monitoring and status information. To this end the Web Based Monitoring (WBM) system was developed to present data to users located anywhere from many underlying heterogeneous sources, from real time messaging systems to relational databases. This system provides the power to combine and correlate data in both graphical and tabular formats of interest to the experimenters, including data such as beam conditions, luminosity, trigger rates, detector conditions, and many others, allowing for flexibility on the user side. This paper describes the WBM system architecture and describes how the system was used during the first major data taking run of the LHC., Comment: 22 pages, 15 figures. Submitted to JINST
- Published
- 2014
29. Mathematical modeling of rail gun
- Author
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Young, Kwon, Naval Postgraduate School (U.S.)., Mechanical Engineering and Astronautical Engineering, Pratikakis, Nikolaos, Young, Kwon, Naval Postgraduate School (U.S.)., Mechanical Engineering and Astronautical Engineering, and Pratikakis, Nikolaos
- Abstract
The exit velocity of the launch object along with the values of electric and thermal conductivity at the interfaces between the rails and the armature of a rail gun are critical issues. This thesis, using finite element method, estimates the former by solving the proper multiphysics governing equations, along with exploiting the contact theory between flat surfaces. A parametric analysis in the vicinity of the standard deviation of the normalized distance between the references planes of the rough surfaces was made for a variety of materials and textures at the interfaces. Furthermore, the amount of ohmic heat that is generated due to the application of the electric potential and the resistance of materials is estimated along with the average temperature at the interfaces. Finally, thermal stresses were also studied., http://archive.org/details/mathematicalmode109452604, Approved for public release; distribution is unlimited.
- Published
- 2012
30. Calixarene Derivatives as Novel Nanopore Generators for Templates of Nanoporous Thin Films
- Author
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Department of Physics, University of Michigan, Ann Arbor, Michigan 48109, USA, Division of Advanced Materials Engineering, Kongju National University, 182, Sinkwan-dong, Gongju City, Chungnam 314-701, Korea ; Division of Advanced Materials Engineering, Kongju National University, 182, Sinkwan-dong, Gongju City, Chungnam 314-701, Korea., CSE Center, Samsung Advanced Institute of Technology (SAIT), San 14-1, Nongseo-ri, Kiheung-eup, Yongin-si, Kyungki-do 449-712, Korea, Department of Chemistry, Kangwon National University, Chun-Chon 200-701, Korea, Flex. Display Program Team, Samsung Advanced Institute of Technology (SAIT), San 14-1, Nongseo-ri, Kiheung-eup, Yongin-si, Kyungki-do 449-712, Korea, Faculty of Environmental Engineering, University of Seoul, 90 Jeonnong-dong, Dongdaemun-gu, Seoul 130-743, Korea, Department of Chemical Engineering, Kongju National University, Gongju 314-701, Korea, Yim, Jin-Heong, Kim, Jongseob, Gidley, David. W., Vallery, Richard S., Peng, Hua-Gen, An, Duk Keun, Choi, Byoung-Ki, Park, Young-Kwon, Jeon, Jong-Ki, Department of Physics, University of Michigan, Ann Arbor, Michigan 48109, USA, Division of Advanced Materials Engineering, Kongju National University, 182, Sinkwan-dong, Gongju City, Chungnam 314-701, Korea ; Division of Advanced Materials Engineering, Kongju National University, 182, Sinkwan-dong, Gongju City, Chungnam 314-701, Korea., CSE Center, Samsung Advanced Institute of Technology (SAIT), San 14-1, Nongseo-ri, Kiheung-eup, Yongin-si, Kyungki-do 449-712, Korea, Department of Chemistry, Kangwon National University, Chun-Chon 200-701, Korea, Flex. Display Program Team, Samsung Advanced Institute of Technology (SAIT), San 14-1, Nongseo-ri, Kiheung-eup, Yongin-si, Kyungki-do 449-712, Korea, Faculty of Environmental Engineering, University of Seoul, 90 Jeonnong-dong, Dongdaemun-gu, Seoul 130-743, Korea, Department of Chemical Engineering, Kongju National University, Gongju 314-701, Korea, Yim, Jin-Heong, Kim, Jongseob, Gidley, David. W., Vallery, Richard S., Peng, Hua-Gen, An, Duk Keun, Choi, Byoung-Ki, Park, Young-Kwon, and Jeon, Jong-Ki
- Abstract
Summary: We report herein calixarene derivatives, which could adapt to various fields of application, as novel pore generators for making nanoporous materials. The pore structure of nanoporous materials exhibits disordered pores with small mesopore diameter (2–3 nm), which is similar to the micelle-like assembled structure of the calixarene compounds. The electro-optical properties such as dielectric constants and refractive indexes of these porous thin films can easily be manipulated. The calixarene-templated nanoporous films could find a variety of potential applications, such as low-dielectric constant ( k ) materials and high-surface area materials for catalysis and biotechnology. PM3-optimized structures of CA[4] and CA[6].
- Published
- 2007
31. Mathematical modeling of rail gun
- Author
-
Young, Kwon, Naval Postgraduate School (U.S.)., Mechanical Engineering and Astronautical Engineering, Pratikakis, Nikolaos, Young, Kwon, Naval Postgraduate School (U.S.)., Mechanical Engineering and Astronautical Engineering, and Pratikakis, Nikolaos
- Abstract
The exit velocity of the launch object along with the values of electric and thermal conductivity at the interfaces between the rails and the armature of a rail gun are critical issues. This thesis, using finite element method, estimates the former by solving the proper multiphysics governing equations, along with exploiting the contact theory between flat surfaces. A parametric analysis in the vicinity of the standard deviation of the normalized distance between the references planes of the rough surfaces was made for a variety of materials and textures at the interfaces. Furthermore, the amount of ohmic heat that is generated due to the application of the electric potential and the resistance of materials is estimated along with the average temperature at the interfaces. Finally, thermal stresses were also studied.
- Published
- 2006
32. Structural health monitoring: numerical damage predictor for composite structures
- Author
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Young Kwon, Mechanical Engineering, Lannamann, Daniel L., Young Kwon, Mechanical Engineering, and Lannamann, Daniel L.
- Abstract
The use of composite materials in both civil and military applications is increasing as composites potentially offer many advantages over traditional structural materials. Composites typically provide superior strength to weight ratio, better resistance to corrosion, and especially for military applications, greater ballistic protection. Wide use of composites is found in aircraft, armored vehicles, ships and civil structures This present research demonstrates the ability to numerically detect damage in a composite sandwich structure using a robust non-linear finite element model (FEM). FEM techniques are used to directly represent damage and the model's response is investigated. Changes in elemental strain and strain frequency, through a Fast Fourier Transform (FFT), is evaluated. Both a cantilevered beam and a simply supported plate are studied.
- Published
- 2001
33. Structural health monitoring: numerical damage predictor for composite structures
- Author
-
Young Kwon, Mechanical Engineering, Lannamann, Daniel L., Young Kwon, Mechanical Engineering, and Lannamann, Daniel L.
- Abstract
The use of composite materials in both civil and military applications is increasing as composites potentially offer many advantages over traditional structural materials. Composites typically provide superior strength to weight ratio, better resistance to corrosion, and especially for military applications, greater ballistic protection. Wide use of composites is found in aircraft, armored vehicles, ships and civil structures This present research demonstrates the ability to numerically detect damage in a composite sandwich structure using a robust non-linear finite element model (FEM). FEM techniques are used to directly represent damage and the model's response is investigated. Changes in elemental strain and strain frequency, through a Fast Fourier Transform (FFT), is evaluated. Both a cantilevered beam and a simply supported plate are studied., http://archive.org/details/structuralhealth1094510861
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