Seoul National University
  • Seoul, South Korea
Recent publications
6016-T4 aluminum alloy and DP490 steel were systematically tested under 24 proportional loading paths, including uniaxial tensile tests with a 15° increment, uniaxial compressive and simple shear tests with a 45° increment, and biaxial tensile tests using cruciform specimens. Cruciform specimens in the rolling/transverse and 45°/135° sampling directions were tested with seven and four different stress ratios, respectively. The normal and diagonal planes plastic work contours and the yield stresses under uniaxial tension and compression were measured to investigate the anisotropic yield. Meanwhile, the normal and diagonal planes directions of plastic strain rate and the rα-values under uniaxial tension and compression were characterized to confirm the plastic flow. Several existing asymmetric yield criteria under the associated and non-associated flow rules were comprehensively evaluated to describe the asymmetric plastic anisotropy of 6016-T4 aluminum alloy and DP490 steel. The results suggest that in the investigated yield criteria, the non-associated models can predict the tension and compression asymmetry of materials more accurately than the associated models, and the function of stress triaxiality can more effectively describe the asymmetric yield behavior than the first stress invariant. In addition, the pure shear stress states are helpful in assessing the validity and applicability of advanced asymmetric yield stress functions, and the inspection of diagonal plane plastic work contours containing more pure shear stress states should prioritized over that of normal plane plastic work contours. The evaluation of plastic potential functions should not only consider the prediction accuracy of the normal plane directions of plastic strain rate, but also further check the diagonal plane directions of plastic strain rate. Expressing mechanical properties as a function of equivalent plastic strain to calibrate parameters of the yield criterion allows the continuous capture of anisotropic evolution of the asymmetric yield surface and the changes in the asymmetric plastic potential surface.
In the processes for designing and assessing structural systems, it is essential to evaluate their reliability against stochastic loads caused by natural or human-made hazards, e.g., wind loads, earthquakes, and collisions. The first-passage probability is a crucial measure of a system's reliability under such conditions. However, the first-passage probability estimation generally requires repetitive dynamic simulations and thus may result in high computational cost. This paper proposes a new active-learning-based surrogate method that efficiently estimates the first-passage probability under stochastic wind excitations to address the computational issue. The proposed method introduces an alternative formulation using the conditional distribution of the maximum response given time-invariant uncertain parameters to handle the high dimensionality of stochastic excitation sequences. The method employs the Gaussian-process-based surrogate model with heteroscedastic noises to fit the distribution parameter functions considering uncertainties arising from the structural system and the environmental loads. In addition, an adaptive training process of surrogates is introduced to identify the best experimental designs achieving efficient convergence. The numerical examples of an eight-story building and a transmission tower demonstrate that the proposed method can produce accurate estimation results with fewer structural simulations than existing methods.
Microalgal biomass harvesting and cell disruption are the main bottlenecks for downstream processing of microalgae such as high-value bioproducts extraction and biofuels production. In this study, we evaluated the performance of dual flocculation between cationic surfactants and bio-polymer of chitosan for simultaneous biomass harvesting and bioproducts extraction from Chlorella sorokiniana microalgae. First, the effects of individual natural flocculants of chitosan and two cationic surfactants: cetyltrimethylammonium bromide (CTAB) and dodecyltrimethylammonium bromide (DTAB) on biomass harvesting were studied. Next, the synergistic effect of dual flocculation between the cationic surfactants and chitosan on harvesting efficiency, time and flocculant dosage was investigated. Finally, we evaluated the potential of high value bioproducts extraction from microalgae after the individual and dual flocculation processes. Zeta potential analysis and microscopic images were employed to achieve mechanistic understanding. Maximum biomass harvesting efficiencies of 85 %, 88 % and 78 % were achieved using individual flocculants of chitosan, CTAB and DTAB, under their optimum dosages of 100, 400 and 4000 mg/L, respectively. A significant synergistic effect of dual flocculation between chitosan (C) and cationic surfactants on biomass harvesting efficiency (CTAB-C: 99 % and DTAB-C: 97 %), settling time (CTAB-C: 2 min and DTAB-C: 5 min) and optimum dosage of surfactants (CTAB-C: 100 mg/L and DTAB-C: 1000 mg/L) was observed. The synergistic effect was associated with multiple flocculation mechanisms of charge neutralization and bridging induced by cationic surfactants and chitosan, respectively. Furthermore, bioproducts recovery efficiencies of 12 %, 25 % and 15 % of cell dry weight were achieved for protein, carbohydrate and lipid, respectively by using dual flocculation of CTAB surfactant and chitosan at much lower dosage of 100 mg/L.
This study explores travelers’ preference for shared micromobility in the context of last-mile travel from shared parking lots to their final destination in the city center. Based on the results of the stated preference experiment and error component logit model incorporating latent variables, we found that the preference for shared micromobility is affected by the uncertainty of availability as well as both travel time and fare. More specifically, our alternative-specific part-worth utility approach shows that their marginal effects are non-linear, and this suggests several policy implications. Also, we found that there is a significant substitution between shared micromobility modes. Furthermore, various latent perspectives, including safety and management concerns of shared micromobility, have significant impacts on the preference.
CTLA4-CD28 gene fusion has been reported to occur in diverse types of T cell lymphoma. The fusion event is expected to convert inhibitory signals to activating signals and promote proliferation and potentially transformation of T cells. To test the function of the CTLA4-CD28 fusion gene in vivo, we generated a murine model that expresses the gene in a T cell-specific manner. The transgenic mice have shorter life spans and display inflammatory responses including lymphadenopathy and splenomegaly. T cells in turn show higher levels of activation and infiltrate various organs including the lung and skin. T cells, in particular CD4+ helper T cells, were also readily transplantable to immunocompromised mice. Transcriptomic profiling revealed that the gene expression pattern in CD4 + T cells closely resembles that of adult T cell leukemia/lymphoma (ATLL) and that of angioimmunoblastic T cell lymphoma (AITL) tissues. Consistently, we detected supernumerary FOXP3+ cells and PD-1+ cells in transgenic and transplanted mice. This is the first report demonstrating the transforming activity of the CTLA4-CD28 fusion gene in vivo, and this murine model should be useful in dissecting the molecular events downstream to this mutation.
For clinical application by dendritic cell (DC)-based cancer immunotherapy, a proper adjuvant system to elicit a strong anticancer immune response is needed. Here, we investigated the potential of chorismate mutase (TBCM, Rv1885c), a putative Mycobacterium tuberculosis (TB) virulence factor, as an immunoadjuvant in DC-based tumor immunotherapy. First, we found that TBCM functionally activated DCs by upregulating costimulatory molecules, increasing the secretion of proinflammatory cytokines, enhancing migration and inducing the Th1-type immune response in a dose-dependent manner via TLR4-mediated signaling. In addition, subcutaneous injection of TBCM-activated DCs loaded with cell lysates led to reduced tumor mass, enhanced mouse survival and lowered tumor incidence in lung carcinoma (LLC) cell-bearing mice. This is mainly mediated by functional cytotoxic T lymphocyte-mediated oncolytic activity and inhibition of cancer proliferation- and metastasis-related genes. Moreover, TBCM-induced DCs can also generate memory CD4 T cells and exert long-term tumor prevention effects. In conclusion, our findings suggest that TBCM (Rv1885c), a novel TLR4 agonist, could be used as an immunoadjuvant for DC-based cancer immunotherapy.
Alternative splicing (AS) contributes to diversifying and regulating cellular responses to environmental conditions and developmental cues by differentially producing multiple mRNA and protein isoforms from a single gene. Previous studies on AS in pathogenic fungi focused on profiling AS isoforms under a limited number of conditions. We analysed AS profiles in the rice blast fungus Magnaporthe oryzae, a global threat to rice production, using high-quality transcriptome data representing its vegetative growth (mycelia) and multiple host infection stages. We identified 4,270 AS isoforms derived from 2,413 genes, including 499 genes presumably regulated by infection-specific AS. AS appears to increase during infection, with 32.7% of the AS isoforms being produced during infection but absent in mycelia. Analysis of the isoforms observed at each infection stage showed that 636 AS isoforms were more abundant than corresponding annotated mRNAs, especially after initial hyphal penetration into host cell. Many such dominant isoforms were predicted to encode regulatory proteins such as transcription factors and phospho-transferases. We also identified the genes encoding distinct proteins via AS and confirmed the translation of some isoforms via a proteomic analysis, suggesting potential AS-mediated neo-functionalization of some genes during infection. Comprehensive profiling of the pattern of genome-wide AS during multiple stages of rice-M. oryzae interaction established a foundational resource that will help investigate the role and regulation of AS during rice infection.
Burning mouth syndrome (BMS) is a chronic pain condition accompanied by unpleasant burning sensations of the oral mucosa. While multiple factors were proposed for the etiology, evidence suggested a neuropathic pain origin while others suspected the use of antibiotics as the underlying cause. Interestingly, several reports demonstrated the intimate interaction of the nervous system and the microbiome. The current study aims to elucidate the correlation of the oral microbiome with the pathophysiology of the primary BMS. Microbiome samples obtained from the unstimulated whole saliva of 19 primary BMS patients and 22 healthy controls were sequenced and analyzed of the V3-V4 region of 16S rRNA gene. There was a distinct difference in the microbial composition between the BMS and the control groups at all taxonomic levels. Alpha diversity indexes of the oral microbiome were significantly lower in the BMS group. The samples were readily distinguished by multidimensional scaling analysis and linear discriminant analysis effect size. Streptococcus, Rothia, Bergeyella, and Granulicatella genus were dominant in the BMS group, while Prevotella, Haemophilus, Fusobacterium, Campylobacter, and Allorevotella genus were more abundant in the healthy group. Distinct microbiome signatures of BMS patients suggested a diagnostic value and a potential role in the pathogenesis of BMS.
The gut microbiome influences the development of allergic diseases during early childhood. However, there is a lack of comprehensive understanding of microbiome-host crosstalk. Here, we analyzed the influence of gut microbiome dynamics in early childhood on atopic dermatitis (AD) and the potential interactions between host and microbiome that control this homeostasis. We analyzed the gut microbiome in 346 fecal samples (6-36 months; 112 non-AD, 110 mild AD, and 124 moderate to severe AD) from the Longitudinal Cohort for Childhood Origin of Asthma and Allergic Disease birth cohort. The microbiome-host interactions were analyzed in animal and in vitro cell assays. Although the gut microbiome maturated with age in both AD and non-AD groups, its development was disordered in the AD group. Disordered colonization of short-chain fatty acids (SCFA) producers along with age led to abnormal SCFA production and increased IgE levels. A butyrate deficiency and downregulation of GPR109A and PPAR-γ genes were detected in AD-induced mice. Insufficient butyrate decreases the oxygen consumption rate of host cells, which can release oxygen to the gut and perturb the gut microbiome. The disordered gut microbiome development could aggravate balanced microbiome-host interactions, including immune responses during early childhood with AD.
Despite a short history since its first isolation, Akkermansia muciniphila has been extensively studied in relation to its effects on human metabolism. A recent human intervention study also demonstrated that the bacterium is safe to use for therapeutic purposes. The best-known effects of A. muciniphila in human health and disease relate to its ability to strengthen gut integrity, modulate insulin resistance, and protect the host from metabolic inflammation. A further molecular mechanism, induction of GLP-1 secretion through ICAM-2 receptor, was recently discovered with the identification of a new bacterial protein produced by A. muciniphila. However, other studies have suggested a detrimental role for A. muciniphila in specific host immune settings. Here, we evaluate the molecular, mechanistic effects of A. muciniphila in host health and suggest some of the missing links to be connected before the organism should be considered as a next-generation biotherapeutic agent.
Nonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae, significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL (SIRT1 and SREBF2) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis.
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17,083 members
Inhong Song
  • Rural Systems Engineering, College of Agriculture and Life Sciences
Gun-Do Lee
  • Department of Materials Science and Engineering
YounJoon Jung
  • Department of Chemistry
Gwanak-ro 1, 08826, Seoul, South Korea