Seong-Wan Park

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.

Parkinson's disease (PD) is a progressive neurodegenerative disorder. However, cell type-dependent transcriptional regulatory programs responsible for PD pathogenesis remain elusive. Here, we establish transcriptomic and epigenomic landscapes of the substantia nigra by profiling 113,207 nuclei obtained from healthy controls and patients with PD. Our multiomics data integration provides cell type annotation of 128,724 cis-regulatory elements (cREs) and uncovers cell type-specific dysregulations in cREs with a strong transcriptional influence on genes implicated in PD. The establishment of high-resolution three-dimensional chromatin contact maps identifies 656 target genes of dysregulated cREs and genetic risk loci, uncovering both potential and known PD risk genes. Notably, these candidate genes exhibit modular gene expression patterns with unique molecular signatures in distinct cell types, highlighting altered molecular mechanisms in dopaminergic neurons and glial cells including oligodendrocytes and microglia. Together, our single-cell transcriptome and epigenome reveal cell type-specific disruption in transcriptional regulations related to PD.

This volume comprises three keynote lectures by internationally well-known experts in the field of underground construction, the inaugural Fujita lecture to honor professor Keiichi Fujita, and the regular papers presented at the 8th International Symposium on Geotechnical Aspects of Underground Construction in Soft Ground (IS-Seoul 2014). Topics co

Most low-volume roads are primarily thin flexible pavements with an unbound base and subgrades. This is especially true for the behavior of unbound pavement materials, which is very nonlinear and stress dependent, even at low traffic stresses. A need therefore exists for more realistic prediction of pavement response for such pavements, based on proper constitutive models and computational methods. For this reason, the nonlinear, stress-dependent finite-element program for pavement analysis was developed. Stress-dependent models for the resilient modulus and Poisson’s ratio of unbound pavement materials are incorporated into the finite-element model to predict the resilient behavior within the pavement layers under specified wheel loads. The results of this study show that the developed finite-element model with stress dependency is suitable for calculating a reduced horizontal tension in the bottom half of unbound aggregate base layers. Unlike conventional methods for correcting horizontal tension, compressive stresses can be obtained only by the use of proper constitutive material models and the finite-element approach. It is also noted that the effects of nonlinearity and the varying stress-dependent modulus and Poisson’s ratio, especially in the base layers, could be substantial, and the proper selection of material properties is very important to improve the prediction of those behaviors.