• Molecules and Cells
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• v.41 no.11
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• pp.953-963
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• 2018

The stepwise development of T cells from a multipotent precursor is guided by diverse mechanisms, including interactions among lineage-specific transcription factors (TFs) and epigenetic changes, such as DNA methylation and hydroxymethylation, which play crucial roles in mammalian development and lineage commitment. To elucidate the transcriptional networks and epigenetic mechanisms underlying T-cell lineage commitment, we investigated genome-wide changes in gene expression, DNA methylation and hydroxymethylation among populations representing five successive stages of T-cell development (DN3, DN4, DP, $CD4^+$, and $CD8^+$) by performing RNA-seq, MBD-seq and hMeDIP-seq, respectively. The most significant changes in the transcriptomes and epigenomes occurred during the DN4 to DP transition. During the DP stage, many genes involved in chromatin modification were up-regulated and exhibited dramatic changes in DNA hydroxymethylation. We also observed 436 alternative splicing events, and approximately 57% (252) of these events occurred during the DP stage. Many stage-specific, differentially methylated regions were observed near the stage-specific, differentially expressed genes. The dynamic changes in DNA methylation and hydroxymethylation were associated with the recruitment of stage-specific TFs. We elucidated interactive networks comprising TFs, chromatin modifiers, and DNA methylation and hope that this study provides a framework for the understanding of the molecular networks underlying T-cell lineage commitment.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.48-56
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• 2005

Purpose: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000~15,000 female births worldwide. The disease-causing gene has been identified as MECP2 (methyl-CpG-binding protein). In this study, we carried out diagnostic mutational analysis of MECP2 gene in RTT patients. Methods: We analyzed four exons and putative promoter of MECP2 gene from the peripheral blood of 43 Korean patients with RTT by PCR-RFLP and direct sequencing. Results: Mutations were detected in MECP2 gene about 60.5% of patients. The mutations consisted of 14 different types including 9 missense mutations, 4 nonsense mutations and 1 frameshift mutation. Of these, three mutations (G161E, T311M, P385fsX409) were newly identified and these were determined as disease-causing mutations by PCR-RFLP and direct sequencing analysis. Most of the mutations were located within MBD (42.3%) and TRD (50%). T158M, R270X, and R306C mutations were identified with high frequency. An intronic SNP (IVS3+23C>G) was newly identified in only three of the patients. It may be a disease-related and Korea-specific SNP with RTT. The L100V and A201V have been reported to be unclassified variant and SNP. However, these mutations were not found in more than 100 normal Korean control samples. These base substitutions seem to be the disease-causing mutations in Korean RTT contrary to previous studies. Conclusion: Disease-causing mutations and polymorphisms would be very important for diagnosing of RTT in Korean. The experimental procedure used in this study might be considered for molecular biologic diagnosis used in clinical field.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.6
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• pp.379-391
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• 2003

The present study was undertaken to evaluate bone regenerative capacity around titanium screw implants placed in irradiated rat's tibiae. At one week after single 15-Gy dose irradiation, miniaturized titanium screw implants were inserted into anterior aspect of the upper tibia of rats weighing 200-250g. Seventy rats were involved: 35 rats were control and 35 rats radiation group. The rats were killed at different intervals as 1, 2, 3, 4, 6, 8, 12 weeks after implantation for histologic observation, histomorphometric analysis and immunohistochemical study with fibronectin and CD34 antibody. 1. Histologically, various stages of bone maturation and ossification can be seen at 4 weeks and regenerated bone close to edges demonstrates more advanced calcification, and network of new bone are well formed at 12 weeks in non-irradiated group. In contrast, active bone formation with increased contact of newly formed bone to implant surface was noted at 4 weeks and a significant amount of new bone formation and bone-implant contact is oberved at 12 weeks in irradiated group. 2. Histomorphometrical analysis confirmed these histologic findings. A significant difference in implant-bone contact and bone density was measured between the control and radiation group. Mean MBD was 62.2% in control group and 27.5% in radiation group, mean MBIC was 86.6% in control group and 47.7% in radiation group, and mean TBIC was 87.3% in control group and 45.6% in radiation group at 12 weeks after implantation. 3. In immunohistochemical study with fibronectin and CD34, radiation reduced hematopoietic progenitor cells severely and disturbed differentiation of osteoblast in bone marrow. The results of this study revealed bone healing capacity around implant after radiation therapy was severely impaired and irradiation reduces the capacity for osseointegration of titanium implants. Many factors including radiation dose, period between radiation and implantation, bone quality, time elapse between first and second surgery, type of prosthetics and hyperbaric oxygen therapy must be considered carefully in postradiation implantation.

• Journal of the Computational Structural Engineering Institute of Korea
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• v.26 no.1
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• pp.1-7
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• 2013

Structural design and analysis of a coiling arm unloading machine for submarine cable have been originally conducted in this study. Three-dimensional CAD modeling process is practically applied for the structural design in detail. Finite element method(FEM) and multi-body dynamics(MBD) analyses are also used to verify the safety and required motions of the designed coiling arm structure. The effective moving functions of the designed coiling arm with respect to rotational and radial motions are achieved by adopting bearing-roller mechanical parts and hydraulic system. Critical design loading conditions due to its self weight, carrying cables, offshore wind, and hydraulic system over operation conditions are considered for the present structural analyses. In addition, possible inclined ground conditions for the installation of the designed coiling arm are also considered to verify overturn stability. The present hydraulic type coiling arm system is originally designed and developed in this study. The developed coiling arm has been installed at a harbor, successfully tested its operational functions, and finished practical unloading mission of the submarine cable.