• Bulletin of the Korean Chemical Society
• /
• 제25권9호
• /
• pp.1379-1384
• /
• 2004

Rearrangements of 1,3-oxathiolane sulfoxides 8 and 9 in the presence of base are described from a mechanistic viewpoint of sigmatropic and elimination reactions. In the presence of triethylamine the (Z)-sulfoxide 8 gave the corresponding thiolsulfinate 10 by way of dimerization of the sulfenic acid intermediate 2 at room temperature while the (E)-sulfoxide 9 was recovered even after refluxing in ethyl acetate by the reversal of the [2,3]-sigmatropic rearrangement of the sulfenic acid 4. Triethylamine promoted the developing charge separation in the transition state of the sigmatropic rearrangement of the (Z)-sulfoxide 8 to facilitate the ring opening to the sulfenic acid 2. The reason for more facile ring opening of the (Z)-sulfoxide 8 in comparison with the corresponding (E)-sulfoxide 9 is attributable to the differences in the reactivity of the hydrogen adjacent to the carbonyl group. Triethylamine was not strong base to deprotonate the carbonyl-activated methylene hydrogen of the (E)-sulfoxide 9 but enough to catalyze the sigmatropic process of the sulfoxides. The sulfenic acid 2 dimerized to the thiolsulfinate 10 while the sulfenic acid 4 proceeded the sigmatropic ring closure. In the presence of strong base such as potassium hydroxide, the elimination reaction was predominant over the sigmatropic rearrangement. In this reaction condition, both sulfoxides 8a and 9a gave a mixture of the disulfide 12, the isomeric disulfide 14, and the sulfinic acid 13. Under the strong alkaline condition an elimination of activated hydrogen from the carbon adjacent to the carbonyl group to furnish the sulfenic acid 2a and the isomeric sulfenic acid 18. The formation of the transient intermediate in the reaction was proven by isolation of the isomeric disulfide 14. The reactive entity was regarded as the sulfenic acid rather than sulfenate anion under these reaction conditions.

• Journal of Navigation and Port Research
• /
• 제36권8호
• /
• pp.665-671
• /
• 2012

A remarshalling is studied as an important operational strategy in an automated container terminal to enhance the productivity of container handling. This means the rearrangements of the containers scattered at a vertical yard block. The dispatching problem for remarshalling is selecting the remarshalling operation considering the available operation time and deciding the operation sequencing to maximize the effectiveness of remarshalling. This study develops the optimal mathematical model for yard crane dispatching problem with mixed integer program and explains dispatching problem using an example. However it is difficult to apply this model to a field problem because of its computational time. Therefore, we compare the representative 5 dispatching rules for real world adaption. In a numerical experiment, maximum weight ratio(MR) rule shows an overall outstanding performance.

• Journal of Genetic Medicine
• /
• 제7권2호
• /
• pp.111-118
• /
• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
• /
• 제26권1호
• /
• pp.9-16
• /
• 2008

Korea's GIS market has been proliferating since the 1990s, but still its scale and the structure require overall rearrangements. Recently as the needs and initiatives from central and local governments go stronger to drive 'u-City(ubiquitous City)' developments, there are much more demand of spatial information from sectors like city management, construction, environment and so on. Through the merge between GIS and the advanced Information and Telecommunication Technology, the introduction of new Ubiquitous IT is swiftly changing GIS market environments, so the GIS industry is to be prepared for this trend. The pioneering developments of Ubiquitous-related GIS technologies are expected to highly boost spatial data and related industries, and the pre-occupancy of those technologies in the world would enable the expansion of overseas export market. In the context of these epoch-making chances, by looking into the actual status of GIS industry, this study is to investigate the actual accomplishments to foster the GIS industry through Korea's National GIS Master Plan. Thereby, impending issues will be discussed to provide useful problem-solving suggestions.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권6호
• /
• pp.2909-2916
• /
• 2016

Background: Canine malignant lymphoma is classified into B- or T-cell origin, as in the human case. Due to differences in prognosis, a suitable method needs to be developed for lineage identification. Aims: To determine the accuracy of immunophenotypic and molecular information between three methods: immunocytochemistry (ICC), immunohistochemistry (IHC) and heteroduplex polymerase chain reaction for antigen receptor rearrangements (hPARR) in spontaneous canine lymphomas. Materials and Methods: Peripheral blood, fine needle aspiration and tissue biopsies from enlarged peripheral lymph nodes prior to treatment of 28 multicentric lymphoma patients were collected. Cytopathology and histopathology were examined and classified using the updated Kiel and WHO classifications, respectively. Anti-Pax5 and anti-CD3 antibodies as B- and T-cell markers were applied for immunophenotyping by ICC and IHC. Neoplastic lymphocytes from lymph node and white blood cell pellets from peripheral blood were evaluated by hPARR. Results: In this study, low grade B-cell lymphoma accounted for 25% (7/28), high grade B-cell lymphoma for 64.3% (18/28) and high grade T-cell lymphoma for 10.7% (3/28). According to the WHO classification, 50% of all cases were classified as diffuse large B-cell lymphoma. In addition, ICC showed concordant results with IHC; all B-cell lymphomas showed Pax5+/CD3, and all T-cell lymphomas exhibited Pax5-/CD3+. In contrast to hPARR, 12 B-cell lymphomas featured the IgH gene; seven presented the $TCR{\gamma}$ gene; five cases showed both IgH and $TCR{\gamma}$ genes, and one case were indeterminate. Three T-cell lymphomas showed the $TCR{\gamma}$ gene. The percentage agreement between hPARR and ICC/IHC was 60%. Conclusions: Immunophenotyping should not rely on a single method. ICC or IHC with hPARR should be used concurrently for immunophenotypic diagnosis in canine lymphomas.

• Polymer(Korea)
• /
• 제33권2호
• /
• pp.183-188
• /
• 2009

Structural rearrangements of uni-axially deformed polyethylenes containing 1-octene comonomer and HDPE upon heating were investigated by time-resolved small and wide angle X-ray scattering techniques. During heating, structural changes including crystal transformation and lamellar rearrangement noted were very different depending on the comonomer contents. At low comonomer content below 2 wt%, inverse martensitic transformation of crystal lattice from monoclinic to orthorhombic cell and the rearrangement of broken lamellar units into more ordered and perfect lamellar stacks were noted with the temperature increase. At high contents above 9.5 wt%, however, polyethylene copolymers showed neither the crystal transformation nor lamellar rearrangement that can be attributed to low crystallinity and high content of branch units.

• Journal of Gynecologic Oncology
• /
• 제29권6호
• /
• pp.90.1-90.12
• /
• 2018

Objective: We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations. Methods: All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis. Results: In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer. Conclusion: Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients.

• Genomics & Informatics
• /
• 제19권3호
• /
• pp.29.1-29.10
• /
• 2021

In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H₂O₂. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: -15 vs. -13.8 kcal/mol; and dissociation constant, K_d of wild-type vs. mutant: 7.2E^-12 vs. 7.0E^-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG(0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

• Biomolecules & Therapeutics
• /
• 제30권4호
• /
• pp.360-367
• /
• 2022

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor. Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion. KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.

• Journal of Marine Life Science
• /
• 제1권2호
• /
• pp.88-94
• /
• 2016

Determining the infection history of living organisms is essential for understanding the evolution of infection agents with their host, particularly for key aspects such as immunity. Viruses, which can spread between individuals and often cause disease, have been widely examined. The increasing availability of fish genome sequences has provided specific insights into the diversity and host distribution of retroviruses in fish. The shortspine spurdog (Squalus mitsukurii) is an important elasmobranch species; this medium-sized dogfish typically lives at depths of 100~500 m. However, the retroviral envelope polyprotein in dogfish has not been examined. Thus, the aim of the present study was to identify and analyze the retroviral envelope polyprotein in various tissues of dogfish. The 1334-base pair full-length novel cDNA of dogfish envelope polyprotein (dEnv) was obtained by 3' and 5'-rapid amplification of cDNA end analysis from S. mitsukurii. The open reading frame showed a complete coding sequence of 815 base pairs with a deduced peptide sequence of 183 amino acids that exhibited 34~50% identity with other fish and bird species. It was also expressed according to reverse transcription and real-time polymerase chain reaction in the kidney, liver, intestine, and lung, but not in the gill. This distribution can be assessed by identifying and analyzing endogenous retroviruses in fish, which consists of three main genes: gag, pol and env. Dogfish envelope polyprotein sequence is likely important in evolution and induces rearrangements, altering the regulatory and coding sequences. This is the first report of the identification and molecular characterization of retroviral envelope polyprotein in various tissues of S. mitsukurii.