Association between Genetic Polymorphism of Multidrug Resistance 1 Gene and Sasang Constitutions

Multidrug resistance 1 (MDR1) is a gene that expresses P-glycoprotein (P-gp), a drug transporter protein. Genetic polymorphisms of MDR1 can be associated with Sasang constitutions because Sasang constitutional medicine (SCM) prescribes different drugs according to different constitutions. A Questionnaire for Sasang Constitution Classification II (QSCC II) was used to diagnose Sasang constitutions. Two hundred and seven healthy people whose Sasang constitutions had been identified were tested. Genotype analyses, restriction fragment length polymorphism (RFLP) and pyrosequencing were used in MDR1 C1236T, and in MDR1 G2677T/A and C3435T, respectively. Significant differences in MDR1 C1236T genotypes were found between So-yangin and So-eumin. MDR1 G2677T/A genotype also showed significant differences in allele distribution between So-yangin and Tae-eumin. So-yangin and So-eumin showed significant differences in the distribution of both 1236C-2677G-3435C and 1236T-2677G-3435T, haplotypes of MDR1. The genetic polymorphism of the MDR1 gene was thus shown to be an indicator that could distinguish So-yangin from other constitutions

Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas

Background The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs), and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of tumoral PD-L1/immune cell PD-L1/CD8+ TILs may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.This work was supported by the Basic Science Research Program of the National Research Foundation of Korea, which is funded by the Ministry of Education (2016R1D1A1B01010316)

In situ induction of dendritic cell–based T cell tolerance in humanized mice and nonhuman primates

Administration of an ICAM-1–specific antibody arrests dendritic cells in a semi-immature state and facilitates antigen-specific T cell tolerance to islet allografts in humanized mice and Rhesus monkeys

Contact morphology and constitutive equation in evaluating tensile properties of austenitic stainless steels through instrumented spherical indentation

We evaluate representative stress and strain of austenitic stainless steels using instrumented indentation tests with a spherical indenter by taking into account the real contact depth and effective radius. We investigate the relation between material pileup underneath the spherical indenter and the strain-hardening exponent in uniaxial tensile tests for these steels. We evaluate the suitability of three constitutive equations, the Hollomon, Ludwigson, and Swift equations, for describing linear-type strain-hardening of austenitic stainless steels. Using the real contact depth and effective radii developed for the austenitic stainless steels, we find good agreement between representative stress and strain in instrumented indentation and uniaxial tensile tests.close3

Extended expanding cavity model for measurement of flow properties using instrumented spherical indentation

We propose an extended expanding cavity model (ECM) in instrumented spherical indentation to evaluate flow properties measured in uniaxial mechanical testing. We describe the mean pressure of the projected surface from radial stress at the hemispherical core boundary with a scaling factor for strain-hardening metals. Plastic constraint factors determined by the strain-hardening exponent, yield strain and scaling factor successfully illustrate flow stress-strain points in uniaxial tension tests. We suggest a novel way to determine the strain-hardening exponent from the ratio of indentation loading slope, and a modified Meyer relation to measure yield strengths.close2

The first record of leucism in the Rhabdophis tigrinus (Boie, 1826) (Squamata, Colubridae) in South Korea

Abstract Leucism, in which pigmentation is lost over part or the entire body of an animal, has a range of possible genetic causes. Here, we report leucism in an individual tiger keelback (Rhabdophis tigrinus) found on Jeung Island, Shinan‐gun, Jeollanam‐do, South Korea, during a survey of the distribution of reptiles in the area. The individual was observed sunbathing in the bushes next to a pond. This individual exhibited ecdysis, thus it considered that have normal feeding activity. Our report represents the first observation of leucism in R. tigrinus, and thus, further analysis is needed of this phenotype to more clearly understand its impact on the species and its natural history

Constitutive equations optimized for determining strengths of metallic alloys

We investigate compatibilities of three constitutive equations, the Hollomon, the Swift, and the Voce equations for determination of yield and ultimate tensile strengths based on tensile true stress-strain curves of 27 metal alloys including those with power-law type and linear-type strain-hardening. We analyze each constitutive equation in terms of yield strength determined by the intercept of the linear elastic loading curve and plastic flow curve and ultimate tensile strength evaluated by the concept of instability in tension. We found that the describing plastic flow is very sensitive in determination of the yield strength and tensile strength from parameters of constitutive equation. Voce equation gives estimate yield strength and tensile strength better than Hollomon and Swift equations.close1