• Title/Summary/Keyword: bearing mechanism

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Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

  • Elhag, Osama A.O.;Hu, Xiao-Jing;Wen-Ying, Zhang;Li, Xiong;Yuan, Yong-Ze;Deng, Ling-Feng;Liu, De-Li;Liu, Ying-Le;Hui, Geng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4031-4036
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    • 2012
  • Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

Geochemistry and Mineralogy of Metapelite and Barium-Vanadium Muscovite from the Ogcheon Supergroup of the Deokpyeong Area, Korea (덕평지역(德平地域)의 옥천누층군(沃川累層群)에 분포(分布)하는 변성이질암(變成泥質岩)과 바륨-바나듐 백운모(白雲母)의 지구화학적(地球化學的) 및 광물학적(鑛物學的) 특성(特性))

  • Lee, Chan Hee;Lee, Hyun Koo
    • Economic and Environmental Geology
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    • v.30 no.1
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    • pp.35-49
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    • 1997
  • The coal formation of the Deokpyeong area are interbedded along metapelites of the Ogcheon Supergroup, which are composed mainly of graphite, quartz, muscovite and associated with small amounts of biotite, chlorite, pyrite and barite. The ratios of $SiO_2/Al_2O_3$, $Al_2O_3/Na_2O$ and $K_2O/Na_2O$ of the coaly metapelite are variable and wide range from 1.80 to 10.21, from 27.8 to 388.8 and from 7.6 to 61.8, respectively. These coal formation were deposited in basin of marine environments, and the REE of these rocks are not influenced with metamorphism and hydrothermal alterations on the basis of $Al_2O_3$ versus La, La against Ce, the ratios of La/Ce (0.19 to 0.99) and Th/U (0.02 to 4.75). These rocks also show much variation in $La_N/Yb_N$ (1.19 to 22.89), Th/Yb (0.14 to 21.43) and La/Th (0.44 to 13.67), and their origin is explained by derivation from a mixture of sedimentary and igneous rocks. The wide range in trace and REE element characteristics as Co/Th (0.12 to 2.78), La/Sc (0.33 to 10.18), Sc/Th (0.57 to 5.73), V/Ni (8 to 2347), Cr/V (0.02 to 0.67) and Ni/Co (1.56 to 32.95) of these coaly metapelites argues for inefficient mixing of the various source lithologies during sedimentation. Deep to pale green barium-vanadium muscovites (vanadium-oellacherite) have been found in this coal formations. Modes of occurrence and grain size of muscovite are heterogeneous, but most of the barium and vanadium-bearing muscovites occur along the boundaries between graphite and quartz grains, ranging from 200 to $350{\mu}m$ in length and from 40 to $60{\mu}m$ in width. Results of X-ray diffraction data of the minerals characterized to be monoclinic system with $a=5.249{\AA}$, $b=8.939{\AA}$, $c=20.924{\AA}$ and ${\beta}=95.894^{\circ}$. Representative chemical formula of the muscovite was $(Na_{0.09}K_{1.44}Ba_{0.46})(Al_{2.75}Ti_{0.07}V_{0.56}Fe_{0.08}Mg_{0.50})(Si_{6.12}Al_{1.88})O_{22}$. The V possibly substitute octahedral Al, and the Ba is coupled substitution of $K^+Si^{4+}=Ba^{2+}Na^+Ca^{2+}$, which compositional ranges of V and Ba are from 0.42 to 0.69 and from 0.34 to 0.56 based on $O_{22}$, respectively. Formation mechanism of the barium-vanadium muscovites in the coaly metapelite is shown that the formed by high pressure and temperature from regional metamorphism origanated during diagenesis at the interface between a basinal brine and organic matter.

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Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

  • Zhang, Yong-Chun;Jiang, Gang;Gao, Han;Liu, Hua-Min;Liang, Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2353-2358
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    • 2014
  • Purpose: We aimed to detect the expression of HIF-1${\alpha}$, VEGF, HPSE-1 and CD31 in SKOV3 xenografts in nude mice treated with different doses of ionizing radiation, trying to explore the possible mechanism of hypoxia and radioresistance. Methods: Nude mice bearing SKOV3 xenografts were randomly divided into 4 groups: Group A (control group, no ionizing radiation), Group B (treated with low dose of ionizing radiation: 50cGy), Group C (treated with high dose of ionizing radiation: 300cGy), Group D ( combined ionizing radiation, treated with ionizing radiation from low dose to high dose : 50cGy first and 300cGy after 6h interval). The mRNA levels of HIF-1 and VEGF in each group were detected by real time polymerase chain reaction, while HPSE-1 expression was measured by ELISA. The microvessel density (MVD) and hypoxic cells were determined through immunohistochemical (IHC) staining of CD31 and HIF-1a. Results: Significant differences of HIF-1${\alpha}$ mRNA level could be found among the 4 groups (F=74.164, P<0.001): Group C>Group A>Group D> Group B. The mRNA level of VEGF in Group C was significantly higher than in the other three groups (t=-5.267, P=0.000), while no significant difference was observed among Group A, B and D (t=1.528, 1.588; P=0.205, 0.222). In addition, the MVD was shown to be the highest in Group C (t=6.253, P=0.000), whereas the HPSE-1 level in Group A was lower than in Group B (t=14.066, P=0.000) and higher than in Group C (t=-21.919, P=0.000), and similar with Group D (t=-2.066, P=0.058). Through IHC staining of HIF-1a, the expression of hypoxic cells in Group A was (++), Group B was (+), Group C was (+++) and Group D was (+). Conclusion: Ionizing radiation with lowerdoses might improve tumor hypoxia through inhibiting the expression of HIF-1 and HPSE-1, whereas higherdoses worsen tumor hypoxic conditions by up-regulating HIF-1${\alpha}$, HPSE-1, VEGF and CD31 levels. A protocol of low-dose ionizing radiation followed by a high-dose irradiation might at least partly improve tumor hypoxia and enhance radiosensitivity.

Mineralogical Changes in the Weathering Profiles of Carnin Gneiss in the Yoogoo Area, Korea (유구지역 화강암질 편마암의 풍화작용에 의한 광물 조성의 변화)

  • 이석훈;김수진
    • Journal of the Mineralogical Society of Korea
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    • v.13 no.3
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    • pp.121-137
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    • 2000
  • Weathering profiles which were developed under a temperate, humid environment and relatively steep geography, show a thick saprolite and soil horiaon in the Precambrian granitic gneiss of the Yoogoo area. In the weathering profiles, secondary minerals such as interstratified biotite/vermiculite, tri- or di-octahedral vermiculite, halloysite, kaolinite, illite, smectite, gibsite and geothite were observed. Kaolinization of biotite is the most prevalent mechanism but vermiculitization is a minor from all ofweathering profiles. Biotite altered to B/V mixed layer-vermiculite, to illite and to halloysite, kaolinite and gibbsite. Halloysite is the most frequently observed weathering product of biotite in these profiles. Goethite is observed at the around or opened fissures of altered biotite. Tubular halloysite aggregates was fDrmed from dissolution-precipitation of plagioclase. The occurrence of halloysite aggregates is divided into a preferentially oriented type and a wrinkled one which were resulted from the dissolved type of plagioclase. Fe-bearing minerals have also been subjected to dissolution leaving the precipitation of geothite along dissolution voids. The profile of granitic gneiss is a typical weathering pattern showing a clay minerals increase toward the surface. Weathering of minerals were controlled by locally acidic and good-drainage environment, and formed a various and complicated secondary minerals in this study area.

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Distribution of Radionuclide Labeled Liposome in Experimental Study (방사성동위원소표지 Liposome의 분포에 대한 실험적 연구)

  • Lee, Bum-Woo;Jeong, Jae-Min;Kim, Sang-Eun;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon;Ha, Sung-Whan
    • The Korean Journal of Nuclear Medicine
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    • v.24 no.2
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    • pp.317-324
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    • 1990
  • Liposome was labelled with $^{99m}Tc$ after negative charged liposome was formed with combination of a few lipid components. $^{99m}Tc$ liposome was injected through the tail vein of C3H mice bearing fibrosarcoma and biodistribution of $^{99m}Tc$ liposome was evaluated. The results were as follows: 1) We confirmed formation of liposome which was small unillamellar and multilamellar vesicles. 2) In this experiment the optimal concentration of $SnCl_2$ was $156{\mu}g/ml$ to label liposome with $^{99m}Tc$ and labelling efficiency was 95%. 3) The labelled liposome was stable when it was incubated with human serum for 24 hours. Mean labelling efficiency was 94% at 24 hour. 4) The main uptake sites of Tc-99m liposome were liver and spleen. It showed significantly higher uptake than $^{99m}Tc$ HSA (p < 0.001). 5) $^{99m}Tc$ liposome uptake in tumor tissue was not significantly higher than $^{99m}Tc$ HSA uptake. In conclusion, $^{99m}Tc$ liposome disclosed high labelling efficiency and was highly stable. Liver and spleen were main uptake sites of $^{99m}Tc$ liposome. The uptake mechanism of $^{99m}Tc$ liposome also seemed to be different from that of $^{99m}Tc$ HSA. We conclude that $^{99m}Tc$ liposome would be a promising agents for the imaging of some tumor.

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Germanium-Fortified Yeast Activates Macrophage, NK Cells and B Cells and Inhibits Tumor Progression in Mice. (게르마늄 강화효모의 마우스에서의 암세포 억제 및 대식세포, NK 세포, B 세포의 활성화에 관한 연구)

  • Baek, Dae-Heoun;Jung, Jin-Wook;Sohn, Tsang-Uk;Kang, Jong-Koo
    • Microbiology and Biotechnology Letters
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    • v.35 no.2
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    • pp.118-127
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    • 2007
  • Germanium-fortified yeast (GY) is a organic germanium-fortified yeast with potent immune modulating activities including anti-inflammatory effect. Through cell line studies, we observed that GY can modulate the diverse immune activity but little evidence was provided on the mechanism of GY in modulating immune activities in other higher animals. In this study, we investigated the effect of GY on modulation of immune function in mice. GY was administered in normal mice or tumor-bearing mice and then effect of GY on modulation of host immune system was analyzed by using ex vivo isolated macrophages, B cells, NK cells. Admistration of GY in mice induced macrophage activation thereby increased effector function of macrophage such as increased phagocytosis, chemotaxis, adherence, $O_2-release$, NO, $TNF-{\alpha}$ production. In addition, GY administration Increased B lymphocyte activation and plaque forming cells. Furthermore, GY administration increased NK-cell mediated cytotoxicity. Furthermore, GY administration suppressed progression of tumor in mice by increasing $TNF-{\alpha}$ production and effector function of NK cells. Our results showed that GY has a potent immunostimulatory function in vivo mice model. Proper modulation and administration of GY in human could be helpful to maintaining immunological homeostasis by modulating host immune system.

The effect of Swd2's binding to Set1 on the dual functions of Swd2 in Saccharomyces cerevisiae (Saccharomyces cerevisiae의 Swd2와 Set1의 결합이 Swd2의 이중적인 기능에 미치는 영향)

  • Park, Shinae;Lee, Jung-Shin
    • Korean Journal of Microbiology
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    • v.53 no.4
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    • pp.286-291
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    • 2017
  • In eukaryotic cells, histone modification is an important mechanism to regulate the chromatin structure. The methylation of the fourth lysine on histone H3 (H3K4) by Set1 complex is one of the various well-known histone modifications. Set1 complex has seven subunits including Swd2, which is known to be important for H2B ubiquitination dependent on H3K4 methylation. Swd2 was reported to regulate Set1's methyltransferase activity by binding to near RNA recognition motif (RRM) domain of Set1 and to act as a component of CPF (Cleavage and Polyadenylation Factors) complex involved in RNA 3' end processing. According to the recent reports, two functions of Swd2 work independently of each other and the lethality of Swd2 knockout strain was known to be caused by its function as a component of CPF complex. In this study, we found that Swd2 could influence the Set1's stability as well as histone methyltransferase activity through the association with RRM domain of Set1. Also, we found that ${\Delta}swd2$ mutant bearing truncated-Set1, which cannot interact with Swd2, lost its lethality and grew normally. These results suggest that the dual functions of Swd2 in H3K4 methylation and RNA 3' end processing are not independent in Saccharomyces cerevisiae.

Differences in Static Lower Extremity Alignment according to the History of Lateral Ankle Sprain: Efficacy and Limitation of Static Lower Limb Alignment Measurement as a Predictor of Lateral Ankle Sprain (외측 발목 염좌 병력에 따른 정적 하지 정렬 차이: 외측 발목 염좌의 예측인자로서 정적 하지 정렬 검사의 효용성과 한계점)

  • Jeon, Hyung Gyu;Ha, Sunghe;Lee, Inje;Kang, Tae Kyu;Kim, Eun Sung;Lee, Sae Yong
    • Korean Journal of Applied Biomechanics
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    • v.31 no.1
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    • pp.1-15
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    • 2021
  • Objective: The aim of this study was to investigate 1) the difference in static lower extremity alignment (SLEA) according to a history of lateral ankle sprain (LAS), 2) to identify SLEA factors affecting LAS, and 3) to present the cut-off value and 4) the usefulness and limitations of the SLEA measurement. Method: This case-control study recruited 88 men (age: 27.78±4.69 yrs) and 39 women (age: 24.62±4.20 yrs) subjects with and without LAS. SLEA measurement protocol included Q angle, tibiofemoral angle, genu recurvatum, rear foot (RF) angle, tibal varum and torsion, navicular drop, ankle dorsiflexion range of motion (DF ROM). Independent t-test, logistic regression and receiver operating characteristic (ROC) curve were used for statistical analysis. Results: Men with a history of LAS had significantly smaller Q angles both in standing and in supine position, while women with a history of LAS had significantly greater DF ROM in non-weight bearing (NWB; p < 0.05). Logistic regression model suggests tibial varum (OR = 0.779, p = 0.021) and WB DF ROM (OR = 1.067, p = 0.045) were associated with LAS in men. In case of women, there were no significant SLEA factors for LAS, however, ROC curve analysis revealed standing RF angle (AUC = 0.647, p = 0.028) and NWB DF ROM (AUC = 0.648, p = 0.026) could be affecting factors for LAS. Conclusion: There are differences in SLEA according to the history of LAS, furthermore, the identified items were different by sex. In case of men, tibial varum and WB DF ROM affect LAS occurrence. Standing RF angle and NWB DF ROM of women could be a predictor for LAS. However, since the sensitivity and specificity in most of the SLEA measurements are low, kinematic in dynamic tasks should be considered together for a more accurate evaluation of LAS risk.

Performance Evaluation of Pull-out Load of a New Type of Double-wall Pile Foundation for Easy Demolition (기초구조물 회수가 용이한 신형식 이중벽 말뚝기초의 인발하중 성능평가)

  • Kim, Jae-Hyun;Kim, Jeong-Soo;Lee, Minjy;Sven, Falcon Sen;Choo, Yun Wook;Hwang, Sung-Pil
    • Journal of the Korean Geotechnical Society
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    • v.38 no.4
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    • pp.21-32
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    • 2022
  • Steel pile foundations are widely used for offshore constructions due to their high bearing capacity and efficiency. Typically, offshore structures that have reached the end of their design life are required to be demolished. However, pile foundations are often left on site due to technical and economic limitations. The pile left on the site not only pollutes the environment, but can also cause obstacles for the construction of new structures. Therefore, research is required to completely eliminate these foundations at the site. In this study, a new type of double-wall pile foundation that can drastically reduce the pull-out load was conceptually proposed, and a series of model tests were performed to validate the performance of the double-wall pile foundation. The installation and extraction of the double-wall pile were simulated in dry sand in the model test, and the measured up-lift load was compared to that of the conventional pile. According to the result, the maximum up-lift load induced by the decommissioning of the double-wall pile was reduced by 45% when compared to the traditional pile in dense sand. This study verified the mechanism for reducing the up-lift load of the double-wall foundation and confirmed the possibility of completely decommissioning a pile that has reached the end of its nominal service life.

Immunological mechanism of Aging : T & B cell changes (면역학적 노화 기전에 관한 연구: T 및 B 세포의 변화)

  • Kim, Jay Sik;Lee, Won Kil;Suh, Jang Soo;Song, Kyung Eun;Lee, Joong Won;Lee, Nan Young;Weksler, Marc E.
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.236-243
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    • 2001
  • Background: An immunological approach for aging mechanism appears to be important. Lymphocyte subsets analysis in peripheral blood is widely performed to assess the immune status and to diagnose and monitor various diseases. Some lymphocyte subsets are known to change with age, but only few data about age-related reference ragnes for these subsets in healthy individuals have been reported. So we attempted to report reference ranges for these subsets in each age group and review changes of the results with age for the secondary studies about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement (VDJ) including recombination activating genes (RAG-1 and RAG-2). Methods: Lymphocyte subset analysis was performed on 302 subjects, 189 males and 113 females with age group of all decades of life. Two color direct immunofluorescene flow cytometry (FCM) was done using $Simultest^{TM}$ IMK-Lymphocyte kit (Becton Dickinson, USA), $FACScan^{TM}$ (Becton Dickinson, USA) and $FACSCalibur^{TM}$ (Becton Dickinson, USA). Lymphocyte subsets analysed were T ($CD3^+$) and B cells ($CD19^+$), helper/inducer T ($CD4^+$) and suppressor/cytotoxic T cells ($CD8^+$), helper/suppressor ($CD4^+/CD8^+$) ratio and natural killer (NK) cells ($CD3^-CD16^+/CD56^+$). The absolute numbers of each subset were calculated from total lymphocyte counts. Data collected was analysed using SAS 6.12. A P-value of < 0.05 was considered significant. Results: We reported the counts and percentages of lymphocyte and these subsets in each age group. There were no statistically significant differences between male and female subjects. The percentage of $CD4^+$ T cells, and the count of NK cells did not show the significant difference among the various age groups. The age-related changes observed in our study were as following: 1) a decrease in the percentages of T cells, B cells and $CD8^+$ T cells ; 2) a decrease in the counts of B cells and $CD8^+$ T cells ; 3) an increase in the percentage and count of NK cells ; and 4) an increase in the $CD4^+/CD8^+$ ratio. Conclusion: The characteristics of aging process appeared to be showing a marked decrease of lympocyte subsets T and B cells as well as T8 ($CD8^+$). The age-related increase of the percentage of cells bearing NK marker can be interpreted as a compensatory consequence to cope with the decrease of T cells related to the thymic involution. These changes with age appeared to be for the secondary study about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement.

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