• Title/Summary/Keyword: Tim-3L

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The Binding Properties of Glycosylated and Non- Glycosylated Tim-3 Molecules on $CD4^+CD25^+$T Cells

  • Lee, Mi-Jin;Heo, Yoo-Mi;Hong, Seung-Ho;Kim, Kyong-Min;Park, Sun
    • IMMUNE NETWORK
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    • v.9 no.2
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    • pp.58-63
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    • 2009
  • Background: T cell immunoglobulin and mucin domain containing 3 protein (Tim-3) expressed on terminally differentiated Th1 cells plays a suppressive role in Th1-mediated immune responses. Recently, it has been shown that N-glycosylation affects the binding activity of the Tim-3-Ig fusion protein to its ligand, galectin-9, but the binding properties of non-glycosylated Tim-3 on $CD4^+CD25^+$T cells has not been fully examined. In this study, we produced recombinant Tim-3-Ig fusion proteins in different cellular sources and its N-glycosylation mutant forms to evaluate their binding activities to $CD4^+CD25^+$T cells. Methods: We isolated and cloned Tim-3 cDNA from BALB/C mouse splenocytes. Then, we constructed a mammalian expression vector and a prokaryotic expression vector for the Tim-3-Ig fusion protein. Using a site directed mutagenesis method, plasmid vectors for Tim-3-Ig N-glycosylation mutant expression were produced. The recombinant protein was purified by protein A sepharose column chromatography. The binding activity of Tim-3-Ig fusion protein to $CD4^+CD25^+$T cells was analyzed using flow cytometry. Results: We found that the nonglycosylated Tim-3-Ig fusion proteins expressed in bacteria bound to $CD4^+CD25^+$T cells similarly to the glycosylated Tim-3-Ig protein produced in CHO cells. Further, three N-glycosylation mutant forms (N53Q, N100Q, N53/100Q) of Tim-3-Ig showed similar binding activities to those of wild type glycosylated Tim-3-Ig. Conclusion: Our results suggest that N-glycosylation of Tim-3 may not affect its binding activity to ligands expressed on $CD4^+CD25^+$T cells.

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer

  • Byun, Kyung Do;Hwang, Hyo Jun;Park, Ki Jae;Kim, Min Chan;Cho, Se Heon;Ju, Mi Ha;Lee, Jin Hwa;Jeong, Jin Sook
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.406-414
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    • 2018
  • Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

Efficiency Verification of Small-Scale Sewage Treatment Plant Using Discussed Vinyl as Biofilm Media (폐비닐 재활용 여재를 이용한 소규모 오수종말처리장의 효율검증)

  • Rim, Jay-Myoung;Kim, Byoung-Ug;Koo, Bon-Soo
    • Journal of Industrial Technology
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    • v.18
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    • pp.1-6
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    • 1998
  • This study was conducted to use disused vinyl as biofilm for biological sewage treatment. Efficiency verification was performed on laboratory and on-site plant. In laboratory study, total biochemical oxygen demand(TBOD) removal rate was ranged 94.8~97 % in each hydraulic retention tim(HRT), 12, 16, 20, 24 hr, respectively. At that time, filling rate was 50 %. And effluent TBOD concentration was low ranged 3.64~6.28 mg/L. In on-site plant, TBOD removal rate was ranged 88.2~96.8 % and effluent TBOD concentration was 4.8~17.7mg/L. This concentration was lower than disign effluent concentration, 30mg/L. Total kjeldhal nitrogen(TKN) removal efficiency was ranged 56.8~90.9%. This was resulted higher than Lab. scale treatment efficiency.

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BIOASSAYS ON MARINE ORGANISMS II. ACUTE TOXICITY TEST OF MERCURY, COPPER AND CADMIUM TO CLAM, MERETRIX LUSORIA (해양생물에 대한 생체실험 II. 백합에 대한 수은, 구리 및 카드뮴의 독성)

  • PARK Joo-Suck;KIM Hak-Gyoon
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.12 no.2
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    • pp.113-117
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    • 1979
  • The short-term acute toxicities of mercury, cadmium and copper for the clam, Meretrix lusoria were determined from 28 June to 15 July, 1978. In the test with mercury and copper, the rate ot mucus excretion increased gradually at a higher concentration. But the clams did not excrete mucus in the solutions of cadmium and natural sea water. The rate of mucus excretion in mercury was $42.9\%$, and that in copper was $14.3\%$ in a test solution of 1mg/l. mercury was more toxic than copper. The median lethal concentration after 96 hours (96 hr-Lc 50) was 0.67mg/l in mercury, 7.04mg/l in copper and 7.10mg/l in cadmium. Consequently it was found that mercury was the most toxic substance and cadmium was the least. meanwhile, it was considered that exposure time by stimulation in a fixed concentration caused the test animals to respond.

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Intersubunit Communication of Escherichia coli Tryptophan Synthase (대장균 트립토판 생성효소의 소단위체간 상호조절)

  • Cho, Won Jin;Lim, Woon Ki
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1410-1414
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    • 2017
  • Escherichia coli tryptophan synthase (TS) contains ${\alpha}_2{\beta}_2$, which catalyzes the final two steps in Trp biosynthesis. A molecular tunnel exists between the two active sites of ${\alpha}$ and ${\beta}$ subunits in TS. Via intersubunit communication, TS increases catalytic efficiency, including substrate channeling. The ${\beta}$ subunit of TS is composed of two domains, one of which, the COMM (communication) domain, plays an important role in intersubunit communication. The ${\alpha}$ subunit has a TIM barrel structure. This protein has functional regions at the C terminal of ${\beta}$ pleated sheets and in its loop regions. Three regions of the ${\alpha}$ subunit (${\alpha}L6$ [${\alpha}-loop$ L6], ${\alpha}L2$, and ${\alpha}L3$) are implicated in intersubunit communication. In the present study, conformational changes in ${\alpha}L6$ were monitored by measuring the sensitivity of mutant proteins in these regions to trypsin. The addition of a ${\alpha}$ subunit-specific ligand, D,L-${\alpha}$-glycerophosphate (GP), partially restored the sensitivity of mutant proteins to trypsin. In contrast, the addition of the ${\beta}$ subunit-specific ligand L-serine (Ser) resulted in varied sensitivity to trypsin, with an increase in PT53 (substitution of Pro with Thr at residue 53) and DG56, decrease in NS104 and wild type, and no change in GD51 and PH53. This finding may be related to several reaction intermediates formed under this condition. The addition of both GP and Ser led to a highly stable state of the complex. The present results are consistent with the current model. The method used herein may be useful for screening residues involved in intersubunit communication.

SURFACE DEFORMATION MONITORING USING TERRASAR-X INTERFEROMETRY

  • Kim, Sang-Wan;Wdowinski, Shimon;Dixon, Tim
    • Proceedings of the KSRS Conference
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    • 2008.10a
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    • pp.422-425
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    • 2008
  • TerraSAR-X is new radar satellite operated at X-band, multi polarization, and multi beam mode. Compared with C-band or L-band SAR, the X-band system inherently suffers from more temporal decorrelation, but is more sensitive to surface deformation monitoring due to short wavelength (3.1 cm) and high spatial resolution (1m-3m). It is generally expected that sensitivity to estimate surface movement using TerraSAR-X will be increased by the factor of 10, compared to current C-band system with low spatial resolution such as ERS-2, Envisat. Many urban areas are experiencing land subsidence due to water, oil and natural gas withdrawal, underground excavation, sediment compaction, and so on. Monitoring of surface deformation is valuable for effectively limiting damage areas. In addition high accuracy and spatially dense subsidence map can be achieved by X-band InSAR observation, promoting identification and separation of various subsidence processes and leading to enhanced understanding via mechanical modeling. In this study we will introduce some initial InSAR results using new TerraSAR-X SAR data for surface deformation monitoring.

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Study on High Accurate Schemes for Simulation of Free-surface Flow (자유표면 유동 시뮬레이션을 위한 고정확도 수치도식의 검토)

  • Park, Jong-Chun;Lee, Byoung-Hyuk;Kim, Jeung-Hu
    • Journal of Ocean Engineering and Technology
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    • v.20 no.4 s.71
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    • pp.31-36
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    • 2006
  • Numerical schemes for spacing and time are tested to accurately simulate the wave propagation. The tested numerical schemesinclude 2nd-order central differencing, l-order upwind scheme, 2nd-order Leith scheme, 3rd-order MUSCLE, QUICK and QUICKEST schemes in spacing and the Euler and 4th-order Runge-Kutta(R-K) schemes in time. It is seen that more accurate results are expected when the higher-order schemes, especially the schemes combined with a TVD control limiter, are used for solving the wave equation. The 3rd-order upwind scheme with limiter and the 4th-order R-K scheme in tim£ are finally applied to the wave-making simulation in a digital wave tank.

Characterization of the main component of equal width welded I-beam-to-RHS-column connections

  • Lopez-Colina, Carlos;Serrano, Miguel A.;Lozano, Miguel;Gayarre, Fernando L.;Suarez, Jesus M.;Wilkinson, Tim
    • Steel and Composite Structures
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    • v.32 no.3
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    • pp.337-346
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    • 2019
  • The present paper tries to contribute fill the gap of application of the component method to tubular connections. For this purpose, one typical joint configuration in which just one component can be considered as active has been studied. These joints were selected as symmetrically loaded welded connections in which the beam width was the same as the column width. This focused the study on the component 'side walls of rectangular hollow sections (RHS) in tension/compression'. It should be one of the main components to be considered in welded unstiffened joints between I beams and RHS columns. Many experimental tests on double-sided I-beam-to-RHS-column joint with a width ratio 1 have been carried out by the authors and a finite element (FE) model was validated with their results. Then, some different analytical approaches for the component stiffness and strength have been assessed. Finally, the stiffness proposals have been compared with some FE simulations on I-beam-to-RHS-column joints. This work finally proposes the most adequate equations that were found for the stiffness and strength characterization of the component 'side walls of RHS in tension/compression' to be applied in a further unified global proposal for the application of the component method to RHS.

Etiologies, Prognostic Factors, and Outcomes of Pediatric Acute Liver Failure in Thailand

  • Getsuwan, Songpon;Lertudomphonwanit, Chatmanee;Tanpowpong, Pornthep;Thirapattaraphan, Chollasak;Tim-Aroon, Thipwimol;Wattanasirichaigoon, Duangrurdee;Treepongkaruna, Suporn
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.23 no.6
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    • pp.539-547
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    • 2020
  • Purpose: Pediatric acute liver failure (PALF) is a serious condition; however, data on PALF in developing countries are sparse, particularly concerning molecular diagnosis and liver transplantation (LT). This study aimed to determine the causes, outcomes, and prognostic factors of PALF. Methods: We retrospectively reviewed the medical records of children (age <15 years) with PALF diagnosed using the American Association for the Study of Liver Diseases criteria at our center from 2011 to 2016. The collected data included laboratory results, complications, outcomes, and potential factors associated with death and LT. Results: We included a total of 27 patients, with a median age of 2 years (interquartile range, 3 months to 4 years). Viral infection was the most common etiology (n=8, 30%), predominantly dengue infection (n=4). A total of 16 patients (59%) died and 11 patients survived (3 patients with LT). The prognostic factors associated with death or LT requirement were grade IV hepatic encephalopathy (p<0.01), hypotension (p=0.02), gastrointestinal bleeding (p=0.03), increased intracranial pressure (p=0.04), and higher peak serum lactate level (p=0.01). Peak serum lactate ≥6 mmoL/L had a sensitivity of 79% and a specificity of 88% for predicting mortality or the necessity of LT. Conclusion: Viral infection was the most common cause of PALF. The mortality rate remained high, and a considerable number of patients required LT. In addition to several clinical factors, peak serum lactate could be a potential marker for predicting poor outcomes in PALF.

Effects of purified lignin on in vitro rumen metabolism and growth performance of feedlot cattle

  • Wang, Yuxi;McAllister, Tim A.;Lora, Jairo H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.3
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    • pp.392-399
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    • 2017
  • Objective: The objectives were to assess the effects of purified lignin from wheat straw (sodium hydroxide dehydrated lignin; SHDL) on in vitro ruminal fermentation and on the growth performance of feedlot cattle. Methods: In vitro experiments were conducted by incubating a timothy-alfalfa (50:50) forage mixture (48 h) and barley grain (24 h) with 0, 0.25, 0.5, 1.0, and 2.0 mg/mL of rumen fluid (equivalent to 0, 2, 4, 8, and 16 g SHDL/kg diet). Productions of $CH_4$ and total gas, volatile fatty acids, ammonia, dry matter (DM) disappearance (DMD) and digestion of neutral detergent fiber (NDF) or starch were measured. Sixty Hereford-Angus cross weaned steer calves were individually fed a typical barley silage-barley grain based total mixed ration and supplemented with SHDL at 0, 4, 8, and 16 g/kg DM for 70 (growing), 28 (transition), and 121 d (finishing) period. Cattle were slaughtered at the end of the experiment and carcass traits were assessed. Results: With forage, SHDL linearly (p<0.001) reduced 48-h in vitro DMD from 54.9% to 39.2%, NDF disappearance from 34.1% to 18.6% and the acetate: propionate ratio from 2.56 to 2.41, but linearly (p<0.001) increased $CH_4$ production from 9.5 to 12.4 mL/100 mg DMD. With barley grain, SHDL linearly increased (p<0.001) 24-h DMD from74.6% to 84.5%, but linearly (p<0.001) reduced $CH_4$ production from 5.6 to 4.2 mL/100 mg DMD and $NH_3$ accumulation from 9.15 to $4.49{\mu}mol/mL$. Supplementation of SHDL did not affect growth, but tended (p = 0.10) to linearly reduce feed intake, and quadratically increased (p = 0.059) feed efficiency during the finishing period. Addition of SHDL also tended (p = 0.098) to linearly increase the saleable meat yield of the carcass from 52.5% to 55.7%. Conclusion: Purified lignin used as feed additive has potential to improve feed efficiency for finishing feedlot cattle and carcass quality.