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MiR-21 Upregulation Induced by Promoter Zone Histone Acetylation is Associated with Chemoresistance to Gemcitabine and Enhanced Malignancy of Pancreatic Cancer Cells

  • Song, Wei-Feng;Wang, Lei;Huang, Wei-Yi;Cai, Xun;Cui, Jiu-Jie;Wang, Li-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7529-7536
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    • 2013
  • Background and Aims: MicroRNA-21 (miR-21) is reported to be overexpressed and to contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation of miR-21 expression by epigenetic change and its impact on chemoresistance and malignant properties of of pancreatic cancer. Materials and methods: We retrospectively collected 41 cases of advanced pancreatic cancer patients who were sensitive or resistant to gemcitabine and assessed levels of serum circulating miR-21 for correlation with cytotoxic activity. Histone acetylation in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine-resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were transfected with pre-miR-21 precursors (pre-miR-21) and antisense oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT level was evaluated in these cells. Results: Serum miR-21 levels were increased in gemcitabine-resistant PDAC patients compared with gemcitabine-sensitive subjects. The miR-21 levels were increased in 6 PDAC cells treated with gemcitabine significantly, associated with 50% inhibitory concentrations ($IC_{50}s$). Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine. Conclusions: MiR-21 upregulation induced by histone acetylation in the promoter zone is associated with chemoresistance to gemcitabine and enhanced malignant potential in pancreatic cancer cells.

A Novel Complement Fixation Pathway Initiated by SIGN-R1 Interacting with C1q in Innate Immunity

  • Kang, Young-Sun
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2008.05a
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    • pp.23-25
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    • 2008
  • Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

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Prediction and Experiment of Pressure Drop of R22, R407C and R410A on Design Conditions of Condenser (응축기의 설계조건에서 R22, R407C, R410A의 압력강하 예측 및 실험)

  • 김창덕;박일환;이진호
    • Korean Journal of Air-Conditioning and Refrigeration Engineering
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    • v.16 no.1
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    • pp.42-53
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    • 2004
  • An experimental study on the refrigerant-side pressure drop of slit fin-tube heat exchanger has been carried out. A comparison was made between the predictions of previously proposed empirical correlations and experimental data for the pressure drop on design conditions of condenser in micro-fin tube for R22 and its alternatives, R407C (R32/125/134a, 23/25/52 wt.%) and R410A (R32/125, 50/50 wt.%). Experiments were carried out under the conditions of inlet refrigerant temperature of 6$0^{\circ}C$ and mass fluxes varying from 150 to 250 kg/$m^2$s for R22, R407C and R410A. The inlet air conditions are dry bulb temperature of 35$^{\circ}C$, relative humidity of 40% and air velocity varying from 0.68 to 1.43 m/s. Experiments show that pressure drop for R410A and R407C were 17.8∼20.2% and 5∼6.8% lower than those of R22 respectively for the degree of subcooling of 5$^{\circ}C$. For the mass fluxes of 200∼250 kg/$m^2$s, the deviation between the experimental and predicted values for the pressure drop was less than $\pm$20% for R22, R407C and R410A.

The effects of Government R&D subsidies on Private R&D investment - The case of Korean industry after 2000 - (정부 연구개발 보조금의 기업자체 R&D투자에 대한 효과 분석 - 2000년 이후 국내기업 사례를 중심으로 -)

  • Choi, Seok-Joon;Kim, Sang-Shin
    • Journal of Korea Technology Innovation Society
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    • v.10 no.4
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    • pp.706-726
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    • 2007
  • This study attempts to empirically investigate the effects of government R&D subsidies on private firm's R&D investment in Korean industry. The R&D subsidy effect is defined as the average percentage change in firm's R&D expenditures between what was actually observed among firms that received a subsidy and what these firms would have spent had the subsidy not been received. To measure the effect we use Difference-in-Differences (DID) model which sign as to whether the relationship between government subsidies and private R&D investments is on stimulating or displacing private R&D expenditures. The differences between this study and previous studies are that we tries to measure the effect of Government R&D across various sited firm groups such as large, small & medium, and venture firms and we add one lag of the subsidy indicator in order to capture the effect of the subsidies on private R&D during 2 consecutive period. Empirically, a firm with government R&D subsidy increases its own R&D investment by 13.9%. Also on average, 1% of government R&D subsidy leads to 0.031% of private R&D increase. The main results of this study are as follows : First, Government R&D subsidies stimulate private firm's R&D expenditures. Second, Government R&D subsidies greatly increase (statistically significant) company financed R&D expenditures only for large firms but had no effect on the R&D expenditures of small & medium sized firms and venture firms.

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Condensation Heat Transfer of R32 and R454B Inside a Microfin Tube as an Alternative Refrigerant to R410A (R410A 대체냉매 R32와 R454B의 미세핀 관내 응축 열전달)

  • KARAGEORGIS, ANDREAS;HINOPOULOS, GEORGE;KIM, MAN-HOE
    • Journal of Hydrogen and New Energy
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    • v.33 no.4
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    • pp.413-418
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    • 2022
  • This paper presents two-phase condensation heat transfer and pressure drop characteristics of R32 and R454B as an alternative refrigerant to R410A in a 9.52 mm OD microfin tube. The test facility has a straight, horizontal test section with an active length of 2.0 m and is cooled by cold water circulated in a surrounding annular space. The heat transfer coefficients of the annular space were obtained using the modified Wilson plot method. Average condensation heat transfer coefficient and pressure drop data are presented at the condensation temperature of 35℃ for the range of mass flux 100-400 kg/m2s. The average condensation heat transfer coefficients of R32 refrigerant are 35-47% higher than R410A at the mass flux considered in the study, while R454B data are similar to R410A. The average pressure drop of R32 and R454B are much higher than R410A and they are 134-224% and 151-215% of R410A, respectively. R32 and R454B have relatively low GWP and high heat transfer characteristics, so they are suitable as alternatives for R410A.

A Study on Occupational Diseases of Fire Officials (소방공무원의 직무질환에 관한 연구)

  • Cho, Kwang-Rae
    • Korean Security Journal
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    • no.61
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    • pp.109-135
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    • 2019
  • The purpose of this study is to investigate the occupational diseases(the number of medical treatment) of fire officials by using time-series analysis. The results of the study are as follows. First, the average rates of the occupational diseases of fire officials were as follows: ① internal diseases were the highest at 9.24% in December, the lowest at 7.76% in February, ② otolaryngologic diseases were the highest at 9.29% in December, the lowest at 6.74% in August, ③ dermatological diseases were the highest at 10.03% in July, the lowest at 7.35% in January and February, ④ surgical diseases were the highest at 10.38% in November, the lowest at 5.62% in February, ⑤ orthopedic diseases were the highest at 9.69% in March, the lowest at 7.52% in November, ⑥ neurosurgical diseases were the highest at 9.33% in April, the lowest at 6.82% in February, ⑦ neurological diseases were the highest at 9.47% in December, the lowest at 7.06% in October, and ⑧ mental health diseases were the highest at 9.93% in December, the lowest at 6.51% in May. Second, the seasonal decomposition of the disease occurrence of fire officials were described by assigning seasonal factor(S), trend factor(T), circulation factor(C) and irregular factor(R): ① internal diseases were 1.075(S) × 189.355(T·C) × 1.174(R) = 238.975(F), ② otolaryngologic diseases were 1.023(S) × 69.605(T·C) × 1.040(R) = 74.000(F), ③ dermatological diseases were 1.002(S) × 73.088(T·C) × 0.874(R) = 64.000(F), ④ surgical diseases were 1.099(S) × 27.229(T·C) × 0.669(R) = 20.000(F), ⑤ orthopedic diseases were 1.115(S) × 73.182(T·C) × 1.213(R) = 99.000(F), ⑥ neurosurgical diseases were 0.993(S) × 27.836(T·C) × 1.303(R) = 36.000(F), ⑦ neurological diseases were 1.029(S) × 62.417(T·C) × 1.152(R) = 74.000(F), and ⑧ mental health diseases were 1.210(S) × 8.781(T·C) × 1.035(R) = 11.000(F).

REMARK ON A SEGAL-LANGEVIN TYPE STOCHASTIC DIFFERENTIAL EQUATION ON INVARIANT NUCLEAR SPACE OF A Γ-OPERATOR

  • Chae, Hong Chul
    • Korean Journal of Mathematics
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    • v.8 no.2
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    • pp.163-172
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    • 2000
  • Let $\mathcal{S}^{\prime}(\mathbb{R})$ be the dual of the Schwartz spaces $\mathcal{S}(\mathbb{R})$), A be a self-adjoint operator in $L^2(\mathbb{R})$ and ${\Gamma}(A)^*$ be the adjoint operator of ${\Gamma}(A)$ which is the second quantization operator of A. It is proven that under a suitable condition on A there exists a nuclear subspace $\mathcal{S}$ of a fundamental space $\mathcal{S}_A$ of Hida's type on $\mathcal{S}^{\prime}(\mathbb{R})$) such that ${\Gamma}(A)\mathcal{S}{\subset}\mathcal{S}$ and $e^{-t{\Gamma}(A)}\mathcal{S}{\subset}\mathcal{S}$, which enables us to show that a stochastic differential equation: $$dX(t)=dW(t)-{\Gamma}(A)^*X(t)dt$$, arising from the central limit theorem for spatially extended neurons has an unique solution on the dual space $\mathcal{S}^{\prime}$ of $\mathcal{S}$.

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ALMOST PRINCIPALLY SMALL INJECTIVE RINGS

  • Xiang, Yueming
    • Journal of the Korean Mathematical Society
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    • v.48 no.6
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    • pp.1189-1201
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    • 2011
  • Let R be a ring and M a right R-module, S = $End_R$(M). The module M is called almost principally small injective (or APS-injective for short) if, for any a ${\in}$ J(R), there exists an S-submodule $X_a$ of M such that $l_Mr_R$(a) = Ma $Ma{\bigoplus}X_a$ as left S-modules. If $R_R$ is a APS-injective module, then we call R a right APS-injective ring. We develop, in this paper, APS-injective rings as a generalization of PS-injective rings and AP-injective rings. Many examples of APS-injective rings are listed. We also extend some results on PS-injective rings and AP-injective rings to APS-injective rings.

고객 지식의 활용을 위한 R&D 지원 지식 경영시스템 구현

  • 김선우;이창용;박용태
    • Proceedings of the Technology Innovation Conference
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    • 2005.08a
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    • pp.217-237
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    • 2005
  • R&D의 발전과 함께 필요한 지식과 정보가 증가하며 참여자들도 확대되었다. 따라서 기업은 외부의 지식을 관리할 필요가 발생하였으며, 고객의 지식은 가장 주요한 혁신의 원천이다. 본 연구는 고객의 지식을 R&D에 활용할 수 있도록 해주는 고객지식관리시스템(CKMS)의 설계를 목적으로 한다. CKMS는 고객을 성공적인 지식 창출 사이클로 유도하며, 기업의 고객 지식 획득을 지원하고 고객의 관점에서 생성된 지식을 R&D에 유용한 형태로 전환하는 과정을 지원한다. 시스템 설계를 위하여 R&D 프로세스를 기반으로 CKMS의 기능을 정의하였다. TFT-LCD 디스플레이 산업을 대상으로 R&D 초기단계의 플랫폼 개발에 필요한 고객 지식경영 시스템의 기능을 구현하였다. 제시된 시스템은 기업 내부의 연구원을 위한 KMS와 연계하여 R&D 전체 프로세스의 혁신과 효율성을 증진할 것이다.

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